Dutta 1

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Modern Ophthalmology, 3rd edition (Vol 1)
© 2005, LC Dutta, Nitin K Dutta
All rights reserved. No part of this publication should be reproduced, stored in a retrieval system,
or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or
otherwise, without the prior written permission of the editors and the publisher.
This book has been published in good faith that the material provided by contributors is original.
Every effort is made to ensure accuracy of material, but the publisher, printer and editors will
not be held responsible for any inadvertent error(s). In case of any dispute, all legal matters to
be settled under Delhi jurisdiction only.
First Edition: 1994

Second Edition: 2000
Reprint: 2003
Third Edition: 2005
ISBN 81-8061-470-0 (Set)

Typeset at JPBMP typesetting unit
Printed at Paras Offset Pvt Ltd., C-176, N.I.A., Phase-1, New Delhi
Dedicated to
students who help us to
continue to learning and the patients
who constantly stimulate our search
for better methods of managing their eye ailments
Contributors
Mary Abraham MS DOMS M Baskaran MD Dipak Bhuyan MS
Consultant Ophthalmologist, Chennai Consultant Assistant Professor
Shankara Nethralaya Regional Institute of Ophthalmology
Anil Kumar Agarwal
Chennai Guwahati
Fellow, Shri Sankaradeva Nethralaya,
Guwahati
Samar K Basak MD DNB VA Bidaye MS DO
BK Ahluwalia MS DOMS Disha Eye Hospitals and Research Medical Director
Professor of Ophthalmology Centre, Barrackpore Bidaye Hospital
Medical College, Rohtak West Bengal Baroda
David J Apple MD Surendra Basti MS Jyotirmay Biswas MS
Professor of Ophthalmology and Ex-Consultant Medical and Vision Research Foundation
Pathology LV Prasad Eye Institute Shankara Nethralaya, Chennai
Director Hyderabad
David J Apple Laboratories for Gagandeep S Brar
Ophthalmic Devices Research H Bhattacharjee MS Assistant Professor
John A Moran Eye Center Medical Director Department of Ophthalmology
University of Utah Shri Shankaradeva Nethralaya Post Graduate Institute of Medical
Salt Lake City, Utah, USA Guwahati Education and Research
Chandigarh
N Arivazhagan Kasturi Bhattacharjee MS
LV Prasad Eye Institute, Hyderabad Consultant Sanghamitra Burman
Hemamalini Arvind MS Shri Shankaradeva Nethralaya Oncology Oculoplasty Service
Glaucoma Service Guwahati LV Prasad Eye Insitute, Hyderabad
Shankara Nethralaya
Chennai Pankaj Bhattacharjee Girish Chandra MS FRCS FRC Ophth
Fellow Consultant Ophthalmologist
Supratik Bandopadhyay Shri Shankaradeva Nethralaya Harley Street
Senior Resident Guwahati London, UK
Department of Ophthalmology
Post Graduate Institute of Medical RP Bhatia MS Aman Chandra MBBS
Education and Research, Chandigarh Ex-Professor of Ophthalmology Senior House Officer
Institute of Medical Sciences London, UK
Souvik Banerjee MS DO PhD Varanasi
Assistant Professor Hari Charan FRCS FICS
A Bhatnagar MD
Department of Ophthalmology Director
Sir Gangaram Hospital
Ramakrishna Mission Seva Pratishthan KC Memorial Eye Hospital, Jaipur
New Delhi
Vivekananda Institute of Medical
Sciences, Kolkata Nitul S Bhatt MS DOMS
Neha Charan MS DNB
Consultant
Consultant
Ashish Kumar Bansal MS Vitreoretinal Centre, Mumbai
KC Memorial Eye Hospital, Jaipur
Consultant
Corneal Service Muna Bhende MS
LV Prasad Eye Institute Consultant Rohit Charan MS
Hyderabad Shankara Nethralaya Consultant
Chennai KC Memorial Eye Hospital, Jaipur
CK Barua MS
Director Pramod S Bhende Samrat Chatterjee MS
Regional Institute of Ophthalmology Consultant Consultant
Guwahati Medical College Shankara Nethralaya Cornea and Anterior Segment
Guwahati Chennai 139, MC Road, Guwahati
viii Modern Ophthalmology
Navneet Chauhan Nibaran Gangopadhyay MS SK Handique MD

Resident of Ophthalmology Consultant Senior Consultant Radiologist
AIIMS New Delhi Cornea and Anterior Segment Institute of Radiology
LV Prasad Eye Institute Guwahati Neurological Research
Sumit Choudhury MS DO Hyderabad Centre, Guwahati
Consultant
Eye Care and Research Centre Deepak Garg Madhavi G Hirode MS
Kolkata Consultant Consultant
Shankara Nethralaya, Chennai Vitreoretinal Surgeon
Tanuj Dada MD Gobind Clinic, Baroda
Assistant Professor Amala Elizabeth George DNB FRCS
Clinical Ophthalmology Consultant Santosh G Honavar MD
Dr Rajendra Prasad Centre for Sankara Nethralaya Consultant
Ophthalmic Sciences Chennai Ocular Oncology Service
All India Institute of Medical Sciences, LV Prasad Eye Institute, Hyderabad
New Delhi Viji K George MS
M and I Institute of Ophthalmology Anjli Hussain MS
Subhash Dadeya MD Ahmedabad Consultant
Senior Resident Vitreoretinal Service
Guru Nanak Eye Centre Stephen C Gieser MS LV Prasad Eye Institute, Hyderabad
New Delhi Christian Medical College
Schell Eye Hospital, Vellore Nazimul Hussain MS DNB
Hrishikesh Das Consultant
Resident Ruchi Goel LV Prasad Eye Institute
RP Centre for Ophthalmic Sciences Resident Hyderabad
AIIMS, New Delhi Safdarjung Hospital
New Delhi Tomohiro Iida MD
Subhra Das MS Professor and Chairman
Assistant Professor Lingam Gopal MS Department of Ophthalmology
Regional Institute of Ophthalmology Senior Consultant Fushikima Medical University
Guwahati Shankara Nethralaya Japan
Chennai
Tara Prasad Das MS Shyama Jain MD
Director AK Grover MS MNAMS Guru Nanak Eye Centre
Smti Kannuri Santhamma Chief Ophthalmic Surgeon New Delhi
Retina Vitreous Centre Sir Gangaram Hospital
LV Prasad Eye Institute New Delhi Subhadra Jalali MD
Hyderabad Consultant
Amit Gupta MS LV Prasad Eye Institute
Satyen Deka MS Resident Hyderabad
Consultant Department of Ophthalmology
Shri Shankaradeva Nethralaya Post Graduate Institute of Medical Barrie Jay MD FRCS FC Ophth
Guwahati Education and Research, Chandigarh Professor
Clinical Ophthalmology
B Dutta Institute of Ophthalmology
Consultant Amod Gupta MS University of London
Aditya Jyot Eye Hospital, Mumbai Professor and Head of Ophthalmology London, UK
Post Graduate Institute of Medical
LC Dutta DO (London) FRCS Education and Research, Chandigarh Marcelle Jay PhD
Director Senior Lecturer
Ex-Professor and Chief Organiser SK Gupta MD Institute of Ophthalmology
Regional Institute of Ophthalmology Senior Consultant University of London
Medical College, Guwahati LV Prasad Eye Institute, Hyderabad London, UK
Eye Foundation, Guwahati Vishali Gupta MS
Senior Resident, Ophthalmology Elizabeth Joseph MS
Nitin K Dutta DO Post Graduate Institute of Medical Consultant
Consultant Education and Research Little Flower Hospital
Eye Foundation, Guwahati Chandigarh Angamally
Contributors ix
Kamlesh MD M Kumar Jnanankar Medhi MS
Professor Resident Trainee Consultant
Guru Nanak Eye Centre Guru Nanak Eye Centre Shri Shankaradeva Nethralaya
New Delhi New Delhi Guwahati
Chitra Kannabiran PhD K Lakshmanamurthy N Medhi MD

Scientist Consultant Senior Consultant Radiologist
Kallam Anji Reddy Molecular Genetics Arvind Eye Hospital, Madurai PRIMUS, Guwahati
Laboratory, LV Prasad Eye Institute
Hyderabad Sanjiv Lal MS AS Mehrotra MS FICS MAMS
Fellow Ex-Professor of Ophthalmology
Deva Prasad Kar MS Arvind Eye Hospital, Madurai SMS Medical College, Jaipur
Arvind Eye Hospital
Madurai Paolo Lanzetta MD Shantanu Mitra DOMS
Department of Ophthalmology, Eye Care and Research Centre
Sushismita Kaushik BS M Phil Ophth University of Udine, Udine, Italy Kolkata
Postgraduate Institute of Medical
Education and Research Bharti Lavingia MS Dinesh Mittal MD
Chandigarh Professor Formerly Senior Resident
M and I Institute of Ophthalmology RP Centre of Ophthalmic Sciences
Bakulesh Khamar MS Ahmedabad All India Institute of Medical Sciences
Assistant Professor of Ophthalmology New Delhi
NHL Municipal Medical College Lakshmi Mahesh MD
Ahmedabad Consultant, Shankara Nethralaya Soma Sheila I Murthy MD
Chennai Consultant
Mayuri Khamar MS Cornea and Anterior Segment
Assistant Professor of Ophthalmology Ajit B Majji MD Ocular Immunology and Uveitis Service
M and I Institute of Ophthalmology Consultant LV Prasad Eye Institute
Ahmedabad LV Prasad Eye Institute Hyderabad
Hyderabad
Sarfaraz Ali Khan MD Ramesh Murthy FRCS
Department of Vision Rehabilitation Sarmi Malik MD Oncology Oculoplasty Service
L V Pradad Eye Institute Resident LV Prasad Eye Institute
Hyderabad Sir Gangaram Hospital Hyderabad
New Delhi
AK Khurana MS MAMS Ranabir Mukherji MS DOMS PhD FC Ophth
Associate Professor of Ophthalmology KPS Malik MD Director
Postgraduate Institute of Medical Head Eye Care and Research Centre
Science, Rohtak Department of Ophthalmology Kolkata
Safdarjung Hospital
Kamal Kishore MS New Delhi PN Nagpal MS
RP Centre of Ophthalmic Sciences Director
All India Institute of Medical Sciences Nick Mamalis MD Retina Foundation
New Delhi Professor of Ophthalmology Ahmedabad
John A Moran Eye Center, University
S Krishnaiah MSc MPS of Utah, Salt Lake City, Utah, USA Milind Naik
Department of Ophthalmology Fellow
Postgraduate Institute of Medical Himanshu P Matalia MS Oculoplasty
Education and Research, Chandigarh Adjunct faculty LV Prasad Eye Institute, Hyderabad
Cornea and Anterior Segment Service
K Krishnakumar BS MPhil Opt Sudhakar and Sreekanth Ravi Stem Cell P Namperumalsamy MS
Lecturer, Sankara Nethralaya Biology Laboratory Director
Chennai LV Prasad Eye Institute Arvind Eye Hospital
Hyderabad Madurai
Amol D Kulkarni MD
Department of Ophthalmology Annie Mathai MS FRCS (Ed) Priya Narang
University of California LV Prasad Eye Institute M and I Institute of Ophthalmology
Irvine, California Hyderabad Ahmedabad
x Modern Ophthalmology
S Narang Suresh K Pandey MD Jagat Ram MS

M and I Institute of Ophthalmology Assistant Professor Professor Ophthalmology
Ahmedabad John A Moran Eye Center Post Graduate Institute of Medical
Department of Ophthalmology and Education and Research
SK Narang MS Visual Sciences, University of Utah Chandigarh
Director Salt Lake City, Utah, USA
M and I Institute of Ophthalmology Kavita Ramakrishnan MS
Ahmedabad Arvind Eye Hospital
Sobi Pandey MS Madurai
R Narayanan MD Consultant Ophthalmologist
Department of Ophthalmology Nav Dristi Eye Care Centre R Ramakrishnan MS FACS
University of California, Irvine, USA Kanpur Chief Medical Officer
Arvind Eye Hospital
S Natarajan DO Maurizio Battaglia Parodi MD SN High Road
Director Eye Clinic Tirunelvel
Aditya Jyot Eye Hospital, Mumbai University of Trieste, Trieste, Italy Tamil Nadu
G Natchiar MS Avinash Pathengay FRCS Sreeram Ramalingum MS

Deputy Director Consultant Consultant
Arvind Eye Hospital, Madurai LV Prasad Eye Institute Shankara Nethralaya, Madurai
Hyderabad
D Dwarak Nath MD KM Ranganath MS
Arvind Eye Hospital, Madurai Mahesh Pillai MD FRCS Consultant
Felow Ocular Immunology and Uveitis Udhi Eye Centre, Chennai
Arvind Neelakanthan MS Immunology Laboratory
Shankara Nethralaya, Chennai National Eye Institute B Sridhar Rao MS
Bethesda, Maryland, USA Ex-Consultant
Neena MD Shankara Nethralaya, Chennai
Senior Resident Mukesh Porwal MS
Ophthalmology Consultant GN Rao
RP Centre of Ophthalmic Sciences Retina Foundation Chairman
All India Institute of Medical Sciences Ahmedabad LV Prasad Eye Institute
New Delhi Hyderabad
Neelam Pusker MD
Randall J Olson MD Resident Anju Rastogi MS
Professor of Ophthalmology and RP Centre of Ophthalmic Sciences Associate Professor
Chairman All India Institute of Medical Sciences Guru Nanak Eye Centre, New Delhi
Department of Ophthalmology and New Delhi
Visual Sciences, John A Moran Eye KS Ratnakar MD FICS FIMSA
Center, University of Utah Suresh Puthalath MS Professor Pathology
Salt Lake City, Utah, USA Consultant Dean, Nizam’s Institute of Medical
Arvind Eye Hospital, Madurai Sciences, Hyderabad
Jyoti S Padalay MS
Ex-Professor Ophthalmology Biju Raju Dhanashree Ratra MS
JJ Hospital, Mumbai Ranjini Eye Care Consultant
Vyttila Cochin 682919 Shankara Nethralaya
Nikhil Pal MD Chennai
Resident Seemant Raizada MS
RP Center of Ophthalmic Sciences Research Fellow R Raveendran MS DO
All India Institute of Medical Sciences Medical and Vision Research Consultant Ophthalmologist
New Delhi Foundation Udhi Eye Centre, Chennai
Chennai
Anita Panda MS
Professor Ophthalmology LS Mohan Ram K Ravishankar FRCS DO DNB
RP Centre of Ophthalmic Sciences Retina-Vitreous Service Consultant
All India Institute of Medical Sciences LV Prasad Eye Institute Shankara Nethralaya
New Delhi Hyderabad Chennai
Contributors xi
Mantosh Ray MD Pratik Sen Tarun Sharma MS
Senior Resident Consultant, Ophthalmologist Vitreoretinal Surgeon
RP Centre of Ophthalmic Sciences Shankaradeva Shankara Nethralaya
All India Institute of Medical Sciences Nethralaya, Chennai Chennai
New Delhi
Harinder Singh Sethi MD FRCS Vidushi Sharma MD FRCS (Edin)
Vijay Anand Reddy Senior Research Associate Senior Resident
Oncology Oculoplasty Service Dr Rajendra Prasad Centre for Dr Rajendra Prasad Center
LV Prasad Eye Institute Ophthalmic Sciences for Ophthalmic Sciences
Hyderabad All India Institute of Medical Sciences, All India Institute of Medical Sciences
New Delhi New Delhi
Madhukar Reddy MS
Consultant Ophthalmologist Vinay A Shah Yog Raj Sharma MS
Dristi Eye Centre University of Florida Professor
Hyderabad College of Medicine, Jacksonville RP Centre of Ophthalmic Scineces
Florida, USA All India Institute of Medical Sciences
N Rishita MSc PhD New Delhi
Community Ophthalmology Service Alpesh R Shah
LV Prasad Eye Institute Consultant Surendra Shetty MS
Hyderabad Ila Devi Cataract and Shankara Nethralaya, Chennai
IOL Research Center
JN Rohatgi MS DO FRCS FIAMS FC Ophth Raghudeep Eye Clinic Rajan Shonek MD
Ex-Professor of Ophthalmology Ahmedabad Fellow
Medical College, Patna Shankara Nethralaya
BR Shamanna Chennai
Shailendra Sabherwal MD MD Dip NBE (MCH) Dip NBE (SPM)
Fellow Consultant
LV Prasad Eye Institute, Hyderabad LV Prasad Eye Institute, Hyderabad Deepender V Singh
Resident
Mahipal S Sachdev MD Mahesh P Shanmugam MS RP Centre, AIIMS
Ex-Associate Professor Consultant, Shankara Nethralaya New Delhi
RP Centre, Centre for Sight Chennai
New Delhi Vinita Singh MS
B Shantha MS Professor of Ophthalmology
B Saharia MD Consultant KG Medical College
Senior Consultant Radiologist Shankara Nethralaya, Chennai Lucknow
Institute of Radiology
Guwahati Neurological Research Centre Dhananjay Sharma Archana Sood MS
Hyderabad Arvind Eye Hospital Senior Resident
Madurai RP Center for Ophthalmic Sciences
JS Saini MD MAMS AIIMS, New Delhi
Professor Ophthalmology Namrata Sharma MD
Post Graduate Institute of Medical Senior Resident Devindra Sood MBBS DO
Education and Research, Chandigarh RP Centre of Ophthalmic Sciences Consultant
All India Institute of Medical Sciences Glaucoma Imaging Centre
Virender S Sangwan MS New Delhi New Delhi
Head of Cornea and Anterior Segment
Service, Uvea and Immunology RK Sharma MS NN Sood DO FRCS FAIMS FC Ophth
Sudhakar and Sreekanth Ravi Stem Cell Consultant Ex-Professor
Biology Laboratory Retina Foundation RP Centre of Ophthalmic Sciences
LV Prasad Eye Institute Ahmedabad All India Institute of Medical Sciences
Hyderabad New Delhi
Savitri Sharma MD
Sandeep Saxena MS Devchand Nagin Das Jhaveri Manjula Sridhar MD
Associate Professor (Retina Vitreous) Microbiology Centre Consultant
Eye Department LV Prasad Eye Institute Shankara Nethralaya
KG Medical University, Lucknow Hyderabad Chennai
xii Modern Ophthalmology
M Srinivasan MS Sandeep Thakur MD Geeta G Vemuganti MD

Consultant, Arvind Eye Hospital Shankara Nethralaya, Chennai Ophthalmic Pathologist
Madurai LV Prasad Eye Institute, Hyderabad
Mathew A Thomas MD
L Vijaya MS DO
Kallukuri Sumasri BS Ophth Assistant
Head
LV Prasad Eye Institute Clinical Professor of Ophthalmology
Glaucoma Service
Hyderabad Washington University School of
Shankara Nethralaya, Chennai
Medicine
Subhuram MS MCh USA Usha H Vyas MS
Associate Professor of Neurology Professor
Medical College Ravi Thomas MS Ophthalmology
Thanjavur Director Nagari Hospital, Ahmedabad
LV Prasad Eye Institute
TS Surendran MS Hyderabad Ajeet Madhab Wagle MS
Medical Director Ex-Fellow
Medical Research Foundation Nitin Trivedi MS Shankara Nethralaya, Chennai
Shankara Nethralaya Assistant Professor
Chennai M and I Institute of Ophthalmology Liliana Werner MD PhD
Ahmedabad Assistant Professor
Sudha Sutaria MS David J Apple Laboratories for
Honorary Professor of Ophthalmic Devices Research
Ophthalmology (Retd) R Vadhani MS University of Utah, Salt Lake City
Mayo Hospital Retina Foundation Utah, USA
Nagpur Ahmedabad
M Edward Wilson Jr MD
Jaya Thakur MD Abhay R Vasavada MS DO FRCS Professor and Chairman
Consultant Ila Devi Cataract and IOL Research Storm Eye Institute
Tilganga Eye Center Center, Raghudeep Eye Clinic Medical University of South Carolina
Kathmandu, Nepal Ahmedabad Charleston, USA
Preface to the Third Edition
A major change of this edition is the inclusion of around 50 new chapters relating to amongst others, the
latest technology of imaging systems in diagnosis of ophthalmic diseases like Ultrasound Biomicroscopy,
OCT, Computerized Tomography and Magnetic Resonance Imaging study of the retina and some neuro-
ophthalmological conditions. The chapters of the section on Retina —Vitreous has been completely reorganized
by Dr TP Das as Section Editor. I thank Dr Das for his efforts to make the section more attractive.
I congratulate the authors for their outstanding academic collaboration.
The first edition of Modern Ophthalmology was published in 1994 in one volume. More and more authors
joined for the second edition published in 2000 in two volumes and that edition had one reprint in 2003. I
thank Shri JP Vij, Chairman and Managing Director of M/s Jaypee Brothers Medical Publishers Pvt Ltd, for
bringing out the third edition in 3 volumes as an international publication. The publishers have shown utmost
promptness in publication of this edition. Mr Tarun Duneja, General Manager (Publishing) and his team
deserve special praise for their active support.
Dr Nitin K Dutta deserves special thanks for his immense involvement in bringing out this edition.
LC Dutta
Preface to the First Edition
This multiauthored book contains contributions from different authors in their fields of prime interest.
Though all the dedicated researchers and clinicians in their diverse fields were approached, the editor was
unable to include the contributions from all of them.
Modern Ophthalmology is the first Indian text of its kind which has contributors spread over a number of
disciplines and specialties highlighting the recent trends on the subject. The chapters written on selected
topics have been contributed by ophthalmic clinicians, surgeons and research scientists most of whom have
dominated the national and international scene of ophthalmology, making significant contributions to the
advancement of knowledge. The text has been supplemented by other non-ophthalmic teachers and research
workers such as pathologists and geneticists who have been contributing to the world literature in their
respective specialties.
Almost each of the eleven sections of the book covers the topics over several chapters; the contributors
have attempted to give a broad view of the topic to the readers, keeping brevity and clarity of mind in a
comprehensive and lucid manner. The book strives to serve as a handy basic text to the postgraduate
students in ophthalmology. Also, the chapters have been structured so as to make the text a storehouse of
knowledge and an excellent resource book for the practicing ophthalmologists and clinicians enabling them
to sharpen their diagnostic, clinical and surgical skill in handling ophthalmic cases.
The book has been profusely illustrated with original black and white and color photographs, supplemented
by clearly drawn line diagrams wherever required. The text, which is replete with generous bibliographic
references, is also aimed to serve as a foundation/resource book for the research workers engaged in
different specialty areas of ophthalmology and other interdisciplinary subject areas.
The editor is indebted to the contributors who have willingly devoted a large amount of their valuable
time to share their most up-to-date knowledge and unique perspective by means of the written word. I am
specially grateful to my friends Dr BT Maskati and Dr PN Nagpal for helping me in the preparation of the
list of contributors. I wish to thank M/s Jaypee Brothers Medical Publishers (P) Ltd., for their valuable
technical assistance in publishing this book.
LC Dutta
Contents
11. Viral Conjunctivitis 71
VOLUME 1 Bakulesh Khamar, Mayuri Khamar
Nitin Trivedi, Usha H Vyas
Section 1
12. Trachoma 76
DISORDERS OF THE EYELIDS Bakulesh Khamar, Mayuri Khamar
1. Anatomy of the Eyelids 1 Nitin Trivedi, Usha H Vyas
Bakulesh Khamar, Mayuri Khamar, 13. Bacterial and Special Conjunctival
Nitin Trivedi, Usha H Vyas Conditions 80
2. Congenital Eyelid Anomalies 4 Bakulesh Khamar, Mayuri Khamar,
Bakulesh Khamar, Mayuri Khamar, Nitin Trivedi, Usha H Vyas
Nitin Trivedi, Usha H Vyas 14. Laboratory Diagnosis of Extraocular
3. Anomalies of the Eyelid Margin and Cilia 7 Infective Organisms 85
Bakulesh Khamar, Mayuri Khamar, LC Dutta, Nitin K Dutta
Nitin Trivedi, Usha H Vyas 15. Allergic Conjunctivitis and
4. Blepharitis and Meibomian Allied Conditions 90
Gland Dysfunction 17 LC Dutta, Nitin K Dutta
Samrat Chatterjee, Nibaran Gangopadhyay 16. Dry Eyes 99
5. Inflammatory Diseases of the Eyelids 30 Bakulesh Khamar, Mayuri Khamar,
Nitin Trivedi, Usha H Vyas 17. Ocular Surface Squamous Neoplasia 110
6. Anomalies of the Eyelid Position 35 Samrat Chatterjee, Santosh G Honavar
Bakulesh Khamar, Mayuri Khamar, 18. Conjunctival Tumors 123
Nitin Trivedi, Usha H Vyas LC Dutta, Nitin K Dutta
7. Tumors of the Eyelids* 48 19. Degenerative Conditions of Conjunctiva 127
Bakulesh Khamar, Mayuri Khamar, Bakulesh Khamar, Mayuri Khamar,
Nitin Trivedi, Usha H Vyas Nitin Trivedi
8. Miscellaneous Conditions of the Eyelids 57
Bakulesh Khamar, Mayuri Khamar, Section 3
Nitin Trivedi, Usha H Vyas DISEASES OF CORNEA
Section 2 20. Applied and Functional Anatomy of
the Cornea 131
DISEASES OF CONJUNCTIVA Nitin K Dutta, LC Dutta
9. Anatomy of the Conjunctiva 61 21. Various Methods of Examination
Bakulesh Khamar, Mayuri Khamar, of the Cornea 137
Nitin Trivedi, Usha H Vyas S Basti, S Sabherwal, S Gupta
10. Clinical Manifestations of 22. Specular Microscopy 147
Conjunctival Diseases 66 M Srinivasan
Bakulesh Khamar, Mayuri Khamar, Nitin Trivedi, 23. Applications of Corneal Topography 154
Usha H Vyas Anita Panda, M Ray
xviii Modern Ophthalmology
24. Corneal Ulcer 161 42. Displacement of the Lens: Etiology

M Reddy, Savitri Sharma, GN Rao and Management 322
YR Sharma, Nikhil Pal, D Mittal, Deepender V Singh
25. Diagnostic Methods in Ocular
Microbiology 181 43. Etiopathogenesis of Senile Cataract:
Savitri Sharma Prospects of Medical Therapy 327
YR Sharma, Nikhil Pal, Kamal Kishore,
26. Keratomycosis 191 Deepender V Singh
Samar K Basak
44. Work-up for Cataract Surgery 332
27. Viral Keratitis 199 Sudha Sutaria
Anita Panda, Archana Sood, Navneet Chauhan
45. Evolution of Modern
28. Corneal Degenerations and Dystrophies 213 Intraocular Lens Surgery 335
CK Barua, LC Dutta Suresh K Pandey, Liliana Werner, David J Apple
29. Keratoconus 222 46. History of IOL 344
Bharti Lavingia, VK George Neha Charan, R Charan, H Charan
30. Peripheral Corneal Ulcers 226 47. Foldable IOLs 352

J Ram , SK Pandey Tanuj Dada, Harinder S Sethi
48. Anesthesia for Cataract Surgery 361
31. Ocular Chemical Burns 231
J Ram, SK Pandey
JS Saini, A Gupta
49. Extracapsular Cataract Extraction
32. Eye Banking 242 and IOL Implantation 367
JS Saini, SK Gupta Alpesh R Shah, Abhay R Vasavada
33. Penetrating Corneal Transplantation 252 50. Techniques of Nonphaco Small
AK Bansal, GN Rao Incision Cataract Surgery (SICS) 378
34. Current Status of Lamellar Keratoplasty 268 KPS Malik, Ruchi Goel
Anita Panda 51. Concept and Principles of Phacomachine 387
35. Evolution of Refractive Keratoplasty 276 Jagat Ram, Suresh K Pandey
LC Dutta, Nitin K Dutta
52. Removal of Subincisional Cortex in
36. Photorefractive Keratectomy Technique Small Incision Cataract Surgery 391
and Postoperative Regimen 279 Vilas A Bidaye
MS Sachdev, Namrata Sharma
53. Phacoemulsification in Difficult Situations 395
37. Laser-Assisted In Situ Keratomileusis K Ravishankar, Deepak Garg
(LASIK) 286
Dipak Bhuyan 54. Phacoemulsification for Surgeons
38. Limbal Transplantation of Stem Cells 298 in Transition 402
Anita Panda, Namrata Sharma Jagat Ram
39. Mooren’s and Ulcer 303 55. Complications of Phacoemulsification 409
M Srinivasan Mary Abraham
40. Scleritis and Episcleritis 307 56. Posterior Capsule Opacification:
JS Saini Pathogenesis, Management and Prevention 414
Jagat Ram, Gagandeep S Brar,
Section 4 Supratik Bandopadhyay
DISEASES OF THE LENS 57. Multifocal IOLs 421
Gagandeep S Brar, Jagat Ram
41. Anatomy-Histology of the
Human Crystalline Lens 315 58. Piggyback IOLs 430
Suresh K Pandey, Liliana Werner, Sushismita Kaushik, Jagat Ram,
David J Apple, Vidushi Sharma Supratik Bandopadhyay
Contents xix
59. Secondary Intraocular Lens Implantation 434 77. Lasers Applications in Glaucoma 588
G Natchiar, Deva Prasad Kar S Ramalingum
60. Scleral-Fixated PCIOL 438 78. Phacotrabeculectomy 597
Dinesh Mittal, YR Sharma R Raveendran, KM Ranganath
61. Management of Postoperative 79. Antimetabolites in Glaucoma
Endophthalmitis 442 Filtration Surgery 603
S Natarajan, B Dutta, R Ramakrishnan, Kavitha Ramakrishnan
62. Ophthalmic Viscosurgical Devices 448 80. Management of Bleb-related Problems 608
Suresh K Pandey, Jaya Thakur, Liliana Werner, Hemamalini Arvind, L Vijaya
Nick Mamalis, Vidushi Sharma, David J Apple,
81. Artificial Drainage Devices in
Aman Chandra, Girish Chandra
Glaucoma Surgery 618
63. Complications of Intraocular R Thomas, SC Gieser
Lens Implantation 464
G Natchiar, Deva Prasad Kar
VOLUME 2
Section 5
Section 6
GLAUCOMA
64. Gross and Microanatomy of the Angle of DISEASES OF ORBIT
the Anterior Chamber 468 82. Applied Anatomy of the Orbit 625
S Choudhury AK Khurana
65. Gonioscopic Appearances of 83. Investigation of Orbital Space
Normal and Pathological Conditions 473 Occupying Lesions 631
S Choudhury AK Khurana, BK Ahluwalia
66. Primary Open Angle Glaucoma 479 84. Lymphoproliferative, Leukemic and
Devindra Sood, NN Sood
Histiocytic Lesions of the Orbit 646
67. Normal Tension Glaucoma 502 Ramesh Murthy, Sanghamitra Burman,
S Choudhury Santosh G Honavar, Geeta K Vemuganti,
68. Optic Nerve Head and Retinal Milind Naik, Vijay Anand Reddy
Nerve Fiber Layer Imaging 509
B Shantha, K Krishnakumar 85. Ultrasonography-guided Fine Needle
Aspiration Cytology in Orbital Lesions 653
69. Automated Perimetry 515
Anju Rastogi, S Jain, M Kumar
B Shantha
70. Primary Angle Closure Glaucoma 522 86. Phakomatosis 660
A Neelakanthan, S Rao P Namperumalsamy, K Lakshmanamurthy,
Madhavi Hirode
71. Secondary Glaucoma 536
NK Dutta, LC Dutta 87. Orbital Involvement in Diseases
72. Malignant Glaucoma 551 of the Paranasal Sinuses 671
SK Narang AK Khurana
73. Primary Pigmentary Dispersion Syndrome 88. Metastatic Tumors to the Orbit 676
and Pigmentary Glaucoma 555 Lakshmi Mahesh, Nitin K Dutta
LC Dutta, Nitin K Dutta 89. Orbital Blow-out Fractures 682
74. Pseudoexfoliation Syndrome 561 AK Khurana
Mayuri Khamar 90. Orbital Cellulitis 689
75. Pharmacognosy and Pharmacokinetics AK Khurana
of Ocular Hypotensive Agents 566
91. Painful Ophthalmoplegia 695
R Ramakrishnan, S Puthalath
Subhra Das, LC Dutta
76. Current Trends in Drug Therapy
of POAG 578 92. Thyroid Ophthalmopathy 699
LC Dutta, NK Dutta Subhra Das, LC Dutta
xx Modern Ophthalmology
93. Anatomy, Physiology and Diseases 110. Nystagmus Surgery: Current Concepts 864
of the Lacrimal System 708 Elizabeth Joseph
AK Grover, A Bhatnagar, Sarmi Malik 111. Evaluation of Strabismus 867
94. Radiographic Study of Lacrimal Passage 726 TS Surendran, Manjula Sridhar
AS Mehrotra 112. Sensory Adaptation in
95. Lacrimal Gland Tumors 729 Concomitant Squints 879
LC Dutta, KS Ratnakar JN Rohatgi
113. Introduction to Heterophoria 886
Section 7 SK Narang, S Narang, Priya Narang
114. Esodeviations 889
PEDIATRIC OPHTHALMOLOGY Sabi Pandey
INCLUDING STRABISMUS 115. Exodeviation 898
96. Neonatal Conjunctivitis 733 Kamlesh, S Dadeya
Samrat Chatterjee 116. A and V Syndrome 901
97. Amblyopia 744 JN Rohatgi
JN Rohatgi 117. Management of Double Elevator Palsy 906
98. Nutritional Blindness: Vitamin A Kamlesh, S Dadeya
Deficiency Disorders 751 118. Vertical Strabismus 908
Samar K Basak JN Rohatgi
99. Congenital Glaucoma 759 119. Special Forms of Strabismus 912
B Sridhar Rao LC Dutta, NK Dutta
100. Glaucomas Associated with 120. Nonsurgical Treatment of Squint 920
Developmental and Congenital Anomalies 765 Kamlesh, S Dadeya
S Choudhury, S Mitra 121. Surgical Treatment of Strabismus 924
101. Childhood Cataract and Other Vinita Singh
Abnormalities of the Crystalline Lens 774
Nitin K Dutta, LC Dutta Section 8
102. Management of Infantile-Pediatric Cataract 780 NEUROOPHTHALMOLOGY
Suresh K Pandey, M Edward Wilson,
Jagat Ram, Liliana Werner, David J Apple 122. Anatomy of Visual Sensory System 943
103. Lens Subluxation and its Management 808 G Natchiar, Subhuram
Kasturi Bhattacharjee,Harsha Bhattacharjee, 123. Neuroophthalmological Evaluation 948
Pankaj Bhattacharjee LC Dutta
104. Ophthalmic Manifestations of 124. Normal and Abnormal Pupils 958
Inborn Errors of Metabolism 818 G Natchiar, Subhuram
LC Dutta 125. Chiasmal Lesions: Chiasmal Syndromes 962
105. Pediatric Orbital Space Occupying Lesions 824 LC Dutta
126. Visual Field Defects 969
106. Pediatric Posterior Uveitis 833 G Natchiar, Subhuram
V Gupta, A Gupta
127. Optic Neuritis: Optic Neuropathies
107. Retinopathy of Prematurity 838 Demyelinating Diseases 973
S Natarajan, B Dutta LC Dutta
108. Retinoblastoma 849 128. Ocular Motor Palsies 980
Ramesh Murthy, Santosh G Honavar, G Natchiar, Subhuram
Milind Naik, Vijay Anand Reddy
129. Supranuclear Disorders of the Eye
109. Infantile Nystagmus 860 Movements and Visual Integration 986
LC Dutta G Natchiar, Subhuram
Contents xxi
130. Papilledema 992 145. Color Vision and Color Blindness 1144
LC Dutta YR Sharma, Nikhil Pal, Deependra V Singh
131. Idiopathic Intracranial Hypertension 146. Indocyanine Green Angiography in
(Pseudotumor Cerebri) 997 Neovascular Age-related Macular
LC Dutta, NK Dutta Degeneration 1151
Sandeep Saxena, Tomohiro Iida
132. Abnormalities of Optic Disk and
Optic Nerve 1001 147. Low Vision Devices 1160
G Natchiar, Subhuram Sarfaraz A Khan
133. Intracranial Space Occupying Lesions of 148. Amniotic Membrane Transplantation in
Ophthalmic Importance 1004 Ophthalmic Disorders 1169
LC Dutta Anita Panda, Hrishikesh Das
149. Limbal Stem Cells of Corneal Epithelium:
Section 9 Concepts, Disease and Management 1179
MISCELLANEOUS TOPICS Himanshu P Matalia, Virender S Sangwan
134. Applied Anatomy of the Eye and Adnexa 1011 150. Miscellaneous Aspects of Conjunctiva 1192
AS Mehrotra LC Dutta, Nitin K Dutta
135. Introduction to Computed Tomography 151. Neoplasms of Conjunctiva and Cornea 1201
and Magnetic Resonance Imaging in Anita Panda
Ophthalmic Practice 1020 152. Management of Corneal Epithelial Defects 1208
N Medhi, SK Handique Anita Panda, Neelam Pushker
136. Computed Tomography and Magnetic 153. Ocular Manifestations in Tropical Diseases 1215
Resonance Imaging of the Eye and Orbit 1028 R Mukherji
SK Handique, N Medhi, B Saharia
154. Eye in Connective Tissue Disorders 1220
137. Applications of Ultrasound Biomicroscopy 1062 Jyoti S Padalay
M Baskaran, M Bhende
155. Oxidative Stress and Antioxidants in
138. Laboratory Techniques in Ophthalmic
Ophthalmology 1227
Pathology 1071
Souvik Banerjee
Geeta K Vemuganti
156. Contact Lenses 1234
139. Viscoelastic Substances in Ophthalmology 1086
RP Bhatia, LC Dutta
Anita Panda
140. Principles of Biostatistics 1092
S Krishnaiah, N Rishita, BR Shamanna
VOLUME 3
141. Genetics in Ophthalmology 1100
Chitra Kannabiran Section 10
142. Molecular Genetics in Clinical DISEASES OF THE UVEAL TRACT
Ophthalmology* 1108
B Jay, M Jay 157. Anatomy of the Uveal Tract 1249
Jyotirmay Biswas
143. Infection Control Practices for
Ophthalmologists 1121 158. Uveitis: Classification, History-Taking,
Savitri Sharma Examination and Incidence 1254
Jyotirmay Biswas
144. Acquired Immunodeficiency Syndrome
and the Eye 1127 159. Clinical Approach to a Patient with Uveitis 1261
J Biswas, A George Virender S Sangwan
xxii Modern Ophthalmology
160. Anterior Uveitis: Diagnosis Section 11

and Management 1268
Virender S Sangwan RETINA-VITREOUS
Section Editor: TP Das
161. Intermediate Uveitis: Pars Planitis 1280
Jyotirmay Biswas 179. Anatomy of Retina and Vitreous 1435
162. Posterior Uveitis 1289 B Khamar
Annie Mathai, Virender S Sangwan 180. Retinal Viewing System: The Diagnostic,
Laser and Surgical Lenses 1442
163. Common Panuveitis Entities 1303 Vinay A Shah, R Narayanan, Amol Kulkarni
Soma Sheila Murthy, Virender S Sangwan 181. Electrophysiological Tests of the Eye 1455
164. Viral and Rickettsial Uveitis 1324 Subhadra Jalali, LS Mohan Ram
Jyotirmay Biswas 182. Clinical Application of Optical
165. Ocular Toxoplasmosis 1344 Coherence Tomography 1474
Vishali Gupta, Amod Gupta Anjli Hussain, Kallukuri Sumasri,
Tara Prasad Das
166. Ciliochoroidal Detachment 1352
Jyotirmay Biswas, S Raizada 183. Fluorescein Angiography 1480
Nazimul Hussain, Anjli Hussain,
167. Presumed Ocular Tuberculosis 1356 Kallukuri Sumasri, LS Mohan Ram
184. Indocyanine Green Angiography (ICGA) 1489
168. Fuchs’ Heterochromic Uveitis 1362 Nazimul Hussain, LS Mohan Ram
Jyotirmay Biswas, S Raizada
185. Peripheral Retina, Pars Plana and
169. Serpiginous Choroiditis 1366 Vitreous Base 1496
Vishali Gupta, Amod Gupta Harsha Bhattacharjee, Satyen Deka, Jnanankar Medhi
170. Anterior Uveitis and Arthritis 1372 186. Retinal Telangiectasis 1511
Jyotirmay Biswas, A Wagle Vishali Gupta, Amod Gupta
171. Sympathetic Ophthalmia 1378 187. Age-related Macular Degeneration 1521
Vishali Gupta, A Gupta Raja Narayanan, Vinay A Shah,
Amol D Kulkarni, Paolo Lanzetta
172. Investigational Approach to Uveitis 1384 188. Endophthalmitis 1539
Jyotirmay Biswas Tara Prasad Das, Savitri Sharma, Subhadra Jalali
173. Management of Endogenous 189. Etiopathogenesis of Retinal Detachment 1552
Non-infectious Uveitis 1388 P Namperumalsamy, Madhavi G Hirode,
Virender S Sangwan D Dwarak Nath, S Lal
174. Uveal Malignant Melanoma 1397 190. Principles and Alternative Surgical
Jyotirmay Biswas Techniques for Retinal Detachment 1568
T Sharma
175. Intraocular Metastatic Tumors
191. Ocular Ischemic Syndrome and Retinal
Arterial Obstruction 1577
176. Vascular Tumors of the Choroid and Retina 1414 Subhadra Jalali, TP Das
Mahesh P Shanmugam, Surendra Shetty, 192. Retinal Venous Occlusive Diseases 1584
Sandeep Thakur Subhadra Jalali, TP Das
177. Intraocular Biopsy Techniques 1422 193. Ocular Manifestations in 1599
Ajeet Madhab Wagle, Mahesh P Shanmugam Systemic Hypertension
TP Das, R Shonek, Subhadra Jalali
178. Controversies and Preferred Treatment of
Malignant Melanoma of the Choroid 1431 194. Diabetic Retinopathy 1605
Mahesh P Shanmugam Subhadra Jalali, TP Das
Contents xxiii
195. Vitreous Hemorrhage 1624 208. Subretinal Surgery 1721
Harsha Bhattacharjee, Kasturi Bhattacharjee, S Saxena, MA Thomas
Anil Kumar Agarwal
209. Scleral Buckling: Concepts,
196. Proliferative Vitreoretinopathy 1633 Materials and Techniques 1730
Ajit Babu Majji PN Nagpal, RK Sharma, M Porwal
197. Retinitis Pigmentosa and Associated 1641 210. Pars Plana Surgery 1737
Retinal Degenerations P Namperumalsamy, Madhavi G Hirode, KL Murthy
Subhadra Jalali, LS Mohan Ram, Arivazhagan N
211. Vitreous Substitutes 1753
198. Familial Exudative Vitreoretinopathy 1650 PN Nagpal, RK Sharma, Rajshree Vadhani
Dhananjay Shukla
212. Laser Application in Retinal Disorders 1757
199. Degenerative Myopia 1656 Yog Raj Sharma, Deependra Vikram Singh
Maurizio Battaglia Parodi, Paolo Lanzetta
213. Retinoschisis 1767
200. CMV Retinitis 1668 YR Sharma, Deependra Vikram Singh
Avinash Pathengay
214. Central Serous Chorioretinopathy 1772
201. Eales’ Disease 1675
Avinash Pathengay
Subhadra Jalali, TP Das
202. Coats’ Disease 1681 215. Epiretinal Membrane 1779
Pratik Sen, Pramod S Bhende YR Sharma, Neena, D Mittal
203. Surgery for Macular Diseases 1689 216. Ocular Ischemic Syndrome 1783
Lingam Gopal Avinash Pathengay
204. Perfluorocarbon Liquids and 217. Management of Dislocated Nucleus 1788
Silicone Oil in Vitreoretinal Surgery 1701 Dhanashree Ratra
S Saxena, L Gopal
218. Laser Tissue Interactions 1793
205. Management of Giant Retinal Tears 1708 Biju Raju
Annie Mathai
219. Principles of Lasers in Retinal Diseases 1797
206. Principles and Techniques of Internal ` Biju Raju
Tamponade for Retinal Detachment 1714
NS Bhatt Appendix 1801
207. Retinotomy and Retinectomy 1719
PN Nagpal, RK Sharma, M Porwal Index 1805
SECTION 1: DISORDERS OF THE EYELIDS
Chapter 1
Anatomy of the Eyelids

DEVELOPMENT OF THE EYELIDS Lid fold or crease is a fold of overhanging skin in

upper lid and is situated about 7-8 mm from lid
Both ectodermal and endodermal tissue take part in
margin. It almost disappears on looking down and is
the development of the lid. The lid fold starts at the
accentuated in upgaze. Presence of the fold indicates
7th week of intrauterine life. The upper lid is formed
the action of levator palpebrae superioris.
from the lateral and medial aspect of the frontonasal
process and lower lid from the maxillary process. The Structure of Eyelids
margins of the two lids unite with flimsy tissue by the
Structurally, the lid can be grossly divided into two
9th week of gestation. The two lids again separate at
laminae, viz. anterior lamina containing skin and orbi-
5th month of gestation. Failure of separation results
cularis, and posterior lamina containing tarsal plate
in cryptophthalmos, incomplete or abnormal sepa-
and conjunctiva. Layer wise, it is composed of the fol-
ration results in ankyloblepharon or ankyloblepharon
lowings (Fig.1.1):
filiforme adnatum. Failure of union of the frontal and
a. Skin
maxillary processes leads to coloboma of the lower
b. Subcutaneous tissue,
lid and failure of union between lateral and medial
c. Orbicularis muscle,
frontonasal processes results in coloboma of the upper
d. Submuscular areolar tissue,
lid.
e. Fibrous layer,
Two lids are the movable folds of skin which close
f. Mucous membrane with Muller’s muscle, and
the eyes for protection and rest. The upper lid is much
g. Cilia.
more mobile, the lower lid being more or less static.
The upper eyelid extends upward up to eyebrow
whereas the lower one passes on to cheek without
much demarcation except in the presence of malar and
nasojugal folds.
Palpebral fissure is an almond shaped opening
bounded by the two lids. In an adult, the average
height and width of lids are 10 mm and 25-30 mm
respectively. Normally in straight gaze, upper lid
covers about 2 mm of upper part of cornea and cuts it
at 11 and 1 O’clock position.
Medial and lateral canthi are the angles formed at
the junctions of lids. Lateral angle is more acute than
the medial one. Medial angle lies below the lateral
canthus and so the fissure has an upward slant away
from midline. Increase in this obliquity is a mongoloid
slant whereas reduction or reversal is called an anti-
mongoloid slant. Fig. 1.1: Schematic diagram of the cut section of the upper lid
2 Section 1: Disorders of the Eyelids
Skin Skin of the lid, about the thinnest in the body, is

highly elastic with sparse hairs.
Subcutaneous areolar tissue It contains loose con-
nective tissue and no fat.
Orbicularis oculi It is a striated muscle, runs circu-
larly around palpebral fissure. A narrow strip of the
muscle near the lid margin is known as Riolan’s
muscle. The muscle is supplied by the 7th cranial nerve
and its main function is normal closure of the lids.
The adhesion of the muscle to the tarsus helps in
maintaining the shape of the lid (Lamination effect).
Submuscular areolar tissue It is a potential space Fig. 1.2: Schematic diagram of the levator aponeurosis with
in front of the tarsal plate. It is continuous above with Whitnall’s ligament
the subaponeurotic layer of the scalp and so the blood
or fluid in the space above trickles down into this
of sphenoid in front of the optic foramen by a small
plane. It contains the major nerve plexus supplying
tendon. At about 1 cm behind the orbital septum it is
sensory nerves to the lid. By entering this space at gray
converted into a vertical aponeurotic part. It inserts
line on lid margin, the two laminae of the lid can be
into many structures, i.e. (1) lower part of the front
easily separated.
and upper border of the tarsal plate, (2) skin through
Fibrous layer It consists of the orbital septum and orbicularis muscle (3) fornix through the common
the tarsal plates. The orbital septum is a curtain like tendinous sheath with superior rectus muscle, and (4)
structure initiated from the orbital rim and extended fuses with lacrimal fascia laterally and superior
up to the borders of tarsal plates. In upper lid, the oblique pulley medially. Horns of levator are the
definition is disturbed as it is massively perforated expansions at the insertion which, check the
by levator muscle, which it lines anteriorly. In movement of the muscles (Fig.1.2). The medial horn
Caucasians, it fuses with the front surface of the levator fuses with the medial palpebral ligament and the
muscle at about 10 mm above the upper border of the tendon of the superior oblique muscle whereas the
tarsal plate, but in Orientals, it comes down low lateral horn passes between the two parts of the
allowing the orbital fat to prolapse and giving the lacrimal gland. Superior transverse (Whitnall’s)
typical oriental look. In older people, the septum ligament is a fascial condensation about 14-20 mm
weakens and so pouches of fat are seen under the skin. above the upper border of the tarsal plate; it works as
Tarsal plate, one in each lid, is a fibrous structure a sling for the muscle. The muscle is supplied by the
containing sebaceous glands called the Meibomian superior division of the 3rd cranial nerve by a branch
glands. The free or ciliary border of the tarsus is which passes through superior rectus or curves round
thickened and its flanging effect, helps in the stability its lateral border to reach the muscle.
of the lid margin and supports the lid. Medial and Conjunctiva lines the back of the lid and continues
lateral ends of the tarsal plates are anchored to the to the globe forming fornices. A nonstriated muscle
bony orbit by thickened bands of fascia known as lies between the conjunctiva and the levator, called
palpebral or check ligaments. Medial palpebral liga- the Muller’s muscle supplied by the sympathetic nerve.
ment is a tough triangular structure passing through This involuntary muscle is about 20 mm long and
the medial ends of the upper and lower tarsal plates helps in elevation of the lid by about 2-3 mm.
to the anterior lacrimal crest. A posterior extension As the levator-Muller complex maintains the mobi-
from the ligament bridges across the fossa and fuses lity of the upper eyelid, capsulopalpebral ligament
with the fascia of the sac. The two limbs of the Y shaped present in the lower lid, helps in its downward
anterior portion form the medial canthus and are very retraction during downgaze (Fig 1.3). It is a conti-
close to the canaliculi. nuation of the inferior rectus muscle sheath and
Levator palpebrae superioris is about 60 mm long attaches to the lower border of tarsal plate. It has three
striated muscle running along the roof of the orbit. It components i.e. Tenon’s capsule, inferior tarsal
originates from the under surface of the lesser wing muscle, and lower lid aponeurosis. It keeps the lower
Chapter 1: Anatomy of the Eyelids 3
the plexus to supply skin and orbicularis superficially
and tarsus and conjunctiva deeply.
Main venous drainage is into ophthalmic vein, but
a small amount also drains into the veins of forehead
and temple.
Lymphatics
The lymphatics of the lids are arranged in pre and
posttarsal plexuses that communicate by cross
channels. The pretarsal group drains the dermis,
pretarsal orbicularis muscle, and adjacent structures,
and post tarsus group drains the palpabral conjunctiva
and tarsal glands. Medial side of both the lids drain
into the submandibular glands. Lateral parts empty
into the parotid and preauricular group.
Nerve Supply of the Eyelids

Fig. 1.3: Schematic diagram of the cut section of the lower lid
to show the retractors of the lower lid (capsulopalpebral Orbicularis oculi muscle is supplied by the seventh
ligament) cranial nerve (Facial nerve-supplying all the muscles
of facial expression) through its temporal and
zygomatic branches. The facial nerve divides into two
lid margin in proper position, and its weakness in old divisions—upper division temporofacial and lower
age or due to other reasons, leads to lower lid division cervico-facial (The upper division further
entropion. subdivides into the temporal and zygomatic branches
Lid margin is a 2 mm wide strip with a rounded for supply to the frontalis and orbicularis oculi muscles
anterior and square sharp posterior border. It has a respectively. The lower division subdivides to supply
row of anteriorly curving cilia at the front. Gray line the buccal and cervical muscles. Sensory supply to the
lies between the cilia in front and openings of eyelids comes from the ophthalmic and maxillary
Meibomian glands on the back. There is a zone of division of the trigeminal nerve through the
transitional epithelium behind the openings of supraorbital, supratrochlear and lacrimal branches.
Meibomian glands where keratinized epithelium of Zygomaticotemporal branch of the maxillary nerve
skin changes over to nonkeratinized stratified supplies the lateral part of the upper eyelid, brow and
epithelium of the conjunctiva. Modified sebaceous forehead and the skin over the bridge of the nose.
glands of Zeis are attached to the roots of cilia. Infratrochlear branch of the maxillary nerve carries
Cilia These are highly sensitive specialized hairs about the sensation of the lower eyelid. The zygomatico-
150 in upper lid and its half the number in lower lid. facial branch from the maxillary nerve innervates the
Unlike other hair follicles, they are devoid of piloe- skin of the lateral portion of the lower lid.
rector muscle. Glands of Moll, modified sweat glands,
communicate with roots of cilia. FURTHER READING
1. Anderson RL, Beard C. The levator aponeurosis:Attachments
Blood Supply and their clinical significance. Arch Ophthalmol 1979;95:1129-
31.
Eyelid is richly supplied by the vascular plexus formed 2. Dixon RS. The role of Whitnall’s ligament in ptosis surgery.
by marginal tarsal arcades. They are formed by lateral Arch Ophthalmol 1979;97:705-07.
palpebral branches of lacrimal artery on the temporal 3. Malone B, Maisel RH. Anatomy of the facial nerve. Am J
Otolaryngol 1988;9:144.
side and medial palpebral artery on the nasal side. 4. Mustarde JC. New horizons in eyelid reconstruction. Int
Some branches from the surrounding area also con- Ophth Clinics 1989;29:4; 237-46.
tribute to it. Upper lid has another arcade at the upper 5. Warwick R. Wolfe’s anatomy of the eye and orbit. HK Lewis
border of the tarsal plate. Branches are given off from & Co.Ltd: London, 1976.
Chapter 2
Congenital Eyelid Anomalies

This is a heterogenous group of defects, the only is to utilize the relatively excessive skin on sides to
common factor being the presence of the disease since make up for the vertical shortening. The flaps are very
birth. The conditions may be inherited, racial or spora- small; so, care has to be taken in fashioning and sutu-
dic. Amblyopia, exposure keratitis, and cosmesis are ring them so that the scarring is minimized. For proper
the three aspects to be considered while planning the mobilization of the flaps, undermining of the skin is
management of a case. For the first two conditions, to be exercised.
early treatment is mandatory, while the third can be
tackled at a later date. TELECANTHUS
EPICANTHAL FOLDS This is a bilateral condition where the medial canthal
tendons are abnormally long increasing the distance
These are the vertical curved folds of skin present over
between the two medial canthi. Normal intercanthal
the canthal area, almost always the medial canthus.
distance in an adult is about 30 mm, i.e. half of the
The folds are bilaterally symmetrical with concavity
interpupillary distance. It has to be differentiated from
laterally. In general population, it affects about 20%
hypertelorism where the two bony orbits are wide
of children and gets attenuated after the age of 2 years,
apart and the intercanthal distance is secondarily
but in oriental races it is found invariably with no
increased. This is also only a cosmetic problem and as
attenuation. They are of the following four distinct
may be frequently associated with epicanthus, a com-
configurations:
mon treatment plan is necessary.
1. Epicanthus superciliaris, where the fold arises
along the brow and runs down on the side of the Treatment
nose.
2. E. palpebralis, where the fold starts above the The ideal treatment is shortening of medial canthal
tarsus in upper lid and runs down covering the tendons by transnasal wiring. This procedure leads
medial canthus and then along the lower orbital to formation of epicanthal skin fold and so
margin. transposition of the flaps must be undertaken
3. E. tarsalis, where the fold starts over the superior simultaneously.
tarsus and involves the lower lid minimally.
4. E. inversus, where the fold originates from and pri- EPIBLEPHARON
marily involves the lower lid. Epiblepharon is a common congenital deformity in
The basic pathology is vertical shortage of skin with Asians—particularly in mongoloid population and is
relative horizontal redundancy. They do not cause any often bilaterally symmetrical. The condition is
functional problem but are of cosmetic concern. They characterized by redundancy of skin of the medial part
frequently give a false appearance of convergent of both the eyelids and the eyelashes assume a vertical
squint. orientation. Usually in the process of post natal
development the condition resolves spontaneously in
Treatment the first few years of life. The important clinical interest
Different surgical procedures have been described by of this condition is that the parents frequently are
Spaeth, Blair, and others, the basic principle of which worried about the watering from the eyes of the new
Chapter 2: Congenital Eyelid Anomalies 5
born due to irritation by the misdirected eye lashes.
Surgical intervention, if necessary, consists of excision
of the redundant skin along with the adjacent
orbicularis muscle fibers.
BLEPHAROPHIMOSIS
Per se, this is a condition where the horizontal and
vertical size of the palpebral fissure is reduced leading
to its narrowness. But it is almost always associated
with other anomalies of lids and face giving rise to
blepharophimosis syndrome (Fig. 2.1). The
constituting features are blepharophimosis, moderate Fig. 2.2: Schematic diagram of the Mustarde’s operation for
to severe ptosis, telecanthus, epicanthus inversus, epicanthus-telecanthus
lower lid ectropion, and rarely hypertelorism. The con-
dition is autosomal dominant and gives a mongoloid of the lower punctum, strabismus and telecanthus.
contour to the face. Treatment is canthoplasty.
COLOBOMA OF LID
These are the full-thickness lid margin defects due to
absence of fusion between two growing edges during
development. They may be associated with other
ocular anomalies like corneal opacities, dermoid cysts,
limbal dermoids, iris coloboma, and conical cornea.
There are two associated syndromes (Fig. 2.3):
1. Goldenhar’s syndrome, where the upper lid colo-
boma of variable degree, mostly at the junction of
medial and middle thirds, is associated with limbal
Fig. 2.1: Blepharophimosis syndrome dermoid and dermolipoma of orbit (Fig. 2.4); sys-
temically the patient may have extra-auricular
Treatment appendages and anomalies of vertebral column.
Ptosis part is tackled by the general principles of ptosis 2. Treacher Collins syndrome, where the lower lid
correction. Epicanthus-telecanthus part is managed by colobomas are associated with hypolasia of the
a classical procedure described by Mustarde (Fig. 2.2) malar bones (Fig. 2.5).
in which multiple skin flaps are transposed. Skin
grafting is necessary for the lower lid ectropion.
Hypertelorism is difficult to manage and requires an
extensive surgery in collaboration with plastic
surgeons and neurosurgeons.
EURYBLEPHARON
Euryblepharon is characterized by congenital
symmetrical enlargement of the horizontal palpebral
fissure, downward and anterior displacement of the
lateral canthus and ectropion of the lateral third of
the lid. Euryblepharon may be present as an isolated
anomaly or may be associated with any one of a group
of congenital anomalies which include blepharoptosis,
double row of meibomian glands, lateral displacement FIg. 2.3: Colobomatous defect in the upper lid
ANKYLOBLEPHARON
Variable portions of the two lids are joined together
reducing the horizontal width of the palpebral fissure.
Sometimes the union can be in the form of few strands
and the condition is termed ankyloblepharon filiforme
adnatum.3 Adhesions on the lateral side are without
major consequences and can be corrected by lateral
canthoplasty. The adhesions on the medial side require
extensive surgery as the lacrimal drainage apparatus
is also affected.
Other congenital conditions include ptosis, entro-
pion, ectropion, epiblepharon, and distichiasis which
are described later.
CRYPTOPHTHALMOS
This is an extremely rare anomalous developmental
Fig. 2.4: Goldenhar’s syndrome showing lid coloboma condition which is due to failure of separation of the
and limbal dermoid lids during the 4th to 6th week of intrauterine life. The
lid folds are absent, instead a continuous sheet of skin
extends from the eyebrows over the eyes to the cheeks.
It may be associated with syndactyly 1 and renal
agenesis2. Waring and Shields3 describe a case of
partial cryptophthalmos associated with syndactyly,
brachycephaly and renal anomalies. The eye ball may
be externally normal in all aspects except that the
cornea becomes completely opaque and the
conjunctival sac is filled with a brownish white fluid.
The orbicularis oculi muscle is well developed but the
tarsal plates are not formed. As anterior segment
agenesis is the rule, virtually there is no treatment for
restoration of vision.4 - 7
REFERENCES
Fig. 2.5: Treacher Collins syndrome showing both 1. Poswillo D. Pathogenesis of craniiofacial syndromes
lower eyelid colobomas exhibiting colobomas. Trans Ophthalmol Soc UK 1976;96,69.
2. Roper-Hall MJ. Congenital coloboma of the lids. Trans
Treatment Ophthalmol Soc UK 1964;88, 557.
3. Akkermang CH, Stern LM. Ankyloblepharon filiforme
Small defects may be left alone or may be closed by adnatum. Br J Ophthalmol 1979;63:129.
direct suturing, but bigger defects require prompt 4. Waring GO, Shields JA. Partial unilateral cryptophthalmos
syndrome with syndactyly and renal anomalies. AJO
treatment as they commonly lead to exposure keratitis 1975;79:437.
and amblyopia. In larger defects, Tanzel semicircular 5. Brazier DJ, Hard man IS, Collins JR. Cryptophthalmos.
rotation flaps may be used. In severe cases, Cutler- Surgical treatment of congenital smyblepharon variants. Br J
Beard technique or switch rotation flap utilizing full Ophthalmol 1986;70,391.
thickness of lower lid is necessary. In the cases of lower 6. Codere F, Brownstein S, Chen MF. Cryptophthalmos
syndrome with bilateral agenesis. Am J Ophthalmol
lid defects, Hughe’s procedure is useful. Hypoplasia 1981;91,737.
of the malar bones is corrected by implanting bone 7. Sugar HS. The cryptophthalmos—snydactyly syndrome AJO
graft or silastic material. 1968;66,897.
Chapter 3
Anomalies of the Eyelid

Margin and Cilia
TRICHIASIS 4. Laser Lasers of different types are also used with

good results.
Misdirected lashes when turned inside, produce
5. Surgery It aims at anterior separation of the ciliary
irritation of cornea and conjunctiva leading to water-
border by dividing the lid at the gray line and
ing, redness, foreign body sensation, and if persistent
inserting some coverage with skin, or mucous
for some time, corneal abrasion, ulceration, and
membrane preferably from oral cavity (Fig. 3.1).
opacification. Cilium which falls down due to condi-
tion of lid inflammation like stye, blepharitis,
trachoma, conjunctivitis or injury due to mechanical,
thermal or chemical trauma, does not grow back in
the normal position, as fibrosis accompanies the
healing process. In case of trachoma, there is a necrosis
and softening of the tarsal plate which contributes to
the inturning of lashes.
Treatment
It varies according to the number of lashes involved.
1. Epilation Mechanical removal is useful in cases of
isolated cilia. But recurrence is almost always
present.
2. Electrolysis A current of 5 mA is passed through a
fine needle into the root of the affected cilium after Fig. 3.1: Mucous membrane grafting at the gray line for trichiasis
anesthetizing the lid margin. Nascent hydrogen is
liberated in the form of froth which loosens the
DISTICHIASIS
cilium which is easily plucked out with an epilation
forceps. Here is fibrosis in the root of the cilium In this congenital condition, a second posteriorly
preventing its regrowth. positioned row of eyelashes emerge from meibomian
3. Cryotherapy It is a newer procedure and requires gland orifices. They can be present in both the lids. It
a specialized probe. Temperature of upto –20oC may be asymptomatic if the cilia are fine and then no
using freeze-thaw-freeze technique is effective in treatment is necessary. If symptomatic, early treatment
cases of isolated lashes. Depigmentation is is necessary to prevent scarring and vascularization
common but temporary. of cornea. In cases of few lashes, electrolysis can be
done. When more lashes are present, 2 mm wide hori-

zontal strip of the tarsal plate containing the
distichiasis lash follicles is removed and a graft of oral
mucosa is put to fill up the gap (Figs 3.2 A and B)1.
Alternatively, after separating the posterior
distichiasis strip from the anterior row surgically at
the gray line, the posterior lip is subjected to full
thickness cryoapplication.
ENTROPION
It is an inturning of the eyelid margin and is perhaps
the commonest lid anomaly an ophthalmologist faces.
It is most commonly seen in the lower lid. It has to be
differentiated from trichiasis where the individual cilia Fig. 3.3: Both eye lower lid congenital entropion
are directed backward. Etiologically, it can be classi-
fied into congenital, senile or involutional, cicatricial, margin in. Exact etiology is not known but it may be
acute spastic, and mechanical. due to hypertrophy of the marginal portion of
orbicularis, absence or weak tarsal plate or weak
Congenital Entropion retractors of the lower lid. If symptomatic, minimal
resection of skin, and orbicularis can be carried out or
Condition is seen in the lower lids in infants (Fig. 3.3). minimal tucking of the orbital septum is sufficient.
As the cilia are soft and short, they hardly ever
produce any symptom. It may be associated with Senile (Involutional/Atonic) Entropion
epiblepharon in which a fold of skin pushes the ciliary
By definition, this develops in the lower lid in old age
due to senile and degenerative changes in the different
tissues of the lid (Fig. 3.4). Stretching, dehiscence or
disinsertion of the lower lid retractors is of prime
importance in the development of involutional
entropion as it allows the anterior rotation of the lower
tarsal border and turning in of the lid margin2. There
is also a horizontal laxity of the whole lid, more
marked at the canthi, due to the lengthening of the
medial and lateral palpebral ligaments. Another
contributing factor is the upward gliding of the
peripheral pretarsal fibers of the orbicularis oculi
which normally remain adherent to the orbital septum
at the lower border of the tarsal plate. Relative
anophthalmos due to loss of orbital fat leads to loss of
posterior support and enhances the effect of inward
rotation of the lower lid margin.
Spastic Entropion
It develops due to ocular irritation resulting from any
corneal or conjunctival pathology.12 Removal of the
cause or anesthetizing the ocular surface alleviates the
condition and helps in differentiating it from the senile
Figs 3.2A and B: Mucous membrane grafting for distichiasis. entropion. However, spastic entropion may eventually
(A) Separation of the posterior row. (B) Suturing of the graft in stretch the inferior retractors predisposing the patient
the defect to develop senile entropion.
Chapter 3: Anomalies of the Eyelid Margin and Cilia 9
Fig. 3.4: Senile entropion
Treatment
Before undertaking any surgical procedure, it is advis-
able to examine the patient to pinpoint the area of
weakness.
a. Pinch test If the lower lid can be pulled out by more
than 1 cm, it indicates generalized lid laxity. It also
differentiates the condition from cicatricial
entropion.
b. Snap test When pulled out and released, if the
lower lid takes sometime to go back to touch the
globe, indicates tissue laxity.
c. Medial canthal tendon laxity It can be tested by
pulling the lid outward. Normally the punctum
does not go beyond the limbus.
d. Lateral canthal tendon laxity It is gauged by pulling
the lid medially. The lateral canthus does not move Figs 3.5 A and B: Lower lid retractors’ tucking for senile
entropion. (A) Front view. (B) Cut section
from its position in normal circumstances.
e. Conjunctival examination A white line may be seen
in the fornix, or orbicularis is visible under the
c. Orbital septum is incised horizontally to expose
conjunctiva, due to disinsertion or dehiscence of
the lower lid retractors which are identified by the
the retractors of the lower lid.
presence of orbital fat in its front.
The surgical procedures can be divided into four
d. Tucking is effected by 3-4 sutures vertically passing
categories, viz., 1. Shortening or reattachment of lower
first through the lower border of the tarsal plate
lid retractors (Lester Jones Procedure); 2. Horizontal
and then through the retractors about 3-4 mm
shortening of the lid; 3. Horizontal shortening and
below.
fixing the orbicularis to the lower tarsal border; 4.
Instead of isolating the retractors and plicating
Creation of scar barrier between the pretarsal and
them, deep stitches may be taken through the orbi-
preseptal orbicularis to prevent overriding.3
tal septum which practically brings about the same
effect.
Lower Lid Retractor Tucking4 (Figs 3.5A and B)
e. All the stitches are tied together and care is taken
a. A paramarginal incision is made, about 2-3 mm not to overcorrect.
below the lash line, cutting the skin and orbicularis. f. Skin incision is closed separately. Alternatively, the
The incision should not extend medially up to the skin incision is closed along with the plication in a
punctum to prevent its eversion and ectropion. single bite. A barrier suture which prevents the
b. Skin-muscle lamina is undermined to identify the upward sliding of the marginal fibers of orbitcu-
orbital septum. laris, minimizes the chances of recurrence.
Full Thickness Horizontal Shortening of the Lid

In case of extreme laxity of the whole lower lid, a full
thickness resection is carried out at the lateral canthus.
Lid Bracing Sutures (Snellen-Quickerdt)

In debilitating old patients, 3 sutures are passed
through the lid from skin side, out on the conjunctival
side and back to the skin and tied to produce the
desired effect. One needle of a double arm 4-0 silk is
passed vertically deep in the lower fornix through the
conjunctiva and lower lid retractors below and then
anterior to tarsal plate to come out on the skin about
3 mm below the margin. The second is passed along
the same plane about 3 mm apart. When tied, these
sutures bring about the desired eversion of the lid
margin.
Modified Wheeler’s Procedure

(Orbicularis Bracing)
After cutting it in the center, the two flaps of the orbi-
cularis muscle are overlapped and sutured to the
lower border of the tarsal plate (Figs 3.6A and B). A
triangular piece of tarsus base down is resected
separate from the conjunctiva. This procedure may
be combined with lower lid retractor tucking.6, 11
Cicatricial Entropion
Cicatricial entropion is due to contracture of
conjunctiva due to fibrosis. It occurs as a result of
Figs 3.6 A and B: Schematic diagram of modified Wheeler’s
inflammation followed by fibrosis of the conjunctiva
procedure. (A) Resection of the tarsal plate and the orbicularis.
and tarsus, which may be shortened or become boat (B) Bracing of the muscle and fixing it at the lower border of the
shaped with concavity inwards. Trachoma, chemical tarsal plate
burns, pemphigus and Steven-Johnson’s syndrome are
common causes of cicatricial entropion. Trichiasis
Treatment
leads to vascularization with complete corneal opacity
which causes blindness. Damage of the cornea due to 1. Tarsal wedge resection When the upper lid tarsus is
trichiasis may be avoided by wearing contact lens. thickened and bent posteriorly to create posterior
When the inturned eyelashes are few in number, they laminar shortening, resection of a horizontal ante-
may be epilated with cilia forceps but this has got to rior wedge of the tarsus is useful (Figs 3.8A and B).
be repeated every few weeks. By electrolysis the hair a. A skin incision is put along the whole length of
follicles may be destroyed and recurrence minimized. the lid in the crease. Tarsus is exposed by blunt
In electrolysis operation a cathode needle is inserted dissection to just above the lash buds.
into the hair root and the follicle is destroyed by b. By sharp lamellar dissection, a 4 mm wide hori-
applying a current of 2 milliamps for a few seconds. zontal wedge of tarsal plate is excised with a
The eye lash is then just picked up with a forceps. knife. Care is taken not to go through and
However many of the eye lashes will grow again and through to perforate the conjunctiva.
the procedure may damage the root of the adjacent c. The tarsal wedge gaping is closed by passing
normal eye lash follicles causing those lashes to be double arm sutures from first the upper and
misdirected. (Fig. 3.7). then the lower edge, and then taking out the
Fig. 3.7: Cicatricial entropion of the upper lid with

retention cyst in the conjunctiva
needles at the lid margin or just above the cilia.

The knots are tied.
d. Skin incision is usually closed separately, but
may be sutured along with first set of stitches.
e. As an adjunctive measure, the lid margin can
be separated at the gray line to enhance the
effect of rotation. Sutures taken out at the ciliary
border can be kept long and pulled over a gauze
or a cotton swab to be fixed to the forehead to
achieve extrarotation.
2. Weiss procedure This procedure, with its modifica-
tion, is commonly employed to correct cicatricial Figs 3.8A and B: Tarsal wedge resection.
entropion in either lid. Transverse blepharotomy (A) Front view. (B) Side view
with marginal rotation is done.
a. A full length incision is put 3 mm below the lid
margin, piercing the skin and orbicularis.
b. Another such incision is put on the conjunctival 3. Posterior lamellar grafting For severe cicatricial
side through the tarsal plate so that a through entropion with marked contracture of tarsus and
and through gap is produced. conjunctiva, a graft must be placed in the conjunc-
c. Incision is extended with scissors on sides if tival surface to lengthen the posterior lamina. The
some tissue is left uncut. material most commonly and conveniently used
d. Three to 4 double armed sutures are passed is a piece of preserved sclera. But buccal mucosa,
through the conjunctiva and tarsus, 1 mm from bulbar conjunctiva, nasal or auricular cartilage has
the cut edge of the proximal segment and been used by different surgeons (Figs 3.9A and B).
coming out on the anterior tarsal surface. a. An incision is put on the conjunctiva, about 5
e. The sutures are then passed subcutaneously in mm above the posterior lid margin.
the distal segment and the needles brought out b. It is deepened to cut through the tarsal plate.
on the skin about 3 mm below the lash line. c. Fibers of levator exposed are separated to make
f. The sutures are then tied and the tension is room to accommodate the graft.
adjusted to place the lid into a position of mild d. The graft is fashioned and placed in the space.
eversion. e. It is fixed by the stitches passed from the skin
g. The sutures are removed after 10 to 14 days. side. Care is taken to keep the sutures under
ECTROPION
It is an outward turning of the eyelid margin. As the
lid falls away from the globe, drainage of the lacrimal
fluid is disrupted. As the capillary action can not be
maintained and the punctum, which is not in the lacus
lacrimalis, is unable to pass the tears into the
canaliculus. Hence the main complaint of the patient
is persistent watering which is made worse if the
condition is not corrected early. In long standing cases,
there are changes of scarring of the skin due to
dermatitis caused by tears, which results into
cicatricial ectropion. There is keratinization and
thickening of exposed conjunctiva and hence
repositioning of the lid becomes impossible even with
surgical correction.
Etiologically, it can be classified into congenital,
senile or involutional, paralytic, cicatricial, and
mechanical.
Congenital Ectropion
It is a rare condition mostly of the lower lid due either
shortening or lengthening of the skin. The shortening
can be associated with some other congenital
anomalies like blepharophimosis syndrome and
strabismus fixus. Temporary intermarginal stitches
may help to correct the condition of the upper lid. For
lower lid, skin grafting is necessary. For lengthening
of skin, surgeries as described in the senile group, can
be performed.
Senile or Involutional Ectropion

The canthal tendons and the lid tissues are lax as in
the case of the senile entropion but here the posterior
support by the globe is good and that forces the lid
out (Fig. 3.10). Besides, there is a factor of gravity
working exclusively in the lower lid. Clinically it can
be graded into four stages:
1. There is a minimal falling apart of the punctum,
which become more evident in the up gaze.
2. There is a minimal falling apart of the whole lid
margin.
Figs 3.9A and B: Posterior scleral grafting for severe cicatricial 3. The tarsal conjunctiva is exposed.
entropion. (A) Making a space for the graft. (B) Suturing the
4. The whole lid is everted with exposure of lower
graft in place
fornix.
the surface so that they do not come out and Treatment
rub against the cornea.
f. When sclera is used, it will get epithelized from As in the case of involutional entropion, examination
the surrounding conjunctiva in 4 to 6 weeks. of the patient to determine the individual tissue laxity
Fig. 3.10: Senile ectropion

Fig. 3.11: Tarsoconjunctival resection
is important. Examination of the lid in supine position
should be carried out as the lid may assume a more
normal position in this posture.
1. Minimal cauterization Minimal cauterization of the
conjunctiva just below the punctum with heat
cautery or diathermy gives good results in early
cases.
2. Tarsoconjunctival resection For minimal eversion of
the punctum, a diamond shaped area of the
conjunctiva and partial thickness of tarsus below
the punctum are resected. The defect is closed with
absorbable sutures to effect the inversion of the
punctum (Fig. 3.11).
3. Lazy ‘T’ procedure In cases of punctum eversion
with falling apart of the lid margin, a diamond
shaped resection of tarsoconjunctiva can be com-
bined with horizontal full thickness shortening of
the lid at medial and lateral to the punctum. A
vertical pentagonal excision is done and the ends
are sutured (Fig. 3.12).
4. Modified Kuhnt-Szymanowski procedure For mode-
rate degrees of ectropion, shortening of the two
laminae of the lid is carried out separately (Fig.
3.13).
a. A paramarginal skin incision, starting short of Fig. 3.12: Lazy ‘T’ procedure
the punctum medially, extends up to the lateral
canthus and then goes down for 1 cm.
b. Skin muscle flap is undermined.
c. A triangular piece of tarsoconjunctiva is
resected and the defect repaired by standard
technique.
d. The skin is pulled temporally to determine the
amount of redundant skin to be excised.
e. Incision is then closed by interrupted nonabsor-
bable sutures.
5. Full thickness lid resection As for the entropion, a Fig. 3.13: Modified Kuhnt Szymanowski
full thickness resection can be carried out at the procedure
lateral canthus in cases of severe lid lengthening.

An overcorrection is aimed at to prevent
recurrence.
Paralytic Ectropion
This condition is due to the paralysis of the facial nerve
which may result from injury, tumor or more
commonly from inflammation (Fig. 3.14). It may be
aggravated by laxity of tarsoligamentous sling. It is
more striking in older patients. Wiping of tears in
downward direction and secondary changes in the
skin due to running down of tears accentuate the
Fig. 3.14: Left side facial palsy leading to
condition. In acute stage no active treatment is lower lid ectropion
required except for protection of cornea. If exposure
keratitis develops, a temporary tarsorrhaphy is useful.
If recovery is slow, a permanent canthoplasty is
necessary. Dynamic function can be achieved by
encircling the palpebral fissure with silicone rod,
fascialata or temporalis muscle-fascia slips.
When upper lid lag is severe, gold ballasts can be
implanted to increase the weight of the upper lid and
close it by creating mechanical ptosis. Lower lid can
be lifted up by combining lateral canthal sling surgery
with medial canthoplasty. A lateral canthal sling
shortens the lid and raises the lateral canthus. Lower
limb of the lateral canthal ligament is cut (Fig. 3.15A).
The lid is shortened and a new lateral canthus is
created out of tarsal plate. A buttonhole is created in
the intact upper limb of the lateral canthal tendon (Fig.
3.15B) to hold the lid posteriorly against the globe.
This is achieved by suturing the newly created lateral
canthal sling to the lateral orbital rim at a higher level. Figs 3.15A and B: Lateral canthal sling
This also improves tear drainage by gravity. Medial
canthoplasty is performed joining the margins of the
two lids medial to the puncta. Canalicular damage is
prevented by putting lacrimal probes inside the two
canaliculi (Figs 3.16A and B).
Cicatricial Ectropion
This condition may result from thermal or chemical
burns or mechanical injuries to the facial area affecting
the lids. It may affect both the upper and lower lid
skin. Osteomyelitis of bones of orbital margin produ-
cing a sinus frequently pulls the eye lid by a fibrous
band extending from the skin around the sinus.
Partial thickness injuries of the lid are associated
with vertical shortening of the tissues in the outer
layers of the lid. In full thickness injury contraction of
entire lid tends to form notching of the lid margin. Figs 3.16A and B: Medial tarsorrhaphy
Surgical correction for cicatricial entropin should
not be endeavoured before at least six months of the
injury; the shortened skin and fibrotic tissue should
be released undermining sharp dissection and the
vertical fibrous band can be excised. Accurate
assessment of what is necessary is to be made after
this preliminary dissection. In severe cases after
freeing the tissue and removing the scar, skin grafting
may be necessary.
1. V-Y operation For minimal localized scarring, exci-
sion of the scar and suturing back in Y fashion cures
the condition (Figs 3.17A and B).
2. Z-plasty A localized band of scarring can produce
ectropion. This can be corrected by doing trans-
position of the skin flaps changing the direction of
the scar from vertical to horizontal direction.
Multiple Z-plasties can be done if the scar is large.
3. Skin grafting (Figs 3.18A and B) When there is a Figs 3.17A and B: V-Y operation. (A) V-shaped incision to
more extensive scarring, release of the scar with release the traction. (B) Suturing of the skin edges to give a Y-
skin grafting is the only alternative. Contractures shaped closure
are totally released by excising the scar and under- the supraclavicular area or from the medial side
mining the surrounding skin. The raw area is then of the arm. Lid with the graft must be put on trac-
covered by free skin grafts taken from convenient tion by a lid stitch or preferably by tarsorrhaphy.
site. Graft size should be 15 to 25% larger than the Graft is sutured with 6-0 silk and the ends are cut
defect to allow for the contraction. For upper lid a long. A gauze or tulle is put on the graft and the
split thickness skin graft, or a full thickness skin long ends are tied over them to compress the
graft taken from the opposite upper lid can be underlying graft. Sutures and stent are removed
utilized so that the movement is possible. For lower carefully after 8-10 days. Shrinkage of the graft can
lid, a full thickness graft is preferably taken from occur up to 4 weeks postoperatively, so tarsor-
the postauricular area but it can also be taken from rhaphy should be opened after that.
Figs 3.18A and B: Full thickness free skin grafting for excessive scarring
Mechanical Ectropion 5. Hornblass A, Hanig CJ. Oculoplastic, Orbital, and Reconstruc-

tive Surgery, Vol.1, Williams and Wilkins, Baltimore, 1990.
The underlying problem is eliminated by excision of 6. Jones LT. The anatomy of the lower eye lid and its relation to
the mass or treating the edema. the cause and cure of entropion. Am J Ophthalmol 1960;49:29.
7. Quickert MH, Rathbun E. Suture repair of entropion. Arch
Ophthalmol 1976;94:1149.
FURTHER READING
8. Smith B. The Lazy-T correction of ectropion of lower
1. Anderson RL, Harvey JT. Lid splitting and posterior lamellar punctum. Arch Ophthalmol 1976;94:1149.
cryosurgery for congenital and acquired distichiasis. Arch 9. Smith BC, Della Rocca RC. Ophthalmic Plastic and Recon-
Ophthalmol 1981;99:631-36. structive Surgery. The CV Mosby Co. St. Louise Vol.1, 1987.
2. Dalgleish R, Smith JLS. Mechanics and histology of senile 10. Tanzel RR, Miller GR, Rubenzik R. Cicatricial upper lid
entropion. Br J Ophthalmol 1966;50:79. entropion treated with banked scleral graft. Arch Ophthalmol
3. Fein W. Surgical repair for distichiasis, trichiasis, and entro- 1975;93:999-1010.
pion. Arch Ophthalmol 1976;94:809-81. 11. White JH. Correction of distichiasis by tarsal resection and
4. Hargiss JL. Inferior aponeurosis tucking revisited. Ophthal- mucous membrane grafting. Am J Ophth 1975;80:507-51.
mology 1980;87:1001-04. 12. Wies FA. Spastic entropion. Trans Am Acad Ophthalmol
Otolaryng 1955;59:503-05.
Chapter 4
Blepharitis and Meibomian

Gland Dysfunction
Samrat Chatterjee, Nibaran Gangopadhyay
INTRODUCTION Table 4.1: Classification schemes of blepharitis

Blepharitis is a generalized term that refers to Author Classification
inflammation of the eyelid margins and associated Fuchs, 1908 2
• Blepharitis squamosa
eyelash follicles, apocrine and meibomian glands. It Small, dry scales
can be broadly categorized into staphylococcal • Blepharitis ulcerosa
blepharitis affecting the anterior eyelid margin and Marginal crusting, frank ulcers and
meibomian gland dysfunction (MGD) affecting the microabscesses
posterior eyelid margin. 1 Blepharitis also causes Gifford, 19213 • Simple hypersecretion
secondary changes in the ocular surface including the Semi-solid white waxy material with
minimal symptoms
tear film. Despite being commonly present, it is often • Simple chronic meibomitis
overlooked in daily ophthalmic practice. There exists Yellowish/whitish cloudy secretion
many lacunae in our understanding of the patho- with inflammation
genesis, which coupled with a chronic waxing and • Chronic meibomitis with hyper-
waning disease course and poor patient compliance trophy
due to a protracted treatment regimen, make them a More advanced than Group 2 with
group of disorders frustrating to both patient and distended meibomian glands
• Chronic meibomitis with chalazia
physician.
• Chronic meibomitis secondary to
various chronic conjunctivitis like
CLASSIFICATION trachoma
• Chronic meibomitis with
Fuchs’ and Gifford’s classification of blepharitis and
concretions
MGD were the foundations on which further works Thygeson, 19464 • Seborrheic blepharitis
were based (Table 4.1).2,3 Thygeson emphasized the • Staphylococcal blepharitis
role of staphylococci in causation. He classified • Blepharitis due to H duplex (Morax-
blepharitis into three types: staphylococcal, seborrheic axenfeld diplobacillus)
and diplobacillary.4 He reported a large number of McCulley,19825 • Staphylococcal:
patients who had mixed features of staphylococcal and Anterior blepharitis with collarettes
seborrheic blepharitis and also observed the presence and crusting
• Seborrheic:
of underlying meibomitis in those cases of Anterior blepharitis with greasy
staphylococcal blepharitis that were resistant to scales and crusting
conventional treatment. This was corroborated by • Mixed staphylococcal and Sebor-
other studies and the classification gained widespread rheic
acceptance. However today the exact role of Contd...
Contd... respectively, which is simple and practical. Though

Author Classification several other useful and elaborate classifications have
been presented 6,7 none have gained universal
Features of both the above two acceptance.
categories
• Seborrheic with primary meibomian
seborrhea: Anterior Blepharitis
Pure meibomian gland It includes staphylococcal blepharitis, seborrheic
hypersecretion
blepharitis and mixed staphylococcal/seborrheic
• Seborrheic with secondary
meibomitis: blepharitis. The etiopathogenesis of staphylococcal
Patchy occluded and inflamed glands blepharitis though partly understood, probably
• Primary Meibomitis: involves bacterial colonization of the eyelids, effect of
Diffuse obstruction of meibomian its toxins and an immunological response of the host.
glands Other factors implicated in causation of blepharitis are
• Others uncorrected refractive error, allergy to various
Atopy, psoriasis, fungi
substance, vitamin deficiency, endocrine disturbances
Mathers, 19916 • Seborrheic MGD:
Low osmolarity and gland dropout,
and hereditary predisposition.4
normal Schirmer’s test, and increased
secretion Pathogenesis
• Obstructive MGD:
High osmolarity and gland dropout,
Historically S. aureus has been considered the single
normal Schirmer’s test, and reduced most important etiologic factor in blepharitis. 4
secretion Staphylococci colonizes the eyelids, skin, nasopharyn-
• Obstructive with sicca: geal passages and gastrointestinal tract.8-10 More recent
High osmolarity and gland dropout, studies have shown that staphylococci are not
low Schirmer’s test and minimal associated with all cases of blepharitis. McCulley et al
secretion were able to isolate significant number of S. aureus
• Sicca:
from only staphylococcal and mixed staphylococcal/
High osmolarity , low gland dropout,
low Schirmer’s and normal secretion seborrheic group (Table 4.1), while the organisms
Bron, 19917 • Absence/deficiency of meibomian more commonly isolated from the other groups were
glands S. epidermidis, P. acnes and Corynebacterium spp 5,11 In
Congenital absence or secondary to another study the organisms more commonly isolated
lid diseases were S. epidermidis (96%), P. acnes (93%),
• Replacement of meibomian glands Corynebacterium spp. (77%), Acinetobacter spp. (11%)
Primary and secondary distichiasis
and S. aureus (10%). 12 The frequently reported
• Meibomian Seborrhea
• Meibomitis
staphylococcal isolates in many studies probably
• Meibomian neoplasia represent a commensal organism rather than a
Wilhelmus, 19921 • Anterior blepharitis Anterior to the pathogenic one.13 S. epidermidis and P. acnes have been
gray line: Staphylococcal isolated together in significantly higher proportion of
• Posterior blepharitis Posterior to the blepharitis patients, suggesting that P. acnes may play
gray line: Meibomian gland dys- an adjuvant role by promoting hypersensitivity to
function S. epidermidis. 12
Staphylococcus blepharitis is probably mediated
staphylococci in various types of the disease is less by the bacterial toxins 14,15 or a hypersensitivity
certain. McCulley, et al suggested an expanded response to its antigens.16-20 Though a number of
classification that included both anterior and posterior toxins like alpha-lysin, beta-lysin, delta-lysin and a
blepharitis as a spectrum of changes affecting the dermonecrotic toxin have been detected from
eyelids.5 Based on the anatomic delineation in relation staphylococcal isolates none were conclusively shown
to the gray line and specific clinical features, to cause blepharitis. 21 Lipases, a group of enzymes
Wilhelmus classified blepharitis into anterior and present in S. aureus, S. epidermidis and P. acnes can
posterior, representing staphylococcal and MGD predispose the host to the disease. 5,22
Chapter 4: Blepharitis and Meibomian Gland Dysfunction 19
Many clinical manifestations of blepharitis could thickened eyelid margin).1 In seborrhea, scurf, foam,
be due to cell-mediated immunity manifesting as and loose greasy scales are present (Fig. 4.2). Other
delayed hypersensitivity reaction to staphylococcal associated features are folliculitis, hordeolum, dry eye,
antigens. 16-20 The hypersensitivity is to peptidoglycan, and angular blepharitis.8
ribitol- teichoic acid and protein A which are antigens
present in the bacterial cell wall.17 Of these, ribitol-
teichoic acid was demonstrated to be the major
antigenic determinant.18
Clinical Features
Blepharitis is a chronic disease that may begin early
in life and often persist with frequent waxing and
waning phases.8 It may be asymptomatic or present
with red itchy eyes, the itching characteristically
around the eyelid margins. There is associated
burning, irritation, matting of eyelashes, which are
typically worse in the morning and accompanied often Fig. 4.1: Staphylococcal blepharitis with severely inflamed
with watering and photophobia. Many persons eyelid margins and collarettes
complain of vague discomfort and soreness that is
often attributed to asthenopia.
Clinically the disease is differentiated into
staphylococcal or seborrheic (Table 4.2), though both
the conditions may co-exist. The characteristic features
(Table 4.3) of staphylococcal blepharitis are hard,
brittle, fibrinous crusting scales that surround
individual eyelash and are called collarettes (Fig. 4.1).8
The crusts when removed leaves behind bleeding
ulcerated areas. The eyelid margins are inflamed with
erythema and dilated blood vessels (rosettes). The
eyelashes are matted and often the collarettes formed
at the base of the eyelashes are carried forward as the
eyelashes grow. 23 Chronic inflammation leads to
permanent changes like trichiasis, poliosis (white Fig. 4.2: Seborrheic blepharitis with small, dry, greasy scales
lashes), madarosis (lash loss) and tylosis (irregular and mild inflammation
Table 4.2: Differentiating features of staphylococcal and seborrheic blepharitis4

Features Staphylococcal blepharitis Seborrheic blepharitis
Ulceration of lid margins Often present Absent
Presence of Seborrhea Uncommon Always
Laterality Unilateral/bilateral Bilateral
Symptoms Burning, itching, photophobia Minimal symptoms
Scales Small, hard, tenacious Flaky, greasy and easily removable
Recurrent stye and chalazion Commonly associated Absent
Associated skin conditions Otitis externa, impetigo, acne Seborrheic dermatitis
Conjunctivitis Always present Minimal
Keratitis Common Minimal
Polymorphonuclear leucocytes Present Absent
Table 4.3: Signs of anterior blepharitis

Lids
• Colarettes
• Rosettes
• Ulcerations
• Hyperemia
• Trichiasis
• Poliosis
• Madarosis
• Tylosis
• Scurf, foam or greasy scales
• Folliculitis, external and internal hordeolum Fig. 4.3: Staphylococcal blepharitis with severely inflamed
ulcerated eyelid margins, collarettes and marginal keratitis
Conjunctiva
• Hyperemia
• Papillary conjunctivitis healing. The residual corneal lesions are peripheral
subepithelial opacities, wedge shaped or fascicular
Cornea
pannus, vascularization and Salzmann’s nodular
• Punctate keratopathy
• Marginal keratitis (catarrhal ulcer)
degeneration.1
• Phlyctenulosis As high, as 50% of the patients with anterior
blepharitis may have associated dry eye. 5 Other
Skin
commonly associated systemic conditions are atopy
• Rosacea
• Seborrheic dermatitis and rosacea. Patients with atopic diseases have a
• Atopy predilection for staphylococcal and herpetic infections.
• Psoriasis This is because of a cell-mediated immunity defect and
impaired IgA antibody response. Patients with rosacea
Others
• Dry eye
also have a greater than normal predisposition to
• Angular blepharitis staphylococcal infection and frequently suffer from
• Pediculosis blepharoconjunctivitis.8
There is usually conjunctival hyperemia along with Differential Diagnosis

associated chronic papillary conjunctivitis8 attributed The other causes of eyelid margin ulcers are vaccinia
to staphylococcal toxins.14 Toxic epithelial keratitis, virus, some of the other poxvirus, herpes virus,
marginal keratitis and phlyctenulosis characterize the Malassezia furfur, Demodex sp., etc. Moraxella may also
corneal manifestations. 8 Toxic epithelial keratitis cause angular blepharitis. The toxic epithelial keratitis
caused by staphylococcal toxins affect predominantly seen in blepharitis needs to be differentiated from the
the inferior cornea. These are small, flat, punctate blotchy, amorphous lesions and filaments of dry eye.
erosive lesions and stain with fluorescein. Incomplete 8
In viral keratitis, the superficial punctate keratitis are
blinking by the patients because of inflamed eyelids large, elevated and appears in clusters anywhere in
may also cause an inferior punctate keratopathy.24 the cornea. Exposure keratitis may also simulate
Marginal keratitis (catarrhal ulcer) are sterile lesions staphylococcal keratitis. Marginal type keratitis
separated from the limbus by a clear interval bridged caused by herpes simplex manifests initially with an
by blood vessels (Fig. 4.3). They occur most often at epithelial defect followed by sub-epithelial infiltrate,
10, 2, 4, 8 O’clock positions where the eyelid margins have reduced corneal sensation and symptoms rather
are in close contact with the peripheral cornea rich in than catarrhal ulcers. Other causes of marginal
antigen presenting cells.8 The infiltrate appears first keratitis are toxic conditions, other bacterial, fungal
followed by ulceration and fluorescein staining. or acanthameba infections and immunological
Phlyctenulosis initially appears at the limbus and diseases.
subsequently may affect the conjunctiva, the cornea
or both. These are a manifestation of delayed Management
hypersensitivity and the lesions run a 10 to 14-days’
course with ulceration of the central area followed by The aim of treatment is to control symptoms, prevent
complications and reduce relapses. Treatment is Systemic antibiotics are indicated in acute
divided into an intense phase lasting for a couple of folliculitis, severe secondary meibomitis, localized
weeks followed by a maintenance phase, which at cellulitis and severe ulcerative blepharitis. In such
times may continue indefinitely to prevent relapses. cases oral doxycycline, tetracycline, minocycline,
10,25
Treatment comprises of eyelid hygiene, antibiotic erythromycin or cephalosporin are used in
ointments and solutions, systemic antibiotics and combination with topical antibiotics.10
topical steroids. 8,10,25 Microbial culture is usually not Indications of topical corticosteroids are marginal
required unless there is doubt in the diagnosis or in keratitis and phlyctenulosis. 0.1% Dexamethasone,
case of recurrent disease not responding to therapy.10
0.1% betamethasone or 0.1% flurometholone is given
Lid scrubs and warm compresses are highly
6-8 times a day and are quickly tapered over a period
effective and form the cornerstone of blepharitis
of week or two once the desired response is obtained.
treatment.26,27 Warm compresses loosen collarettes 8,10
and crusts, removes debris and desquamated skin and As dry eye is frequently present artificial tear
help in melting lipids from obstructed meibomian supplements are indicated. Eyelashes are epilated to
glands.10,28 Various lid scrub preparations used are drain pus in folliculitis and to facilitate search for
baby shampoo (Johnson and Johnson), antiseptic soaps Demodex infestation. 8
and commercial scrub solutions. 26,27,29 Though Treatment is continued over months and a subset
homemade solutions like sodium bicarbonate (7.7 g of patients requires lid scrubs throughout life. Incase
in 0.57 L of water) are reported effective they carry of poor compliance the physician must not hesitate to
risk of microbial contamination and inadvertent injury cleanse the eyelids in the clinic. Indiscriminate use of
due to inappropriate strength of the alkali solution. 30 antibiotics, steroids or fixed steroid-antibiotic combi-
Commercial eye scrubs are superior to antiseptic soaps nations is discouraged to prevent development of
and shampoo 29 but are not available in India where bacterial resistance and to avoid steroid induced
an adequate substitute is diluted baby shampoo. 27 A complications. Underlying meibomitis that frequently
cotton-tipped applicator is soaked with it and the complicates anterior blepharitis will need simul-
margins are scrubbed lightly with a to-and-fro motion taneous attention.4
along the entire length after everting the eyelids. The
frequency of eyelid scrub should be two to three times
a day initially and tapering to once daily to twice a Meibomian Gland Dysfunction
week in the later maintenance phase. It is best done in
the morning as bacteria and crusts tend to accumulate Gutsgell coined the term Meibomian Gland Dysfunction
at night. If there is associated seborrhea of the scalp to describe the changes in the meibomian glands seen
then anti-dandruff, (selenium sulfide) shampoo in posterior blepharitis. 31 Terms like meibomitis and
should be advised. 8 meibomianitis used earlier in literature are inappro-
An antibiotic ointment is applied to the eyelid priate as they imply an exclusive inflammatory
margin two to four times a day, which is reduced to condition. 32,33 The three types of acquired MGD are
once daily when the symptoms lessen. However, the hypersecretory, hyposecretory and obstructive. 34
final aim should be control of the symptoms with lid Hypersecretory MGD or meibomian seborrhea is
scrubs only. Antibiotics can be used empirically characterized by release of large volumes of secretion
without a prior culture in most cases of blepharitis. at the lid margin due to a hypersecretory state of the
Bacitracin, erythromycin, tetracycline, tobramycin, meibomian glands, paralleling that encountered in
and ciprofloxacin are some of the antibiotics of choice. sebaceous glands in cystic acne. It is associated in most
Concurrent treatment of anterior nares may prevent of the cases with seborrheic dermatitis and acne
re-colonization of the eyelids. Topical antibiotic rosacea. An obstructive disease may co-exist, as partial
solutions like 0.3% gentamicin, 0.5% tobramycin, 0.3% obstruction would cause damming of secretions,
ciprofloxacin and 0.3% ofloxacin, are indicated in those which would be expressed in greater quantities
with co-existent conjunctivitis. 10 To prevent deve- mimicking a hypersecretion. A hyposecretory state has
lopment of resistance, patients who require prolonged been observed only in animal models where there is
treatment may be rotated to different antibiotics gland destruction without accompanying hyper-
though many patients will show preferential improve- keratinization. The most common form of MGD is the
ment with a particular type. obstructive type. A less common type of obstructive
MGD is cicatricial MGD seen in cicatrizing conjunc-

tival disease like trachoma, cicatricial pemphigoid,
erythema multiforme, chemical and thermal burns.
The cicatricial process results in anatomic derange-
ment of the ducts and orifices resulting in MGD.
ANATOMY AND PHYSIOLOGY

OF MEIBOMIAN GLANDS
The eyelid margin, 2.5 mm wide, is covered in the Fig. 4.4: Diagram of the Meibomian orifices and mucocutaneous
posterior three-fourth by marginal conjunctiva and the junction of the lid margin. (From Bron AJ, Benjamin L, Snibson
anterior one-fourth by skin. 7 The orifices of the GR. Meibomian gland disease. Classification and grading of
lid changes. Eye 1991;5:395, with permission from authors and
meibomian glands emerge just anterior to the
publishers)
mucocutaneous junction (Fig. 4.4). The muco-
cutaneous junction is an important watershed zone
separating the tear-wetted conjunctival mucosa from
the oil-wetted skin. The cutaneous location of the
orifices is essential for delivery of meibomian
secretions or meibum onto the anterior face of the tear
film. The meibomian glands are modified sebaceous
glands, tubulo-acinar in structure with a holocrine
mode of secretion. There are about 30-40 glands in the
upper tarsus and 20-30 in the lower tarsus (Fig. 4.5).7
The acinar lobules on either side of the central main
duct are distinctly visible as yellow, grape-like
clusters, arranged longitudinally in the tarsal plate
(Fig. 4.6). They are richly innervated by sensory,
sympathetic and parasympathetic fibers. 7,35 These Fig. 4.5: Posterior view of the eyelids showing the tarsal glands.
imply a neural regulation involving autonomic and (From Snell RS, Lemp PA: Clinical Anatomy of the Eye, Boston,
peptidergic innervation. The epithelium of the central Blackwell Scientific Publications Inc, 1989, p 84, with permission
main duct consists of a basal cell layer and two from authors and publishers)
separate layers of intermediate and horny cells
containing keratohyaline granules.36 The three types
of cells in the acini are basal, differentiating and
degenerating cells and these exist in various stages of
holocrine differentiation.
The meibomian secretions are delivered to the tear
film through a steady secretory process and in aliquots
during blinking. The fibers of muscle of Riolan are
arranged elliptically around the ducts in a limpet-like
manner. During a blink, they contract, compressing
the glands and preventing outflow. 37 Conversely,
during blinking, the fibers of orbicularis oculi promote
outflow by a milking action and a little secretion is
expressed. The meibomian secretion constitutes the
lipid layer of the tear film and plays a vital role in the
Fig. 4.6: Schematic representation of meibomian glands.
health of the ocular surface (Table 4.4 ).7,32 Its melting
Meibomian gland with lobules emptying into a duct system that
point is 35-40°C and remains liquid at lid tempe- opens onto the ocular surface. Inset: Detail of a lobule showing
rature.37,38 The composition of normal meibomian mechanism of lipid secretion ( rom Lemp MA, Marquardt R (Eds):
secretion (Table 4.5), meibum, differs significantly The Dry Eye. A Comprehensive Guide. Berlin. Springer-Verlag,
from secretions of sebaceous glands of the skin.35,39 1992, p 92, with permission of the authors and publishers)
Table 4.4: Functions of the meibomian lipid Pathogenesis
layer of the tear film
The entire epithelium of the meibomian gland duct is
• Reduction of evaporation of the aqueous phase of the committed to the process of keratinization similar to
tear film that of keratinized epidermis.40 An important feature
• Enhancing tear film stability by lowering surface tension in the pathogenesis of MGD is hyperkeratinization of
• Prevention of spill-over of tears from the lid margin the ducts.31,41 Increased keratinization leads to stenosis
of the duct and its orifice. Increased desquamation of
• Prevention of contamination of the tear film by sebum
the squamous cells into the lumen causes further
• Sealing the apposed eyelid margins during sleep blockage that affects acinar cell differentiation and
• Prevention of maceration of skin of the eyelids by tears results in gland dysfunction. 42 Histologically
• Providing a smooth surface for refraction of incident dilatation and keratinization of the ducts, enlargement
light rays of the acini with stagnation, acini devoid of secretory
contents and granuloma formation have been reported
in obstructive disease.31
There is an accompanying alteration in the lipids
Table 4.5: Composition of human secreted by meibomian glands (Table 4.6).35,43-47 An
meibomian gland lipids35
increase in chain length or sterol ester fraction, shift
Synthesized lipids % from cholesterol ester to cholesterol, or decrease in
(Acinus) branching or unsaturation of lipids would all tend to
Wax esters 44 increase the melting point with increased viscosity and
Sterol esters 33 plugging of the gland orifices.32 Increased cholesterol
Triglycerides 5 results in a rigid polar lipid phase, accumulation of
Diglycerides 2 unsaturated fatty acids,48 plugging of glands because
Monoglycerides Trace of its high melting point,43 and thus in the process
Fatty alcohols Trace provides a rich substrate for bacterial growth.49 The
Hydrocarbons 2 presence of esterified cholesterol may be a necessary
precondition to the development of the diseased
Membrane Derived
(Plasma membranes and other membrane state.48 The triglyceride fraction that is responsible for
structure, also originally synthesized) the transition from polar to nonpolar lipids is also
Cerebrosides 4 altered.47 Free fatty acids cause ocular toxicity, irri-
Ceramides Trace tation, foam formation and destabilization of the tear
Phospholipids film.42,44 Patients with meibomian seborrhea with
Zwitterionic 6
excess secretion have been shown to have high levels
Polar lipid 2
of monounsaturated fatty acid like oleic acid that
reduces viscosity.50 There is also decreased amounts
Degradation Products of polar lipids, particularly phosphatidylethanolamine
(Bacterial, peroxisomal or lysosomal lipases)
and sphingomyelin, two important surfactants
Free fatty acids 2
necessary for creating a smooth transition from
Table 4.6: Lipid alteration in meibomian gland dysfunction35

Lipid class Function Mechanism of alteration Effects
Polar lipids Surfactant (helps spread of lipids) Fatty acid unsaturation Open structure decreases surfactant
Structure for nonpolar lipids Esterase activity Submerge into water layer; loss of
surfactant; increased evaporation
Nonpolar lipids Water barrier Lipase and esterase Loss of barrier; increased evaporation;
irritation by free fatty acids
Lubricant Decreased saturation Loss of fluidity; decreased melting;
inspissation or orifice plugging
hydrophilic tear-mucin phase to a hydrophobic lipid include burning, redness, grittiness, watering and
phase in the tear film.51 This results in decreased tear fluctuating vision. 32 There is often discomfort after
breakup time, increased aqueous evaporation and dry prolonged reading or working on computers. The
eye symptoms. clinical signs of MGD are enumerated in Table 4.7 (Figs
The eyelid margins are also commonly colonized 4.7 to 4.12). Thickening, hyperemia and irregularity
by S. epidermidis, S. aureus, P. acnes and Corynebacteria of the posterior eyelid margin are common features
spp. 5,12 These bacteria are capable of producing of MGD.7 An early sign is pouting of the orifices, which
hydrolyzing enzymes called lipases that break down are often capped with a solidified dome of oil. In
meibomian lipids.5,22 Lipases hydrolyze wax and health, the meibum is clear while in the diseased state,
sterol esters releasing fatty acids, which cause their the consistency varies from cloudy to granular in the
own deleterious effects. initial stages to a thick inspissated tooth-paste-like
The meibomian gland acini express receptors for semisolid plug that is considered as hallmark of the
both androgens and estrogens.52-54 Androgens cause disease.7 Another feature often noted is meibomian
increase in the transcription of certain proteins related foam (Fig. 4.13) that results from the presence of soaps
to synthesis and secretion of meibomian gland lipids in the tear film.
thus stimulate lipid layer formation besides regulating Clinical signs of the disease need to be differen-
numerous pathways of lipid metabolism.55 Aging, tiated from morphological changes brought about by
anti-androgen therapy, hormone replacement therapy age. 61 The age-related signs are lid vascularity,
and complete androgen insensitivity syndrome (CAIS) hyperkeratinisation of the skin of the eyelids, lower
cause meibomian gland abnormality, altered lipid lid telengiectasia, upper lid rounding, narrowing of
profile, decreased tear film break up time and
functional dry eye.52,56-58 Table 4.7: Signs of meibomian gland dysfunction
Another recent concept is the role of inflammatory Eyelid Margins
mediators like reactive oxygen species (ROS). 59 • Thickening and irregularity
Reactive oxygen species like hydrogen peroxide, • Increased rounding of the posterior lid margin
oxygen radicals (superoxide), and hydroxyl radicals • Increased vascularization (invasion till the outer cuffs
can have significant impact on all kinds of blepharitis. of the orifice)
• Hyperkeratinization
Lipase or esterase activity could result in release of
linoleic acid from meibomian gland secretion that Mucocutaneous junction
induces differentiation of meibomian gland duct • Anteroplacement and retroplacement
keratinocytes. These activated keratinocytes produce • Mucosal absorption
• Ridging (elevation of the junction)
cytokines and chemokines. Cytokines are proteins that
affect specific cellular processes while chemokines Orifices
attract proinflammatory cells. This results in • Reduced number
recruitment of phagocytic leukocytes and in turn more • Capping of the orifices with solidified dome of oil
• Pouting
production of ROS and cytokines. Nitric oxide formed
• Fiber optic sign
from amino acids is synthesized also by commensal • Distortion and obliteration
organisms of the lid and is strongly inflammatory.
Another aldehyde, hydroxynonenal also attracts Ducts
• Exposure
inflammatory cells as well as reduces levels of polar
• Cystoid dilatations
lipids like phosphatidylethanolamine. Phospholipase
A2 are hydrolyzing enzymes that cause polar lipid Secretions
breakdown and has been shown to have increased • Cloudy
• Granular
activity in tears of blepharitis patients which results
• Inspissated toothpaste-like
in destabilization of the tear film.60 • Foam on the eyelid margins
Clinical Features Tear film

• Rapid breakup time
Clinical features of MGD may be subtle to severe and • Foam
often there is no correlation between symptoms and • Prominent interference pattern
signs. The patients’ complaints are non-specific or • Debris
Fig. 4.10: Meibomian gland dysfunction with capping of the

meibomian orifices with solidified dome of oil
Fig. 4.7: Severe Meibomian gland dysfunction with multiple

cappings, pouting orifices and lid margin telengiectasia
Fig. 4.11: Meibomian gland dysfunction with hyperkerati-

nization, foamy discharge and obliterated orifices
Fig. 4.8: Meibomian gland dysfunction with capping(arrow),

obstructed glands with pouting orifices and papillary congestion
Fig. 4.12: Meibomian gland dysfunction with telengiectasia

around stenosed and pouting orifices
orifices with pouting and decrease gland secretion.

However, these changes are not associated with
increased viscosity or opacification of the expressed
lipid, which are markers for the disease.
The meibomian glands are visualized through the
tarsal conjunctiva on slit-lamp microscopy or with
Fig. 4.9: Meibomian gland dysfunction with pouting orifices, infrared photography (meibography).32 The features
ridging of the eyelid margin and blocked orifices in meibography are gland dropouts (Fig. 4.14), duct
gland dropout have been found to have a higher tear

evaporation rate.64 Ocular discomfort, increased tear
evaporation and epithelial changes as evidenced by
fluorescein and Rose Bengal staining have been
associated with gland dropout in obstructive MGD.66
Two other closely associated dermatological
conditions are seborrheic dermatitis (36-100%) 5,63 and
rosacea(4-63%).5,67 MGD is also associated with contact
lens intolerance,68 giant papillary conjunctivitis,69
chalazia, floppy eyelid syndrome, recurrent corneal
erosions32 and concretions.3
Fig. 4.13: Meibomian gland dysfunction with foamy
discharge at the medial canthus Treatment
The mainstay of treatment is hot compresses and lid
massage along with systemic tetracyclines.25,32 Hot
compresses increase the flow of meibomian secretions
by raising the temperature above melting point. Lid
massage expresses out the secretion relieving the
blockage and establishing normal flow of lipids onto
the tear film. This forms the core of the therapy as
tear film break-up time has been shown to revert to
normal or supernormal levels following expression of
the meibomian glands.63 Hot compresses are applied
for 10 minutes with a cloth soaked in warm water.
Lid massage is performed by compressing the length
of the eyelid against the globe with one’s fingers with
vertical movements, downwards for the upper eyelid
and upwards for the lower. This is repeated 10 to 15
times for each eyelid. It is best done in the morning
and in the acute stages needs to be repeated during
the day. Lid scrubs are often used to cleanse the eyelid
margins of oily secretions, bacteria and debris in the
manner described earlier (Table 4.8).
Systemic tetracyclines are beneficial in MGD and
are reserved for those with prominent sympto-
matology.32,70 Tetracyclines achieve their therapeutic
Figs 4.14A and B: Meibography showing normal meibomian
glands appearing (A) and meibomian gland dysfunction with Table 4.8: Scheme for investigating meibomian gland
gland dropouts (B) dysfunction62
Technique Assessment
dilatation, hypotranslucent cysts and large hyper-
translucent scars (chalazia). Gland dropout is a reliable Symptom questionnaire: Clinical history
indicator of the diseased state.6 Other tools for evalua- Fluorescein Break up time: Tear film stability
ting patients with MGD are meibometry, evapori- Fluorescein/Rose Bengal/
metry, interferometry and chemical analysis, which Lissamine green: Ocular surface damage
have not yet been standardized and are available in Schirmer’s test: Tear secretion
only a few research centers.62
Lid and meibomian
MGD is closely associated with keratoconjuncti-
gland morphology
vitis sicca in 25-40% of cases and is the major cause of and Meibomian expression: Meibomian gland function
evaporative dry eye.5,51,63-66 Patients with meibomian
value by inhibiting bacterial lipase production at An aspect of utmost importance is patient
dosages that do not affect the growth of these education. As the disease may take weeks to months
organisms.70 They act more by decreasing the lipolytic to respond to therapy, patients need constant
activity of the organisms rather than eliminating them reassurance and encouragement. The technique of lid
from the lid margin. Long-term oral treatment with massage needs to be repeatedly demonstrated.
tetracycline was observed to decrease NO synthesis. Treating MGD requires patience and persistence from
Minocycline, a long acting congener, decreases the both the patient and the physician.
levels of free fatty acids, diglycerides and cholesterol
in the meibomian secretions, acts as an anti- CONCLUSION
inflammatory agent by decreasing neutrophil
Blepharitis and MGD are chronic diseases, which need
activation, ROSs and phospholipase activity and
to be diagnosed more frequently as they cause
reduces bacterial load from the eyelid margins.71,72
evaporative dry eye resulting in significant morbidity.
Therapy consists of oral oxytetracycline 250 mg four
These are associated with generalized disorders of
times daily or doxycycline 100mg daily. 32 Therapy is
sebaceous glands. Knowledge regarding their
continued for a minimum period of three months but
pathogenesis and their impact on the ocular surface
some patients may require low dose tetracycline for
is still evolving. The current treatment strategies are
longer periods. The common side effects are
limited and time taking during which the patients
gastrointestinal discomfort like dyspepsia, pain,
need constant reassurance and encouragement. Lid
diarrhea and vomiting that may necessitate disconti-
scrubs and expression of blocked meibomian glands
nuation or changing from oxytetracyline to
remain the bulwark of management policies.
doxycycline which is better tolerated. 73,74 Dairy
products interfere with tetracycline absorption from
REFERENCES
the gastrointestinal tract and hence tetracycline should
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5. McCulley JP, Dougherty JM, Deneau DG. Classification of
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Selection of antibiotic ointment is similar as in anterior 6. Mathers WD, Shield WJ, Sachdev MS, et al. Meibomian gland
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8. Smolin G, Okumoto M. Staphylococcal blepharitis. Arch
acne vulgaris or seborrheic dermatitis should be
treated. As there is a high prevalence of dry eye, 9. Seal DV, Ficker LA, Wright P. Staphylococcal blepharitis. In
artificial tears are given simultaneously. As they are Pepose JS, Holland GN, Wilhelmus KR (Eds): Ocular infection
required for a prolonged period preservative free or and immunity. St Louis: Mosby; 1998;788.
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blepharitis. Ophthalmol Clin of N America1 1999;2:9.
With the recognition of inflammatory process
11. Dougherty JM, McCulley JP. Comparative bacteriology of
underlying blepharitis, new modalities have been tried chronic blepharitis. Br J Ophthalmology 1984;68:524.
to modulate such responses. Resveratrol, a flavonoid 12. Groden LR, Murphy B, Rodnite J, Genvert GI. Lid flora in
compound derived from grapes is an inhibitor of blepharitis. Cornea 1991;10:50.
nitrite formation, nitric oxide synthetase synthesis and 13. Seal DV, McGill JI, Jacobs P, Liakos GM, Goulding NJ.
nuclear factor kappa B (NF-kB) activation.75Other Microbial and immunological investigations of chronic non-
ulcerative blepharitis and meibomianitis. Br J Ophthalmol
drugs reviewed are Silymarin, a flavonoid, azelaic acid 1985;69:604.
and gycolic acid that inhibits S.epidermidis and have 14. Seal DV, Ficker L, Ramakrishnan M,Wright P. Role of
antikeratinizing properties and adapalene gel that staphylococcal toxin production in blepharitis. Ophthlalmol
inhibits keratinocyte proliferation.59 1990;97:1684.
15. Dougherty JM, McCulley JP. Bacterial lipases and chronic 39. Nicolaides N, Kaitaranta JK, Rawdah TN, et al. Meibomian
blepharitis. Invest Ophthalmol Vis Sci 1986;27:486. gland studies: comparison of steer and human lipids. Invest
16. Allen JH. Staphylococcic conjunctivitis. Experimental Ophthalmol Vis Sci 1981;20:522.
reproduction with staphylococcus toxin. Am J Ophthalmol 40. Jester JV, Nicolaides N, Smith RE. Meibomian gland
1939;20:1025. dysfunction I. Keratin expression in normal human and rabbit
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18. Mondino, BJ, Kowalski R, Ratajczak HV, et al. Rabbit model changes in the rhino (hrrhhrrh) mouse. Invest Ophthalmol Vis
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1981;99:891. 42. Jester JV, Nicolaides N, Kiss-Palvalgyi I, Smith RE.
19. Mondino BJ, Kowalski RP. Phlyctenulae and catarrhal Meibomian gland dysfunction II. The role of keratinization
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staphylococcal blepharitis. Arch Ophthalmol 1987;105:409. composition of meibomian secretions in chronic. Invest
22. Ficker L, Ramakrishnan M, Seal D, Wright P. Role of cell Ophthalmol Vis Sci 1986;27:52.
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Ophthalmol 1991;111:473. sterol esters of meibomian secretions in chronic blepharitis.
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29. Key JE. A comparative study of eyelid cleaning regimens in with meibomian secretion polar lipid abnormality.Arch
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histologic and ultrastructural investigations. Invest Ophthalmol Vis Sci 2002;120:1689.
Ophthalmol Vis Sci 1981;20:537. 57. Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone
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Br J Ophthalmol 1961;45:718. 2001;286:2114.
38. Brown SI, Dervichian DG. The oils of the meibomian glands. 58. Cermak JM, Krenzer KL, Sullivan RM, et al. Is complete
Arch Ophthalmol 1969;82:537. androgen insensitivity syndrome associated with alterations
in the meibomian gland and ocular surface. Cornea 67. Jenkins MS, brown SI, Lempert SL, Weinberg RJ. Ocular
2003;22:516. rosacea. Am J Ophthalmol 1979;88:618.
59. McCulley JP, Shine WE. Changing concepts in the diagnosis 68. Henriquez AS, Korb DR. meibomian glands and contact lens
and management of blepharitis. Cornea 2000;19:650. wear. Br J Ophthalmol 1981;65:108.
60. Song CH, Choi JS, Kim DK, Kein JC. Enhanced secretory 69. Mathers WD, Billborough M. Meibomian gland function and
group II PLA2 activity in tears of chronic blepharitis patients. giant papillary conjunctivitis. Am J Ophthalmol 1992;114:188.
Invest Ophthalmol Vis Sci 1999;40:2744. 70. Dougherty JM, McCulley JP, Silvany RE, Meyer DR. The role
61. Hykin PG, Bron AJ. Age-related morphological changes in of tetracycline in chronic blepharitis. Invest Ophthalmol Vis
lid margin and meibomian gland dysfunction. Cornea Sci 1991;32:2970.
1992;11:334. 71.. Frucht-perry J, Sagi E, Hemo I, Ever-Hadani P. Efficacy of
62. FoulksGN, bron AJ. Meibomian gland dysfunction. A clinical doxycycline and tetracycline in ocular rosacea. Am J
scheme for description, diagnosis, classification and grading. Ophthalmol 1993;116:88.
The ocular Surface 2003;1:107. 72. Shine WE, McCulley JP, Pandya AG. Minocycline effect on
63. McCulley JP, Sciallis GF. Meibomian keratoconjunctivitis. Am meibomian gland lipids in meibomianitis patients. Exp Eye
J Ophthalmol 1977;84:788. Res 2003;76:417.
64. Mathers WD.Ocular evaporation in meibomian gland 73. Ta CN, Shine WE, McCulley JP, et al. Effects of Minocycline
dysfunction and dry eye. Ophthalmol 1993;100:347. on the ocular flora of patients with acne rosacea or seborrheic
65. Mathers WD, Lane JA, Sutphin JE, Zimmerman MB. Model blepharitis. Cornea 2003;22:545.
for ocular tear film function. Cornea 1996;15:110. 74. Salamon SM. Tetracyclines in ophthalmology. Surv
66. Shimazaki J, Sakata M, Tsubota K. Ocular surface changes Ophthalmol 1985;29:265.
and discomfort in patients with meibomian gland 75. Tsai S-H, Lin-Shiau S-Y, Lin J-K. Suppression of nitric oxide
dysfunction. Arch Ophthalmol 1995;113:1266. synthetase and down-regulation of the activity of NFkb in
macrophages by resveratrol. Br J Pharmacol 1999;126:673.
Chapter 5
Inflammatory Diseases
of the Eyelids
STYE (HORDEOLUM EXTERNUM) Treatment

It is an acute purulent infection of the glands of Zeis As it mostly evacuates by itself, no active intervention
attached to the cilium, due mostly to Staphylococcus is necessary. Hot fomentation helps in localization of
(Fig. 5.1). Symptoms are out of proportion to the lesion and relief of symptoms. Local antibiotics
disease process. Severe pain is accompanied by prevent the spread of the disease to the surrounding
relatively small swelling at the root of the cilium. Red- area. Systemic anti-inflammatory drugs are also
ness and heat are present. Following this, a pus point advocated for reduction of inflammation and relief of
develops at the root of the cilium and gets evacuated pain which is sometimes very severe. The pus can be
spontaneously. One lesion can infect the adjacent folli- evacuated by pulling out the cilium once the lesion is
cles producing a crop of lesions. Local bad hygiene, localized and points on the surface. It should
chronic blepharitis, refractive error, malnutrition, and preferably be done under cover of broad spectrum
systemic uncontrolled diabetes mellitus can lead to systemic antibiotics. If lesion is big involving multiple
frequent recurrence of the lesion. Very rarely the lashes, a small opening is made with a pointed knife
infection can spread to the meninges along the or needle after proper anesthetization of the area, and
draining venous channels producing cavernous sinus no squeezing is attempted. Recurrence is prevented
thrombosis or meningitis. by the treatment of chronic blephartis.
CHALAZION (MEIBOMIAN CYST)

This is a chronic inflammatory granuloma of the tarsal
glands caused by infection of the retained sebaceous
material inside the gland (Fig. 5.2). Clinically, it starts
slowly and symptomlessly. In the beginning it is small
and hard, free from the overlying skin. It is much more
common in upper lid and is seen more frequently in
adults. Patients with chronic inflammatory conditions
of lid margin can have multiple lesions in the same
lid (Figs 5.3A and B). Mostly the lesions remain
stationary after growing to a certain size, but some-
times spontaneous regression or secondary infection
can take place. Rarely, the chalazion develops in the
duct of the gland and then sprouts out on the lid mar-
Fig. 5.1: Stye with blepharitis involving the upper lid gin (marginal chalazion). Chalazion may occasionally
Chapter 5: Inflammatory Diseases of the Eyelids 31
plasma cells, and epitheloid cells. In the center of the
mass there is deposition of lipid, producing a picture
of lipogranuloma. Fibrosis may take place along with
necrosis in the center. Sometimes there is liquefaction
forming a meibomian cyst comparable to a cold
abscess. The final picture can be at any intermediate
stage between necrosis and fibrosis. Pathogenesis of
chalazion is still not very clear but it is largely accepted
now that there is a chronic low grade infection
producing accumulation of sebaceous material in the
acini which initiates the development of granulation
tissue due to toxic irritation. Varieties of organisms
can be found in the lesion, but they may be just
Fig. 5.2: Chalazion of the lower lid
incidental rather than real culprits. Recurrently
occurring chalazia at the same site must be closely
watched and tissue must be examined for malignancy.
Some rare specific infections like tuberculosis,
tularemia, gumma or fungal infection can mimic the
condition.
Treatment
If asymptomatic, it can be left alone. Medical manage-
ment includes hot fomentation and expressing out the
material by massaging the lid. Intralesional injection
of 1 mg triamcinolone is successful in some patients.
The rest require surgical intervention. After proper
Fig. 5.3A: Multiple chalazia in the upper lid
anesthetization of the conjunctival sac by instillation
of anesthetic drops and injecting in the lid around the
lesion, vertical incision is made on the conjunctival
side of the lesion to prevent damage to the vertically
running blood vessels and the ducts of the tarsal
glands. Evacuation of the granulation tissue is done
with a scoop, and light cauterization is done with
carbolic acid. Marginal chalazion is nipped off at the
lid margin and the duct vertically slit open.
HORDEOLUM INTERNUM (ACUTE MEIBOMITIS)

Fig. 5.3B: Everted lid showing congestion and It is an acute infection of the meibomian glands by
projection of the chalazia Staphylococcus aureus leading to suppuration. As the
tarsal gland is deeply situated and covered by thick
have to be differentiated from some malignant
layer on either side, the disease is more chronic and
tumors of the lid margin, e.g. Sebaceous gland carci-
violent than the common stye. As the pus points on
noma (Meibomian carcinoma). The condition is
the conjunctival side, drainage is planned from inside.
mostly asymptomatic, but sometimes it may produce
blurring of vision and eye strain due to astigmatism
TARSITIS
induced by pressure.
Pathologically, there is a unique inflammation of As the tarsal plate is a tough fibrous avascular struc-
the meibomian glands producing granulation tissue. ture, diffuse specific primary inflammation is not
It affects the areas around the acini and leads to common. Mostly trachoma and sometimes spring
fibrosis. There is an infiltration of lymphocytes, catarrh can affect the tarsal plate. Tuberculosis,
leprosy, and syphilis can be responsible for production

of inflammatory granuloma. Mostly symptomless,
thickening of tarsal plate leads to mechanical ptosis,
sometimes closing the eye totally.
BLEPHARITIS
It is a chronic inflammation of eyelid margin which
sometimes leads to secondary changes in conjunctiva
and cornea (Fig. 5.4). Its occurrence is quite common
but most of the time, it is ignored and goes
undiagnosed. Etiology is varied and difficult to pin-
point; so treatment remains unsatisfactory. The com-
monest cause is staphylococcal infection; seborrhea
and rarely parasitic infections are responsible for some
other cases. Fig. 5.4: Acute ulcerative blepharitis. Sticking together of
eye lashes and madarosis
Clinical Features
In both the conditions, due to dragging of the
Itching in the eye, especially at the lid margin, is a conjunctiva over the lid margin, posterior margin
common complaint. Red eye with watering and burn- looses its sharpness and hence there is loss of capil-
ing may be present. The condition is more common larity leading to spilling over of the tears on to the lid
in young females. Lid margin is thickened and ede- skin. This leads to chemical irritation and eczema
matous and may show some dilated blood vessels. which, if persistent, gives rise to cicatricial ectropion,
Gray or yellowish scales are often observed along the made worse by constant downward wiping of the
lid margin, scraping of which may give rise to tiny tears by the patient. Punctal eversion also contributes
ulcers with fine bleeding points. In chronic cases, cilia to tearing and a vicious cycle is established. Tear film
fall off (madarosis) with fibrosis at that site. New is disturbed causing dryness of the conjunctiva and
growing cilia may be misdirected (trichiasis). Lurking cornea (sicca). So this condition is also called triple ‘S’
infection can lead to recurrent stye and angular syndrome- combination of staphylococcal infection,
blepharoconjunctivitis. Rarely notching of the lid seborrhea, and sicca.
margin, entropion or ectropion may ensue. Sometimes Rarely, blepharitis can be due to parasites; blepha-
secondary changes are seen in conjunctiva and cornea ritis acarica due to demodex folliculorum, and phthi-
due to hypersensitivity to staphylococcal exotoxins; riasis palpebrum due to crab louse and head louse.
they may be in the forms of chronic papillary conjunc- Nits may be found at the roots of the cilia.
tivitis, punctate epithelial erosions in the lower part
of cornea, marginal corneal ulcer or phlycten. Treatment
Some individuals are prone to have excessive seba- It is long-term and sometimes unsatisfactory as total
ceous secretions all over the body including that on eradication may not be possible.
the lid. Lipolytic enzymes produced by certain orga- 1. Hygiene of the lid margin with antiseptic soap and
nisms like pityrosporum ovale and corynebacterium, warm water, at least twice day, is important.
digest the fat to produce a free fatty acid which in turn Mechanical expression of excessive secretion from
causes seborrheic blepharitis. Scales in this case are meibomian glands is advised to reduce the amount
uniformly distributed all over the margin in contrast of irritating lipids.
to conglomeration of the white discharge around the 2. Local and systemic antibiotics help in control of
root of the cilia in the infective type. Lid margin is infection and should be ideally started after getting
less inflamed. Sometimes cystic nodules are seen at specific sensitivity reports. Scales are softened by
the openings of meibomian ducts with foamy dis- wetting with sodium bicarbonate (NaHCO 3 )
charge floating on the tear meniscus. Secondary solution and then mechanically removed by gentle
changes in the conjunctiva and cornea are rare. scraping. Antibiotic ointment containing drugs like
Chapter 5: Inflammatory Diseases of the Eyelids 33
gentamicin, bacitracin or sulphacetamide is rubbed
on the lid margin. Tetracycline is a good adjunct
for systemic administration in severe cases with
acne.
3. Once the primary infection is under control, local
corticosteroids can be used to treat secondary
effects in the conjunctiva and cornea.
4. Treatment with antibiotics and astringents should
be continued for at least 2 to 3 weeks after visible
cure as the infection might be lurking in the roots
of cilia. In very chronic cases, lid margin can be
painted daily with 2% povidone iodine solution.
5. Simultaneous treatment of seborrheic dermatitis
and dandruff with medicated shampoo is
necessary. Improvement of general health with Fig. 5.5: Acute state of herpes zoster involving
vitamins and minerals is essential to prevent right upper lid
relapses.
6. In parasitic infection, mechanical removal of the Treatment
organisms is mostly sufficient. Na- fluorescein or
isoflurophate eye ointment can be helpful. It is mostly palliative and aims at promoting rapid
healing with minimum scarring and neuralgia. Use
HERPES ZOSTER of specific antiviral agent, such as acyclovir (Zovirax)
This is a common viral infection of the eyelid caused administered orally in the dose of 800 mg five times a
by a virus similar to that causing chickenpox, a day for seven days, reduces the vesicle formation.
varicella group of viruses. It morphologically resem- Early treatment attenuates the skin and ocular lesions
bles to the herpes simplex virus, but differs from it but has no effect on postherpetic neuralgia. Local
clinically and antigenically. The virus may lie dormant application of antibiotic-corticosteroid combination
in the gasserian ganglion and may come out on the should be done till the crusts fall off. Analgesic-anti-
face along the distribution of the ophthalmic division inflammatory agents have little effect on pain.
of the trigeminal nerve when the patients’ body
resistance is reduced as in old age or in immuno- DERMATITIS
suppressed state. Though usually unilateral, it may Being the thinnest and most extensible in the body,
have bilateral affections and very rarely affects the skin of the lid is a very common site for inflammation
maxillary division. The Hutchinson’s rule state that even with very mild irritants. Acute dermatitis is
involvement of tip of the nose indicates that the eye is characterized by erythema, vesiculation and crusting
also affected as the nasociliary nerve supplies both the (Fig. 5.6), whereas the chronic condition leads to
areas. But there are many exceptions to the rule thickening of the skin and itching. Drugs and
(Fig. 5.5). cosmetics are the common irritants. In atopic
Clinical Features dermatitis, the patient is sensitive to allergens to a
much greater degree than the normal people. They
Initially the patient complains of headache and may have a past history of hay fever or asthma and
burning sensation on one side of the head, which may blood may show increased levels of IgE. Chronic
be accompanied by malaise and fever. Severe cutting keratoconjunctivitis, keratoconus, and lenticular
pain is followed by the development of vesicles. The opacities may be associated with atopy.
skin becomes inflamed and edematous. The vesicles
or pustules rupture to leave behind crusting ulcers. Treatment
Intensity of the pain may reduce once the vesicles
erupt, but the neuralgic pain continues even months Irritants have to be identified and removed from the
after the disease subsides. There is anesthesia and patient’s surroundings. In acute stage, cold
parasthesia due to demyelination of the involved compresses and nonfluorinated short-term cortico-
nerves. steroids like hydrocortisone are helpful.
Fig. 5.6: Allergic dermatosis due to Fig. 5.8: Multiple warts distributed in
instillation of eye drops a linear fashion
this lesion can produce follicular conjunctivitis due to

liberation of the viruses into the conjunctival sac.
Microscopically, intracytoplasmic inclusion bodies can
be seen which can displace and compress the nucleus
to one side (Fig. 5.7).
WARTS (VERRUCA VULGARIS)

These are small elevated lesions with a papillomatous
surface, caused by wart virus belonging to PAPOVA
group. Surgical excision often leads to recurrence.
Cryo application is another method of treatment
(Fig. 5.8).
FURTHER READING
Fig. 5.7: Molluscum contagiosum 1. Caccamise WC. Phthiriasis palpebrum. Am J Ophthalmol
1956;43:305.
2. Duke Elder: System of Ophthalmology. Vol.VIII, Part 2, Henry
Kimpton, London, 1977.
MOLLUSCUM CONTAGIOSUM 3. Dougherty JM, McCulley JP. Comparative bacteriology of
chronic blepharitis. Br J Ophthalmol 1984;68:524-28.
Multiple, skin colored, dome shaped nodules measur-
4. McCulley JP, Dougherty JM, Deneau DG. Classification of
ing from 1-3 mm, sometimes umbilicated are seen. It chronic blepharitis. Ophthalmology 1982;89:1173-80.
is due to infection caused by viruses belonging to a 5. Perry HD, Serniuk RA. Conservative treatment of chalazia.
group of poxviruses. If present close to the lid margin, Ophthalmology 1980;87:218-21.
Chapter 6
Anomalies of the Eyelid Position

PTOSIS (BLEPHAROPTOSIS) Table 6.1: Showing the causes of ptosis

Ptosis, by itself, means drooping of the tissue. Classification of Ptosis
Blepharoptosis is a condition in which the upper eyelid a. Myogenic ptosis:
comes down lower than its normal position, i.e. Levator maldevelopment
Simple
covering about 2 mm of upper part of cornea (Figs
With superior rectus weakness
6.1A and B). It mostly leads to a cosmetic blemish but Blepharophimosis syndrome
may cover the pupillary area obstructing the vision. Chronic progressive external ophthalmoplegia
More than 50% of the cases are congenital, but Oculopharyngial syndrome
acquired ptosis is also common. It is unilateral in 75% Progressive muscular dystrophy
of cases and bilateral in the rest (Fig. 6.2). Myasthenia gravis
Until recently all the cases of ptosis were grouped Congenital fibrosis of the extraocular muscles
b. Aponeurotic ptosis
under two heads, i.e. congenital and acquired. Almost
Senile ptosis
all the cases of congenital ptosis are due to dystrophic Late developing hereditary ptosis
levator muscle and the results of the levator resection Stress or trauma to levator aponeurosis
surgery are different from those obtained in other Following cataract surgery
cases. Following other local trauma
Blepharochalasis
Myogenic Ptosis Associated with pregnancy
Following Graves’ disease
This is a major cause of ptosis comprising more than c. Neurogenic ptosis
60% of all the cases. Levator maldevelopment is due Ptosis caused by lesions of third nerve
to deficiency of striated fibers in the muscle which Post-traumatic ophthalmoplegia
leads to inelasticity of the structure causing defective Misdirected third nerve ptosis
elevation. This results in ptosis and also lid lag on Marcus Gunn jaw-winking ptosis
Horner’s syndrome
down gaze, as the muscle fails to relax. It is mostly Ophthalmoplegic migraine
sporadic, but some familial cases have been reported. Multiple sclerosis
In 15 to 20% of cases, it may be associated with d. Mechanical ptosis
superior rectus weakness. It is thought to be due to e. Apparent ptosis:
the fact that both the muscles develop from the same Due to lack of posterior eyelid support
mesodermal bud. Due to hypotropia
Myasthenia gravis is another common cause of Due to dermatochalasis
ptosis seen in clinical practice. It is due to deficiency
of acetyl choline at the myoneural junction. Thought diseases or Lambart-Eton syndrome or due to use of
to be autoimmune in nature, it may be associated with certain drugs like chloroquine. In most of the cases,
thymus hyperplasia or rarely with dysthyroidism. ptosis, unilateral or bilateral, is the presenting feature.
Cases have been reported associated with collagen Later on the extraocular muscles may be involved
exercise. Difficulty in deglutition and respiration are

present in advanced cases which may terminate in
death. The condition is highly underdiagnosed as
diagnostic neostigmin or tensilon test is not routinely
performed in idiopathic cases of ptosis. Cogan’s lid
twitch sign is useful in which the patient is asked to
look up and down repeatedly or to stare in the upgaze.
Due to fatigue, the lid shows flickering and gradually
droops down. Neostigmin test is very helpful: 2-4 mg
of the drug is injected intramuscularly after prior
administration of atropine injection, and the patient
is examined after 10 minutes for the improvement of
the drooping and other features (Figs 6.3A and B).
Tensilon can be injected intravenously which gives a
much faster but short lasting effect. It is safer than
neostigmin, but is not readily available in the market.
Tonometry can be done before and after injection of
the drugs which can detect mild form of the disease
due to rise of the IOP in positive cases. Detection of
specific antibodies in the blood, chest laminography
to detect the presence of enlarged thymus and thyroid
Figs 6.1A and B: Congenital unilateral ptosis.

(A) Looking straight, (B) Looking down (lid lag)
Fig. 6.2: Bilateral congenital ptosis with head posture
followed by muscles of all over the body. The Figs 6.3A and B: Myasthenia gravis neostigmin test.
symptoms are classically more in the evening and after ( A) Before injection. (B) After injection
Chapter 6: Anomalies of the Eyelid Position 37
function tests may be helpful laboratory tests.
Treatment is almost always medical in the form of oral
neostigmin (Prostigmin) or pyridostigmin (Mestinon).
The former is a short acting drug which can be used
to initiate the therapeutic response and the later, a long
acting choline esterase inhibitor is used for mainte-
nance. As the condition is considered to be auto-
immune in nature, systemic oral corticosteroids are
used with good results. Thymectomy is advocated in
cases of thymomas and minimal ptosis surgery can
be performed in long standing cases with caution.
Different forms of myopathies are rare conditions
mostly associated with affections of extraocular mus-
cles. As the Bell’s phenomenon is absent in almost all
cases, surgery is contraindicated and elevation of the
lids by mechanical means like crutches or contact Fig. 6.4: Senile ptosis due to dehiscence of aponeurosis
lenses is the only way of management.
APONEUROTIC PTOSIS
This is a common condition usually found in the old
age (Fig. 6.4). Levator aponeurosis is either disinserted
from the tarsal plate or there are areas of dehiscence
in it. As the muscle is not completely detached and
the functioning is normal, voluntary elevation is
possible. Lid crease recedes up and so the margin-
crease distance is increased. The skin is also thin and
transparent due to the aging changes and so
sometimes the cornea and iris are visible through the
part of the lid above the tarsus. Secondary enoph-
thalmos due to absorption of orbital fat contributes to
the drooping of the lid. It is usually bilateral. The other
causes of aponeurotic ptosis are trauma, inflammation
including Graves’ disease, ocular surgeries including
cataract extraction, pregnancy, and use of certain
drugs like corticosteroids which lead to water logging
in the tissue. Very rarely it is congenital. Treatment is
always surgical which includes repair of the
dehiscence, reattachment of the levator slip to the Fig. 6.5: Schematic diagram showing repair of the
tarsal plate or vertical shortening of the aponeurosis aponeurotic defect
by plication (Fig. 6.5).
done after proper assessment of the squint.
Spontaneous recovery is possible up to 6 months; so
Neurogenic Ptosis
any surgical intervention should be done after that
Third nerve palsy due to any lesion along the course time interval.
of the nerve leads to ptosis of variable degree Horner’s syndrome is due to paralysis of the Muller’s
depending upon the amount of paresis. It may be muscle supplied by the sympathetic nerve. Ptosis
congenital or due to trauma, vascular lesions, tumors, produced is 2-3 mm and the function of the levator is
demyelination, inflammation or systemic diseases like normal. The other features of the disease include
diabetes mellitus. Ocular movements are mostly ipsilateral miosis, enophthalmos, and anhydrosis of
affected therefore, management of the case should be ipsilateral face.
Ophthalmoplegic migraine is a rare condition in In cases of hypotropia, as the globe remains turned
which a temporary ptosis is associated with other down, the lid covers it producing ptosis when the
classical features of migraine like headache and aura. normal eye is fixing. But when the patient fixes with
After a time the defect may become permanent. the hypotropic eye, the ptosis disappears. Sometimes
Synkinetic ptosis is due to aberrant connections in these cases true ptosis may also be present.
within the central nervous system. The most common In dermatochalasis the fold of skin can cover some
variety is the Marcus Gunn jaw winking phenomenon part of the palpebral fissure giving an appearance of
in which trigeminal nerve supplying the muscles of ptosis. Sometimes in old patients, enophthalmos due
mastication aberrantly involves the levator. Clinically, to absorption of orbital fat leads to loss of posterior
the ptotic lid shoots up on opening the mouth or shift- support and ptosis.
ing the jaw to the same side (Figs 6.6A and B).
Evaluation of Ptosis
Mechanical Ptosis Before undertaking any operative procedure for the
Excessive weight of the upper lid due to any cause correction of ptosis, it is necessary to evaluate the
like edema or mass lesion, or scarring of the conjunc- patient thoroughly to choose an appropriate surgery
tiva with tethering of the levator muscle can lead to to have a desired postoperative result and to minimize
drooping of the upper lid with normal muscle func- the rate of complications.
tion. Removal of the cause is enough to correct the 1. History
condition. 2. Examination of the eye
3. Examination of the lid
Pseudoptosis 4. Assessment of lid position
5. Assessment of levator function
Due to the synkinetic movements, when the globe 6. Ocular movements
turns down, the lid follows it and so keeps it covered. 7. Abnormal synkinetic movements
8. Bell’s phenomenon
9. Tear film
10. Corneal sensations
11. Phenylephrine test.
History
It is very essential to ascertain whether the ptosis is
congenital or acquired as the amount of levator
resection required for the former group is more than
A that for the latter. History of previous surgery should
be inquired and if possible the nature of the surgery
should be determined.
Examination of the Eye

Visual acuity is assessed to detect the presence of
amblyopia.
Examination of Eyelid
Lid crease is a good guide to determine the function
of the levator. Absence of lid fold indicates very poor
levator action. Higher lid crease indicates disinsertion
of the levator in aponeurotic ptosis. The patient is
B asked to look down and the level of the two lids is
Figs 6.6A and B: Marcus Gunn (Jaw winking) phenomenon. seen. If the ptotic lid remains at a higher level than
(A) Severe ptosis of the right side while mouth is closed. the normal, it indicates lid lag and is a sure sign of
(B) Lid retraction on opening the mouth congenital ptosis due to muscle maldevelopment.
Assessment of Lid Position
Amount of ptosis is determined by measuring the
distance of the lid margin from different structures
like limbus, pupil or orbital margin, and then
comparing it with the other eye or the standard. The
most commonly practiced method is to assess the
vertical height of the palpebral fissure and to subtract
it from the normal size. As the vertical diameter of
the cornea is 11 mm and the upper 2 mm is normally
covered by the upper lid, the size of the palpebral
fissure is on an average 9 mm. The ptosis can be graded
according to the amount of ptosis (Fig. 6.7):
i. Mild ptosis means 2 mm or less
ii. Moderate ptosis means 3 mm
iii. Severe ptosis means 4 mm or more.
Assessment of Levator Function Fig. 6.7: Assessment of eyelid position and grading
the amount of ptosis
The action of the levator muscle is quantitatively
determined by measuring the amount of eyelid
excursion, or movement which is normally about 12-
15 mm. The action of the frontalis is eliminated by
pressing the brow with one hand. The patient is asked
to look down and the level of the eyelid margin is
noted. With the ruler in position, patient is asked to
follow an object which is shifted up. The difference
between the two gives an idea of the power of the
levator which can be graded as (Fig. 6.8):
• Normal 15 mm
• Good 8 mm or more
• Fair 5 to 7 mm
• Poor 4 mm or less.
Ocular Movements
Examination of the ocular movements and assessment
of the alignment between the two eyes by cover test is
very important. This also helps in detecting presence
of pseudoptosis in cases of hypotropia.
Abnormal Synkinetic Movements

Asking the patient to open the mouth and/or turn the Fig. 6.8: Assessment of levator function
by eyelid excursion
jaw from side to side to demonstrate the Marcus Gunn
phenomenon. Size of the palpebral fissure is assessed, normal Bell’s phenomenon. Levator resection surgery
while the patient is asked to look from side to side, to invariably leads to lid lag and so the eye is likely to
detect the presence of Duane’s retraction syndrome. remain open during sleep. Presence of normal Bell’s
phenomenon helps in covering the cornea during sleep
Bell’s Phenomenon
and prevents exposure keratitis. Absence or weak
When the patient closes the lid forcibly against Bell’s phenomenon should be an absolute contra-
resistance, the eyeball is seen to roll up. This indicates indication for any type of ptosis.
Tear Film 4. Amount of ptosis and levator function Both these

interrelated effects decide the nature of the surgery
Presence of normal tear film is necessary as the change
to be undertaken.
in the lid movements postoperatively may put stress
• Mild ptosis → Excellent levator function →
on it leading to dryness.
Fassnella Servat Operation
Corneal Sensations • Moderate ptosis → Good levator function →
Levator resection surgery
Altered corneal sensations also make the cornea • Severe ptosis → Poor levator function → Fron-
vulnerable to exposure and dryness. So they should talis sling surgery.
be checked preoperatively.
Fassanella Servat Operation
Phenylephrine Test
In cases of minimum ptosis, vertical shortening of the
In cases of mild to moderate ptosis, a drop of
lid is achieved by resecting a strip of upper part of
phenylephrine should be instilled into the eye. If this
tarsus along with some part of conjunctiva and
elevated the lid by 2-3 mm, Fassanella Servat surgery
underlying Muller’s muscle. Histopathological exami-
can be performed with good results.
nations have shown that the resected tissues hardly
ever include the fiber of levator muscle. Its indications
Surgical Treatment are minimum congenital ptosis, Horner’s syndrome
Before undertaking a surgical procedure for blepharo- and minimal residual ptosis. The only objection to the
ptosis, certain points have to be kept in mind to decide surgery is a possibility of development of dry eye due
the time and type of surgery. to removal of the lipid secreting tarsal plate and mucin
1. Age It is better to defer a formative surgery up to secreting goblet cells (Figs 6.9 A to D).
the school going age, i.e. about 3 years, because it a. The surgery is performed as an outdoor procedure
is not possible to assess the child thoroughly before under local anesthesia. Anesthetic agent with
this age. Further, the structures of the lid are very dilute adrenaline is injected into the upper lid
tender and friable and hence it is difficult to under the skin and under the conjunctiva after the
identify and handle them during operation. eversion of the lid.
Besides, as ptotic lid rarely induces amblyopia, and b. Three lid stitches are applied at the lid margin. Two
remarks of others have little psychological impact small incisions are put at the two extremes of the
at this age, it is not imperative for surgery. If the lid crease for passing a nonabsorbable suture (Fig
ptosis is severe and bilateral, giving rise to an 6.9A).
abnormal head posture, temporary sling surgery c. Another row of 3 stitches are passed at the lower
can be performed. border of the everted lid, i.e. at the upper border
2. Laterality If unilateral, the level has to be adjusted of tarsal plate. This helps in applying traction on
to the opposite normal side. But if it is bilateral the lid and avoids the use of clamps which were
and unequal, and if an attempt is made to bring employed traditionally (Fig. 6.9B) surgery.
the worse lid to the height of the better lid to avoid d. A continuous mattress stitch is passed through the
second surgery, the better lid may come down full thickness of the lid distal to the proposed site
postoperatively below the preoperative level of resection (Fig. 6.9 C).
because of the decrease in the reciprocal innerva- e. Tarsomullerectomy is done with scissors, keeping
tion. This makes the surgery in the other eye neces- tension on the lower row of stitches. In Horner’s
sary about which the patient should be informed. syndrome, 1 mm resection gives 1 mm correction
3. Age of onset of ptosis Levator resection gives less but in other cases 1.5 or more resection is required
correction in cases of congenital ptosis (dysmyo- to achieve the same result (Fig. 6.9D).
genic) and hence chances of over correction are f. If a nonabsorbable suture is used, it can be pulled
minimum, whereas in acquired ptosis, it is vice out from the skin side on the seventh day. In any
versa. Lid lag is always present and more marked case, care is taken to avoid rubbing of the stitch on
in congenital cases. the cornea.
Fig. 6.9A: Fassanella Servat surgery: Traction sutures at the Fig. 6.9C: Fassanella Servat surgery: Passing a continuous
eyelid margin and two small skin incisions for passing a suture suture just beyond the desired line of incision
Fig. 6.9B: Fassanella Servat surgery: Three sutures at the Fig. 6.9D: Fassanella Servat surgery: Excision of
upper border of tarsal plate in place of a clamp the Tarso-Muller complex
Levator Resection
most of the surgeons. As the levator is the primary
This is the surgery with wide scope in all types of elevator of the lid, its shortening for the correction of
ptosis and in most of the cases, it is the first choice for the drooping lid is the most physiological procedure.
The muscle can be exposed from the skin side,

called the Everbusch surgery, or the conjunctival side
as suggested by Blascovisc. The anterior approach is
favored by most of the surgeons as the orientation is
better, more resection is possible and advancement of
the aponeurosis onto the tarsal plate can be done
simultaneously. Scar formed by the healing of the skin
incision helps in the formation of the lid fold. The
posterior approach is useful for ptosis of 3-4 mm. As
the exposure of the other tissues especially the orbi-
cularis, is less, reaction to the surgery is minimum and
the lid function returns to normal almost immediately.
The most critical decision in this surgery is to
determine the amount of levator to be resected. Rycroft
had advocated 4 mm resection for every mm of
correction. But this is an oversimplified formula which
is not accepted well. Most of the surgeons have obser-
ved that resection up to 8 mm does not produce any
substantial lift of the lid, and then each 3 mm resection Fig. 6.10A: Levator resection surgery skin approach.
gives rise to 1 mm of correction. This is true for the Skin incision
dysmyogenic or congenital ptosis, but in acquired
cases, each mm of ptosis requires 2 mm of resection.
Berke has suggested that the lid level should be
adjusted in relation to the cornea on the operation table
only, keeping in mind preoperative evaluation. In
moderate to severe cases, the lid is adjusted 1 mm
above the upper limbus; in moderate cases, it is kept
at limbus; and with good action, it is adjusted to
remain 1 mm below the limbus.
a. Surgery is preferably done under local anesthesia
so that the lid level can be adjusted with patients’
cooperation. Traction sutures are applied at the lid
margin. Lid plate is inserted into the upper fornix
with ointment on its under surface. Skin incision
is put along the lid crease, if it is visible. Otherwise
it is made at the proposed site of lid fold in
accordance with the other eye or about 7-8 mm
from the ciliary border. It should extend almost
the whole width of the lid and should be muscle
deep (Fig. 6.10A).
b. The skin-muscle lamina is separated from the
deeper layers by inserting and spreading the blades
of scissors. Orbital septum is perforated and the Fig. 6.10B: Levator resection surgery skin approach. Separating
the skin muscle complex from the underlying aponeurosis
underlying aponeurosis is exposed which is seen
as a white sheet under the prolapsing pad of fat tarsal plate. The stitches are lifted up and the
(Figs 6.10B and C). aponeurosis is separated from the underlying tarsal
c. Dissection is carried upward for about 20 mm plate below and conjunctiva higher up. Reddish
where a horizontal glistening tarsal (Whitnall’s) fibers of the Muller’s muscle are visible in this plane
ligament is visualized. (Fig. 6.10D).
d. Three sutures are passed through the lower end of e. The two horns of the muscle which are seen as
the levator which is attached to the front of the expansions on the sides are severed with straight
Fig. 6.10E: Levator resection surgery skin approach.

Fig. 6.10C: Levator resection surgery skin approach.
The horns are cut
Incising the orbital septum
Fig. 6.10F: Levator resection surgery skin approach. Three

Fig. 6.10D: Levator resection surgery skin approach. Elevation rows of sutures passed at the desired site
of the lower most part of levator from the tarsal plate by traction
sutures
scissors preventing damage to the lacrimal gland then passed through the overlying levator at the
on the lateral side and the superior oblique and its estimated distance. Provisional knots are tied and
pulley on the medial side (Fig. 6.10E). the lid level is checked in relation to the limbus
f. Three pairs of double armed sutures are inserted and readjustment is done, if necessary. Final knots
into the anterior surface of the tarsal plate about 3 are tied and the excess muscle is excised (Figs 6.10F
mm below the superior edge. These sutures are and G).
Frontalis Sling Surgery (Fig. 6.11)

Patients in whom there is no detectable function of
the levator or in whom the previous levator resection
surgery has not given a satisfactory lift to the lid, lifting
of the lid is achieved by means of a sling attached to
the frontalis muscle. The other indications of the
surgery include Marcus-Gunn phenomenon in which
the levator muscle has to be sacrificed to get rid of the
lid retraction component.
Different materials are used as the sling, but
autogenous fascia lata is most commonly used as it is
well tolerated and maintains strength. The other
materials employed are strips of sclera, silicon rods
Fig. 6.10G: Levator resection surgery skin approach. Sutures or bands, and synthetic sutures. Another material used
tied after adjustment of lid level and extra muscle excised is the levator muscle itself which can be divided into
2 strips and attached to the frontalis. Lid lag is a
g. Three interrupted sutures are passed from the constant feature of this surgery so an attempt should
edges of the skin incisions taking superficial bites be made to minimize it without compromising with
of the levator muscle to form the lid fold. The rest the height.
of the skin incision is closed by interrupted or a. Surgery is commonly done under general anes-
continuous stitches (Figs 6.10H and I). thesia. Skin incision is put along the proposed site
h. A stitch passed through the lower lid is pulled over of lid crease. Skin and orbicularis are separated up
the forehead and stuck there to close the eye, and to the tarsal plate.
is kept in place till the Bell’s phenomenon becomes b. Three small skin incisions are put on the forehead
normal (frost suture). just above the brow, the central one a little above
i. The dressing is opened up from the next day and the rest and the deeper tissues are exposed.
the patient is encouraged to keep the lid mobile.
Fig. 6.10H: Levator resection surgery skin approach. Sutures

passed through skin edges and the deeper tissue to form the
lid crease
Fig. 6.10I: Skin incision closed Fig. 6.11: Schematic diagram of the frontalis sling surgery
c. The two blades of artery forceps are passed from
the upper incisions to come out in the lower
incision in the submuscular space. The material to
be used is caught between the two open blades and
pulled up. Alternatively, a Wright’s fascia needle
can be used to bring out the material onto the
forehead.
d. The lower ends of the material are fixed to the front
of the tarsal plate.
e. The lateral two ends in upper part are fixed to the
frontalis and then they are taken out from the
central incision. A knot is applied in the center and
tightened to give a desired height.
f. The skin incisions are closed with interrupted
stitches.
In cases of Marcus Gunn phenomenon, the levator
Figs 6.12 A and B: Schematic diagram of the
muscle is cut at the upper border of the tarsal plate split level lid resection
and is allowed to recede up.
Aponeurotic Repair
In cases of aponeurotic ptosis, an attempt is made to
identify the disinserted head of the muscle or its
dehiscence. In either case, the defect is repaired. In
absence of an obvious defect, about 10 mm plication
of the sponeurosis is done.
Other Surgical Procedures

1. Split level lid resection As advocated by Mustarde,
this is a vertical shortening procedure, in which
the skin muscle lamina is shortened anteriorly and
tarsoconjunctiva is resected posteriorly. As it
preserves the levator Muller’s complex, it is
claimed to have minimum lid lag with good lift. Figs 6.13A and B: Hess procedure
In severe cases a sling is made of the levator on
which the tarsal plate is hanged, called the levator 5. Mc Cord method This is a full thickness resection of
hitch (Figs 6.12A and B). lid in which a measured amount of tarsus, levator
2. Hess procedure This is a surgery in which a non- aponeurosis, Muller’s muscle and attached
absorbable material like supramid suture is used to conjunctiva are removed.
have a brow suspension for temporary lid eleva- 6. Puttermann and Urist operation This is a modifica-
tion. This procedure is useful in children before the tion of Fassanella Servat surgery where only a
age of three or in the cases of traumatic ptosis where section of conjunctiva and Muller’s muscle is
improvement is expected (Figs 6.13A and B). resected keeping tarsal plate intact.
3. Jone’s levator advancement operation Instead of
Complication of Ptosis Surgery
resecting the aponeurosis, the muscle is advanced
over to the tarsal plate anterior to the aponeurosis 1. Undercorrection
after isolation at the Whitnall’s ligament. 2. Overcorrection
4. Berke-Motais operation Superior rectus muscle is 3. Lid lag-lagophthalmos-keratitis
attached to the front of the tarsal plate for the 4. Entropion ectropion-lash ptosis
elevation of the lid. 5. Conjunctival prolapse
6. Loss of lashes ded doses should also be tried. For temporary

7. Asymmetrical lid contour-lid fold improvement in cosmesis, tarsorrhaphy or cantho-
8. Hemorrhage edema. plasty can be performed. Isolated upper lid retraction
can be corrected by mullerectomy. In severe cases,
LID RETRACTION levator recession with or without spacer is necessary
(Fig. 6.15). This can be in the form of preserved sclera,
This is the abnormal elevation of the upper lid, seen
fascia lata, temporalis fascia or ear cartilage. In lower
most commonly in cases of dysthyroidism (Fig. 6.14).
lid, the retractors are recessed and spacer grafts
Other causes include sympathetic stimulation in
inserted in between (Figs 6.16A to C). Amount of
Claude Bernard syndrome, prolonged high doses of
scleral graft required is approximately three times the
steroids, scarring of the skin, Marcus Gunn pheno-
correction necessary.
menon, hydrocephalus, and lesions involving
midbrain.
In dysthyroid patients, upper lid retraction is often
associated with the same pathology in lower lid. No
permanent surgery should be done till the hot stage
of the disease is over and condition is stabilized.
Besides, a medical line of treatment in the form of
systemic corticosteroids (1.50-2.00 mg) daily in divi-
Fig. 6.14: Right upper lid retraction
Figs 6.16A to C: Correction of lower lid

Fig. 6.15: Levator recession with spacer graft retraction by preserved sclera
FURTHER READING 6. Blascowicz L. A new opeeration for ptosis with shortening
of levator and tarsus. Arch Ophthalmol 1923;52:563.
1. Beard C. Ptosis (3rd edn) St Louis: CV Mosby, 1981. 7. Fassanella RM, Servat J. Levator resection for minimal ptosis:
2. Berke RN. Results of resection of the levator muscle through Another simplified operation. Arch Ophthalmol 1961;65:439.
a skin incision in congenital ptosis. Arch Ophthalmol 8. Freuh B: Surgery of the Eye (1st edn). New York: Churchill
1959;61:177. Livingstone, 1988.
3. Berke RN, Wordsworth JAC. Histology of levator muscle 9. Jones LT, Quickert MH, Wobig JL. A cure of ptosis by
in congenital and acquired ptosis. Arch Ophthalmol aponeurotic repair. Arch Ophthalmol 1975;94:629.
1955;53:413. 10. Mustarde JC. Repair and Reconstruction in the Orbital Region
4. Betharia SM, Kumar S. Levator sling for Marcus Gunn ptosis. (2nd edn). Churchill Livingstone, London, 1980.
Br J Ophthalmol 1987;71:681-89. 11. Putterman AM, Urist MJ. Mueler’s muscle conjunctiva
5. Betharia SM, Grover AK, Kalra BR. The Fassanella Servat resection. Arch Ophthalmol 1975;93:619.
operation: A modified simple technique. Br J Ophthalmol
1983;67:58-60.
Chapter 7
Tumors of the Eyelids*

Benign tumors of the eyelids occur much more

commonly than malignant tumors. Tumors of the lids
can be classified, according to the structure of origin,
into the following groups:
1. Epithelial
2. Melanocytic
3. Glandular
4. Vascular
5. Neurogenic.
EPITHELIAL TUMORS
Tumors of the surface epithelium can be divided, on
the basis of their clinical behavior and histologic Fig. 7.1: Papilloma arising from the lid margin
features, into three main groups; benign, precan-
cerous, and malignant. the malignant lesions. They are characteristically
associated with a chronic inflammatory process and
Benign Epithelial Tumors may be caused by some mycotic infections, burns or
The most important benign lesions originating from radiation therapy. Histopathologically, they show
the surface epithelium are squamous papilloma, inflammatory reaction and epithelial hyperplasia.
pseudocarcinomatous hyperplasia, keratoacanthoma,
seborrheic keratosis, and inverted follicular keratosis. Keratoacanthoma
This is a specialized variant of the previous lesion
Squamous Cell Papilloma occurring on the exposed areas of the skin. It is seen
These are the most common benign lesions of the as a dome shaped nodule with a central keratin-filled
eyelid (Fig. 7.1). These lesions can be sessile or pedun- crater and elevated rolled margin. It can occur in
culated and have a color similar to that of adjacent immunosuppressed individuals.
skin. They are often multiple and tend to involve the
lid margin. Histologically, they are composed of finger Seborrheic Keratosis
like projections of vascularized connective tissue It is one of the common lid conditions involving the
covered by hyperplastic epithelium. Treatment is by face and eyelids of the middle aged and elderly
surgical or carbon dioxide laser ablation. individuals. The lesion is tan to dark brown in color
and appear as well demarcated, lobulated cerebriform
Pseudocarcinomatous Hyperplasia excrescences, with verrucous, slightly friable surface
These are usually a little elevated lesions with irregular (Fig. 7.2). The acanthotic epidermis often contains
surface that may be ulcerated or crusted mimicking keratin-filled cystic inclusions, called horn cysts.
*Note: See also Chapter 17.
Chapter 7: Tumors of the Eyelids 49
Actinic Keratosis
This is the most common precancerous lesion and is
seen in sun exposed areas of the body of fair-skinned
middle aged individuals. It appears as a single or
multiple, scaly keratotic, flat topped lesions. The
patients may have other cutaneous premalignant and
malignant lesions elsewhere. If untreated, it may get
converted into squamous cell carcinoma.
Bowen’s Disease (Intraepithelial Epithelioma)

It appears as an erythematous, pigmented, crusty,
scaly, fissured, keratotic plaque. It is more common
in sun sensitive individuals. About 5% of the lesions
will show changes of invasive carcinoma and so
Fig. 7.2: Seborrheic keratoiss showing waxy looking crusts immediate treatment is necessary. At least 25% of cases
have primary internal or extracutaneous cancers.
Microscopic examination shows pigmentation with Microscopically, the lesion shows hyperkeratosis,
keratinocytes and may resemble squamous cell acanthosis, and hypogranulosis. There is a strong
carcinoma. evidence to suggest that the cause of the disease is
arsenic.
Inverted Follicular Keratosis
It presents as a nodular or wartlike keratotic mass Radiation Dermatosis
mostly present at the lid margin. It may present as a The injurious effect of radiation depends upon the total
cutaneous horn (Fig. 7.3) and has a tendency to recur dosage applied. Doses of more than 8000-10000 rads
if incompletely excised. It was previously thought to cause severe damage. Carcinogenic effect is seen about
be related to hair follicle hence named follicular. 20 years after exposure. About two third of the tumors
Precancerous Lesions are basal cell carcinomas and the second common
tumor is squamous cell carcinoma. Changes of der-
These include actinic (solar) keratosis, Bowen’s matosis precede the changes of neoplasia.
disease, radiation dermatosis, and xeroderma
pigmentaosum. Xeroderma Pigmentosum
This progressive disorder affects sun exposed areas
of the body in early childhood (Fig. 7.4). It is an
autosomal recessive condition and may be associated
with retarded growth or delayed sexual development.
It affects all races. The fibroblasts in the skin are highly
sensitive to ultraviolet light and the replication of RNA
is reduced during the process of repair. This is related
to an enzymatic deficiency. Clinically, there is a slight
erythema associated with scaling and numerous freck-
les. Later on pigmentation with telangiectasia may be
seen which then changes over to either basal or squa-
mous cell carcinoma.
Malignant Epithelial Tumors

Basal Cell Carcinoma
This accounts for about 85-95% of all malignant
Fig. 7.3: Cutaneous horn epithelial tumors of the eye lid. It commonly involves
Fig. 7.5: Noduloulcerative type of basal cell carcinoma
Fig. 7.4: Xeroderma pigmentosum
fair skinned elderly individuals and is rarely seen in

children. The lesion is found most commonly on the
lower lid (50%), followed by at the inner canthus
(25%), on the upper lid (10-15%) and rarely at the outer
canthus (less than 5%). This bias seems to be due to
the differential exposure of different parts of the lids
to actinic rays.
Clinical Features
Several clinical types may be seen, but 4 types are most
common. They are 1. noduloulcerative, 2. pigmented
3. morphea or sclerosing, 4. superficial. The nodulo- Fig. 7.6: Extensive rodent ulcer
ulcerative is the most common variety and is seen
initially in the form of a pearly, firm, raised nodule,
with small telangiectatic vessels on the surface (Fig.
7.5). As the nodule slowly increases in size it may
undergo central ulceration. Eventually the lesion may
appear as a slowly enlarging ulcer surrounded by a
prominent rolled border (Rodent ulcer) (Fig. 7.6).
Pigmented variety shows a little pigmentation in the
noduloulcerative type of lesions (Fig. 7.7). The
morphea or sclerosing type appears as pale, indurated
plaque with an ill-defined border. In superficial type,
erythematous scaly lesions may show ulceration or
crusting.
Basal cell carcinoma is a locally malignant tumor
and metastasis to the distant sites is very rare. The
spread into the surrounding area is gradual and
relentless. Posteriorly, it invades the orbit in a circular
fashion, so that it involves the tissue in the anterior Fig. 7.7: Basal cell carcinoma with pigmentation
plane initially and then goes backward. Involvement 3. Exenteration of the orbit If there are signs of
of the orbital tissues is heralded by diplopia, pain, and involvement of orbital structures, exenteration is
limitation of movements. Death, which may be due the only choice.
to spread of the tumor into the cranial cavity, is very 4. Cryotherapy Cryotherapy using liquid nitrogen at
uncommon. minus 25° to 30° is claimed to be a new effective
Histopathologically, basal cell carcinoma is seen method of treatment of Basal Cell carcinoma of
to arise from the pluripotential primary germ cells of eyelids. Long term complications like pigmentation
the basal layer of the epidermis. Solid cords of cells and damage of tissue including stenosis of
with basophilic scanty cytoplasm and palisading nasolacrimal duct does not occur. It can be used in
nuclei are seen invading the deeper tissues. A variant recurrent tumors also but not in tumors affecting
of this, called metatypical or basosquamous carci- the bone. However it is a new method of treatment
noma, shows some features of squamous cell carci- and further clinical trial is required before it is
noma, which clinically behaves as basal cell carcinoma. claimed to be superior to radiotherapy.
The tumor may also show adenoid, cystic or keratotic
differentiation. In the morphea variety, elongated Nevoid Basal Cell Carcinoma Syndrome
strands of basaloid cells are embedded in a dense In this autosomal dominant syndrome, basal cell
fibrous stroma. In superficial variety, multicentric carcinoma of the lids and other parts of the body like
pattern with diffuse involvement of epidermis and nose, lids, cheeks, etc may be associated with cyst of
dermis, is seen. the jaw, skeletal anomalies, neurological abnor-
malities, and endocrine disorders.
Treatment
Squamous Cell Carcinoma (Fig. 7.8)
1. Radiation Although the tumor is sensitive to
radiation, except for the morphea variety, it is It typically affects the fair skinned elderly individuals.
reserved for only those cases where the surgical Incidence is much less than the basal cell carcinoma
excision and reconstruction of the area is difficult. (1:40) and constitutes only 5% of all malignant tumors
The total dosage advocated is 4000 to 7000 rads. of the lid. It has a predilection for transitional zones
2. Surgical excision and lid reconstruction Best treatment and so is commonly seen at the lid margin and the
is complete excision of the tumour including 1–2 limbus. Lower lid is more commonly affected, but
mm wide strip of normal looking skin and adjacent upper lid and outer canthus are more frequently
tissue which should be better be proven to be involved than in basal cell carcinoma. The tumor may
tumor free on frozen section study. Dr. Mohs at arise de novo or from precancerous conditions.
the University of Wisconsisn devised a micro- Clinically, the lesion usually presents as an
elevated, indurated plaque or nodule that tends to
scopixally guided chemosurgical technique for
ulcerate and shows irregular borders. It may show a
excising basal cell carcinoma of the ocular adnexa.
This method evolved fixing the tissue with zinc
chloride paste making serial sections, staining these
immediately and then proceeding deeper and
deeper until all the cancerous tissue has been
removed. The tumor is excised in blocks of 5 to 10
mm square and 2 to 3 mm thick. Instead of using
zinc chloride as fixative, fresh tissue examination
technique may also be used. However Moh’s
technique offers the most accurate method of
tumor eradication and salvage of healthy tissue in
the orbital area. The gap may be allowed to be filled
up with granulation tissue followed by Thiersch
graft or full thickness graft at the same sitting with
skin from mastoid or supraclavicular area. Fig. 7.8: Kissing nevus at the outer canthus
papillomatous growth. Early lesions rarely metas-

tasize and have a very good prognosis. If neglected, it
may spread to the lymph nodes.
Histopathological picture varies according to the
stage of the disease. In well differentiated tumors, the
cells are polygonal with abundant acidophilic cyto-
plasm. Dyskeratotic cells with formation of keratin
pearls are observed. Nuclei are prominent and hyper-
chromatic. Intercellular bridges can be easily found
in well differentiated tumors.
Adenoid squamous cell carcinoma is a variant of
the squamous cell carcinoma showing hyaluronic acid Fig. 7.9: Kissing nevus of left eyelid
within the adenoid structure. figuration. Presence of hairs in an elevated pigmen-
Treatment Adequate surgical excision with reconstruc- ted nodule usually indicates that the lesion is
tion of the defect is usually curative. intradermal.
4. Kissing Nevus This type of nevus is quite extensive,
MELANOCYTIC TUMORS affecting both the upper and lower lid margins
These tumors arise from three sources, i.e. nevus cells, equally and identically. This is thought to be due
melanocytes of epidermis, and melanocytes of dermis. to an abnormal collection of melanocytes derived
Nevus cells do not have dendritic processes. Epi- from the neural ectoderm at the site of fusion of
dermal melanocytes demonstrate shorter dendritic the eyelids in intrauterine life (Fig 7.9).
processes than the dermal counterparts.
Dermal Melanocytic Tumors
Benign Melanocytic Tumors
These lesions arise from the deeply situated melano-
Nevus Cell Tumors cytes.
1. Blue nevi and cellular blue nevi These lesions arise
These melanocytic lesions vary in their clinical appear-
from the melanocytes which have been arrested in
ance and are frequently seen on the surface or margin
the dermis before reaching the epidermis. The blue
of the lid. Histologically they are divided into three
nevus is a dome shaped small lesion, which attains
types, i.e. junctional, compound, and intradermal.
its color due to scattering of light by melanin
Intermediate type can also be seen. Hormonal factors
pigments. Cellular blue nevus has islands of deeply
associated with puberty or pregnancy may cause
pigmented melanocytes interspersed with bundles
increased pigmentation and enlargement of the lesion.
of nonpigmented cells exhibiting a neuroid
1. Junctional nevus The lesion arises from the deeper
appearance.
layers of epidermis and does not involve the
2. Nevus of Ota (Oculodermal melanocytosis) Sub-
dermis. Clinically it appears as flat, pigmented
epithelial conjunctival melanosis may be associated
lesion. It has capacity to evolve into a malignant
with melanosis of the face along the distribution
lesion.
of the first and second divisions of the trigeminal
2. Compound nevus The lesion originates in the
nerve. It may involve other ocular structures like
epidermis and drops off into the deeper layer, i.e.
uveal tract and sclera. Although usually benign,
dermis. It is more frequently seen than the pure
malignancy of orbit or uveal tract is reported.
junctional lesion and like the former type, may
Secondary glaucoma in cases with uveal tissue is
undergo malignant changes. Sometimes, the nevus
also known.
involves an equal portion (mirror image) of the
upper and lower eyelid margins (kissing nevus)
Epidermal Melanocytic Tumors
(Fig. 7.8).
3. Intradermal nevus It is the most common variety of 1. Freckle (ephelis) This is a small, brown macular
the three and is rarely converted into a malignant lesion scattered over the sun exposed areas of the
lesion. The surface of the lesion may have a skin. Exposure to sunlight deepens the color of the
papillomatous, dome shaped or pedunculated con- lesion.
2. Lentigo simplex This is a flat, brown to black lesion Melanoma Arising From Nevus
measuring about 1-2 mm in size. It is not affected
Intraepidermal nevus frequently undergoes malignant
by exposure to sunlight.
changes. The signs which suggest malignant transfor-
3. Lentigo senilis It occurs in about 90% of elderly
mation are:
white race people. The lesions are multiple and
1. Change in size
appear as dark brown macules with irregular
2. Change in surface characteristics (crusting, oozing,
outlines.
bleeding ulceration)
3. Symptoms of pain, itching and tenderness
Malignant Melanocytic Tumors
4. Change in shape (rapid elevation)
Malignant Melanoma 5. Change in surrounding skin (redness, swelling,
satellite lesions).
According to the western literature, it constitutes
about 1% of all malignant tumors of the eyelid. Four
Dysplastic Nevus Syndrome
different types of primary cutaneous melanomas are
recognized. They are: 1. lentigo meligna melanoma, A familial disorder involves upper part of the body
2. superficial spreading melanoma, 3. nodular in the form of multiple large nevi.
melanoma, and 4. acral lentiginous melanoma. All Prognostic factors According to the level of involve-
virtually arise from melanocytes. ment of the tissue it has been graded into 4-5 levels,
1. Lentigo maligna (Hutchinson’s freckle) It is a pre- most superficial one involving only the epidermis
cursor to the melanoma and is seen as a flat macule having the best prognosis. Tumor thickness is also
with irregular borders. Amount of pigmentation considered as a useful guide. Lentigo maligna has the
is variable. Malignant transformation occurs in one best prognosis and nodular melanoma has the worst.
fourth of the cases (Fig. 7.9). Amelanotic tumors are more aggressive. Histo-
2. Superficial spreading melanoma (Pagetoid) The lesion pathologically, mitotic activity is considered insigni-
is seen in 5th decade in the form of small faintly ficant. Denser the inflammatory infiltrate, better is the
palpable pigmented macule with variable color on prognosis.
the unexposed area of the skin.
3. Nodular melanoma It appears as a blue-black or GLANDULAR AND OTHER ADNEXAL TUMORS
amelanotic pedunculated nodule, involving any
The eyelids contain a large number of different types
area of the skin and mucous membrane and
of glands and hence are prone to develop a variety of
increasing fast in size up to 1-3 cm (Fig. 7.10).
tumors:
Deeper invasion is faster and more extensive than
the other types. Sebaceous Gland Tumors
4. Acral lentigo maligna It appears on the soles and
palms and looks like lentigo maligna. Benign Lesions
Senile sebaceous nevus may be seen as a small,
nodular, umbilicated lesion of yellowish color. In
Torre’s syndrome, multiple sebaceous gland lesions
are associated with multiple visceral carcinomas.
Gardener’s syndrome is characterized by intestinal
polyposis whereas in Oldfield’s syndrome, familial
polyposis of the colon is associated with multiple
sebaceous cysts. Very rarely a multiple hamartoma
syndrome (Cowden’s disease) is encountered where
the sebaceous gland lesions are associated with lesions
of thyroid and breast.
Sebaceous Gland Cell Carcinoma

It is also called meibomian cell carcinoma. It forms
Fig. 7.10: Extensive nodular melanoma of the lower lid about 1-3% of all malignant tumors of the lid. It is
commonly seen in elderly ladies with sometimes a hair follicles, called trichoepithelioma, are seen as
prior history of radiation. In India and other Asian multiple firm nodules all over the face. Pilomatrixoma,
countries, the incidence is found to be much higher also called calcifying epithelioma of Malherbe, appears
than in the western world. As the sebaceous glands as a solid or cystic freely movable subcutaneous
are more numerous in the upper lid, the occurrence is nodule.
more there than in the lower lid.
VASCULAR TUMORS
Clinical Features
Primary angiomatous lesions of the eyelids are
It starts as a small, firm to hard, painless nodule with hamartomas that may be present at birth or appear in
the skin over the swelling free mimicking a chalazion. first few weeks. A group of secondary angiomatous
It gradually enlarges in size and then may be fixed to lesions arise at any age.
the skin (Fig. 7.11). It may break open on the
conjunctival side with a fungating or papillomatous Capillary Hemangioma
appearance. Sometimes there is a diffuse growth, pre-
It is the most common vascular tumor of the lids
senting as a thickened tarsal plate. Initially it may
occurring in one of every 200 live births. It is reddish
present as a case of blepharitis, persistent conjunc-
purple in color, elevated, soft in consistency, with
tivitis or meibomitis (masquerade syndrome).
small surface invaginations and is called strawberry
This is a highly malignant tumor having a fast
nevus (Fig. 7.12). Though termed congenital, it appears
growth and spread to the lymph nodes. Prognosis is
in first few weeks of life and enlarges in size for 6
poor in tumors situated in the upper lid and/or having
months. Then there is a regression of the lesion; 30%
a size of more than 1 cm.
regress completely by the age of 3 years and by the
Histopathologically the tumor contains many neo-
age of 7 years, 75-80% undergo regression. Micro-
plastic cells exhibiting sebaceous differentiation. These
scopic examination shows lobules of small capillaries
cells have an abundant, finely vacuolated cytoplasm
interspersed with sparse fibrous septa. If small, it can
that often appears foamy or frothy. The vacuoles often
be left alone without any treatment hoping for the
cause notching of the nuclear membrane. The nuclei
regression to take place. If large, it can lead to
are centrally placed or slightly displaced toward peri-
amblyopia due to mechanical ptosis or astigmatism,
phery of the cells.
and so an early treatment is mandatory. Cryotherapy,
sclerosing agents, irradiation, systemic steroids, etc
Treatment
have been tried in the past. But now intralesional
Early diagnosis with wide surgical excision gives good injection of corticosteroids, a combination of beta-
results. Radiation is used only as a palliative therapy. methasone 40 mg and triamcinolone 10 mg, is a well
Other glandular tumors include syringoma arising accepted mode of treatment with better results and
from sweat glands. They are usually seen as multiple less complications.
yellowish waxy nodules of 1-2 mm size. Tumors of
Fig. 7.11: Meibomian cell carcinoma showing fungating Fig. 7.12: Capillary hemangioma
mass projecting from conjunctival side (Strawberry mark)
Nevus Flammeus nevus syndrome is characterized by cutaneous
cavernous hemangiomata which are soft and com-
It is a flat lesion that exhibits a deep purple hue. It
pressible with similar lesions in the gastrointestinal
does not blench on pressure and is called port wine
tract.
staining. It may be associated with Sturge-Weber
syndrome (Fig. 7.13) in which the skin lesion is associa-
Lymphangioma
ted with glaucoma and complex cerebellar manifesta-
tions. Histopathologic examination shows large It is a hamartomatous lesion involving lid and orbit.
dilated cavernous spaces in the dermis. The cutaneous The lesions are diffuse, without any well formed
lesion does not require any treatment except in white capsule, slowly progressive and without any chance
races where it is cosmetically unacceptable, and can of spontaneous regression. Sometimes spontaneous
be hidden by application of some skin cream. Other rupture of the lesion can take place leading to sudden
lesions require proper management after thorough increase in size or proptosis. The lesion can undergo
investigation. degeneration giving rise to a chocolate cyst. Micro-
scopically, it is composed of irregular anastomosing
Cavernous Hemangiomas lymphatic channels lined by a single layer of endothe-
lial cells without pericytes.
It develops in 2nd-4th decades of life. It is slowly pro-
gressive and has no tendency for spontaneous
Glomus Tumor
regression. It is less well defined and its color depends
upon its depth. It does not possess the prominent A vascular hamartomatous lesion, it is clinically seen
arterial blood supply as it is present in cases of as a solitary, reddish purple nodule that is small and
capillary hemangiomas and hence the vascular usually tender.
channels become stagnant and separated from the
systemic blood supply. Secondary changes like Angiosarcoma
calcification, fibrosis and hemosiderin deposition can
This rare lesion is sometimes found on the face. The
occur. Microscopically, it shows large dilated blood
lesions can be single or multiple looking like blood
filled spaces lined by a thin layer of endothelium. Local
blisters which may ulcerate and bleed profusely.
excision is required which is mostly satisfactory
Histopathologic examination shows pleomorphic
without any chance of recurrence. In Kasanbach-Merrit
anaplastic cells that are difficult to differentiate from
syndrome, cavernous hemangioma is associated with
carcinoma or fibrosarcoma. The fatality rate is about
thrombocytopenic purpura. The blue rubber bleb
40%. It responds poorly to radiotherapy.
NEUROGENIC TUMORS
Neurofibromatosis
(von Recklinghausen’s disease)
Along with the Sturge-Weber syndrome, it forms a
part of the phakomas. There is a developmental defect
of neuroectodermal tissues in which the peripheral
nerves all over the body may be affected. It is domi-
nantly inherited and the only evidence at birth may
be a pigmented spot. It grows slowly and progresses
fast during puberty or pregnancy, but may remain
stationary. It is usually multiple and not encapsulated.
The lesions may involve uvea, retina, orbit, conjunc-
tiva and angle of the anterior chamber giving rise to
glaucoma or buphthalmos. Pathologically, there is an
irregular overgrowth of Schwann’s cells associated
Fig. 7.13: Sturge Weber syndrome having portwine with an increase in reticulin and collagen, intimately
stain on both sides penetrated by nerve fibers either singly or in bundles.
Plexiform Neurofibroma
It characteristically affects the upper lid. Present at
birth, it grows slowly in size but rapidly at puberty.
The lesion is along the distribution of trigeminal and
cervical nerves. The upper lid becomes thickened and
opens with difficulty. The skin over the lesion is
normal but may be pigmented and mostly movable.
It may spread to frontotemporal region and rarely
penetrate the orbit producing proptosis (Fig. 7.14).
Fig. 7.15: Nodular neurofibroma

(Molluscum fibrosum)
well demarcated, firm, and mobile. Sometimes it may

be massive giving rise to pendulous folds.
Treatment of all the varieties is difficult, but in cases
Fig. 7.14: Plexiform neurofibroma of the left upper lid of plexiform neurofibroma producing cosmetic dis-
figurement and ptosis, surgical excision from the sub-
Diffuse Neurofibroma cutaneous layer or full thickness lid resection with
It leads to thickening of one side of face giving rise to reconstruction can be performed.
facial hemihypertrophy and is also known as elephan-
tiasis neuromatosis. FURTHER READING
1. Dutton JJ, Anderson RL, Schelper RL, Purcell JJ. Orbital malig-
Molluscum Fibrosum (Fibroma Molluscum) nant melanoma and oculodermal melanocytosis. Ophthal-
mology 1984;91:497-507.
Multiple small to moderate size nodules cover the 2. Spender WH. Ophthalmic Pathology. An Atlas and Textbook
whole face including lids (Fig. 7.15). The lesions are Philadelphia: WB Saunders Company: 1985.
Chapter 8
Miscellaneous Conditions
of the Eyelids
Xanthelasma a day may at least change the coloration of the lesion.

Surgical excision, carbon dioxide laser ablation are
It is the most common cutaneous xanthomatous lesion
other treatment modalities. Recurrences are however
in the skin of the lids. It appears as a soft yellowish or
common.
creamy yellow plaque/patch which first starts in the
upper medial, then in lower medial part of the skin of
Essential Blepharospasm
the lid. Frequently forming a continuous circular patch
all around the lids (Fig. 8.1). The genesis of formation It is a repeated involuntary contraction of the orbicu-
of xanthelasma is that lipid content of the cells falls laris oculi muscle. The earliest feature is an increased
out of suspension and produces a foreign body frequency of blinking. There is an inability to see
reaction. The lipid patches are engulfed by macro- during the spastic phase. The patient also has some
phages which appear as distended “foam cells “ or physical and emotional discomfort. It mostly affects
xanthoma cells. On histological sections the foam cells elderly females. The exact etiology is not known but
appear empty because the lipid material is dissolved is thought to be due to disturbance of basal ganglia. It
during processing of the histological slide. About 50% has to be differentiated from hemifacial spasm where
of patients with xanthelasma are associated with the most common cause is compression or irritation
hyperlipidemia. Most of the patients do not require of the facial nerve during its course and is mostly
any treatment except for cosmetic reason. Local unilateral. The essential blepharospasm is not seen
application of 25% trichloroacetic acid twice or thrice during sleep. Secondary blepharospasm, due to any
irritating ocular lesion is also to be differentiated from
this condition. Medical treatment consists of injection
of botulinum toxin in the orbicularis oculi muscle.
Doxorubicin, a chemotherapeutic agent is also tried
to produce chemomyectomy, leading to a permanent
cure. Surgically, differential section of the seventh
nerve or excision of lid protractors with brow
suspension can be done.
Blepharochalasis
This is a relatively rare condition seen in young healthy
females in pubertal age where a fold of skin hangs
down from the upper lid, sometimes narrowing the
Fig. 8.1: Xanthelasma at medial canthus palpebral fissure (Fig. 8.2). It is mostly sporadic but
Fig. 8.2: Blepharochalasis Fig. 8.3: Schematic diagram of tarsorrhaphy (Acknow-

ledgement: Shri Niranjan K Shah, Artist, M & J Institute for
drawing the schematic diagrams for the text)
may be familial with dominant inheritance. The cause
is not exactly known but many a times it is preceded
types can help in reduction of the palpebral fissure.
by recurrent attacks of inflammation. Clinically, it
Swimmers’ glasses or a moist chamber decreases the
presents as wrinkled, atrophic and lax skin which may
tear evaporation. Artificial tears (methyl cellulose
have pigmentation and telangiectasia. Due to
0.5%), bland ointments or hydroxypropyl cellulose
associated laxity of orbital septum, the orbital fat
ophthalmic inserts (lacriserts) can keep the cornea wet
bulges forward giving rise to a typical facial appear-
for some time.
ance. Sometimes the levator is also affected producing
Punctal plugs or destruction of the puncta by
acquired ptosis. Pathologically, there is a mild dermal cauterization or surgical laceration, can help in
lymphocytic infiltration and degeneration of elastic reducing the amount of tear drainage. Implantation
tissue. Sometimes it is associated with thickened upper of gold buttons or metal springs in the upper lid may
lip due to hypertrophy and inflammation of the labial help in producing a dynamic effect.
salivary glands (Ascher’s syndrome).
Dermatochalasis is a similar condition found in old
Micropigmentation of the Eyelids
age due to senile changes of the lid tissues. The lower
lid also shows prolapse of fat giving rise to pouches This is a surgical procedure by which minute metaboli-
below the lower lids. This can sometimes be a hind- cally inert pigments are mechanically placed beneath
rance in wearing glasses besides cosmetic blemish. the epidermis. It gives rise to a permanent marking
Both the conditions are treated surgically by a for the purpose of cosmesis. The main purpose is for
procedure, called blepharoplasty. It consists in eye liner or eyelash enhancement and for creating an
excision of extra skin and orbicularis, excision of the illusion of brow hairs after surgical reconstruction. The
prolapsing fat, and repair of the defective orbital pigments commonly used are iron oxide and titanium
septum. dioxide.
Exposure Keratitis FLOPPY EYELID SYNDROME

Facial palsy due to any cause, scarring of the lid skin, This is a syndrome consisting of chronic papillary
lid colobomas or tear film deficiency can lead to conjunctivitis with a rubbery and easily everted floppy
corneal opacification or ulceration. In cases where upper eyelid. It was first described by Culbertson and
recovery is expected, temporary measures are taken, Ostler in 1981.1 Although reported in obese men, this
either to reduce the palpebral fissure or to reduce loss syndrome may occur in women also.2 The character-
of tears, either by evaporation or by drainage through istic features consist of a triad of (a) diffuse papillary
the punctum. Tarsorrhaphies (Fig. 8.3) of different conjunctivitis; (b) a loose upper lid that readily everts
Chapter 8: Miscellaneous Conditions of the Eyelids 59
while pulling it downward; (c) soft rubbery tarsus that to keratoconjunctivitis seen in the syndrome. Some
can be folded on. An external upward force applied workers have found abnormal EEG due to apnea or
to the upper eyelid causes the tarsus to evert in a hypopnea. 8,15 This may be due to a common
gradual rolling motion instead of the usual all or underlying connective tissue disorder with abnor-
nothing popping out. Large papilla covers the upper malities in the pharynx as in the tarsus. Though reports
palpebral conjunctiva with mucus or mucus strands are available9 in literature that hyperglycemia16 was
over the surface of the papilla. Bulbar conjunctiva is found in floppy eyelid syndrome, there is no
mildly hyperemic. The upper lid is pliant with lash explanation about the mechanism in causation of this
ptosis and an abnormal type of blepharoptosis. There lid abnormality.
may be thinning of the ptotic eyelid above the tarsus. The eyelash ptosis is due to matting or deformation
Levator function is not diminished. It was initially of the cilia by chronic mechanical injury. Alternatively,
postulated that eyelid eversion during sleep, with the changes in tarsal laxity may have affected the
cornea-pillow contact as the cause of keratocon- stability of the tissue into which the cilia are anchored,
junctivitis. Patients who tend to sleep on one side may causing changes in the direction of the cilia. The
have more serious changes on that side whereas quantitative change in the elastin in the pretarsal orbi-
patients who sleep face down may have bilateral cularis muscle may also contribute to eyelash ptosis.
problem. Parvinovic3 doubted this etiology and some
workers4 suggested that the mechanism of injury Management
might be related to a poor interface between the loose As the exact cause of floppy eyelid syndrome is not
eyelid and the bulbar conjunctiva. An association of known, therapy is aimed at preventing the probable
floppy eyelid syndrome with keratoconus also has nocturnal eyelid eversion. An eyelid shield while
suggested that rubbing or mechanical pressure may asleep may give relief to some symptoms and prevent
be a contributing factor.5 Similarly, association of the lid rubbing. Topical lubricant and antibiotics may give
condition with blepharochalasis13 has suggested that some relief of symptoms. Surgical treatment consists
chronic inflammation may lead to many of the mainly of shortening of the eyelids.10 Full thickness
findings seen in advanced floppy eyelid syndrome.6 shortening by full thickness excision of 10 to 15 mm
The condition is usually found in obese persons. of the lateral part of the upper eyelid11 and lateral
tarsorrhaphy12 gives immediate relief of symptoms.
Pathology Shortening may be achieved by tarsal strip procedure
also.13-19
The pathologic basis of the tarsal laxity is not known.
Chronic mechanical injury and irritation may have a
role in progression of the condition, but the exact cause FURTHER READING
of initiation of the process has not been so far 1. Bates AK. Surgical management of essential blepharospasm.
identified. Standard histopathologic studies have B J Ophthalmol 1991;75:487-90.
found no abnormalities in the tarsus except some 2. Burton JL, Ebling JG. Disorders of connective tissue. In Rook
amount of meibomian dysfunction.14 Most studies A et al (Ed): Textbook of Dermatology. Oxford University
Press: Bombay 1987;3.
focused on the tarsal collagen which has been found
3. Freuh BR. Essential Blepharospasm: Surgery of the Eye.
to be normal in appearance by light and electron Churchill Livingstone: New York 1988;577.
microscopic studies. However, immunohistochemis- 4. McLeish WM. Advances in Blepharospasm therapy. Ophth
try shows decrease in quantity of elastic fibers in the Cl N Am 1991;4:193-99.
tarsus. Elastic fibers were nearly absent except for a 5. Sharif KW. The treatment of recurrent trichiasis with argon
laser photocoagulation. Eye 1991;5:591-95.
few clumps of positive staining material around the 6. Wirtchafter JD. Botulinum toxin injection for treatment of
meibomian gland acini and in the perimysium and blepharospasm and hemifacial spasm. Int Ophth Clinics
endomysium of the pretarsal orbicularis muscle.7 1991;31:117-32.
The meibomian glands show cystic degeneration 7. Wirtschschaster JD. Clinical doxorubicin chemomyectomy:
An experimental treatment for benign essential
and metaplasia as well as abnormal keratinization and
blepharospasm and hemifacial spasm. Ophthalmology
granuloma formation. These abnormalities of the 1991;98:357-66.
meibomian glands may result in qualitative abnor- 8. Culbertson WW, Ostler HB. The floppy eyelid syndrome. Am
mality of the tear film, which may in turn contribute J Ophthalmol 1981;92:568.
9. Paciue M, Mier ME. A woman with floppy eyelid syndrome 14. Netland PA, Sugrue SP, Albert DM et al. Histological feature
(letter). Am J Ophthalmol 1982;93:255. of the floppy eyelid syndrome. Ophthalmology 1994;101:174.
10. Parunavic A. Floppy eyelid syndrome. Br J Ophthalmol 15. Woog JJ. Obstructive sleep apnea and floppy eyelid
1983;330(67):264. syndrome. Am J Ophthalmol 1990;110:314
11. Schwartz LK, Gelender H, Forster RK. Chronic conjunctivitis 16. Gerner EW, Hughes SM. Floppy eyelid syndrome with
hyperglycinemia. Am J Ophthalmol 1984;98:614.
associated with floopy eyelid. Arch Ophthalmol
17. Dutton JJ. Surgical management of floppy eyelid syndrome.
1983;101:1884.
Am J Ophthalmol 1985;99:557.
12. Parunovic A, Illie B. Floppy eyelid syndrome associated with 18. Moore MB, Harrington J, Mc Cullen JP. Floppy eyelid
keratoconus. Br J Ophthalmol 1998;72:634. syndrome management including surgery. Ophthalmology
13. Goldberg R, Seiff S, Mc Farland J et al. Floppy eyelid 1986;93:184.
syndrome in blepharochalasis. Am J Ophthalmol 1986; 19. Bouchard CS. Lateral tarsorrhaphy for noncompliant patient
102:376. with floppy eyelid syndrome. Am J Ophthalmol 1992;114:367.
SECTION 2: DISEASES OF CONJUNCTIVA
Chapter 9
Anatomy of the Conjunctiva

The conjunctiva is a vascularized mucous membrane 6. Keratinization seen in Stevens-Johnson syndrome,

covering the anterior surface of the globe. Like all cicatricial pemphigoid, vitamin A deficiency.
mucous membranes, it also consists of epithelial and
stromal layers. The epithelial layer is continuous with ANATOMY
the epidermis of the lids at the lid margin and the
epithelium of the cornea at the limbus. The conjunctiva lines the posterior surface of the upper
The conjunctiva produces mucus which is essential and the lower lids and the anterior surface of the globe.
for tear film stability and corneal transparency. The While reflecting from the lids onto the globe, it forms
conjunctiva has enormous potential for combating two recesses namely superior and inferior fornices.
infection because of following reasons: The superior fornix is located at the level of the orbital
1. Highly vascular layer. margin, some 8 to 10 mm from the limbus. The inferior
2. Different types of cells initiate and participate in fornix is about 8 to 9 mm from the limbus (Fig. 9.1).
defensive inflammatory reactions.
3. Contains many immunocompetent cells which con-
tribute a rich supply of immunoglobulins.
4. Microvilli and enzymatic activity enable it to engulf
and neutralize organisms including viruses.
Clinically, the conjunctiva is an extremely valuable
ally of the ophthalmic surgeon and diagnostician due
to the following:
1. Bulbar conjunctiva which is loosely adherent is
used to a great advantage in glaucoma surgery.
2. Conjunctiva has great capacity to heal rapidly
which ensures success to many surgical proce-
dures, e.g. conjunctival flap placed on nonhealing
ulcer, conjunctival transplant from one eye to the
other eye in leaking filtration bleb, chemical burns
of the cornea, etc.
3. Pathognomic vascular changes are seen in conjunc- Fig. 9.1: Distances of fornices in mm from open
palpebral fissure
tival vessels in sickle cell anemia.
4. Scleral icterus in jaundice, pigmentary changes in Medially, the fornical structures are replaced by
ochronosis, Bitot’s spots in vitamin A deficiency. the caruncle and the plica semilunaris, allowing the
5. Conjunctival biopsy material can be obtained with inferior punctum to dip and drain tears. Laterally, the
little discomfort and with virtually no loss of tissue fornix extends just beyond the equator of the globe
integrity. and is quite deep about 14 mm from the limbus.
62 Section 2: Diseases of Conjunctiva
For clinical purpose the conjunctiva is divided into

three parts, viz. palpebral conjunctiva, bulbar conjunc-
tiva, and fornical conjunctiva (Fig. 9.2). The palpebral
conjunctiva is markedly adherent to the tarsus. It is
translucent. Normal blood vessels and meibomian
ducts are seen through it (Fig. 9.3). The follicle
formation and papillae formation are the two changes
visible in this conjunctiva. Follicles are thought to be
identical to lymphoid follicles found elsewhere in the
body. Papillae are composed of chronic inflammatory
cells like lymphocytes and plasma cells, and are
distinguished from follicles by the presence of blood
vessles at the center.
The bulbar conjunctiva is thin and so translucent
that the underlying sclera is seen through it. It is loose
and can be moved easily.
It is attached to the tendons of the rectus muscles
which in turn are covered by the Tenon’s capsule.
Approximately 3 mm from the limbus, the con-
junctiva, the Tenon’s capsule and the sclera become Fig. 9.2: Section showing various parts of conjunctiva
firmly adhered to one another and the conjunctiva
cannot be picked up easily. This is appreciated
routinely during dissection of the limbal based
conjunctival flap in ocular surgery.
Conjunctival Glands
The conjunctiva contains following two types of
glands:
1. Mucin secretors
2. Accessory lacrimal glands.
1. Mucin Secretors
Goblet cells They are unicellular mucus glands located
within the epithelium of the conjunctiva and are
involved in the secretion of mucus. Mucus lubricates
and protects the epithelial cells and lowers the surface Fig. 9.3: Everted lid showing meibomian ducts and
tension of the tear film to assure its stability. It is most conjunctival blood vessels for upper lid
dense in the inferonasal part and hence it is the best
site for diagnostic biopsy. Goblet cells are relatively may give rise to increase in goblet cells. The other
large cells with numerous mucus pockets in the source of mucin in the eye is from conjunctival
cytoplasm. Mucus is secreted from an opening in the epithelial cells.
surface of the goblet cells and emptied completely
2. Accessory Lacrimal Glands (Fig. 9.2)
when its apex is opened up.
A decrease in goblet cell density is observed in the The glands of Krause They are located in the conjunctival
Stevens-Johnson syndrome, ocular pemphigoid, and stroma. They are 40 to 45 in number in the upper fornix
the acute alkali burns. Destructive diseases of the and 6 to 8 in the lower fornix. It is extremely important
conjunctiva frequently damage the mucin secretors to preserve the integrity of the superior border of the
and give rise to dry eye, while chronic inflammation upper tarsus during surgical procedures otherwise it
Chapter 9: Anatomy of Conjunctiva 63
can give rise to a dry eye due to damage of these
The epithelial cells in the limbal conjunctiva appear
glands.
to be much more irregular in shape and larger in size
Glands of Manz They are found in the circumferential than those in the upper tarsal conjunctival surface.
ring of the limbal conjunctiva. According to Wolff,
they are not found in humans. The crypts of Henle Epithelial Cysts
are found in the upper and lower third of the lateral
These are in the conjunctiva under normal circum-
conjunctiva.
stances. They may be subepithelial and intraepithelial.
The intraepithelial cysts occur exclusively in the upper
Conjunctival Epithelium quadrant of the bulbar conjunctiva while subepithelial
The conjunctival epithelium is a stratified squamous cysts occur on the semilunar fold. These vary in size
epithelium that rests on a very loose connective tissue and may produce mucoid substance (Fig. 9.4).
called the substantia propria. The epithelium rests on
an undulating basal cell membrane. However, it does
not provide a strong barrier to cell migration through
it. The surface epithelial cells contain numerous micro-
villi.
Tarsal Conjunctival Epithelium

Tarsal conjunctival epithelium is about 5 to 6 layers
thick; in the lower tarsal conjunctiva it has 3 to 4 layers
of cells. The basal epithelium of the fornix tends to be
more columnar while that of the palpebral conjunctiva
is more cuboidal. In electron microscopy the cells
contain tonofilaments, rough surface endoplasmic
Fig. 9.4: Conjunctival cyst
reticulum, Golgi apparatus, mitochondria in varying
number, many electron dense lysosome like structures
and smooth walled vesicles close to the surface and Wound Healing and Inflammation
microvilli. It is proposed that microvilli play an The vascular conjunctiva has a better healing
important role in absorbing viral particles during capability than the avascular conjunctiva. When the
infection. entire corneal epithelium is abraded it is the peripheral
Concretions-Yellowish spots are found in upper conjunctival epithelial cells which migrate and
tarsal conjunctiva; they are products of cellular resurface the cornea. However, this healing is weaker
degeneration without any calcified spots. as compared to healing of corneal abrasion by corneal
epithelial cells. Topical steroids slow down the process
Limbal Conjunctival Epithelium of migration of epithelial cells but nonsteroidal anti-
inflammatory agents do not affect either conjunctival
The number of layers of epithelial cells of conjunctiva
or corneal epithelial migration.
increases to 10 to 15 as they approach the corneal
periphery. Goblet cells are absent in the limbal epithe-
Arteries
lium and general organization of the epithelial layer
becomes increasingly similar to corneal epithelium. The conjunctival arteries are derived from two sources
Lymphocytes and Langerhan’s cells are found in basal (Fig. 9.5):
and suprabasal layers of limbal conjunctival epithe- 1. The palpebral branches of the nasal and lacrimal
lium. The conjunctival epithelium and stroma form arteries of the lids.
rete pegs and papillae at the corneal periphery. The 2. The anterior ciliary artery.
papillae radiate from the corneal edge into the The post-tarsal plexus of the lid which is formed
conjunctiva to form the palisades of Vogt. Small by the marginal and peripheral artery of the upper
nerves, vessels, and lymphatics run the length of the lid supplies the palpebral conjunctiva. The perforating
papillae. vessels from the peripheral palpebral arcade supply
1. Superficial plexus consisting of small vessels

placed below the capillaries.
2. Deeper plexus of larger vessels in the fibrous por-
tion of substantia propria. These are important in
the mediation of immunological reactions that
occur in certain ocular diseases and surgical condi-
tions.
3. The superficial plexus drains the limbal area. There
are larger channels running circumferentially 7 to
8 mm behind the limbus to form an incomplete
pericorneal lymphatic ring.
The recurrent nasal group and descending
Fig. 9.5: Section of lid and globe showing temporal group drain by way of medial canthus. Large
blood supply of the conjunctiva
connecting vessels from the inferior fornix empty by
most of the fornical conjunctiva. This arcade sends way of the lateral canthus. Laterally placed lymph
descending branches to supply the tarsal conjunctiva vessels flow to the preauricular lymph nodes; medially
and also anastomoses with vessels from the marginal placed vessels flow to the submaxillary lymph nodes.
arcade and ascending branches which pass into the
superior or inferior fornix to continue around the
Nerve Supply
fornices to the bulbar conjunctiva as the posterior
conjunctival arteries. The conjunctiva derives its entire nerve supply from
The anterior ciliary arteries give off anterior the first division of the trigeminal nerve. The nerves
conjunctival arteries just before piercing the globe. to the lid supply most of the conjunctiva. These are
These arteries send branches to the pericorneal plexus the infratrochlear branch of the nasociliary nerve, the
and the bulbar conjunctiva of the limbal area. Here lacrimal nerve the supratrochlear and supraorbital
there is free anastomosis in the subconjunctival and branches of the frontal nerve and the infraorbital nerve
episcleral tissues between the anterior conjunctival from the maxillary division of the trigeminal nerve.
vessels and the terminal branches of the posterior The limbal area is supplied by branches from the
conjunctival vessels resulting in the zone of palisades ciliary nerves. All nerves form a network in the
of Busaca; thus, there is a close connection between conjunctiva and terminate either peripherally in
superficial and deep vascular system in the limbal various forms of specialized endings or on blood
area. Clinically, this has diagnostic importance. In case
vessels and epithelial cells. The majority of nerve
of conjunctival inflammations and infections super-
endings are free nonmyelinated nerve endings.
ficial posterior vessels are engorged, in deep keratitis
and/or iritis, the deeper ciliary vessels are injected.
Caruncle
Veins It is a small fleshy body that lies in the lacus lacrimalis
The conjunctival veins are more numerous than medial to the plica semilunaris. It is a part of the
arteries. The major part of the drainage from the tarsal margin of the lower eyelid that becomes cut off during
conjunctiva and the bulbar conjunctiva is to the the development of the inferior canaliculus. It is
palpebral veins. Few tarsal veins empty directly into covered by a stratified squamous epithelium similar
the superior and inferior ophthalmic veins. Small to that of skin, but it does not undergo keratinization.
vessels of the bulbar conjunctiva have anterior venous It also contains accessory lacrimal glands and goblet
communications but these are not true anastomoses cells, its deep connective tissue is made up of parts of
as it has no muscular walls. septum orbitale and medial check ligament. Its blood
supply is from the superior palpebral arteries but it is
Lymphatics quite abundant. The nerve supply is from the
The conjunctiva has lymphatics arranged in the infratrochlear nerve. Lymphatics from the caruncle
following plexuses: drain to the submaxillary lymph nodes.
Chapter 9: Anatomy of Conjunctiva 65
in lower vertebrates. In man, it is a vestigial structure
with characteristics of bulbar conjunctiva.
Epitarsus
Epitarsus is a mobile fold of conjunctiva extending
between the inner surfaces of the two lids (Fig. 9.6). It
is mostly congenital but may be acquired due to some
inflammation of conjunctiva. It is considered to be
equivalent to nictitating membrane (third eyelid) of
the lower animals like the frog, certain birds,
herbivora, and fish. Simple surgical excision gives
Fig. 9.6: Epitarsus. A congenital fold of conjunctival good results.
running, between the two lids
FURTHER READING
Plica Semilunaris
1. Jakobiec FA. Ocular anatomy: Embryology and Teratology,
It is a fold of conjunctiva lying lateral to the caruncle. Harper and Row: NewYork, 1982.
It is more or less vertical with its concavity facing 2. Wolff E. Anatomy of Eye and Orbit. H K Lewis and Co Ltd,
laterally. It corresponds to the nictitating membrane 1976.
Chapter 10
Clinical Manifestations of
Conjunctival Diseases
Conjunctiva is a mucous membrane, covering the 1. Bacterial conjunctivitis with the exception of N
eyeball. Its secretions are necessary for its normal catarrhalis and Morax-Axenfeld bacillus.
functioning. Various disease processes bring out 2. Chemical conjunctivitis.
changes in it in different ways. Detection of these 3. Erythema multiforme.
changes and its interpretation are helpful in arriving 4. Reiter’s syndrome.
at a diagnosis.
DISCHARGE
It is the exudation from the abnormaly dilated blood
vessels filtered through the conjunctival epithelium.
On conjunctival surface, epithelial debris, mucus, and
tears are added in variable amount; characteristic of
discharge varies according to its etiology.
A. Watery discharge Serous exudates and tears are its
main constituents. It is seen in viral infections and
toxic inflammation.
B. Mucinous discharge It is typically seen in vernal
Fig. 10.1: Bilateral gonococcal conjunctivitis. Lid edema
conjunctivitis and keratoconjunctivitis sicca. It can and purulent conjunctival discharge is evident
be ropy or thread like.
C. Purulent discharge It is typical of severe bacterial
infections (Fig. 10.1). There may be associated lid
edema.
D. Mucopurulent discharge It is seen in mild bacterial
or chlamydial infection (Fig. 10.2). Stickiness of lid
margins may be associated with it.
The discharge also contains a variable amount of
cells. The cytological findings provide important clues
for diagnosis of conjunctival disease. Usually con-
junctival discharge/scrapping is stained with
Giemsa’s stain.
If a smear shows predominance of polymorpho- Fig. 10.2: Conjunctival congestion and mucopurulent
nuclear cells, it is suggestive of the following: discharge in mucopurulent conjunctivitis
Chapter 10: Clinical Manifestations of Conjunctival Diseases 67
Lymphocytic response is seen in viral infections,
toxic conjunctivitis, allergic conjunctivitis, and chronic
conjunctivitis. Eosinophils are never found in normal
conjunctival smear. Its presence (even one cell is
adequate) indicates allergic conjunctivitis, erythema
multiforme or benign mucous membrane pemphi-
goid. Free eosinophilic granules are typical of vernal
conjunctivitis. In chlamydial infections mixed cellular
pattern with basophilic intracytoplasmic bodies are
seen. Majority of viral inclusion bodies are eosinophilic
in nature. They are intracytoplasmic in vaccinia,
variola, molluscum contagiosum, Newcastle disease
virus, etc. They are intranuclear in herpes, cytomegalo-
virus, adenovirus, and measles.
Fig. 10.3: Conjunctival hyperemia most marked in fornix
Keratinized epithelial cells and goblet cells are seen
in dry eye state. Goblet cells are also seen in chronic
conjunctivitis. suture it is polygonal and variable in size. Papillae
seen with ocular prosthesis are of variable nature.
Hyperemia
Follicles
This is a nonspecific reaction of conjunctivitis. It is
more intense in fornices (Fig. 10.3), when it is Appearance of follicles is more specific than papillae
secondary to conjunctival disease. formation. Follicles appear as multiple, discrete,
slightly elevated lesions (Fig. 10.4). They may be 0.5
Papilla to 5 mm in size depending on severity and duration
of the lesion. Follicles represent lymphocytic response.
Papilla suggests response of vessels of conjunctiva to Vessels are never seen in the center of the follicle. They
the inflammation. It consists of a small glomerulus like usually surround it or lie over it.
capillary network surrounded by a fibrous network. Follicles are commonly seen in lower palpebral
It is very typical of conjunctiva and highly nonspecific conjunctiva, except in trachoma, where they are
response compared to follicles. Anchoring of a commonly seen in upper palpebral conjunctiva.
conjunctival tissue to underlying tissue with fibrous Follicular response is not seen in infants of 2 to 3
septa is a prerequisite for papillary formation to deve- months of age. In children, nonspecific follicular
lop. This is commonly seen in palpebral conjunctiva response is common like lymphoid hyperplasia in
and around limbus. When fibrous septa limiting tonsils.
papilla breaks, there is formation of a giant papilla or When follicles last for less than four weeks, it is
papillary confluence. called as acute follicular response. In chronic follicular
Clinically, papilla appears as polygonal hyperemic conjunctivitis, the follicles are present beyond four
areas separated by pale channels. weeks.
Histological examination reveals a central fibro-
vascular core. There are multiple branches from this Membrane Formations
on reaching the surface. Swelling of tissues is due to
leakage of fluid and cells from vessels as a result of Membranous conjunctivitis suggests severe inflam-
inflammation. Usually fibrous septa intervening the mation. Pseudomembrane or membrane formation is
limits and the size of each papilla to less than 1 mm. due to coagulation of fibrin rich transudation from
Giant papillae are more than 1 mm in size. They the conjunctival vessels. On peeling the membrane, if
are formed due to disruption of anchoring septa. They bleeding occurs, then it is labeled as true membrane,
are seen when inflammation is chronic and/or severe. otherwise it is a pseudomembrane. Pseudomembrane
They are polygonal with flat surface in vernal conjunc- formation suggests milder form of the disease,
tivitis and atopic diseases. They are slightly raised but compared to true membrane. Pseudomembranes are
symmetrical and pale in contact lens wearer (giant usually seen in severe viral infections or less virulent
papillary conjunctivitis). When seen around a nylon mild bacterial infections.
collected there. Ballooning of conjunctiva occurs when

fluid is in large quantity. It is labeled as chemosis.
Besides severe inflammation which accompanies
infection of conjunctiva or surrounding structures, e.g.
lid, lacrimal sac, orbit, sinuses, it is also seen in various
other conditions, which include blockage of
lymphatics, following orbital surgery, erysipelas, or
in chronic hereditary lymphedema. It is also seen as a
hypersensitivitiy reaction to topical application of
allergen or as a part of generalized reaction. This inclu-
des allergy to drugs also.
Increased orbital content causing proptosis or
obstruction of venous flow as in cavernous sinus
thrombosis, heart failure, caroticocavernous fistula
Fig. 10.4: Follicles in follicular conjunctivitis in upper
can give rise to chemosis. In cases of vasomotor
palpebral conjunctiva
instability as a part of angioneurotic edema, or water
retention in premenstrual phase conjunctival edema
Conjunctival Concretions may be seen.
Concretions are seen as small yellow spots. They are Angular Conjunctivitis
usually elevated and commonly seen in tarsal conjunc-
tiva. They are made up of degenerative material Sometimes chronic conjunctival inflammation is seen
(epithelial cells and inspissated mucus). They follow only at angles of the eye. Rest of bulbar and palpebral
chronic inflammation, e.g. trachoma, atopic or vernal conjunctiva appears normal or minimally affected.
conjunctivitis; in these conditions conjunctival fibrosis Usually lateral angles of both eyes are involved.
is evident. In normal looking conjunctiva, they may Etiology of this condition includes infections with
appear in elderly persons without any obvious cause. Morax-Axenfeld diplobacillus (Moraxella lacunata),
They give rise to foreign body sensation. It is usually Staphylococcus aureus, and Candida albicans. It is also
managed by scrapping with a hypodermic needle. seen in riboflavin deficiency.
Calcification never takes place in concretions.
Phlyctenular Keratoconjunctivitis
Conjunctival Ulcers It is a localized conjunctival, limbal or a corneal nodule
Ulcers of conjunctiva are self limiting and do not need of about 1 to 3 mm in size. It may be due to delayed
any attention. However, nonhealing or recurrent hypersensitivity to bacterial proteins, e.g. tuberculo-
ulcers of conjunctiva need attention. They are seen in protein and staphylococci. It is also seen with lympho-
fungal infections and herpes simplex infections. It is granuloma venereum and coccidioidomycosis. It can
also seen in mucous membrane pemphigoid or be due to infection of the conjunctiva. Organisms
granulomatous infections, e.g. tuberculosis or syphilis. found in this condition include Staphylococcus aureus,
Conjunctival ulcers are also seen, following Pneumococcus, and Koch-weeks bacillus. Malnutrition
administration of eyedrops in a toxic dosage. This is is commonly associated with it.
more common with aminoglycosides compared to any Nodule at Limbus
other antibiotics.
Almost all tumors of conjunctiva and inflammatory
Conjunctival Edema (Chemosis) mass lesions have predilection for the limbus.
Differential diagnosis of nodule at the limbus
It is seen whenever the conjunctiva is inflamed and should include following conditions:
hyperemic due to transudation of fibrin and protein 1. Pterygium
rich fluid through damaged blood vessels. This 2. Pinguecula
accumulates beneath the conjunctiva and causes 3. Allergic nodules
translucent swelling fluid of conjunctiva. Due to laxity a. Phlyctenular lesions
of bulbar conjunctiva the fluid commonly gets b. Vernal lesions
Chapter 10: Clinical Manifestations of Conjunctival Diseases 69
4. Granuloma
5. Dermoids
6. Squamous cell carcinoma
7. Intraepithelial epithelioma
8. Epithelial hyperplasia
9. Papilloma
10. Sarcoma
11. Nevus
12. Malignant melanoma
13. Lymphoma
14. Hemangioma
15. Fibrous histiocytoma
16. Ectopic lacrimal gland tissue
17. Benign nodular fascitis
Fig. 10.5: Massive subconjunctival hemorrhage following
18. Amyloidosis subconjunctival injection
19. Nodules associated with skin diseases
a. Acne rosacea (Ocular rosacea)
b. Hereditary benign intraepithelial dyskeratosis
c. Hodgkin’s disease
d. Limbus squamous cell carcinoma in
xeroderma pigmentosa
e. Pityriasis rubra pilaris
f. Psoriasis (Psoriasis vulgaris)
g. Reticulum cell sarcoma
20. Filtering bleb: Cystoid cicatrix, following
antiglaucoma surgery
21. Extension from intraocular lesions:
Inflammatory. (Tuberculosis, Syphilis)
Tumors (Melanoma, Diktyma)
Fig. 10.6: Absorbing subconjunctival hemorrhage
22. Cysts: Retention, implantation, parasitic
23. Nodular form of Kaposi’s sarcoma in AIDS.
6. Increased fragility of vessel wall
SUBCONJUNCTIVAL HEMORRHAGE
a. Diabetes
Subconjunctival hemorrhage appears bright red in b. Hypertension
color. There is no discharge (Fig. 10.5). It is due to c. Atherosclerosis
collection of blood in subconjunctival space. It dis- d. Nephritis.
appears on its own (Fig. 10.6). Time taken for its dis- 7. Rupture of a telengiectatic vessel.
appearance depends on the amount of blood. It may 8. Chronic cough, whooping cough in children
take 4 to 6 weeks. Blood disappears without any 9. Idiopathic.
sequel. Sometimes blood pigments are retained and
they take a longer time to disappear. It is seen in a Lymphadenopathy
variety of clinical situations.
Enlargement of preauricular lymph node is seen in
1. Conjunctivitis—acute hemorrhagic, severe muco-
viral or chlamydial infections. It may also get enlarged
purulent or purulent.
in squamous cell carcinoma, and other malignant
2. Trauma to the conjunctiva or to the surrounding
tumors of conjunctiva.
structures.
It can be surgical or accidental.
Pigmentations
3. Severe fever due to any cause.
4. Blood dyscrasias. Like skin and mucous membrane of body, conjunctiva
5. Vitamin C deficiency. also gets pigmented in various disorders. It can be
congenital. Melanin pigment deposition is the most c. Melanoma

common cause of congenital pigmentation. It is seen d. Acantha nigricans
as a nevus, benign melanosis or around the blood e. Xeroderma pigmentosa
vessels. 4. Copper in chalcosis
5. Iron following iron foreign body
Acquired Pigmentation of Conjunctiva 6. Silver as in argyrosis.
1. Blood pigments following subconjunctival hemor- FURTHER READING

rhage
1. Davison CR, Tuffss, Dart J and G. Conjunctival necrosis after
2. Bile pigments in jaundice
administration of topical fortified aminoglycosides. Am J
3. Melanin Ophthalmol 1991;111:690-93.
a. Vernal conjunctivitis 2. Roy Fedrick Hampton. Ocular Differential Diagnosis.
b. Conjunctival xerosis London, Lea & Febiger 1989;205-36.
Chapter 11
Viral Conjunctivitis
Unilateral or bilateral red eye of sudden origin with Folliculosis

foreign body sensation and follicular conjunctival It is a condition occurring most frequently in children.
hyperemia, suggests viral conjunctivitis. Formation of Follicles are seen in the palpebral conjunctiva. These
follicles is characteristic of viral disease. Follicle are analogous to lymphoid hyperplasia of tonsils in
formation is seen in other conditions also. Since viral children.
infection causes follicular conjunctivitis, the latter is
discussed in detail. Acute Follicular Conjunctivitis
This starts initially as unilateral conjunctivitis of
FOLLICULAR CONJUNCTIVITIS abrupt onset, but the second eye is also involved
Patients with follicular conjunctivitis have problems within a week, frequently accompanied by preauri-
in diagnosis and treatment. Frequently it is viral in cular lymphadenopathy.
origin but there can be other causes also. To reach at Common causes of acute follicular conjunctivitis
appropriate diagnosis good history, clinical exami- are the followings:
nation and simple laboratory test like cytological 1. Adenovirus conjunctivitis
examination of conjunctival scrappings are necessary. a. Pharyngoconjunctival fever adenovirus type-
Follicular conjunctivitis is thought to be a local host 3
response to an exogenous substance or agent. These b. Epidemic keratoconjunctivitis adenovirus
are characterized by formation of subconjunctival type-8
prominent lymphoid follicles; clinically, these follicles 2. Inclusion conjunctivitis
appear as elevated, avascular yellowish to grayish- infants
white lesions of variable size varying from 0.2 to 2 In adults associated with cervicitis or urethritis
mm in diameter. Etiology of follicles is given in 3. Newcastle disease
Table 11.1. 4. Influenza virus A
5. Herpes zoster
Table 11.1: Etiology of follicles 6. Primary herpes simplex infection
Chlamydial Viral
7. Parinaud’s oculoglandular syndrome
8. Trachoma (Chlamydia)
Age Young adult All ages 9. Other chlamydial infection
Systemic involvement Genitourinary Respiratory 10. Ophthalmomyiasis
Course Chronic Self limiting 11. Bacterial infection like Streptococcus, Moraxella,
Molluscum contagiosum, Treponema
Keratitis Upper part Commonly
diffuse 12. Associated with regional adenitis (e.g. floppy
Cytology Inclusion bodies Monocular eyelid syndrome)
Polymorphs cells 13. Toxic follicular conjunctivitis (medicines-miotics,
Tetracycline response + – antivirals, atropine, adrenergic drugs, amino-
glycosides, sulphas).
14. Acute hemorrhagic conjunctivitis. Conjunctivitis is usually unilateral and rarely

Examination for presence of skin lesions, upper becomes bilateral. Conjunctival hyperemia, follicle
respiratory tract infection, type of keratitis, type of formation and subconjunctival hemorrhages are seen.
discharge and any other accompanying systemic Preauricular lymph nodes are enlarged and tender. It
illness is helpful in arriving at a diagnosis. is associated with malaise, myalgia, frontal headache,
It can occur at all ages. Although newborns do not besides pharyngitis and fever. Abdominal discomfort
develop a follicular conjunctival response readily they and even diarrhea may be present. In severe cases
are nevertheless susceptible to the organisms that there may be edema of both lids and conjunctival
cause many of these syndromes. chemosis. Discharge is typically mucoid. Purulent
discharge occurs due to secondary bacterial infection.
Pathophysiology Occasionally serofibrinous or pseudomembranous
Acute follicular conjunctivitis due to adenovirus conjunctivitis may be seen. Corneal involvement is
infection occurs by droplet transmission after 5 to 12 usually absent; when present it may be in the form of
days of incubation period, watery discharge, fine focal or diffuse epithelial keratitis. Subepithelial
conjunctival hyperemia, and follicles are the initial corneal infiltrates may persist for 3 to 4 weeks.
clinical features. This subsides in 7 to 12 days. This is To prevent spread, isolation of a person should be
accompanied by a rise in circulating antibody titer to for 2 weeks. The diagnosis can be confirmed in the
specific adenovirus type involved and a complete laboratory on the basis of a rising titer of neutralizing
immunity thereafter to reinfection with that type of antibody to type 3 virus or by isolating the virus from
adenovirus. Herpes virus is characterized by latent conjunctival scrapings on Hela or other tissue culture
infection with recurrent disease episodes. Newcastle cells.
disease virus infection usually occurs in poultry Management is entirely supportive. The natural
workers and veterinarians due to direct conjunctival course of the disease is not altered by antivirals or
inoculation through infected birds or vaccine corticosteroids.
preparations.
EPIDEMIC KERATOCONJUNCTIVITIS (EKC)
Clinical Manifestations
It is caused by adenovirus types 8 or 19. Other
These are usually unilateral and start with a small
serotypes found responsible include 1,2,3,5 to 11, 13
nontender preauricular node on the affected side. It
to 19, 29,30,32, and 37. Adenovirus 8 is more frequently
can produce a spectrum of findings, ranging from a
seen in hospital acquired infections. It spreads during
very mild follicular response of short duration to a
eye check-up and manipulations. The transmitting
severe follicular keratoconjunctivitis. Usually, it
agents are contaminated fingers, tonometer, and
produces a very mild, transitory and rarely a severe
solutions. Adenovirus 19 is more common in infections
focal infiltrative keratitis.
spreading through relatives and close contacts (Street
PHARYNGOCONJUNCTIVAL FEVER (PCF) acquired). Infection with type 19 shows smaller
infilatrates and less prolonged course. However,
It is a common manifestation of adenovirus infection
clinically it is not possible to identify the serotype of
of the eye. Pharyngoconjunctival fever is caused by
organism as clinical picture is identical in all.
adenovirus types 3 and 7. It is also seen with adeno-
virus type 4. This syndrome is associated with practi-
Clinical Picture
cally all other adenovirus types. Pharyngoconjunctival
fever is more common in children. This occurs spora- The incubation period is very short. The onset is
dically or in epidemics. Infection can be contacted in always acute and presents with red eyes, watering,
swimming pool. Incubation period is up to 3 weeks. follicular conjunctivitis, and with low grade fever. It
An acute nonpurulent unilateral follicular conjuncti- is usually unilateral. Preauricular lymph nodes of the
vitis, preauricular lymphadenopathy, pharyngitis and same side are enlarged and tender. About 1/3 of the
fever are initial feature. The cornea is rarely severely cases show membrane formation followed by scarring
affected. Virus disappears from the conjunctiva and of the conjunctiva. There may be papillary hyper-
throat after 14 days but fecal excretion can continue trophy and subconjunctival hemorrhage. Conjuncti-
for 30 days. vitis lasts for 7 to 21 days and heals spontaneously.
Chapter 11: Viral Conjunctivitis 73
Other eye gets affected within 7 to 10 days after Corticosteroids are not routinely recommended for
involvement of the first eye. It is always mild the treatment of adenoviral keratoconjunctivitis as it
compared to the first eye. suppresses the inflammatory response and do not
Involvement of cornea sets apart EKC from other shorten the natural course. However, they may be
forms of adenovirus conjunctivitis. Adenovirus used when corneal infiltrate causes profound visual
infection can result in 4 different types of keratitis. The loss. Fluoromethalone 1% eye drops 4 to 6 times a day
early epithelial forms of keratitis are probably caused may be prescribed. They reduce the size of infiltrate
by proliferation of the live virus within the corneal and improve the visual acuity. The subepithelial
epithelium, whereas later epithelial and subepithelial infiltrate reappears on withdrawal of steroids and runs
infiltrates are thought to represent sterile immuno- their natural course. Because of this reason many
logical reactions to retained viral antigen. It is seen as people do not recommend use of steroid. Steroids are
diffuse superficial epithelial keratitis, but between 7 also indicated in presence of anterior uveitis.
to 10 days most cases develop multiple scattered
round subepithelial opacities large enough to be seen Prevention
with the naked eye. This gives rise to pain, marked
photophobia and glare and profound visual loss. They Responsibility of an ophthalmologist is the highest as
usually disappear in few weeks. These opacities may it spreads most often during eye check-up. He should
persist for many months, but eventually disappears wash his hands between examination of two patients.
without scarring. Sometimes they are known to persist All instruments particularly tips of tonometer should
for up to two years. In one reported case, it persisted be sterilized regularly. Patients should be asked to
for 40 years. These dry spots do not consist of leuko- remain away from public places for 2 weeks. Patient
cytes or necrotic corneal tissue. Topical corticosteroids is asked to use gloves, goggles, and frequent hand
temporarily diminish the intensity of the opacities. washing while on work.
Diagnosis HERPES VIRUS HOMINIS (HERPES SIMPLEX)

Virus can be isolated on Hela or other tissue culture It is one of the commonest virus affecting man. It
cells. Demonstration of rising titer of neutralizing appears in a variety of forms, e.g. stomatitis, fever blis-
antibody against type 8 adenovirus is also useful. ters, eczema herpeticum or meningoencephalitis.
Fluorescent antibody staining technique for type 8 Herpetic lesions of skin of lids and conjunctiva are
virus in conjunctival or corneal epithelial scraping can seen only in primary infection with herpes virus.
be diagnostic. Dendritic keratitis is usually a manifestation of
recurrent virus infection. However, blepharo-
Treatment conjunctivitis is found to be of recurrent nature which
may follow some nonspecific stimulus such as fever
Therapy is mainly supportive. Antiviral agents are not
or psychological stress. Cornea may be spared at first
found to be effective.
but in some cases keratitis occurs as a marginal
The patient should be informed about the natural
infiltration, a coarse punctate epithelial keratitis or a
course of the disease, and reassured about full
recovery of vision without any permanent damage, typical dendritic ulcer.
and complete spontaneous resolution in 2 to 4 weeks.
Clinical Picture
The patient should be warned about the highly
contagious nature of the disease, and necessary The clinical picture of ocular infection with herpes
precautions, viz frequent washing of the hands, using virus varies widely, but five main types can be
separate towels, avoiding direct contact with people, described.
etc. 1. Typical dendritic keratitis and its variant, the geo-
Cold packs can provide general comfort. Sun graphic ulcer
glasses or dark glasses may provide relief in 2. Disciform or stromal keratitis with edema, infiltra-
photophobia. Topical vasoconstrictor (Naphazoline) tion, and varying amount of cellular infiltration
may be useful in reducing conjunctival hyperemia. and vascularization.
The patient should be instructed to keep the lids 3. Keratouveitis—extension of 2 above with edema
and lashes clean and free of mucus. and infiltration of the iris and ciliary body.
4. Acute follicular or pseudomembranous conjuncti- palpebral rare or bulbar conjunctiva. There is usually
vitis with or without dendritic keratitis. It is seen mild anterior uveitis.
only as a primary infection. There is associated viremia. Patient may complain
5. Vesicular eruption on the lids. of generalized malaise, myalgia, headache, and
The test for corneal sensation is valuable diagnostic pharyngitis.
aid, since reduced or absent corneal sensation is The disease is self-limiting and resolves within 1
characteristic only of herpetic infection. This gives to 2 weeks without sequelae in majority of cases.
warning at once to stop or withhold topical cortico- Purulent discharge suggests secondary bacterial
steroids, as it has a pernicious effect. infection. It should be treated promptly with
Infection in the eye occurs due to type I (oral) or antibiotics. The virus is neurotropic and may cause
type II (genital) virus. paralysis of various nerves, it may include radiculo-
Laboratory confirmation is accompanied by myelitis, and Bell’s palsy. This may last longer and
isolation of virus on the chorioallantois, the rabbit may not recover in occasional patients. Bulbar
cornea or in tissue culture. paralysis when it occurs may prove fatal.
Conjunctival scraping will show lymphocytic
Epidemiology response. It may contain occasional basophilic
inclusions.
Young children are exposed to salivary contamination
Treatment is symptomatic, as disease is self
from adult with active or latent labial herpes simplex.
limiting. Systemic analgesic along with topical
Corneal susceptibility increases by the administration
vasoconstrictors and cool compresses may be given.
of steroids, by fever or sunburn or by trauma,
Topical corticosteroids are not indicated as disease is
emotional upsets or shocks associated with increased
having short course without any sequelae. Superficial
adrenaline in the blood.
punctate keratitis which is occasionally seen is
transient.
Treatment Acute hemorrhagic conjunctivitis is highly conta-
• IDU (5-Iodo-2-deoxyuridin) 0.1%drops 1-2 hourly gious disease, occurring in large and rapidly spreading
or 0.5% ointment every 4-6 hours. epidemics, but is self limiting, usually lasting for 10
• Mechanical removal of infected epithelium or days or less. It spreads by direct contact, e.g. hand to
cauterization. eye. Frequent hand washing and quarantine for 7 days
• The patient should be examined frequently for after onset of symptoms are recommended. Patient
evidence of herpetic keratitis. should be segregated from other family members. He
• The patient should be warned about the recurrent should have separate handkerchiefs, towels, napkins,
nature of the disease and to avoid the trigger that pillowcovers, bedsheets, etc. During epidemic all
irritate the disease episode. medical equipments used for examination or
• Topical steroid therapy is to be avoided treatment should be frequently cleaned and
assiduously. disinfected to prevent spread of the disease.
ACUTE EPIDEMIC HEMORRHAGIC Chronic Follicular Conjunctivitis

CONJUNCTIVITIS Acute follicular conjunctivitis which persists for more
It is caused by picorna virus (usually enterovirus 70), than 16 days should be regarded as chronic follicular
but occasionally by Coxsackie virus A 24 or conjunctivitis. It includes following conditions:
adenovirus 11. The disease was described in 1942 by 1. Trachoma
Hogan and Crausford. It starts as unilateral follicular 2. Inclusion conjunctivitis and other chlamydial
conjunctivitis of sudden onset. This becomes bilateral. infections
There is epiphora, lid edema, conjunctival chemosis, 3. Toxic follicular conjunctivitis
and profuse mucoid discharge. Preauricular lymph a. Molluscum contagiosum
nodes are palpable as a small nontender mass. b. Drug induced
Subconjunctival hemorrhages are seen as diffuse c. Eye make up
hemorrhage temporally or hemorrhages in upper 4. Bacterial-moraxella and others
Chapter 11: Viral Conjunctivitis 75
5. Axenfeld’s chronic follicular conjunctivitis Table 11.2: Differences in adenoviral conjunctivitis
6. Chronic follicular keratoconjunctivitis of Thygeson
Epidemic Pharyngoconjunctival
7. Parinaud’s oculoglandular syndrome Conjunctivitis Fever
8. Use of contact lenses or ocular prosthesis
9. Following anterior segment surgery. Adenovirus type 8 and 9 3 and 7
Systemic symptoms – +++
Keratitis Severe Mild
Chronic Conjunctivitis
(80%) (30%)
When conjunctivitis persists for more than two weeks Eye involvement Bilateral Unilateral
it is labeled as chronic conjunctivities. The manage- Vision Disturbed Normal
ment is problematic many a times. Obvious external
eye disease may be overlooked. This includes chronic
of conjunctival discharge/scraping provide useful
dacryoadenitis, Blepharitis, dry eye state, floppy
information.
eyelid syndrome, Acne rosacea are other conditions
In spite of extensive check-up and laboratory
to be considered besides the list given above.
investigations there remains certain patients who can
Thorough evaluation of the patient is necessary to
not be diagnosed. Differences in adenoviral conjuncti-
arrive at proper diagnosis. History must include
vitis are given in Table 11.2.
medical history, exposure and occupational details,
known allergies, characteristics of ocular complaints,
FURTHER READING
previous diagnostic studies and treatment given.
Examination must include external examination of 1. Dawson CR. Follicular Conjunctivitis. In Thomas Duane (Ed):
eye and adnexa, palpation for preauricular and Ophthalmology, 1982;4:(7).
2. Nauheim RC. Prolonged recoverability of dessicated adeno-
submandibular lymph adenopathy, slit lamp virus type 19 from various surfaces. Ophthalmology
biomicroscopy, study of ocular surface after staining 1990;97:1450.
it with fluoresceine and rose bengal, tear film break 3. Roy. Ocular differential diagnosis. London Lea and Febiger,
up time and Schirmer’s test after anesthesia. 1989;205-36.
Investigations should include culture for aerobic 4. Vincet P de Luise. Viral conjunctivitis in infections of eye.
Edi Tabbara KF, Hyndiuk RA (Eds). Little Brown and Co:
and anaerobic bacteria, immunological test for
Boston Toronto 1986;437-60.
Chlamydia, and herpes virus types 1 and 2 using 5. Hogan MJ, Crawford JW. Epidemic keratoconjunctivitis. Am
monoclonal antibody. Gram stain and Giemsa stain J Ophthalmol 1942;25:1059.
Chapter 12
Trachoma
Trachoma is known to affect eye since ancient times. serotypes causes disease of milder form. Clinically the
The earlier descriptions are available from Egypt, latter group is known as inclusion conjunctivitis. It is
Babylon, and China. Trachoma is attributed to the halt also labelled as nonblinding trachoma.
of Napoleon’s incursions in Egypt. It was one of the
major blinding diseases before the advent of Epidemiology of Trachoma
antibiotics. Trachoma, in Greek, means ‘rough’. Trachoma is a disease seen in dry, dusty environment,
Though the disease is known since long, its etiology where poverty and poor hygienic condition predomi-
was not clear. Inclusion organisms were demonstrated nates. In India, it is common and endemic in north
in 1907. The organism was isolated in 1957. The Gujarat, Rajasthan, Haryana and Punjab. It is not seen
organism isolated is known as Chlamydia trachomatis. in Kashmir, Tamil Nadu, Kerala. It is also endemic in
Middle East, north and central Africa, Australia,
CHLAMYDIA TRACHOMATIS China, and Japan.
Chlamydia trachomatis belongs to Chlamydia group. There are approximately 360 million people
They are neither virus nor a bacterium. They multiply suffering from trachoma in the world. Of this, around
by a binary fission and also have cellular organization. 6 to 9 million people are blind. In India, in the past it
However, like virus, they stay inside the cells. Their was a common cause of blindness. Trachoma is no
stay inside the cells impart them relative immunity longer a blinding disease in India.
from effects of the drugs. The disease is highly contagious and spreads by
The organism is found in conjunctival and corneal direct contact. Transfer of conjunctival secretions takes
epithelium. It is also seen in mucous membrane of the place by fingers, towel or flies. Maintenance of facial
genital tract. cleanliness is found to be the best measure to reduce
Infection of cornea and conjunctiva is known as spread of trachoma.
trachoma or inclusion conjunctivitis, depending upon There is no predilection for any race. In younger
severity of the disease. Inclusion conjunctivitis is a age group prevalence of trachoma is identical in both
milder form of the disease more localized in lower sexes. However, trachoma and its sequelae are more
palpebral conjunctiva with minimal or no corneal frequent in females compared to males.
involvement. For this reason the organism is also Economic development of the region improves
known as TRIC agent (TR for trachoma and IC for hygienic conditions and reduces the prevalence of
inclusion conjunctivitis). trachoma. Prevalence and severity of trachoma is
Studies using immunofluorescent antibodies have related to number of people living in same household,
identified various subgroups of trachoma. They are number of children, latrine ownership, etc.
labeled as A, B, C, D, E, F, G, H, I, J, K, and L types. A
to C types are common in eye while remaining ones Classification of Trachoma
cause genital disease. The disease caused by types A, WHO has streamlined clinical profile of trachoma and
B, C is severe in nature and has devastating sequela. has given a new classification which replaces all the
It is also known as blinding trachoma. Rest of previous ones including McCallan’s.
Chapter 12: Trachoma 77
According to new classification, trachoma is evidence suggesting that immune mechanism is invol-
divided into 5 categories, depending upon clinical ved in progressive scarring seen in trachoma.
presentation. The first two stages suggest active During initial period clinically it is difficult or
disease while remaining are sequelae of the disease. impossible to differentiate trachoma from other causes
1. Active trachoma with follicles (TF) This is a milder of mucopurulent conjunctivitis. Changes specific of
form of infection. Conjunctival blood vessels must trachoma develop 2 to 3 weeks after clinical picture is
be visible through follicles and papillae. The apparent.
number of follicles must be minimum 5 in upper Conjunctival lesion seen in active trachoma are
lid. follicles and papillae.
2. Active trachoma intense (TI) In active trachoma Follicles are enlarged lymphoid nodules under
intense conjunctival blood vessels are not visible. conjunctival epithelium. Necrosis in the center of a
They are obscured by papillae and follicle forma- follicle is the characteristic of trachoma. They may be
tion. This is a severe form of disease and may cause visible with unaided eye. They are most commonly
complications. seen in upper palpebral conjunctiva, but may be also
3. Trachomatous scarring (TS) This represents seque- present at the limbus. Follicles at limbus are known
lae of a previous infection. There is a white scarring as Herbert’s follicles.
in upper tarsus. Papillae are seen on the surface of the conjunctiva.
4. Trachomatous trichiasis (TT) There is in turning of There is a blood vessel in center of the papilla. It
eyelashes following an attack of a trachoma. The imparts velvety look to conjunctiva. Normal conjuncti-
eyelashes may rub against cornea. This requires val vessels are not seen in this area. Follicles are
prompt management. commonly seen in upper palpebral conjunctiva.
5. Corneal opacity (CO) Corneal opacities are situated In milder forms occasional follicles and papillae
in visual axis obscuring vision to less than 6/18. are seen while in severe form, whole of the upper lid
may be obscured by follicles. Repeated infections are
McCallan’s Classification common in endemic area. They are responsible for
Arthur Ferguson McCallan (1908) divided the disease harmful sequelae of the disease. Now there is evidence
into four stages depending on findings mainly in that T-cell mediated immune response may be
upper palpebral conjunctiva. responsible for late complications. Secondary infection
Stage 1 Immature follicles are seen in upper con- with H. aegyptus is common. It makes the condition
junctiva with no evidence of conjunctival cicatrization. worse.
They are small and hard. Like conjunctival epithelium, corneal epithelium
Stage 2 Mature follicles with papillary response. is also involved. Corneal involvement is in the form
This obscures visibility of deep conjunctival vessels. of a punctate or diffuse superficial keratitis. These
Stage 3 Follicles with evidence of cicatrization in changes are more commonly seen in upper part. They
upper palpebral conjunctiva. are usually not visible with naked eye. Slit lamp
Stage 4 No follicles in upper palpebral conjunctiva examination clearly demonstrates it. Fluorescein stain
but cicatrization is present. may reveal diffuse staining.
This has been modified from time to time to include In course of the disease, blood vessels grow into
other findings, e.g. pannus. cornea from limbus gradually. This is known as
pannus. It also includes granulation tissue. Vessels lie
between Bowman’s membrane and corneal epithelium
Clinical Picture
initially. Later on as Bowman’s membrane is destro-
Trachoma usually manifests as a chronic conjuncti- yed, vessels lie in superficial corneal stroma. Corneal
vitis. In milder form it can be asymptomatic. In a epithelium may break down and form ulcer in areas
typical case it presents as an irritable red eye with of pannus. In addition to superficial blood vessels
mucopurulent discharge. In a severe form there may continuous with the conjunctival blood vessels, tracho-
be severe lid edema with photophobia due to matous pannus include vertical parallel running blood
involvement of cornea. The first attack usually passes vessels from upper limbus (Fig. 12.1). They make a
off without any ill effects. However, repeated infection horizontal level in the cornea. They do not anastomose.
leads to complications seen in trachoma. There is some They do not show branching. In cases of active
trachoma there is a zone of infiltration in front of blood

vessels. This is known as progressing pannus. In
regressing pannus this zone of infiltration is seen
between limbus and the corneal end of blood vessels.
It suggests healing stage of trachoma. Cornea in
between the vessels is hazy.
In severe form of the disease superficial vessels
grow from all around the cornea. Cornea becomes
vascularized and opaque. This vascularized corneal
opacity is usually superficial. Corneal ulcers may be
seen at the advancing edge of the pannus. They are
Fig. 12.1: An illustration showing progressive
chronic and indolent. They give rise to severe and regressing pannus
photophobia and lacrimation.
Corneal changes are very useful in judging
response to the treatment. Once Bowman’s membrane The conjunctival epithelium may become kerati-
is destroyed healing is associated with opacity. nized resulting dry appearance.
However, early treatment before breakdown of 3. Cornea The direct damage to corneal epithelium
Bowman’s membrane results in healing without results into opacity in upper part. Opacities rarely
opacity. encroach the pupillary area. Corneal opacity may
Healing takes place by scarring. Usually there is follow chronic rubbing by eyelashes due to entro-
laying of collagen fibers. The scarring in conjunctiva pion. In severe form of trachoma, the whole cornea
may distort the blood vessels. When severe they may may show superficial vascularization, and become
distort anatomy of the eyelid. In cornea, healing takes opaque.
place by scarring, which results in superficial opacity.
This is usually seen in upper part of cornea. The Diagnosis
vascular channels once formed persist for ever. They Diagnosis of trachoma is mainly clinical. In endemic
may or may not contain blood. When blood is not seen area, it should be suspected in early stage of any type
in vessels, it is called ‘ghost vessels’. At limbus the of conjunctivitis. The diagnostic signs include follicles,
scarring of follicles is associated with shrinkage. This epithelial keratitis, pannus, conjunctival scarring
results in formation of the pits at the site of follicles. typical of trachoma, and Herbert’s pits at upper
They are known as Herbert’s pits. They appear as limbus. Diagnosis of trachoma in endemic area is
brownish dimples at upper limbus. This is rarely a problem. However, it poses problem in
characteristic finding of trachoma. Cornea in the nonendemic area for which laboratory investigations
vicinity of Herbert’s pit may show superficial haze. are necessary.
Presence of basophilic intracytoplasmic inclusion
Effect of Scarring in Various Structures bodies in epithelial cells are diagnostic of trachoma.
1. Eyelids Extensive fibrosis may cause thickening of Similarly, mixed cellular reaction with plasma cells
the lid. This may cause mechanical ptosis or are also typical of trachoma. Inclusion bodies can be
madarosis. Later on, due to contraction of collagen demonstrated in few cases only during acute phase
tissue near the lid margin, causes inturning of lid and so its absence dose not rule out trachoma.
margin, known as entropion. When it is not Chlamydia trachomatis can be cultured on irradiated
uniform, the individual hair follicles may turn in McCoy cells. However, this is not practical in all cases.
rather than the lid margin. This is known as Various tests based on immune mechanism are
trichiasis. In both situations the eyelashes rub devised. Use of direct immunofluorescent monoclonal
against the cornea, and can cause corneal ulcers. antibodies against trachoma, is found to be very
The fibrosis may cause obstruction of meibomian reliable. It has specificity of 94% with 100% sensitivity.
glands. Recently, immune dot blot test is also described. It
2. Conjunctiva There is subconjunctival fibrosis detects chlamydial lipopolysaccharide antigen. This
leading to obliteration of fornices. Loss of mucus is found to be more than twice as sensitive as culture
secreting cells result in tears deficient of mucus. technique.
Chapter 12: Trachoma 79
Treatment In persons with genital tract infection, systemic
treatment is also necessary. Systemic treatment for two
Trachoma organisms are sensitive to sulphacetamides
weeks is adequate.
tetracycline, sulphonamides, erythromycin, cipro-
floxacin and azithromycin. Rifampicin is also found
Prevention
to be effective against trachoma. Recent studies have
shown sparfloxacin to be effective in trachoma. Since Improvement in hygienic condition is the best commu-
trachoma organisms live inside the cells, effect of nity measure to control trachoma. During
antibiotics is slow and so treatment should be for a epidemiological studies, it is found that cleanliness of
longer period of time. face is important step in preventing trachoma. If the
Systemic therapy consists of oral tetracycline 1 to face is washed with water on regular basis and kept
1.5 mg daily or oral doxycycline 100 mg b.i.d for clean, the children are least likely to get trachoma in
2 weeks. Single dose azithromycin 20 mg/Kg, has the community.
been reported to be effective as a course of 6 week
course of topical tetracycline.8 REFERENCES
The usual mode of administrating drugs is topical 1. Bishop PN. An immune dot blot test for the diagnosis of ocular
in the form of drops or ointment or suspensions. This infection with chlamydia trachomatis. Eye 1991;5:305-08.
should be given minimum 4 times a day for six weeks. 2. Reacher MH. T-cells and trachoma: Their role in cicatricial
Intermittent treatment in the form of topical disease. Ophthalmology 1991;98:334-41.
3. Courtright P. Latrine ownership as a protective factor in inflam-
instillation of a drug, twice a day for 1 week every
matory trachoma in egypt. Br J Ophthalmol 1991;75:322-25.
month for six months is also helpful. This is 4. West SK. Epidemiology and biostatistics: Facial cleanliness and
particularly helpful for community based treatment. risk of trachoma in families. Arch Ophthalmol 1991; 855-57.
Once upon a time tetracycline eye ointment at bedtime 5. Park JE, Park K. Textbook of preventive and social medicine.
daily was suggested as a community measure to M/s Banarsidas Bhanot: Jabalpur, India, 1987;206-07.
6. Tabbara KF. Chlamydial conjunctivitis in infections of eye.
eradicate/control trachoma. Tetracycline 1% eye
WHO: Geneva. Guide to Trachoma Control 1981. 1986;421-36.
ointment should be applied at bedtime daily for 7. Tabarra KF, Abu El Asrsr, Al-Omar O et al. Single dose
consecutive 60 days or for 10 consecutive days every azithromycin in the treatment of trachoma. Ophthalmology
month for 6 months. 1996;103:842.
Chapter 13
Bacterial and Special

Conjunctival Conditions
Conjunctival sac is rarely sterile. The normal was a common cause of ophthalmia neonatorum. N.
conjunctival flora shares organisms with skin and meningitids infection may cause meningitis.
respiratory tract. It may contain Staphylococcus, Epithelial scrapings reveal numerous polymorpho-
Diphtheroids, Anaerobes, Streptococcus, Pneumococcus, nuclear cells. On Gram’s stain causative organism may
Hemophilus, E. coli, etc.1 be detected, usually these are gram-negative diplococci.
Bacterial conjunctivitis is commonly due to organisms Culture can be done in blood agar or chocolate agar
of exogenous source. It is usually a self-limiting medium. This helps in identification of organism and
disease due to barrier effect of epithelial surface. The selection of proper antibiotics.
exceptions to this are N. gonorrhoeae, Listeria Corneal complications are usually not seen. Super-
monocytogenes, Corynebacterium diphtheriae, and ficial peripheral corneal infiltrates or ulcers are found
Hemophilus group. Bacterial infection invites in infections due to H. influenzae biotype III.
polymorphs. The proteolytic enzymes liberated by Streptococcus and H. influenzae are the common
polymorphs and toxins liberated by organisms may organism causing acute catarrhal conjunctivitis. Other
destory parenchyma of the conjunctiva. The discharge organisms are Staphylococcus, Pneumococcus, E. coli,
produced is initially scanty and serous, it becomes Proteus, etc.
mucoid and purulent later on. The fibrin in discharge Broad spectrum topical antibiotics instilled every
may form a pseudomembrane. The true membrane 2 hours results in a cure. Systemic antibiotics are not
is formed when inflammatory exudate damages necessary except in gonococcal conjunctivitis which
can be treated with a single intramuscular or
conjunctival epithelium (Table 13.1).
intravenous injection of Cefotaxime.
Topical antibacterials, e.g. sulphacetamide 10%
ACUTE PURULENT CONJUNCTIVITIS
applied 2 hourly is usually adequate. When infection
It begins as irritation and/or redness of the eyes. is not responding antibiotics may be selected after
The exudation is purulent. Lids stick to each other culture and sensitivity report of conjunctival secretions.
usually in the morning. It may manifest in one eye
and spread to other eye. ACUTE CATARRHAL CONJUNCTIVITIS
The causative organisms include N. gonorrhoeae, Acute conjunctival hyperemia and a moderate muco-
N. meningitidis, Staphylococcus, Streptococcus, H. purulent discharge mark the beginning of acute
egyptus, E. coli, and Pseudomonas. catarrhal conjunctivitis. It is usually caused by
Infections with N. gonorrhoeae and N. meningitidis Streptococcus or H. influenzae. It may occur sporadically
are relatively serious. N. gonorrhoeae infection may or as an epidermic. Multiple subconjunctival hemorr-
cause peripheral corneal infiltration, corneal ulcer, hages are frequently seen usually under the upper
iritis, lid abscess, dacryoadenitis and septicemia. This lid.
Chapter 13: Bacterial and Special Conjunctival Conditions 81
CHRONIC CATARRHAL CONJUNCTIVITIS Table 13.1: Etiology of membrane formation
The commonest organism include Staphylococcus Infectious — Streptococcus
aureus or Moraxella lacunata. Chronic conjunctival Diphtheria
hyperemia with minimal mucoid discharge is seen. Gonococcal
Moraxella infection manifests as chronic blepharocon- Herpetic
junctivitis with or without involving angles of Adenoviral
Inclusion
palpebral fissure. Follicular reaction of palpebral
Granulomatous
conjunctiva is also seen. Candida conjunctivitis
Staphylococcus aureus is the commonest organism
seen in chronic bacterial conjunctivitis. They may Noninfectious — Vernal conjunctivitis
Ocular cicatrical pemphigoid
cause inferior punctate keratitis, marginal corneal
Stevens Johnson
infiltrates or ulcers and phlyctenular keratoconjuncti- Ligneous
vitis. They may colonize in the lid margin and cause Chemical burns
blepharitis.
Treatment of chronic conjunctivitis is difficult. It photophobia, tearing, and blepharos-pasm. In severe
should include antibiotics after culture and sensitivity cases cornea may be involved resulting an ulcer,
testing. Attention to the hygiene of lid margin is a scarring, and visual disturbances.
must for control of infections. Patients should be It generally affects undernourished children.
instructed to use hot compresses and lid massage. Usually in their first or second decade of life, females
Chronic blepharitis may require Doxycycline 200 mg are affected more frequently than males. It is seen all
first day and 100 mg daily for one month. over the world but is a rarity where tuberculosis is
not prevalent. The disease is more frequently associated
MEMBRANOUS AND PSEUDOMEMBRANOUS with poverty.
CONJUNCTIVITIS The precise mechanism by which phlyctenules are
Commonly Streptococcus pyogenous or corynebacterium produced has not been determined. It is assumed
diphtheria are responsible for this type of conjunctivitis. that patient has been sensitized to the antigen in the
In diphtheric conjunctivitis there is formation of true past, which can be tubercle bacilli, pneumococci, Koch
membrane; when the membrane is peeled off oozing weeks bacillus, staphylococci, and parasites.
of blood occurs from conjunctival surface. The memb- The pathological findings of phlycten are lympho-
rane is grayish-yellow. The nasopharynx or larynx cytes, histiocytes, and plasma cells.
may also be affected. Conjunctival scarring, symble-
pharon, trichiasis, entropion and corneal scarring may Clinical Manifestations
be seen as sequelae. The treatment include 10,000 to It occurs on the conjunctiva or cornea. The different
100,000 units of diphtheria antitoxin. locations give rise to different symptoms, signs, and
In streptococcal conjunctivitis there is edema of prognosis for vision.
the lids with involvement of palpebral conjunctiva.
Cornea may be infiltrated or ulcerated. The chronic Symptoms
form may resemble ligneous conjunctivitis.
Local treatment consists of topical antibiotics. Conjunctival It causes mild to moderate disturbances
Penicillin and erythromycin are effective antibiotics. in the form of watering and irritation. Mucopurulent
discharge is suggestive of secondary bacterial infection.
PHLYCTENULAR KERATOCONJUNCTIVITIS This lasts for one to two weeks.
Greek word ‘Phlyctena’ means blister or bleb. Corneal Moderate to severe symptoms like pain,
Phlycten is a nodular affliction of conjunctiva watering, photophobia, and blepharospasm. The
characterized by the formation of a small, patient hides the face from light.
circumscribed lesion at the limbus. This develops into
a microabscess which heals in 10 to 14 days. This is a Signs
delayed hypersensitivity type of reaction to any
Conjunctival Lesion is found most frequently near
foreign protein. It occurs mainly in children and
young adults. It gives rise to discom-fort, extreme the limbus, as a small, pink-white nodule in the center
of a hyperemic area. Within few days upper part of 2. Tranta’s dots

the nodule becomes gray and soft. The necrotic center 3. Limbal hypertrophy
of the lesion sloughs and clears without scar. 4. Marked itching
5. Moderate photophobia
Corneal phlyctenule Lesion starts at the limbus as a
6. Mild to moderate ocular inflammation.
white mound, bordered on conjunctival side by a fan
It is important to carefully differentiate the
of dilated blood vessels. This may show necrosis,
phlyctenular keratoconjunctivitis as it has different
shelving out and healing or may progress on the clinical course and treatment.
cornea toward the center as a progressing gray,
necrotic, superficial ulcer surrounded by white Treatment
infiltrates of anterior cornea. There is a leash of blood
vessels traversing from limbal conjunctiva. The Corneal phlyctenulosis The treatment is topical steroids
condition is labeled as fascicular ulcer. This heals in given 2 hourly for 4 days followed by 4 times a day
for another 3-4 days and to be discontinued once it
10 to 15 days leaving cicatrix according to the severity
subsides. Cycloplegic drops are prescribed. Dark glass
like small limbal opacity to characteristic wedge
provides comfort from photophobia. If there is secon-
shaped fascicular scar.
dary infection broad spectrum antibiotic drops are
Rarely corneal phlyctenule may perforate and pre-
administered 2 hourly for 3-4 days. Evaluate the
sent as well circumscribed punched out lesion with patient for tuberculosis with the help of a pediatrician.
well-defined margins close to limbus. The inflamma-
tory reaction is minimal. Healing of this perforated Conjunctival phlyctenulosis If not causing much
corneal ulcer may be by formation of a well demarcated symptoms it can be treated by only topical astringents.
leucoma adherence near limbus. If discomfort is considerable topical steroid may be
used.
Differential Diagnosis Nontuberculous phlyctenulosis The lids and conjunctiva
i. Inflamed pinguecula should be evaluated for evidence of chronic stapylo-
coccal blepharitis, acne rosacea or meibomitis. If
ii. Acne rosacea
found to be present then treat it vigorously with
iii. Infective ulcer
antibiotic steroid ointment twice daily accompanied
iv. Marginal ulcer
by shampoo program with an effective antidandruff
v. Vernal keratoconjunctivitis. preparation.
Oral tetracycline (250 mg daily × 3 weeks) found
Inflamed Pinguecula to be safe and effective in adults as an alternative to
1. Failure to evolve into microabscess corticosteroids.
2. Presence of hypertrophic collagen at the limbus
in the palpebral fissure when it subsides. Prognosis
The use of steroids has changed the prognosis for
Infective Ulcers this diseases. Without treatment it is a potentially
1. Lack of demarcating margin blinding disease, but with adequate treatment,
complete resolution can be expected.
2. Central corneal position
3. Clinical course. OCULAR CICATRICIAL PEMPHIGOID
Marginal Ulcers Ocular cicatricial pemphigoid is one of the most severe

and progressive form of cicatricial conjunctivitis.2
1. Position of ulcer just inside the limbus, parallel However, the condition is relatively rare. It is a
to, but usually not connected to the limbus. chronic inflammatory disease primarily and initially
2. Absence of microabscess affecting the mucous membranes, producing a
3. Failure of the ulcer to migrate. blistering rash, followed by inflammatory lesions
which eventually cicatrize. Usually, it develops in the
Vernal Keratoconjunctivitis age group of 60 to 70 years, and females are more
commonly affected than the males. Conjunctiva and
1. Presence of eosinophils in the conjunctiva
Chapter 13: Bacterial and Special Conjunctival Conditions 83
oral mucosa are most frequently affected but is sterile, but when it ruptures secondary infection
esophagus and genitalia and rectal mucosa may also be may set in which causes infiltration of inflammatory
involved. During the later stage of the disease cells. In the mean time perivascular thickening and
progressive subepithelial fibrosis develops with subepithelial proliferation of fibrous tissue lead to
resultant fornix foreshortening, symblepharon, formation of macroscopic fibrous bands in both
trichiasis, and entropion. Obstruction of meibomian bulbar and palpebral conjunctiva.
and lacrimal gland ducts coupled with reduction of
number of goblet cells cause sicca syndrome. Keratini-
Treatment
zation of the ocular surface and sloughing of the
cornea lead to blindness. Systemic steroid, 40 to 60 mg of prednisone daily till
Clinically ocular pemphigoid can be divided into the active process is controlled. After initial control
following stages: the dose of steroid should be tapered to lowest
Stage 0 Absence of conjunctival scarring effective dose and gradually to alternate days dose.
Stage I 25% or less shrinkage of conjunctiva Topical steroid provides little benefit. Steroids act as
Stage II 25 to 50% shrinkage of conjunctiva a suppressive agent and do not produce long-term
Stage III 75% shrinkage of conjunctiva remission of the disease. When steroid is withdrawn
Stage IV Obliteration of conjunctival fornix with abruptly the process is likely to be reactivated. When
keratinization of ocular surface. high dose of steroid manifests undesirable side
effects alternative therapy should be considered.7
Differential Diagnosis Sulfone derivatives like dapsone may be effective
in controlling cicatricial pemphigoid. It is very much
Cicatricial conjunctival pemphigoid should be effective in oral lesions. It has got some side effects
differentiated from severe conjunctival inflammation on hemopoietic system particularly producing
caused in following conditions: hemolytic anemia accompanied by compensatory
a. Erythema multiforme (major and minor) reticulocytosis. Therefore, it should be started in a
b. Toxic epidermal necrosis low dose and gradually increased to full therapeutic
c. Alkali burn range.
d. Infections: trachoma, adenovirus Types VIII and In rapidly progressive and extremely active
XIX keratoconjunctivitis disease more agressive treatment is required.
e. Application of drops and ointments containing epi- Immunosuppre-ssive drugs like cyclophosphamide
nephrine, iodoxuridine aminoglycosides3,4 and and azathioprine alone or in combination with
sometimes betablockers. prednisone are effective drugs. These drugs not only
However, these pseudopemphigoids cannot be suppress activity of the disease but also provide a
differentiated from the pemphigoids clinically. sustained remission.
Correct diagnosis can only be done by direct
immunological studies.5 A biopsy taken from the ERYTHEMA MULTIFORME MAJOR
uninvoled tissue immediately adjacent to a lesion (STEVENS-JOHNSON SYNDROME)
shows linear deposits of IgG along the basement
This is basically a type of hypersensitivity reaction
membrane zone in cicatricial pemphigoid but not in
to drugs like sulfonamides, antibiotics, bacteria, and
pseudopemphigoid.6
viruses working through the auto immune system.
Initially there is vasculitis; therefore, the acute phase
Pathology is characterized by synmmetrical erythematous and
Cicatricial pemphigoid is a systemic autoimmune bullous lesions in the skin and mucous membrane of
disease in which the autoantibodies directed against the body. There may be hemorrhages into the vesicles
the conjunctival epithelial cell basement membrane over the skin.8
initiate a Type II hypersensitivity reaction. The initial Toxic epidermal necrolysis occurs in two forms.
pathology is vesicle formation which may be anywhere One occurring in young children known as Ritter’s
in the conjunctiva. The size of the vesicle may vary type and the opther in adults known as Lyell’s
from few mm to one cm. The fluid inside the vesicle syndrome. The Ritter’s type is caused by exotoxins
of staphylococcus of phase type LXXI while Lyell’s REFERENCES

type in its ocular manifestations is similar to erythema 1. Antonios S, Tabbara KF. Bacterial Conjunctivitis in Infections
multiforme. Ritter’s type is usually unilateral. In the of Eye. Tabbara KF, Hyndiuk RA (Eds), Little Brown and Co.:
conjunctiva, red infarcts and ischemic areas are seen. Boston and Toronto, 1986;413-20.
The conjunctival surface becomes yellowish-red in 2. Duke Elder S. System of Ophthalmology. Henry Kimpton,
color; focal scarring forms fibrotic patches. Those may London 8 (Part 1). 1965;139.
3. Davidson CR, Tuff SL, Dart JKG. Conjunctival necrosis after
involve the whole conjunctiva leading to dry eye state
administration of topical fortified aminoglycosides. Am J
due to blockage of the ductules of the lacrimal gland Ophthalmol 1991;11:690.
in the superior fornix and involvement of the goblet 4. Jacob IH, Goldberg DB, Flore PA. Drug induced pemphigoid:
cells in the scarred areas. Cicatricial entropion with A spectrum of disease. Arch Ophthalmol 1987;105:1660.
trichiasis develops due to contracture of the lid 5. Foster CS, Shaw CD, Wells PA. Scanning electron microscopy
on conjunctival surface in patients with ocular cicatrizing
margins. Symblepharon is also a common compli-
pemphigoid. Am J Ophthalmol 1986;102:554.
cation. Corneal ulceration with pannus formation 6. Power WJ, Naves RA, Rodriguez A et al. Increasing the diag-
leads to blindness. nostic yield of conjunctival biopsy with suspected cicartricial
Treatment consists of administration of topical and pemphigoid. Ophthalmology 1995;105:1158.
systemic steroids in appropriate dosage.9 To prevent 7. Morrison LH, Swan KC. Cicatricial Pemphigoid in Current
symblepharon the fornices should be wiped twice Ocular Therapy. Ed Fraunfelder and Roy, Saunders 1990;3:403.
8. Wright P. Cicatrizing conjunctivitis. Doyne Lecture. Trans
daily with a glass rod anointed with a steroid— Ophthalmol Soc UK 1986;105,1.
antibiotic ointment. Surgical treatment is indicated 9. Mondive BJ, Brown SJ. Immunosuppresive therapy in ocular
to tackle the complications after healing of the active cicatricial pemphigoid. Am J Ophthalmol 1983;96,453.
pathology.
Chapter 14
Laboratory Diagnosis of
Extraocular Infective Organisms
The detection of organisms or finding out the cause and later seen in the smears from patients by
of the infection is based on the two sets of tests, i.e. Halberstaedter and von Prowazek in 1907.
standard methods, and tests for rapid identification Immunochemical methods like immunofluorescent
of organisms. and immunoperoxidase staining are more sensitive
than standard Giemsa’s stain. Immunoperoxidase has
STANDARD METHODS
the advantage of possibility of making permanent
There are four laboratory tests: preparations, and normal light field microscopy can
be used for the examination. The development of
Cytological Tests antichlamydial monoclonal antibodies and their use
In these tests the cause of the disease is inferred from in immunochemical staining allows chlamydial
the type of the inflammatory cells present in the elementary bodies to be identified reliably in such
conjunctiva.1 The conjunctival cells are spread in a specimen. Commercially, available fluorescein labeled
slide by scraping and the smear is stained with monoclonal antibodies to herpes simplex virus have
cytological stains like Giemsa. The results are however been used to detect virus infected cells in smears from
not confirmative because polymorphonuclear leuko- skin vesicles. Enzyme immunoassay is another
cytes predominate in acute stage of inflammation and method to detect microbial elements in clinical
mononuclear leukocytes predominate in chronic specimens. Enzyme labeled antibodies and substrates
infections. The polymorphonuclear leukocytes found are used to produce a color which can be read
in acute stage of trachoma may contain the inclusion spectrophotometrically.2
bodies.
Direct Detection Tests
Culture and Isolation Test
In these tests specimen obtained from the patients
are tested directly either for presence of relevant In this test the specimen is cultured to grow the
microorganisms or of the antigen specific of that organism. It is important that the specimens collected
microorganism. The microorganisms donot need to contain sufficient epithelial cells and they must be
be viable but they may be present in small quantity transported to the laboratory in a manner designed
just to make the least sensitive. Chlamydia to preserve the viability of the organism. It was
trachomatis was first detected in Giemsa stained difficult to get cell culture of C trachomatis but egg
conjunctival smear and later from the eye of an culture was easy. Special preparation of the cells is
orangutan which had been experimentally inoculated necessary to make them suitable for culture of C
with materials from the eyes of trachoma patients trachomatis.3
Serological Tests methods are relatively quick and simple to perform

In these tests the patient’s sera or local secretions are and easier to interpret:5
a. Ink-potassium hydroxide preparation A mixture of 10%
tested for antibodies to the microorganisms. The
potassium hydroxide and ink (Parker blue-black
presence of specific antibodies indicates the patient’s
super) is prepared in 9:1 ratio. The specimen is
exposure to a particular infection in the past or
placed in the glass slide; a drop of the mixture is
present. The presence of specific IgM antibodies or a
added and coverslip is placed on the top. The slide
high titre of IgG antibodies in blood is suggestive of
is stored in moist chamber and examined by light
the present infection. In some cases the presence of
microscopy one, two, and 18-24 hours later.
antibodies in local secretions has been seen to correlate b. Calcofluor Calcofluor is a stilbene derived fluore-
active disease. The absence of antibodies to a scent dye that stains cellulose and chitin. 1%
particular organism argues against it being the cause calcofluor and 0.1% Evans Blue (to decrease non-
of the infection unless the specimen has been taken specific fluorescence) in distilled water is used.
so soon after the onset that there has not been enough Specimen is placed on a glass slide. After one
time for antibody production. A definite diagnosis minute the slide is rinsed in distilled water, and
can be obtained if a second sample is tested at least putting a nonfluorescent mounting medium the
two weeks after the first.4 specimen is covered with a glass cover slip. The
slide is examined with an epifluorescence micro-
TEST FOR RAPID IDENTIFICATION
scope using an exciter filter that transmits a wave
OF ORGANISMS length of 365 nm and a barrier filter that transmits
The main laboratory techniques for ocular microbial a wave length of 420 nm.5,6 Blankophor and unitex
agents are the following: (a) Culture of organisms, are two other nonspecific chemicals used for
(b) Chemical assays, and (c) Direct examination of fluorescein stain for rapid diagnosis of mycotic
clinical specimen. infections in tissue section and cytopathological
Depending upon the type of organisms it takes preparation. The chitin present in the fungal cell
about 48 hours to 14 days to get the culture result. wall absorbs the nonspecific fluorescein stains.
Direct examination of the specimen can be done by
conventional methods like Gram, Giemsa or by newer Fluorescein Conjugated Lectin
technique like fluorescent antibody staining lectins, Lectin is a type of protein found in plant seeds; it has
etc. the property of binding specifically to carbohydrate
In case of smears from corneal ulcers or conjunctival group. Most of the cell wall macromolecules of fungi
discharge one can have a gross impression of the consist of oligosaccharides, and fluorescein
causative organism by studying the nature of inflamma- conjugated lectin can easily bind with these particles.7
tory cell by Gram’s and Giemsa’s stain. For example, Using epifluorescein microscope mycotic organisms
there is preponderence of polymorphonuclear leuko- are easily detected in smears and tissue section which
cytes in bacterial and fungal infection, mononuclear have been treated with brief exposure with
cell in viral diseases and macrophages and plasma fluorescein conjugated lectin.
cells in chlamydial infections. Bacteria, fungi, and cysts
of acanthameba can be identified rapidly by a good Affinity Membrane Test for
Gram’s stain. Giemsa’s stain is also helpful in the Superficial Corneal Herpes
detection of mycotic organisms in about 75% of cases. A protein binding affinity membrane is gently
touched to the corneal lesion. The membrane is
Fungus Identification allowed to dry for five minutes and is immersed in a
Accurate diagnosis of mycotic infection can be made 0.5% casein-blocking buffer containing 1:1000 dilution
only by examination of scrapings or biopsy specimens horseradish peroxidase conjugated anti herpes
from the affected parts. Culture of fungus requires a simplex virus antibody for 15 minutes at room
minimum of 48 to 72 hours for diagnosis. Current temperature. The membrane is washed in three
staining methods are either insensitive (Gram and changes of 0.1% solution of Triton 100 detergent in
Giemsa) or tedious to perform and difficult to phosphate buffer saline and two changes of deionized
interpret without some experience (Gomori’s water, and then immersed in a substrate solution
methenamine silver and PAS). The following two made as follows: 100 mg of tetramethyl benzidine
Chapter 14: Laboratory Diagnosis of Extraocular Infective Organisms 87
dissolved in 10 ml of dimethyl sulfoxide and one ml and intraocular lesions caused by gram-negative
of tetramethyl benzidine solution diluted in 100 ml organisms like pseudomonas and proteus can be
of 0.1 M sodium acetate/citrate buffered at pH 6.0, made.8,9 The principle of this test is based on the fact
and 0.1 ml of 30% hydrogen pero-xide.7 that the endotoxin of the gram-negative bacteria
Membranes which adsorbed herpes virus antigen activates clotting of proteins extracted from amebo-
from contact with an infected cornea develop a cytes of the horse shoe crab limulus polyphemus. This
pattern of intense deep blue staining almost test is more sensitive than Gram stain smears of the
immediately upon contact with the tetramethyl specimens obtained from the lesion. Moreover, the
benzidine solution. The reaction is complete in 3 to 5 test is positive even after initiation of antibiotic
minutes. Membrane without antigen and those therapy because the endotoxin remains at the site of
blotted on nonherpetic corneal lesions remain the lesion even after starting of treatment. The result
colorless. The total time needed to obtain the result of the test may be obtained within one hour.10
of this test is about 30 minutes. Some newly developed tests are very costly and
difficult to perform. As kits for these tests are becoming
Limulus Amebocyte Lysate Assay
increasingly available in well-equipped laboratories
By this new test rapid diagnosis of ulcerative corneal in developed countries, ophthalmologists should
know about their applications (Table 14.1).11
Table 14.1: The rapid laboratory methods for identification of ocular microbial infections
and their clinical application and reliability (Rao, NA, 1989)
Methods Time required Infectious Practical Reliability

to perform agent application
the test
Conventional Techniques
Gram’s stain 15 min to ½ hr Bacteria Simple technique, low cost Positive in 60 to 70% of cases.
Giemsa’s stain 15 min to ½ hr Chlamydia, fungi Simple technique, low cost Useful in chlamydial infections,
reliable in identification of fungi
in 75 to 90% of cases.
KOH 10-15 min Fungi Simple technique, low cost Less reliable, yields positive
result in 33% of cases.
Gomori’s stain 2-3 hr Fungi Special technique, low cost Yields positive result in 85% of
cases.
Newer Methods
Endotoxin assay 1 hr Gram-negative Special technique, requires More sensitive than Gram’s stain,
Limulus bacteria aseptic precautions, strict can be used in treated cases,
amebocyte adherence to time/ some compounds can induce
lysate test temperature needed false-positive or false-negative
results.
Fluorescein stains 30 min Fungi acanthamoeba Simple technique, Reliable techniques, species
Conjugated lectins microscope differentiation when a panel of
lectins is used.
Nonspecific 30 min Fungi acanthamoeba Simple technique Reliable, claimed to be better than
fluorescein stains requires special Gomori’s methenamine silver
Calcofluor white microscope stain.
Blankophor Uvitex
2B
Electron 1 hr Major groups of Special technique, Organisms need to be present at
microscopy with viruses needs sophisticated concentrations of 1 x 106
negative staining equipment and skilled particles/ml.
observer
Use of Monoclonal Antibody Immunofluorescent Staining

Monoclonal antibody also can be used in diagnosis This method is used in diagnosis of viral infections
of viral, bacterial, and chlamydial infections. caused by herpes simplex, 12 herpes zoster,
Monoclonal antibodies are highly specific and are adenovirus,13 enterovirus, and cytomegalovirus.14,15
produced by hybridoma cell lines. This procedure The principle of the method is demonstration of
consists of immu-nizing a mouse to a particular fluorescein isothiocyanate conjugated antibody com-
antigen of a pathogenic organism and fusing spleen plex with viral antigen in specimen using ultraviolet
cells of the immunized animal with myeloma cells to illumination. Such antigen-antibody complexes can
produce hybrid cells. These hybridoma cells have the be visualized by the following (a) direct, (b) indirect,
capacity to produce antibody specific to the antigenic and (c) anticomplement immunofluorescent methods:
determinant of the pathogen. a. Direct method This method consists of examination
of the specimen after application of fluorescein
Nucelic Acid Hybridization Reactions conjugated antibody to the fresh or preserved
specimen.16 This method is more specific than the
Hybrid means offspring of parents of two species.
indirect one (described below), but it requires high
The principle of the test is that the structure of the
titred antisera for conjugation.
double stranded DNA is to be denatured by exposing
b. Indirect method In this method the specimens are
the test material at extreme temperature. When such
treated first with unlabeled antisera after which
dena-tured single stranded DNA of the specimen
the fluorescein labeled immunoglobulins are
comes in contact with single stranded DNA probe, a added. This secondary antibody is directed
double stranded molecule is formed consisting of one against the animal species in which primary
strand from the infectious agent and one strand from antisera are prepared. However, the indirect
testing DNA probe. This is the hybridization of method is less specific because additional reagents
nucleic acid. are introduced into the reaction system.
With specific kits detection of infectious agents c. Anticomplement immunofluorescent method In this
like human immunodeficiency virus, adenovirus,13 method addition of primary antibody is followed
cyto-megalovirus, Epstein Barr virus, herpes simplex by addition of complement and then addition of
virus12, mycobacterium tuberculosis, and chlamydia fluorescein tagged antibodies.
can be done within few hours.
Fluorescent-antibody staining is more sensitive REFERENCES
than the traditional method of Giemsa’s staining for
1. Thygeson P. The cytology of conjunctival exudates. Am J
detection of chlamydial inclusions in conjunctival
staining. Culture in irradiated McCoy cells is more 2. Darougar S, Woodlands RM, Jones BR et al. Comparative
sensitive than the direct demonstration of chlamydial sensivity of fluorescent antibody staining the conjunctival
inclusions in Giemsa’s stained smears.2 scraping and irradiated McCoy cell culture for the diagnosis of
hyperendemic trachoma. Br J Ophthalmol 1980;64:276.
Electron Microscopy 3. Darougar S, Woodlands RM, Walpita P. Value and cost
effectiveness of double culture for diagnosis of viral chlamydial
For detection of virus of vesicular lesions, the inclusion infection. Br J Ophthalmol 1987;71:673.
bodies in the cells may be detected by light micro- 4. Woodland RM. Laboratory diagnosis of chlamydial and viral
scopy. Special preparations like Papanicolaou smear disease. Eye 1988;(2 Suppl) 5:70.
or Tzanck tests are methods for rapidly detecting 5. Arffa RC, Avni I, Robin J et al. Am J Ophthalmol 1985;100:719.
some viral infections but are of limited use because 6. Day DM, Akrabawl PI, Head WS et al. Laboratory isolation
techniques in human and experimental fungus infection. Am J
of their low sensitivity in detecting the agent. Ophthalmol 1979;87:688.
Electron microscopy with negative staining is 7. Robin JB, Arffa RC, Avni I, Rao NA. Rapid visualization of
particularly useful in rapid detection of viruses in three common fungi using fluorescein conjugated lactins. Invest
vesicular lesions. This technique needs 15 minutes to Ophthalmol Vis Sci 1986;27:500.
one hour to prepare the specimen and half an hour 8. Wolters RW, Jogresson JH, Calzada E et al. Limulus lysate
assay for early detection of certain gram negative corneal
to identify the major group of viruses. By this method
infections. Arch Ophthalmol 1979;97:875.
the morphology of the infectious agent can be directly 9. Ellison AC. The limulus lysate test: A rapid test for diagnosis
identified and the concentration of the agent must of pseudomonas keratitis or endophthalmitis. Arch Ophthalmol
be about 1 × 10 6 or more particles per ml of the 1978;96:1268.
specimen.
Chapter 14: Laboratory Diagnosis of Extraocular Infective Organisms 89
10. McBeath I, Forester RK, Rebell G. Diagnostic limulus lysate 14. Repose JS, Nestor MS, Holland GN et al. Analysis of retinal
assay for endophthalmitis and keratitis. Arch Ophthalmol cotton wool spots and cytomagalovirus retinitis in the acquired
1978;96:1265. immunodeficiency syndrome. Am J Ophthalmol 1983;95:118.
11. Rao NA. A laboratory approach to rapid diagnosis of ocular 15. Pepose JS, Holland GN, Nestor MS et al. Acquired immuno-
infections and prospects for the future. Am J Ophthalmol deficiency syndrome. Pathogenic mechanism of ocular disease.
1989;107:283. Ophthalmol 1985;92:472.
12. Egerer I, Stary A. Erosive ulcerative herpes simplex blepharitis. 16. Vastine DW, Schwartz HB, Yamashroya HM et al. Cytologic
Arch Ophthalmol 1980;98:1760. diagnosis of epidemic keratoconjunctivitis by direct immuno-
13. Darougar S, Walpita P, Thaker U et al. Rapid culture test for fluorescence. Invest Ophthalmol Vis Sci 1977;10:195.
adenovirus isolation. Br J Ophthalmol 1984;68:405.
Chapter 15
Allergic Conjunctivitis and

Allied Conditions
Allergic ocular disease is a common clinical condition a. Seasonal nature of the disease: SAC is associated with
faced by practitioners. About 15 to 20 percent of the rhinorrhea and hence called rhinoconjunctivitis
world population suffer from some sort of allergic also. It is usually caused by seasonal blooms of
ocular disease. Allergic conjunctivitis may be the most pollen producing plants. VKC is more common
common clinical condition in the group of allergic and exacerbated during spring (hence called
ocular diseases. Spring Catarrh) and summer than during other
Allergic conjunctivitis can be classified into the seasons of the year.
following five categories:1 b. Papillae formation: Papillae formation is
characteristic feature of VKC, GPC and AKC; Very
• Seasonal allergic conjunctivitis (SAC)
occasionally found in SAC.
• Vernal keratoconjunctivitis (VKC) c. Visual complication: AKC has got the greatest
• Atopic keratoconjunctivitis (AKC) propensity for causing visual loss. VKC may cause
• Giant papillary conjunctivitis (GPC) mild visual disturbance. SAC has got no threat
• Contact Hypersensitivity. for visual impairment.
Each of the above categories are characterized by d. Age: SAC begins in early age. VKC in children and
the following common factors: young adults. AKC persists through life.
Table 15.1: Types of allergic conjunctivitis and their treatment

Name of the condition Drug therapy Visual prognosis
1. Seasonal allergic conjunctivitis Antihistaminics, Decongestants, No threat for visual
Mast cell stabilizers loss
2. Vernal conjunctivitis Cromolyn Sodium, Lodaxamide, Possibility of visual loss due
Azelastine, NSAID, Steroid, Cyclosporin-A to corneal pathology
3. Atopic conjunctivitis Cromolyn sodium, Loteprednol, NSAID Threat for visual loss
due to corneal pathology
4. Giant papillary conjunctivitis Cromolyn sodium, Loteprednol, NSAID Usually no visual loss
5. Contact hypersensitivity Avoidance of possible allergens, very short Low possibility of visual loss
term steroid due to corneal scar
Modified from Stock and Pendletoni

Chapter 15: Allergic Conjunctivitis and Allied Conditions 91
SEASONAL ALLERGIC CONJUNCTIVITIS inflammatory drugs (NSAIDS) are effective for
treatment of SAC. Aspirin is the first NSAID to be
Seasonal allergic conjunctivitis (SAC) starts as a mild
used for SAC. 3 However, there is no topical
inflammation of the conjunctiva. Airborne allergens
preparation of aspirin. Long time oral administration
like pollen, molds, dust, mites, and animal dander
of aspirin may cause some systemic complications
can trigger an allergic response in the nose and
including melena. Topical antihistaminics and
conjunc-tiva. When the conjunctivitis is associated
combination of antihistaminic and decongestant
with allergic rhinorrhea it is called rhinoconjunctivitis.
preparations should be the first line of therapy in
In specific seasons and specific areas it may be
management of SAC. It is important to note that
associated with hay fever. The allergens from the
rebound phenomenon may develop on sudden
above mentioned sources dissolve in the tear film
discontinuation after prolonged use of any
and come in contact with the specific Type I, IgE
decongestant therapy. Topical decongestant may be
receptor bound to the conjunctival mast cell
combined with topical steroid. However, long term
membrane and induces the conjunctival pathological
use of steroids is threat for complications like cataract
changes associated with antigen— antibody reaction.
and open angle glaucoma.
Clinical Features
VERNAL KERATOCONJUNCTIVITIS
Ocular itching, tearing and occasional photophobia
are the presenting features of SAC. However, the Vernal keratoconjunctivitis (VKC) is a chronic, recur-
ocular symptoms may be severe enough to interfere rent, often severe, bilateral external ocular allergic
with the daily functioning. Generally patients do not disease that affects primarily children and young
develop keratitis or structural change in the adults. Vernal comes from the Greek word meaning
conjunctiva. Therefore, these patients do not have “occurring in spring”. 80% cases of VKC are younger
any risk for visual loss due to SAC. Conjunctival than 14 years of age. Boys are affected more than
redness and edema may lead to chemosis and girls. As the disease exacerbates during the spring
swelling of the lids. During the acute attack there is season, it is also known as spring catarrh. Family
clear or white exudates but chronic stage is history of allergic disease and personal history of
characterized by muco-purulent thick and stringy one of the major atopic diseases like asthma, hay fever
exudates. Palpebral conjunctiva may appear pale due and eczema may be present.
to edema. Papillae formation is rare in SAC. VKC is a common disease worldwide and affects
all races. The incidence is more in dry and hot
Management environments such as South Africa, Mediterranean
countries and parts of India, and Central and South
Avoidance of offending allergens is the essential
America.4
approach to minimize the attack of SAC. Persons with
history of general allergic manifestations should take
Clinical Features
adequate precaution to avoid pollens in the air by
staying indoors and do not expose to such environ- The presenting clinical features of VKC are intense
ment when the plants producing the offensive pollen itching of the eyes, tearing, photophobia, mucous
grow. Patients with SAC should take precautions to discharge and foreign body sensation in the eyes.
minimize their exposure to yearlong allergens such One of the characteristic signs of VKC is thick,
as house dust, molds and animal dander. The lardaceous, tenacious, yellowish ropy discharge
measures to get relief of the symptoms and signs of consisting of mucus, epithelial cells, eosinophils and
SAC are cold compress to the eye, topical astringents, neutrophils. The discharge may be found to be
avoidance of light and to avoid rubbing of the eyes collected in the lower conjunctival fornix with
because rubbing of the eye increases release of more extension up to the medial canthus. The patients seem
inflammatory mediators.2 to get temporary relief after removing the discharge
Systemic histamine antagonist drugs are prescri- from the fornix. The other diagnostic sign of VKC is
bed in allergic ocular disease to reduce the immediate the presence of macro papillae mainly in the upper
effect of circulating histamines released from tarsal conjunctiva (Fig. 15.1). Depending upon the sites
degranu-lated mast cells. Nonsteroidal anti- of the formation of the papillae VKC is broadly
of the cornea adjoining the limbus. This could be a

macroscopical ulcer. There may be associated
opacification of the underlying Bowman’s membrane.
Such ulcers are thought to be due to toxic effects of
the chemical mediators like eosinophilic major basic
protein released as a part of the ongoing immune
reaction. The lesions may result in permanent corneal
opacity. Rarely, peripheral corneal stromal dege-
neration may develop which leads to astigmatic type
of refractive error. Keratoconus and keratoglobus
have been reported to be complications of VKC.6
Fig. 15.1: Vernal conjunctivitis
Pathogenesis of VKC
divided into (i) palpebral, and (ii) limbal types. The Pathogenesis of allergic conjunctivitis in general and
third type may be a combination of both palpebral VKC in particular revolve round a special type of cell
and limbal types. in the conjunctiva, named as mast cells. In addition
The palpebral type is manifested by large cobbles- to conjunctiva, mast cells are present in the mucosa
tone papillae on the upper palpebral conjunctiva. The of the respiratory system. That is why SAC is common
diameter of the papillae may vary from 2 mm to 8 mm. association of rhinorrhea. Mast cells are one type of
The palpebral form is common in males. The limbal granulocytic cell-like basophils. However, mast cells
form of VKC is common in tropical and subtropical may be present in the connective tissue also. The
countries among the darkly pigmented people.5 This conjunctiva has a high population of mast cells. One
is also known as endemic limbo-conjunctivitis. This mm3 of conjunctiva contains about 5000 mast cells.1
form is less often associated with personal clinical The total number of mast cells in the conjunctiva and
history of atopic diseases like asthma and eczema. adnexal tissue will be around 50 million. In healthy
The limbal type of VKC is characterized by formation human eyes mast cells have been identified in the
of Horner–Trantas dots which are chalky white, substantia propria; but in patients with allergic
raised superficial dots over the corneoscleral limbus. conjunctivitis the mast cells have been found in
These dots are composed of eosinophils and epithelial conjunctival epithelium also.
debris. In addition to the Horner-Trantas dots, there Allergic conjunctivitis is a typical mast cell
may be gelatinous nodules resembling flat limbal mediated hypersensitivity reaction. The surface of
tumours. Histopathological examination of the the mast cell is coated with IgE antibody. There are
papillae shows mainly collection of mast cells and about 10000 to 50000 IgE receptors in one mast cell
eosinophils along with large collection of other of which 16% are occupied. Exposure of appropriately
mononuclear cells and fibroblasts. As a matter of fact sensi-tized IgE coated mast cell to airborne allergen
the papillae are formed due to benign hyperplasia of is the initiating stimulus for the drama of allergy.
the substantia propria of the conjunctiva. Horner- The allergen binds to two separate IgE molecules
Trantas dots are formed as a result of collection of creating a dimer that initiate a chain of reactions in
eosinophils, degenerated epithelial cells and the mast cell plasma membrane, and the mast cell
inflammatory cells. membrane ruptures leading to extrusion of the
Corneal involvement occurs in about 50% of contents of the cell to the surrounding tissue. The
patients of VKC. Keratopathy starts as superficial contents of the mast cell act like mediators of the
punctate epithelial keratitis with superficial pannus. allergic reactions. These mediators consist of the
The so called flour dusting consisting of fine grey following groups:
punctate defects within the superior mid-peripheral • Group I Histamine and Prostaglandin
cornea may develop. The typical vernal (shield) ulcer • Group II Eosinophilic granule major basic protein7
of the cornea is a horizontally oval shallow and • Group III Eosinophil chemotactic factor
vascularized area which develops in the upper half • Group IV Platelet activating factor.
These mediators and many other cell mediators provide some relief in mild cases.
stimulate the proliferation of fibroblasts and recruit-
ment of many cell types in the conjunctiva. These Mast Cell Stabilizers
events play an active role in development of papillae Cromolyn sodium (Disodium cromoglycate) 8,9 4%
in patients with VKC. cromal cipla is considered as an effective drug for
VKC. Its mode of action is stabilization of the mast
Treatment of VKC cell membrane by preventing calcium influx across
the cell membrane which prevents degranulation of
Basically there are three aspects in the treatment of
the mast cells. This prevents chemotactic activation
VKC viz. (a) allergen avoidance, (b) systemic
and cytotoxicity of the neutrophils and eosinophils.
antihistaminic drugs, (c) topical drug therapy.
Cromolyn sodium is equally effective in SAC, VKC,
To keep the patient effectively away from the
and AKC.
allergens is not practicable. This involves maintenance
Lodoxamide 0.1% (Almide, Alcon) Lodoxamide
of allergen-free ambient air. The most difficult aspect
tromethamine is another mast cell stabilizing drug
is that it is not possible to pin point the allergen which
used for treatment of VKC.10-13 It is about 2500 times
is responsible for the particular allergic manifestation.
more potent than cromolyn sodium. The high potency
Even an expert allergist will find it difficult to achieve
is due to additional inhibiting action of the drug on
it. However, it is customary to instruct the parents
the CD4 cells and eosinophils thereby reducing the
to be attentive to keep the child away from the
inflammatory process. Lodoxamide also helps in
probable allergens.
resolution of corneal epitheliopathy. Unfortunately
this formulation is not marketed in India till the time
Drug Therapy
of submitting this manuscript to the press.
Antihistaminic treatment: The role of antihistaminic Azelastine (Azelastine hydrochloride): Azelastine 0.5%
drugs, cold compress and vasoconstrictive drugs has is another drug developed for allergic conjunctivitis.14
been described along with the treatment of SAC. This is marketed in India by Sun-Milmet. Its action
Conservative measures like cold compress, use of starts within 3 minutes and the effect last for 8 to 10
artificial tears to wash off the allergens from the hours. One drop (0.03 ml) of Azelastine contains 0.015
conjunctival sac and vasoconstrictive drugs may also mg of Azelastine hydrochloride. Unlike the other
Table 15.2: Currently used therapeutic agents for allergic conjunctivitis

Class of Agent Drugs Mode of action
1. Topical antihistaminics Pheniramine-Naphazoline Histamine reaction antagonist,
vasoconstriction
2. Oral antihistaminic Acetyl salicylic acid, Astemizole Inhibition of cyclo-oxygenase
preformed mediator
3. Topical mast cell stabilizer Di sodium cromoglycate Inhibition of mast cell degranulation
Lodoxamide and direct action on LD4 cells and
eosinophils
4. Topical mast cell stabilizer and Azelastine Inhibition of mast cell degranulation and
high potency antihistamine leucocytic chemotaxis
5. Topical NSAID Indomethacin, Flurbiprofen, Inhibition of cyclo-oxygenase
Ketorlac tromethamine the preformed mediator
6. Topical steroid Prednisolone, Dexamethasone, Multiple sites of inhibition of the allergic
Fluoromethalone, Loteprednol etabonate response including lipo-oxygenase
inhibition
7. Topical immunosuppresors Cyclosporine Inhibition of cell mediated response
Source: Modified from EI-Defrawy and Jackson40

drugs available for the treatment of allergic (in case of systemic use) and elevated intraocular
conjunctivitis, Azelastine exhibits effect on the pressure ( in case of topical administration). Depo
multiple components of the allergic response viz. corticosteroids may also be administered by
ability to inhibit preformed mediator release from supratarsal injection.16,17
the mast cells (a mast cell stabilizer), release of
histamine leukotrine and biosynthesis of eosinophil Method of Injection
chemotaxin. Clinical trial with azelastine has A drop of 4% Xylocaine is instilled in the conjunctival
demonstrated its activity to decrease the number of sac. A cotton tipped applicator soaked in 2% xylocaine
inflammatory cells including neutrophils, eosinophils, is held on the upper tarsal border of the superior
basophils and lymphocytes. Azelastine eye drops are tarsus of the everted lid for about one minute. With
well-tolerated. Symptoms of mild transient ocular a 26G needle 0.25 ml of 2% xylocaine with epinephrine
stinging, burning and taste perversion are the (1:20,000) is injected under the conjunctiva. After
predominant adverse effects. Azelastine is the unique 2 minutes with 26G 5/8 inch needle 10.5 mg of
drug amongst the clinically useful antihistaminic and triamcinolone is injected subconjunctivally under the
antiallergic compounds. upper border of the upper tarsus.16, 17
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Cyclosporine

In ophthalmic practice NSAIDs have been used to Cyclosporine A is a potent immunosuppressive agent
inhibit intraoperative miosis in cataract surgery, to which can control cell mediated immunity by inhibi-
control postoperative inflammation and in the treat- tion of activated T-lymphocytes. In uncontrolled
ment of cystoid macular edema. The NSAIDs have cases of VKC after treatment with sodium cromo-
also been found to be effective drugs for the glycate and topical steroids, 2% cyclosporine has been
treatment of allergic disease of the eye. Basically it is reported to improve the condition.18 Subjective and
an antipros-taglandin drug. NSAIDs can be objective improvement occurs within 3 days and
administered orally as well as topically. As topical complete improvement achieved in 60% of the
administration is more effective, oral administration patients after 6 weeks of treatment.19,20 In another
is unreasonable. Aspirin is the first drug of NSAID study cyclosporine 2% topical therapy reduced
group. But aspirin has no topical preparation. symptoms of VKC in children more effectively
Indomethacin is the first drug available to be compared to placebo and sodium cromoglycate. An
administered topically. It was used in 1% aqueous Immunohistochemical study revealed that topical
suspension. Indocid 0.1% aqueous solution is an cyclosporine causes significant reduction in the
effective NSAID and is better than 1% aqueous number of T-cells and plasma cells in conjunctiva of
suspension. patients with VKC.21
Ketorolac Tromethamine 0.5% aqueous solution To summarize the therapeutic modalities for VKC:
is available in the brand name of Acular (Allergan) a. Milder cases can be treated by cold compress,
and Ketorid (Sun-Milmet). One drop 4 times a day is vasoconstrictive drugs and topical antihistaminics.
effective in reducing the symptoms of SAC and b. More advanced cases treated by combination of
VKC.15 steroid / NSAIDs and mast cell stabilizer.
Flurbiprofen 0.03% and Diclofenac 0.1% topical c. Advanced VKC with large cobblestone papillae
solutions are also safe effective NSAID preparations. and severe limbal involvement/shield ulcer,
refractory and recalcitrant cases need supratarsal
Corticosteroids steroid injection and topical cyclosporine in
Glucocorticoids are potent antiallergic agents with addition to (b) above.
broad range of cellular effect. In the treatment of
ocular allergic diseases oral corticosteroids are ATOPIC KERATOCONJUNCTIVITIS
indicated for severe inflammation of the cornea and
Atopic keratoconjunctivitis (AKC) is the most sight
conjunctiva in order to preserve vision and avoid
threatening allergic manifestation of the eye. AKC
structural damage. However, corticosteroids are
and blepharitis represent the ocular manifestation of
associated with increased risk for cataract formation
atopic and hereditary conditions characterized by
eczema, rhinitis and other allergic diseases. AKC was and glaucoma as well as systemic complications like
first described by Hogan in 1952 as a severe chronic super infection, hypertension, signs of fluid retention,
keratoconjunctivitis associated with atopic dermatitis diabetes and cushingoid state with osteoporosis of
and eczema in old persons.22 Clinical features of AKC long bones. Topical 1% prednisolone is reported to
appear late in teen age and continue for 4 to 5 decades be a better drug than sodium cromoglycate in the
and may spontaneously regress.23 treatment of AKC.25 Cyclosporine A has been used
Ocular features include itching, burning sensation in several ocular diseases like sarcoidosis and
in the eye, photophobia, blurred vision, watering, granulomatous uveitis due to immunogenic causes
conjunctival hyperemia, ropy mucus discharge and with satisfactory results. In AKC also administration
papillary hypertrophy of the conjunctiva leading to of Cyclosporine A both by systemic and topical
small papillae in the lower palpebral conjunctiva. A method is indicated when sight threatening AKC fails
common associated feature of AKC is dermatitis of to respond to conventional therapy. It should be
the eyelids. The eyelids are inflamed, thickened, remembered that continued therapy with
indurated and macerated. Crusting and scaling may Cyclosporine A might cause serious side effects.
also be present. Recommended daily dose of Cyclosporine A is 5 mg/
The mechanisms involved in the pathogenesis of kg body weight for about 1 year along with 5mg
AKC are believed to be a combination of IgE prednisolone daily.26 Cyclosporine is contraindi-cated
mediated Type I hypersensitivity and a T-cell during pregnancy. Topical Cyclosporine also should
mediated immune reaction. Histopathological be started. 1% Cyclosporine in balance salt solution
examination shows mast cells and eosinophils; this is 4 times a day is the recommended dosage.21
a conclusive evidence in favour of AKC in case of
any doubt in differentiating cases of AKC from ocular GIANT PAPILLARY CONJUNCTIVITIS
pemphigoid. As the name implies giant papillary conjunctivitis
The progressive chronic form of the disease leads (GPC) is characterised by the formation of large
to subconjunctival fibrosis with scarring, foreshor- number of prominent papillae in the upper tarsal
tening of the fornix and symblepharon formation. conjunctiva along with symptoms of itching and
Corneal ulceration followed by scarring and opafica- increased mucous discharge from the conjunctival
tion of the cornea may lead to major visual impair- sac.27-29 TF Spring from Australia first described this
ment. 24 The other corneal pathological features clinical condition in an non-ophthalmic medical
include stromal neovascularization, superficial journal. GPC is basically related to contact lens wear,
punctate keratitis, corneal ulcer and thinning of the it is a reversible ocular inflammation because soon
cornea which can ultimately lead to corneal after discontinuation of the contact lens, the
perforation. In about 25% to 40% of patients with inflamma-tion subsides. GPC can occur both in hard
atopic dermatitis is associated with ocular lesions. gas permeable (PMMA) and soft (hydrogel) contact
Occasionally atypical forms of AKC may be associated lens wear. It is more common with soft lens wear (1-
with characteristic features of systemic atopy. 5%) than in hard lens wear (less than 1%). In soft
lens wear GPC develops after about 8 months and in
Management the case of hard lens wear the condition develops
In the early stage of the disease the treatment is the years after wearing of the contact lens.
GPC can be due to surgical suture barb and also
same as for other forms of allergic ocular diseases.
may develop in patients wearing ocular prosthesis.30,31
In the late stage, when dry eye type of complications
During blinking of the lids, the cut ends of the
are present, ocular lubricants and saline irrigation
exposed suture rub against the upper tarsal
are indicated. The patient should be advised to keep
conjunctiva and causes development of the papillae
away from possible allergens. When the standard
in the tarsal conjunctiva.32 Nirankari et al described
treatment does not show anticipated result then more
this syndrome of suture barb33 in patients who had
aggressive therapy may have to be employed with penetrating keratoplasty.
short term systemic steroid which will provide relief Normally very fine papillae of about 0.1 to 0.3
during the periods of exacerbation. Prolonged use mm diameter may be seen in normal healthy
of steroid is undesirable due to the probable ocular conjunctiva. The diameter of the macropapillae is less
complications of steroid therapy like steroid cataract than one mm. Papillae with diameter of more than 1
mm are called giant papillae. The giant papillae may The abrasive effect of the contact lens upon the
be as large as 8 mm in diameter. The number of conjunctival mucosal surface allows immunogenic
papillae found in the upper tarsal conjunctiva in GPC recognition of antigen (bacterial residue) on the
may be between 5 to 100. Apices of the papillae are surface of the lens. The chronic inflammation caused
flat and may stain with fluorescein dye due to by the resulting immunogenis response leads to
ulceration of the conjunc-tiva at the apex of the subepithelial collagen tissue hyperplasia in the form
papillae. Histopathological examination shows that of giant papillae. On the other hand the result of the
the core of individual papilla consists of mast cells mechanical trauma repeated with each excursion of
and eosinophils and has a single blood vessel. The the upper lid (about 16,000 times per day) over the
presence of mast cells and improvement of he deposits on the worn contact lens is coupled with
condition after the use of mast cell stabilizing drugs antigen-antibody reaction in formation of the papillae.
suggest the presence of an allergic component in the It is very unlikely that the pathological lesions of GPC
etiopathology of GPC. are caused by reaction to contact lens material itself.
Histopathological examination shows lympho-
Pathomechanism of Formation of Papillae cytes, plasma cells, basophils, mast cells, and eosino-
Conjunctival papillary disorders are the result of: phils in the papillae. In the cytoplasm of the plasma
a. Patient’s personal (genetic) background cells and mast cells, acidophilic hyaline PAS positive
b. Presence of a triggering agent electron dense intracytoplasmic granular inclusion
c. Sufficient duration of exposure to the agent bodies are found. These are called Russell bodies.36
d. Sufficient area of exposure in the conjunctival They are thought to represent inspissated
surface to the agent immunoglo-bulins. They are prominent in quiescent
e. Particular geometry of the exposure, in case of stage of GPC. It is presumed that degranulation of
larger contact lens wear the cells contai-ning Russell bodies act as a chemotactic
Coatings on worn contact lenses are normal. This effect for cellular infiltration. Scanning electron
coating is present both on the anterior and posterior microscopy of the surface of the giant papillae shows
surface of the worn lens. Such coatings may be distortion of the cells with increased number of
necessary for proper wetting and essential for the microvilli. This cellular morphology may be secondary
wearer’s comfort. However, the amount of coating to stretching and elongation of cells and enormous
required for comfort and the amount that might cause growth of tissue.27, 33
discomfort is difficult to differentiate. Although a
normal amount of coating may be physiologically Differential Diagnosis from Vernal Conjunctivitis
advantageous, it does provide a sticky base that may
Clinically GPC closely resembles vernal keratocon-
act as an attachment for bacteria and other particulate
junctivitis (VKC). Both the conditions are
matter from the environment.
characterised by ocular irritation, itching and
Contact lens coatings appear to consist of mucus
production of mucus. Limbal and corneal lesions may
like material, which may be derived from secretory
appear in both the conditions. Similarly Trantas dots
cells of the conjunctiva and the lacrimal gland.
may be present in both the conditions.37 The simplest
Material found on the upper tarsal conjunctiva that
test to differentiate GPC from VKC is that in the
is believed to be mucus, is morphologically similar
former the symptoms disappear immediately on
to lens coating and could be rubbed onto the surface
discontinuation of contact lens but there is no
of the upper tarsal conjunctiva during blinking. Mucus
immediate relief in VKC without treatment. The Table
coating increases the hydrophility of a polymer
15.3 shows the differentiating points of VKC and
substance by facilitating the spreading of a watery
fluid. Mucus has also been found to play an essential GPC.38
role in wetting the corneal surface. In the absence of
Management
mucus, the cornea becomes less hydrophilic.
There are two types of structures on and in the It is an established fact that an increased coating of
lens deposits (a) bacteria34 and (b) structures that worn contact lens exacerbates the signs and
resemble cells or their membranes alone.35 The cell symptoms of existing GPC and also may contribute
types of structures are similar to those seen on the to the onset of the disease. The following factors that
surface of used IOL.
Table 15.3: Differentiation between VKC and GPC38
VKC GPC
A: CLINICAL
Age Common in children Common in adults
Sex Common in males No sex difference
Major atopic disease Usually associated Rarely associated
Season Common in spring Not seasonal
Mucus Characteristically severe Mild to moderate
Itching Common feature Variable
Corneal lesion Common Rare
Trantas Dots Common Very rare
B: HISTOLOGICAL Mast cell in epithelium 100% 8%
Eosinophils in epithelium 100% 45 2% per 25x field
Eosinophils in substantia propria 100% 38%
Basophils in epithelium 60% 5%
Basophils in substantia propria 100% 27%
C: TEAR FLUID Histamine content is 4 times more than normal Histamine content is equal to or lower than normal
increase the patient’s exposure to lens coating may Topical sulphacetamide and penicillin preparations
enhance the clinical course. Therefore for treatment are com-mon drugs causing allergic manifestations.
these should be taken into account. Some preservatives that are used in ophthalmic
a. Not to wear the lens for a long time during the preparations may also cause contact hypersensitivity
day. reaction. In resistant cases supratoised injection of
b. Not to wear the same lens for more than three steroid gives good result.41
months. Clinical features of contact hypersensitivity include
c. Not to wear larger lenses that present a greater conjunctival hyperemia, ocular pruritus and swelling
surface area to the conjunctival epithelium. of the lid margin. Conjunctival edema may be severe
d. Adequate cleaning of the lens. enough to cause chemosis of the conjunctiva.
The fluid for cleaning the lens should be free of Treatment is discontinuation of the drug and use
preservatives because even its lowest concentration, of antihistaminic and vasoconstrictive drugs. Steroid
it is notorious for causing keratitis. Sterilization by eye drops 3 to 4 times a day for a few days relieve
hydrogen peroxide has been found to be the latest the signs and symptoms.
method tolerated by the compromised conjunctiva.
Sterilization by boiling may bake the coatings and
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the treatment of vernal kerstoconjunctivitis. Am J Ophthalmol inflammation associated with soft contact lens wear. Am J
1986;101:278. Ophthalmol 1980;89:66.
20. Bleik JH, Khalid F, Tabarra F. Topical cyclosporine in vernal 38. Allansmith MR, Baird RS, Greiner JV. Vernal conjunctivitis
keratoconjunctivitis. Ophthalmology 1991;98:1679. and contact lens associated giant papillary conjunctivitis
21. Abu-EL-Asan AM, Tabarra KF, Gebos K. An immune compared and contrasted. Arch Ophthalmol 1979;87:544.
histochemical study of topical cyclosporine in vernal
39. Woods TS, Stewart RH, Bowman RW et al. Suprofen treatment
keratoconjunctivitis. Am J Ophthalmol 1996;121:156.
of contact lens associated giant papillary conjunctivitis.
22. Hogan MJ. Atopic keratoconjunctivitis. Am J Ophthalmol
1952;36:937. Ophthalmology 1988;95:822.
23. Foster CS, Calong N. Atopic keratoconjunctivitis. 40. EI-Defrawy S, Jackson WB. New directions in therapy for ocular
Ophthalmology 1992;97:992. allergy. Int Ophthalmol Clin 1996;36:25.
24. Akova YR, Jabbar NS, Newmann et al. Atypial ocular allergy. 41. Sing S, Pal VEP, Dhull CS. Supratarsal injection of steroid in
Ophthalmology 1997;104:1367. the treatment of refractory vernal conjunctivitis. Am J
25. Bajpayee RB, Gupta AK, Uppal RK. Evaluation of sodium Ophthalmol 2001;240.
Chapter 16
Dry Eyes
Dry eye state is a form of noninfectious ocular surface

disorder due to deficiency or absence of tear fluid. The
ocular surface is defined as the entire sheet of
epithelium which extends from the gray line back over
the lid margin onto the back of the eyelids, into the
inferior fornix up over the globe and onto the cornea.
The ocular surfaces rub against each other with each
blink. For smooth functioning, it is provided with
lubricating fluid. The lubricating fluid is known as
tears.
PHYSIOLOGY OF TEARS
Tears are constantly formed by lacrimal gland and
drained into nasolacrimal passages. During their
movement from lacrimal gland to nasolacrimal
passage they pass over all parts of eyeball covered by
conjunctiva and over the cornea. Because of its
properties and mechanical factors, it forms a thin layer Fig. 16.1: Tear film layer over conjunctiva showing tear
over the eyeball (Fig. 16.1). This thin layer is known meniscus and volume a various parts of tear film
as tear film. The tear film is made up of three layers,
i.e. 1. Lipid, 2. Aqueous, and 3. Mucin (Fig. 16.2).
Lipid Layer
Lipid layer is the outermost. Its thickness varies accor-
ding to the size of palpebral fissure. It is thin in eyes
with wide palpebral fissure and thick in eyes with
narrow palpebral fissure.
In normal individuals it is never more than 0.1 μm
thick. Increased thickness of lipid layer makes it visible
due to interference colors. Lipid layer is mainly secre-
ted by meibomian glands. Meibomian gland openings
are situated on the lid margin immediately behind the
lash follicles. Some amount of lipids are also secreted
by glands of Zeis and Moll. Lipids (meibum) of tear
film consists of waxy and cholesterol esters with polar Fig. 16.2: Three layers of tear film
components. It is fluid at body temperature. It differs tear film. Mucin is a form of glycoprotein. Its macro-
from sebum by its higher molecular weight and lower molecular structure is responsible for its attachment
polarity. This is important for formation and stability to the corneal surface. It changes the hydrophobic
of tear film. Sebum like lipids results in increase in corneal surface to hydrophilic one. This is necessary
spreading speed resulting in ‘dewetting’ of ocular for spreading of aqueous layer. Excess of mucin is
surface. dissolved in aqueous mucin layer. It provides
Main function of lipid layer is to stabilize the tear surfactant and stability to aqueous film. Recent studies
film, help in uniform spreading, and reduce evapora- showed that glycocalix thread on microvilli of epithe-
tion of aqueous layer. lium and its integrity is more important than mucus.
The mucin content or goblet cell function can not be
Aqueous Layer assessed. Impression cytology provides information
Aqueous layer consists of secretions by lacrimal glands on numbers and health of goblet cells. Goblet cell
(main as well as accessory). Accessory lacrimal gland density, reflects vitamin A level in absence of other
is situated in fornical conjunctiva and is believed to disease. Its number is reduced in vitamin A deficiency.
be responsible for basic tear secretion. Its thickness
ranges between 6 to 10 μm. It provides more than 90% FLUIDS OF TEAR FILM
of thickness of tears. The aqueous layer contains
lactoferrin, tear specific prealbumin, immunoglobulin- Tear film is spread out between two lids. On closure
A, lysozymes as secreted by lacrimal glands and serum of the lids, the lipid layer of the film is compressed. It
proteins and glycoproteins. Proteins make up 1% of increases in thickness by a factor of 1000 resulting in
aqueous volume. Lysozome accounts for 20-30% of thickness of 0.1 mm.
total proteins. Water makes 98% of tear volume. It also The aqueous layer remains spread out up to
contains inorganic salts, glucose, urea, trace elements, fornices. On opening the lids the aqueous layer
etc. Glucose level of tears is lower than but spreads first on which the monomolecular lipid level
proportional to that of blood. Colloidal osmotic spreads rapidly and covers it. The excess lipids and
pressure of normal tears is approximately 2 mm of other macromolecules spread over tear film later on.
Hg. This is only 5% of colloidal osmotic pressure of The movement stabilizes within one second of opening
stroma. However, this is higher than that of aqueous of the eye. The duration between two blinks is usually
humor (0.1 mm Hg). Basic tear secretion is 1-2 micro 4 seconds with a blink rate of 15 per minute. The
ml per minute. blinking helps to replenish volume of tear film. It also
helps in uniform spreading of the tears. When eyes
Aqueous functions Aqueous layer is important for the remain open for a longer time, discontinuity on the
normal functioning of cornea and conjunctiva. It tear film over cornea develops. The time interval taken
provides hydration, lubrication, and oxygen. It helps for discontinuity to develop is known as tear film
by removing debris constantly. It provides protection break up time, and discontinuity are called dry spots.
against infection by its antimicrobial properties due Tear film break up time can be measured after staining
to lysozyme and immunoglobulins. the tear film with fluorescein and examination with
slit lamp or using a noninvasive technique, e.g.
Mucin Layer
toposcope. Normal tear film break up time using
It is the innermost layer of the tear film. It covers fluorescein ranges from 10-40 seconds and with the
cornea and conjunctiva. It provides anchorage to the toposcope it is between 3 to 5 minutes. But when tear
tear film. It accounts for up to 10% of thickness of tear film break up is less than blink rate it can produce
film. Its main source is mucus secreting goblet cells of corneal epithelial damage, which in turn may further
the conjunctiva. The goblet cells are scattered over the reduce the tear film break up time and start a vicious
conjunctival surface. Some amount of mucin glycopro- circle.
teins are secreted by the lacrimal gland and superficial Probable causes for tear film break up include
epithelial cells. However, they do not seem to have desiccation of tissues at the sites of drainage of tears
effect on the tear film. Mucin comes to lie over cornea through damaged epithelium, unstable mucous layer
during blinking of the lids. It forms a foundation of and surface tension gradients driven flow.
Chapter 16: Dry Eyes 101
TEAR FILM ABNORMALITIES chronic thyroiditis, chronic hepatobiliary disease,
chronic pulmonary fibrosis, purpura, hyperglo-
Abnormalities of tear film can be classified depending
bulinemia, lymphoma, Raynaud’s phenomenon, graft
on the layer of tear which is principally affected.
versus host disease, etc.
Accordingly, these can be the following:
Sjögren’s syndrome can be differentiated from
1. Aqueous deficiency
other causes of KCS by oral labial gland biopsy. This
2. Mucin deficiency
gland is involved in Sjogren’s syndrome and not in
3. Lipid abnormality
other diseases. Histological findings in KCS include
4. Lid abnormality
focal lymphocytic and plasma cell infiltrates with
5. Epitheliopathy.
degeneration of glandular tissue. These findings
suggest role of autoimmune mechanism in KCS.
Aqueous Deficiency
Aqueous deficiency results from decreased aqueous
Drugs Affecting Tear Production
secretion. This may be due to disease of lacrimal gland
or its nerve supply. Hyposecretion is seen in congeni- From animal studies, it is found that drugs with anti-
tal alacrimia or Riley-Day syndrome is rare. In cholinergic properties reduce aqueous secretion. The
alacrimia there is absence of lacrimal gland. Riley-Day drugs of this group include, atropine, phenothiazines,
syndrome (familial dysautonomia) affects autonomic antihistamines, etc. Beta blockers, e.g. timolol used
nervous system. It is seen in Jews of eastern Europe. topically, and atenolol used systemically, reduce tear
Other causes of hyposecretion include primary or secretion. Cyclosporine increases tear secretion when
secondary Sjogren’s syndrome, obstruction or oblitera- applied topically or systemically.
tion of lacrimal gland/duct due to scarring following
radiation, chemical or thermal burns, surgery or Mucin Deficiency
trauma to lids and orbit.
Mucin makes corneal surface hydrophilic. It is
The normal tear secretion fluctuates widely and
necessary for adherence of tear film to corneal
its upper and lower limits are not known. However,
epithelium. Its deficiency results in rapid tear film
it is believed that even 0.1 μl/minute is adequate
break up time due to unstable tear film.
under favorable circumstances.
Mucin deficiency is secondary to diseases affecting
The dry eye state due to aqueous deficiency is
goblet cell population. This is seen in vitamin A defi-
collectively known as keratoconjunctivitis sicca (KCS).
ciency, trachoma, ocular pemphigoid, Stevens Johnson
It is most commonly seen in postmenopausal women.
Syndrome, chemical burns, and radiation damage.
The main complaints are foreign body sensation, burn-
ing sensation or mucus threads, and corneal filaments.
The precorneal tear film is usually one mm wide Lipid Abnormality
at lower lid margin with convexity anteriorly Usually lipids are never absent except in rare cases of
(Fig. 16.1). It becomes thin. There may be obvious absence of meibomian gland. However, meibomian
discontinuity in tear film. Excess of debris in secretion may be altered in cases of inflammations,
precorneal film also suggests KCS. Mucus thread seen e.g. chronic blepharitis. There is increase in free fatty
in KCS does not suggest increase in mucin production; acid content of meibum. They have adverse effect on
on the contrary mucin secretion by goblet cells may corneal epithelium. It causes instantaneous dry spot
be reduced. Mucin is precipitated. This may be due to on the cornea. When associated with increased
increase in lipid content and/or defective drainage. secretion of meibum, the effect gets negated.
Increased frequency of KCS in postmenopausal
women suggests role of estrogen. Estrogen receptors
Impaired Eyelid Function
are known in conjunctiva. Conjunctival secretion also
shows cyclic changes which correlate with estrogen Tear film is usually unstable. It needs blinking of lids
level. As in Sjogren’s syndrome it is commonly seen for its spread. When an area of cornea or conjunctiva
with connective tissue and vascular disorders. Other is not covered by a blink, it results in an area of
causes are rheumatoid arthritis, systemic lupus erythe- nonwetting. Epithelium in this area gradually gets
matosus, scleroderma, polymyositis, polyarteritis, desiccated and/or keratinized. Exposure keratitis is
its classical example. It is seen in Bell’s palsy, Graves’ epithelium and punctate staining of cornea.
disease, orbital tumors, etc. Ectropion, entropion, Fluorescein stain is best seen using cobalt blue light.
symblepharon, notched lid or pterygium may cause
Tear film break up time It gives an idea about stability
localized nonwetting of the cornea.
of tear film. After staining the conjunctival film with
fluorescein, patient is asked to blink and keep the eyes
Epitheliopathy
open. The time between last blink and first appearance
Abnormalities of cornea, e.g. scar or anesthesia can of the dry spot is measured. Time less than 10 seconds
also cause nonwetting of cornea. This may result in suggests mucus deficiency. Normally it is 30 seconds
persistent epithelial defect. to one minute. In severe cases time is too short to be
measured.
CLINICAL FEATURES The noninvasive method of evaluating tear film
involves projecting an image of the grid on the tear
Clinical manifestations of dry eye may be trivial like film. The tear film break up time is longer with
itching or burning to serious one like blindness. The noninvasive technique than with fluorescein.
spectrum of complaints found in dry eyes in order of
frequency includes foreign body sensation (gritty Rose Bengal stain Rose Bengal stains devitalized tissue
feeling), excessive secretion, burning, redness, (Fig. 16.3). It stains damaged conjunctival and corneal
photophobia, blurred vision, itching, pain, inability epithelium as well as mucus threads and corneal
to tear in response to irritation or emotions. There may filaments. It sugests deficiency of tear components like
be crusting of eyelids and sticking. This is commonly mucin, albumin. It is very sensitive test and stains
seen in the morning on waking up. Nonspecific bulbar conjunctiva and cornea in early stage of the
symptoms include headache, heaviness of eyes or disease or incipient stage. It is also helpful in serial
tiredness. Fatigue may be experienced while reading evaluation of the condition. Usually, a micro drop of
or watching TV. Occasionally, patient may complain 0.5 to 1% solution of Rose Bengal is used. It is irritating
of excessive watering or mucus secretion due to and so it should be the last test to be performed to
imbalance of tear constituents. avoid false reading of other tests, e.g. Schirmer’s test.
Examination
Slit lamp biomicroscopy Slit lamp examination is most
important in diagnosis of dry eyes. Slit lamp
examination should involve inspection of a tear
meniscus. Tear meniscus should be examined at lid
margin. Normal thickness at this point is 1.0 mm. Less
than 0.5 mm is indicative of tear deficiency. The other
important findings may be increased debris and/or Fig. 16.3: Rose Bengal staining of ocular surface.
mucin strands within the tear film. There may be Minimal in all three zones
filaments or mucus plaques on ocular surface. Bulbar According to some, this is the mainstay
conjunctival vessels may be dilated and cause red eye. examination in evaluation and prognostication of dry
Corneal surface may show irregularity. Blinking may eyes. The interpalpebral fissure is divided into three
be incomplete or infrequent. Meibomian gland zones. They are cornea and bulbar conjunctiva
dysfunction or blepharitis may be seen. temporal and nasal to cornea. Each zone is evaluated
Early symblepharon may be visible with slit lamp separately and given 1 to 3 points. Score of 9 suggests
in fornices. It may give some idea about underlying highest damage.
pathology. Obvious dry areas over cornea can be
appreciated by slit lamp examination. Investigations
Fluorescein staining Staining with fluorescein stains Schirmer’s Test
makes the tear film easily visible. The height of the
tear film meniscus at lower lid margin is between 0.1 The test is devised to measure the aqueous tear
to 0.6 mm. It also shows area of denuded corneal production or tear flow in dry eye patients, it is done
reading is taken at the interval of 72 hours. The value
of lactoferrin level obtained closely approximates tear
secretion by lacrimal gland and lysozyme content of
the tears. It is more a practical test than measurement
of lysozyme content of tears. It is more specific and
sensitive than any other tests for dry eye. However,
this test alone has low specificity and sensitivity in
milder cases; hence it should be combined with
Schirmer’s test.
Fluorescein Dilution Test

The speed with which 1.5 μl of 5% fluorescein gets
diluted gives an idea of tear flow. Fluorophotometer
with slit lamp is used for this. It also gives an idea
Fig. 16.4: Diagram showing position of Schirmer’s strip for about tear film thickness and tear dynamics. Though
performing Schirmer’s test this test provides accurate and useful information it
is not routinely used due to nonavailability of
instruments.
with a strip of filter paper measuring 5 by 35 mm. It is
kept at junction of outer 1/3 and middle 1/3 of lower
Tear Osmolarity
lid (Fig. 16.4). The amount of wetting in 5 minutes is
measured. Traditionally, Whatman’s filter paper Tear osmolarity in normals is 203 + 6.31 liter. In KCS
No. 41 is used. Normal wetting is 15 mm. Reading less due to reduced aqueous secretion the osmolarity
than 5 mm indicates severe keratoconjunctivitis sicca. increases. Increased tear osmolarity is a good indicator
This is also known as Schirmer’s I. When nasal mucosa of KCS. It is found to be better than Schirmer’s test or
is stimulated by a cotton tip application to induce tear film break up time test. It is measured with 0.2 μl
reflex secretion it is known as Schirmer’s II. Basic tear of tears by measuring freezing point depression.
secretion is measured after anesthetizing the
conjunctival sac. In a modified Schirmer’s test instead Conjunctival Scraping
of a filter paper, a fine thread is used. To study kinetics
Conjunctival scraping can be stained with Giemsa’s
of tear flow, plastic cuff is applied which prevents
stain. In dry eyes it shows numerous goblet cells with
evaporation of the tears. Dynamics of tear can be
pink cytoplasm and nucleus on one side of the cell. It
measured by studying it at different time intervals.
also contains devitalized cells with pyknotic nucleus
and pale blue staining cytoplasm. Epithelial cells may
Tear Lysozyme Assay
be absent. Fern pattern appears when mucus is
Tear lysozyme makes 30% of tear proteins. It is allowed to dry on the slide and viewed through a
produced by tubuloacinar cells of main and accessory microscope.
lacrimal glands. It is reduced when aqueous tear
formation is reduced. Most often tear lysozyme Conjunctival Impression Cytology
decreases before dry eyes are clinically evident. Thus
Impression cytology is a substitute for conjunctival
it is of great diagnostic and prognostic value.
biopsy. It is simple, easy, reliable, accurate, low cost,
However, measurement of lysozyme content requires
reproducible, and noninvasive technique which can
elaborate laboratory setup. Because of this reason it
be repeated as often as required. Abnormal pattern
has not become a popular test.
precedes the ocular signs of xerophthalmia and it is a
more sensitive test. Abnormalities of goblet cells and
Lactoferrin Radial Immunodiffusion Assay
epithelium can be easily detected. The test is also
This is an immunological test for measurement of useful in detecting hypovitaminosis A.
lactoferrin content of tears. It is performed using It helps in identifying the pathological changes
readily available kits. Tear is put on a plate and occurring in the conjunctiva known as squamous
metaplasia which also takes place in the respiratory Table 16.1: Kinds of fixative solution for
urinary, and gastrointestinal tract mucosa. The conjunctival biopsy
pathological transition of a nonkeratinized, stratified
Solution Time
epithelium (secretary or nonsecretary) to nonsecretary
keratinized epithelium is called squamous metaplasia, 1. Tap water 2 min
a process involving abnormal epithelial differen- 2. 0.05% periodic acid 2 min
tiation. These cytological changes occur in a variety 3. Fresh tap water 2 min
4. Schiff’s reagent diluted 8 min
of disorders, e.g. xerophthalmia, Stevens-Johnson
1:1 with distilled water
syndrome, trachoma, alkali burns, keratoconjunctivitis 5. Tap water 2 min
sicca, pemphigoid, etc leading to dry eye and accounts 6. 0.05% sodium metabisulfite 2 min
for most of the clinical symptoms, corneal 7. Tap water 2 min
complications, and corneal morbidity. Hence it is 8. Harris hematoxylin 2 min
important to carefully evaluate the extent and severity 9. Tap water 30 sec
of the condition for further management. 10. 95% ethyl alcohol 2 min
11. Absolute alcohol 3 min
12. Xylene 20 min.
Technique
The conjunctival cells samples are collected on Stage 0 Normal conjunctival epithelium, moderate
Millipore cellulose acetate paper strips (3 × 10 mm number of goblet cells scattered among uniform small
size with a diagonal edge). The paper is applied near epithelial cells.
the limbus on the bulbar conjunctiva inferonasally and Stage 1 Early loss of goblet cells without keratini-
inferotemporally with the help of blunt smooth edge
zation, decreased goblet cell density, mild enlarge-
forceps, and a glass rod is pressed on the paper
ment of epithelial cell, N/C ratio 1:2 to 1:3.
keeping in position for 3 to 5 seconds. Then it is
removed with a peeling motion. A disc applicator is Stage 2 Total loss of goblet cells without keratini-
available for the same. Its advantages are that the cell zation, epithelial cells moderately enlarged, N/C ratio
adhesion is better, targeting of sample sites is precise, 1:4.
and pressure applied is uniform. Local anesthetic is S t a g e 3 Early and mild keratinization, epithelial cells
not mandatory. The specimens are dropped into a markedly squamous, and metachromatic change of
bottle containing the fixative solution (ethyl alcohol, cytoplasm, and keratin filaments. visible in some
formaldehyde, and glacial acetic acid in 20:1:1 volume epithelial cells, N/C ratio 1:6.
ratio). The strips are transferred to the laboratory for
Stage 4 Moderate keratinization in midst of squamoid
staining with periodic acid Schiff and hematoxylin or
and metachromatic large epithelial cells, more cells
PAS and modified Papanicolaou’s stain. The slides are
containing densely packed keratin filaments,
examined under light microscope and staged
according to the degree of squamous metaplasia. The keratohyaline granules and pyknotic nuclei, N/C ratio
goblet cells are recognized by intracellular mucin 1:8.
which is deeply PAS positive with smooth border Stage 5 Advanced keratinization, more keratinized
(Table 16.1). cells and shrunken cytoplasm and densely packed
keratin filaments in which nuclei markedly pyknotic,
Staining Procedure lytic or enucleated.
It can be applied for clinical use, for population
Tseng has classified squamous metaplasia into six
survey and can be used to evaluate therapeutic efficacy
stages. It is based on presence or absence of goblet
of treatment. Thus, it is an easy and simple diagnostic
cells, goblet cell density (GCD), morphological
and prognostic parameter.
changes in the nucleus, nucleus/cytoplasm ratio,
metachromatic changes of cytoplasmic color, and
Tear Fern Test
emergence of keratinization. However, in advance
cases of dry eye it may not be possible to follow these Like secretions of any other mucous membrane, e.g.
stages and it can be done in three stages of vaginal discharge, tears when dried on slide shows
morphological changes of epithelial cells, cohesion of ferning. The fern patterns can be classified in the
cells, N/C ratio and keratinization. following 4 groups:
A. Uniform arborization and numerous branching are be ruled out by thorough investigation of each
seen. There is a little or no space between ferns. clinical entity. Labial salivary gland biopsy is the
B. Branching is less and there is abundant spaces bet- most useful single investigation.
ween ferns. 3. Stevens-Johnson syndrome (Erythema multiforme
C. Ferns are thicker and smaller with little branching m a j o r ) It is characterized by generalized
and very large spaces between them. exudations, fever, conjunctivits, and inflammation
D. No ferning but amorphous pattern is seen. of buccal mucosa. It usually follows exposure to
Pattern A is normal while D suggests severe drug, the commonest being the sulfa group. The
disease. Pattern C and D are associated with lack of conjunctivitis may be of variable nature, e.g.
lactoferrin and lysozymes in tears. They are prone to catarrhal to purulent; usually it is
frequent infections. Clogging of soft lenses and pseudomembranous. It leads to scarring of
discomfort while wearing is associated with pattern conjunctiva with symblepharon formation. In
C and D. severe form corneal epithelium gets desiccated,
hazy, irregular with development of superficial
pannus. Ultimately, keratinization of epithelium
Natural Course of Disease takes place. The corneal epithelium may be
Clinical course of the disease is variable and somewhat replaced by epithelium of conjunctival type.
subjective. It shows waxing and waning. Similarly, Cornea may thin out and lead to ulceration and
manifestations of symptoms is also valuable. With perforation.
identical measurements, symptoms may be of 4. Ocular pemphigoid Most of the patients are old
different magnitude. women (70 years or above). There is subepithelial
Majority of persons have milder nonprogressive bullae formation. It leads to conjunctival scarring.
form of disease. They are benefited by artificial tears Clinical picture may be of chronic conjunctivitis
and mucolytic agents. Some may be able to with progressive subepithelial scarring. Scarring
discontinue the therapy. In a long-term follow-up of destroys goblet cells and accessory lacrimal glands.
Sjogren’s patients, 16% have shown to deteriorate each The pathophysiology and sequelae are identical to
year requiring additional therapy. Severe sight Stevens-Johnson’s syndrome. However, unlike S-J
threatening complications are seen in less than 1% of syndrome this is progressive. Steroids do not stop
patients. They include, corneal ulcers, leucoma, progress of the disease. Antimetabolites are also
tried without much success. Dapson has been
pannus formation, corneal melting, and central sterile
found to yield good results.
perforations of the cornea.
5. Drug induced pemphigoid Certain drugs like
Since enzymes in tears are reduced, bacterial
epinephrine, pilocarpine, phenylephrine and
infection is more likely due to decreased defense
preservatives cause conjunctival scarring. The
mechanism. However, they are not found clinically
clinical picture resembles trachoma stage IV. It is
to be a major problem.
important to know this complication of prolonged
drug use. Drugs should be discontinued at the
DIFFERENTIAL DIAGNOSIS OF DRY EYE earliest evidence of subconjunctival scarring or
The commonest causes of dry eyes are trachoma where symblepharon.
endemic, Sjogren’s syndrome, Stevens-Johnson synd- 6. Thermal or chemical burns Effect of initial healing
rome, ocular pemphigoid, conjunctival scarring results in irregular hazy corneal epithelium,
following thermal or chemical injuries, and graft subepithelial pannus, vascularization, and stromal
versus host disease. Following are the specific dry eye scarring. It manifests clinically as photophobia,
syndromes which cause dry eyes due to factors other burning, tearing, and rapid tear film break-up time.
than local conjunctival changes. It causes mucus deficiency. Signs of dryness
1. Trachoma Trachomatous scarring of conjunctiva continue in spite of adequate aqueous tears.
results in reduction in goblet cells and obliteration
DRY EYE SYNDROMES
of lacrimal gland ductules. All components of tears
are deficient. Dacryoadenitis
2. Sjogren’s syndrome Sjogren’s syndrome should be Any inflammation of lacrimal gland can cause
suspected in each patients with KCS and should decreased tear production. The etiology includes
mumps, infectious mononucleosis, sarcoidosis, tuber- treated by closure of lids and/or use of lubricating
culosis, syphilis or lymphoma. drops and ointment.
Congenital Absence of Lacrimal Gland Environmental Factors

Absence of lacrimal gland or hypoplasia or congenital High altitude with increased evaporation, low
neurological deficiency can produce keratoconjuncti- humidity, windy environment particularly in dry,
vitis sicca. dusty area of desert can cause irregularity of corneal
surface and dryness. Patching of eyes and change of
Riley-Day Syndrome environment is the treatment of choice.
Congenital dysautonomia results in diminished lacri-
mation, hyperhidrosis, labile blood pressure, unstable Hypovitaminosis A
temperature control and corneal hypoesthesia. There In vitamin A deficiency there is a loss of goblet cells
is reduced tears secretion. resulting in mucin deficiency. This condition responds
promptly to vitamin A therapy.
Cholinergic Blockade
DRY EYE ASSOCIATED CONDITIONS
Drug induced reduction in tears is seen with chronic
use of cholinergic blocking drugs, e.g. atropine. The Rheumatoid Arthritis
effect is temporary and returns to normal after
Dry eyes are commonly seen in patients with
discontinuance of the drugs. rheumatoid arthritis (14-30%). This is due to reduced
tear secretion.
Chronic Blepharoconjunctivitis
Decreased tear production is a common finding in Salivary Gland Dysfunction
chronic blepharoconjunctivitis. It appears to be due Mumps, xerostomia, Miculicz’ disease sarcoidosis, etc
to raised threshold secondary to prolonged irritation. are diseases in which lacrimal as well salivary glands
Chronic blepharitis also changes lipids of tear fluids are affected.
and thereby disturbs tear film break up resulting in
dry spots. Rosacea keratoconjunctivitis is a condition Systemic Lupus Erythematosus
characterized by bulbar and conjunctival hyperemia In this multisystem disease, dry eye is commonly seen
with multiple chalazia, and blepharitis. Corneal lesion along with peripheral corneal infiltration and marginal
is seen early in the disease and includes epithelial corneal ulcer.
degeneration and corneal vascularization in lower
part. MANAGEMENT OF DRY EYES
Principles of management of dry eyes include supple-
ATYPICAL DRY EYE SYNDROMES mentation of tears, preservation of tears and treatment
Trigeminal Nerve Paralysis of associated conditions.
Most of the patients with dry eyes have aqueous
Trigeminal nerve paralysis reduces corneal sensation
deficiency and efforts are made to preserve or replace
and reflex lacrimation. There is decreased tear film
tears.
break-up time and desiccated corneal tissue setting a
vicious cycle which may result in corneal ulceration. Tear Substitutes
Facial Nerve Paralysis A drop of normal saline gives instantaneous soothing
effect. However, the effect is short lived and repeated
In absence of nerve supply to lacrimal gland reduces
instillations are necessary. To increase retention time
tear secretion remarkably. This is seen in a variety of various formulations are made. Each one has different
congenital and acquired conditions. properties. Those containing methylcellulose or
identical substances are viscous in nature. Polyvinyl
Exposure Keratitis alcohol improves tear retention by forming a film.
Inability to close lid results in dry eye in exposed area There are formulations which are less viscous and/or
due to lack of spreading mechanisms. This is best hypoosmotic; choice depends on liking by a person.
Any formulation used requires frequent instillations.
For prolonged action lacriserts made of methyl
cellulose or gels containing carbopool or carbophill
are available. They maintain tear film break up time
for a longer period. Lacriserts release methyl cellulose
gradually into tears. They are inserted into lower
fornix. Preservatives used in formulations are known
to cause dry eyes and so formulations without
preservatives for single use (refresh) or with a preser-
vative (Polyquad) which do not have any action on Fig. 16.5: Freeman’s punctum plug with introducer for
cells are to be used. Formulations containing temporary closure of punctum
bicarbonate buffer are better tolerated compared to
other buffers.
All these drugs do not have any effect on basic
pathophysiology and they provide only symptomatic
relief. Artificial tear substitutes made with sodium
hyaluronate have shown to have objective evidence
of improvement in cellular morphology.
At night time ointment may be used to provide
long lasting lubrication when tear production is
markedly reduced.
Since tear substitutes have to be instilled frequently
an effort is made to provide continuous irrigation. This
is accomplished by tear tank fitted in a spectacle and
feeding silicone tube implanted into the fornix or
canthal region.
Tear Conservation
Preservation of available tear is another approach in
management of dry eyes. This can be done by Fig. 16.6: Method of introducing Herrick’s punctum plug
occluding the puncta or minimizing evaporation. (silicone plug) into canaliculus for permanent occlusion
Permanent closure of puncta can be achieved by
application of cautery, heat, laser or cyanoacrylate glue they have not been used in clinical practice. Bromo-
to the puncta. The other way is blocking the puncta hexidine chloride and cloisin are used in Europe for
with silicone plugs or collagen rods (Figs 16.5 and similar purpose. They may be used topically or
16.6). They are useful as a short-term measure to assess systemically.
the effect of occluding puncta before resorting to Anti-inflammatory Therapy
permanent measures. Cautery and cyanoacrylate
blockage usually last for about one week only. Low grade inflammatory changes are known in
Tears can also be conserved by reducing the keratoconjunctivitis sicca. Anti-inflammatory agents
exposed ocular surface. This can be attained by lateral are not employed due to their low grade and
tarsorrhaphy. chronicity. Steroids and other anti-inflammatory
To prevent evaporation of tears tight fitting eye agents are used in erythema-multiforme and ocular
pemphigoid. It can be used topically or systemically.
wear like swimming glasses can be used. They retain
In severe cases of ocular pemphigoid, antimetabolites
the moisture inside and help in conserving tears by
and Dapson (antileprosy agent) are found useful in
reducing evaporation.
checking progress of the disease.
Tear Stimulants Contact Lenses
Cholinergic drugs increases the tear production from Bandage contact lenses provide prompt relief in cases
lacrimal gland by stimulating secretion. However, of filamentary keratitis. However, there is increased
deposits on the contact lens. The dry eye patients using transplantation of autologus nasal mucous membrane
bandage contact lens are at greater risk of developing is attempted with good results.
corneal infection. As far as possible, use of contact lens
should be avoided in dry eyes. Keratoprosthesis
In corneal blindness with dry eyes keratoplasty is not
Decreasing Tear Viscosity successful. Keratoprosthesis of various designs are
Use of acetyl cystein 10 to 20% solution 4 to 5 times a attempted for visual rehabilitation. Long-term results
day are useful in presence of mucous plaques or are poor in majority of cases due to extrusion of
filaments. The solution is irritating initially. It is to be keratoprosthesis.
prepared fresh. It can be stored in refrigerator for 3 to
4 weeks. BIBLIOGRAPHY
1. American Academy of Ophthalmology. External disease and
Estrogen cornea. Section 7 Basic and Clinical Sci course.
2. Aguilar AJ. Sjögren’s syndrome: A comparative study of
KCS is more frequent in postmenopausal women. impression cytology of the conjunctiva and buccal mucosa
Estrogens are known for its effect on mucous and salivary gland biopsy. Corneal 1991;10:203-06.
membrane of the body. There is no clear cut evidence 3. Farris RL. A comparison of diagnostic tests for keratoconjunc-
tivitis sicca: Lactoplate, Schirmer, and tear osmolarity. CLAOJ
showing its role in dry eyes. However, it appears that 1990;16:109-12.
women with estrogen deficiency, as revealed by 4. Farris RL. Staged therapy for the dry eye. CLAOJ 1991;17:207-
studying cervical smears, may benefit by estrogen 15.
therapy. 5. Goren MB, Goren SB. Diagnostic tests in patients with
symptoms of keratoconjunctivitis sicca. Am J Ophthalmol
1988;106:570-74.
Topical Vitamin A
6. Jones DP, Webber WRS, Wright P. Fluorophotometric
Tretinoin when applied topically is useful in reversing measurements of tear turnover rate in normal healthy
persons. Evidence for circadian rhythm. Eye 1987;1:615-20.
squamous metaplasia seen in various dry eye
7. Kogbe O, Litotet S. An interesting use of tear ferning pattern
conditions. Tretinoin is used in a dosage of 0.01% to in contactology. Ophthalmology 1990;97:303-07.
0.1% weight to weight or weight to volume. It is 8. Kramar P. Cyclic changes in conjunctival smears from
applied one to three times a day. menstruating females. Ophthalmology 1990;97:303-07.
9. Katsukai K. A new thread test using silicone tubing.
Surgical Measures Ophthalmologica 1987;195:192-98.
10. Lamberts D. Punctal occlusion. Int Ophth Cli 1987;27:44-46.
Various surgical methods are devised for use in dry 11. Lawrence AG. Estrogen and progestrone receptors and
eye patients. It includes mucous membrane grafting, human conjunctiva. Am J Ophthalmol 1990;109:474-77.
12. Leibowitz HM (Ed). Corneal disorders: Clinical diagnosis and
conjunctival transplant, parotid duct transplant, management. Saunders: Philadelphia, 1984.
blepharoplasty or tarsorrhaphy, keratoprosthesis, etc. 13. Lemp M. Recent developments in dry eye management.
Parotid duct transplantation once popular is not Ophthalmology 1987;94:1299-1304.
advocated any more.Parotid secretion do not match 14. Lemp M. General measures in management of dry eye. Int
the conjunctival secretions. The flow is difficult to Ophth Cli 1987;27:36-43.
15. Liolet S, Van Bijsterveld OP, Kogbe C. A new hypothesis on
regulate. The procedure has its own complications and tear film stability. Ophthalmologica 1987;195:119-24.
may get blocked on its own. 16. Mondino BJ. Cicatricial pemphigoid and erythema
Tarsorrhaphy by shortening exposed area helps in multiforme. Ophthalmology 1990;97:939-52.
reducing evaporation of tears. It is also useful in eyes 17. Mondino BJ. Bullous disease of skin and mucous membranes.
with exposure keratitis. In Thomas Duane (Ed): Ophthalmology 1982;4(12).
18. Naumann GOH. Autologus nasal mucosa transplantation in
Correction of lid deformity, e.g. ectropion, entro-
severe bilateral conjunctival mucus deficiency syndrome.
pion, trichiasis are must for successful management Ophthalmology 1990;97:1011-17.
of dry eyes. 19. Putterman AM. Canaliculectomy in the treatment of keratitis
sicca. Ophth Surg 1991;22:478-80.
Mucous Membrane Grafting 20. Pflugfelder SC. Amplification of epstein-barr virus genomic
sequences in blood cells, lacrimal glands, and tears from
Usually there is no treatment for persons having dry primary Sjogren’s syndrome patients. Ophthalmology
eyes secondary to mucin deficiency. In severe cases 1990;97:976-84.
21. Reddy M. Conjunctival impression cytology in dry eye states. 23. Tauber J. Systemic chemotherapy for ocular cicatricial
Ind J Ophthalmol 1991;39:22-24. pemphigoid. Cornea 1991;10:185-95.
22. Stulting RD, Waring GO. Diagnosis and Management of Tear 24. Whitcher JP. Clinical diagnosis of the dry eye. Int Ophth Cli
1987;27:7-24.
Film Dysfunction in Corneal Disorders. Clinical Diagnosis
25. Wills RM, Folberg R, Holland EJ. The treatment of aqueous
and Management. Leibowitz HM (Ed): Saunders, Philadel- deficient with removable punctal plugs: A clinical and
phia, 1984;445-64. impression cytologic study. Ophthalmology 1987;94:514-18.
Chapter 17
Ocular Surface Squamous

Neoplasia
Samrat Chatterjee, Santosh G Honavar
INTRODUCTION long potential for clonagenic expansion. This micro-

environment is sensitive to external stimuli, like
Ocular Surface Squamous Neoplasia (OSSN), a term
ultraviolet rays making it predisposed for aberrant
coined by Lee and Hirst,1 describes a spectrum of
changes. Ultraviolet-B rays cause formation of
conjunctival and corneal epithelial neoplasia manifes-
pyrimidine dimers that damage DNA strand and
ting as dysplasia, carcinoma-in situ (CIS) and
results in delay or failure in DNA repair.16, 17 This may
squamous cell carcinoma (SCC). The condition has
lead to somatic mutations and development of neo-
been termed by various authors as Epithelioma, Bowen’s
plasia. In xeroderma pigmentosa, a rare autosomal
disease, Epidermalization, Dyskeratosis, Conjunctival
recessive disorder with predilection for malignancies
Intraepithelial Neoplasia, Corneal Intraepithelial Neoplasia
of the skin and eyes, such delay in repair has been
and Ocular Surface Epithelial Dysplasia.
demonstrated.17 There may also be abnormal cell-cell
and cell-matrix interaction with alteration in the regu-
EPIDEMIOLOGY latory mechanism of limbal stem cell function
Incidence of OSSN has a wide geographical variation, resulting in abnormal phenotypes. These tumors occur
declining considerably with increase in latitude.2 A in regions with high ambient solar radiation and are
population survey in Uganda reported the incidence associated with other solar –damage related lesions
to be 0.13 per 100,000 while in urban Australia it was like pterygium, pinguecula, nuclear sclerosis, solar
1.9 per 100,000. 3,4 Worldwide it is the third most elastosis, climatic droplet keratopathy, and collagen
common tumor after retinoblastoma and melanoma,1 degeneration in the conjunctiva and skin.2,9-11,18,19
though it may rank higher in some regions.5,6 Males Histopathological evidence of actinic changes have
are affected more often than females.7-12 The average also been demonstrated in the presence of neoplasia.18,19
age of presentation is usually in the sixth and seventh Phenotypic features such as fair skin, pale irides,
decade,7-12 but it has also been reported in patients as propensity to sunburn, history of actinic skin lesions
young as 2 years and as old as 97 years.7 Younger before fifty years of age, and being outdoors more than
patients presenting with OSSN often have associated 50% of time in the first six years of life while living in
xeroderma pigmentosa13,14 or immunodeficiency.15 regions 30° or less from the equator are known risk
factors for development of OSSN.20
A close association between OSSN and Human
ETIOLOGY
Papilloma virus (HPV) has been observed with HPV
The exact pathogenesis of OSSN is unknown but is being detected in 39-88% of patients.21-26 HPV are
probably multifactorial. The tumors commonly occur epitheliotropic viruses, of which Type 6 and 11 are
at the limbus.7-12 The limbus is a dynamic transitional associated with benign tumors and types 16,18, 31,33
zone containing stem cell population that has a life and 35 with malignant tumors. These viruses have
Chapter 17: Ocular Surface Squamous Neoplasia 111
however also been detected in normal control fellow Morphologically there are three types of lesions:
eyes of unilateral dysplasia, in eyes where OSSN has gelatinous (leukoplakic or papilliform), nodular and
recurred after years, and in eyes with benign diffuse.1 The gelatinous type is the commonest and
conjunctival lesions.23,24,26 These findings cast a doubt appears as a thick placoid lesion, with a shiny velvety
about the role of this virus in the etiopathogenesis but surface, tufted vessels (Fig. 17.1) and with or without
nevertheless existing data suggests at least a partial a white patch (Fig. 17.2) while the nodular type is a
role. circumscribed elevated focal mass with a mulberry
Squamous cell carcinoma is the third most common appearance (Fig. 17.3). The localized lesions are
malignancy associated with HIV, particularly in the relatively sharply demarcated, pearly gray to reddish
oral cavity and rectum. OSSN is present in 70-90% of gray depending on intrinsic tumor vascularity and
patients in endemic areas. 15,27-33 Majority of the accompanied by a leash of feeder vessels that are
patients with OSSN are not aware of underlying HIV straighter and less tortuous than the surrounding
infection, thus the appearance of these tumors can be conjunctival vessels. The diffuse type, without distinct
an indicator for AIDS.15 It is recommended that HIV margins, represents radial growth pattern and has an
testing and counseling be offered to all patients below appearance that can be deceptive enough to delay
fifty years of age with OSSN.31 In HIV patients, the diagnosis as it often mimics chronic blepharo-
tumor occurs in a younger age group, tends to be bila- conjunctivitis and focal corneal or scleral inflammation
(Fig. 17.4).37-40 In elderly patients with chronic unila-
teral and multifocal, exhibits rapid growth and is of
teral conjunctival inflammation, diagnostic cytology
greater severity with a higher recurrence rate. It is not
should be mandatory to rule out squamous cell
clear whether HIV infection has a permissive or
carcinoma.34 The tumor may rarely be pigmented due
causative effect. Immunodeficiency may promote
to the presence of melanocytes, melanosomes or mela-
HPV infectivity, reduce tumor surveillance and
nin granules within the neoplastic cells (Fig. 17.5).41,42
facilitate oncogenesis by altering local immunity.
These tumors are characteristically located at the
The other factors implicated in etiology are dust,
limbus encroaching on the corneal surface but may
wind, smoking, petroleum products, chronic ocular occur elsewhere in the conjunctiva.7-12 They are less
surface inflammation, ocular surface injury, Vitamin commonly confined only to the cornea. The bulbar
A deficiency, infection and exposure to chemicals like conjunctiva is the predominant site of the tumor but
trifluridine, arsenicals, and beryllium have not been palpebral conjunctiva may be also involved as is seen
validated.1 in the diffuse variant.8 It is usually unilateral but in
rare circumstance may be bilateral with simultaneous
Clinical Features or sequential presentation.12,35,43
OSSN on the cornea (Fig. 17.6) presents as an eleva-
Clinically it is difficult to distinguish between ted gray intraepithelial plaque with fimbriated margin
dysplasia, carcinoma in situ and invasive squamous and clusters of isolated gray spots that have a beaten
cell carcinoma. The terms leukoplakia and Bowen’s metal sheen under retroillumination.44-46 Fluorescein
disease has been often used to describe these lesions. and Rose Bengal dye causes diffuse punctate staining
Leukoplakia is actually a clinical description for any of the surface of the lesion.
white patch on a mucus membrane that may micros- The different variants of OSSN are mucoepi-
copically prove to be carcinoma but is often only dermoid carcinoma, adenoid squamous cell carci-
benign acanthosis or hyperkeratosis. 34 Classical noma, and spindle cell carcinoma. These tumors are
Bowen’s disease is a rare occurrence in the conjunc- more aggressive, are frequently recurrent and carry a
tiva.34 OSSN can present as a growth in the limbal area, poorer prognosis (Fig. 17.7). Mucoepidermoid carci-
symptoms of chronic ocular irritation or decreased noma is characterized by the presence epidermoid
vision. A chronically irritated or an inflamed red eye (squamous) cells and mucin producing cells.47-49 This
may at times be a commoner presentation than the type of tumor is morphologically indistinguishable
others.11,12 Patients may also remain asymptomatic from squamous cell carcinoma and needs to be
with the tumor being detected during routine exami- histologically differentiated. Histology reveals
nation.11,12 Delayed presentations are characterized by variable amount of squamous and mucin-secreting
a large necrotic mass with destruction of the eyeball.36 cells with a signet ring appearance and clear cytoplasm
Fig. 17.1: The common gelatinous papilliform variant of Fig. 17.2: Leukoplakic type of ocular surface squamous
ocular surface squamous neoplasia neoplasia often misdiagnosed
Fig. 17.3: The localized nodular type of ocular surface squa- Fig. 17.4: The diffuse type of OSSN can
mous neoplasia is characterized by pronounced vascularity and be easily missed
episcleral feeder vessels
Fig. 17.5: Ocular surface squamous neoplasia may be Fig. 17.6: Corneal invasion of ocular surface squamous
pigmented and simulate melanocytic tumors. Note the leash of neoplasia is commonly restricted to the epithelium
feeder vessels
Fig. 17.7: The mucoepidermoid variant of ocular surface Fig. 17.8: OSSN with a late manifestation with
squamous neoplasia has a higher risk of intraocular extension massive orbital extension
that stains with mucicarmine, alcian blue and Periodic other systemic malignancies. It is associated with
Acid-Schiff stain. squamous and basal cell carcinoma in 10-20% of cases
In adenoid squamous carcinoma, a characteristic and cancer of lungs, colon, kidneys, pancreas, cervix,
pseudoglandular appearance is seen.50 The pseudo- liver and breast in 8-12%.10,12,43
glandular formation is because of the lumina within
the lobules and special stains reveal the presence of Diagnosis
extracellular hyaluronic acid without of intracellular
Clinically, it is often difficult to diagnose OSSN, parti-
mucin. Spindle cell carcinoma presents as single or
cularly early lesions in which the morphology is not
multiple lesions or with diffuse involvement of the
distinctive enough to distinguish it from benign
conjunctiva with surface ulceration. 51,52 They are
lesions like pterygium, papilloma, pinguecula,
composed of spindle shaped cells with elongated and
keratoacanthoma and amelanotic nevus.1,9 The other
vesicular nuclei. The cells are arranged haphazardly
lesions that need to be considered in the differential
in interlacing fascicles.
diagnosis are malignant melanoma, pyogenic granu-
Local extension and metastases occur in 10-20% of
loma, dermoid, lymphoma, pseudoepitheliomatous
patients.10,12 Clinical signs of intraocular and orbital
hyperplasia and complex choristomas. In the cornea
extension in the early stages are subtle.53-55 Notable
pannus, keratinization, Epithelial Basement Memb-
signs are circumciliary injection, anterior chamber
rane dystrophy and Herpes Simplex virus keratitis
reaction, peripheral anterior synechia, opaque sheet
need consideration for differential diagnosis. 1
of cells on the iris surface, undiagnosed corneal
Diagnosis of the lesions are done by cytology or
perforation and irregular sclera with focal vascular
excisional biopsy.
tufts. In late stages they present with intra-ocular and
orbital mass with disorganized anterior segment
CYTOLOGY
(Fig. 17.8).54,55 Risk factors are longstanding recurrent
tumors, and variants of SCC such as mucoepidermoid The cornea and the conjunctiva are desquamating
and adenoid squamous carcinomas. The route of tissues. The cells of the basal layer undergo matura-
invasion is through canals for the perforating vessels tion, become superficial and finally desquamate. The
at the limbus and the scleral trabeculae. The supra- abnormal maturation of neoplastic cells is reflected in
choroidal space is invaded with infiltration of the angle the morphology of the surface cells and their study
structures, iris, ciliary body and choroid.1,53 Tumor forms the underlying principle of cytology
cells may detach from the main body and set up (Table 17.1). These cells are studied either by exfolia-
multiple focal metastatic sites. Distant metastases are tive or impression cytology. Specimens for exfoliative
to the parotid gland, preauricular, cervical and cytology are obtained by scraping the lesion with a
submandibular lymph nodes and the lungs and bone. heat sterilized platinum spatula56,57 or a cytobrush.1
OSSN is also associated with cutaneous tumors and The smear is stained with Papanicolaou stain, 57
Table 17.1: Characteristics of atypical cells on cytology an alternative to excision biopsy in those patients
unwilling or unfit to undergo the surgical procedure.
Normal • Small round uniform epithelial
cells
HISTOPATHOLOGY
Conjunctival • Large basophilic cytoplasm
epithelium • Nucleocytoplasmic ratio 1:1/1:2 Histopathology is the gold standard for diagnosis and
• Plump PAS positive goblet cells grading of OSSN (Figs 17.9 to 17.14). Excision biopsy
(> 500/mm2) is an important tool, which is diagnostic and
Metaplasia • Loss of Goblet cells simultaneously curative. There is usually no indication
• Keratinization evident as pinkish for incisional biopsy unless the tumor is extensive and
cytoplasm orbital exanteration has been planned. 60
• Enlargement of cells Histopathological differentiation of dysplasia, CIS and
• Nucleocytoplasmic ratio reduced invasive SCC is dependant on the extent of epithelial
(1:4 – 1:8) involvement and breach of the basement membrane
• Pyknotic nuclei with densely
(Table 17.2). The different cell types are spindle cells,
packed keratin filaments in the
cytoplasm in advanced stages
epidermoid cells, mucoepidermoid and clear cells
(Table 17.3).9 Majority of the tumors have a mixed
Dysplasia • Pleomorphism pattern of spindle and epidermoid cells.9,10 Various
• Enlarged and hyperchromatic degree of keratinisation is generally found in the
nuclei
• Irregular nuclear contour with
lesions. There is usually a sharp vertical or oblique
coarse chromatin demarcation between the abnormal and normal cells
• Prominent nucleoli in sections.
• Nucleocytoplasmic ratio increased Electron microscopy of the lesions reveal excessive
• Increased number of Mitotic intracellular organelles, condensed tonofilaments
figures around the nucleus, reduced number of desmosomes,
• Loss of normal cellular matura- and wide intercellular spaces.61,62 Keratinization seen
tional polarity
in light microscopy corresponds to cells with pyknotic
Invasive Squamous • Severe changes than dysplasia
cell carcinoma • More bizarre cell types and nuclei or with nuclear material dispersed among
patterns tonofilaments. Microcysts and altered basement
• Tumor diasthesis—necrotic tumor membrane, which is thrown up in fronds by
cells, debris, blood and leukocytic fibrillogranular material, are the other features. Newer
exudates molecular markers have given fresh insights into the
Giemsa56or hematoxylin-eosin. In impression cyto-

logy, either cellulose acetate paper58 or modified Table 17.2: Grades of OSSN
devices such as the Biopore membrane are used for Type Description
sampling.59 Dysplasia
Cytology is accurate in 80-90% of cases. 57,59 Mild • Dysplastic cells restricted to the
However, inadequate sampling may yield false lower one-third of the epithelial
negative results. Cytology is unreliable in assessing layer
depth of stromal involvement and differentiating CIS Moderate • Dysplastic cells occupying three-
from invasive SCC. The presence of abundant surface fourth the thickness of epithelium
keratin in a keratinizing dysplasia or a squamous cell Severe • Involvement of the entire thickness
with sparing of the surface cell
carcinoma may prevent accurate sampling of
layer
dysplastic cells.59 Sampling procedure and staining are Carcinoma in situ • Complete involvement of the
cumbersome and paucity of specific criteria for epithelium including surface layer
diagnosis in literature has limited its widespread use. but no breach of the basement
Yet it is still valuable as a noninvasive office procedure, membrane
in distinguishing benign from malignant lesions, in Invasive SCC • Breach of the basement membrane
surveillance for recurrences, establishing diagnosis in with involvement of substantia
propria
whom topical chemotherapy is contemplated and as
Table 17.3: Types of cells in OSSN
Type Characteristics
Spindle cells Small uniform cells with elongate
scant slightly basophilic cytoplasm
and ellipsoid moderately chromatic
nuclei without prominent nucleoli
and frequent mitotic figures
Epidermoid cells Large polyhedral cells with abundant
(Squamous cell) eosinophilic cytoplasm, variable
degrees of hyperkeratosis and
parakeratosis and large hyper-
chromatic pleomorphic nucleoli and
infrequent mitotic figures
Clear cell Small cells with scant, clear, slightly
basophilic cytoplasm and hyper-
chromatic nuclei
Mucoepidermoid Cuboidal cells with intracellular Fig. 17.10: Light photomicrograph of neoplastic cells with
cell droplets and arranged in nests and moderate amount of cytoplasm, hyperchromatic nuclei and
cords with extracellular mucin mitotic figures (arrow). (H&E, x 400. Courtesy: Dr Geeta K.
Vemuganti)
Fig. 17.9: Ocular Surface Squamous Neoplasia. Histology Fig. 17.11: Carcinoma in situ. Neoplastic cells are involving
section showing normal conjunctival epithelium (extreme right), the full thickness of the epithelium but not the underlying stroma
dysplastic epithelium (arrowhead) and carcinoma in situ (H&E, x 200. Courtesy: Dr Geeta K. Vemuganti)
(arrow).(H&E, × 200. Courtesy: Dr Geeta K. Vemuganti)
behavior of tumor cells as well as in aiding diagnosis Table 17.4: Tumor markers
(Table 17.4).35, 63-65 • Bromodeoxyuridine65
• Proliferating cell nuclear antigen (PCNA)66
Treatment • Argyrophilic nucleolar organizer regions
• (AgNOR/NOR)66
The treatment of choice for OSSN is surgical excision
with cryotherapy to the excised edge, which may be • p53 protein66,67
combined with other adjuvant treatment modalities • Bcl-2 protein67
like topical chemotherapeutic agents, immunotherapy • Ki-67 or MIB-1 index9,67,68
and radiotherapy as appropriate. • Involucrin71
Fig. 17.12: Carcinoma in situ. An in situ lesion with an Fig. 17.13: Invasive SCC. This section shows tumor
intact basement membrane (PAS, × 400. Courtesy: cells infiltrating the underlying stroma (arrow) (H&E, x
Dr Geeta K. Vemuganti) 100. Courtesy: Dr Geeta K. Vemuganti)
Fig. 17.14: Actinic keratosis. Histology section shows epithelial hyperplasia and keratinization with areas of
elastotic degeneration in the underlying stroma (H&E, × 200. Courtesy: Dr Geeta K. Vemuganti)
Fig. 17.15A: Preoperative appearance of ocular Fig. 17.15B: Nine months following excision and
surface squamous neoplasia edge cryotherapy
surgery subtle signs may me lost under the operating
microscope.
A minimal or no touch technique should be
followed during surgery as these tumors can be friable
and shedding of viable tumor cells carries risk of
seeding. Though intra-operative frozen section
controlled excision has been advocated,12 this facility
is not widely available and its absolute necessity has
also not been demonstrated. 60 Buuns et al have
described a modification of Moh’s microscopic tumor
surveillance where instead of the horizontal frozen
sections originally described, vertical permanent
sections are made.68 In case of scleral involvement, a
thin slice of sclera is included and its undersurface
studied to exclude deeper involvement. However all
excised tissues must be properly oriented and
accurately labeled before histology.
Fig. 17.16A: A recurrent tumor predominantly The essential surgical steps are delineation of the
involving the cornea surgical margin with bipolar cautery, alcohol
keratoepitheliectomy, excision with minimal touch
technique, cryotherapy of the edges and closure of the
wound. 60,69 Multiple applications with a bipolar
cautery are placed about 3 mm from the visible tumor
margins. The cornea is meticulously dried and a
cotton-tipped applicator saturated with absolute
alcohol is applied over the affected area including 2-3
mm of normal epithelium. A number15 Bard Parker
blade is used to gently peel the epithelium like a scroll
taking care not to breach the Bowman’s membrane.
The Bowman’s membrane is a natural barrier to tumor
cells and should be preserved during surgery.60 The
conjunctival portion of the tumor along with the
underlying Tenons’s fascia is widely excised with
scissors along the preplaced cautery marks. If scleral
involvement is suspected, a partial lamellar
sclerectomy is done and the scleral bed treated with
absolute alcohol. Cryotherapy is done with a double
freeze-thaw technique. The conjunctiva is lifted and
Fig. 17.16B: One year after completion of topical mitomycin-C
the tip of the cryo-probe is touched to posterior
treatment, the patient is tumor-free and maintains 20/30 Snellen
visual acuity
conjunctival surface, which minimizes accidental
damage to the uvea and retina. The conjunctiva is
closed with interrupted 6-0 or 7-0 absorbable suture.
SURGICAL EXCISION
Smaller defects left to granulate heal within days with
The goal of surgery is an wide excision of the tumor no cosmetic blemish. Larger defects may be repaired
as a single mass with a tumor-free conjunctival margin. with conjunctival autograft or amniotic membrane.
A meticulous preoperative evaluation is necessary to Local extension is usually managed with enuclea-
demarcate tumor margin and detect intra-ocular or tion or exanteration though localized intraocular
intra-orbital invasion. Slit-lamp biomicroscopy with masses have been removed with success by less
Rose Bengal stain66 to delineate tumor margins and a destructive surgical procedures.55,70,71 Where extensive
diagrammatic representation is helpful, as during limbal dissection is done, stem cell transplantation
may mitigate the complications arising out of limbal SCC with only topical MMC and obtained a complete
stem cell loss.72 cure with no recurrence over a median follow-up of
15 months. 5-FU (1%) has been used for three to four
Cryotherapy times a day for two to three weeks or for three to four
days and repeated after 30-45 days and in cycles.86-88
Cryotherapy achieves a better cure rate when it is
Complications of MMC are tearing, painful red eye,
combined with excision.73 OSSN has been likened to
conjunctival hyperemia, corneal erosions, punctate
roots of a tree where simple excision may miss small
epithelial keratopathy, pannus, dry eye, limbal stem
root tips at both the surgical margin and bed.
cell deficiency, tissue necrosis, cataract, punctal
Superficial freezing will destroy these small foci.
stenosis and ectropion. The complications reported
Cryotherapy acts by direct mechanical disruption,
with 5-FU are conjunctival inflammation, corneal
electrolyte imbalance, ischemic necrosis and
epithelial defect, punctate epithelial keratopathy and
immunologic responses to release of tumor
erythema of the skin of eyelids. Such adverse events
antigens.74,75 A rapid freeze and slow thaw technique
are avoided with close monitoring, proper patient
is preferred as it results in expanding intracellular ice
education, and punctal occlusion. The other topical
crystals, which is responsible for direct cellular
agents that have been used are urea,89 thiotepa10 and
disruption.74 The potential complications are rise in
dinitrochlorobenzene.90
intra-ocular pressure, iritis, transient hyphema,
sectorial iris atrophy, synechiae, local retinal pigment
Radiotherapy
epithelial changes, corneal scarring and
vascularization. These tend to be more with heavy and Radiotherapy has also been used as an adjunct to
extensive treatment.73-76 Such complications can be excision. Its popularity has waned in recent years with
avoided by the “reverse cryotherapy” technique the introduction of effective chemotherapy. Treatment
where the probe is held under the conjunctiva lifting by beta radiation with Strontium-90 has been reported
it away from the sclera. by many authors.91, 92 X-rays have also been used but
are associated with more complications. The surface
Chemotherapy dose used by various authors varied between 4500
rads given as 750 weekly fractions to 10,000-18,000
The indications for chemotherapy are multiple rads in daily fractions of 1000 rads. The limiting factor
recurrences with treatment failures, diffuse lesions with radiotherapy is complications like cataract,
with clinically indistinguishable margins not secondary glaucoma, inflammation, dry eye and tissue
amenable to complete surgical excision, chemoreduc- necrosis.
tion prior to excision, positive excision edge on histo-
pathology, and in elderly and debilitated patients
unable to tolerate surgery or those who refuse Immunotherapy
surgery.77 The prerequisite to start chemotherapy is a Immunotherapy for OSSN was first reported with the
definite diagnosis. Mitomycin C (MMC) and 5- use of Dinitrochlorebenzene. 89 In recent times,
Fluorouracil (5-FU) are the two agents extensively encouraging results with use of interferons have
used. They treat the entire ocular surface and hence rekindled interests.93-95 Interferons are a group of
are particularly suited for the diffuse lesions. They also glycoproteins, which are made by cells in response to
can eradicate isolated foci that persist after excision. stimuli. These proteins then bind to sell surface
Surgical trauma over the central cornea can be avoided receptors and trigger multiple intracellular responses,
with possibility of good vision after tumor regression. which promote antitumor and antiviral properties.
MMC is used in concentrations of 0.02-0.04% for Interferon alpha 2-b is given topically and injected
periods ranging from 1-3 weeks or in cycles of 7 days around the lesion. No complications or side effect with
treatment and 7 days off treatment, for 3-4 cycles.78-84 its use for treatment of OSSN has yet been reported.
The rationale of a drug holiday is to allow normal cells
to heal and repair.85 There has been no consensus on
Prognosis
dosage or duration of either MMC or 5-FU. Their use
in invasive carcinoma is debatable though Shields et OSSN are low-grade malignancy and infiltration and
al have reported favorably.83 They treated invasive metastases are rare.1,7-9,34 The rate of recurrence
Table 17.5: Treatment and recurrences
Author, Year Number of cases Treatment modalities Recurrence
2
Ashe and Wilder 93 Excision 58 6/93
Enucleation 29 6%
Ni et al,4 212 Excision 142 13/209

Shanghai Enucleation 24 (6%)
Exanteration 46
Boston 126 Excision 58 14/55

Enucleation 4 (25%)
Fraunfelder 38 Excision 6 2/6 (33%)

and Wingfield,73 Excision + Cryotherapy 23 2/23 (9%)
Cryotherapy 9 3/9 (33%)
Erie et al,5 120 Excision 97

Excision + Irradiation* 11 32/120
Excision + Thiotepa 7 (27%)
Enucleation 3
Exanteration 2
Lee and Hirst,6 288 Excision 237 67/271

Excision + Irradiation 18 (25%)
Excision + Thiotepa 4
Excision + Cryotherapy 6
Others/unknown 4
Tabin et al, 79 Excision 70 31/79

197744 Excision + Irradiation 4 (39%)
Tunc et al,7 60 Excision 11 3/60

Excision + Irradiation 4 (5%)
Excision + TCA 2
Enucleation 1
Exanteration 2
Sudesh et al,76 28 Excision 9 5/28

Excision + Cryotherapy 19 (18%)
Peksayer et al,75 57 Excision + Cryotherapy 57 7/57

(12%)
LVPEI data 144 Excision 27 18/137

Excision + Cryotherapy 91 (13%)
Topical MMC 3
Exanteration 11
Others 5
*patient treated with radium plaque. TCA: Topical cytotoxic agents

LVPEI: LV Prasad Eye Institute, Hyderabad
reported varies between 6-39% (Table 17.5). Partially GLOSSARY

excised tumors recur with behavior that is more Term Definition
aggressive and after a first recurrence, there is a
Abnormal polarity •Loss of normal transition from basal
tendency for more.9,10,43 The most significant prognos- cells to superficial cells which indicates
tic factors for recurrence are presence of neoplastic neoplasia
cells in the tumor margin after excision,10-12,43 histologi- Acanthosis •Thickening of the squamous layer as a
cal type (SCC > CIS > Dysplasia),11 and Ki-6735 score. result of increase mitosis in the basal
Less significant are age and tumor size while cell layer signifying active cell
recurrence has not been correlated to individual cell proliferation, benign or malignant
type, location, type of treatment or sex.10,11,43 Anaplasia •Severe dysplasia indicating malignancy
The causes of inadequate surgical excision are Atrophy •Decrease in size of cell or tissue
difficulty in delineating the true margin during Cellular atypia •Increase nucleus—cytoplasm ratio or
surgery, diffuse lateral growth, multiple foci and hyperchromasia, increase in size or
probable presence of remnant tumor cells deep at the number of nucleus and irregularity in
limbus that escapes excision. Erie et al10 and Tabin shape or presence of mitotic figures
et al43 have reported 5% and 33% recurrence respecti- Dyskeratosis •Keratinzation of individual cells that lie
vely in those cases with free surgical margins which within the epidermis or epithelium
increased to 53% and 56% in those with involved than on the surface signifying active cell
margins. Most of the recurrences occur during the first proliferation, benign or malignant
two years thus close follow-up during this period is Dysplasia •Abnormal growth of cells
necessary. 10-12, 43 Recurrences have also been observed Hyperkeratosis •Increased thickness of the keratin layer
as late as 10 years thus all patients require lifelong of epidermis which when occurring on
monitoring.43 Recurrences are managed either by mucosa is also called as
excision with cryotherapy for localized lesion supple- Epidermalization signifying active cell
proliferation, benign or malignant
mented at times with chemotherapy or immunothe-
Hypertrophy •Increase in cell or tissue without
rapy.
increase in numbers
The development of regional nodal metastases may
not necessarily always be associated with poor Hyperplasia •Increase in number of cells in excess of
normal but not progressive
prognosis. Tumor related mortality has been seen to
be commoner with intra-ocular and orbital Leukoplakia •A clinically descriptive term to
designate an opaque white placoid
extension.34,36,49 Death due to tumor, though rare, has lesion on a mucus membrane
also been documented and is either as a result of
Metaplasia •Transformation of one type of tissue
extension into the cranial cavity, nasopharynx or into another
distant metastases. 1,9,35,36 Metastases and local
Neoplasia •Unregulated cell proliferation
extension are managed by enucleation, exanteration
and palliative radiation, along with chemotherapy, Parakeratosis •Hyperkeratosis in which nuclei are
present in the superficial cells
parotidectomy and radical neck dissection.36, 71 signifying rapid cell turnover, benign
or malignant
CONCLUSION Precancerous lesion •Lesions where malignant transfor-
mation has occurred at cellular level but
Ocular surface squamous neoplasia has a spectrum no invasion has occurred
of clinical manifestations and often presents as a
nodular bulbar conjunctival growth straddling the
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Chapter 18
Conjunctival Tumors
Conjunctiva contains all tissue elements except not found.

muscles and bones. So any of the tumors seen else-
where can be found in the conjunctiva. Conjunctival EPITHELIAL TUMORS
tumors can be benign or malignant. Congenital benign
Papilloma
tumors may be hamartomas 1 or choristomas.
Hamartoma are composed of tissues normally found Conjunctival papillomas can be neoplastic or caused
in that organ while choristomas are made up of tissue by papillovirus.3,4 Neoplastic papillomas are sessile,
normally not found in the organ.2
DERMOIDS
Dermoids are choristomas. They can be in the form
of a dermoid or dermolipoma. They are derived from
displaced embryonic tissue destined to be the skin.
They are smooth and solid round lesion. They are
situated close to the limbus (Fig. 18.1). They are
known as dermoid cyst when sebaceous material is
more. They are labeled as dermolipoma (Fig. 18.2)
when fat content is more. They may extend to the
orbit involving extraocular muscles. Usually they are
stationary and do not grow in size.
Epibulbar dermoid may be associated with other
congenital anomalies of the body. Goldenhar
syndrome includes epibulbar dermoids,
Fig. 18.1: Dermoid at the limbus
abnormalities of ears (preauricular skin tags and aural
fistulae), colobomas of upper lid, and vertebral
anomalies.
Dermoids when large can cause corneal astigma-
tism. They are removed mainly for cosmetic reasons.
As far as possible it should be excised. When large
and extends into the orbit, only the external part may
be removed. When removing a large lesion, care must
be taken to safeguard the muscles.
EPISCLERAL OSSEOUS CHORISTOMA

There is a solitary nodule of bone surrounded by
fibrous tissue. Other congenital anomalies are usually Fig. 18.2: Epibulbar dermolipoma situated temporally
solitary bengin lesion seen at limbus in older people. vascularized. They may manifest as a fleshy lesion at
They may spread to the cornea. Complete excision is limbus or a gelatinous avascular mass. Complete
the treatment of choice. This may be supplemented excision biopsy is the treatment of choice.
with cryotherapy and/or beta radiation. Cryotherapy may be used as an adjuvant.
Viral papillomas are pedunculated. They are
Squamous cell carcinoma When malignant cells invade
multiple and can affect palpebral conjunctiva. They
the basement membrane it is a malignant lesion
may recur following incomplete removal.
(Fig. 18.3). It can spread locally and involve the globe
Both types of papillomas are known to regress
and/or have distant metastasis (rare) also. Treatment
spontaneously. Patients with papillomas may present
is complete excision. This usually involves lamellar
with bloody tears.
dissection of sclera. In extensive lesion, removal of
the eyeball and/or exenteration of orbit may be
Keratoses
necessary.
There is abnormal keratinization of epithelial layer;
Mucoepidermoid carcinoma These are malignant tumors
it may be labeled as hyperkeratosis (keratinization),
of mucous membrane. There are malignant changes
parakeratosis (keratin in nuclear layer) or
in goblet cells along with the epithelial cells. This is
dyskeratosis (premature keratinization), depending
more aggressive than squamous cell carcinoma and
on the type of keratinization.
involves the globe faster.
Leukoplakia
Melanotic Lesions
These are white plaque like lesions of conjunctiva.
This may be benign or malignant.
Premalignant and Malignant Lesions

This category includes pseudocancerous lesions,
precancerous lesions, carcinoma in situ, and
squamous cell carcinoma. Human papilloma virus is
thought to be responsible for malignant changes in
conjuctiva.
Pseudocancerous lesions Pseudoepitheliomatous
hyperplasia and keratoacanthoma are reactive inflam-
matory lesions. They do not need any treatment on
their own. However, if required they can be excised.
Precancerous lesions They are potentially malignant Fig. 18.3: Squamous cell carcinoma
lesions. They usually arise at limbus and spread to
other areas. There may be gelatinous thicknening of
conjunctival epithelium and varying degrees of
leukoplakia. They may follow exposure to actinic
rays. The excision of lesion with cryotherapy to
surrounding region is advised when it involves
cornea; simple scraping of it from Bowman’s
membrance is needed since they are intraepithelial
lesions.
Carcinoma in situ (intraepithelial epithelloma; Bowman’s
disease) There is severe anaplasia and dysplasia
throughout the epithelium. However, they do not
infiltrate beyond epithelium. Conjunctiva is freely
mobile over episcleral tissues. These lesions are Fig. 18.4: Benign melanosis of conjunctiva
Chapter 18: Conjunctival Tumors 125
Melanoses These are diffuse flat melanotic lesions of
conjunctiva. They may be congenital (Fig. 18.4) or
acquired. Acquired lesions are slowly growing and
may show malignant transformation. The develop-
ment of nodularity suggests malignant transfor-
mation, and excision biopsy should be performed.
Deposition of melanin pigment is also seen in vernal
conjunctivitis, trachoma, vitiligo, keratomalacia,
acanthosis nigericans, and Addison’s disease. It is
also associated with use of chlorpromazine
systemically, epinephrine and silver (argyrosis)
locally.
Malignant melanoma They are more common at limbus Fig. 18.5: Malignant melanoma of the conjunctiva
(Fig. 18.5) compared to palpebral conjunctiva. Forty
percent of them arise from pre-existing nevus, thirty
percent of them develop from acquired melanosis.
Only 3% develop as de novo lesion. Prognosis is
better when they develop from a nevus (20%
mortality) compared to other (40% mortality).
Inflammatory Lesion
Granulomatous inflammation (Fig. 18.6) may be seen
following retained foreign material. They can be seen
in mycobacterial infection, fungus (coccidiosis
immitis), parasites, sarcoid, rheumatoid disease, etc.
They may be treated by local steroids and/or Fig. 18.6: Granuloma at the limbus
excisional biopsy.
VASCULAR TUMORS
Telangiectasia
It is a dialation of pre-existing terminal vessels. They
are seen with prolonged irritation or inflammation.
They may occur as an autosomal dominant disease.
Similar changes may be seen in skin, and mucous
membrane of other parts of body including brain.
They should be differentiated from dilated vessels
seen in various other conditions, e.g. carotico-
cavernous fistula, feeder vessel for intraocular
malignancy, etc. Fig. 18.7: Hemangioma of conjunctiva
Hemangiomata Lymphangiomas
They are formed by dilation and proliferation of Abnormal dilation and proliferation of lymphatics is
vessels (Fig. 18.7). They are commonly seen on rarely seen in conjunctiva (Fig. 18.8). They are benign
palpebral conjunctiva. Capillary hemagiomata occur slowly progressive lesions. There may be lymph-
early in life. They are self-limiting. Cavernous angioma of orbit, sinuses, face, palate, and nose
hemagiomata are slowly growing tumors. Unlike associated with it. When progressive it may need
capillary hemangiomata they do not show repeated excision till it becomes stationary.
spontaneous resolution.
Lymphomas
organs and skin of the limbs and cephalic region of

the body. It may also develop in the skin of the eyelids
and caruncle.
In AIDS Kaposi’s sarcoma can be a major cause of
morbidity and mortality affecting 24% of all males
with AIDS.6
Histopathological examination reveals vascular
proliferation and neoplastic changes in the blood
vessels with predominance of endothelial cells and
spindle cells proliferations containing vascular slits.
Mitotic changes are common. Red blood cells appear
in cuboidal form.7 On histopathological basis Kaposi’s
sarcoma may be divided into 3 types:
Fig. 18.8: Lymphangioma of conjunctiva
Type I Thin, dilated vascular channels filled with RBC
without any mitotic cells
Type II Fusiform and plump cells with hyperchromatic
nuclei but without any mitotic figures. Some inflam-
matory cells may be seen amidst the tumor cells.
Type III Large aggregates of densly packed spindle
cells with hyperchromatic nuclei and mitotic figures.
Treatment
Need for treatment depends upon the extent of the
tumor, patient’s general health condition as well as
functional loss and cosmetic blemish caused by the
tumor. The treatment options include cryotherapy,
irradiation, thermotherapy and immunotherapy.8
Fig. 18.9: Lymphoma of conjunctiva
REFERENCES
Lymphomas of conjunctiva (Fig. 18.9) are very rare.
They are diffuse, pinkish in color, and situated 1. Crawford J, Brooks. Conjunctival tumors in Ophthalmology.
Thomas Duane (Ed) 1982;4:10.
subepithelially. Usually they are away from the limbus 2. John W, Gittinger Jr. Manual of Clinical Problems in Ophthal-
and primary lesions. They are radiosensitive like any molgy. Little Brown and Co: Boston-Toronto 1996;10-12.
other lymphomas of the body. 3. Lauer SA. Human papillomavirus type 18 in conjunctival
intraepithelial neoplasia. Am J Ophthalmol 1990;110:23-27.
Kaposi’s Sarcoma 4. Odrich MG. A spectrum of bilateral squamous conjunctival
tumors associated with human papillomavirus type 16.
Kaposi first described this special type of sarcoma in Ophthalmology 1991;98:628-35.
1872. It is a tumor of vasculoformative mesenchymal 5. Holland G, Goteib M, Yee R et al. Ocular disorders associated
tissue with pericytes and endothelial cell components. with the new severe acquired cellular deficiency syndrome Am
J Ophthalmol 1982;93:393.
Prior to the outbreak of AIDS Kaposi’s sarcoma was 6. Dugel P, Gill P, Frangich G et al. Ocular adnexal Kaposi’s
scarcely described in literature. Such lesions were sarcoma in acquired immunodeficiency syndrome. Am J
reported to occur in exposed areas of skin of the body Ophthalmol 1990;110:500.
in persons aged 70 years and above. Kaposi’s sarcoma 7. Dugel P, Gill P, Frangich G et al. Particles resembling retro-
is a potentially fatal vascular neoplasia that develops virus in conjunctival Kaposi’s sarcoma. Am J Ophthalmol
1990;110:86.
from the pleuripotential vascular cells.5 It usually 8. Hummue J, Gas JDM, Huang JW. Conjunctival Kaposi’s
appears as a reddish purple plaque or nodule on the sarcoma treated with Interferon Alpha 2a. Am J Ophthalmol
mucosal surface commonly the conjunctiva, visual 1993;116:502.
Chapter 19
Degenerative Conditions
of Conjunctiva
Bakulesh Khamar, Mayuri Khamar, Nitin Trivedi
PINGUECULA The major complaint of the patient is cosmetic or

dimness of vision. Diminished vision is mostly due to
Pinguecula is a small yellowish fleshy (Fig. 19.1)
astigmatism but may be due to encroachment of the
elevation of the exposed conjunctiva mostly present
pupillary area of the cornea by the lesion (Fig. 19.4).
on the nasal side near the limbus. The exact etiology
Some patients may also be conscious of some fleshy
is not known, but old age and exposure to sunlight
are found to be the contributory factors. Rarely seen
before the age of 20 years, it is more frequent in hot
dry sandy climate. Histological picture is very similar
to that of pterygium, and hence is considered to be its
precursor. There is an elastotic degeneration of the
collagen fibers in the subepithelial conjunctiva. No
treatment as such is necessary unless required by the
patient for cosmetic reasons. Rarely it gets infected
(Fig. 19.2) which can be treated with local antibiotics.
PTERYGIUM
This is a wing like encroachment of the conjunctiva
over the cornea mostly on the nasal side (Fig. 19.3) Fig. 19.1: Pinguecula
but may also be occasionally on the temporal side. It
can be seen on both sides of cornea. Many a times it
affects both eyes simultaneously in a similar pattern.
Pterygium is a Greek word meaning wing (of a
butterfly); like the butterfly it has got a head, neck
and body. The triangular apex of the pterygium over
the cornea is called the head, the main mass over the
sclera is the body and the junction of the head and the
body at the limbus is the neck of the pterygium. In
front of the head there is sometimes a line of infiltration
indicating the progress of the lesion. Sometimes a
pigmented line is found ahead of the apex called
Stoker’s line, which is due to deposition of hemo-
siderin pigment on the Bowman’s membrane. Fig. 19.2: Infected pinguecula showing congestion
tendency for growth is inherited. Dellen formed at the

limbus due to dryness of eye, is covered by the ptery-
gium. Ultraviolet light acts upon the DNA in fibro-
blasts which multiply and invade the cornea.
Microscopically histological section shows an
elastotic degeneration of the collagen tissue of the
stroma of the conjunctiva. There may be cystic changes
in the lesion. Rarely some secondary changes like
calcification and neoplastic transformation are seen.
Treatment
This is mostly surgical. Local injection of cortico-
steroids have been tried with little success. Use of dark
glasses have been suggested to prevent the occurrence
Fig. 19.3: Early nasal pterygium of the lesion. Recurrence after surgical excision is in
the range of 30 to 50%.
1. Primary excision (Figs 19.5 A to C) Head of the
pterygium is lifted and dissected off the cornea.
The dissection is preferably done under the
microscope as it provides precision and a good
judgement about the depth of the lesion. A very
superficial dissection increases the chances of
recurrence and a deeper level may land up into
perforation of the cornea. The surface of the cornea
should be smooth and even. A diamond burr can
be used to polish the surface at the end of the
shaving off the pterygium head. The tissue is then
separated from the sclera underneath, and
conjunctiva superficially. The pterygium tissue is
Fig. 19.4: Nasal pterygium encroaching pupillary area then excised taking care not to damage the medial
rectus muscle. A part of the conjunctiva is also
excised and then the edge sutured with the
mass growing on to the cornea. Apparently the episcleral tissue keeping a part of the sclera bare
pterygium may be thick and fleshy with rapid growth, (Fig. 19.5D). Necessary cauterization can be done
or vascular having color indicating the progressive to stop the bleeding.
nature of the lesion; or, thin and papery, dry, and pale 2. Transfixation (Fig. 19.6) To prevent the regrowth
in color suggesting that it will most probably remain of the pterygium onto the cornea, the apex of the
stationary. pterygium is diverted into one of the fornices and
Pseudopterygium is a similar looking lesion found sutured there. The pterygium tissue can also be
anywhere around the limbus and is mostly due to divided into two and each half transfixed into the
some inflammatory condition of the conjunctiva and corresponding fornix.
cornea. It is not firmly and closely attached to the 3. Free mucous membrane grafting (Fig. 19.7) The bare
underlying structures, i.e. cornea and sclera, and so area of the sclera left behind as in the primary
separation from them is easy. Sometimes a probe can treatment, can be covered up by a mucous
be passed underneath its neck which is not possible membrane graft. The material used is preferably
in a true pterygium. the free conjunctiva from the same or opposite eye
Exact etiology is not known but as with pinguecula, or rarely the buccal mucosa.
it is thought to be most probably due to dryness of 4. Corneal grafting (Fig. 19.8) The corneal defect
the conjunctiva produced by dust, heat, sunlight, and created by the dissection can be filled up by
hot winds. Rarely seen before the age of 20 years, lamellar corneal graft to make the tissue even.
Chapter 19: Degenerative Conditions of Conjunctiva 129
Figs 19.5A to D: Schematic diagrams of simple pterygium excision. (A) Dissecting the head off the cornea. (B) Excising the
pterygium tissue under the conjunctiva. (C) End to end suturing of the cut conjunctiva. (D) Bare sclera with suturing the conjunctiva
to the episcleral tissue
Fig. 19.6: Schematic diagram showing transfixation of the Fig. 19.8: Schematic diagram showing
pterygium tissue into the lower fornix corneal graft in position
Lamellar keratoplasty is also indicated when

pterygium is in the pupillary area. Dissection alone
results in irregular scarring. To improve visual
acuity lamellar keratoplasty is required.
5. Traction suture (Fig. 19.9) In cases with recurrence
and dense fibrosis in the medial canthal area, a
pullover suture is passed under the medial rectus
and is taken out onto the skin at the lateral canthus.
The eyeball is kept in the position of abduction for
one week. This helps in immobilization of the graft
put on the sclera and prevents anchorage of the
Fig. 19.7: Schematic diagram showing free
graft put in the bare area globe in the position of adduction.
REFERENCES
1. Cameron. Histology of pterygium. Br J Ophthalmol

1983;67:604.
2. Char DH. In the Cornea, Scientific Foundation and Clinical
Practice.
3. Smolin G, Thoft RA. Little Brown and Co, Boston/Toronto,
1983.
4. Dunn JP. Development of scleral ulceration and calcification
after pterygium excision and mitomycin therapy. Am J
Fig. 19.9: Schematic diagram showing a pullover suture Ophthalmol 1991;112:343.
passed to keep the eyeball abducted 5. Foirier RH, Fish JR. Lamellar keratoplasty for recurrent
As the recurrence rate is high after simple excision pterygium. Ophthalmol Surgery 1976;7:38.
certain postoperative measures have been suggested 6. Hilgers JH. Pterygium. Its incidence, heredity, and etilogy.
Am J Ophthalmol 1960;50:634.
by different workers:
7. Jaros PA. Diagnostic and surgical technique for pinguecula
1. Beta radiation from strontium 90 source can be
and pterygium. Surv of Ophthalmol 1988;33:41.
used in the dose of 2500-3000 rads. 8. Naib K. Conjunctival graft following excision of recurrent
2. Mitomycin-C eyedrops in the concentration of 2 pterygium. Am J Ophthalmol 1964;58:861.
μg powder dissolved in 5 ml of normal saline or 9. Rajiv. Pterygium and dry eye: A clinical correlation. Ind J
5% glucose are started from the first postoperative Ophthalmol 1991;39:15-16.
day and continued for 7 days. Intraoperative use 10. Small RG. In oculoplastic, orbital, and reconstructive surgery:
of Mitomycin-C has been practiced with doubtful Edited by Hornblass, Williams and Wilkins, vol 1 1988.
effect. 11. Stark T. Conjuctiva autograft for primary and recurrent
3. Argon laser has been applied to obliterate the pterygia: Surgical technique and problem management.
neovascular fronds. Cornea 1991;10:196-202.
SECTION 3: DISEASES OF CORNEA
Chapter 20
Applied and Functional

Anatomy of the Cornea
Nitin K Dutta, LC Dutta
Cornea is the anterior transparent portion of the coat is demarcated by a sulcus, due to difference of
of the eye ball. It also is a part of the ocular surface, curvature of the cornea, and that of the rest of the
major part of which is contributed by the conjunctiva. eyeball.
It is a highly specialized tissue that refracts and The central one-third of the cornea measuring
transmits light through the aqueous humor and about 4 mm, is the optical zone of the cornea. Towards
crystalline lens to the retina. The diameter of the the periphery, the cornea becomes slightly flatter and
cornea is 11.5 mm to 12.5 mm; average measurement tends to flatten more on the nasal side.
is 11 mm in vertical meridian and 12 mm in the
horizontal meridian. Curvature of the cornea is 8 mm
on the anterior surface and 7mm in the posterior
surface. The difference of curvature of the anterior and
posterior surfaces is due to difference in thickness of
the central part of the cornea, and its peripheral part:
Thickness of the peripheral part is 1mm, and that of
the central part 0.57 mm. 1 There exists a diurnal
physiological variation of thickness of the cornea. In
intact human cornea, a slight increase in thickness of
0.0085 mm (at least 1.55%) immediately on waking
from natural sleep, followed by the gradual thinning
in the daytime until late afternoon. The cornea is
thickest in the early morning on getting up from bed.
This variation of thickness is due to evaporation of
fluid from the corneal surface, when the eye remains
wide open.
Horizontally oval shape of the cornea, is the result
of encroachment of the sclera and conjunctiva in upper
and lower portion. Viewed from the posterior surface,
the cornea appears to be circular. The junction of the
clear cornea and the opaque sclera is the limbus. As
the radius of curvature of the cornea is 7 mm and that
of the eyeball is 12 mm, the corneal apex forms an
anterior prominence. The junction of cornea and sclera Fig. 20.1: Section of the cornea
132 Section 3: Diseases of Cornea
Microanatomy of the Cornea Bowman’s Membrane

Cornea has got five distinct layers: It is formed by condensation of the superficial fibers
A. Epithelium of the substantia propria. Under light microscopy, it
B. Bowman’s membrane is called a membrane, but under electron microscopy
C. Substantia Propria it may be called a layer, as it consists of randomly
D. Descemet’s membrane dispersed collagen fibrils, and it is 12 to 14 microns
E. Endothelium thick; its posterior border is seen to merge with the
corneal stroma. Numerous pores are seen in the
Epithelium membrane for passage of the terminal branches of the
corneal nerves.
Anterior surface of the cornea is derived from surface
ectoderm, and is composed of nonkeratinized
Substantia Propria
stratified squamous epithelium of four to six layers
thickness. The basal columnar cell layer is attached to Substantia propria or corneal stroma is about 500
the basement membrane or basal lamina by microns thick and contributes to 90 % of corneal
hemidesmosomes. thickness. It is composed of collagen producing
fibroblasts better known as keratocytes or corneal
corpuscles, ground substance and collagen lamellae.
The lamellae are very uniformly arranged. Ground
substance consists of mucoprotein and glycoprotein.
Corneal corpuscles (keratocytes) contribute to about
2.5% of the volume of the stroma. These cells are
basically fibroblasts and they are found throughout
the stroma between and occasionally extending into
the lamellae. In addition to collagen, the keratocytes
synthesize mucoprotein.
Descemet’s membrane (The Posterior Elastic

Membrane)
It is a strong well defined sheet in between the
substantia propria and endothelium; structurally and
functionally, it is a basement membrane of the
endothelial cells . It is formed by a cuticular secretory
product from the endothelial cells. At birth its
Fig. 20.2: Structure of Hemidesmosomes thickness is 3 to 4 microns, and as the secretory product
goes on depositing during the postnatal life, in adult
Arising from the basal layer, there are two or three its thickness is about 10 to 12 microns. The anterior
layers of polygonal cells with wing like lateral portion of the membrane, which begins to develop
extensions, and hence they are also called wing cells. during intrauterine life, shows a banded character and
Superficial cells are extremely long and thin with the portion developed during post natal life is of
highly irregular surfaces due to presence of microvilli. uniform appearance. Descemet’s membrane continues
The precorneal tear film makes their surfaces to appear peripherally beneath the sclera as a meshwork known
optically smooth. There appears to be a continuous as pectinate ligament from which strands may pass
migration of epithelial cells from the basal layer to be inserted into the ciliary muscle and sclera. In
towards the surface, and the superficial cells are elderly people excrescences may be deposited over
constantly shed off. In the peripheral part of the cornea the posterior surface of the Descemet’s membrane in
histiocytes, macrophages, lymphocytes, and the peripheral part of the cornea. These are known as
melanocytes are also found in between the epithelial Hassall-Henle bodies; when these bodies are
cells. deposited in the central zone, the condition is known
Chapter 20: Applied and Functional Anatomy of the Cornea 133
as corneal guttata. In Fuchs’ corneal dystrophy large a. Superficial lipid layer
number of deposits may be found with loss of b. Middle aqueous layer
endothelial cell population. c. Deep mucus layer
a. The lipid or oily layer consists of waxy and
Endothelium cholesterol esters, secreted from the Meibomian
glands and the glands of Zeiss and Moll. This layer
The corneal endothelium is continuous across the helps to keep the epithelial surface moist by
angle of the anterior chamber with the endothelial preventing evaporation of tear fluid, and also
layer of the anterior surface of the iris. The apical lubricates the eyelids, as they pass over the surface
surface of the hexagonal cells with the nuclei and of the globe. This layer increases surface tension
abundant mitochondria lies in contact with aqueous and assists in the vertical stability of the tear film
humor of the anterior chamber. Endothelial cells play so that tears do not overflow the lid margin. Lipid
a major role in active transport and maintenance of layer contributes to about one fifth of the whole
deturgescence of normal corneal stroma. Endothelial thickness of the film.
cells do not regenerate and the overall number of b. Aqueous layer forms the main thickness of the tear
endothelial cells decreases with age. film. The aqueous contains in dissolved form
The area of the posterior surface of the cornea is inorganic salts, glucose, urea and some proteins.
about 147 mm2. The normal cornea has about 3,00,000 Functions of this layer are supply of nutrition and
to 6,00,000 endothelial cells. Human endothelial cells atmospheric oxygen to the cornea, prevention of
cannot be replaced, as there is no mitotic division; but bacterial activity with the help of lactoferrin, and
the gaps produced by the defunct cells are covered lysozyme content of tear fluid and smoothening
by spread of the adjacent cells. Therefore there is of any minute irregularity of the corneal surface.
diminution of the population of endothelial cells with The aqueous layer is formed from the secretion of
age, and the size of the endothelial cells of elderly the main lacrimal gland as well as from the
people are larger than those of children, a condition accessory lacrimal glands, situated in the upper
known as polymegathism. conjunctival fornix.
c. The mucus of the mucous layer is secreted from
Development of the Cornea the goblet cells of the conjunctiva. Mucin acts as a
natural wetting agent. It is absorbed over the
After formation of the lens vesicle, mesodermal cells surface of the corneal epithelium . With every blink,
invade the space in between the surface ectoderm and the mucin is spread over the epithelial surface and
the lens. A single row of mesodermal cells grow acts like a primer paint to allow the aqueous, tear
parallel to the surface ectoderm to form the endothelial and lipid component to spread by the blinking
layer which by secreting a cuticular substance form action to create a three layered tear film.
the Descemet’s membrane by the fourth month of Immediately after each blink, evaporation begins
intrauterine life. Substantia propria is formed from the and the film becomes thin and breaks up by
mesoderm in between the ectoderm and Descemet’s forming dry spots. With each subsequent blink the
endothelial layer. surface is recoated and the cycle repeats itself. The
time between the blink and the appearance of the
Precorneal Tear Film first dry spot is known as the break-up-time (BUT)
The cornea and conjunctiva are kept constantly of the tear fluid. Normally the BUT is greater than
lubricated by the secretions of the mucous and the interval between two consecutive blinks. BUT
lacrimal glands. These secretions form a film in front can be ascertained by instilling a drop of mixture
of the cornea called the tear film or the precorneal tear of 1% Rose Bengal and 2% Fluorescein into the
film. The film can be observed with the slit lamp, when conjunctival sac and the tear film break up spots
the beam is focused upon the fine particles which are can be identified under the slit lamp biomicroscope.
suspended in the film. If the lower lid is moved CONGENITAL ABNORMALITIES OF CORNEA
upwards over the globe with the finger, the fine
particles can be seen to move upwards. Microcornea (Anterior Microphthalmos)
The precorneal tear film is composed of three When corneal diameter is less than 11 mm, it is called
layers: microcornea. True microcornea unassociated with
other ocular abnormalities is a recessive hereditary may be affected and there may be arcades of vessels
disorder and is not a very common occurrence. overlying the opacity. Occasionally, it is associated
Persistent pupillary membrane, microphthalmos and with cornea plana, microphthalmos and anterior
colobomatous defects are associated developmental chamber anomalies. It may be inherited as autosomal
anomalies. The cornea is otherwise normal. The recessive trait.
anterior segment of the eye is frequently shortened.
These eyes have a tendency to develop glaucoma.
Congenital Corneal Opacity (Leucoma)
Megalocornea (Anterior Megalophthalmos) This is usually a bilateral condition, in which there is
It is a recessive sex linked condition. Horizontal a dense central corneal opacity. Usually the iris is
corneal diameter is more than 13mm. It may occur adherent to the back of the opacity. It may be
without other associated abnormalities of the eye or associated with raised intraocular pressure due to
with an enlargement of the entire anterior segment peripheral anterior synechia or some abnormalities in
(anterior megalophthalmos). This should be the trabecular meshwork. The pathological process
differentiated from megaloglobus secondary to involves all the layers of the cornea. The cause of the
buphthalmos, where the entire globe is enlarged with lesion is not definitely known; adhesion of iris or lens
horizontal breaks in Descemet’s membrane, known to the leucoma may be the effect rather than the cause.
as Haab’s Line and secondary corneal edema. It is important to differentiate the condition from
clouding of the cornea due to birth trauma, buph-
Cornea Plana thalmos, metabolic disorders or congenital
dystrophies.
In this rare condition the anterior corneal curvature is
reduced so that it may be almost flat. The anterior
sclera may also be flattened. There may also be other Congenital Anterior Staphyloma
congenital abnormalities like corneal opacity, In this condition the cornea is opaque and bulges
coloboma, cataract, etc.
forwards; as in acquired anterior staphyloma, the iris
is adherent to the cornea. Congenital staphyloma may
Anterior Embryotoxon
be a further pathological change of congenital leucoma
This is a ring shaped opacity, 1 mm broad, involving or due to intrauterine corneal infection.
the anterior part of the stroma and concentric with
the limbus, leaving a clear cornea in between the
Posterior Keratoconus
limbus and the opacity. This is also called Arcus
Juvenilis as opposed to arcus senilis, that occurs in In posterior keratoconus, the anterior surface of the
elderly persons. cornea is of normal curvature but the posterior surface
has increased curvature with dome shaped excavation.
Posterior Embryotoxon It is due to some developmental defect of the cornea,
This is nothing but an excessively prominent and is not considered as a primary dystrophic change.
Schwalbe’s line (Peripheral termination of Descemet’s Usually this condition is not associated with visual
membrane) that is usually seen on gonioscopy. There defect, and hence treatment is also not necessary.
may be other congenital abnormalities in the
structures of the angle of the anterior chamber. When PIGMENTATION OF THE CORNEA
the iris processes are inserted into the Schwalbe’s line,
it is known as Axenfeld’s anomaly. Following types of pigmentation may occur in the
cornea:
Congenital Sclerocornea
Iron
Due to non-differentiation of the mesoderm forming
the sclera and cornea, the latter may become a. Siderosis: Brownish pigment deposited in the
completely opaque and cannot be differentiated from corneal stroma in intraocular iron foreign body
the cornea. Sometimes only the periphery of the cornea retained for a long time.
Chapter 20: Applied and Functional Anatomy of the Cornea 135
b. Fleischer Ring at the base of the cone of keratoconus female, it is thinner than in males and adults.
due to deposition of hemosiderin pigment in the Posteriorly scleral thickness is about 0.7 mm. At the
epithelium of the cornea site of insertion of the rectii muscles, it is less than 0.5
c. Hudson-Stähli’s line, which is also due to deposi- mm. The sclera has got three sets of apertures for
tion of hemosiderin pigment resulting from linear passage of nerves and vessels to and from the eyeball.
break in the epithelium horizontally at the junction a. Opening for the optic nerve is bridged by fibrous
of the upper two-thirds, and the lower one third tissue known as lamina cribrosa and around this
of the cornea commonly found in elderly persons. opening there are apertures for long and short
d. Stoker-Busaca line, a brownish line in the epithe- posterior ciliary arteries and ciliary nerves.
lium of advancing head of pterygium, is also made b. Middle sets of apertures are just posterior to the
up of hemosiderin pigment. equator for passage of the vortex veins and
e. Ferry’s line develops from hemosiderin pigment perivascular lymphatics.
around the filtration bleb. c. The anterior set of apertures near the limbus is for
f. Epithelial hemosiderin pigment deposition may the passage of the anterior ciliary vessels and
also be seen in the superficial scars of radial nerves occasionally with some lymphatics.
keratotomy (Probable source of hemosiderin The sclera consists of dense bands of collagenous
pigment is perilimbal blood vessels and transferrin tissue, closely packed and arranged in an irregular
present in the tear fluid).
fashion. The water content of the sclera is about
65%(that of the cornea is about 80%). Criss-cross
Silver arrangement of the collagenous tissue and less water
content are the main factors for lack of transparency
Deposition of silver salts in corneal stroma, known as
of this structure.
argyrosis results from prolonged use of silver nitrate
eye drops; however this preparation is rarely used Extending from the margin of the cornea upto the
now. optic nerve, the sclera (globe) is enveloped in a thin
avascular fibrous membrane known as the Fascia Bulbi
or Tenon’s capsule. Underneath the Tenon’s capsule
Copper
is a layer of loose vascular tissue known as episclera
Kayser-Fleischer Ring found in Hepato-Lenticular that contains a few fibroblasts, melanocytes,
(Wilson’s) disease, is deposition of copper in the macrophages, and lymphocytes.
peripheral part of the Descemet’s membrane; this Sclera is developed by condensation of the paraxial
forms a golden yellow ring adjacent to the limbus. mesoderm around the seventh week of intrauterine
life. Condensation starts anteriorly and reaches the
Gold posterior pole by the fifth month.
Gold salt used for treatment of joint diseases may be Blood Supply
deposited in the substantia propria and is known as
Blood vessels of the episclera are not easily seen in a
chryasis.
uninflammed eye, but when the eye becomes
congested following inflammation three separate
Melanin vascular plexuses become prominent.
Krukenberg’s spindle seen in the central rear portion 1. Superficial bulbar conjunctival plexus
of the cornea is due to melanin pigment deposited on 2. Episcleral plexus, anterior and posterior: anterior
the endothelium, usually found in Pigment dispersion from the rectii muscles and posterior from the
syndrome. oblique muscles as well as from the vessels of the
optic nerve sheath.
ANATOMY OF THE SCLERA 3. Scleral or deep episcleral plexus from the anterior
The sclera forms the posterior five-sixths of the fibrous ciliary vessels. At the limbus superficial and deep
protective coat of the eye. Sclera ends anteriorly at the episcleral plexuses merge into one another and
limbus and posteriorly at the optic nerve. Thickness terminate in the superficial marginal plexus of the
of sclera varies with age and sex; in children and in cornea.
Congenital Anomalies of Sclera tissue in the dermis and subcutaneous tissue of the
Blue Sclera: Blue sclera may be due to the color of the skin, and articular ligaments giving rise to
choroidal structure as a result of thinning of the sclera. hyperelasticity and hyper-extensibility of the skin.
It is a common occurrence in children. Blue sclera may Ocular abnormalities consist of thinning of the sclera
be a congenital anomaly occurring alone or associated showing the appearance of blue sclera, keratoconus,
with brittle bones or osteogenesis imperfecta and microcornea, subluxation of lens due to laxity of the
deafness. zonules, angiod streaks and degenerative changes in
Bruch’s membrane. This syndrome is usually
Ehler-Danlos Syndrome autosomal dominant, but autosomal recessive
This syndrome is characterized by loss of collagen inheritance may also occur.
Chapter 21
Various Methods of Examination

of the Cornea
S Basti, S Sabherwal, S Gupta
The examination of the cornea involves evaluation of remain the same. They essentially consist of the
its structure and function. The examination techniques following two primary components:
assess these two aspects individually or simul- i. The slit lamp illuminator—originally fashioned
taneously. Most of these techniques are simple and by Gullstrand.1
can be performed routinely in the office. The various ii. The biomicroscope—a refined version of the
techniques used for corneal examination are the original Czapski’s stand mounted binocular
following: corneal microscope.
1. Slit Lamp biomicroscopy The slit lamp illuminator provides the precise and
2. Pachometry widely adjustable lighting required for the assessment
3. Fluorophotometry of subtle changes. The biomicroscope provides a
4. Keratometry
magnified three dimensional view that can be
5. Corneal topography
observed or photographed.
6. Aesthesiometry
The slit illuminator has controls that allow adjust-
7. Specular microscopy (Detail in Chapter 22)
ment of the intensity, height, and width of the beam.
8. Ultrasound biomicroscopy.
Additional features include filters (red free, fluorescein
SLIT LAMP BIOMICROSCOPY exciter, neutral density, and polarizing) that may be
placed in the path of light. A gauge to indicate the
Clinical slit lamp biomicroscopy and photo slit lamp height of the slit beam for the purpose of measure-
biomicrography, due to their dynamic flexibility, ment, adjustments that permit small horizontal or
permit examination of the cornea with a wide choice vertical displacements of the slit beam from the usual
of magnification, angles of view, and forms of illumi- vertical display to an oblique or even horizontal
nation. The sophistication of modern photographic presentation, are also present. The biomicroscope is
instruments makes possible the documentation of less complex and incorporates adjustments for
even minute changes. The success in slit lamp bio- observer’s interpupillary distance and variable
microscopy and biomicrography requires a clear magnification. Slit Lamp biomicroscopy requires
understanding of the principles and applications of considerable flexibility in instrument design to permit
all the available forms of examination and illumi- the simple and independent manipulation of both the
nation. slit illuminator and the biomicroscope. Also, the slit
illuminator and biomicroscope are coupled co-
Modern Clinical Slit Lamp Biomicroscope pivotally to provide the necessary parfocal and
While several designs of the slit lamp biomicroscope isocentric relationship between the two, i.e. they focus
are currently available, their basic operating principles on the same plane simultaneously and the slit centers
in the field of view regardless of the angle between two should be increased as much as possible. In
the slit illuminator and the biomicroscope. addition, careful positioning of the slit will
maximize the information about the abnormality
Forms of Illumination: under study. If it is located at the level of the
Principles and Applications endothelium, its features will be diffuse if viewed
through illuminated epithelium and stroma.
The slit lamp permits various modes of illumination.
Topographic information can also be effectively
Appreciation of subtle corneal details often
demonstrated with a narrow slit beam. Defects in
necessitates examination by more than one method.
the cornea are seen as deviations of the slit away
from the source, whereas elevations such as bullae
Direct Illumination
are deviated toward the illuminating source.
Methods of direct illumination that are useful in c. Specular reflection A specular reflection (from Latin
examining the eye include direct focal illumination ‘specularis’ meaning mirror like) is the reflected
with a wide slit beam, optical sectioning, and specular image of the light source itself. Snell’s Law of
reflection. optics, i.e. the angle of incidence equals the angle
a. Direct focal illumination Using a wide slit beam is of reflection, dictates that the specular reflection
one of the simplest means of appraising the general will only be seen when viewed from the correct
condition of the eye at low magnification. It is the position. The brightness or intensity of the reflec-
first step in the slit lamp examination that provides tion depends on the reflectivity of the surface, that
an overview, which may prompt and further is, the efficiency with which the incoming light is
investigate the more selective illumination. reflected. The clarity or definition of the reflection
b. Optical sectioning This is achieved by the projection is influenced by the texture of the reflecting surface.
of a very narrow precisely delineated and highly A common example is the sun’s reflection on the
concentrated slab of light through the transparent surface of a lake. The undisturbed water reflects a near
cornea without illuminating adjacent areas. This mirror image of the sun. The broken reflection indi-
optical section may be likened to a surgical section cates irregularity of surface.
of the cornea, where half of the cornea is actually Specular reflection permits assessment of the
cut away producing a cross sectional view. This integrity of the optical surfaces such as the front and
cross sectional view of the cornea permits simul- back surfaces of the cornea. The specular reflection
taneous examination of the epithelium, stroma and from the normal anterior corneal surface (in actuality,
endothelium, and is best seen when there is a the tear film layer overlying the cornea) is very bright
considerable angular difference between the and mirrors the shape of the illumination source
illuminating source and the biomicroscope. To faithfully. When the corneal surface is irregular, the
produce an optimal section, both the biomicro- specular reflection will be irregular.
scope and the slit illuminator should be placed Perhaps the most frequent application of specular
approximately at 30 degrees on either side of the reflection is in the examination of the endothelial layer
optical axis of the eye. of the cornea. The normally flat surface of the
With a standard relationship between the eye, endothelial cells is highly reflective, whereas their
the biomicroscope, and the slit illuminator, the slit junctional borders being of slightly uneven topo-
beam permits appreciation of relative distances graphy do not reflect the light and are seen by negative
between certain surfaces. Thus, projecting a narrow contrast. Similarly, disturbances in the normally flat
slit beam on to the cornea at an angle of 45 degrees cellular layer results in an alteration in the specular
gives a section from which one can assess the reflection making abnormal areas ‘visible’ as dark
relative thickness of the cornea. Depending upon nonreflective area (Fig. 21.1). At magnifications of 25
the angle at which the slit beam strikes the cornea X and 40 X, individual cells themselves may be
relative to the position of the biomicroscope, a appreciated.
variable amount of overlapping of the illuminated To locate the specular reflection and the cellular
anterior and posterior corneal surfaces will be seen. pattern on the endothelium, the bright reflection on
The smaller the angle between the illuminator and the front surface of the cornea should be focused and
the biomicroscope, the greater the overlapping. To centered in the field. With the slit illuminator set to a
diminish this overlapping, the angle between the moderate slit beam approximately 30 degrees from
Chapter 21: Various Methods of Examination of the Cornea 139
Although this may not give information about
the texture of an abnormality, it can help to deter-
mine and record its general size, shape, and
location (Figs 21.2A and B).
b. Sclerotic scatter Subtle corneal abnormalities not
readily visible or visible only in isolated corneal
sections, may be effectively demonstrated with
sclerotic scatter. Sclerotic scatter is especially useful
to show the distribution of changes within the
cornea which are best seen against a dark unillumi-
nated background. With the slit illuminator offset
from its usual isocentric position, a broad slit beam
is directed at the limbus. This results in the
absorption of light by the sclera; light is then
Fig. 21.1: Slit lamp photograph demonstrating cornea scattered or piped throughout the cornea by total
guttata on specular reflection internal reflection. When the cornea is normal,
nothing disturbs the passage of this light, which
therefore is not visible. Only a halo of light is seen
the biomicroscope, the endothelial reflection will be at the limbus which is reflected by the greater
seen as an area of considerably less reflectance adjacent optical density of the scleral tissue. When an
to the bright epithelial reflection on the side opposite abnormality is present in the cornea it becomes
from the illuminator. By moving the microscope
forward towards the cornea (0.52-0.57 mm), the
endothelial cells would be visualized. By moving the
subject eye rather than the illuminator, a considerable
area of the endothelium may be examined. Slight
movement of the subject eye not only in the horizontal
but in the vertical direction as well, helps to locate the
endothelial reflection.
Indirect Illumination
Indirect illumination is especially useful for examining
and photographing subtle changes which require
enhancement of contrast for visualization.
Specific techniques include proximal illumination,
sclerotic scatter, and retroillumination. Indirect illumi-
nation is the secondary illumination of a structure by
reflected light either by its surround or another
surface, which in turn becomes the actual source of
illumination for the target. Thus, indirect illumination
effectively places an illumination source within the
eye, behind or beside the subject of interest.
a. Proximal illumination Occasionally, direct visuali-
zation of an abnormality within the eye may be
blocked by light reflecting from overlying tissue.
With a moderate slit beam directed adjacent to the
area of interest, the absorption and scattering of
light around and behind the abnormality will Figs 21.2A and B: (A) Keratoprosthesis seen on diffuse
increase its contrast producing a silhouette against illumination, (B) Finer details of the prosthesis and sutures are
a new lighter background. seen using proximal illumination
visible by deflecting or scattering part of the light

toward the biomicroscope.
c. Retroillumination Light reflected from the iris or
fundus can indirectly illuminate subtle abnor-
malities in structures anterior to these surfaces.
With these techniques, abnormalities are viewed
against the bright background created by the
reflecting surface. Retroillumination from the
fundus makes possible the simultaneous exami-
nation and photography of the lens and cornea.
Direct and indirect retroillumination from the iris
is also an excellent technique for demonstrating
subtle corneal abnormalities, which may be only
slightly less transparent than the normal cornea
(Figs 21.3A to C).
Direct Retroillumination from the iris2: Here, the bio-
microscope is focused on the cornea and the slit is
deflected to one side and the beam directed to strike
and illuminate the iris surface behind the region of
the cornea being observed. Thus, the cornea is
secondarily illuminated from behind by the light
reflected from the iris surface. Abnormalities of the
cornea overpowered by direct focal illumination
become visible. A moderately wide beam is most
effective and should be directed at a sufficiently
tangential angle to avoid directly illuminating the area
under study.
Indirect Retroillumination from the Iris: A
modification of the direct technique, this control
method is even more effective in delineating subtle
pathologic changes. The slit beam here is directed even
more tangentially onto the iris surface.
The intended area of cornea is seen against a region
of dark unilluminated iris or even the darker pupillary
background. Light scattered by distant illuminated iris
provides sufficient illumination to seem transparent
and remain invisible.
In practice, direct and indirect retroillumination
from the iris are usually used in combination and may
be most effective at the interface between light and
dark backgrounds where optimum information is Figs 21.3A to C: (A) Fluorescein stained epithelial defect (B)
generally achieved. The same illuminated with cobalt blue light, (C) The defect
Retroillumination from the Fundus: Retroillumination visualised using Kodak Wratten (15) barrier filter
from the fundus provides a brighter background to
visualize corneal changes. With the pupil well dilated, enhance the intensity of this ‘red reflex’ slight side
a moderately wide slit beam is introduced into the adjustments of the nearly coaxial slit illuminator can
eye; light reflected from the fundus gives a be dramatically effective.
characteristic orange color to the reflection (The color For a large area of useful information, the slit beam
and density of the retinal pigment epithelium and should be introduced at the pupillary margin. If the
choroid and therefore their reflectivity can vary widely slit beam is left in the usual isocentric position the
influencing individual exposure requirement). To subject eye must be greatly decentered. Configuring
the slit into a half moon (not possible with all slit Seidel test4 The Seidel test is used to determine the
lamps) optimizes light input without producing integrity of the cornea. When a corneal perforation is
artifacts from an illuminated iris. suspected, the applications of fluorescein can demon-
Another factor may be used to increase the strate the leakage of aqueous humor from the anterior
intensity of retroillumination. By rotating the subject chamber. The moistened tip of a fluorescein strip is
eye nasally, the optic nerve head should be positioned applied directly to the suspected site of leakage. Then,
to act as a reflecting surface of the slit beam. Because if the aqueous is indeed flowing, it dilutes the applied
of its greater reflectivity more intense retroillumi- fluorescein which is seen being washed down the
nation may be obtained. surface of the cornea (Fig. 21.4).
Diffuse Illumination3 Rose bengal

Here a broad beam slightly out of focus is thrown at Rose bengal stain was believed to be a vital dye which
an obtuse angle over a wide area. This technique thus would stain only degenerated or devitalized cells.
permits examination of a large area of the cornea However, recently it has been proven in experimental
though not in detail. settings5 that rose bengal staining ensures wherever
there is poor protection of surface epithelium by the
Role of Vital Dyes in Corneal Examination preocular tear film. Thus in normal settings, it is the
Vital dyes or stains provide additional information in protective function of the tear components like mucin
certain situations. Rose bengal is a bright magenta dye and albumin, which is responsible for negative
which is highly effective in delineating small areas of staining.
epithelial compromise where cells are unhealthy but Rose bengal permits definition of epithelial
still in place. damage. In cases of toxic epithelial keratopathy, the
Fluorescein, on the other hand, stains areas where fine punctate areas of rose bengal staining of the
the epithelial cells are missing. corneal epithelium are demonstrable by direct
illumination. Rose bengal may demonstrate such fine
Sodium Fluorescein areas of staining not demonstrable by fluorescein.
Additionally, an exciter filter is not necessary permit-
Staining Topical application of fluorescein is
ting the use of normal settings for correct exposure.
performed either with sterile fluorescein strips or with
Excess rose bengal must be irrigated out to avoid
a freshly prepared 2 percent solution of sodium
confusing the desired information with pooling of the
fluorescein. Direct contact of the fluorescein strip with
dye. Rose bengal may be poorly tolerated by some
the cornea must be avoided. The excess fluorescein
patients due to its irritating nature. A drop of
from the conjunctival sac should be irrigated out or
anesthetic fluid may be instilled in the conjunctival
mopped away with a sterile cotton swab.
sac prior to instillation of rose bengal
High concentrations of fluorescein are readily
visible with white light. An exciter filter enhances its
visibility which is especially important when only
minute quantities are present. The most common filter
used is “Cobalt Blue” filter often a Kodak Wratten 47A.
While this filter is quite satisfactory for this purpose,
a more refined filter such as the Spectrotech SE 40
(exciter filter) is far more efficient. The commonly seen
blue background is a direct result of the illuminating
light passing through the blue filter. The yellow of the
exited fluorescein is seen in relief against the blue
background. When greater selectivity is desired a
barrier filter such as the Kodak Wratten 15, (Figs 21.3A
to C) or the more selective matched barrier filter for
the Spectrotech, the SB 50, may be used. The barrier is Fig. 21.4: Positive Seidel test—leak of fluorescein from the 4
placed either at the camera in front of the film plane O’clock graft host junction (Note: The presence of epithelial
or directly over the objective lens of the biomicroscope. defect is responsible for staining centrally)
Other Techniques Optical Focusing

Corneal iron lines such as the Ferry’s line seen near Certain specular microscopes are so calibrated that
the head of the pterygium and the Fleischer’s ring at when the endothelium is in focus, the thickness of the
the base of the cone of keratoconus are best visualized cornea is automatically displayed digitally. At the start
with the cobalt blue filter. The blue filter in this of the measurement, care must be taken to establish
application is not used as an exciting agent. Instead, the zero by focusing on the interface between the
the iron line absorbs the blue color resulting in a darker contact element and the epithelial layer.
more visible pattern.
Ultrasonic Pachometry9
PACHOMETRY (PACHYMETRY) Ultrasonographic techniques have been refined to the
point that corneal thickness can be measured. The
Corneal thickness is an important indicator of corneal technique used is according to the principles of
endothelial function; the collagen fibers of the stroma ultrasonographic measurement of the axial length of
and an increase in corneal hydration can manifest itself the globe.
only as an increase in corneal thickness.6 Pachometry Increased use of ultrasonic pachometry, especially
(or pachymetry) is currently done by the following in keratorefractive surgery bears out the main
three different methods.7 advantages of this technique. It is a rapid and accurate
test; it can be used in supine or sitting positions and it
Optical Doubling8 readily scans the entire cornea.
The ultrasonic pachometer averages multiple
An attachment to the slit lamp (Fig. 21.5) gives a split readings taken in one to two seconds by the sound
image of the corneal section. When the amount of waves of a probe when it is held within ten degrees of
doubling is adjusted so that the anterior surface in one the perpendicular to the corneal surface. Earlier
image lines up with the posterior surface in the other models were difficult to use but gel or solid tips are
image, the corneal thickness can be read off directly now replacing the original water filled probes.
from a dial. Measurement of the thickness must be Although various studies suggest that inter and intra-
made perpendicular to the cornea; failure to do so is observer ultrasonographic reading errors are less than
the major source of error in the measurement. 0.005 mm, the degree of accuracy depends on the
While taking the measurement, the images of the measurement site. Even small movements of the probe
from the initial measurement location invalidate the
two small lamps must be on the epithelial line and
accuracy of the values recording changes in thickness
equidistant from the horizontal dividing line. This
produced by measuring adjacent parts of the cornea.
ensures the perpendicular alignment of the optical
Some assessment errors in using this method result
section. from the following: (1) incorrect alignment of the
ultrasonic probe with the cornea. (2) The varying
speed of sound through corneal tissue, and (3)
Difficulty in relocating exactly the same area to
measure corneal thickness sequentially.
Measuring corneal thickness is often a useful
maneuver when subclinical edema is suspected in the
presence of guttata or after disease or surgery. The
normal central corneal thickness is about 0.52 mm;
higher values indicate some endothelial dysfunction.
Epithelial edema with consequent decrease in vision
usually does not occur until the cornea has swelled to
a thickness of 0.65 to 0.75 mm, provided the intraocular
pressure is normal. However, if the pressure is eleva-
ted, epithelial edema occurs at a lesser thickness.10 The
Fig. 21.5: The Haag Streit pachometer value of pachometry lies in estimating the functional
attached to the slit lamp reserve of the endothelium in a clear cornea. A reading
close to 0.50 mm is reassuring for the future whereas size into corneal radius of curvature using simple
one around 0.70 mm means borderline decom- vergence relationships of convex mirrors (Fig. 21.5).
pensation and risk of imminent epithelial edema. Because of the small but continuous movement of the
patient’s eyes, the conventional keratometer doubles
FLUOROPHOTOMETRY the reflected image and measures the image against
itself rather than against a fixed scale.
The barrier function of the endothelium may be The critical element determining the accuracy of
evaluated by measurements of its permeability to the measurement is sharp focusing on the reflecting
various substances, including fluorescein. 11 The image and precise determination of its size. This is
fluorescein can be ingested (10% Fluorescein possible by using the four apertures optical system
solution—5 mg/kg body wt), injected intravenously whose 2 vertical apertures create a single image only
or driven into the corneal stroma from the surface by when the image is in perfect focus. The instrument is
iontophoresis and the diffusion across the calibrated using spherocylinders14,15 and hence any
endothelium can be measured. Fluorophotometers are irregular aspheric cornea (such as diseased or
used to measure fluorescein concentration in the postsurgical corneas) may result in a significant error.
corneal stroma and the aqueous.12 In the peripheral The keratometer samples corneal curvature at only
cornea, fluorescein enters the corneal stroma directly 2 paracentral spots. Different brands of keratometers
from the limbal vessels but in the center, the dye is use different size zones of reflection (0.1-0.4 mm) and
transferred exclusively from the aqueous across the different size separations of the 2 images (2 to 3.6 mm).
endothelium. Hence different instruments record different radius
The fluorescein concentration in aqueous and of curvatures for the same cornea.
corneal stroma changes with time. The cornea contains Different keratometer use different values of
a significant amount of protein that binds fluorescein, “keratometric index of refraction”, which is used to
making it unavailable for diffusion. As a result, only convert the radius of curvature to dioptric power on
about 57 percent of the fluorescein present in the the dial of the keratometer. For example, Bausch and
corneal stroma is diffusible and in equilibrium with Lomb keratometer uses a value of 1.3375, whereas
aqueous fluorescein. The transfer coefficient, an index Zeiss keratometer, of 1.332 and American optical
of endothelial permeability, is markedly increased in instruments, of 1.336. Hence it is difficult to accurately
the eye soon after surgery and is reduced in value with compare readings of two different keratometers.
the passage of time. Thus, measurement of the
endothelial permeability to fluorescein permits
evaluation of the damage to the barrier function of Automated Keratometers
the endothelium and the process of its repair. They focus the reflected corneal image onto an
Patients with cornea guttata and some increase in electronic photosensitive device that instantly records
corneal thickness also have increased permeability to the size and computes the radius of curvature. No
fluorescein suggesting that in early Fuchs’ dystrophy doubling device is used and the measurement can be
swelling is due to a breakdown of the barrier function made faster than the eye movement.
rather than to a low endothelial pump rate.13 The device also measures the image size in many
meridians and then computes the angle of both major
KERATOMETRY meridians, as well as the power in those meridians.
The keratometer (also called ophthalmometer) first A special type of automated keratometer is the
described by Helmholtz14 measures the central corneal hand held keratometer (Fig. 21.6). The principles of
its working are similar to other automated
curvature. Both manual and automated keratometers
keratometer. This is useful for recording keratometry
are available. The principle by which the instrument
readings in pediatric age groups for IOL power calcu-
measures the curvature is contingent upon accurately
lations or monitoring of postoperative astigmatism in
determining the size of a reflected image from the front
cases of penetrating keratoplasty, etc.
surface of the cornea (the first Purkinje Sanson image).
Keratometry forms an important adjunct in
assessing corneal curvature in all cases of astigmatism
Manual Keratometers
and also in conditions with known abnormalities of
It measures the size of an image reflected from the the corneal curvature, such as keratoconus, kerato-
corneal surface. The device then converts the image globus, etc. The average radius of curvature measured
(Fig. 21.7). Currently used esthesiometers are Cochet

and Bonnet’s26 improvisations of the Boberg esthesio-
meters based on the fact that the length of the thread
used to check the corneal threshold is inversely
proportional to the force produced when the thread
is applied to the cornea. There are 2 models of the
Cochet and Bonnet esthesiometer.
The first one, equipped with a nylon monofilament
of 0.08 mm diameter, produces pressures ranging
between 2 and 90 mg per 0.005 mm27. The second one
using a nylon monofilament with a diameter of 0.12
mm produces pressures ranging from 11 to 200 mg
per 0.0113 mm.28 The end surface of the nylon thread
Fig. 21.6: Photograph of the Nidek KM 2000 hand-held covers 4 to 10 corneal epithelial cells and thus
portable keratometer
stimulates one sensitive nerve unit.27,28
by a keratometer ranges from 7.2 to 8.4 mm. Standard More recently, more sophisticated esthesiometers
keratometry also gives the clinician an idea of the have been developed. These include those of
corneal topography when multiple keratometric Schirmer29, Larson30 and Draeger.31 The newer ones
readings are taken by changing the direction of the work on electronic optical device, first fixed on a slit
patient’s fixation.17 lamp and later built as a portable instrument. It
Note Any particular set of keratometer values could presumably provides greater precision when
be associated with an unlimited number of corneal measuring corneal sensitivity thresholds than with the
shapes.18 This follows from the wide variations that esthesiometer of Cochet and Bonnet. Furthermore, the
may occur in the topography, central and peripheral, instrument of Draeger is automatically disinfected
to the keratometer measurement points. This after each measurement by means of heating the
limitation of the keratometer is most likely a major metallic contact thread.31
determinant of the poor correlation that has been Measurement of corneal touch threshold with the
noted between keratometer and refraction Cochet and Bonnet esthesiometer is carried out as
measurements in clinical studies of refractive surgical follows.
procedures.19-24 The subject fixates a point in front of him while
the observer moves the nylon monofilament
CORNEAL ESTHESIOMETRY perpendicularly toward the cornea until the nylon
thread necessary to obtain a response is 50 percent of
Corneal sensitivity is an important parameter in the number of stimulations.
clinical neuro-ophthalmological evaluation. Studies
have shown that the sensory nerves of the cornea exert
a profound influence on the general well being of the
cornea, particularly its epithelial component.25
Testing of Corneal Sensation

In simple clinical method for testing corneal sensation,
the patient is instructed to look straight ahead keeping
the eyes wide open in primary position of gaze. A wisp
of cotton is prepared from a sterilized dry cotton pad.
The cornea is touched lightly with the wisp of cotton.
If normal corneal sensation is intact then there will be
an objective blink of the eyelids and if asked the patient
can feel the soft touch of the cotton wisp. The sound
eye is tested first.
Precise quantitative evaluation of corneal
sensitivity is possible with the use of esthesiometers Fig. 21.7: The Luneau aesthesiometer
Physiological Variations in
Corneal Sensitivity32
Corneal sensitivity is greatest at the apex and least at
the superior limbus.33 It also varies during the day
with the lowest values being measured in the morning
and the highest in the evening. 34 Corneal touch
threshold increases by some 30 percent in the morning,
after a night’s sleep presumably because of prolonged
eyelid closure. Corneal sensitivity also gradually
decreased with advancing age, particularly after the
age of 50 years.35
People with blue iris have been found to have the
most sensitive corneas while people with brown iris
have least sensitive cornea.36 Corneal sensitivity has Fig. 21.8: Ultrasound biomicroscopic evaluation shows
Echodense area in the anterior subepithelial area,
been found to decrease after the 31st week of
demonstrating location of scar. Accurate measurement of scar,
pregnancy.37 Another study has found that the corneal thickness of the scar is possible. Also once central Descemet’s
sensitivity decreases from the 13th week of gestation thickening in this case
onwards.38 Significantly decreased corneal sensitivity
may be due to congenital disorder such as congenital
trigeminal anesthesia, congenital corneal hypoesthesia
and corneal dystrophies and a variety of acquired
disorders such as diabetes, herpes simplex keratitis,
neuroparalytic keratitis, leprosy, Adie’s tonic pupil,
myasthenia gravis, and toxic injury. Surgical proce-
dures such as limbal corneal incisions and corneal
grafts, refractive corneal surgery, and retinal reattach-
ment surgery can also induce a reduction in corneal
sensitivity. Contact lens wearing and laser retinal
photocoagulation are other causes of reduced corneal
sensitivity. Topical beta blockers, atropine, and anes-
thetics also decrease corneal sensitivity which becomes
normal on discontinuation of the drug.32 Fig. 21.9: Ultrasound biomicroscopic evaluation in a patient
scheduled for penetrating keratoplasty demonstrates iris
Ultrasound Biomicroscopy adhesions to cornea
Ultrasound biomicroscopy (UBM) uses a high
frequency (50-100 MHz) and provides high resolution
images of the anterior segment. Imaging with UBM
has an axial and lateral resolution of upto 20 m
although its penetration is limited to approximately
5mm. Thus detailed visualization of the cornea and
other anterior segment structures is possible with this
technique.39 This modality can be used to document
the exact depth of a pathology like dystrophy or a
corneal scar (Figs 21.8 and 21.9) and thus can help in
assessing the patient prior to phototherapeutic
keratectomy (PTK). 41 Details of anterior segment
behind the edematous or opaque cornea can also be
visualized.42 Corneal endothelium can be examined
with specular microscope (Fig. 21.10). Fig. 21.10: The keeler wide field contact specular microscope
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Hamburg, Germany, leopold voss, 1909. 36. Millodot M. Do blue eyed people have more sensitive corneas
15. Dabezies OH, Holladay JT. Measurement of corneal curva- than brown eyed people? Nature 1975;255:151.
ture: Keratometer (ophthalmometer). In Dabazies OH Jr, 37. Millodot M. The influence of pregnancy on the sensitivity of
Cavanagh HD, Farris RL, Lemp HA (Eds). Contact Lenses: the cornea. Br J Ophthalmol 1977;61:646.
The CLAO Guide to Basic Science and Clinical Practise. 38. Riss B, Riss P. Corneal sensitivity in pregnancy. Ophthal-
Orlando, Grune and Stratton, 1986;29:1-17. mologica 1981;183:57.
16. Mandell RB. Contact Lens Practise. Springfield, Charlesc 39. Pavlin CJ, Sherar Md, Fester FS. Subsurface ultrasound
Thomas 1988;928-35. microscopic imaging of the intact eye. Ophthalmology
17. Sampson WG, Soper JW. Keratometry. In Girard LJ (Ed): 1990;97:244-50.
Corneal Contact Lenses. St Louis: CV Mosby Co, 1970;65-92. 40. Rutnin SS, Pavlin CJ, Slomoric AR et al. Preoperative ultra-
18. Wilson SE, Klyce SD. Advances in the analysis of corneal sound biomicroscopy to assess ease of haptic removal before
topography. Surv Ophthalmol 1991;35:269. penetrating keratoplasty combined with lens exhange. J
19. Arffa RC, Klyce SD, Busin M. Keratometric and epikerato- Cataract Refract Surg 1997;23:239-43.
phakia. J Refract Surg 1986;2:61. 41. Reinstein DZ, Chir MBB, Aslanede IM. High frequency
20. Arffa RC, Marvelli T, Morgan KE. Keratometric and refractive ultrasound digital signal processing for biometry of the cornea
results of pediatric epikeratophakia. Arch ophthalmol in planning phototherapeutic keratectomy. Arch Ophthalmol
1985;103:1656. 1993;111:431.
21. Arrowsmith PN, Marks RG. Visual, refractive, and kerato- 42. Laing RA, Sandstorm MM, Leibowitz HM. Invivo Photo-
metric results of radial keratotomy. Arch Ophthalmol micrography of the corneal endothelium. Arch Ophthalmol,
1987;105:76. 1993;93:143.
Chapter 22
Specular Microscopy
M Srinivasan
HISTORY
Observation of the corneal endothelium by specular
reflection dates back to the early part of 20th century.
Vogt demonstrated the first direct visualization of the
corneal endothelial cells using the principle of specular
microscopy in 1918 using a slit lamp microscope. He
demonstrated that the endothelial mosaic could be
visualized in the axis of a reflected beam. But he faced
problems due to fine continuous movements, limited
magnification and annoying light reflexes.
In 1968, David Maurice1 modified the metallurgic
microscope and obtained specular reflection from the
endothelial surface of excised corneas through a fluid
medium at high magnification. But it was nit until a
suitable modification of the equipment was made by
Laing et al in 19752 and later Bourne et al3,4 that
clinical specular microscopy became a viable method
to study the corneal endothelium. Fig. 22.1: Optical principles
The initial specular microscopes were of narrow
field with a field of view of only 0.04 mm. The current the reflected and scattered light is collected by the
wide field specular microscope has a view of 1 mm.2 objective of the photomicroscope producing an image
at the film plane. The larger the difference in refractive
OPTICAL PRINCIPLES (Fig. 22.1) index between the two regions, the more intense will
be the light beam.
Specular microscope is a reflected light microscope, The fraction of Incident light reflected (R) is given
(epi-illuminated) that projects light on to the cornea by the formula
at nearly normal incidence, and images the light
reflected from an optical interface of the corneal R=
 n1-n2 
tissue—most typically the interface between the  n1-n2 
corneal endothelium and the aqueous humor. Of
primary importance in clinical specular microscopy When n1 and n2 are the indices of refraction of the
is that the light that is, reflected specularly i.e. mirror two regions considered.
like, where the angle of incidence is equal to the angle Considering the refractive index of
of reflection. Light that passes through the slit of the *Lens = 1.1517
specular microscope encounters a series of interfaces * Saline = 1.330
between optically distinct regions. Some light is *Cornea = 1.376
scattered by various cornel tissue layers. A portion of *Aqueous Humor = 1.336
Using the above relation, the following is Zone I: Bright region—by light reflected from the lens
calculated: coupling fluid and coupling fluid—epithelium inter-
• Reflection from lens —Saline interface = 0.365 face or both.
• Reflection from Saline—cornea interface =
Zone II: Shows part of the stroma.
0.025%
• Reflection from cornea—Aqueous humor Zone III: Shows endothelial layer.
interface = 0.022%
Zone IV: Shows part of the Aqueous region.
Reflection from the intra-corneal interfaces cannot
Interface between Zones III and IV, is called the Dark
be calculated as the refractive indices of the separate
Boundary. It separates the illuminated cornea from
layers of the cornea have never been measured.
the non- illuminated area. One side of the boundary
The current Specular Microscope has multiple
is dark because negligible light is scattered from the
advantages:
aqueous humor.
i. Wider field of view utilizes optic improvements
Interface between Zones II and III, is called Bright
to minimize annoying reflections from incident
Boundary. It separates the endothelial reflection from
light
the overlying illuminated corneal tissue. Neither side
ii. Wide field microscope offers a full field of view
of the boundary is dark, as substantial amount of light
providing better examination of the endothelial
is scattered from this tissue. It is less distinct than the
mosaic.
dark boundary.
iii. Addition of highly sensitive video cameras and
recording systems, as well as a variety of optic
Using a Wide Slit of Light
improvements such as the scanning mirrors
systems, and the modification of the applanating When a wider slit of light is used, a larger field of view
objective cone for the contact specular microscope, of the endothelial cells result. But here a wider beam
have improved the resolution of the endothelium illuminates more of the corneal tissue anterior to the
and increased the field of view. endothelium. As a result, the volume of interfacing
stroma increases and a greater amount of scattered
CLINICAL SPECULAR light reaches the film plane. The net result is reduced
MICROSCOPY could either be contrast of endothelial image, and a loss of cellular
definition. Here the region produced by scattered light
1. Higher magnification, and resolution using contact
exclusively of stromal origin as seen with a narrow
objective lenses, that touch the cornea and inhibit
slit beam—progressively disappears. So a greater
eye movement
number of cells visible with a wider slit is obtained at
2. Lower magnification, and resolution using non-
the expense of masking information about abnor-
contact objective lenses, that don’t touch the cornea.
malities confined to the corneal stroma.
By changing the objective lenses, specular
Therefore it appears that a “Tradeoff” between the
microscope can be used either as contact or non-
contrasts of the photographs and the number of cells
contact ones.
able to be photographed must be made. This limitation
is not due to the instrument but rather to the light
Using a Narrow Slit of Light
scattering properties of the corneal tissues overlying
When a narrow slit of light is focused on to the the endothelium.
endothelial cell-aqueous humor interface, considerable Types of Specular Microscopes
amount of light is reflected specularly back towards 1. Clinical specular microscope
the film by: a. Contact wide field
• Lens coupling fluid interface b. Non-contact wide field
• Coupling fluid—epithelium interface 2. Eye bank specular microscope
• Endothelium—aqueous humor interface 3. Slit lamp attached
At the film plane, light from various regions The advantages of contact microscope are better
overlap: when a bright region overlaps a dark region, resolution and image quality since the numerical aper-
the dark region is not seen. So, not all regions are seen ture of the objective lens is higher than non-contact
in the photograph. Four zones are described: specular microscope. But there are few disadvantages
Chapter 22: Specular Microscopy 149
like the objective lens getting contaminated, when Factors affecting Image Quality
used in eyes having infection or in patients with AIDS. The image quality has been improved a lot through
Clinical specular microscopes somewhat inhibit eye the advances, made in currently available specular
movements, also enable stromal, epithelial and lens microscopes. The objective lens should be clear from
epithelial cells to be observed and generally give a oily film, mascara, debris from cleaning materials,
read out of the corneal thickness. In the past few years, otherwise the image quality may be degraded.
several non-contact instruments have been developed, For eye bank specular microscopes, the viewing
that have the advantage of not having to touch the system should be without distortions particularly the
cornea. vials and plastic caps-optic distortions in these
materials can adversely affect the image quality. It is
Techniques of Specular Microscopy important to cover the specular microscope with a
dust cover when it is not in use.
In clinical specular microscopy, the technique used
depends on the particular instrument that is used. In Indications for Specular Microscopy
all cases, however, the basic technique is to align the 1. Early diagnosis of Fuchs’ endothelial dystrophy
instrument to the patient’s eye so that the conditions (Fig. 22.3)
for specular imaging are obtained. 2. In certain eyes before cataract surgery
Necessary condition for normal observation of the a. Previous trauma
corneal endothelium. b. Pseudoexfoliation
As with any microscope, the endothelium being c. Recurrent uveitis
observed must be at the correct distance from the d. Corneal edema in contra-lateral eye
objective lens, so that its image is in focus on the focus e. Clear graft with operable cataract
plane of the specular microscope. In addition, to see f. Glaucomatous eye with cataract
the sharp cell borders, the corneal endothelium must g. Subluxated lens, choosing the IOL
h. Posterior polymorphous dystrophy
satisfy the conditions of specular imaging. For eye
i. Ice syndrome, congenital glaucoma
bank specular microscopes and clinical contact
j. Use of various types and designs of IOL
specular microscopes, this essentially requires that the
k. Effect of various irrigating solutions and intra-
region of the endothelium being observed be
cameral products used during cataract on
perpendicular to the optical axis of the objective lens. endothelium
For clinical non-contact specular microscope, this l. Different techniques of cataract surgery; related
essentially requires that the region of the endothelium instruments and endothelial response.
being observed be perpendicular to the line bisect- 3. Evaluation of donor endothelium (Eye Banking).
ing the optic axis of the illuminating objective, and 4. Various refractive surgical procedures like LASIK,
the optical axis of the light collecting objective LASEK and their long-term effect over corneal
(Fig. 22.2). endothelium.
Fig. 22.2: Normal Corneal endothelium Fig. 22.3: Fuch’s endothelial dystrophy
5. Contact lenses and Phakic IOLs; How they involve scopy may provide additional useful information to
the endothelium? These are the few areas, where more accurately screen donor corneal tissue to
specular microscopy is applied frequently if not determine suitability for transplantation, More
routinely. From a practical point of view, specular accurate information are made, for example, the use
microscopy probably has become the most useful of older donor tissue with adequate cell density and
tool in the evaluation of donor corneas, specially reduce the number of primary donor failure (Fig. 22.5).
for screening and donor material for endothelial Although corneal endothelial cell density declines
dystrophy. with age, it occurs with wide variation. Suitable cornea
Specular microscopy can also be employed to from older donor, that have passed the specular micro-
study the corneal epithelium, using a special plastic scopic criteria of high cell density, low polymegathism
element over the objective lens, or soft contact lens or pleomorphism, and a normal endothelial appear-
over the corneal epithelium5; the reflection from the ance have provided excellent grafts.
epithelium can be reduced, permitting observation of
the epithelial cells. Instrumentation
This method could be applied to study corneal Konan’s Eye bank specular microscope is a compact
epithelial wound healing, following surgery or trauma design with a built-in high resolution camera that
to the cornea. In keratoconus the corneal epithelium gives high quality images of the donor cornea. A built-
shows various changes, spindle shaped cells, specially in cell analysis system allows rapid and accurate cell
surrounding the apex of the cone. Persistent elongated count, as well as other parameters such as poly-
cells are also observed in extended wear soft contact megathism and pleomorphism. Its XYZ and rocking
lens wearers; aphakic patients, diabetics after kerato- platform mechanism makes tracking of the endothelial
plasty and those with persistent epithelial defects. In cells easy. The built in pachometer will provide the
these patients the epithelium is considered clinically capability of measuring corneal thickness.
abnormal, with increased susceptibility to trauma and Prior to examination of the donor corneas they
infection. must be warmed to room temperature for at least 1 to
2 hours before evaluation to eliminate artifacts asso-
Methods of Evaluation of Corneal Endothelium ciated with the appearance of the endothelium at low
1. Quantitative Assessment temperature. The corneas can be examined, as they
2. Qualitative Assessment are kept inside the storage media, even without view-
This is mainly applicable in Eye Banking and donor ing chamber, thus decreasing the chance of conta-
endothelial evaluation (Fig. 22.4). mination. Warming the preserved corneas will not
affect the endothelial viability.6
Eye Bank Specular Microscopy for Examination The center method of Konan specular microscope
and Evaluation of Donor Corneal Endothelium is an accurate method to determine cell density.
Every eye bank is required to examine and document Four most important parameters for assessing the
the overall condition of the cornea. Specular micro- state of the cornea are:
Fig. 22.4: Cornel Endothelium Fig. 22.5: Konan Eye Bank Specular Microscope
1. Cell density
2. Cell size variations
3. Cell shape variations
4. Corneal thickness.
Qualitative Analysis
Cell Density
Although the endothelial density is a very important
parameter for assessing the health of donor cornea,
cell density alone cannot determine the stability of the
cornea. A high percentage of hexagonal cells and an
absence of polymegathism imply a stable endothelial
monolayer.
The causes of polymegathism include long-term Fig. 22.6: Eye Bank Specular Photograph;
contact lens wear, diabetes, post cataract surgery, post Young donor— hexagonality 71%
penetrating keratoplasty, keratoconus, inflammation
and ageing. v. Intracellular dark structures
It has been reported that corneas with considerable vi. Intracellular vacuole or bleb
polymegathism or pleomorphism have increased vii. Intercellular dark structures often seen in eyes of
incidence of post-surgical decompensation and patients with anterior uveitis, representing
reduced functional reserve. invading inflammatory cells.
When the endothelium is insulted, not only does
the cell density decreases but also the shape and size
of the cells change. The majority of the human Quantitative Cell Analysis
endothelial cells are hexagonal in shape (48% to 90%) The aim of quantitative analysis, is to assign a number
(Fig. 22.6), with pentagonal (15% to 35% and to the specular-photomicrograph that can produce a
heptagonal (25% to 38%) cell constituting the greater measure of the endothelial status.
portion of the remaining endothelium. The cornea 1. Cell area: Expressed in units of square micrometers
with greater number of hexagonal cells demonstrates per cell (N):mm2
minimal variation in cell size. The cornea with a low 2. Cell density: Expressed in units of cells per square
coefficient of variation and higher percentage of
millimeter
hexagonality will be the more stable cornea to
At birth: 3000 to 4000 cell/mm2
withstand the trauma of surgical procedure.
> 40 years: 2500 to 2700 cell/mm2
3. Although high endothelial cell density alone
Altered Cell Shape
doesn’t guarantee a healthy functioning endo-
a. Elongated enlarged cell thelium, there’s a positive correlation between
b. Cells with scalloped boundaries normal endothelial morphology and the functional
c. Round cells reserve of the endothelium. The donor endothelial
d. Square cells cell density should probably be greater than 1500
e. Triangular cells cell/mm2 to ensure sufficient density for corneal
Alteration in cell shape has not been directly deturgescence (Fig. 22.7).
correlated with changes in physiologic function of the
affected cells. Quantitative cell analysis is done by
Miscellaneous endothelial structures a. Fixed frame analysis of cell size
i. Isolated smooth excrescences (Corneal Guttata) — One counts the number of cells within a frame
ii. Multiple coalesced excrescences as seen in Fuchs’ of constant area
dystrophy b. Variable frame analysis
iii. Intracellular bright structures — Computer based analysis has less counting
iv. Pigment deposits on the endothelium errors.
At least 30 to 50 cells should be counted to be

accurate. However, when only a few cells are visible
and analyzable data obtained is not correct, but
represent only the average of cells analyzed.
Parameters Obtained by Cell Analysis

Cell density is an inversion of cell area, i.e. 1,00,000
divided by average cell area, given in cell/mm2
At birth : 300 to 400 cells/mm2
Ageing cell loss : 0.5% per year
40 years : 2500 to 2700 cells / mm2
300-500 : Very tenuous
500-1000 : At risk for any surgical trauma
1000-2000 : At less risk, but still suscep- Fig. 22.7: Eye Bank Specular Photograph—71 years-old
tible to corneal decom- donor has good epithelial reserve
pensation.
Coefficient of Variation
Coefficient of variation of the cell area is calculated as
SD/ average cell area, therefore larger the CV, which
means there is a wide variety in cell sizes, higher
polymegathism. The normal range of CV is 02 – 03;
again, the lower the CV, the more stable the cornea.
Percentage of Hexagonality
Percentage of hexagonal cells represent the shape
factor of cells, expressed as pleomorphism; irregular
cell shape as observed in traumatized or diseased
endothelium such as elongation of abnormally shaped
cells (triangle, square). Percentage of hexagonal cells Fig. 22.8: Eye Bank Specular Photograph—
is calculated as number of hexagonal cells divided by Poor quality in 82 year old donor
the number of cells entered, therefore the higher the
percentage of hexagonal cell, the more stable the
corneal wound healing and response to various agents.
cornea. Any cornea with more than 50% hexagonality
It is non-invasive and affordable.
and 30% coefficient of variation might be adequate.
Recent publications7 favor confocal microscopy
It is prudent to reject those corneas for transplantation
over non-contact specular microscopy in evaluation
that appear qualitatively or quantitatively poor
of corneal endothelium in certain disorders like Fuchs’
(Fig. 22.8).
dystrophy. But specular microscopy is a quicker, non-
contact and well established technique.
SUMMARY
The specular microscope is a valuable tool for use in REFERENCES
the evaluation of corneal endothelium. Specular 1. Maurice DM: Cellular membrane activity in the corneal
microscopy has become a routine technique in endothelium of the intact eye. Experentia 1968;24:1094.
evaluation of donor corneas in all eye banks globally. 2. Laing RA, Sandstorm MM, Leibowitz HM: Clinical specular
microscopy. 1. Optical principles. Arch Ophthalmol
Thus it improves the surgical outcome by using
1979;97:1714.
quality donor tissue. Clinically, used to evaluate the 3. Specular Microscopy: In Krachmar JH, Mannis MJ, Holland
function and functional reserve of the cornea, as a tool EJ, Editors Cornea: Fundamentals of corneas and external
in diagnosing various corneal disorders and study of diseases, St. Louis, 1997, Mosby.
4. Bourne WM, Kanfman HE: Specular microscopy of the 6. Tsubota K, Kasai H, Sakimoto T: Clinical specular microscopy
human corneal endothelium in vivo. Am J Ophthalmol 1976; of corneal endothelium. Folia Ophthalmol JPM 1981;32:1319.
81,319. 7. Hara M, Morishige N, Chikama T et al: Comparison of Confo-
5. Oak SS et al: Thermal effects on the stored Rabbit cornea. cal biomicroscopy and non-contact specular microscopy for
Invest Ophthalmol Vis Sci 1989;30:1584. evaluation of the corneal endothelium. Cornea 2003;22(6):512.
Chapter 23
Applications of
Corneal Topography
Anita Panda, M Ray
The cornea is the most important refractive structure corneal topography is characterized by distortions of
in the eye, which provides 43D of refractive power the shape of the corneal rings. However, at present
out of total 60D. The shape of the corneal surface is Placido’s disk is used only for gross qualitative
the major determinant factor for the corneal refractive assessment of corneal surface due to the following
power and any minor alteration in surface can lead to factors:
significant degradation of images formed by the retina. 1. There is no image magnification; hence, minor
With the advancement of keratorefractive surgery and degrees of corneal abnormalities are not picked up
increase demand of use of contact lenses, the by this device.
understanding of corneal topography is essential in 2. When any effort is made to increase the image size
recent years. The advent of corneal topography has either by devising larger disk or bringing the disk
obviated the need for manual keratometry. Corneal closer, the image quality deteriorates as the part
topography can be used to detect regular and irregular of the object is obscured by ocular adnexa.
astigmatism, preclinical and clinical keratoconus, 3. It cannot be used in cases having corneal ulcers or
corneal warpage from contact lens use, different any epithelial defects.
marginal degenerations, and postoperative refractive In 1854, Van Helmholtz developed the ophthalmo-
effects of keratorefractive surgery. meter (keratometer) for measuring the corneal
Currently, computerized videokeratography is the curvature. Working of keratometer is based on the
most commonly used technique to assess the corneal principle of formation of images by convex reflector,
curvature. Newer technologies, with a potentially where cornea acts as a convex mirror. Keratometer
greater range of technical capabilities are under measures relatively small area (3 mm), that of 1.25 mm
development, and yet to find widespread application on either side of a point in the central cornea. Different
in clinical practice. types of keratometers are available nowadays, e.g.
Bausch and Lomb, Javal-Schiotz (Haag-Streit), Terry’s
EVOLUTION OF CORNEAL TOPOGRAPHY
intraoperative keratometer, and Weseley auto-
Placido disk photokeratoscopy was the origin of keratometer. However, Bausch and Lomb is the most
modern videokeratoscopy. However, a number of commonly used keratometer. Some keratometers (e.g.
important advances were made to adopt this tech- Javal-Schiotz) deploy doubling prisms in one meridian
nology for the automatic analysis of corneal contour at a time, so that they have to be rotated to measure
over a fairly broad region of the surface. Placido disk the radius of curvature in the axis perpendicular to
devised by Antonio Placido in 1880 consists of equally the initial one. On the other hand, other keratometers
spaced alternating black and white rings with a hole (Bausch and Lomb) can measure the radius of
at the center to observe the patients’ cornea. Abnormal curvature in two principal meridians simultaneously,
Chapter 23: Applications of Corneal Topography 155
hence called one position keratometer. Working of The major deficiency of this method was that a large
keratometer is based on certain assumptions: segment of the physician audience had difficulty in
• Object distance is taken to be very large easily interpreting the wire model graphics.
• Refractive index of cornea is assumed as 1.3375 Different types of photokeratoscopes project,
• Posterior surface of cornea is parallel to the anterior varying number of concentric rings over the cornea,
surface. which cover various amounts of corneal area. Majority
Keratoscopic image can be photographed and the of photokeratoscopes use 8-12 rings, which are
size of the photographed image can be modified. This numbered from inside out. The following two systems
technique is known as ‘Photokeratoscopy’ and was are used to resolve the data prints on the mires:
introduced by Gullstrand in 1896. Interpretation of • Manual digitalization system,
photokeratoscopy is based on the closeness of the • Automated digitalization system.
image rings. The closer rings, the steeper is the cornea
and farther apart the rings, the flatter is the surface. Normal Corneal Topography
Disadvantage of photokeratoscopy is that, though it The normal cornea is asymmetrically aspheric with
covers the larger area of the cornea the central part is 90 percent of the refractive power at the anterior
not studied. However, this disadvantage can be surface. There is a changing radius of curvature in the
overcome by the use of hemispherical target. normal cornea with the steepest area at the center and
Studies have shown that keratometry readings gradual flattening peripherally. Normal corneal
obtained after radial keratotomy, myopic kerato- topography, using computerized videokeratography,
mileusis and epikeratophakia correlate poorly with 23 percent corneas have a round pattern, 21 percent
changes in refractive error. The keratoscope, an are oval, 18 percent have symmetric bowtie shape, 32
improved version of Placido’s disk provides detailed percent have an asymmetric bowtie shape, and 7
information of the topography of pericentral, percent are irregular.
midperipheral, and peripheral cornea. Trained
observers can obtain qualitative and semi quantitative Available Corneal Topography Systems
information about the shape of the cornea from simple
visual inspection of a keratoscopic photograph. More • Louisiana State University Corneal Topography
exact quantitative information can only be obtained System (LSUCTS)
by more sophisticated analysis of keratoscope mires. • Corneal Modeling System (CMS)
Early efforts to computerize corneal topography • Eye sys 2000 corneal analysis system
analysis related to manual digitalization of kerato- • Topographic Modeling System (TMS-I)
scope photographs, an expensive and intensive • Computerized corneal topographer EH 270
process which demonstrated feasibility and utility, but • PAR corneal topography system.
required automation for widespread use. Such
automation was first developed commercially by CLINICAL APPLICATIONS OF
Computed Anatomy Inc, New-York, who introduced CORNEAL TOPOGRAPHY
video image capture, automated mire acquisition, and
Keratoconus
a novel Placido disk cone that project mires onto a
large area of corneal surface without interference from Videokeratography is possibly the best method for
nose and orbital ridge. monitoring the progression of keratoconus (Figs 23.1
In 1981, Doss and coworkers described an algo- to 23.3). Modern keratographic techniques can even
rithm by which optical power distribution along the pick up the very early changes in keratoconus and
anterior corneal surface could be determined by facilitate the understanding of the underlying
analysis of the raw data obtained from keratoscope pathology. Several studies have shown that central
photographs. Rowsey and colleagues used this keratoscopic ring is distorted and becomes pear-
information to create a numerical plots that identify shaped in early keratoconus. CVK maps in both
corneal surface power at selected points on each clinical and preclinical keratoconus demonstrate cone
keratoscopic ring. In 1984, Magnire et al introduced a like or asymmetric bowtie like steepening, usually
computer based analysis system that produced three inferiorly, although the entire cornea may be involved.
dimensional wire models of corneal surface distortion. Initial steepening develops at the inferotemporal
portion of the cornea, which subsequently progresses

to involve the nasal and superotemporal area
(Fig. 23.2). In most advanced stage of keratoconus, the
superonasal area is also involved (Fig. 23.1). Preclinical
forms of keratoconus are contraindications to
keratorefractive surgery. Photokeratoscopic staging of
keratoconus (Amsler) are:
Stage I Oblique astigmatism with irregular kerato-
scopic mire.
Stage II More severe signs as described in stage I.
Stage III Conical cornea with marked corneal
thinning.
Stage IV Opacity at the apex of the cone.
Fig. 23.1: Videokeratography of keratoconus
(preoperative)
Contact Lens Fitting in Keratoconus
Contact lens is chosen between two keratometric
readings or a steep trial lens is fitted over the irregular
cornea. Next, the fluorescein pattern is observed under
biomicroscope. Ideally, the contact lenses should show
a ‘3-point touch’, i.e. central 3-4 mm and peripheral at
any two points usually at 3 and 9 o’clock positions.
There should be adequate movement and good
centration. The lenses should touch markedly outside
the apex. Three-point touch is best when achieved. The
edge should not stand off in the upper half of the lens;
otherwise it should be intolerable due to upper lid
irritation. The corneoscope can be used for fitting
contact lenses in cases of keratoconus, using the
superior outermost ring as a guide.
Fig. 23.2: Videokeratography of keratoconus
(pre and postoperative) Corneal Diseases
Corneal topography may aid in early diagnosis of
various corneal diseases. Alteration of visual acuity
is not a reliable guide to detect the early corneal
disease, as the abnormality may not involve the
pupillary area. Very early changes also cannot be
appreciated by slit lamp biomicroscopy. Neither
keratometry is helpful as it measures only central
3 mm of cornea. Infectious keratitis, bullous kerato-
pathy, contact lens induced corneal edema, epithelial
and basement membrane dystrophy, corneal scarring,
etc (Fig. 23.4) cause alteration of corneal topography
by changing the tear film morphology. It either
becomes flatter or steeper at the affected place leading
to irregular astigmatism. Decreased visual acuity may
Fig. 23.3: Videokeratography of keratoconus result from irregular reflection of light from the corneal
(preoperative) surface. Any compressive lesion in the adjacent area
designed lens is based on topographic analysis and
modified by the individual eye characteristic.
A well-fit rigid contact lens provides maximal
visual comfort and maximum visual correction. But
the aim is not to alter the corneal physiology.
Following are the basic qualities for a well-fit lens:
• Good centration
• Stable vision
Fig. 23.4: Videokeratography of corneal scar • Crisp retinoscopic reflex
• Clear undistorted mires
can also alter the corneal topography. Examples are • Clear endpoint on overrefraction.
upper lid tumors, limbal dermoid, conjunctival When the contact lens achieves all these qualities,
a corneal topography demonstrates a ‘normal’ cornea
squamous cell carcinoma with corneal involvement,
without any area of excessive steepening or flattening.
etc. Pterygium also causes surface irregularity and
On the other hand, base curve and other parameters
corneal topographic changes. Further, corneal
of contact lens can be modified on the basis of corneal
topography is helpful in diagnosis of marginal topography. By using the software program available
degenerations, e.g. Pellucid and Terrien’s dege- with the instrument the design of contact lens can be
neration both of which cause against the rule finalized by getting the desired fluorescein pattern on
astigmatism through entirely different mechanisms. the monitor. It will also be possible to see the change
Pellucid marginal degeneration is a bilateral inferior in fluorescein pattern on the monitor due to changes
corneal disorder characterized by narrow band of in the lens diameter and lens base curves.
corneal thinning one to two mm wide. Cornea above
the area of thinning is of normal thickness, but Post-PK Astigmatism
protrudes forward resulting in high irregular Improvement in microsurgical techniques and instru-
astigmatism. Terrien’s marginal degeneration, a mentation, eye banking procedure, and the improved
bilateral condition, on the other hand, begins management of postoperative complications have
superonasally in most of the cases. When the thinning enabled corneal surgeons to expect a very high rate of
is restricted to superior area of peripheral cornea, there clear grafts after penetrating keratoplasty. Although
is relative steepening of approximately 90o away from the graft may be clear, the patient may not regain good
the midpoint of the thinned area resulting in high vision because of residual high astigmatism. In an
against-the-rule astigmatism. attempt to correct the problem, contact lens or even
In pellucid marginal degeneration, corneal topo- spectacles with cylindrical power are often tried, but
graphy demonstrates inferior steepening with against- in some cases they fail to restore useful vision.
the-rule astigmatism. Pellucid marginal degeneration An understanding of corneal topography is the
basis for formulation of a sensible treatment plan. A
is a contraindication to keratorefractive surgery.
topographic evaluation of pre and postoperative
Stromal thinning extending to the limbus in the zone
refractive surgical procedure may prove to be of value
of topographic steepening is sometimes evident with
in improving results. Corneal topography helps in
careful slit lamp biomicroscopy. diagnosis and correction of post-PK astigmatism in
Rigid Contact Lens Fitting the following ways (Figs 23.5 and 23.6):
i. Selective suture removal Interrupted tight sutures
Topographic analysis of rigid contact lens is of are easier to remove. Removal of a segment of
immense help in the fitting of rigid contact lens. The running suture is more difficult but can be
best method of contact lens fitting is based on corneal performed either with slit-lamp or under an
topography, also known as keratometric method. In operative microscope.
this method, ‘K’ reading is taken, spectacle pres- ii. Excessive flattening of the cornea It can be due to
cription is recorded in minus cylinder and cylinder wound leakage or wound gaping. This is diag-
power is dropped. If the lens is fitted steeper than ‘K’, nosed by typical ‘tear-drop’ conformation in
plus power of contact lens is decreased by 0.25 D of corneal topography. Resuturing or wound-
steeper fit. Rigid contact lens is fitted 0.25 D to 0.50 D revision can be considered based on topographic
steeper than flattest corneal meridian. Custom finding.
1. Diameter of central optical clear zone Smaller optical

zones produces greater flattening than large optical
zones.
2. Number of incisions It is believed, that four
incisions give approximately three-fourth of the
effect of eight incisions.
3. Depth of incisions Incision of less than 80 percent
depth have almost no effect, and incisions pro-
gressive toward 100 percent depth have an
exponentially greater effect, as descemet’s mem-
brane is approached.
Corneal topography has a great role in radial
keratotomy in evaluating postoperative cornea.
Preoperative topography reveals corneas with central
Fig. 23.5: Videokeratography (post PK) steepening, which may have different shapes. Post-
operative topography shows marked central flattening
with relative steepening at the periphery. Flattening
of central cornea decreases the axial length and
Fig. 23.6: Videokeratography (pre and post PK)
Fig. 23.7: Videokeratography (pre and post RK)

iii. Astigmatic relaxing incision It is considered if the
topography indicates that the steeper meridian
is more than 43 D. Over correction of 30-50 percent
is desired after relaxing incision. The desired
effect can be monitored preoperatively by corneal
topography, and size and depth of the incision
can be modified or even compression sutures can
be used till the desired effect is obtained.
iv. Rigid gas permeable contact lens fitting It is also
facilitated by corneal topography in post-PK
astigmatism.
Radial Keratotomy
This surgical procedure is virtually obsolete now.

There are three dominant surgical variables: Fig. 23.8: Videokeratography (pre and post RK)
improves, the vision in myopia. Negative asphericity
of cornea also increases the depth of field. Peripheral
steepening on the other hand, causes spherical
aberration and vision may be slightly compromised.
Marked peripheral steepening can be avoided by
smaller optical zone. Some ophthalmologists believe
that there is a threshold for peripheral steepening. Any
steepness crossing that limit may result in visual
compromisation. Similarly, contact lens fitting in a
post-radial keratotomy patient, can be guided by Fig. 23.9: Videokeratography
(post PRK)
corneal topography (Figs 23.7 and 23.8).
Photorefractive Keratectomy (PRK)

Corneal topography is a useful tool for preoperative
screening of PRK patients to detect undiagnosed
keratoconus, and other corneal curvature anomalies.
The other major value is to compare the preoperative
power map with postoperative map, and thus exact
visualization of procedure induced changes.
Postoperatively, in addition to change from the
preoperative findings, corneal topography (Fig. 23.9)
can recognize different healing pattern after PRK.
Astigmatic Keratotomy (Fig. 23.10)

Fig. 23.10: Videokeratography
The understanding of astigmatism has been drama- (pre and post AK)
tically improved by corneal topography. We know When performing astigmatic keratotomy, it is best
that astigmatism can be symmetrical, asymmetrical, to make the relaxing incisions peripherally in the
regular or irregular. Symmetrical astigmatism occurs carrier portion of the cornea at the 7 or 8 mm optical
when there is equal dioptric power or steepness on zone or even adjacent to limbus. One of the major
either side of optical axis along the primary steep reasons for placing these astigmatic cuts peripherally
meridian or flat meridian, usually both inside and is because the coupling ratio is 1:1 in the peripheral
outside the optic cap. Regular astigmatism is cornea. As the optic cap is approached, the coupling
demonstrated by the classical bow-tie pattern on ratio approaches 2:1 and upto 3:1. It is important to
corneal topography, with an angle between the steep keep coupling ratio 1:1 so that the spherical equivalent
meridian and flat meridian of 90 degrees. In addition, of the expected postoperative refractive result remains
the steep and flat meridians are at the same location the same. This also minimizes the risk of creating
(degrees) at all optical zones. irregular astigmatism Arcuate incisions give slightly
From optical point of view, the cornea can be more effect that straight incisions, as they follow the
divided into 2 concentric zones. The central zone is distance from the visual axis. Relaxing incisions flatten
called optic cap and has an average diameter of 5.2 the steeper meridian of the cornea and steepen the
mm. This is the portion of the cornea used for the sight. flatter meridian. This induced change 90 degree away
According to Stiles-Crawford effect, as pupil dilates from primary curvature change is called coupsing.
beyond 5.2 mm, the remainder of the cornea has little
or no effect on refraction, and vision because of the READING AND INTERPRETATION OF
orientation of the photoreceptors and shape of the CORNEAL TOPOGRAPHY
retina. The remaining peripheral cornea, the carrier Most commonly used formats for corneal topography,
portion extends from 5.2 mm to the surgical limbus. is color coded corneal topography maps. On the left
In this area corneal thickness begins to increase side of the map, there is a color scale which displays
dramatically. different colors. Curvature of the cornea can be
indirectly determined from dioptric powers. Klyce- 6. Videokeratographic recording may be difficult in
Wilson scale and Magurire-Waring scale use 1.5 D and highly irregular corneas.
1.0 D power difference in their color-coding, respecti- 7. Interpretation may be difficult for the common
vely. practitioners.
Conventionally, ‘hot’ colors represent the steeper 8. Sometimes after unsuccessful PRK, corneal topo-
areas of cornea and ‘cool’ colors, are used for the flatter graphy may show normal recording, although
areas. For example, red and near red-blue spectrums there is actual changes in corneal thickness.
are considered as ‘cool’ colors. Therefore, pro-
gressively decreasing refractive power of the cornea SUMMARY
can be represented as red-orange-yellow-green- Corneal topography can be used for therapeutic,
purple-blue, etc. diagnostic, as well as research purposes, as summari-
At the bottom of the right side of the map, there is zed below:
a box, which displays various information, e.g. major
meridians, radius of curvature average keratometry, Therapeutic
and depending on the capability of the system some Topography guided contact lens fitting is considered
special data like surface regularity index (SRI), as the best method, as it provides more physiological
simulated keratometry, surface asymmetry index, etc. and ideal fit. It can be used in the following:
Some systems may provide both absolute and a. Routine contact lens fitting
normalized scale. Absolute scale, on the other hand, b. Contact lens fitting in postkeratoplasty astig-
uses smaller intervals (e.g. 0.5 D). However, absolute matism
scale is rated better than normalized scale, as the latter c. Keratoconus
one exaggerates the clinically insignificant infor- d. Contact lens manufacturing unit for verification of
mation. complex specification.
e. Corneal topography helps in accurate intraocular
LIMITATIONS OF CORNEAL TOPOGRAPHY lens power calculation.
1. The system assumes that the refractive index of
cornea is 1.33 and thus underestimates the corneal Diagnostic
power changes especially after photorefractive Corneal topographic system aids in diagnosis of early
surgery, as the actual refractive index of cornea is keratoconus, toxic epitheliopathy, infectious keratitis,
1.376. bullous keratopathy, various marginal degenerations,
2. Oblate cornea is one, when there is marked central dystrophies, etc.
thickening with loss of positive asphericity. An It helps in monitoring the disease like keratoconus,
oblate cornea or negative asphericity results after pathological myopia, etc.
myopic PRK. In corneal topography central corneal
power is interpolated from central rings, and thus
Research Purposes
it may overestimate the oblate corneas.
3. Normal cornea is an aspheric surface. Power calcu- Measurement of corneal thickness is possible by laser
lation in corneal topography is based on spherical pachymetry, using the corneal modeling system
optical system, and this might give rise to false (CMS). This system uses dual beam laser scanning slit
interpretation. lamp.
4. It cannot show the sharp boundaries in post- Mechanism of radial keratotomy, astigmatic
operative PRK cornea, as the data is averaged keratotomies are better explained by corneal topo-
across the major and minor meridians. graphy.
5. While, calculating the corneal power, it considers In near future, preoperative topography system
the apex of the cornea, which may not correspond may develop to modify the suture techniques and thus
to the visual axis. reduce the postoperative astigmatism.
Chapter 24
Corneal Ulcer
M Reddy, Savitri Sharma, GN Rao
Corneal blindness accounts for 20-30 percent of all Progressive Stage

blindness in the developing countries of the world.
Infective corneal disease is the leading cause of this It includes adherence and entry of the organism,
problem in South Asia.1 By definition, a corneal ulcer invasion of the stroma, host response, multiplication
is a break in the epithelium with underlying stromal of the organism, diffusion of toxins and enzymes, and
necrosis. A host of different etiologic factors through resultant tissue destruction.
a common pathology of tissue destruction produce Within 2 hours of corneal injury PMNs are seen in
this ulcer. the wound. These disappear within 48 hours if no
infection ensues and the epithelium promptly heals.
PATHOGENESIS OF CORNEAL ULCERATION If infection occurs the inflammatory process progre-
Among the several agents that can elicit an inflamma- sses. In case of bacterial corneal infection, bacteria gain
tory response in the cornea, the two most common access to the stroma through the injured epithelium
are microbial infections (either bacterial, viral, fungal or stroma after they adhere to the injured surface.
or protozoal) and various immunologic conditions Enzymes released by the bacteria and PMNs cause
including hypersensitivity, allergy, and autoimmu- alteration of the corneal stroma which further
nity. Microbial pathogens cause corneal tissue damage facilitates invasion of bacteria to the stroma. Early in
directly or by the release of toxins and enzymes or by the disease process the tear film is the source of the
activating the immune mechanism. Antigens initiate PMNs. Phagocytosis and digestion of bacteria by
the immune response with B and T lymphocytes PMNs is evident in the wound at 4 hours after infection
responsible for antibody and cytotoxic components, and in anterior stroma by 8 hours. This is the first line
respectively. Two other components are macrophages of defense against many bacteria.
playing an important role in processing antigens and
polymorphonuclear neutrophil leukocytes (PMNs) Regressive Stage
whose proteolytic enzymes have extensive destructive
potential. The complement system also plays a central It is essentially a regression of the above events. The
role in inflammation mediated by antigen-antibody infiltrates decrease in size, ulcer becomes more demar-
interactions. cated, the collagen destruction is halted and bacterial
multiplication is controlled. Necrotic areas may slough
Histopathology and Stages off minimizing progression of the inflammatory process.
of Corneal Ulceration
Healing Stage
The course of infective corneal ulceration can be
divided into three main stages on the basis of histopa- During this stage, the necrotic stroma is replaced by
thologic changes: scar tissue laid down by fibroblasts, which are trans-
a. Progressive stage, formed histiocytes and keratocytes. Thin areas may
b. Regressive stage, and be replaced by fibrous tissue, and vessels growing
c. Healing stage. toward the ulcer bring in fibroblasts with resultant
healing. When the healing is completed, the vessels staphylococcus affects the eye and acts on cell memb-
regress. ranes to cause increased permeability. Beta toxin is
cytotoxic to red cells, leukocytes, and macrophages.
Mechanisms of Corneal Stromal Ulceration The different enzymes produced are coagulase, lyso-
zyme, hyaluronidase, deoxyribonuclease, staphyloki-
In infections and sterile injuries, the inflammatory
nase and lipase.
stimulus (antigen, toxic agent or cellular degradation
Streptococcus pneumoniae produces a hemolytic
products) combine with antibody (gammaglobulin)
agent which has toxic effects on the cornea. It is
and this complex binds complement. The complement
designated as cytolysin or ocular toxin. When injected
binding complex is chemotactic for the PMNs, attrac-
into rabbit cornea it causes complete opacification of
ting a large number of these cells to the corneal stroma
the whole cornea in 24 hours.
for defense of the injured tissue.
Pseudomonas sp. produces a unique toxin known
Stromal melting is preceded by a corneal epithelial
as exotoxin A. It is highly toxic and human macro-
defect and appears to be associated with an inappro-
phages are extremely sensitive to this exotoxin. It
priate inflammatory response. Such ulceration is known
causes inhibition of protein synthesis. The glycocalyx
to be secondary to the action of tissue collagenases
which perform the initial cleavage of stromal collagen of Pseudomonas enables the bacteria to adhere to
fibril with further degradation of collagen and suscep-tible cells and to each other to produce large
glycosaminoglycan involving proteases, peptidases, aggre-gates that resist phagocytosis. The pathogenesis
and cathepsins. Collagenases are released by epithelial of corneal ulceration is depicted in the Flow Chart
cells, fibroblasts, and PMNs. These lysosomes in 24.1.24.1
PMNs contain more than a dozen lytic enzymes
(including collagenase, elastase, and cathepsin) and Herpes Simplex Ocular Disease
are ubiquitous at the site of active ulceration and in The development of a viral infection depends on
the tear film of melting corneas.2 1. The nature of the infecting virus (including its
It is also hypothesized that stromal ulceration is virulence),
initiated by a protease (plasminogen activator) 2. Susceptibility of the host cells,
involved in wound healing. Plasmin activates 3. Host resistance, and
fibroblasts to secrete latent collagenase which is
4. Immunologic and other systemic factors.
converted into active collagenase. Plasmin is also
The subclinical lesions are due to benign strains
believed to cause chemotaxis of PMNs, and ultimately,
affecting primarily and thence caused latency in the
the active collagenase acts on collagen leading to its
neurosensory ganglia.3
degeneration.
Herpes virus itself does not directly stimulate an
inflammatory response. The byproducts of viral
Bacterial Corneal Ulceration replication and immune alteration of the cornea and
The cornea is equipped with a protective lining iris play an important role in destructive corneal
composed of two layers of mucosubstances. The first, conditions including necrotizing keratitis, immune
glycocalyx, is an integral part of cell membrane. The rings, limbal vasculitis, and diskiform edema. It seems
other is a mucous layer produced by the goblet cells likely that the persistence of incomplete viral antigens
of the conjunctiva. and the viral immune alteration of cell membranes in
The lid margins are normally inhabited by bacteria.
Flow Chart 24.1:
The most common organisms found in the conjuncti- Breakdown in corneal defense mechanisms
val sac are Staphylococcus sp, Bacillus sp, and Corynebac- (Eyelids, Tears, Epithelium)
terium sp. The severity of corneal infection usually ↓
depends primarily on the organism itself and the Portal of entry for microorganisms
enzymes and extracellular toxins it elaborates. ↓ ↓ ↓
Staphylococcus aureus is known to produce at least Complement Polymorphonuclear Proteinase
activation leukocyte infiltration exotoxins
30 different biologically active substances. A number ↓
of these are toxins: alpha, beta, gamma, and delta (Oxygen metabolites)
toxins, exfoliative toxin, leukocidin, and enterotoxin. ↓
Alpha toxin is the principal mechanism through which Suppurative corneal ulceration
Chapter 24: Corneal Ulcer 163
the corneal stroma incite inflammatory reactions that the cellular elements of the cornea for sustenance.7 It
involve programmed host lymphocytes, antiviral can use host cells by releasing phospholipases,
antibodies, serum complement, PMNs, and macro- lysozyme, cellulase, and by direct phagocytosis.
phages.4
Latent herpetic reservoirs in the neuronal tissues ETIOLOGIC FACTORS OF CORNEAL ULCER
are the source of recurrent viral infection. It has been
Infective Corneal Ulceration
shown that some strains of herpes virus have a higher
propensity for recurrence.5 Bacteria
Latent HSV infection is apparently established 2
The majority of bacteria cultured from infections of
to 3 weeks after infection and is harbored in the
the cornea are of the same species that normally are
neuronal sensory, trigeminal, or autonomic ganglia
present in the conjunctival sac, on the lids or periocular
and the mesencephalic nucleus in the brain stem and
skin, and in the adjacent nasal passages.8 Their incid-
travels to the affected tissue during reactivation.
ence may vary geographically.
The wide variety of factors able to induce recurrent
herpetic eruptions in humans are sunlight, local trauma,
Gram-positive Cocci
heat, fever, menstruation, immunologic manipulation,
infections, surgery, emotional stress, and others. Staphylococci
Diskiform keratitis is probably caused by a hyper- Staphylococcus aureus
sensitivity reaction due to the presence of viral antigen Coagulase negative staphylococci
in the stroma. The edema may be due to low-grade (Other staphylococci)
stromal inflammation and/or damage to the under- Streptococci
lying endothelium.6 Streptococcus pneumoniae
Alpha hemolytic streptococci (Viridans group)
Fungal Corneal Ulceration Streptococcus pyogenes (Gr-A beta hemolytic strepto-
cocci)
In frank fungal ulcers, the epithelium, Bowman’s
Other beta hemolytic streptococci
membrane and stroma are ulcerated. Invasion of the
Enterococci
stroma often extends beyond the clinically apparent
Peptostreptococci (anaerobes).
ulcer. The hyphae are usually oriented parallel to the
corneal lamellae but may be oriented perpendicular
Gram-positive Bacilli
to the lamellae when steroids have been used. It is
noteworthy that fungi may be absent from the surface Corynebacterium species
area and present only in the deep stroma. Fungi Corynebacterium diphtheriae
elaborate proteases and toxins. Corynebacterium xerosis (diphtheroids)
A number of candida virulence factors have been Listeria monocytogenes
identified. Candida species produce proteolytic enzy- Aerobic spore forming bacilli
mes and lipases which aid host invasion. A surface Bacillus anthracis
protein aids epithelial adherence. Bacillus cereus, Bacillus subtilis
Anaerobic bacilli
Acanthameba Corneal Ulceration Propionibacterium acne
Clostridium species
The mechanism of pathogenesis of Acanthameba
Actinomyces species
keratitis begins with or without minor trauma to the
Nocardia species (N. asteroides, N. brasiliensis).
corneal epithelium followed by inoculation of the
organism through a contaminated contact lens, other
Mycobacteria
foreign bodies or contaminated water. Reported cases
of Acanthameba keratitis have not documented coexis- Mycobacterium tuberculosis
ting infection with bacteria. Also, it is unlikely that Mycobacterium leprae
the pre-existing conjunctival flora support the growth Atypical mycobacteria
of numerous Acanthameba. According to a study by M. chelonei
Samuel and co-workers Acanthameba appears to require M. fortuitum.
Gram-negative Cocci Epidermophyton species

Neurospora species
Neisseria gonorrheae
Glenospora species.
Branhamella catarrhalis.
Dematiaceous Filamentous Fungi
Gram-negative Bacilli/Coccobacilli
Curvularia species (C. lunata, C. senegalensis)
Pseudomonas species (P. aeruginosa, P. cepacia, Bipolaris spicifera
P. maltophila) Exserohilum rostratum
Proteus species Drechslera species
Moraxella species (M. liguefaciens, M. nonliguefaciens) Alternaria species
Acinetobacter calcaceticus Cladosporium cladosporioides
Hemophilus species Phialophora verrucosa
Brucella species Coelomycetes (Botryodiplodia theobromae, Colleto-
Escherichia coli trichum, Phoma).
Klebsiella pnenumoniae
Serratia marcescens Yeasts and Yeast-like Fungi
Aeromonas hydrophila
Capnocytophaga cantmorsus (capnophilic) Candida species (C. albicans, C. tropicalis, C. pseudo-
Citrobacter species tropicalis)
Shigella species (S. flexneri, S. dysenteriae) Geotrichum candidum
Enterobacter species Rhodotorula species
Alcaligenes species Trichosporon species
Eikenalla corrodens Cryptococcus species.
Bacteroides species (anaerobic).
Dimorphic Fungi
Fungi Blastomyces dermatitidis
Atleast 70 genera of fungi have been associated with
Others
keratomycosis with Fusarium species and Aspergillus
species predominating all over the world.9 Fungal Mycelia sterilia group (Rhizoctonia)
infections of the cornea rarely occur in the absence of Zygomycetes (Mucor, Rhizopus, Absidia).
a precipitating event. Septate, filamentous fungi are
most frequently encountered in corneal infections; Viruses
nonseptate fungi being reported only rarely. As far as corneal ulceration is concerned only herpes
Commonly isolated fungi from mycotic keratitis group of viruses are of major interest.
are listed below: Herpes simplex virus—Type I, Type II
Varicella-zoster virus
Moniliaceous (Hyaline) Filamentous Fungi Adenovirus (rarely).
Fusarium species (F. solani, F. oxysporum, F. nivale, Protozoa
F. dimerum)
Aspergillus species(A. flavus, A. fumigatus, A. terreus) Infection of the cornea with protozoa is recently
Cephalosporium species recognized entity. Only two protozoal organisms have
Penicillium species (P. spinulosum, P. citrinum) been reported so far.
Paecilomyces species Acanthameba species (A. castelanii, A. polyphaga, A.
Scedosporium apiospermum rhysodes, A. culbertsoni, A. hatchetti)
Volutella species Nosema species.
Cylindrocarpon tonkinense
Noninfective Corneal Ulceration
Gibberella fujikeroi
Ustilago species The etiologic factors responsible for sterile corneal
Tritirachium species ulceration are as follows:10
Postinfectious — Metaherpetic malnutrition, infancy, old age, alcoholism, immunosu-
(H simplex, bacterial, fungal) ppressive therapy, drug addiction, malignancies and
Traumatic — Chemical injury, thermal burn extensive burns.
Postsurgical — Delayed epithelial healing
diabetes mellitus Fungal Keratitis
homograft reaction The role of trauma, frequently with vegetable material
Lacrimal — Primary keratoconjunctivitis is well documented in the initiation of fungal corneal
sicca infection. In tropical regions trauma is the most
Sjogren’s syndrome prominent predisposing cause of filamentous kerato-
Graft versus host disease mycosis. The majority of yeast infections are endoge-
Lids and lashes — Entropion/ectropion nous ones which occur in structurally altered eyes,
Lid defects particularly in patients with collagen vascular diseases
Cicatricial exposure or keratitis sicca. Candida keratitis is commonly encoun-
Trichiasis tered in patients with lowered ocular immunity or
Lagophthalmos lowered systemic immunity11 including AIDS. There
Exophthalmos seems to be a seasonal variation in the fungi flora of a
Incomplete blink, idiopathic particular region. This is reflected in the fungal
Neurological — Neurotrophic keratitis (HZO, conjunctival flora of the residents of that region. This
diabetes, 5th nerve lesion) may account for variations in frequency of various
Neuroparalytic exposure species in mycotic keratitis.12
(7th Nerve palsy)
Immunological — Collagen-vascular disease Viral Keratitis
(RA, allergic Wegener’s PAN,
Man is the only natural reservoir of herpes simplex
SLE)
virus (HSV). The new born babies may get the primary
Mooren’s ulcer
infection from the mother or close relatives and
Staphylococcal hypersensitive
attendants. Both the children and adults are asymp-
marginal ulcer
tomatic carriers. Immunologically compromised
Vernal conjunctivitis
patients such as patients with leukemia or organ
Dermatologic — Pemphigoid
transplant recipients are at high risk of severe systemic
Erythema multiforme
and ocular herpetic infections. Host factors, including
Rosacea
hereditary characteristics (HLA types), systemic
Nutritional — Keratomalacia
immune diseases (atopy), and other forms of immune
Others — Acute leukemia
incompetence are believed to play a role in the nature
Cutaneous porphyria
and severity of reaction to HSV. Newborns are
Gold toxicity. protected by maternal antiherpetic antibodies for
about 6 months. Recurrent disease may occur in the
RISK FACTORS eye even if the primary involvement was clinically
manifested elsewhere in the body. Mild trauma,
Bacterial Keratitis exposure to strong sunlight, menstruation, psychiatric
An intact epithelium acts as a barrier against most disturbances, and fever often precede recurrent
organisms except Neisseria gonorrheae, Listeria, Coryne- episodes and generally are accepted as precipitating
bacterium diphtheriae, and Haemophlus influenzae. For factors.
all other bacteria a breach in the epithelium is essential.
Local risk factors include ocular trauma, ocular burns, Acanthameba Keratitis
dry eye states, chronic corneal edema, corneal surgery Acanthameba keratitis was first recognized in 1973.
and contact lens wear. Soft contact lens, especially of Since then until 1983, a total of 12 cases were
the extended wear type, is a very common predispo- published. Since 1984, numerous reports have been
sing factor in the causation of bacterial corneal ulcers. documented about acanthameba corneal infection.
Systemic risk factors include pregnancy, severe Corneal infection with acanthameba is believed to
result from direct corneal contact with any material

or water contaminated with the organism. Acantha-
meba are free-living amoebae and are found in soil,
fresh water, well water, sea water, brackish water,
sewage, and air. 13 A variety of sources of conta-
mination have been described such as, mild trauma
associated with vegetable matter, an insect, paint
thinner, glass wool dust, wind blown contaminant,
hot tub use, salt water diving, etc. However, in recent
times contact lens wear has emerged as the leading
predisposing factor in the causation of Acanthameba
keratitis.14 In the United States 85 percent cases of
Acanthameba keratitis are associated with contact lens Fig. 24.1: Pseudomonas corneal ulcer with hypopyon
wear.15 The first case of A. keratitis published in
international literature was diagnosed by culture of proteinaceous flare, fibrinous exudates, and hypopyon
corneal scrapping was from Aravind Eye Hospital, that commonly accompany a bacterial corneal ulcer.
Madurai, India in 1990. 16 Infections have been Rarely organisms are capable of passing through
reported with extended and daily-wear hydrogel Descemet’s membrane.
contact lenses, gas-permeable contact lenses, and hard With appropriate therapy the narcotizing processes
contact lenses. Acanthamoeba species have been regress corneal infiltrate to necrotic material is shed
cultured from soft contact lenses, saline solutions, off and the ulcer may become larger. The walls and
distilled water, and solution in soft contact lens cases.17 floor of the ulcer become smoother and more transpa-
A high incidence of lens storage case contamination rent. Cicatrization occurs as a part of healing process.
by bacteria and acanthameba was reported.18 Acantha- Complications include anterior and posterior syne-
meba have also been cultured from disposable lenses chiae, adherent leucoma, glaucoma, cataract, and
that had been stored in cases rinsed with well water. anterior ectasia of the cornea.
However, in a series of 34 patients 1.5 to 4 % of the Ulcer caused by gram-negative organisms like
laboratory proven infective keratitis in India is found pseudomonas corneal infection, leads to perforation.
to be caused by acanthameba keratitis and majority Ulcers caused by anaerobes, Actinomyces, Nocardia,
of them are in absence of contact lens wear.19 usually follow corneal injuries contaminated with soil.
Nocardia ulcers simulate fungal ulcers in that they are
CLINICAL FEATURES occasionally elevated, have hyphate edges and often
produce wreath shaped satellite lesions (Fig. 24.2).
Bacterial Keratitis
The hallmark of untreated bacterial keratitis is Fungal Keratitis
polymorphonuclear leukocytic suppuration, distin-
Trauma, usually with vegetable matter, is frequently
guished on slit lamp biomicroscope by its dense,
a precipitating factor in an otherwise normal eye.
yellow-white to gray-white color and usually associa-
ted with epithelial and stromal ulceration. This dense
focal infiltrate is typically in the superficial stromal
lamellae with stromal edema and striae near the
infiltrate margins (Fig. 24.1). A crescentic or ring
shaped infiltrate may be present between the infecti-
ous focus and the corneoscleral limbus. A limbal,
conjunctival and circumcorneal hyperemic area with
a mucopurulent exudate is generally prominent. The
iris is swollen as reflected by blurring of its surface
markings and the pupil is constricted. The products
of inflammation are seen on the surface of the ulcer Fig. 24.2: Typical wreath shaped corneal ulcer
itself as well as manifest as anterior chamber cells, due to Nacardia asteroides
At early stage the epithelium may heal over the Viral Keratitis
inflammatory focus, although there may be recurrent
Primary Herpes Simplex Infection
episodes of epithelial loss. The cornea becomes slightly
thickened and “satellite” lesions develop peripheral Primary ocular herpes is a disease of infants and young
to the focal area of infiltration. adults although sporadic cases may occur at all ages.
It may be possible to see feathery hyphate margin The incubation period varies from 2 days to 2
of the infiltrate with the filaments coursing through weeks after contact. Eye involvement is usually mild.
the stroma parallel to the lamellae with high magnifi- Unilateral redness, irritability and watery discharge
cation. In some cases a Wesely ring may develop are the principal symptoms. Typically the ipsilateral
indicating antigen-antibody interaction with resultant preauricular node is swollen and slightly tender.
chemotaxis of polymorphonuclear leukocytes (Fig. Single or group of vesicles may be hidden among the
24.3). lashes. The conjunctiva is injected and edematous.
“Satellite” lesions, is a strong clinical evidence of Follicles in the fornices and tarsal plates and small
fungal infection. Left untreated, a permanent break- subconjunctival bleeding may be seen. Corneal
down of epithelium, stromal ulceration, descemetocele involvement develops in about 50 percent of patients
formation and neovascularization may result. Dema- with primary herpetic conjunctivitis. Fine punctate
tiaceous fungi can cause brown or black discoloration keratitis may develop which stains poorly with fluore-
of the ulcer surface20 (Fig. 24.4). scein and variably with Rose Bengal but as it desqua-
mates fluorescein staining becomes more intense. In
some patients a coarse punctate epithelial keratitis
may appear and progress to form one or several
dendritic figures.
Recurrent Herpes Simplex Infection
Although the primary herpes infection resolves, virus

remains in CNS and possibly in other tissues. The
trigeminal ganglion is a major site of inactive HSV.
Single or multiple dendritic lesions on the cornea
are the hallmark of epithelial disease (Fig. 24.5). The
lesion is associated with diminished corneal sensi-
tivity. After a few days anterior stromal infiltrates
begin to appear under the ulcer but resolve rapidly
Fig. 24.3: Early fungal corneal ulcer with immune ring once the epithelium has healed. In some patients,
and satellite lesions
particularly those treated inadvertently with topical
Fig. 24.4: Dematiaceous fungal corneal ulcer with Fig. 24.5: Fluorescein stained dendritic corneal ulcer due to
crescentic pigmentation of the corneal infiltrate Herpes simplex keratitis
Fig. 24.6: Ameboid epithelial viral keratitis due to Herpes Fig. 24.7: Corneal stromal edema and Descemet’s folds
simplex virus in a patient with stromal viral keratitis
corticosteroids or those receiving immunosuppressive If the inflammation is intense, the cornea may
therapy, a large epithelial ulcer develops. This lesion, become extremely thin, a descemetocele may result
known as geographic or amoeboid ulcer, can at times leading to perforation. Occasionally, the intraocular
encompass the whole corneal surface like the dendrite; pressure may be elevated.
it is the result of active viral replication in epithelial
cells (Fig. 24.6). If this type of ulcer enlarges stromal Acanthameba Keratitis
involvement becomes more marked and the accom-
panying uveitis becomes more intense. Rarely a The symptoms of Acanthameba keratitis include pain
herpetic dendritic lesion may cross the limbus and which is often severe, tearing, photophobia, blepharo-
encroach upon the conjunctival epithelium. spasm and blurred vision, often preceded by a foreign
Stromal necrotic keratitis is a rare phenomenon. It body sensation. Corneal sensation may be diminished
is caused by active viral invasion and destruction. The at some point in some cases.21 It evolves over several
stroma may have a cheesy, necrotic appearance, or it months as a gradually worsening keratitis with
may show a profound interstitial opacification. Anterior periods of temporary remission.22,23 On the other hand
uveitis with keratic precipitates may be present. it may present as rapid deterioration initially and later
Symptoms of pain, photophobia and ciliary injection on giving way to more characteristic chronic slowly
are common findings. Diminution of corneal sensation progressive course.
is an important diagnostic sign of hereptic keratitis. Initial corneal changes are coarse, opaque streaks,
A more typical presentation of a stromal herpes fine epithelial and subepithelial opacities, corneal
keratitis is diskiform keratitis. Viral replication epithelial stippling, and microcystic edema. Some
appears to occur only briefly in the stroma and is not cases present as a diskiform central or paracentral
a major factor in the persistent deeper inflammation. stromal infiltrate with an overlying epithelial defect
However, it does produce complete virus particles, and an area of clear or only mild edematous peripheral
viral components, and soluble viral antigens within cornea separating the infiltrate from the limbus.
the corneal stroma. A typical diskiform keratitis Acanthameba has a predilection for nerve tissue and
consists of a central zone of epithelial edema overlying in several cases of Acanthameba keratitis, a “radial
an area of edematous stromal thickening (Fig. 24.7). keratoneuritis” with infiltrates along corneal nerves
Occasionally, the lesion may be eccentric. Other has been noted clinically, a finding that may explain
features include folds in Descemet’s membrane, a mild the decreased corneal sensation noted in several cases.
to moderate anterior uveitis and keratic precipitates. Acanthameba keratitis usually involves a marked
More severe attacks may develop into interstitial fluctuating nongranulomatous anterior uveitis.
keratitis with stromal neovascularization, scarring, Hypopyon was noted in four out of nine reported
lipid deposition, and stromal thinning. cases in a series.16
Initial improvement or stabilization of the keratitis, platinum spatula or Bard-Parker blade No. 15, under
apparently in response to antibacterial, antifungal or topical anesthesia. Essential requirements for collec-
antiviral therapy, has occurred in majority of cases. tion and processing of corneal scrapings are shown in
In a number of cases acanthameba infection has been Figure 24.8. Proparacaine hydrochloride (0.5%) or
considered only after failure of treatment for suspec- lignocaine hydrocloride (4%) can be used for this
ted, viral and fungal infection. Therefore, diagnostic purpose. Scrapings are collected under direct
methods must always include those required for the visualization through either the slit lamp biomicro-
visualization and isolation of acanthameba in all scope or the operating microscope.
corneal ulcers.24 It is imperative to collect multiple corneal scrapings
from the edge as well as center of the ulcer. If the lids
DIAGNOSIS OF KERATITIS are sticky or loose debris is found over the ulcer it
The distinctive clinical features, for infectious keratitis should be cleaned with sterile cotton swabs before
help the ophthalmologist to suspect strongly that the collection of corneal material. The edge of the spatula
keratitis is due to bacteria, fungus, virus or protozoa. or blade should not be allowed to touch the lid mar-
However, it is impossible to make an absolute etiologic gins or conjunctiva. Multiple scrapings are taken and
diagnosis on the basis of clinical findings alone. processed one after the other in a sequential manner.
Clinical appearance depends on the size of original The usual sequence in the preparation of diagnostic
inoculum of the organisms, the duration of infection, specimens is shown in Table 24.1. If the ulcer is fairly
pre-existing corneal disease, concomitant systemic big it is usually possible to obtain many samples but
disease or debility, and prior antibiotic and corti- when the ulcer is small whatever number is possible
costeroid therapy. Similar features may be present in should be collected sequentially. The platinum spatula
noninfectious keratitis as well. The corneal changes is sterilized in a spirit lamp flame prior to each corneal
produced by infecting organisms are too varied to
provide a reliable and accurate basis for an etiologic
diagnosis. Inability to make a specific diagnosis and
to institute rational treatment on the basis of clinical
morphology demands meticulous laboratory investi-
gation in each case of ulcerative keratitis. A single
protocol designed to identify bacteria, fungus or acan-
thameba should be followed in the evaluation of all
cases of corneal ulcers that are not apparently viral.
Viral corneal ulcers may be subjected to a different
protocol.
Fig. 24.8: Acanthameba keratitis presenting with a persistent
Bacterial, Fungal, and epithelial defect stained with fluorescein and minimal
Acanthameba Keratitis hypopyon
The initial procedure is collection of material from the

conjunctival sacs and lid margins of each eye with Table 24.1: Sequence in the preparation of diagnostic
specimens in bacterial, fungal or Acanthameba keratitis
cotton swabs dipped in brain heart infusion broth or
trypticase soy broth. 8 A total of four swabs thus 1. Blood agar culture
collected are to be inoculated separately on blood agar, 2. Potassium hydroxide mount
thioglycollate broth, and Sabouraud’s dextrose agar. 3. Gram-stained smear
These cultures are taken to assess the possibility of 4. Brain heart infusion culture
contamination of the corneal cultures by organisms 5. Sabouraud’s dextrose agar culture
6. Nonnutrient agar culture
in tear film.25
7. Thioglycollate broth culture
8. Chocolate agar culture
Collection and Processing of
9. Blood agar for anaerobic culture
Corneal Scrapings 10. Brain heart infusion culture
Corneal material is best obtained by scraping, multiple 11. Giemsa-stained smear
areas of ulceration and suppuration with the Kimura 12. Additional smears for special stains.
curettage. It is more convenient to use multiple

spatulas or blades to save time and obtain better
cooperation from the patient.
All solid (agar) media are inoculated on the surface
without cutting the agar and “C”-shaped inoculations
are made at multiple sites (Fig. 24.9).
For the preparation of potassium hydroxide mount
the corneal scraping is first transferred on a precleaned
slide marked with a wax pencil on the reverse. One to
two drops of 10 percent potassium hydroxide contai-
ning 0.1 percent glycerol is placed over the smear and
covered with a coverslip.26
Smears for acid-fast staining and Lowenstein-
Jensen medium for mycobacteria are included when
usual cultures and smears have been negative, the Fig. 24.10: ‘C’ streak inoculation of blood agar
ulcer has been recalcitrant to usual line of treatment showing Staphylococcal colonies
and there is clinical suspicion.
Interpretation of Smears
Gram stain remains a fairly rapid test. It can detect
bacteria, fungi, actinomycetes, and cysts of acantha-
meba. Inability to see organisms on the slide may be
due to insufficient material, failure to examine the
entire slide, or prior antibiotic therapy.
Potassium hydroxide mount is extremely reliable
in experienced hands for recognition of fungal
filaments (Figs 24.10 and 24.11) and acanthameba cysts
(Fig. 24.12).27 Detection of thin, branching filaments Fig. 24.11: Hyaline, filamentous, septate, branching
fungal hyphae in potassium hydroxide mount of
of Nocardia species has also been reported.28 Better corneal scraping
clarity has been reported with the use of ink-potassium
hydroxide preparations of corneal scrapings.
In the diagnosis of acanthameba keratitis, smears
stained with calcofluor white, Gram or Giemsa’s stain
Fig. 24.12: Acanthameba cysts in potassium

hydroxide mount of corneal scraping (X 400)
provides early diagnosis. Culture confirmation on
non-nutrient agar (NNA) with Escherichia coli may
Fig. 24.9: Essential requirements for the take 1 to 3 days. The medium however should be
investigation of a corneal ulcer incubated for upto two weeks before taking it to be a
negative culture. Another NNA in flat-bottomed tissue tification and antibiotic susceptibity testing should be
culture flask containing suspension of Escherichia coli employed.29 The majority of fungi causing keratitis
in ¼ Ringer’s solution. The flask is incubated at 37°C can be detected in culture within 3 days. Aspergillus
and examined daily using an inverted microscope for and Fusarium species colonies appear within 48 hrs in
trophozoites. Acanthameba may grow on blood agar blood agar, SDA and BHI (Fig. 24.13). However,
and chocolate agar. Corneal biopsy materials and appreciably characteristic colonies develop only after
corneal scrapings may be processed in the similar 1-2 weeks. Culture media should be observed for at
manner. In addition to calcofluor, Gram or Giemsa’s least 2 weeks before they are considered negative. Rate
staining, fluorescein conjugated lectin, hemotoxylin of growth, colony characteristics, pigmentation,
and eosin delineate the cysts of acanthameba and show microscopic appearance, etc. are taken into account
the characteristic morphology of polygonal double for identification of a fungus species (Figs 24.13 and
walled trophozoites (Fig 24.1). Sometimes, however, 24.14). Unidentifiable strains must be sent to reference
the trophozoites may be difficult to distinguish from centers such as Centers for Disease Control, Atlanta
inflammatory cells. Immunostaining like indirect or Institute of Microbial Technology, Chandigarh.
fluorescein antibody or immunoperioxidase technique
are also used in staining of scrapings or corneal tissue Viral Keratitis
sections. Other staining methods are periodic-acid- The diagnosis of viral keratitis is primarily a clinical
schiff (PAS), Massson’s trichrome stain, Gomor’s one. However, there are several laboratory tests
methanine silver stain may also be used for demons- available if the diagnosis is in doubt. Because of limited
tration of cysts and trophozoites.
The value of Giemsa’s stain for distinguishing
infectious from noninfectious keratitis by the type of
inflammatory cells has not been established. Allergic
keratitis may be suspected by the presence of eosino-
phils. Bacterial and fungal keratitis produce abundant
polymorphonuclear leukocytes. Both fungal filaments
and bacteria appear purple-blue in Giemsa’s stain.
Acanthameba cysts stain dark blue, and the cytoplasm
stains pale-blue.
Gomori methinamine silver stain remains the best
stain for visualization of fungus but suffers the
drawback of being a lengthy procedure. Cell walls and
septa stain black and are easily recognized against the
transparent light green background. Fig. 24.13: Flat, rugose, velvety, light pink colored colonies
Ziehl-Neelsen stain is used when mycobacterial of Fusarium solani on Sabouraud’s dextrose agar
keratitis is suspected. Cold carbol fuchsin or Kinyoun
stain is specific for Nocardia species.28
Lactophenol cotton blue stain, which is generally
used for microscopic examination of fungal cultures,
has been effectively used for demonstration of fungal
elements and acanthameba cysts in corneal scrapings.
Interpretation of Cultures
All culture plates should be examined daily with

magnification, and liquid media should be observed
for turbidity.
Bacterial identification may be accomplished with-
in 48 hours along with its antibiotic susceptibility
pattern. However, it may take longer for slow growing Fig. 24.14: Fan shaped sporulating head of
bacteria and anaerobes. Standard procedures for iden- Asperguillus flavus
amount of infected corneal material, laboratory

diagnosis is generally accomplished by obtaining
conjunctival exudate and scraping for viral cultures
and immunofluorescence antibody tests. The material
should be inoculated in viral transport medium and
smeared on glass slides. Smears for Giemsa’s stain can
be fixed in methanol and those for fluorescence test
can be fixed in cold acetone. Smears for Papanicolaou
stain may also be made. Herpes simplex virus and
Varicella-zoster virus show typical intranuclear
inclusion bodies (Lipshutz bodies) in Papanicolaou
and immunofluorescence stained smears. Ballooning
degeneration of epithelial cells and a monocytic white
cells infiltrate is demonstrated by Giemsa’s stain. Fig. 24.15: Banana shaped multicellular macroconidia
and unicellular microconidia of Fusarium solani
Techniques of Diagnosis
Following techniques are being evaluated to
improve on the sensitivity and specificity of
conventional tests. An excellent review has been
presented by Narasing A Rao.30
i. Limulus amebocyte lysate assay has proved to
be more sensitive than the gram stained smears
of corneal scraping in the diagnosis of gramnega-
tive bacterial infection. The test detects endotoxin
produced by gram-negative bacteria in subnano-
gram quantities.
ii. Bacteria, fungi as well as acanthameba have been
demonstrated with high sensitivity in smears and
tissues using lectins conjugated with fluorescein
or peroxidase. Concanavalin A, wheat germ agg- Fig. 24.16: Fluorescence of fungal hyphae in corneal
lutinin and lens culinaris agglutinin are the lectins scraping stained with fluorescein tagged lectin (F-con-A)
that are being evaluated. Fungal filaments and
acanthameba cysts in corneal scrapings stained
with fluorescein conjugated concanavalin A (F.
Con-A) are seen in Figures 24.15 to 24.17,
respectively. Nonfluorescent stains like calcofluor
white, blankophor, and uvitex 2B have also been
introduced for rapid diagnosis of mycotic infec-
tions. Electron microscopy, with negative staining
is very useful for rapid diagnosis of viruses,
however, it is less sensitive than culture.
iii. Tagged antibodies in immunoassarys have been
used for the diagnosis of mycotic, viral, and
acanthameba infection. Immunofluorescence and
enzyme immunoassays are highly sensitive and
specific. Specificity of the immunoassays has been
enhanced by the availability of monoclonal anti-
bodies. They have been used in the diagnosis of Fig. 24.17: Fluorescence of acanthamoeba cyst
herpes infections. stained with F. Con-A (fluorescein tagged lectin)
iv. DNA hybridization and use of DNA probes to Gram-negative cocci Gram-negative cocci are sus-
detect infectious agents have been introduced ceptible to a wide range of antibiotics but generally
recently. Such probes to detect HSV, Mycobac- are most sensitive to benzyl penicillin. If gram-
teria, Adenovirus, etc. are available in diagnostic negative cocci bacilli are seen on the initial smear,
test kit forms. They have the potential to detect chloramphenicol or ampicillin should be used for
even a single organism. possible hemophilus keratitis.
Gram-positive rods Pencillin G is the drug of choice for
TREATMENT gram-positive filaments. Topical trimethoprim-sulfa-
Medical Treatment methoxazole has been shown to produce dramatic
cure in Nocardia keratitis.
Bacterial Keratitis
Gram-negative rods A wide range of gram-negative
Specific antibacterial therapy should not be instituted rods can cause bacterial keratitis, pseudomonas being
without appropriate microbiological evaluation. Ina- the most common. Gentamicin is the initial antibiotic
dequate antibacterial treatment may suppress but not of choice while tobramycin is equally effective.
eliminate replicating bacteria within the cornea and
mask the typical features. The treatment of bacterial Acid fast bacilli Rarely, acid fast bacilli, such as
keratitis involves the rational choice of the appropriate Mycobacteria, may cause corneal ulceration following
antibacterial agent, based on the microscopical local trauma or surgery.
examination of corneal scrapings, culture and Both these species belong to atypical mycobacteria
sensitivity findings and the selection of the optimal group. An aminoglycoside such as amikacin sulphate
route and frequency of drug delivery, as determined has been shown to be effective when these organisms
by the severity of the corneal inflammation. are identified. Fortified amikacin drops (50-100 mg/
ml) have been used half or an hourly. Atypical
Initial Treatment Mycobacteria may be resistant in vitro to many antibio-
The initial management of bacterial corneal infection tics including antituberculous drugs.
includes a topical cycloplegic-mydriatic agent to No organisms identified Topical fortified Gentamicin (14
minimize the pain of ciliary spasm and to prevent iris mg/ml) and fortified Cefazoline (50 mg/ml) provide
synechiae. Maximum effect can be achieved with the widest antibacterial cover.
combination of 1 percent atropine and 10 percent
phenylephrine hydrochloride. Intraocular pressure
should be monitored and if found elevated nonmiotic Selecting the Route and Frequency
antiglaucoma medication such as topical 0.5 percent for Drug Delivery
timolol maleate or an oral carbonic anhydrase inhibitor Tables 24.2 to 24.4 elaborately show antibiotics and
should be begun. The patient is preferably hospi- their doses in detail. Systemic therapy usually is not
talized. Carefully selected patients can be treated as necessary for the adequate treatment of bacterial
outpatients.31 In contact lens, wearing the develop- corneal ulcers except for those caused by Neisseria
ment of a corneal ulcer is an indication for discon- gonorrheae and Haemophilus influenzae. However, if the
tinuing contact lens wear till the ulcer is fully healed. infectious process involves the sclera or penetrates into
the anterior chamber, intravenous therapy should be
Choosing the Appropriate Antibacterial Agent considered as an adjunct to topical and periocular
The selection of the initial antibacterial agent is based treatment. Preparation of topical antibiotics (commer-
on the smear morphology and a knowledge of the cially not available) is shown in Table 24.3.
responsible microorganisms.
Viral Keratitis
Gram-positive cocci A first generation cephalosporin
such as cephazolin sodium for corneal ulceration Primary Herpes Simplex Virus Infection
caused by gram-positive cocci and third generation Antiviral ointment (Acyclovir 3%) should be applied
cephalosporin antibiotics may provide for anti- to the eye five times a day for about 21 days in primary
staphylococcal coverage. HSV ocular infection. Goal of treatment should be to
Table 24.2: Initial antibiotic therapy

Routes Drugs Alternatives Durations
Topical Cefazolin (33 mg/ml) Bacitracin (9,600 units/ml) 4 weeks dosage
tapering (eye drops)
Subconjunctival (once a day) Cefazolin (100 mg) Ticarcillin (6.3 mg/ml) 5-7 days
Tobramycin (40 mg)
Other Drugs (4 times/day) Cycloplegics Oxacillin or Methicillin 4 weeks
Anticollagenolytic Acetylcysteine Gentamicin (40 mg) 1 week
(every 2 hours) (Mucomyst) 20 percent
Table 24.3:32 Preparation of topical antibiotics Table 24.4: Subsequent antibiotic therapy for
commercially unavailable specifically diagnosed bacterial corneal ulcers
1. Penicillin G A. Pseudomonas corneal ulcer
a. Remove 5 ml of “tears” from 10 ml tear substitute Topical
bottle. 1. Topical gentamicin 15 mg/ml (1.5%)
b. Add 5 ml of “tears” to 1 vial of penicillin G (5 million 2. Tobramycin 15 mg/ml (1.5%)
units). 3. Carbenicillin 4 mg/ml (0.4%)
c. Replace 2.5 ml of reconstituted penicillin into tear 4. Ciprofloxacin 3 mg/ml (0.3%)
substitute bottle (5 + 2.5 = 7.5 ml). Subconjunctival
d. Final concentration of penicillin = 333,333 units/ml. 1. Gentamicin 40 mg (1.0 ml)
2. Cefazolin/Cephaloridine 2. Tobramycin 40 mg (1.0 ml)
a. Remove 2 ml of “tears” from a 10 ml tear substitute
B. Staphylococcal corneal ulcer (penicillin sensitive)
bottle and discard.
Topical
b. Add 2 ml of sterile saline to 1 ampoule of Cefazolin
1. Penicillin G 333,000 u/ml
(500 mg).
2. Bacitracin 10,000 u/ml
c. Add 2 ml of reconstituted Cefazolin into tear bottle
Subconjunctival
(8 + 2 = 10 ml).
1. Penicillin G 0.5-1.0 million units
d. Final concentration of Cefazolin = 50 mg/ml.
2. Gentamicin 40 mg
3. Gentamicin (If patient allergic to penicillin)
a. Add 2 ml of parenteral Gentamicin to the 5.0 ml
dropper bottle of commercial ophthalmic gentamicin C. Staphylococcal corneal ulcer (penicillin resistant)
(3.0 mg/ml). Topical
b. Final concentration of Gentamicin = 14 mg/ml. 1. Cefazolin 50 mg/ml
2. Bacitracin 10,000 mg/ml
4. Tobramycin
Subconjunctival
a. Add 1.5 ml (60 mg) of parenteral tobramycin to
1. Cefazolin 100 mg
3.0 ml dropper bottle of commercial tobramycin
2. Oxacillin 100 mg
(3.0 mg/ml).
b. Final concentration of Tobramycin = 15 mg/ml. D. Pneumococcus-Streptococcus
5. Carbenicillin Topical
a. Reconstitute 1 vial of Carbenicillin (1 gram) with 1. Penicillin G 333,000 units/ml
9.5 ml of sterile water. 2. Bacitracin, 10,000 u/ml
b. Add 0.5 ml of reconstituted Carbenicillin into 10 ml Subconjunctival
tear substitute bottle. 1. Penicillin G 0.5-1.0 million units.
c. Final concentration of Carbenicillin = 4.5 mg/ml. 2. Cefazolin 100 mg.
6. Bacitracin
a. Remove 6 ml of “tears” from a 10 ml tear substitute
prevent viral replication in cornea and to prevent the
bottle. virus from reaching the corneal nerves and thence to
b. Add 3 ml of “tears” to each of 2 commercial vial of the trigeminal ganglion.
Bacitracin (50,000 units each).
c. Replace 6 ml of reconstituted Bacitracin into tear bottle Recurrent Herpes Simplex Virus (HSV) Keratitis
(6 ml + 4 ml = 10 ml). Epithelial keratitis In dendritic and geographic ulcers
d. Final concentration of Bacitracin = 10,000 units/ml. even without treatment, about 50 percent of active
lesions heal without residue. The cure rate with antivi- lesions with antiviral agents. If after 2 weeks there is
ral treatment is in the order of 95 percent. no evidence of active epithelial disease, but the epithe-
The different antiviral agents available are: (1) lium is still not healed, treatment is similar to that of
acycloguanosine, 3 percent ointment; (2) trifluoro- trophic keratitis, i.e. lubricant ointments, pressure
thymidine, 1 percent drops; (3) adenine arabinoside, patching or a bandage contact lens. However, in
3 percent ointment and 0.1 percent drops; and (4) resistant cases with incapacitating symptoms and
idoxuridine, 0.1 percent drops. severe anterior uveitis, the cautious use of corticoster-
1. Acycloguanosine is administered five times a day. oids combined with topical antiviral and antibiotic
It is more potent than both idoxuridine and cover will be necessary.
adeninearabinoside and as effective as trifluoro-
thymidine, but less toxic. Its mode of action is Stromal diskiform keratitis Diskiform keratitis may
unique, in that it is phosphorylated by the thymi- occur with or without epithelial disease. The first aim
dine kinase specified by herpes virus, and in the is to heal any associated epithelial lesion. Small lesions
form of triphospate it inhibits herpes virus DNA away from the visual axis may be treated conser-
polymerase. Acyclovir is able to penetrate the intact vatively with cycloplegics alone. However, if the
epithelium achieving therapeutic levels in the visual axis is involved topical corticosteroids combi-
aqueous humor. ned with an antiviral cover (acyclovir, trifluoro-
2. Trifluorothymidine is administered every 2 hr thymidine) are required. The steroid drops are initially
during the day. Like Acycloguanosine it heals given three to five times a day and the antiviral agent
about 95 percent of dendritic ulcers within 2 weeks. twice a day. Corticosteroids should be tapered over a
It shows no cross resistance with other drugs and period of several weeks, although some patients will
has little tendency to produce resistant strains.33 need a minimum maintenance dose of steroid for a
3. Adenine arabinoside is administered 5 times a day.
prolonged period of time in order to prevent rebound.
It is as potent as idoxuridine but is less toxic than
Trophic keratitis or metaherpetic keratitis is treated
trifluorothymidine and idoxuridine.
with lubricants, patching and bandage contact lenses
4. Idoxuridine is administered as one drop of 0.1
percent solution hourly during the day and 2 in order to promote epithelial healing.
hourly during night. 0.5 percent of idoxuridine is
applied five times a day. It cures about 80 percent Herpes Zoster Ophthalmicus (HZO)
dendritic ulcers in 2 weeks like adenine arabino- HZO treatment includes cycloplegics for treatment of
side. Its main disadvantages are poor solubility, keratitis, scleritis, and uveitis. The corneal lesions are
the emergence of resistant strains, and toxicity. The insensitive to antiviral agents but usually respond well
toxic effect of idoxuridine are: (a) corneal punctate
to topical steroids. The dose should be very slowly
erosion, epithelial opacification, and superficial
reduced, as an abrupt stoppage may precipitate a
pannus; (b) conjunctival cicatrization; (c) lacrimal
relapse.
obstruction; and (d) contact dermatitis.
Systemic use of cytosine arabinoside and acyclovir
By 4th day of treatment with antivirals, the lesion
should start to diminish in size and by 10th day it have been tried but there is no clear evidence as to the
should have healed. If by 7th day there is no response, usefulness of these drugs. However, in a prospective,
resistance to the antiviral agent should be assumed double-masked placebo-controlled trial oral acyclovir
and either another agent substituted or debridement (600 mg 5 times daily for 10 days) was tried in the
carried out. treatment of HZO. Patients who received the drug
within 72 hours of eruption of vesicles showed prompt
Risk of recurrence There is a one in four chance of second resolution of signs and symptoms and had a signi-
attack of HSV keratitis within 5 years of the initial
ficantly shortened duration of virus shedding.34
episode. If a second attack occurs, the risk of further
recurrence within the next two years is increased to Fungal Keratitis
about 50 percent.
Corneal scrapings and cultures are done prior to
Stromal necrotic keratitis In stromal necrotic keratitis instituting therapy. Extensive curettage of the ulcer is
treatment is controversial, difficult and frequently very helpful in removing not only devitalized tissue
unsatisfactory. The first aim is for healing of epithelial but also fungal elements. The smear is evaluated and
if fungi are seen, topical therapy is started without midine isothionate, 0.15 percent dibromopropamidine
waiting for the culture report. If the smears are nega- isothionate, 1 percent miconazole, neosporin and
tive antifungal therapy can be continued provided the systemic ketoconazole.44
history and clinical appearance warrant this approach. Treatment of Acanthameba keratitis is unsatisfactory.
Antifungal agents can be broadly divided into: (1) Ocular pain associated with the disease should be
polyenes, (2) imidazoles, and (3) pyrimidines. The controlled with retrobulbar alcohol injection, and
mainstay of therapy has been the polyene antifungal medical therapy should be used in all cases postponing
antibiotics. They include amphotericin B, nystatin and keratoplasty.21 Other workers consider penetrating
natamycin. Natamycin 5 percent suspension is the keratoplasty to have a major role in the treatment of
drug of choice for filamentous fungi.35 Polyenes bind this disease.45,46 A recent case report has suggested
preferentially to ergosterol of the fungal plasma that if the diagnosis is made early, the disease may be
membrane, thereby altering membrane permeability eliminated by simple epithelial debridement and
and disrupting the fungal cell. Amphotericin “B” is topical medication. 47 Interpretation of results of
effective against candida.36,37 It is used in a concen- medical or surgical therapy is difficult for numerous
tration of 0.15 to 0.3 percent.38,39 reasons;14 for example, there are cases reported that
Imidazole compounds are also useful. The avail- have achieved successful visual outcome through
able imidazoles are clotrimazole, miconazole, medical therapy alone, following penetrating kerato-
ketoconazole, and econazole.40 plasty without medical therapy or by a combination
Ketoconazole can be given topically in a dose of of medical and surgical treatment. Cryotherapy to the
1.0 percent.41,42 It has been tried orally also. Miconazole host cornea before a penetrating keratoplasty as an
1 percent has had success againt Candida, Aspergillus adjunctive treatment to medical and surgical therapy
and few other fungi. The halogenated pyrimidine, has been shown to decrease recurrence of the infection
flucytosine is effective against Candida. Resistance can after penetrating keratoplasty.48
be induced with prolonged therapy and it should
possibly be used as a combination with other antifun-
Noninfectious Corneal Ulceration
gals. Its antifungal activity is related to deamination
by a fungal enzyme. The one important fact to The management of sterile corneal ulcerations requires
remember is that there is no place for steroid therapy a three tiered approach (Table 24.5). First, the etiology
in filamentous fungal corneal infection due to only and primary therapy must be determined. Second,
fungistatic effect of the available antifungal agent.43 epithelial healing must be promoted. Third, the
It has been shown that the stromal penetration and ulceration must be limited.
efficacy of all available antifungal agents is better
when the epithelium is debrided. Hence it is recom- Determination of Etiology and Primary Therapy
mended that the corneal epithelium be scraped daily
especially in deep stromal fungal infiltrate.43 The initial evaluation of the melting cornea is crucial,
because etiological factors determine both the selection
Acanthameba Keratitis of therapy and the prognosis. The choice of appropri-
Current medial therapy for Acanthameba keratitis ate antimicrobial and anti-inflammatory therapy is a
includes the empiric use of topical 0.1 percent propa- particularly critical and difficult therapeutic decision.
Table 24.5: Three-step management of noninfected corneal ulcers
Steps Procedures
I. Determine etiology and primary therapy Examination of eyelids: sensation; culture and scraping;systemic work-up
(Collagen-vascular); dermatological evaluation (rosacea); debridement of
devitalized tissue; antimicrobial therapy; anti-inflammatory therapy
II. Promote epithelial healing Tears and lubricants: eyelid closure (patch, tape, trasorrhaphy); soft contact
lens; conjunctival transplantation; mucous membrane graft
III. Limit ulceration and support Enzyme inhibitors: ascorbate; citrate; medroxy progresterone acetate;
immunosuppression; tissue adhesive and soft contact lens glued on hard
contact lens; conjunctival flap; conjunctival resection; keratoplasty (patch,
lamellar keratoplasty, penetrating keratoplasty); keratoprosthesis
The choice of antibiotic and antiviral drugs depends
primarily on the pathogenic organism, but judgment
must be exercised carefully as epithelio-toxic antiviral
drugs (idoxuridine) and allergenic antibiotics
(neomycin) may confound the healing process.
The use of anti-inflammatory drugs, particularly
corticosteroids, can be a most difficult point to decide.
The ability of topical steroids to suppress anterior
segment inflammation, thereby promoting epithelial
recovery and limiting inflammatory cell mediated
stromal destruction, is highly beneficial. Corti coster-
oids usage during the first week after chemical or
thermal burn suppresses the acute inflammatory
response. On the other hand, corticosteroids can
suppress repair processes to the extent of potentiating Fig. 24.18: Corneal ulceration in the inferior half of cornea
further ulceration and perforation. Thus, in the pre- due to neurotrophic keratitis
sence of clinically progressive ulceration, topical
steroids must be rapidly tapered or discontinued.
Promotion of Epithelial Healing

Although stromal thinning sometimes occurs in the
presence of a continuous corneal epithelium or
beneath a conjunctival flap, rapid ulceration is highly
unlikely when the overlying epithelium is intact.
Therefore, the closure of an epithelial defect should
be encouraged by every possible means. In cases of
minimal corneal exposure of decreased sensation,
particularly following herpes simplex or herpes zoster
keratitis, copious artificial tears or ointments help to
protect the vulnerable epithelium until it adheres
Fig. 24.19: Bandage contact lens given for a persistent
tightly to the stroma. epithelial defect
Eyelid closure with tape or pressure patching may
be especially useful in cases of neuroparalysis and stromal ulceration. A combination of corticoster-
(Fig. 24.18). When more permanent eyelid closure is oids, fibronectin and epidermal growth factors have
needed, a tarsorrhaphy is extremely useful. been shown to heal epithelial defects faster.49,50
The continuous wear, ultrathin, therapeutic soft
Limitations of Ulceration and Support of Repair
contact lens used as a bandage to protect loosely
attached or nonadherent regenerating epithelium Every effort must be made to suppress or delay
from the wind shield action of the blinking eyelids, stromal degradation until newly generated blood
has significantly reduced morbidity and simplified vessels can deliver serum antiproteases, macro-
therapy of many recurrent erosions and persistent globulins, and other inhibitors of collagenolytic
epithelial defects (Fig. 24.19). Frequent use of lubricants, enzymes, and until normal healing processes provide
prophylaxis with antibiotics and close follow-up are adequate structural reinforcement. Since proteolytic
mandatory. enzymes play a fundamental role in the biochemistry
In patients with unilateral chemical burns, conjunc- of ulceration, inhibitors of these enzymes, predo-
tival transplantation is another means of restoring minantly metal binding agents may be used. In topical
epithelial integrity of the ocular surface and thereby form 0.20 percent acetyl cysteine or 0.20 percent
decreasing inflammation and lessening the frequen- cysteine (mucomyst) or 0.2 percent ethylenediamine-
cies of recurrent erosion, persistent epithelial defects tetraacetic acid (EDTA) can be given every 2 hourly.
Ascorbate deficiency of the ocular anterior segment conjunctival flap may be indicated to prevent
following experimental alkali burns can be treated by perforation and to halt further destruction. Alternati-
topical and systemic administration of ascorbate; vely, when the ulcerative process is peripheral or
hence, the use of systemic ascorbate and topical limited in area, a partial or bridge conjunctival flap,
sodium ascorbate 5 percent every 2 hours may prove particularly of vertical orientation, may spare the
beneficial. A combine treatment with citrate and central cornea and facilitate visual recovery as well.
ascorbate topically has been shown to have better In case of central corneal ulcer, which requires
penetrating keratoplasty for ultimate visual rehabilita-
result. 51,52 Systemic tetracyclines have shown an
tion, procedures such as glue application or conjuncti-
inhibitory effect on corneal ulceration probably by an
val flap may buy time till the inflammatory process
anticollagenolytic action.53
quietens and the eye becomes structurally stable. This
Unlike corticosteroids, progestational steroids may is especially to avoid extensive peripheral anterior
have the important pharmacological effect of reducing synechiae and severe secondary glaucoma. Intensive
inflammation without suppressing wound repair. steroid should be used pre and postoperatively if non-
Immunosuppressive therapy with antimetabolites or infectious etiology is the cause of the perforation, to
high dose corticosteroids is gaining attention as a reduce the inflammation.
treatment for the devastating ulcerative disorders A therapeutic penetrating keratoplasty helps in
including Mooren’s ulcer, ocular pemphigoid and debridement and structural support, however, recur-
rheumatoid keratitis for which an autoimmune etio- rence of infection is not uncommon in fungal keratitis
logy is suspected. as shown in Figure 24.21.
Tissue Adhesives
Tissue adhesives, particularly isobutyl cyanoacrylate
is used as an adjunct to the surgical management of
corneal perforations. Although, structural support is
perhaps the most important contribution of tissue
adhesives to the treatment of corneal perforation, these
adhesives also aid in: (1) tectonic support, (2) exclusion
of polymorphonuclear leukocytes in tears, (3) exclu-
sion of intrastromal polymorphonuclear leukocytes,
(4) exclusion of damaged epithelium, and (5) promo-
tion of neovascularization.
The area to be glued is first debrided and then
carefully dried. The adhesive polymerizes instantly Fig. 24.20: Sterile corneal ulceration with a descematocele
when it comes in contact with moisture. After
application, a soft contact lens is applied over the
adhesive to diminish any irritation caused by the
irregular surface of the adhesive and to prevent
dislodging of the adhesive by the eyelid movements.
Surgical Management of Corneal

Ulceration and Perforations
When stromal ulceration progresses relentlessly
despite aggressive pharmacological approaches and
the application of tissue adhesive when available, then
a conjunctival flap, a blow-out patch and other kerato-
plasty procedures should be considered (Fig. 24.20).
When the prospect of visual restoration is limited by Fig. 24.21: Therapeutic penetrating keratoplasty
extensive scarring and stromal destruction, a total with recurrence of infection in host cornea
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4. Meyers ER, Petit TH, Maxwell A. Viral antigens in the 26. Arffa RC, Avni I, Ishibashi Y et al. Calcofluor and Ink-
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Ophthalmol 1980;98:897. J Ophthalmol 1985;100:719.
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6. Easty DL. Virus Diseases of the Eye. Year Book Medical literature. Ind J Ophthalmol 1990;38:50.
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1989;107:283.
9. Ormerod LD, Hertzmark E, Gomez DS et al. Epidemiology
31. Croden LR, Brinsen JH. Outpatient treatment of microbial
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32. Osborn E, Baum JL, Ernst C, Koch P. The stability of ten
10. Kenyon K. Decision making in the therapy of external eye
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11. Parrish CM, O’Day DM, Hoyle TC. Spontaneous fungal 33. Coster DL, Jones BR, McGill JI. Treatment of amoeboid
corneal ulcer as an ocular manifestation of AIDS. Am J herpetic ulcers with adenine arabinoside and trifluro-
Ophthalmol 1987;104:302. thymidine. Br J Ophthalmol 1979;63:418.
12. Puttanna S. Primary keratomycosis. J All India Ophthalmol 34. Lobo LM, Foulks GN, Liesegang T et al. Oral Acyclovir in
Society 1969;17:171. the therapy of acute herpes zoster ophthalmicus. Ophthal-
13. Balows A, Hauster WJ, Herrmann KL et al. Manual of Clinical mology 1986;93:736.
Microbiology (5th ed), American Society for Microbiology: 35. Johns KJ, O’Day DM. Pharmacologic management of kerato-
Washington DC, 1991. mycosis. Surv Ophthalmol 1988;33:178.
14. Auran JD, Starr MB, Jakobiec FA. Acanthamoeba keratitis: A 36. Wood TO, Williford W. Treatment of keratomycosis with
review of literature. Cornea 1987;16:2. Amphotericin B, 0.15%. Am J Ophthalmol 1976;81:847.
15. Stehr-Green JK, Bailey TM, Visvesvara GS. The epidemiology 37. O’Day DM, Robinson RD, Head WS. Efficacy of antifungal
of Acanthamoeba keratitis in the United States. Am J agents in the cornea. 1. A comparative study. Invest
Ophthalmol 1989;107:331. Ophthalmol Vis Sci 1983;24:1098.
16. Sharma S, Srinivasan M, George C. Acanthamoeba keratitis 38. O’Day DM, Ray WA, Head WS et al. Efficacy of antifungal
in noncontact lens wearers. Arch Ophthalmol 1990;108:676. agents in the cornea. II. Influence of corticosterorids. Invest
17. Neuheim RC, Brockman RJ, Stopak SS et al. Survival of Ophthalmol Vis Sci 1984;25:311.
acanthamoeba in contact lens rinse solutions. Cornea 1990;9: 39. O’Day DM, Ray WA, Head WS et al. Efficacy of antigungal
290. agents in the cornea. IV. Amphotericin B Methyl ester. Invest
18. Larkin DFP, Kilvington S, Easty DL. Contamination of contact Ophthalmol Vis Sci 1984;25:851.
lens storage cases by acanthamoeba and bacteria. Br J 40. Fitzimons R, Peters AL, Med M. Miconazole and ketoconzole
as a satisfactory first line treatment of keratomycosis. Am J
19. Savithri Sharma, Garg P, Rao GN. Patient characteristics,
41. Komadina TG, Wilkes TKI, Shock JP. Treatment of Asper-
diagnosis and treatment of non-contact lens related
gillus fumigatus keratitis in rabbits with oral and topical
Acanthameba keratitis.Br J Ophthalmol 2003;84:1103.
ketoconazole. Am J Ophthalmol 1985;99:476.
20. Berger St, Katsev DA, Mondino BJ et al. Macrospcopic 42. Torres MA, Mohammed J, Cavazos AH et al. Topical
pigmentation in a dematiaceous fungal keratitis. Cornea ketoconazole for fungal keratitis. Am J Ophthalmol
1991;10:272. 1985;100:293.
21. Moore MB, McCulley JP, Luckenback MD et al. Acan- 43. O’Day DM, Ray WA, Head WS et al. Influence of the corneal
thamoeba keratitis associated with soft contact lenses. Am J epithelium on the efficacy of topical antifungal agents. Invest
Ophthalmol 1985;100:396. Ophthalmol Vis Sci 1984;25:855.
22. Wright P, Warhurst D, Jones BR. Acanthamoeba keratitis 44. Larkins DFP. Acanthamoeba keratitis. Int Ophthalmol Clin
successfully treated medically. Br J Ophthalmol 1985;69:778. 1991;31:163.
45. Hirst LW, Smiddy WE, Stark WJ. Corneal perforations: 50. Tripathi BJ, Kwait PS, Tripathi RC. Corneal growth factors:
Changing methods of treatment 1960-80. Ophthalmology A new generation of ophthalmic pharmaceuticals. Cornea
1982;89:630. 1990;9:2.
46. Cohen EJ, Perlato CJ, Arentsen JJ et al. Medical and surgical 51. Pfister RR, Haddox JL, Barr DY. The combined effect of citrate
treatment of Acanthamoeba keratitis. Am J Ophthalmol and ascorbate treatment in alkali injured rabbit eyes. Cornea
1987;103:615. 1991;10:100.
47. Holland GN, Donzis PB. Rapid resolution of early Acan-
thamoeba keratitis after epithelial debridement. Am J 52. Pfister RR, Haddox JL, Snyder TL. Topical citrate inhibits the
Ophthalmol 1987;104:87. adherence of neutrophils to postcapillary venules. Cornea
48. Perry S Binder. Cryotherapy for medically unresponsive 1990;9:238.
acanthamoeba keratitis. Cornea 1989;8:106. 53. Perry HD, Golub LM. Systemic tetracyclines in the treatment
49. Singh G, Foster CS. Growth factors in treatment of nonhealing of noninfected corneal ulcers: A case report and proposed
corneal ulcers and recurrent erosion. Cornea 1989;8:45. new mechanism of action. Am Ophthalmol 1985;17:742.
Chapter 25
Diagnostic Methods in Ocular

Microbiology
Savitri Sharma
Clinical microbiology plays an important role in the RECEPTION PROCEDURES

diagnosis and management of many infectious ocular
All laboratories must have clear criteria for sample
diseases. Several major advances have been made in
collection and transportation. The methods should be
the recent past in this subspecialty.
efficient and provide means for documentation of time
The responsibility of the ocular microbiologists lies
of receipt and specimen acceptability. All samples
in working closely with ophthalmologists to provide
brought to the laboratory must be accompanied by a
diagnosis and expedite management of infectious eye
laboratory requisition form with proper labeling and
diseases. Significant morbidity can be reduced when
accession system.
treatment modality is guided by the knowledge of the
causative organism and its antimicrobial Accessioning System
susceptibility. An ideal ocular microbiology laboratory
should have proper procedures in place for accurate A logbook or a computer file should be maintained in
and responsible maintenance of records, clinical the laboratory for all incoming samples to the
sample collection, appropriate processing of samples, laboratory. Samples and requisitions should be given
recovery and specific identification of causative a laboratory number or accession number which must
organisms, proper quality control, antimicrobial appear on all copies of the requisition, worksheets,
testing of the causative organisms, and rapid reporting culture media, slides, etc related to the sample.
of results. Prompt reporting of initial smear Before processing of samples, the sample and the
examination, results of cornea and conjunctival requisition forms must be examined for acceptability
scrapings or vitreous fluid may provide invaluable which will avoid labeling errors and unnecessary
information in making early decisions on the course processing of poor quality samples. Unlabeled
of therapy. Several findings that may not be obtained samples are not acceptable under any circumstances
by standard culture techniques, may first be available in the laboratory. Adequate measures must be in place
using special stains of smears. Technical advances in to avoid mix up of samples which can have serious
laboratory procedures and instrumentations such as consequences. The sample must be in a proper
monoclonal antibodies, genetic probes, gas liquid container and appropriate transport medium. In
chromatography, enzyme-linked immunoassay, ocular microbiology, however, the samples are
polymerase chain reaction techniques, and serologic directly placed on slides or culture media and
evaluation of immune responses, are all useful in the transport media are generally not recommended.
diagnosis of ocular infections. It is often necessary to
include a combination of tests rather than just one. Reporting System
The following factors are intended as guideline to All results of smears, cultures, and other tests must
various diagnostic methods in ocular microbiology. be recorded in a laboratory logbook, and date and time
of report despatch should be maintained. While some cooling to directly inoculate media plates, media tubes
test results are immediately sent out, some may and to make smears.
require preliminary or interim report followed by a
final report. Smear reports are provided within few Bard Parker Blade Number 15
minutes whereas culture reports are generally sent out
This is an alternative to Kimura spatula and being
at 1 day, 2 days and 7 days.
disposable, multiple blades can be used for collection
Laboratory Data Management of several scrapings (Fig. 25.1).
The final copy of the report should be maintained in a
file in the laboratory for easy retrieval whenever
required. Ideally, a database containing information
regarding all samples received in the laboratory
should be maintained with periodic analysis of the
data. Dissemination of information based on this data
can serve useful purposes for the clinicians, infection
control practitioners, and the microbiologist of a
hospital.
PROTOCOL FOR COLLECTION OF SAMPLES

The quality of a clinical microbiology laboratory’s
output is largely dependent on proper collection and
expeditious handling of samples. The microbiologists Fig. 25.1: Bard Parker blade no.15 used for collection of
must assist the clinicians in choosing a rational corneal ulcer scrapings and conjunctival scrapings
approach to sample collection by explaining the role
of various organisms in eye disease processes. The
Calcium Alginate Swab
ophthalmologists, on the other hand, must also
familiarize themselves with various tests that are Moistured with trypticase soya broth this swab has
performed in the laboratory in terms of their scope been reported to yield statistically significant and
and limitations. higher retrieval rate of bacteria compared to platinum
In general, the quantity of clinical material spatula, from cases of bacterial keratitis.2 However,
available from the eye is very small, therefore, special in another study no significant difference was found
procedures are required to collect and process them, between Bard Parker blade no.15 and calcium alginate
which will ensure optimum utilization of the sample. swab for bacterial as well as mixed corneal ulcers.3
Direct inoculation of culture plates or tubes at the Calcium alginate swab is superior to cotton swab in
patient’s side in the clinic or ward ensures a better being soluble in special medium, thereby releasing all
chance of recovery of many fastidious organisms that organisms collected by it. However, calcium alginate
cause eye infections. The laboratory should make sure swabs are not freely available in India, so it requires
that the materials needed for specimen collection are to be imported.
available in the outpatient unit, inpatient ward, and
the operating room. Advice should be accessible from Needle and Syringe
the laboratory regarding selection of media and tests,
These are useful for collecting fluids (aqueous or
which may be modified according to individual
vitreous) or pus for routine and anaerobic cultures.
circumstances.
They may be used to transport sample to the
laboratory directly with the needle stuck in a sterile
Sample Collection Devices
rubber cork to prevent air entry.
Kimura Platinum Spatula
Cotton Swabs
This is one of the most commonly used device for
collection of corneal and conjunctival scrapings.1 The Though commonly used, cotton swabs are not ideal
platinum tip can be used repeatedly after heating and for collecting clinical samples from the eye.1 They have
Chapter 25: Diagnostic Methods in Ocular Microbiology 183
been shown to adversely affect the isolation of certain laboratory diagnosis of infectious keratitis is corneal
organisms. However, samples from lids and scraping collected directly from the ulcer bed and
conjunctiva may be collected using swabs moistened margins with the help of spatula or blade. Multiple
in sterile saline or a liquid broth. Dacron or polyester scrapings can be taken under topical anesthesia (0.5%
tipped swabs are preferred. proparacaine hydrochloride or 4% lignocaine hydro-
chloride) with the aid of a slit lamp or operating
Glass Slides
microscope. Prior to collection of scrapings a sterile
These can be used for direct preparation for smears cotton swab may be used to remove loose debris or
for staining. Slides must be cleaned using chromic acid discharge from the surface of the ulcer. Scrapings are
(dichromate-sulphuric acid cleaning solution) or collected for at least three smears and several culture
methyl alcohol and dried well (wrapped in aluminum media. The choice of media in a clinically nonviral
foil in hot air oven) prior to use. The part of the slide ulcer should encompass a wide range allowing for the
containing the sample should be marked on the growth of all bacteria, fungi, and Acanthameba
reverse using wax pencil. Properly labeled slide (Table 25.1). All smears are made and culture media
should be sent to the laboratory. are inoculated at patient’s side and transportation of
the samples to microbiology laboratory in any other
Sample Collection Methods
form is not advisable.
Ophthalmologists require special training during their
residency to perform direct inoculation of culture Table 25.1: Sequence of smear preparation and culture
media and slides at the patient’s side. They must media inoculation for the diagnosis of non-viral keratitis
familiarize themselves with the requirements for Smears
collection of material from various affected parts of 1. Potassium hydroxide and/or calcofluor white
the eye. 2. Gram’s stain
3. Giemsa’s stain
Blepharitis Media
4. Blood agar-aerobic
Using cotton, Dacron or polyester tipped swab which
5. Blood agar-anaerobic
is moistened in a liquid broth (thioglycollate, brain 6. Chocolate agar
heart infusion, trypticase soya, etc) the lid margins 7. Brain heart infusion broth
are rubbed, especially over ulcerated areas. Two 8. Thioglycolate broth
swabs can be collected, one for culture and the other 9. Nonnutrient agar
for smear. The swabs are directly rolled over solid 10. Sabouraud’s dextrose agar
media or swirled in liquid media under laminar flow Optional smears/media
hood. 11. Potato dextrose agar
12. Lowenstein-Jensen medium
Conjunctivitis 13. Brain heart infusion broth with antibiotic
14. Non-nutrient agar
In the presence of discharge in the lower conjunctival
15. Extra smear on slide
sac/lower fornix, any of the moistened swabs can be
used for collection of the material. Care should be
taken to avoid touching the lid margin and the Corneal biopsy material or corneal button collected
surrounding skin. Accumulated discharge at the at penetrating keratoplasty are useful clinical materials
canthi can harbor extraneous contaminant organisms for the diagnosis of infectious keratitis, especially
and must never be collected. when the corneal scrapings have yielded negative
Conjunctival scrapings of upper or lower tarsal results. Tissue is either homogenized or cut into small
conjunctiva is recommended for viral and chlamydial bits aseptically and placed over media selected on the
cultures and smears. basis of clinical suspicion. Normally one medium each
for bacteria, fungus, and Acanthameba is inoculated in
Keratitis the face of ambiguous clinical impression.
It is generally recommended that prior to collecting
Endophthalmitis
corneal scrapings the conjunctival sacs and lid
margins of both eyes are swabbed and cultured.1 The laboratory diagnosis of infectious endophthal-
These cultures are said to be useful in determining mitis requires obtaining intraocular fluid. The
ophthalmologist determines the method of aspiration portion) and the cornea storage medium is
by the site of intraocular suppuration. Ideally, fluid recommended. Bacterial and fungal cultures can be
should be obtained from both the anterior chamber set up using aseptically cut pieces of corneoscleral rim.
and vitreous cavity, however, vitreous cultures are The cornea storage medium can be incubated as such
more valid. 5 In delayed onset pseudophakic and subcultured in case turbidity of the medium is
endophthalmitis the organisms may be demonstrated observed.
in the histopathology and culture of capsular bag.6
If the laboratory is close to the operating room the DIRECT MICROSCOPIC EXAMINATION
sample can be sent in the syringe with a sterile rubber Examination of smears, made from clinical samples
cork stuck on the needle, however, if a delay in and stained by various methods, plays an important
transport is envisaged the sample should be role in the presumptive and definitive diagnosis of
inoculated in appropriate culture media and smears infectious diseases. It may provide important clues
should be prepared in the operating room itself. At which can form the basis for initiation of specific
least two smears each for Gram’s and Giemsa’s therapy. Choices of initial stains in unusual ocular
staining should be made and media for bacterial and infections can be critical in establishing a diagnosis.
fungal growth should be inoculated. In the case of unculturable or nonviable organisms,
smear results assume even greater importance by
Dacryocystitis and Canaliculitis
being the only resource available for determining the
Purulent material or concretions can be expressed cause of infection.
through the punctum by pressure over the sac or Apart from stained smears, microscopy of the
canaliculus. A metal spatula should be used to transfer clinical samples also includes other techniques such
this material to culture media or slides. Alternatively, as fluorescence and electron microscopy. Availability
a moistened swab can be used especially in small of monoclonal antibody procedures such as immuno-
children. Concretions should be crushed on a slide cytochemistry has further expanded the value of initial
with the spatula or by using another slide, to obtain a smear examinations in a variety of ocular infections.
thin smear. Mixed infections with aerobic or anaerobic In most cases a definite diagnosis of an infectious
bacteria as well as fungi are common; therefore, process is achieved by combining smear and culture
appropriate media should be included. results. Examination of more than one smear stained
by 2-3 techniques also provides greater chances of esta-
Orbital Cellulitis blishing a diagnosis and better correlation with
culture.8
From an open drainage site, specimen may be collected
in the same manner as for lacrimal discharge. A closed
Light Microscopy
abscess can be aspirated using syringe and needle and
specimen can be processed like intraocular fluid. A standard light microscope uses 4x, 10x, 40x and 100x
objectives and 10x ocular lens which provide a
Contact Lenses and Solutions magnification of 40, 100, 400, and 1000 times,
respectively. The resolving power of a light
Contact lenses should be removed aseptically and
microscope is 0.2 μm. Most bacteria, fungi, and
placed in 2 ml of sterile saline and transported to the
parasites can be identified using light microscope.
laboratory. The lens cases with solutions can as such
Common staining procedures for light microscopy of
be sent to the laboratory. The solution can be cultured
clinical samples in ocular microbiology are given in
for bacteria, fungus, and Acanthameba as any other
Table 25.2. Several other staining techniques may be
fluid and the lens can be cultured by sandwich
adopted according to the clinical need. Histopatholo-
technique.7 In addition, the lens case can also be
gical stains like Grocott-Gomori Methenamine silver
swabbed and processed for bacteria, fungus, and
and Hematoxylin and eosin can also be performed for
Acanthameba.
smears. Papanicolaou stain for the demonstration of
intranuclear inclusions may be done in suspected viral
Donor Corneal Rims and Media
infections.9 Impression cytology staining procedures
In most corneal services of ophthalmic centers the have their own place in the diagnosis of dry eye
culture of corneoscleral tissue (after excision of donor syndromes.10
Table 25.2: Common staining procedures in ocular Fluorescence Microscopy
microbiology
Fluorochromes are dyes that are excited by ultraviolet
Methods Steps
light of short wavelength. They absorb UV light when
A. Gram’s stain 1. Fix smear in 95 percent methanol excited and then return to normal state by releasing
2. Flood smear with crystal violet
the energy and producing a visible light of longer
for 1 minute
3. Rinse with tap water
wavelength thereby self illuminating, a process called
4. Flood smear with Gram’s iodine fluorescence. Observation of organisms can be
solution for 1 minute enhanced by exploiting this phenomenon which is
5. Rinse with tap water made possible by fluorescence microscopes.
6. Decolorize with acetone-alcohol Knowledge of the affinity of certain organisms have
solution for fluorescent dyes allows us to detect them in clinical
7. Rinse with tap water
samples or to identify them in cultures.
8. Flood with safranin or dilute
Carbol Fuchsin for 30 seconds Calcofluor white stain is a rapid fluorescent
9. Rinse with tap water and allow to dry. staining procedure11 used to detect fungi, Acanthameba
B. Giemsa’s stain 1. Fix smear in fixative for 5 seconds cysts or microsporidia spores in smears. It binds to
(Diff Quik)TM 2. Dip in reagent A for 5 seconds β1-3, β1-4 polysaccharides such as cellulose and chitin
3. Dip in reagent B for 5 seconds and fluoresces apple-green or bluish-white depending
4. Rinse in water and allow to dry.
on the filters used (Table 25.2). It can be used in
C. Giemsa’s stain 1. Flood with Giemsa’s solution for
45-60 minutes combination with potassium hydroxide (KOH) for
2. Rinse in 95 percent ethanol better detection of fungi and Acanthameba cysts. The
D. Potassium 1. Add one drop of 10 percent KOH Acanthameba trophozoites, however, do not fluoresce
hydroxide with 10 percent glycerol with calcofluor white stain.
(KOH) 2. Place a cover slip Acridine orange is a fluorescent stain which binds
preparation 3. Apply nail polish around the to nucleic acid and is a vital stain. It fluoresces green
cover slip edges to prevent drying.
if the organism is alive and red if it is not. However,
E. KOH + 1. Add one drop of 10 percent KOH
Calcofluor 2. Add one drop of 0.1 percent this is only temporary as the dye process itself renders
white calcofluor white with 0.1 percent the organism dead. This stain can be used to highlight
Evans blue solution bacteria in direct smears or cultures.
3. Place a coverslip. Mycobacterial cell wall with mycolic acid has an
F. Z N Acid 1. Flood fixed smear with hot affinity for Auramine and Rhodamine fluorochrome
fast stain (Steaming) strong carbol fuchsin
and they appear bright yellow or orange making
and leave for 5 minutes
2. Rinse with water detection in clinical samples easier. This staining is
3. Decolorize with 20 percent H2SO4 for generally more sensitive and reliable than most acid-
1-2 minutes fast stains.
4. Rinse with water A recently described technique of fluorescent gram
5. Flood with methylene blue counter stain (Live BaclightTM, Molecular Probes Inc) shows
stain for 2 minutes red fluorescence of gram-positive organism and green
6. Rinse with water and allow to dry.
G. Kinyoun’s 1. Flood fixed smear with strong
fluorescence of gram-negative organisms. However,
modification of carbol fuchsin for 2 minutes the method is yet to become a diagnostic tool owing
Acid fast stain 2. Rinse with water to problems with low sensitivity, quenching of
3. Decolorize with 1 percent H2SO4 fluorescence, and change in gram reaction.12
4. Rinse with water Direct fluorescent antibody methods using mono-
5. Flood with methylene blue counter clonal antibodies have emerged as extremely useful
stain for 2 minutes
techniques for the detection of chlamydiae or viruses
6. Rinse with water and allow to dry.
H. Lactophenol 1. Mix specimen or tease small amount in clinical samples or in cell cultures. The monoclonal
cotton blue of fungus colony in a drop of LPCB antibodies labeled with fluorescein isothiocyanate
2. Apply cover slip react specifically with the organism or cell expressing
3. Apply nail polish around edges of the antigen, thereby facilitating detection under
cover slip to prevent drying. fluorescence microscope.
Electron Microscopy chocolate agars (Fig. 25.2) apart from SDA. Recom-
mendation of incubation for 3 weeks is generally not
An electron microscope uses a beam of electrons as
required for ocular fungal pathogens since majority
the source of illumination, the wavelength of which
would appear on the media within one week.
is much shorter than UV light. The resolution achieved
in an electron microscope is 0.005 μm. However, a
Table 25.3: Commonly used media in ocular
major disadvantage with electron microscopy is that
microbiology laboratory
the fixing and preparation process may create artifacts
Media Dehydrated formulation Additives
making many samples difficult to assess.
(Components)
Electron microscopy may sometimes be the only
1. Blood agar Blood agar base or 5-10 percent sheep
method for differentiation of nonculturable viral,
Nutrient agar blood (add to the
microsporidian or other diseases. Cysts of Acanthameba • Peptone base at 42-45oC)
show clear details of ultrastructural components and • Beef extract
nuclei, etc. Bacterial endosymbionts can be observed • Yeast extract
by electron microscopy in Acanthameba trophozoites.13 • NaCl
• Agar
2. Chocolate agar Blood agar base or 5-10 percent blood
CULTURE METHODS
Nutrient agar (add to the base
A variety of culture media may be used in ocular * Peptone at 80°C)
microbiology laboratory (Table 25.3). The choice of * Beef extract
* Yeast extract
media to be inoculated and staining methods for
* NaCl
smears, vary according to the type of sample. Corneal * Agar
scrapings are normally processed for bacteria, fungi, 3. Brain-heart Calf brain infusion Gentamicin or
and Acanthameba and most other ocular samples are infusion Beef heart infusion chloramphenicol
processed for bacteria and fungi. Processing for viral Proteose peptone 5 μg/ml (for
cultures is done whenever indicated. NaCl fungus culture)
Dextrose
Inoculated media plates and tubes must be placed
Na2HPO4
in appropriate atmosphere and temperature for 4. Thioglycollate Tryptose
appropriate length of time (Table 25.4). Once growth broth Yeast extract
is achieved, the careful work-up and processing of the Sodium thioglycollate
isolates begins. It is important that the microbiologist Sodium chloride
becomes familiar with the significance of certain Agar
Cysteine HCl
isolates. An usual “normal flora” of the external ocular
Resazurin
surface can often be a pathogen in eye infections. Sodium bicorbonate
Hemin
Bacterial Cultures Vitamin K
5. Sabouraud’s Peptone Gentamicin
All plates and tubes are examined daily for growth; dextrose agar Glucose (20 μg/ml) or
positive growths are quantitated (on solid media) and NaCl chloramphenicol
identified with sensitivities performed on significant Agar (50 μg/ml)
isolates. Plates or tubes showing no growth are 6. Non-nutrienet Normal saline Live or dead
incubated until 7 days before discarding as “no agar or phosphate Escherichia coli
buffered saline overlay
growth”. Prior to final report a written preliminary
or Pages’ ameba
report should be provided at 24 hrs and after that saline agar
whenever a negative culture turns positive. 7. L J medium Potato flour Whole eggs
Glycerol
Fungal Cultures Asparagine
KH2PO4
Sabouraud’s dextrose agar (SDA) are examined daily Magnesium citrate
for one week. Most ocular fungal pathogens are fast MgSO4
growers and may appear within 48 hrs on blood and Malachite green
Table 25.4: Incubation period and conditions of Acanthameba Cultures
growth for culture media
Since Acanthameba keratitis can mimic fungal, bacterial
Culture media Growth condition Period or viral ulcers it is recommended that all corneal ulcers
(days) be cultured for Acanthameba on two nonnutrient agar
Temperature (oC)Atmosphere (NNA) with E coli overlay. The NNA should be
Blood agar 35 Aerobic 7
incubated at 35oC and 27-30oC and examined daily
under 4x objective to visualize fine serpentine
Blood agar 35 Anaerobic 7 indentation lines with trophozoites on the surface of
Chocolate agar 35 5-10 percent CO2 7 the medium (Fig. 25.3). The media are incubated for
Brain-heart 35 Aerobic 7 7-10 days before reported negative. Initially, appearing
infusion broth trophozoites on the medium surface gradually turn
Brain-heart infusion 25 Aerobic 14
into cysts in 7-10 days time. Detailed morphology of
broth (with antibiotic) trophozoites or cysts can be appreciated by trans-
ferring them in a drop of saline on a slide and obser-
Thioglycollate broth 35 Aerobic 7
ving under the microscope. Subcultures for confir-
Sabouraud’s dextrose agar 25 Aerobic 14 mation of the growth are made by cutting a piece of
Nonnutrient agar 25 Aerobic 7 the agar and placing it inverted on a fresh NNA with
Nonnutrient agar 35 Aerobic 7
E coli.
L-J medium 35 Aerobic 14-42 Viral Cultures
However, longer incubation is required for identifi- In centers where tissue culture facility is available,
cation purposes. Lactophenol cotton blue wet virus isolation techniques may be performed. Both
preparation is the standard procedure for microscopic conventional and shell vial techniques should be
examination of fungal colonies. Fusarium and performed. While choosing cell lines, it is advisable
Aspergillus species are the most common fungi encoun- to maintain one primary cell line (e.g. Primary monkey
tered from ocular samples. Reference laboratories kidney), one continuous cell line (e.g. Vero, HEp 2,
should be contacted whenever unidentifiable isolates HeLa), and one human diploid cell line (e.g. MRC-5).
are seen. Most often, as in ocular virology, results can be given
by 72 hrs using shell vial techniques. Additional cell
Anaerobic Cultures lines may be maintained for specific pathogens like
Chlamydia (e.g. McCoy cells). Specimens collected
Blood agar meant for anaerobic culture are incubated during early stages of an infection and inoculating
in anaerobic jars or cabinets and are examined at 48 them into cell cultures as soon as possible gives best
hrs and thereafter 5 days. Positive isolates must be
gram stained and subcultured aerobically and
anerobically to determine the true anaerobic nature
of the organism. Positive cultures are identified and
sensitivities are performed.
Mycobacterial Culture
Atypical mycobacteria of the group “Rapid growers”
are more commonly found in ocular microbiology
compared to Mycobacterium tuberculosis. M chelonei,
M fortuitum, etc may grow on blood agar as well as
chocolate agar apart from Lowestein-Jensen medium.
All growth need to be stained by gram stain, Zeihl-
Neilsen stain and if possible Auramine-Rhodamine
stain. Cases where mycobacteria are suspected the Fig. 25.2: Aspergillus flavus growth on blood agar and
final “no growth” reports are sent after 6 weeks. chocolate agar after 48 hours from corneal scraping
results. Immunofluorescence and immunoperoxidase

techniques are used to identify viral antigens in
infected cell lines (Fig. 25.4).
INTERPRETATION OF CULTURE RESULTS

The importance of interpretation of laboratory find-
ings in terms of clinical relevance cannot be over-
emphasized. All results must be viewed with the
clinical situation in mind. Familiarity with the normal
flora of the eye is essential for interpretation of culture
and smear results. Also a knowledge of common
laboratory contaminants is mandatory.
The external surfaces of the eye such as lid margins
and conjunctiva are normally not sterile and harbor
certain resident and transient flora. Staphylococcus Fig. 25.3: Surface of nonnutrient agar showing tracks formed
epidermidis, Propionibacterium acnes, and Coryne- by trophozoites of Acanthameba (50 x)
bacterium spp form the most common resident flora
and can be found in 75-80 percent of normal external
microbiota. Staphylococcus aureus, Streptococcus spp and
Branhamella catarrhalis may also be found in 5-40
percent of normal conjunctiva and lids, however,
presence of gram-negative bacilli and fungi is
relatively rare. Corneal surface normally maintains
sterility owing to the efficient defense mechanisms of
the tear fluid and smooth surface, however, occasional
isolation of conjunctival flora contaminating the
corneal surface cannot be ruled out. On the other hand,
inside of the eye behind cornea and conjunctiva is an
absolutely sterile compartment.
Significance of organisms that are normal
commensals is generally uncertain in the etiology of Fig. 25.4: Immunoperoxidase staining of vero cell line infected
an infection in the presence of scanty growth on the with Herpes simplex virus-1 showing presence of viral antigen
primary inoculum or growth in a single liquid in the brown stained cells (500 x)
medium. The same organism, however, may be
significant in the presence of a strong predisposing susceptibility of bacterial isolates. Both the ophthalmo-
factor. We report an isolate as likely to be significant logist and the mircobiologist should be aware,
if the smear results are consistent with culture and/ however, that results of disk diffusion susceptibility
or if the organism is grown on more than one medium tests relate to levels of drug achievable in serum and
and/or the same organism is grown from repeated do not relate directly to the concentration of drug
samples. These criteria are not applicable to the produced in the preocular tear film and ocular tissues
isolation of Acanthameba, since it can grow only in one by standard routes of administration. Estimation of
medium and is neither a normal flora nor a conta- the minimal inhibitory concentrations (MIC) of
minant. In case of fungus, though growth in culture antibiotics may provide more useful information to
has generally been accepted as the gold standard, in the ophthalmologist than simply labeling an isolate
5-10 percent cases fungal elements seen in smears may as susceptible or resistant. The panel of agents to be
fail to grow in culture.14 tested should be based on drugs used in an institution
or community and the relative susceptibility of the
ANTIMICROBIAL SUSCEPTIBILITY TESTING organisms.
Kirby-Bauer disk diffusion technique15 remains the Stringent quality control measures are critical in
most widely used test to determine antimicrobial achieving reliable antibiotic susceptibility results by
disk diffusion method. Density of the inoculum, type usage in the identification of Acanthameba at the
of medium, thickness of the medium, duration of generic and species level as well.21
incubation, and concentration and potency of the drug Efforts are being made to improvise the diagnosis
in the disks all can affect the zone of inhibition. of mycotic keratitis by assaying fungal chitin in corneal
The value of antifungal susceptibility testing for samples.25
therapy of ocular fungal infection is yet to be esta- A recent study compared the PCR assay, based on
blished, however, broth dilution as well as disk 18Sr RNA with conventional microbiological tests for
diffusion methods have been described. Recently, an diagnosis of Acanthameba keratitis and results
E test to determine MIC of antifungal agents has also confirmed the efficacy of the PCR assay, although the
been described.16 Antimicrobial susceptibility test for sensitivity was equal to that of smear examination of
Acanthameba 17 has been reported in the recent corneal scrapings.22 Genus and sub-genus specific
literature though most laboratories are yet to use the oliginucleotid probes for detection of Acanthameba in
method routinely. Minimum cysticidal concentration clinical specimens and cultures have also been
of various antiacanthameba drugs can be measured described.23 Some studies have focused on the tissue
using microtiter plates. reaction and pathogenesis of Acanthameba in the
cornea.24
NEWER METHODS IN THE DIAGNOSIS REFERENCES

OF OCULAR INFECTIONS 1. Jones DB, Leisegang TJ, Robinson NM. Laboratory diagnosis
of ocular infections-Cumitech 13. Washigton DC: American
Advances in techniques such as immunohistoche-
Society for Microbiology, 1981.
mistry, immunocytochemistry, fluorescence micros- 2. Benson WH, Lanier JD. Comparison of techniques for
copy, enzyme immunoassays, radioimmunoassays, culturing corneal ulcers. Ophthalmology 1992;99:800-04.
and molecular biology have made way into the 3. Jacob P, Gopinathan U, Sharma S, Rao GN. Calcium alginate
swab versus Bard Parker blade in the diangosis of microbial
microbiological diagnosis of various ocular infections.
keratitis. Cornea 1995;14:360-64.
In some instances these techniques have been able to 4. Sharma S, Sankaridurg PR, Ramachandran L et al. Is the
replace the conventional methods. conjunctival flora a reflection of the pathogenic bacteria
Immunoassays are generally based on the availabi- causing corneal ulceration? Invest Ophthalmol Vis Sci
(Suppl)35: S1947, 1994.
lity of specific antisera against infectious agents.
5. Forster RK. Etiology and diagnosis of bacterial postoperative
Monoclonal antibodies are available against most endophthalmitis. Ophthalmology 1978;85:320.
organisms and they have been used in the diagnosis 6. Fox GM, Joondeph BC, Flynn HW et al. Delayed-onset
of viral, chlamydial and bacterial infections. Several pseudophakic endophthalmitis. Am J Ophthalmol 1991;111:
163.
antigen detection tests are potentially applicable to 7. Sankaridurg PR, Willcox MDP, Sharma S et al. Haemophilus
ocular infections.18 Manufacturer’s directions need to influenzae adherent to contact lenses associated with
be followed for commercially available systems. production of acute ocular inflammation. J Clin Microbiol
Using cloned nucleic acid sequences unique to 1996;34:2426-31.
8. Vinay Agarwal, Jyotirmay Biswas, Madhavan HN et al.
specific microbes, nucleic acid probes (DNA or RNA) Current perspectives in infectious keratitis. Ind J Ophthalmol
have been developed that can detect the presence of 1994;42(4):171-92.
individual infectious agents. This approach could also 9. Plotkin J, Reynaud A, Okumoto M. Cytologic study of
potentially identify the presence of genes for virulence herpetic keratitis. Arch Ophthalmol 1971;85:597-99.
10. Nelson JD, Havener VR, Cameron JD. Cellulose acetate
factors and determinants of antibiotic resistance. Gene impressions of the ocular surface, dry-eye state. Arch
amplification methods have increased the sensitivity Ophthalmol 1983;101:1869-72.
of this technique manifold. With the use of polymerase 11. Hageage GJ, Harrington BJ. Use of calcofluor white in clinical
chain reaction (PCR) and related methods sufficient mycology. Lab Med 1984;15:109-12.
12. Roychoudury B, Sharma S, Reddy MK et al. Fluorescent Gram
DNA can be generated in the sample for detection by stain in the microbiologic diagnosis of infectious keratitis and
chemiluminescent and colorimetric assays. The endophthalmitis. Current Eye Research 1997;16(6):620-23.
technique has been applied to several viral, chlamy- 13. Fritsche TR, Gautom RK, Seyedirashti S et al. Occurrence of
dial, bacterial,19 and Acanthameba20 infections and is endosymbionts in Acanthamoeba spp isolated from corneal
and environmental specimens and contact lenses. J Clin
being developed for many more. PCR has found its Microbiol 1993;31:2211-16.
14. Sharma S, Silverberg M, Mehta P et al. Early diagnosis of 20. Lehmann OJ, Keys MF, Green SM et al. Early diagnosis of
Mycotic keratitis: Predictive value of Potassium Hydroxide Acanthamoeba keratitis with the polymerase chain reaction.
preparation. Ind J Ophthalmol 1998;46(1):31-35. Invest Ophthalmol Vis Sci (Suppl) 1995;36:S182.
15. Bauer AW, Kirby WMM, Sherris JC et al. Antibiotic suscepti- 21. Vodkin MH, Howe DK, Visvesvara GS. Identification of
bility testing by a signle disc method. Am J Clin Pathol Acanthamoeba at the generic and specific levels using the
1966;45:493. polymerase chain reaction. J Protozool 1992;39:378-85.
16. Mill K, Wanger A. Susceptibility testing of moulds using E 22. Pasricha G, Sharma S, Garg P et al. Use of 18Sr RNA gene
test. Abs. No. C-248, Pg.163, Abstracts of the 97th General based PCR assay for the diagnosis of Acanthameba keratitis
Meeting of the American Society for Microbiology Florida, in non-contact lens wearers in India. J Clin Microbiol 2003;41:
USA, 1997. 3206.
17. Hay J, Kirkness CM, Seal DV et al. Drug resistance and 23. Stothard DR, Hay J, Schroeder-Diedrich JM et al. Fluorescent
Acanthamoeba keratitis. The quest for alternative anti- oligonucleotide probes for clinical and environmental
protozoal chemotherapy. Eye 1994;8:555-63. detection of Acanthameba and the T4 18Sr RNA gene
18. Sobol WM, Torres GJ, Osato MS et al. Rapid Streptococcal sequence. J Clin Microbiol 1999;37:2687.
antigen detection in experimental keratitis. Am J Ophthalmol 24. Vemuganti GK, Sharma S, Garg P et al. Keratocyte loss in
1989;107:60. Acanthameba keratitis. Phagocytosis, necrosis or apoptosis?
19. Jett BD, Shepard B, Gilmore MS. Detection of Staphylococcus Ind J Ophthalmol 2000;48:291.
epidermidis and Staphylococcus aureus in vitreous by poly- 25. Robinson RD, Oeltmann TN, Head WS, O’Day DM.
merase chain reaction. Invest Ophthalmol Vis Sci Quantitative assay of fungal chitin in experimental kerato-
1995;(Suppl)36:S788. mycosis. Invest Ophthalmol Vis Sci (Suppl) 1995;36:S1021.
Chapter 26
Keratomycosis
Samar K Basak
The first case of fungal corneal ulcer was reported by • The estimated prevalence of corneal ulceration in
Leber in 1879 involving a farmer, who was struck in India is about 80-110 per lakh population.
the eye by oat chaff with resultant keratomycosis
caused by Aspergillus glaucus. 1 Since then, the EPIDEMIOLOGY
ophthalmologists and microbiologists have realized The epidemiological pattern of keratomycosis varies
the importance of fungal infection in relation to cornea. significantly from country to country, and even from
In fact, keratomycosis constitutes upto one-third to region to region within the same country. It is also
half of the cases of suppurative keratitis in tropical climate specific. At least 70 different types of fungi
parts of the world.2 In spite of increasing awareness have been identified as causative agent of
and recognition during last 20 years, kerato-mycosis keratomycosis.4
still remains a diagnostic and therapeutic challenge In tropical and subtropical countries, filamentary
to the ophthalmologists because of the following facts: fungi predominate. Candida species, however, is part
• Its tendency to mimic other type of stromal of the indigenous human flora and are present
keratitis. worldwide. Its relative frequency as a cause of kerato-
• It may be enhanced inadvertently if topical mycosis is increasing in the temperate zone.5
corticosteroids are used.
• Its management is restricted by the availability of COMMON FUNGI RESPONSIBLE FOR
existing antifungal drugs and their penetration into KERATOMYCOSIS
the ocular tissue and effectivity. Filamentous Fungi
It is therefore, important to have a rational Septate: Multiple cross walls that divide the filaments
approach to the diagnosis of keratomycosis in the form into definite cells with one or more nuclei.
of clinical and laboratory techniques on one hand, and
on the other hand to know the antifungals, their Moniliaceae: Fusarium, Aspergillus, Alternaria,
therapeutic efficacy and the alternatives. Cephalosporium and Penicillium.
Dematiaceae: Curvularia, Cladosporium, Dreschlera
INCIDENCE and Bipolaris
• Because of awareness, better recognition and Non septate: (Long tubular protoplasm with numerous
improved laboratory diagnostic technique the nuclei) Mucor, Rhizopus and Absidia.
correct diagnosis of keratomycosis has increased.
• Srinivasan et al3 reported the highest incidence Yeast
(upto 51.9%) fungal infections among all culture- Unicellular (may develop pseudohyphae): Candida,
positive corneal ulcer patients. This high preva- Cryptococcus
lence of keratomycosis in south India is signifi- In northern parts of India, coastal Karnataka and
cantly higher than found in similar studies in Nepal Nepal, Aspergillus spp. is found more frequently.
(17%), Bangladesh (36%) and south Florida Whereas in south India, Fusarium spp. are reported to
(35%).2,3 be the leading aetiological agent causing keratitis.
AETIOLOGY otherwise normal eye. Several days or even weeks may

elapse before the presence of infection is recognized
• Healthy adults.
clinically and patient becomes aware of discomfort,
• More common in male.
photophobia and sometimes with discharge.
• Rural population.
• Fungal ulcer involves the central or paracentral
• Mainly farmers and other agricultural workers. cornea with minimum sign of inflammation.
• Majority of the patients are immuno-competent • The lids are usually normal without edema.
without any external diseases. • Minimum conjunctival congestion is present at the
initial stages. However, the picture may vary if the
PREDISPOSING FACTORS patient receives fortified topical antibiotic and/or
corticosteroid preparation including subconjuncti-
Local factors Systemic factors
val injection.
• Trauma with vegetable • Diabetes mellitus. • Early keratitis has yellowish-white infiltrates,
or organic matter. raised creamy or dirty gray surface with irregular
• Prolonged use of • Malnutrition. feathery edge. This feathery branching pattern of
topical steroids.
the margin is best visible using high magnification
• Structurally altered • Alcoholism.
ocular surface.
under slit lamp. There may be satellite lesions (Fig.
• Contact lens wearer. • Patient on systemic 26.1).
steroids or other As the disease progresses, these initial features may
immunosuppressive therapy. disappear. The clinical picture then degenerates to one
• Postoperative, e.g. • Otherwise immuno- of suppurative ulcerative keratitis. When it becomes
following keratoplasty, compromised individual severe, it involves the deeper stroma with deep corneal
cataract and refractive abscess, endothelial plaque, a fibrinous aqueous
surgery reaction and cheesy non-mobile hypopyon with
convex upper border (Figs 26.2 and 26.4A, B). Immune
PATHOGENESIS ring may be seen rarely. If untreated all fungal ulcer
result in total or partial corneal perforation. But,
• Fungi do not invade intact cornea. They require endophthalmitis is rare in phakic eyes.
devitalized or compromised corneal epithelium. Corneal ulcer caused by dematiaceous fungi has a
• After inoculation, the virulence of fungi relates prolonged and indolent course. The surface has dark
their ability to proliferate within corneal tissue, or brown pigmentation (due to deposition of melanin
resist host defenses and produce tissue damage. pigment), and is raised from the surface and may not
• Fungi secrete various toxic substances, including take fluorescein stain (Fig. 26.3).
proteases, hemolysins and exotoxins. The virulence among different strains of the same
• The large size of the hyphae of filamentous fungi fungal species varies enormously. In general, Fusarium
and of the pseudohyphae of yeasts precludes species are more aggressive and less responsive to
complete ingestion by neutrophil and macro- treatment then are Aspergillus spp.7
phages.
• Fungal corneal infections tend to spread deep into Yeast Infection
the corneal stroma, where the organisms are Most cases occur in patients whose immune system is
inaccessible to the usual diagnostic and therapeutic suppressed by therapy or disease, or whose external
measures. Fungi may even penetrate an intact ocular surface defenses have been altered or reduced.
Descemet’s membrane into the anterior chamber Stromal keratitis caused by Candida spp. is more
and the hypopyon contains live fungal element. localized than filamentary fungal keratitis. They have
a typical collar-button configuration, often with a
CLINICAL FEATURES small ulceration and expanding infiltrates (Fig. 26.5).
Although, the descriptions always emphasize the
Filamentous Fungus
slowly progressive nature of fungal infections,
The onset of keratomycosis is almost always insidious. occasionally the infection develops rapidly with
As mentioned earlier, trauma, usually with vegetable explosive signs of inflammation. This is especially seen
matter, is frequently the precipitating agent in an in immuno-compromised individuals and the eye can
Chapter 26: Keratomycosis 193
Fig. 26.1: Fungal corneal ulcer with feathery edges Fig. 26.4A: Deep keratomycosis with endothelial
plaque and hypopyon
Fig. 26.2: Dense hypopyon with convex border Fig. 26.4B: In retro-illumination, the fungal filaments
can be visible in higher magnificatiion
Fig. 26.3: Pigment producing Dematiaceous fungus Fig. 26.5: Candida keratitis: typical collar-button
configuration of the lesion
be quickly lost unless appropriate early vigorous

treatment is instituted.
LABORATORY DIAGNOSIS
Laboratory work up aids in confirmatory diagnosis
of keratomycosis even though one could make clinical
diagnosis in early cases. A standardized general
approach to the management of any suspected
microbial keratitis should include laboratory protocol
first, because it is impossible on clinical grounds to
determine with certainty the specific infectious
etiological agent of the corneal ulcer. In addition,
mixed infection with bacteria and fungi or with several
species of fungi can occur.
Scraping and Debridement of Ulcer Fig. 26.6: KOH-mount of corneal scraping.

• It helps to reduce the microbial load of the cornea. Note the tubular branching filaments
• It helps for better penetration of antifungal or other
antimicrobial agents.
• It helps in diagnosis of specific type of infectious
agent responsible for corneal ulcer.
Technique of Scraping
As with any corneal ulcer, it is preferable to harvest
the diagnostic material by vigorous scraping with a
No. 15 Bard-Parker surgical blade, or with a Kimura’s
spatula.
It is important to remove the epithelium over the
lesion, if it is intact. The base and edge of the ulcer are
to be scraped vigorously after 1 drop of topical
anesthesia.
The infiltrate in keratomycosis feels tough, dry and
leathery; and have gritty feeling during diagnostic Fig. 26.7: KOH-mount of corneal scraping in the same patient
scraping with spatula or 15 No. Bard-Parker blade. as in Figure 26.3. Note the pigment-producing Dematiaceous
This is an important sign. fungus with cell walls and septa
As a routine, corneal ulcer scrapings are smeared
on two glass slides—one for 10% KOH mount prepa- is simple, cheap, and easy to interpret and yields 80-
ration and the other one for Gram staining. At the same 90% sensitivity when compared to other methods (Figs
time, ‘C’-streaks of scrapped material are plated on 26.6 and 26.7). Gram stain and Giemsa’s stains give
one blood agar plate and one on Sabouroud’s dextrose positive results in 65-80% of cases.
agar plate. The blood agar plate is kept at 35°C in an
incubator and Sabouroud’s plate is kept at room Culture
temperature. Sabouraud’s dextrose agar is used most frequently.
Inoculated plate or tube is kept at room temperature
Smear
and discarded after 3 weeks if there is no growth.
Ten percent KOH, Gram stain, Giemsa’s stain, Gomori Usually fungi start growing within 2-3 days and
silver methenamine stain and Lactophenol stains are species identification is done through side culture.
frequently employed wherever the facilities are Fungi can also grow in blood agar and brain heart
available. Among these, 10% KOH-mount preparation infusion.
Corneal Biopsy periodically break down. Therefore, early diagnosis
is very crucial to preserve some amount of vision.
If the primary clinical suspicion is keratomycosis, but
the smear is negative and cultures are negative after Drugs
72 hours; and the patients is not responding to initial
The available antifungal agents are mostly fungistatic
treatment—then the corneal biopsy is recommended
(except amphotericin B in high doses), requiring an
to confirm fungi histopathologically.
immuno-competent host and a prolonged course of
Biopsy can be performed with a 4 mm corneal
therapy to eradicate the infection. With the exception
trephine or 15 No. Bard-Parker blade.
of Natamycin (FDA approved), most of the antifungals
used by ophthalmologists are developed for use in
Other Methods
systemic mycosis (Table 26.1).
• Yet another approach is to pass a sterile braided
80 silk suture through a deeply situated lesion. The Comments
suture is then laid on a culture medium to observe
• Nystatin was the first polyene antibiotic identified.
for subsequent growth. Anterior chamber
Its ointment preparation has been recommended
paracentesis is rarely indicated, except in drastic
for topical use. But corneal toxicity and poor ocular
situation and should be followed by intracameral
penetration limit its value.
amphotericin B injection.
• Amphotericin B – The most common concentration
• PCR and Confocal microscopy are still under
used is 0.15% in distilled water every half to one
evaluation; but, their costs and complex techniques
hourly. Scraping of epithelium aids its penetration.
limit the general use.
It is the drug of choice for Candida keratitis and
may be an alternative in keratomycosis caused by
MANAGEMENT filamentary fungi. Amphotericin B is unstable, gets
easily contaminated when it is kept at room
Medical
temperature, and should be discarded after 5 days.
Treatment of keratomycosis is formidable and • Natamycin 5% suspension is the treatment of choice
frustrating. The course of recovery is painstakingly in Fusarium keratitis. It penetrates ocular tissue
slow. Weeks of intensive topical medication may be poorly. Tolerance seems to be good; debris from
necessary before it becomes apparent that the keratitis crystallization of the suspension may cause mild
is coming under control. During this period, the to moderate irritation and congestions in the
hypopyon may wax and wane and the epithelium may affected eye (Table 26.2).
Table 26.1: Antifungal preparations for ocular use
Class and Drugs Preparation Mode of Action
Polyenes
Natamycin – 5% suspension Interacts with sterol (ergosterol) in cell membrane,
Amphotericin B – 0.15% solution in D/W or 5% dextrose resulting in leakage of vital constituents
(from I/V preparation)
Nystatin – 100,000 units/ml (ointment)
Pyrimidine
5-Flucytosine – 1% aqueous solution; Inhibits RNA synthesis by intra-cellular conversion
100-150 mg/kg/day orally to 5-fluoro-uracil
Imidazole
Clotrimazole – 1% cream Inhibits demethylation of lano-sterol, preventing
Miconazole – 2% cream formation of ergosterol and damaging cell membrane
Ketoconazole – 2% suspension ; 400 mg/day orally
Triazoles
Fluconazole – 0.3% aqueous solution; 200 mg/day orally Same as Imidazole
Itraconazole – 1% cream ; 200-400 mg/day orally
Table 26.2: Antifungal regimens for keratomycosis

Type of fungus First choice Second choice
Fusarium spp.
• Superficial keratitis Natamycin (5% suspension) Amphotericin B (0.15% drops)
• Deep keratitis Add oral fluconazole or ketoconazole*
Aspergillus spp. Amphotericin B (0.15% drops) Natamycin (5% suspension)
• For Deep keratitis Add oral fluconazole or ketoconazole*
Candida spp. Amphotericin B (0.15% drops) Fluconazole (0.3% drops)
• For Deep keratitis Add oral ltraconazole or fluconazole*
Dematiaceous spp. Amphotericin B (0.15% drops) Natamycin (5% suspension)
*Imidazole and Trizole compounds are hepatotoxic. So, liver function should be monitored during therapy with oral fluconazole,
ketoconazole or itraconazole.
• 5-Flucytosine is having synergistic action with may be necessary before it becomes apparent that
amphotericin B. Many ophthalmologists use the ulcer is healing. Then accordingly, the regimen
topical (1% solution) and systemic (150 mg/kg/ may be modified to 8 to 10 drops/day. But this
day orally) 5-flucytosine with amphotericin B. regimen must be continued for at least 6-8 weeks
• Clotrimazole and Miconazole are usually kept or till the keratitis is healed completely.
reserved as second line of drug in the management • The decision to discontinue the treatment is often
of keratomycosis. a crucial point in the management, as all antifungal
• Ketoconazole (200 mg) tab twice daily can be given agents are fungistatic rather than fungicidal. So,
orally and 2% solution may be used to treat the patient should be observed carefully for
keratomycosis. It is only moderately effective in evidence of recrudescence of infection for at least
keratitis. 1 week to 10 days after cessation of therapy.
• Fluconazole has better penetration after oral
administration. 0.25% - 0.5% aqueous solution may Adjunct Therapy
be used in superficial keratomycosis. Topical
• A broad-spectrum antibiotic drop, e.g., cipro-
preparation is effective against candida. But, oral
floxacin to prevent secondary bacterial infection.
form can be added to natamycin in case of
• Cycloplegics, e.g., atropine eye drop—three times
filamentary keratitis.6
daily.
• Itraconazole 9 is moderately effective against
• Antiglaucoma medications in presence of
filamentary fungi. Investigators from India reported
hypopyon, e.g., Timolol (0.5%) eye drop – twice
the effectivity of topical or systemic itraconazole
daily and/or Tab. Acetazolamide – 1 tab 3-4 times
in 69% cases when use as sole therapy for
daily.
keratomycosis.8
• Tab Multivitamins – 1 tab daily.
Anecdotal report suggest that oral itraconazole,
• If the patient is diabetic, strict control of diabetes
fluconazole or ketoconazole may be a useful adjunct
mellitus.
to topical natamycin or amphotericin B in the
• Improvement of nutritional status.
management of severe or deep keratomycosis caused
by filamentous fungi.
Surgical
It is also evident that in the initial stages of manage-
ment of fungal keratitis, natamycin and amphotericin In spite of adequate and appropriate antifungal
B is mainstay of therapy. Together they provide the medication, 20-27% of all keratomycosis cases do not
broadest possible coverage for fungi likely to be respond to maximum therapy.10 They need surgical
isolated from the cornea. intervention as an emergency measure. Though, a
therapeutic penetrating keratoplasty is the ideal
Dosage Schedule answer in these cases, it necessitates eye bank support
• All drops should be administered ½ to 1 hourly and trained corneal surgeons which are lacking in
round the clock. Weeks of intensive topical therapy most developing countries including India.
Recently, other simple measures are described in weeks. It seems that the vascularized tissue brings
literature in these non-responsive cases with encourag- more immune cells and antifungal antibodies to
ing results. the necrotic area.13
• Intracameral amphotericin B injection: Recent reports Intracameral amphotericin B or the vasculoplasty
suggest a favourable response with 5-10 μg procedure should be used to complement an intensive
intracameral injection of amphotericin B in non- antifungal regimen, not to replace it.
healing deep keratomycosis. The injection may be
repeated for 2-3 times and it is non-toxic for corneal
Therapeutic Penetrating Keratoplasty
endothelium or crystalline lens.11,12 75-100% of the
cases respond with this therapy: Penetrating keratoplasty (PK) should be performed
• Vasculoplasty (transplantation of a conjunctival flap sooner rather than later in cases not responding to
with prominent blood vessels) (Fig. 26.8): This may aggressive antifungal medication. This arrests the
also be considered in those cases where the ulcers progression of the disease and retains the anatomical
do not respond with maximum antifungal integrity of the globe. A fresh tissue is always
medication for 4 weeks. In 78% of cases the results preferable, but in emergency situation a preserved
are encouraging with healing of ulcer by next 4-6 tissue may be very much useful. The recipient button
A B
C D
Figs 26.8A to D: Vasculoplasty procedure (A) Preoperative, (B) Conjunctival flap with prominent blood vessels is sutured near
the ulcer margin, (C) 5 days after operation, note the infiltration and hypopyon reduced, (D) Complete healing after 3 weeks
should have a disease-free margin of at least 1 mm. REFERENCES

Intraoperative anterior chamber lavage with 1. Leber T. Keratomycosis aspergillina als Ursache von hypo-
amphotericin B should be done after cutting recipient pyon keratitis. Graefes Arch Clin exp Ophthalmol 1879;25:
285.
button. 2. Thomas PA, Kalavati CM, Rajasekharan J. Microbial keratitis:
The antifungals should be continued till the A study of 774 cases and review of literatures. J Madras St
infection is totally eradicated. Topical steroids should Ophthal Assoc 1986;23:13.
3. Srinivasan M, Gonzales CA, Goerge C, et al. Epidemiology
be avoided even if one of these ‘hot’ transplant is
and aetiological diagnosis of corneal ulceration in Madurai,
rejected. Secondary glaucoma is common and should south India. Br J Ophthalmol 1997;81:965.
be treated appropriately. 4. Jones DB. Diagnosis and management of fungal keratitis in
After large therapeutic penetrating keratoplasty, Tasman W, Jaeger EA (Eds). Duane’s Clinical Ophthalmo-
logy, JB Lippincott: Philadelphia 1993;4:21.
85% cases maintain the structural integrity of the globe
5. Schell WA, Foulk GN, Perfect JR. Fungal infections of the
of which in 30% cases, the patient might get some eye in Albert & Jakobiec’s Principles and Practice of Ophthal-
amount of useful vision. But re-infection of the graft mology (2nd edn). WB Saunders Co: Philadelphia 2000;1:15,
is reported in 5-7% of cases and such recurrences 160-71.
6. O’Day DM. Fungal keratitis in Corneal Disorders, Clinical
detected are the result of spread through apparently
Diagnosis and, Management, Leibowitz and Waring (2nd
uninvolved cornea.14,15 edn). WB Saunders Co: Philadelphia 1998;26:711-18.
7. O’Day DM. Selection of appropriate antifungal therapy.
Evisceration Cornea 1987;6:238.
8. Abad JC, Foster CS. Fungal Keratitis in Albert & Jakobiec’s
Occasionally, the fungi may reach the anterior Principles and Practice of Ophthalmology (2nd edn). WB
chamber and vitreous, with consequent development Saunders Co. Philadelphia 2000;2:69,906-14.
9. Rajsekharan J, Thomas PA, Kalavati CM et al. Itraconazole
of exogenous fungal endophthalmitis. The visual therapy for fungal keratitis. Indian J Ophthalmol 1987;35:157.
prognosis is very poor, and evisceration sometimes is 10. Rosa RH Jr, Miller D, Alfonso EC. The changing spectrum of
necessary to avoid the orbital spread of the infection. fungal keratitis in south Florida. Ophthalmology 1994;101:
1005.
11. Kaushik S, Ram J, Brar GS et al. Intracameral amphotericin
CONCLUSION
B: Initial experiences in severe keratomycosis. Cornea 2001;20:
During the past 15 years, there has been a major 715.
12. Keriakose T, Kothari M, Paul P et al. Intracameral ampho-
change in the outlook for fungal infections of the tericin B injection in the management of deep keratomycosis.
cornea. In any suppurative keratitis, corneal scraping Cornea 2002;21:653.
followed by simple KOH-mount preparation is a 13. Basak SK, Bhattacharya D. Vasculoplasty: a new surgical
simple way to diagnose keratomycosis early. Newer modality for non-healing fungal corneal ulcer. Scientific
poster no. 11. American Academy of Ophthalmology, Annual
antifungal agents with relatively low toxicity are now meeting; Orlando, Florida 2002;242.
available to treat keratomycosis more effectively. 14. Cristol SM, Alfonso EC, Guildford JH et al. Results of large
Emphasis should be given on preventive aspect and penetrating keratoplasty in microbial keratitis. Cornea
early diagnosis. Better understanding of pathogenic 1996;15:571.
15. Killingworth DW, Stern GA, Driebe WT et al. Results of thera-
mechanisms in corneal inflammation will help further peutic penetrating keratoplasty. Ophthalmology 1993;100:
advancement in treating these difficult cases in future. 534.
Chapter 27
Viral Keratitis
Anita Panda, Archana Sood, Navneet Chauhan
INTRODUCTION Herpes Simplex Viruses are ubiquitous human

pathogens, capable of causing both asymptomatic
Viral keratitis is a common infective disease in both
infection and active disease in a wide variety of end
developing and developed countries.1 The frequency
organs. HSV causing oropharyngeal lesions is
of the incidence has become much greater in India
typically responsible for ocular herpes. Humans are
because of the role of antibiotics in eliminating
the only natural sources of HSV. Transmission occurs
bacterial flora. The development of viral infection
by direct contact with oral lesions or secretions.
depends on:
Therefore, close personal contact, poor hygiene, crow-
• The nature of the virus
ded living condition and low socioeconomic status
• Susceptibility of the host cells
have been implicated as predisposing factors for HSV
• Host resistance
infection.
• Immunological and other systemic factors
HSV is characterized by its ability to infect a host
Though there are a number of viruses responsible
and establish an indefinite and latent presence in
for keratitis (Table 27.1), the two most common viruses
ganglionic neurons. This disease thus occurs in two
causing the lesion are discussed in detail.
forms primary and recurrent. Primary HSV infection
manifests in only 1/6th of individuals, whereas recur-
Herpes Simplex Virus (HSV)
rent disease is more common and may be associated
HSV is a member of family Herpes viridae. There are with upper respiratory infection.
two types of HSV:HSV Type 1 and HSV Type 2. Type 1
virus is more commonly associated with labial and Mode of Infection
ocular infections and Type 2 with genital infection HSV-1 infection is acquired by kissing or when in close
contact with a patient suffering from herpes labialis;
Table 27.1: Viruses responsible for keratitis while HSV-2 infection is acquired venereally.Very
occasionally HSV-2 is transmitted to the eye through
DNA Viruses RNA Viruses
infected genital secretions, particularly in neonates
• Herpes simplex virus (HSV) • Picorna virus during passage through birth canal. 2 HSV-1
– Type I • Ecovirus 70 predominantly causes infection above the waist and
– Type II • Paramyxo virus HSV-2 below the waist.
• Varicella zoster virus • Measles virus
• Cytomegalovirus • Mumps virus Clinical Features
• Epstein Barr virus • Virus causing
• Adenovirus New Castle disease Suspicion of viral keratitis arises if there is:
• Variola • Orthomyxovirus i. Associated skin lesions, recurrence of these
• Vaccinia • Influenza virus A, B, C lesions.
• Molluscum contagiosum • Togavirus ii. Stress-induced recurrence,
• Papova virus • Rubella virus
iii. Patient with immunocompromised status,
• Arbovirus
iv. History of contact,
v. Symptomatic eye with minimal conjunctival and Table 27.2: Classification of HSV Keratitis
corneal signs,
1. Infectious epithelial keratitis
vi. Absence of lid matting • Corneal vesicles
vii. Superficial dendrites with loss of corneal • Dendritic ulcer
sensation. • Geographic ulcer (ameboid)
• Limbal ulcer (marginal)
CLASSIFICATIONS OF HSV- 2. Neurotrophic keratopathy
INDUCED OCULAR DISEASE 3. Stromal keratitis
• Necrotizing stromal keratitis
1. Primary infection: • Immune stromal keratitis (interstitial keratitis)
a. Neonatal 4. Endothelitis
b. Children/Adult • Disciform
2. Recurrent infection: • Diffuse
a. Blepharitis • Linear
b. Conjunctivitis
c. Keratitis terminal bulbs and swollen epithelial borders that
d. Uveitis contain live virus. Staining propensities of this ulcer
are that it stains positive for fluorescein along the
Primary Infection length of the lesion, and the swollen epithelial cells at
the ulcer’s border stain positive for rose bengal.
Primary ocular herpes3 is often atypical. It may present
Dendritic ulcer should be differentiated from other
as acute follicular conjunctivitis or keratoconjunctivitis
branching lesions like healed epithelial defects and
with nonsuppurative lymphadenopathy. Nonspecific
Varicella Zoster pseudodendrites, as these lesions do
diffuse punctate keratitis may be seen initially, which
not stain with fluorescein.
evolves into multiple scattered microdendritic figures.
There may be wandering linear serpiginous ulcers Geographic Ulcer
across the entire corneal surface. The diffuse nature
of this primary epithelial involvement is due to the It is an enlarged dendritic ulcer. This also extends
host’s nonimmune state, which allows widespread through the basement membrane and has scalloped
ulceration. Primary disease as a rule is confined to borders. The typical geographic border differentiates
epithelium clinically. Stromal disease is not usually this condition from healing abrasions and
seen. neurotrophic keratopathy which have smooth borders.
These ulcers are associated with longer duration of
Recurrent Infection symptoms and time of healing. They may or may not
be associated with use of topical corticosteroids.
The morphological classification of recurrent HSV
keratitis4 is shown in Table 27.2. Limbal Ulcer
Of all the types of lesions, infectious epithelial
keratitis is most commonly seen. It is caused by This lesion is characterized by its proximity to the
reactivation of live virus. limbus and is typically seen on presentation as an
inferior stromal infiltrate underlying the ulcer and
INFECTIOUS EPITHELIAL KERATITIS (IEK) limbal injections. Due to its location, symptoms are
(CAUSED BY REACTIVATION OF LIVE VIRUS) 5 more pronounced in marginal ulcers because of the
associated intense inflammation. Its etiopathology has
Corneal Vesicle
two aspects—immune and active viral infection. The
Earliest epithelial lesions are corneal vesicles also immune reaction is more long lasting and may require
known as punctate epithelial keratopathy (PEK). topical corticosteroids to suppress this reaction. An
Within 24 hours, these vesicles coalesce to form the important differential diagnosis is with marginal
typical dendritic ulcer. staphylococcal (catarrhal) disease (Table 27.3).
Dendritic Ulcer Sequelae of Infectious Epithelial Keratitis (IEK)

It is the most common presentation of HSV keratitis. There are four recognized sequelae:
This is characterized by a branching linear lesion with a. Complete resolution
Chapter 27: Viral Keratitis 201
Table 27.3: Differentiating features between HSV marginal ulcer and staphylococcal to marginal ulcer
Features HSV marginal ulcer Staphylococcal Marginal Ulcer
Etiology Active HSV Immunologic response to staphylococcal antigen
Epithelial defect Always seen Absent (If present, late)
Neovascularization Often seen Never
Progression Centrally Circumferentially
Blepharitis Unrelated Usually seen
Location Any meridian 2, 4, 8, 10 O’clock
Nature of lesion First ulceration then infiltrate First infiltrate then ulceration
Corneal sensation Diminished in 80% Sensation normal
b. Dendritic epitheliopathy but progresses to neurotropic ulcer, which stains

c. Stromal scarring (ghost figures on footprints) positive but maintains the oval smooth round shape
or dense scarring and has thickened border due to heaped up epithelium
d. Stromal disease: (Table 27.4).
i. Necrotizing keratitis (true viral infection)
ii. Immune stromal keratitis. Complications of Neurotrophic Keratopathy
• Stromal scarring
NEUROTROPHIC KERATOPATHY • Neovascularization
• Necrosis
Etiology • Secondary bacterial infection
Impaired corneal innervation in combination with • Perforation
decreased tear secretion are the major causative
factors. Patients with infectious epithelial keratitis are STROMAL KERATITIS6
prone to develop this keratopathy which is neither It accounts for 2% of initial episodes but 20 to 48% of
immune nor infectious. Excess use of antivirals also recurrent HSV infection.
contributes to its exacerbation. 1. Primary:
a. Necrotizing
b. Immune or interstitial
Signs
2. Secondary to:
This lesion is characterized by persistent epithelial a. IEK
defect which is usually oval in shape with smooth b. Neutrophic keratitis
borders. It may be stain positive with intact epithelium c. Endothelitis
Table 27.4: Differentiating features of infectious epithelial keratitis and neurotrophic keratitis
Features IEK Neurotrophic keratopathy
Staining Positive –ve or +ve
Morphology Dendrite: Branched with terminal bulbs, Smooth round or oval, heaped up
Geographic: Scallop shaped with swollen border epithelium at borders
Location Anywhere on cornea Inter palpebral area
Etiology Active viral infection Damage to gasserian ganglion, also
iatrogenic
Treatment Topical antivirals Lubricants, tape/tarsorraphy, stop
topical antivirals
Course Resolution in 2 weeks Chronic, suspect if IEK persists > 14 days
Necrotizing Stromal Keratitis cornea, overlying stromal edema, and iritis. Clinical
course and sequelae are similar to diskiform keratitis.
Direct viral invasion of the stroma is found in this rare It is responsive to steroid therapy.
manifestation of HSV.
Linear Endothelitis
Clinical Features
It is recognized by a line of KPs on the endothelium
It is characterized by presence of epithelial defect,
that progresses centrally from the limbus. It is immune
necrosis, ulceration and dense infiltration of stroma.
mediated and associated with stromal and epithelial
It may lead to thinning of cornea and perforation.
edema. It is responsive to aggressive corticosteroid
Stromal Immune Keratitis (Interstitial Keratitis) and antiviral therapy. Treatment is apparently
complex.
This condition is a common recurrent manifestation
in 20% of patients with ocular HSV. Retained viral
DIAGNOSIS OF VIRAL KERATITIS
antigen within the stroma triggers an intrastromal
inflammation. Overlying epithelium is usually intact. Diagnostic modalities include:1
1. Clinical presentation
Clinical Features 2. Direct examination of infected samples cytology
It is characterized by stromal infiltration (punctate 3. Electron microscopy
stromal opacities), stromal edema, immune ring (a 4. Growth of virus in tissue culture
complex precipitate), stromal neovascularization and 5. Detection of viral antigens
lipid keratopathy. It may lead to diskiform keratitis. 6. Serologic tests
7. PCR
ENDOTHELITIS
Rapid diagnosis both clinical and laboratory is
It is an inflammatory reaction of the endothelium essential to prevent severe diseases and bacterial
leading to stromal and epithelial edema. K Ps are infection (Tables 27.5 and 27.6).
usually present in the endothelium.
Table 27.5: Schematic diagram of viral keratitis (clinical)
Pathogenesis
Patient with Dendritic
It is immunological (as improves with steroids) and
immunohistological study confirmed presence of History Physical
HSV-1 antigen in endothelial cells. examination
Diskiform Skin lesions No

It is the most common form characterized by disk- (present or skin
history) lesions
shaped area of stromal edema either central or
paracentral, microcystic epithelial edema, K Ps,
underlying epithelial edema and iritis. There may be
Reduced Normal Drug induced No
raised intraocular pressure (IOP) if associated with
corneal corneal • Topical beta medication
trabeculitis. sensation sensation blocker
Sequelae Diskiform keratitis can heal without • Topical IDU
complications. It can progress to an interstitial keratitis
or necrotizing keratitis, with deep scarring. Benign Herps Keratosis
cases run a course of several months and heal with zoster folliculosis
H/o contact No H/o
minimal scarring. In more severe cases, immune rings, lens use C.L. use
late corneal thinning, scar formation and neovascu-
larization. Consider
Consider Consider
varicella virus
Acanthameba Thygeson's SPK
vaccinia virus
Diffuse Endothelitis • Resolving
epithelial defect
It is a rare presentation and is characterized by the • Epstein-Barr virus
presence of epithelial edema, K Ps scattered over entire • HSV
Table 27.6: Schematic diagram for laboratory IMMUNOFLUORESCENCE/
investigations for HSV FLUORESCENT ANTIBODY TEST
Direct Immunoflourescence
Pricinple Fluorescent conjugated antibodies can be
Specific tests Nonspecific tests used to locate antigen in tissues.
 Viral culture  Cytology Advantage: It is a rapid, simple and more sensitive
(gold standard)  Electron microscopy test.
 Antigen detection Disadvantage: Separate fluorescent conjugates have
 PCR
 Serology
to be prepared for each antigen. This can be overcome
by indirect immunofluorescent test in which human
antiglobulin fluorescent conjugate is used.
Sources of Specimen Collection Enzyme-Linked Immunoabsorbent Assay (ELISA)

1. Corneal scraping Principle
2. Conjunctival swab/scraping Conjugation of an enzyme to either an antigen or
3. Tear fluid antibody and use of enzyme activity as a quantitative.
4. Vesicular fluid 1. Microassay plate is coated with antigen.
5. Skin scraping 2. Test serum is added and incubated.
6. Nasopharyngeal swab 3. Antigen antibody reaction occurs if antigen is
present.
Processing of the Infective Sample 4. After washing, antihuman immunoglobulin
1. Smear for staining antibody conjugated with an enzyme is added.
2. Smear for rapid antigen detection 5. Colour development implies a positive test.
3. Culture: 6. Enzyme activity is estimated colorimetrically and
a. Direct inoculation related to antigen concentration.
b. Transport media: Advantages
i. 0. 2 molar sucrose phosphate in buffer
1. Simple and versatile technique
ii. Eagle’s minimal essential medium.
2. Need no special equipment
3. Very sensitive
SPECIMEN EXAMINATION
4. Need only microliter of quantitative test reagent.
Tissue specimens are usually examined directly in
Disadvantages
conjunction with specific stains by light or electron
microscopy. The commonly used stains include High rate of false positively.
Giemsa, Wright, Papanicolaou, eosin hematoxylin and
VIRAL PROPAGATION IN TISSUE CULTURE
methylene blue. Multiple examination may indicate
cytopathic effects characteristic of some infections such This is the most definite method for diagnosis of viral
as Tzanck cells which are multinucleated giant cells infection. However, it is a very slow process and may
with faceted nuclei and Lipschutz bodies which are offer only limited growth. There are three types of cell-
intranuclear inclusion bodies seen in HSV and lines (CL) based on the origin of chromosomal pattern
varicella virus. Viral particles can sometimes be and ability for serial culture.
demonstrated on electron microscopy. Primary cell lines — Rhesus monkey kidney CL
— Human amnion CL
RAPID ANTIGEN DETECTION7 Diploid cell lines — Human embryonic lung strain
— Human embryonic fibroblasts
1. Immunofluorescence: Continuous cell lines — Human carcinoma cervix C
a. Direct Hela
b. Indirect HEP 2 — Human epithelioma of larynx
2. ELISA test Mc Coy — Human synovial cell carcinoma
Methods of Detection of Virus Table 27.7: Polymerase chain reaction (PCR)

Growth in Cell Culture
Advantages Disadvantages
1. Cytopathic effect: • Very sensitive • High rate of false negatives
a. Herpes—balloon degeneration • Highly specific • Requires skill
b. Adenovirus—bunch of grapes-like clumping • Rapid and accurate • Expensive and not
c. Measles—syncitium plaque formation is seen diagnosis when culture easily available
in advanced stages and serology are
equivalent
2. Metabolic inhibition of cells in the culture indicated
• Diagnosis is possible
by pH indicator (phenol red) with wide degraded
3. Hemadsorption samples
4. Interference by adding a noncytopathogenic virus
5. Immunofluorecence Technique of PCR
6. Transformation into tumor-like masses. The PCR cycle consists of three basic steps of
denaturation, annealing, and DNA synthesis
SEROLOGIC TEST (Table 27.7).
Most tests depend on a paired comparative analysis Denaturation

of sera obtained during acute and convalescent phases It is done to melt the template into single strands by
of infection. An increase in antibody titre opening the heating in presence of large molar excess of each of
convalescent phase by four-folds or greater indicates the 2 known oligonucleotides and 4 d NTPs neopyri-
primary infection. Other serodiagnositic tests are thiamine. It is carried out at 94°C for 1-2 minutes
based on analysis of antibody levels of varying specific during regular cycles. Amplification of genomic DNA
antigens, e.g. ELISA, RIA, immunodiffusion. requires a larger initial denaturation of 5 minutes to
i. Antigen-antibody complex formation— comple- melt the strands.
ment fixation and hemagglutination
ii. Effect of antibody as a function such as neutra- Annealing
lization. It is done to allow the primers to hybridize to the temp-
late. This is carried out at the temperature determined
by the strand melting temperature of the primers and
Disadvantages
by the specificity desired. Typical reaction is at an
1. Some infections do not raise IgG levels such as annealing temperature of 55°C for 1 to 2 minutes.
persistent, latent or recurrent disease. Reactions recurring greater stringency may be
2. Antibody titres behave differently in immuno- annealed at 60-65°C.
supressed individuals.
3. Time required may be too long for the immune DNA Synthesis
response to occur. Extensions to synthesize the new DNA strands is
4. These tests are either confirmatory or they are carried out at 72°C which is optimal for Taq poly-
judged in conjunction with other test. merase. The amplification time is determined by the
length of the sequence to be amplified and 20-30 cycles
of PCR are sufficient for many applications.
POLYMERASE CHAIN REACTION (PCR)
It is a technique of gene amplification developed to Management
identify and replicate known gene sequences. Using Currently available antiviral drugs are listed in
this technique, it is possible to detect the genome even Table 27.8.
when it is in very small quantities. Thus, it is superior
to other extensively used techniques of microbiolo- IDU
gical detection like microscopy, staining, culture It inhibits DNA polymerization and incorporates in
methods, etc. which require much more organism load viral RNA to inhibit protein synthesis. It is a toxic drug
than is required for the PCR test. as it also affects the host cells.
Table 27.8: Currently available antiviral drugs
Agent Mechanism of Administration Topical Viral resistance Toxicity
action penetration
IDU Pyrimidine analog. Inhibits Drop 0.1% one Poor. + +++
thymidine kinase, thymidylate hourly by day Effective when
kinase and DNA polymerase. and 2 hourly epithelial
Incorporated into viral DNA by night integrity lost
Oint. 0.5%
Vidarabine Pyrimidine analog Oint. 3% – Less than IDU ++

Inhibits synthesis of viral DNA 5 times/day
Mech. unknown
Trifluorothymidine Pyrimidine analog Drop 1% Good Rare ++
Inhibits thymidylate synthetase 9 times/day
Incorporated into viral DNA
Acyclovir Purine analog Oint 3% Good + +
Activated by viral thymidine 5 times/day
kinase IV
Inhibits DNA polymerase Oral 400 to 800 mg
5 times/day
• It is poorly soluble because of decreased bioavaila- BVDU

bility
It is similar to Acyclovir in all aspects it is available in
• It is less potent
both drop and ointment form.
• Recommended dose schedule is 1% drops 1 hourly
by day and 2 hourly by night Disadvanges
Resistance to mutant viral strains, which take
Vidarabine advantage of host thymidine kinase. Specific antivirals
• It inhibits DNA polymerization are less effective in these cases.
• It is a safe drug with little toxicity effect. Adverse side effects of antivirals
• It is highly insoluble • Lacrimal puncta occlusion/edema
• It is less potent • Follicular conjunctivitis
• 3 ointment 5 times/day • Limbal edema
• Punctate staining of cornea (SPK)
Trifluridine • Superficial vascular pannus
• It has similar action as IDU • Filamentary keratopathy
• It is more potent • Inhibition of healing of epithelial trophic ulcers and
• Recommended dose schedule is 1% drops times/ stromal wounds
day for 2-3 weeks
ROLE OF STEROIDS:9 CONTROVERSIAL
(Table 27.9)
Acyclovir
Advantages
It is more specific and selective agent as it does not
affect host cells as it is not activated by phosphory- It inhibits:
lation in host cells. It is only activated by virus infected • Cellular infiltration
cells containing viral thymidine kinase. Acyclovir • Opacification and scarring
inhibits HSV DNA by binding to DNA polymerase • Release of toxic enzymes
and acts as chain terminator.8 Acyclovir in ointment • Neovascularization
form is efficacious as compared to other drugs, with
less toxicity. Disadvantages
Recommended dose schedule is 3% ointment 5 • Exacerbation and spread of active viral infection
times/day (topical) and 800 μg 5 times/day (oral). by suppression of normal host immune response
Table 27.9: Indications for corticosteroids and antivirals • Endothelitis

in the treatment of different forms of HSV keratitis • Iridocyclitis
• Trabeculitis
No steroids
• HSV conjunctivitis
• Infectious epithelial keratitis Steroid Therapy
• Mild immunostromal keratitis without prior steroids Three schools of thought:
• Mild diffuse endothelitis
• Initial low then increase to high dose
• Noninflamed neurotrophic keratopathy
• Initial high then decrease to low dose
Topical steroids • According to level of inflammation (avoid abrupt
• Marginal keratitis stopping of steroids to prevent recurrence)
• Moderate immune stromal keratitis
• Moderate disciform and diffuse endothelitis
• Inflamed neurotrophic keratopathy Indications of Oral Steroids
• Moderate trabeculitis • Severe immune stromal keratitis
Oral steroids (along with topical) • Disciform endothelitis
• Severe immune stromal keratitis • Diffuse endothelitis
• Severe disciform and diffuse endothelitis • Iritis
• All cases of linear endothelitis • Linear endothelitis
• Severe trabeculitis
Topical antivirals GUIDELINES FOR TREATMENT
• HSV blepharitis
• HSV conjunctivitis Primary Disease
• Infectious epithelial keratitis
Primary disease is usually fairly localized and self-
• Prophylaxis in steroid treatment of immune stromal
keratitis limiting. It responds well to topical antiviral for 14-21
days, supported by antibiotics and cycloplegics.
Oral Acyclovir Healing occurs without scarring. Gentle debridement
• Primary HSV
is recommended before application of topical drugs.
• Selected cases of diffuse endothelitis
• Selected cases of severe trabeculitis
• Linear endothelitis Recurrent Disease
• Immunocompromised patients
Infective Epithelial Keratitis (IEK)
• Pediatric patients refractory to topical medication
• Prophylaxis against recurrent IEK The goal of treatment of IEK is to get rid of line virus
• As prophylaxis for post-PK patients with history of HSV in a timely manner.
keratitis
Gentle debridement with sterile cotton-tipped
applicator is the first step to undertake. If viral culture
• Stimulates viral replication is to be performed, tissue for culture should be
• Enhancement of collagenolytic enzyme production obtained before debridement. Topical antiviral
with corneal thinning therapy [(Acyclovir 3%) ointment 5 times/day] is
• Creation of steroid-dependent ocular tissue by prescribed thereafter. Topical cycloplegics and broad-
allowing build up of viral antigens. spectrum antibiotics are used, especially in larger
• Steroid-induced glaucoma and cataract dendritic and geographic ulcers.
Topical antiviral therapy is continued up to 2
Complications of Steroid Therapy weeks after which it is rarely necessary, as healing of
• Stromal necrosis and perforation IEK is known to occur within this period of time. If
• Secondary microbial invasion ulceration persists after 14 days of treatment, one must
suspect neurotrophic keratitis or stromal involvement.
Steroids are beneficial in The smooth borders of neurotrophic keratitis are
distinguished from the scalloped borders of IEK.
• Marginal keratitis Another reason for non-healing may be resistance
• Immune stromal keratitis to the antiviral medication and an alternative
medication may be considered. Vidarabine, which is reduction of stromal inflammation and decrease
activated by cellular enzymes may be effective against in the duration of immune stromal keratitis.
strains resistant to acyclovir and trifluridine, which Therefore, topical steroids along with topical
rely enzyme thymidine kinase for activation. antiviral coverage and supportive therapy (cyclo-
Topical steroids are not recommended for treat- plegics, antibiotics, lubricants) are the recommen-
ment of IEK unless several immune stromal ded treatment of choice for immune stromal
inflammation is present. keratitis. Oral steroids may be used in severe cases.
The starting dose of steroid may be low initially
Neurotrophic Keratopathy (NK) and slowly increased unto the minimal necessary
dose for control of inflammation. A high initial
NK results from impaired corneal innervation and dose followed by slow tapering cause is also
decreased tear secretion. Chronic use of steroid often suggested to control inflammation rapidly. The
leads to this condition. best option is to customize the initial dose
Therapy is aimed at decreasing exposure of the according to the level of inflammation and avoid
cornea to toxic substances while increasing lubrication. rapid tapering or abrupt discontinuations.
The first step of therapy is to stop all unnecessary
topical medications, especially topical antivirals. Indications for Oral Acyclovir
Artificial tears (without preservatives) promotes Treatment of Active Viral Disease
epithelial healing. Prophylactic antibiotics with broad-
Indications
spectrum topical antibiotic may be considered in • Primary HSV keratitis
significant ulceration. Gentle debridement may be • Immunocompromised patients (AIDS, organ
beneficial for removal of abnormal boggy epithelium transplant recipients)
which acts as a mechanical barrier to new epithelial • Patients with infectious epithelial keratitis and
migration. Therapeutic soft contact lenses are an atopic eczema.
additional option for nonhealing neurotrophic ulcer.
Advantages
It is limited to short-term use for the risk of infectious
• Course of disease is shortened
bacterial keratitis. Cyanoacrylate glue may be used to
• Chance of corneal involvement decreased
seal a perforation. Conjunctival flapping may also be • Decreased morbidity and recurrence.
considered.
Another method is tape or temporary tarsorrha- Prophylaxis Against Recurrence
phy. Botulinum toxin injected into the levator muscle Recommended dose schedule is 400 mg BD (up to 1
induces this atleast for 3 months. Surgical tarsorrs- year in post-PK patients)
haphy is the most effective option and has been known
to resolve persistent neurotrophic ulcers in a few Indications Frequent recurrent infectious epithelial
weeks time. keratitis.
Post-PK patients with history of HSV keratitis.
Stromal Keratitis Advantages of oral acyclovir are:
• To prevent recurrence which is not attainable with
a. Necrotizing stromal keratitis Epithelial ulceration
topical antivirals
and active stromal disease are contraindications for
• Avoids toxic keratopathy and conjunctival
steroid therapy. This rare condition of direct viral
invasion to stroma is treated with topical antivirals scarring.
with prophylactic antibiotics and cycloplegics. As Adjuvant Therapy and Surgical Treatment
perforation may occur, one should be vigilant and
patch graft, conjunctival flapping or cyanoacrylate Use of therapeutic contact lenses is beneficial in
glue should be considered. Steroids are started persistent epithelial defect and ulceration. Tarsorr-
once the epithelium heals completely. haphy is preferred as discussed earlier. The use of
b. Immune stromal keratitis Topical corticosteroids are conjunctival flapping has diminished with the
valuable agents in the management of HSV stromal advancement of the medical therapy. But it may be
keratitis. The results of the Herpetic Eye Diseases useful in patients with chronic ulcers not responding
Study (HEDS)9 in 1994 showed that the topical to conventional therapy and who have functional
corticosteroid regimen resulted in a significant vision in the fellow eye and a contraindication to
immediate penetrating keratoplasty, especially if the and nasociliary branches of ophthalmic nerve, frontal
visual potential is limited or when delay in more branch is most commonly involved.
definitive surgery is necessary. Nasociliary involvement in HZO is associated with
Performing a PK in presence of severe inflam- a 76% chance of ocular complications. When this nerve
mation carries a much higher incidence of failure and is not involved, risk of ocular involvement is 3.4%.
has unrewarding results.10 PK should be considered HZO virus lies dormant in the trigeminal ganglion
when there is a corneal perforation that cannot be and its reactivation is preceded by a prodrome of
treated with other modalities (like Cyanacrylate glue) malaise, fever and headache, which represents
or when there is a central stromal scar that is viremia. Nasociliary involvement occurs in 1/3rd of
precluding adequate vision. This helps to eliminate the patients of HZO. Hutchinson’s sign classically
the antigenic materials responsible for repeated describes vesicles at the side and tip of nose. It is an
episodes of immunemediated keratitis. Standard indicator of future ocular involvement which occurs
postoperative care must be modified to improve in 50% of patients with Herpes Zoster infection.13
likelihood of graft survival. Use of preoperative topical
antivirals, oral acyclovir along with systemic steroids Corneal Manifestations14
is recommended in selected cases. 11 The risk of
In about two thirds of patients with ocular disease in
recurrent HSV disease is 12 to 19% when PK is
acute HZO, corneal manifestations occur. Virus infec-
performed for corneal scarring. Oral acyclovir should
tion, immune reaction, vasculitis, neural involvement
be used for 1 year postoperatively (400 mg BD) in these
cases. and scarring are different mechanisms of the disease.
Most common findings are dendritic and punctate
HERPES ZOSTER KERATITIS keratitis.
Varicella Zoster virus (VZV) also known as Herpes Corneal Changes

virus 3 is a typical herpes virus containing DNA. This 1. Punctate epithelial keratitis (PEK)
virus is morphologically identical to herpes simplex 2. Pseudodendritic keratitis
virus but different both antigenically and clinically. 3. Anterior stromal infiltrates
Chickenpox and Zoster are different entities caused 4. Keratouveitis/endothelitis
by the same virus. 5. Serpiginous ulceration
Chickenpox represents the primary infection after
6. Sclerokeratitis
exposure of a susceptible or seronegative individual
7. Corneal mucous plaque
to VZV. This virus then becomes latent in the cells of
8. Disciform keratitis
dorsal root ganglion throughout the body. Reacti-
9. Neurotrophic keratopathy
vation by unidentified stimulus may occur resulting
10. Exposure keratopathy
in characteristic dermatomal eruption of Herpes
Zoster. 11. Interstitial keratitis
12. Permanent corneal edema
Epidemiology12
No sexual, racial or seasonal predilection has been PEK
found. This entity is usually associated with conjunctivitis
Age There are more incidences in higher age groups and is characterized by blotchy swollen epithelial cells.
and lowest in children (except in children with Coarse PEKs are peripheral, multiple, raised, small
malignancy. and focal in appearance and stain with rose bengal.
OCULAR INVOLVEMENT PSEUDODENDRITES

Herpes zoster ophthalmicus (HZO) was first described The PEK coalesce to form multiple dendritic or stellate
by Hutchinson in 1865. lesions of swollen raised epithelial cells. They are
It commonly involves the ophthalmic division of broader, more plaque like and without central
5th nerve (other branches, i.e. maxillary or mandibular ulceration when compared to herpes simplex
are less commonly affected). Of the lacrimal frontal dendrites. VZV is present in these lesions.15
ANTERIOR STROMAL INFILTRATES NEUROTROPHIC KERATOPATHY
These represent stromal reaction to soluble viral This is a complex event, associated with neuro-
antigen diffusing into the anterior stroma or direct transmitter reduction, delayed epithelial turnover,
viral toxicity. These lesions appear as hazy granular lower blink frequency with diminished wettability of
dry infiltrate just under the Bowman’s membrane. cells with meibomian gland and tear dysfunction.
Residual nummular scars are markers of previous HZ It is characterized by decreased corneal sensation
corneal inflammation. associated with lack of corneal luster, irregular surface,
mild punctate epithelial erosions, epithelial edema and
KERATOUVEITIS/ENDOTHELITIS boggy stromal ulcers in lower cornea. This condition
may be complicated by corneal thinning perforation
This manifestation represents direct viral invasion of
and superinfections.
the endothelium. After a week of onset, there is sudden
onset of Descemet’s folds with stromal and epithelial EXPOSURE KERATOPATHY
edema. The uveitis ranges from a few KPs to severe
granulomatous reaction centered around the Desce- The main causes of exposure keratopathy in HZO are
met’s membrane. cicatricial lid changes, aberrant lashes and meibomian
gland dysfunction.
SERPIGINOUS ULCERATION
INTERSTITIAL KERATITIS
Corneal thinning due to limbal vasculitis by immune
A nummular scar with vascularization and lipid
mechanism occurs with characteristic crescentic shape
deposition is the end result of these corneal
and peripheral location. There may be vascularization
inflammatory conditions.
and perforation.
SECONDARY CORNEAL EDEMA
SCLEROKERATITIS
Endothelial decompensation may result due to
Scleritis may extend onto the cornea after 1 month of endothelial damage caused by VZV. Vasculitis or
HZO. There may be scleralization, vascularization and immune mechanisms are considered in the etiology.
stromal thinning or peripheral faceting of cornea.
Vasculitis or immune complex depositions are Ophthalmic Complications of HZO
probable etiologies.
Lid
CORNEAL MUCOUS PLAQUES There may be lid edema followed by maculopapular
rash and a vesicular reaction. Healing occurs with
These occur suddenly as coarse grey white branching
scarring resulting in trichiasis, ectropion, entropion,
lesions on the surface of swollen epithelial cells. The
madarosis or poliosis.
onset is typically several months after HZO in a
quiescent eye or in an eye with minimal smoldering Conjunctiva
keratitis. They stain with rose bengal and do not have
terminal branches like HS dendrites. They can be The conjunctival changes may be papillary or follicular
wiped off from the surface leaving abnormal but intact reaction, pseudomembrane formation, transitory
epithelium. Neurotrophic or immune mechanisms vesicles, which may rupture. Severe conjunctival
have been implicated in the etiology. scarring may occur with symblepharon formation.
Sclera and Episclera

DISCIFORM KERATITIS
Mild persistent episcleritis is frequent in the course of
This entity is characterized by a deep, central or
HZO. Scleritis may occur in the diffuse or nodular
peripheral disk-shaped stromal edema with minimal
forms.
infiltrate and intact epithelium. Multiple patches of
edema and circular immune rings develop. This entity
Uvea
represents a VZV viral infection of the endothelium
or an immune reaction to soluble antigen or viral Uveitis is characteristically prevalent and marked in
particles in the corneal stroma.16 zoster keratitis. There may be granulomatous or
nongranulomatous iridocyclitis with extensive keratic DIAGNOSIS OF HZO

precipitates and posterior synechia. There may be (DISCUSSED EARLIER IN DETAIL)
hypopyon or hyphema with secondary glaucoma.
1. Typical clinical picture
Posterior subcapsular cataract may develop.
2. Laboratory tests:
• Morphological
Extraocular Muscles
• Immunomorphological
Third, fourth or sixth cranial nerves may be involved • Viral isolation
separately or simultaneously. Horner’s syndrome may • Serological tests
result from involvement of the sympathetic nervous • Tests of cellular immunity17
system. An orbital apex syndrome with or without 3. Systemic workup for malignancy/immuno-
optic neuropathy may occur. deficiency in some cases.
Optic Nerve and Retina MORPHOLOGIC

Zoster optic neuritis is an ischemic vasculitis along • Tzanck technique;
with macular edema from neuroretinitis, or presenting • Multinucleated giant epithelial cells are seen in
as a retrobulbar neutritis or ischemic optic neuropathy. material from base of vesicles.
Local viral transmission within the orbit may be the Pap smear: Intranuclear eosinophilic inclusion bodies
possible cause of optic neuritis. Ischemic retinitis, may be seen.
perivasculitis, central retinal vein or artery occlusion
or multifocal choroiditis may be seen. Immune Detection
• Of viral antigen
Acute Retinal Necrosis • Of nucleic acid in vesicles
This is a syndrome of diffuse uveitis characterized by • ELISA
peripheral necrotizing retinitis and retinal vasculitis, • PCR (polymerase chain reaction) 18
associated frequently with vitritis and papillitis.
VIRAL ISOLATION
Neuralgia It is carried out by culture (though it is definitive, it is
Acute neuralgia is common and is described as aching, not sensitive).
itching or burning with a lancinating pain. Post-
herpetic neuralgia is persistent pain after the acute rash SEROLOGICAL TESTS
has subsided. This is more severe and common in FAMA (fluorescent antibody to membrane antigen
elderly patients. The pain may be deep aching, sharp tests).
intermittent lancinating pain or superficial hyper- This test is most reliable for VZV specific
sensitivity as burning pain. antibodies.
Systemic manifestations
CELL-MEDIATED IMMUNITY
• Cutaneous dissemination
• Visceral dissemination: Measurement of in vitro proliferative response to
— varicella pneumonia peripheral lymphocytes is done.
— hepatitis
TREATMENT OF HZO
Neurologic manifestations
• Acute neuralgia Therapeutic approach should be vigorous and aimed
• Segmental motor weakness at preventing severe ocular hazards and promoting
• Cranial neuropathies rapid healing of skin lesions as the crust formation
• Encephalitis, myelitis, encephalomyelitis leads to severe trigeminal neuralgia.19
• Guillain-Barré syndrome
General
• Delayed cerebral vasculitis
• Multifocal leukoencephalitis High doses of oral acyclovir (800 mg 5 times/day for
• Postherpetic neuralgia 10 days) for acute cases20 should be started preferably
within 72 hours of onset of disease. There is no role of diagnosis because such treatment could be disastrous
oral acyclovir when the disease is full blown, when if the dendrites were actually caused by herpes
scarring has started, or in presence of neurotrophic simplex. In most cases, no treatment has proved to be
keratitis. effective. Oral acyclovir given for acute HZO reaches
Famciclovir 500 mg tid or valacyclovir, 1000 mg tear film and may have some role.
tid for 7-10 days may also be used.
If the condition is severe or the patient is STROMAL KERATITIS
systemically ill, he should be hospitalized and started Anterior stromal infiltration diskiform keratitis, inter-
with acyclovir 5-10 mg/kg IV 8 hourly for 8-10 days stitial keratitis and sclerokeratitis all respond to topical
Topical antibiotic ointment should be applied to corticosteroids.
the skin lesion BID. The dose is increased in a graded manner and a 6
Warm compress should be given to the periocular hourly regimen is usually sufficient for management
skin TID. of subepithelial haze and inflammation. Topical
steroids are a valuable adjunct for suppression of the
Adults inflammatory component in the anterior segment of
Adults with skin rash of more than 3 days duration or the eye. However, long-term topical steroids lead to
without active skin lesion. corneal thinning and perforation. Adjuvant therapy
a. Warm compress to the periocular skin TID in form of topical antibiotics and cycloplegics is
b. Topical antibiotic ointment to skin lesion BID. mandatory.
Children UVEITIS
Treat as in adults unless there is evidence of systemic Topical and oral corticosteroids are the mainstay of
spread. treatment. They may be combined with oral acyclovir.
For systemic spread, hospitalize and prescribe
acyclovir 500 mg/m2/day in three divided doses for Nonhealing Epithelial Defects
7 days. They result from neurotropic keratitis, exposure,
trichiasis, drug toxicity or anterior stromal
ADVANTAGES OF ORAL ACYCLOVIR inflammation. Treatment is in the form of lubricant
drops, ointments and pressure patching. Therapeutic
• Speeds resolution of skin lesions and prevents
contact lenses, lateral/total tarsorrhaphy and
further eruption of skin lesions
conjunctival flapping are some modes of treatment.
• Reduces viral shedding
• Decreases incidence of dendritic keratitis, stromal Corneal Mucous Plaques
keratitis, anterior uveitis, scleritis, subsequent
chronic stromal keratitis The mainstay of treatment is topical steroid, supported
• Decreases the incidence of postherpetic neuralgia. by lubricants and mucolytic agents.
Pain
DERMAL ERUPTION
— Zoster pain can be a serious problem. The main
• Cool lid compresses, burrows solution modalities of treatment are:
• Topical antibiotic ointment • Levodopa:
• Topical acyclovir (effectivity doubtful). — Dose (100 mg TDS for 10 days)
Punctate epithelial keratitis and dendritic keratitis • Cimetidine:
Acyclovir (topical); although demonstrates in vitro — Modulation of lymphocyte function
susceptibility of HZ, but its efficacy is controversial — Dose (300-400 mg for 14 days)
as evidence of active viral shedding from corneal • Topical capsaicin: It is a substance P depletor and
lesions is lacking and trails of topical antivirals on prevents its reaccumalation. Substance P also acts
dendritic ulcers have not proved to be beneficial. as a neurotransmitter in peripheral pain impulses.
Topical steroids also speed up resolution of these — Dose: 0.025% capsaicin cream for topical
lesions,21 but one must be absolutely sure of the application 4 times/day.
Antidepressants in Postherpetic Neuralgia REFERENCES

• Tricyclic antidepressants 1. A Panda. Ocular Emergency. New Delhi: CBS Publishers and
Distributors (1st edn). 1999;101-112.
• Amitriptyline 25-150 mg OD 2. Nahmias A, Alford C Korones S. Infection of the newborn
• Imipramine hydrochloride 100 mg OD with herpes virus hominis. Adv Pediatr1970;17:185.
• Carbamazepine, chlorprothexine, adenosine 3. Baringer J. The virology of herpes simplex virus infection in
monophosphate have also been tried humans. Surv Ophthalmol 1976;21:171.
4. Liesegang TJ. Epidemiology of ocular herpes simplex. Arch
• In intractable cases stellate ganglion block can be
given. 5. Kaufman HE, Rayfield MA. Viral conjunctivitis and
keratitis—herpes simplex virus. In Kaufman H et al (Eds):
Penetrating Keratoplasty The cornea. New York: Churchill Livingstone 1988.
6. Witcher JP et al. Herpes Simplex keratitis in a developing
As success rate of this surgery is very poor, one should country. Arch Ophthalmol 1976;94:587.
wait for at least 1 year after the disease becomes quies- 7. Kowalski RP, Gordon YJ. Evaluation of immunologic tests
for the detection of ocular herpes simplex virus.
cent.
Healthy donor tissue, postoperative protection of 8. Collum L, Benedict Smith A, Hillary I. Randomized double
epithelium with lubricants, and tarsorrhaphy, increase blind trial of acyclovir and idoxuridine in dendritic corneal
the rate of success of PK. ulceration. Br J Ophthalmol 1980;64:766.
9. Wilhelmus KR. Herpetic Eye Disease study, a controlled trial
of topical corticosteroids for herpes simplex stromal keratitis.
Newer Drugs in the Management of HZO Ophthalmology 1994;101:1883.
1. Famciclovir 500 mg orally TDS for 1-2 weeks 10. Foster CS, Duncan J. Penetrating keratoplasty for herpes
simplex keratitis. Am J Ophthalmol 1981;92:336.
2. Valacyclovir 1000 mg orally TDS for 1 week 11. Jay H Krachmer, Mark J Mannis, Edward J, Holland. Cornea
3. Sorivudine and external diseases. Clinical diagnosis and management.
4. Cidofovir St. Louise, Missouri: Mosby, Volume II, 1997;1191-1238
5. Zidovudine 200 mg Q 8 H 12. Cooper M. The epidemiology of herpes zoster. Eye 1987;1:413
13. Harding SP, Lipton JR, Wells JCD. Natural history of Herpes
6. Live attenuated Varicella Zoster virus vaccine used Zoster Ophthalmicus: Predictiors of post-herpetic and ocular
in the prevention of Varicella Zoster systemic and involvement. Br J Ophthalmol 1987;71:353.
ocular infections. 14. Liesegang TJ. Corneal complications from Herpes Zoster
Ophthalmicus. Ophthalmology 1985;92:316.
Summary of Recommended Treatment 15. Pavan-Langston D, Mc Culley JP. Herpes zoster dendritic
keratitis. Arch Ophthalmol 1973;89:25.
for Acute Herpes Zoster 16. Yu DD et al. Detection of varicella zoster virus DNA in
General Oral acyclovir 800 mg diskiform keratitis using polymerase chain reaction. Arch
5 times a day for 10 days
17. Liesegang TJ. Diagnosis and therapy of Herpes zoster
ophthalmicus. Ophthalmology 1991;98:1216.
Skin involvement Burrows solution 18. Dlugosh D et al. Diagnosis of acute and latent varicella zoster
Cool compress virus infections using the polymerase chain reaction. J Med
Mechanical cleaning Virol 1991;35:136.
Epithelial keratitis Debridement or none 19. Gilbert Smolin, Richard A Thoft. The cornea; Scientific
Stromal keratitis Topical corticosteroids foundations and clinical practice, USA; Little Brown and
Cycloplegics Company (3rd edn). 1994;183-185,204-208.
Oral corticosteroids 20. Wood M et al. Efficacy of oral acyclovir treatment of acute
Corneal mucous plaques Lubricants herpes zoster. Am J Med 1988;85:79.
Topical steroids 21. Pavan Langston D. Herpes Zoster ophthalmicus, medical and
surgical management. In G. Spaeth, Katz (Eds): Current
Acetyl cysteine(10%)
therapy in ophthalmic surgery. Philadelphia: BC Decker
1989;99.
Chapter 28
Corneal Degenerations and

Dystrophies
CK Barua, LC Dutta
Corneal degenerations and dystrophies are a vexing further complicated by lack of agreement and
problem to the ophthalmologists regarding the confusing views as regards to pathogenesis, leading
classification, etiology, natural history, management, to confusion in the inclusion of certain conditions in
and ultimate prognosis. Although, in the literature, degeneration or dystrophy group, e.g. Salzmann’s
not infrequently, there seems to be no clear cut nodular dystrophy is described as a degenerative
demarcation between dystrophy and degeneration, process.1
the following four points are virtually true: The different degenerative and dystrophic
i. Corneal degenerations are usually unilateral with conditions of the cornea, as per topography and site
asymmetric lesions seen mostly in the periphery of origin, are listed without going into any controversy
accompanied by vascularization. as regards to inclusion of certain conditions in the
ii. Normal cells of a particular structure undergo particular entity (Table 28.1).
some pathologic changes under some abnormal
circumstances such as ageing, inflammation, CORNEAL DEGENERATIONS
trauma or systemic diseases.
Epithelial and Bowman’s
iii. Usually no inheritance pattern or genetic predis-
Membrane Dystrophies
position seen.
iv. Onset of lesions usually occur in the middle of Meesmann’s Juvenile Hereditary
life or later and are often progressive. Epithelial Dystrophy
In corneal dystrophies: It is an autosomal dominant inherited bilateral
i. Bilateral symmetrical vascular lesions mostly in symmetrical condition starting early in childhood. The
the central part of the cornea. condition is characterized by appearance of small
ii. They are primary lesions not related to any round or irregular vesicles between the epithelium and
systemic or local disease process and are often the Bowman’s membrane with some surface
inherited (usually autosomal dominant). irregularities. the cornea between the vesicles is
iii. Dystrophies occur early in life and may remain normal. It starts in the interpalpebral area of the cornea
stationary or progress slowly causing gradual loss gradually spreading all over as sinuous lines and small
of vision. gray opacities.2
Classification of corneal degenerations and dystro- Meesmann’s dystrophy may be asymptomatic
phies are often confusing and misleading. Although, during the early stage. The symptoms include
there are differentiating points between these two transient visual disturbance, discomfort, and
conditions they sometimes do not behave like two photophobia when the cysts rupture through the
different watertight compartments. The situation is surface with some loss of corneal sensation.
Table 28.1: Topographical classification of corneal be indicated when epithelial irregularities and
degenerations/dystrophies recurrent corneal erosions endanger vision.
Corneal Dystrophies Band-shaped Corneal Opacity
a. Affecting epithelium and Bowman’s membrane
1. Meesmann’s juvenile hereditary epithelial Band-shaped keratopathy is a calcareous opacification
dystrophy due to extracellular noncrystalline deposition of
2. Inherited-band shaped corneal opacity calcium phosphate and carbonate in the Bowman’s
3. Dystrophic recurrent erosion membrane and superficial layers of the stroma. It starts
4. Reis Buckler’s corneal dystrophy
in the periphery of the cornea leaving a clear zone
5. Anterior crocodile shagreen of Vogt.
b. Stromal dystrophies between the opacity and the limbus. The entry of
1. Granular dystrophy—Groenouw’s Type I corneal nerves through the Bowman’s membrane
2. Macular dystrophy—Groenouw’s Type II appear as black dots in the opaque area. The opacity
3. Lattice dystrophy (Biber-Haab-Dimmer) spreads to the center of the cornea involving the whole
4. Gelatinous drop-like dystrophy interpalpebral strip. The overlying epithelial layer is
5. Central crystalline dystrophy (Schneider’s crystal- usually intact with normal corneal sensation. Band
line dystrophy)
shaped corneal opacity can be distinguished from
6. Fleck dystrophy (Speckled dystrophy of François
and Neetens)
calcareous degeneration of the cornea by the fact that
7. Posterior amorphous corneal dystrophy. the latter usually affects the deeper as well as the
c. Endothelial dystrophies anterior layers. Further, calcareous degeneration of the
1. Corneal guttata cornea is seen in seriously injured eye, phthisis bulbi
2. Fuch’s dystrophy and necrotic neoplasms. They are often seen to be
3. Posterior polymorphous dystrophy accompanied by bone formation elsewhere in the
4. Anterior keratoconus globe.
5. Keratoglobus.
Band-shaped keratopathy may be a primary
Corneal Degenerations disorder or may be associated with the following local
a. Central degenerations ocular or systemic diseases.
1. Cornea farinata i. Local degenerative diseases
2. Salzman’s nodular degeneration
• Chronic uveitis
3. Hyaline degeneration
4. Lipid degeneration • Phthisis bulbi
5. Pigmentary degenerations. • Absolute glaucoma
b. Peripheral degenerations • Juvenile rheumatoid arthritis with past uveitis
1. Arcus senilis • Interstitial keratitis.
2. White limbal girdle of Vogt ii. Trauma
3. Pterygium • Chronic exposure to irritants such as mercury
4. Pellucid marginal degeneration
fumes, calomel, calcium bichromate vapor.
5. Terrien’s degeneration
6. Spheroidal or climatic droplet keratopathy
iii. Hypercalcemia due to
7. Mooren’s ulcer • Hyperparathyroidism
8. Hepatolenticular degeneration. • Excessive vitamin D, as with oral intake,
sarcoidosis with liver involvement, osteoporo-
sis
The characteristic pathological finding of juvenile • Renal failure, as with Fanconi’s syndrome
hereditary epithelial dystrophy is intracytoplasmic (Cystinosis)
collection of fibrinogranular material which may be • Hypophosphatasia
either due to a primary degeneration of the cyto- • Milk-alkali syndrome
plasmic filaments or due to generalized disturbance • Paget’s disease
of cytoplasmic ground substance. Both the epithelial • Idiopathic.
cells and basement membrane are thickened. iv. Miscellaneous conditions
With minimal symptoms and without any visual • Discoid lupus erythematosus
loss this type of dystrophy seldom requires treatment, • Gout (urate crystals)
but soft contact lens and lamellar keratoplasty may • Tuberous sclerosis
Chapter 28: Corneal Degenerations and Dystrophies 215
• Anterior mosaic dystrophy, primary type starts in childhood as superficial corneal opacities with
• Spheroidal or climatic droplet keratopathy recurrent erosions developing 3 to 4 times a year with
(Labrador keratopathy) severe pain, photophobia, and conjunctival hyper-
• Icthyosis emia. Gradually, these attacks become less frequent
• Rothmund Thomson syndrome with bilateral with diffuse scarring of the Bowman’s membrane and
cataract, skin pigmentation, and telangiectasia marked decrease of corneal sensation; corneal surface
• Progressive facial hemiatrophy (Parry-Rom- becomes rough and irregular. The opacities may be
berg syndrome). ring-shaped or geographic or may look like frosted
Treatment of BSO is scraping of the deposits and glass, a fishnet or curdled milk. Vision is grossly
application of EDTA. affected due to surface irregularities and opacification.
Two clinical variants of Reis-Buckler’s dystrophy
Dystrophic Recurrent Erosion
are:
(Epithelial basement membrane dystrophy: i. Anterior membrane dystrophy of Grayson and
Cogan’s microcystic epithelial dystrophy: Wilbrandt, and
Finger-print-map-dot dystrophy) ii. Honeycomb dystrophy of Thiel and Behnke.
This type of dystrophy is usually suspected when In these two conditions the corneal sensation and
corneal ulcer caused by sharp edge like fingernail fails the visual acuity are not severely affected.
to heal after standard treatment. It is characterized by Histopathologically there is destruction of the
recurrent attacks of severe pain specially on waking Bowman’s membrane with replacement by scar
up in the morning, photophobia, blepharospasm, and tissue.4 There is abnormal thickness of the epithelium
watering from the eye with slight reduction of vision. due to intra- and extra-cellular fluid accumulation.
The lesions are usually seen to be concentrated in one Electron microscopic study shows lack of adhesion of
area of the cornea either centrally or eccentrically. epithelial hemidesmosomes in places where Desce-
There may be dot, map and fingerprint opacities. met’s membrane is absent.
The pathology of the condition is probably Treatment, in the initial stage, comprises of
increased hydration of the cornea which is related to bandage soft contact lens and application of hyper-
lid closure which prevents adhesion of epithelial cells. tonic solutions and ointments. Keratoplasty is indi-
During sleep the epithelial tags may get adhered to cated to improve the vision, but recurrence in donor
the lid margins and separation of lids on awakening button may occur.5,6
in the morning results in sharp pain. Another
pathological change is abnormal synthesis of basement Anterior Crocodile Shagreen or
membrane and absence of hemidesmosomes in the Anterior Mosaic Dystrophy of Vogt
area of erosion.3 Hydration of the cornea and forma- This is a bilateral superficial condition, involving the
tion of microcysts under the epithelium prevent firm Bowman’s membrane and deeper epithelial cells. It
adherence of epithelium to the Bowman’s membrane. consists of grayish white polygonal opacities
Treatment Patching of the eye for 48 hours followed surrounded by dark lines. The gray patches corres-
by night application of hypertonic ointment may help. pond to intact Bowman’s membrane and dark lines
In severe recurrent cases mechanical removal of the are the sites of its rupture. The condition is inherited
redundant epithelium followed by tight bandaging as sex-linked recessive disorder.
for 48 hours also help in healing. A thin loose fitting
hydrophilic bandage contact lens worn continuously Stromal Dystrophies
for months along with application of hypertonic Granular Dystrophy—Groenouw’s Type I:
solution is also effective. Lamellar keratoplasty is (Bread-crumb dystrophy)
indicated when all these modalities of treatment fail.
This autosomal dominant type of dystrophy was first
Reis-Buckler’s Dystrophy described by Groenouw in 1898. White opacities in
It was first described by Reis in 1917 and subsequently the superficial stroma of the cornea appear around
with more details by Buckler in 1949. It has autosomal puberty. Visual loss is not severe in early stage.
dominant inheritance with strong penetration. Reis Gradually, the opacities enlarge, coalesce, and
Buckler’s dystrophy is bilaterally symmetrical and progress into the deeper layers of the stroma. Until
fourth or fifth decade the condition remains asympto- accompanying findings. The lattice like corneal
matic; thereafter ocular symptoms like irritation and filaments are thicker than those in type I although less
photophobia with deterioration of vision starts. in number. Visual acuity remains good until about
Histochemical studies show that the substances the seventh decade and recurrent erosions occur late
accumulated in the stroma is a noncollagenous protein in life. In type III lattice dystrophy, broad lattice like
containing tyrosine, tryptophan, arginine and sulphur lines and diffuse subepithelial opacities are seen.
containing amino acid7 and phospholipid. Electron Changes occur after the age of 40 years and the vision
microscopic examination shows amorphous deposits remains good till the seventh decade. Recurrent
produced by abnormal keratocytes in the anterior erosions do not occur.
layer of the stroma. The epithelium, basement memb- Histochemistry shows the deposits in lattice dys-
rane and Bowman’s membrane become irregular in trophy to be amyloid in nature. The epithelium may
thickness or absent in places. vary in thickness with loss of hemidesmosomes and
the basement membrane may be fragmented.10
Treatment In early granular dystrophy usually no
Recent works have shown protein AA and protein
treatment is necessary as the patient is usually
AP in the stromal deposits of lattice dystrophy. In type
asymptomatic. As the disease progresses, penetrating
III a ribbon of amyloid is seen beneath Bowman’s layer
keratoplasty gives excellent visual prognosis.
which remains intact.
However recurrence in donor graft may occur.
Treatment is the keratoplasty but recurrence in graft
commonly occurs.
Macular Dystrophy (Groenouw II)
It is a bilaterally symmetrical autosomal inherited Gelatinous Drop-like Dystrophy
disease. The condition affects the central portion of
This condition starts in the first decade of life. Presen-
the anterior layers of the stroma. It is characterized
ting feature is blurring of vision with photophobia,
by appearance of grayish white opacities in the stroma
lacrimation, and foreign body sensation. In the early
and by the third decade diffuse clouding of the cornea
stage, numerous tiny hemispherical protuberances of
develops which progressively increases in density to
milky opacities are seen 11 which later become
involve the whole corneal thickness extending upto
prominent, yellowish gray colored gelatinous masses.
the limbus.8
They are bilateral and the periphery of the cornea
Macular dystrophy is a localized form of acid
remains clear but rarely neovascularization occurs in
mucopolysaccharide deposition within and around
very late stage.
the keratocytes, between the stromal lamellae and
Histopathologically there is thinning of the
even within the endothelial cells. This is probably due
epithelial layer with amyloid substance in the basal
to deficiency of an enzyme called Alfagalactosidase
cell of the epithelium. Gradually the Bowman’s layer
in the keratocytes and fibroblasts. The treatment is
is replaced by amyloid.
keratoplasty.
Treatment of the condition is preferably deep
lamellar keratoplasty. After a few years the same
Lattice Dystrophy (Biber-Haab-Dimmer)
condition may develop in the transplanted cornea.
Lattice dystrophy has an autosomal dominant inheri-
tance but the Type III variety may be autosomal
Central Crystalline Dystrophy
recessive. Symptoms of recurrent erosion appear by
(Schneider’s Crystalline Dystrophy)
the end of the first decade. Clinically small white
round dots, small refractile lines and a faint central It is a bilateral condition with autosomal dominant
haze appear in the anterior stroma. It is bilateral inheritance12 although a few sporadic cases have been
though unilateral cases have been reported.9 Recurrent reported. Fine needle shaped crystals appear in the
erosions with pain, photophobia, and redness are the anterior part of stroma and Bowman’s membrane
early features of lattice dystrophy. Type II lattice during the first decade of life. These crystals are aggre-
dystrophy is associated with a familial form of gated together to form an oval, discoid or annular
systemic amyloidosis. Progressive cranial and central corneal opacity. The condition seldom pro-
peripheral nerve palsies, dry itchy skin, floppy ears, gresses after second or third decade of life. Central
protruding lips and a mask like facies may be the crystalline dystrophy is frequently seen to be
associated with hyperlipidemia, genu valgum and specular reflection they appear as dark spots against
xanthelasma. The opacification occurs typically in the hexagonal pattern of endothelial surface. The
Bowman’s layer and anterior portion of the stroma. corneal thickness and endothelial cell counts are
Apart from typically in Bowman’s layer and anterior usually normal. Secondary corneal guttata may be
portion of the stroma. Apart from the opacity the associated with trauma, inflammation or degenerative
stroma appears normal with smooth epithelial surface. conditions of the cornea. Treatment is usually not
Recurrent erosion is rare and there is minimum visual required.
impairment.
Histochemically, the crystalline deposits are Fuchs’ Dystrophy
natural lipids or esterified cholesterol; serum
Fuchs first described this condition as epithelial
cholesterol and lipoprotein are found to be normal in
degeneration which was later found to be primarily
most of the patients. This suggests that Schneider’s
endothelial dystrophy with secondary epithelial
dystrophy is associated with abnormal lipid meta-
involvement. The condition occurs mostly in elderly
bolism localized to cornea only.13 Vascularization,
women than men in which bilateral and central cornea
which is a common feature in other types of lipid
is affected first. There is progressive loss of
keratopathy, is not seen in central crystalline dys-
endothelium which results in reduction of vision. The
trophy; this suggests that the lipid is not derived from
inheritance pattern is not clearly understood but
vascular source.
occasionally autosomal dominant. The main features
The benign course of the condition seldom
are corneal guttata, folds in Descemet’s membrane,
warrants any treatment; however keratoplasty may
stromal edema and microcystic epithelial edema.
be indicated if the vision is grossly affected.
Corneal guttata are usually found as a primary
condition. There are excrescences of Descemet’s
Fleck Dystrophy (Speckeled dystrophy of
membrane in the 5th or 6th decade of life. Patho-
Francois and Neetens)
logically similar lesions that are found in the
This autosomal dominant type of corneal dystrophy peripheral part of the Descemet’s membrane are
occurs in the first decade of life or even may be Hassall-Henle warts; these are part of the normal
congenital. The condition is characterized by presence ageing process. The guttata can be seen on specular
of small semiopaque, discrete dandruff like specks reflection as a fine isolated dark structure smaller than
throughout the cornea. All layers of the stroma and the individual endothelial cells. There may be
the peripheral cornea are affected. This dystrophy is associated fine pigment dusting. At this stage the
often seen to be associated with central cloudy corneal visual acuity remains normal.
dystrophy, keratoconus, limbal dermoid, pseudo- The basic pathomechanism of corneal edema is
xanthoma elasticum, lenticular opacities and reduced derangement of endothelial pump mechanism.
corneal sensation but it is not clear whether they are Initially, the condition is asymptomatic with fine
accidental or casually related. The opacities vary in pigment dusting and guttata in the posterior surface
shape and size often with wreath-like clear center and of cornea. In the second phase corneal edema appears
distinct margins. The pathogenesis is not known. No and patient experiences glare and hazy vision.
treatment is required. Initially, the edema is just anterior to the Descemet’s
membrane but gradually spreads over the entire
Endothelial Dystrophies stroma. Epithelial edema appears as small cysts which
coalesce to form large bullae. Rupture of these bullae
Corneal Guttata
leads to severe pain and loss of visual acuity. In the
Corneal guttata becomes manifest after middle age; third phase, there is growth of subepithelial connective
females are more affected than males and inheritance tissue and decrease of epithelial edema. Although, the
is autosomal dominant or undeterminable. The lesions patient at this stage is less symptomatic, the vision is
are bilateral, symmetrical and appear initially as a usually poor and there may be diminished corneal
golden hue on the posterior surface of the central sensation. Complications like elevated intraocular
cornea and gradually spreads peripherally. The pressure, peripheral neovascularization and epithelial
endothelium takes beaten metal appearance. On erosion can occur in this phase.14 Specular microscopy
shows decreased population of endothelial cells and iridocorneal adhesion, secondary glaucoma, anterior
polymegathism. chamber cleavage syndrome, band keratopathy,
Histological examination shows that starting from abnormal iris processes, corectopia, cornea guttata,
early guttata condition the number of isolated dark posterior keratoconus, and epithelialization of corneal
structures are increased which enlarge and may fuse endothelium.17, 18
with adjacent guttata to disrupt the normal endothelial Posterior polymorphous dystrophy may be
integrity. This roughened endothelial surface gives a difficult to distinguish clinically from iridocorneo-
‘beaten metal’ appearance. The endothelial pathology endothelial syndrome because in both the conditions
thus produced leads to loss of endothelial pump there may be corneal edema, peripheral anterior
resulting in stromal edema and microcystic epithelio- synechia, secondary glaucoma and a variety of
pathy. Specular microscopy and corneal pachymetry changes in the iris.19
are used to assess the status of endothelial cells Iridocorneal endothelial syndrome represents a
including their population, size and the corneal single disease entity of which Chandler’s syndrome,
thickness. In advanced stage the endothelium becomes essential iris atrophy, and iris nevus syndrome are the
unobservable using conventional specular micro- main clinical variants. There is corneal endothelial
scope. However, by confocal microscopy technique, overgrowth across the trabecular meshwork and iris
the endothelium may be examined.15 abnormalities. Females in the age group of 30-50 years
Treatment In case of mild epithelial edema application are most commonly affected in this syndrome. The
of hypertonic solution during the day and ointment initial symptoms are diminished visual acuity and
at night may be helpful. Application of warm dry air pupillary distortion. The condition is usually unila-
from a hair dryer held at arm’s length distance teral and the uninvolved eye frequently shows
specially in the morning may give some relief. A abnormal endothelial pleomorphism.
loosely fitted thin high water content soft contact lens The pathology of these conditions is epithe-
may be effective in reducing the pain associated with lialization of the posterior surface of the cornea. These
rupturing of the epithelial bullae. When visual acuity cells show microvillous projections and epidermal
is greatly reduced a full thickness keratoplasty is keratins. In addition to epithelial like cells on the
indicated; however the duration of graft clarity is posterior surface of the cornea there may be other
limited.16 In eyes with narrow angle, the lens should lesions like the following:
be removed along with keratoplasty to prevent angle a. nodules in the deep stroma,
closure by formation of peripheral anterior synechiae. b. annular ridges in the deep corneal stroma,
In patients with Fuch’s dystrophy and lenticular c. gray haziness of the deep corneal lamellae, and
opacity, combined procedure gives good results. d. cornea guttata.
Evidence of previous endothelial dystrophy was
found in majority of patients who developed Treatment In cases associated with secondary glau-
pseudophakic bullous keratopathy following IOL coma, initial treatment with glaucoma surgery is
implantation. advocated. This can be followed by keratoplasty.
Posterior Polymorphous Dystrophy
Keratoglobus
This is a bilateral condition with an autosomal domi-
nant inheritance. It may be congenital or develop in It is a rare bilateral condition where the cornea is
early childhood. Multiple small, discrete, round uniformly thinned out, particularly in the periphery.
vesicle like lesions appear anywhere in the posterior Corneal scarring may be seen. It may be congenital or
surface of the cornea. These lesions may be stationary acquired in adults. Acquired keratoglobus may
or progress slowly. The lesions may bulge forward develop in eyes in late stages of keratoconus. This form
into the stroma or into the anterior chamber in the of keratoglobus may be associated with vernal
forms of ridge-like projections. In severe cases there keratoconjuntivitis and blepharitis. Even the slightest
may be stromal and epithelial edema with trauma may cause rupture of the cornea. Large
deterioration of vision. Additional disorders asso- penetrating or lamellar keratoplasty is indicated for
ciated with this type of dystrophy are broad peripheral improvement of vision when corneal scar develops.
LOCATIONAL CORNEAL DEGENERATIONS condition is suspected. Treatment if necessary is
lamellar keratoplasty.
For descriptive purpose, the corneal degenerations
will be discussed according to their location, viz.
Lipid Degeneration
central and peripheral.
The lipid degeneration of the cornea may be primary
Central Degenerations or secondary, the latter being more common. Lipid
Cornea Farinata deposition can occur following vascularization and
necrosis or following some diseases like Herpes
This senile degenerative condition is characterized by Zoster. The primary type of lipid degeneration is
floury or dust like opacities in the posterior stroma usually bilateral, avascular with no history of previous
adjacent to the Descemet’s membrane.1 These opacities corneal disease. The corneal opacities are dense,
can also be found in a lesser degree in the middle or yellowish white with feathery edges. Histochemistry
anterior layers of the stroma. Although, this is a shows presence of neutral fat, phospholipid, and
bilateral condition unilateral cornea farinata is also cholesterol.21
reported. The deposits consist of lipofuscin which is a
degenerative pigment that accumulates in old cells. Pigmentary Degeneration (Depositions)
Vision is not affected in this condition.
Pigment deposition in the cornea may be iron, blood
Salzmann’s Nodular Degeneration pigment, melanin, and other metallic pigments like
copper, silver, gold, etc.
Salzmann’s nodular degeneration is reported to be late Iron can be deposited in the cornea in the following
sequelae of corneal diseases like phlyctenulosis, inter- conditions:
stitial keratitis, trachoma, keratoconjunctivitis, measles a. Following trauma caused by iron foreign bodies
and other viral diseases. Clinically, there may be a as a ring at the level of the Bowman’s membrane
variable number of lesions consisting of bluish white or superficial stroma. It is called Coat’s white ring.
nodules elevated above the surface of the cornea. The b. Hudson-Stahli line—a horizontal line at the lower
lesions are usually arranged in a circular manner half of the cornea due to deposition of hemosiderin
around the pupil. A pigment line at the base of the pigments following break in the epithelial layer.
nodule is also sometimes seen. This degeneration is c. At the base of the cone of keratoconus-Fleischer’s
bilateral in 80 percent of cases and is more common ring.
in females than males. d. Stocker-Busaca line in front of a pterygium (Fig.
Histopathological examination shows 28.1).
degenerative change in the corneal epithelium over e. Ferry’s line in front of filtering bleb.
the nodular area. The Bowman’s membrane is absent
over the nodule. Hyaline degeneration of the collagen
with, cellular debris, and hyaline deposits in the
collagen of the nodule are seen.20
Treatment is not usually needed. When there is
photophobia and lacrimation, the nodules may be
excised. Central nodules leading to diminished vision
demand keratoplasty.
Hyaline Degeneration
It appears as a band-like yellowish brown granular
opacity in the lower half of the cornea. This condition
clinically resembles Salzmann’s nodular degeneration
and granular dystrophy. There is no vascularization
and the limbal area is usually clear. Histologically the
opacities are found to be masses of hyaline beneath
the epithelium. As this condition is seen to occur in Fig. 28.1: Pterygium showing Stoker’s line.
certain geographic areas its relation to climatic (Courtesy: Dr Nitin Dutta, Eye Foundation, Guwahati)
Iron pigmentation may also be seen in superficial cornea. As age progresses, opacities develop in nasal
in scar as radial keratotomy. Except in cases of iron and temporal quadrants and gradually the ring is
foreign body, the pathogenesis of deposition of iron completed. The arcus is formed by intercellular
in the cornea is not definitely known. The probable deposition of cholesterol, cholesterol esters, phospho-
source of iron may be peripheral blood vessels and lipids, and triglycerides in the substantia propria.24
tear transferrin. The size of arcus senilis has got no relationship with
Metallic foreign bodies and heavy metals used coronary artery disease risk factor.25 If corneal arcus
therapeutically or in the industries such as gold, silver, develops in young individuals the plasma lipid level
copper, etc. may also be deposited in the cornea.22 should be measured. Juvenile arcus occurs in children
Melanin can be deposited in corneas of patients with familial lipidaemia, megalocornea, keratoconus
receiving phenothiazides or chloroquin systemically. and vernal keratoconjunctivitis.
Fine stippling of melanin starts at the level of the
Descemet’s membrane but the overlying stroma or White Limbal Girdle of Vogt
even the Bowman’s layer may also be involved. In
It is present in about 55 percent of population between
chloroquin users, a whorl like pattern of melanin is
the age of 40-60 years. It is a narrow crescent shaped
seen near the Descemet’s membrane.
chalky line seen in the nasal and temporal periphery
of interpalpebral area of cornea. It is composed of
Wilson’s Disease (Hepatolenticular degeneration)
flecks lying beneath the epithelium. Limbal girdle of
Wilson’s disease is a disorder of copper metabolism Vogt is an elastotic degeneration of the subepithelial
and is characterized by progressive neurological collagen tissue.
impairment, ataxia, hepatosplenomegaly and cirrhosis
of liver. There is deposition of copper in all the body Pellucid Marginal Degeneration
tissues specially in the liver, basal ganglion of the
It is a bilateral corneal thinning disorder characterized
brain, kidney, and the cornea.
by a narrow band of corneal thinning in the periphery
Presence of ring like deposition of copper in the
with normal tissue between the limbus and
deep corneal stroma—the Kayser-Fleischer ring is said
degenerated cornea. This degeneration is usually seen
to be the diagnostic sign of Wilson’s disease.23 The
in the inferior quadrant of the cornea. The cornea
ring can be detected in the corneal periphery by slit
above the area of thinning is of normal thickness but
lamp biomicroscopy and in some cases by gonioscopy.
it protrudes. There may be high irregular astigmatism
It may be golden brown, green or ruby red in color.
due to the protruded cornea and astigmatism against
Initially, the ring appears in the upper part, then lower,
the rule because of vertical flattening. Unlike
medially, and finally laterally in that order. The
keratoconus, pellucid marginal degeneration has no
pigment is deposited in the peripheral part of the
cone, iron ring or scarring. Concomitant presence of
Descemet’s membrane. Decreased plasma level of
keratoconus in a majority of patients with this
ceruloplasmin, the protein that carries copper in the
degeneration leads to the belief that pellucid marginal
blood, leads to elevated serum copper level.
degeneration may be a variant of keratoconus.26
Spectacle correction, hard contact lens in mild and
Peripheral Degenerations
moderate cases and lamellar keratoplasty in severe
Arcus Senilis cases have been advocated as treatment of this
condition.
Arcus senilis is a ring like opacity about 1.5 mm broad
in the periphery of the cornea. There is always a clear
Terrien’s Degeneration
zone of cornea between the limbus and the opacity.
The outer border of the arcus is sharp but the inner This is a marginal corneal degeneration that can occur
border appears feathery. It is found in about 60 percent at any age, but most commonly in males in the age
of persons between the age of 40-60 years and almost group of 40-45 years. Terrien’s degeneration is usually
in all persons above the age of 80 years. Arcus senilis a bilateral condition and when unilateral the other eye
is most frequently seen in males. The corneal arcus shows corneal thinning. In the early stage fine white
appears as yellowish white deposits initially as subepithelial opacities appear in the superonasal
semilunar opacity in the upper and lower parts of the periphery of the cornea. These opacities often coalesce
concurrent with progressive thinning of the cornea in 9. Raab MF, Blodi F and Boniuk M. Unilateral Lattice Dystrophy
the area with a gutter formation between the limbus of the cornea. Trans Am Acad Ophthalmol and Otolaryngol
1974;78: 440.
and unaffected part of the cornea. This degenerative 10. Yanoff M. Lattice corneal dystrophy. Arch Ophthalmol
condition progresses gradually over the years and 1977;95: 651.
slightest trauma may cause perforation of the cornea 11. Weber FL, Babel J. Gelatinous drop-like dystrophy. Arch
along the gutter. The eye in this condition remains Ophthalmol 1980;98:144.
quiet and white unless there is inflammation, necrosis 12. Karsears AG, Price DC. Central crystalline corneal dystrophy.
Br J Ophthalmol 1970;54:695, 622.
and neovascularization of the peripheral cornea, when
13. Hirst LW, Waring GU. Clinical specular microscopy of
symptoms like pain and photophobia occurs.27 There posterior polymorphous endothelial dystrophy. Am J
may be progressive deterioration of vision due to Ophthalmol 1983;95: 143.
development of astigmatism. 14. Stocker FW. The Endothelium of the Cornea and its Clinical
The cause of Terrien’s degeneration is not known. Implications (2nd edn) Springfield III. Thomas 1971;79.
15. Kaufman SL, Beurman RW, Kaufman HE. Diagnosis of Fuchs’
Unlike Mooren’s ulcer the level of circulating immune
endothelial dystrophy with confocal microscope. Am J
complexes are not raised. Histopathological Ophthalmol 1993;116, 652.
examination shows splitting of Bowman’s membrane 16. Stocker FW, Irish A. Fate of successful corneal graft in Fuchs’
and corneal lamellae. There may be stromal endothelial dystrophy. Am J Ophthalmol 1969;68: 820.
vascularization and histiocytes with phagocytized 17. Hirst LW, Waring GU. Clinical specular microscopy of
necrotic materials are seen. posterior polymorphous endothelial dystrophy. Am J
Treatment consists of correction of refractive error 18. Tripathy RC, Casey TA, Wise G. Hereditary posterior
either with spectacle or contact lens. In late stages polymorphous dystrophy: An ultrastructural and clinical
corneoscleral graft may be considered. report. Trans Ophthalmol Soc UK 1974;94:211.
19. Buxton JN, Lash RS. Results of penetrating keratoplasty in
REFERENCES the iridocorneal endothelial dystrophy. Am J Ophthalmol
1984;98:297.
1. Smolin G. Dystrophies and degenerations. In: The Cornea. 20. Vannas A, Hogan NJ, Woods I. Salzman’s nodular
Smolin G and Thoff RA (Eds). Little Brown 1987;9: 427. degeneration of the cornea. Am J Ophthalmol 1975;79:221.
2. Stocker FW, Holt LB. Rare form of hereditary epithelial 21. Baum JL. Cholesterol keratopathy. Am J Ophthalmol 1969;67:
dystrophy. Arch Ophthalmol 1955;53:536. 372.
3. Tripathy RC, Bron AJ. Ultrastructural study of nontraumatic 22. Broderick JD. Pigmentation of the cornea. Am J Ophthalmol
recurrent corneal erosion. Br J Ophthalmol 1972;56:73. 1979.11:855.
4. Hogan MJ and Wood J. Reis Buckler’s corneal dystrophy. 23. Ellis PP. Ocular deposition of copper in hypercupremia. Am
Trans Ophthalmol Soc UK 1971;91:41. J Ophthalmol 1969;68 423.
5. Caldwell DR. Postoperative recurrence of Reis-Buckler’s 24. Coga D, Kuwabara T. Arcus senilis and its pathology and
corneal dystrophy. Am J Ophthalmol 1978;85:577. biochemistry. Arch Ophthalmol 1959;61:553.
6. Olson RJ, Kaufman HE. Recurrence of Reis-Buckler’s corneal 25. Pein J, Vidaurri J, Haltose ST, et al. Association between
dystrophy in a graft. Am J Ophthalmol 1978;85:349. corneal arcus and some of the risk factors for coronary artery
7. Garner AL. Histochemistry of corneal granular dystrophy. disease. Br J Ophthalmol 1983;67:795.
Br J Ophthalmol 1969;53:799. 26. Kayazawa F. Keratoconus with pellucid marginal corneal
8. Duke Elder S, Leigh AG. System of Ophthalmology Vol. 8 degeneration. Arch Ophthalmol 1984;102: 895.
Diseases of the outer eye; part 2, Cornea and Sclera. Henry 27. Austin P and Brown SI. Inflammatory Terrien’s marginal
Kimpton: London, 1965. degeneration. Am J Ophthalmol 1981;98:189.
Chapter 29
Keratoconus
Bharti Lavingia, VK George
It is a clinical entity characterized by noninflammatory Stage IV

and noninfective, progressive, bilateral thinning of the
• Refractive error not measurable
cornea with ectasia of conical shape.
• Corneal radius > 55D
This is bilateral in most of the cases. Girls between
• Corneal scar/perforation
15-20 years of age are more affected. The overall
• Corneal thickness 200 μm
incidence of keratoconus is estimated to be 0.15 to 0.20
percent.
ETIOLOGY
It manifests by youth or adolescence, resulting in
considerable visual impairment owing to the develop- Definite etiology is unknown. Ninety-five percent of
ment of high degree of irregular myopic astigmatism. patients do not show evidence of specific hereditary
Sometimes the progress is arrested after a few years pattern. Pattern of inheritance is variable. Several
giving an abortive form of keratoconus, which is theories have been put forward to explain the etiology
characterized by asymmetrical astigmatism— of keratoconus.
horizontal axis being usually abnormal due to
presence of ectasia. It may be seen in the fellow eye of Enzyme Theory
the unilateral keratoconus patient and in the relatives
Alteration in the levels of enzymes the following have
of patients with keratoconus.
been noted:
Keratoconus is classified into four stages by
a. Increased level of epithelial lysosomal enzymes.
Krumeich et al.1
b. Decreased level of alpha-1 proteinase inhibitor in
Stage I the epithelium.
• Eccentric corneal steepness c. Decreased levels of glucose-6 phosphate-
• Myopia and/or astigmatism < 5D dehydrogenase levels in the epithelium.
• Corneal radius < 48D
• Vogt’s striae — no corneal scar Connective Tissue Abnormality Theory
Stage II There is association of keratoconus with some
• Myopia and/or astigmatism > 5D < 8D connective tissue disorders.
• Corneal radius < 53 D
• No corneal scar Genetic Theory
• Corneal thickness > 400 μm Due to the occasional association of trisomy-21 with
Stage III keratoconus, genetic abnormality may be the cause.
• Myopia and/or astigmatism > 8D < 10 D
• Corneal radius > 53 D Hormonal Theory
• No corneal scar It is proposed because of the manifestations of the
• Corneal thickness 200–400 μm disease in adolescence.
Chapter 29: Keratoconus 223
Eye Rubbing Munson’s sign In advanced cases of keratoconus,
bulging of the lower eyelid is seen when looking down.
Habitual eye rubbing in some diseases like vernal
This is a nonspecific sign in advanced keratoconus.
catarrh, Down syndrome and poorly sighted patients
of Leber’s tapetoretinal degeneration are associated
Slit Lamp Examination Findings
with keratoconus.
1. Vogt’s bands are vertical stress lines in deep
ASSOCIATIONS stroma and Descemet’s membrane, at the apex of
the cone.
Systemic Diseases
2. Thinning of the cornea to half of one-fifth the
• Connective tissue and mesodermal dysplasia normal thickness at the apex of the cone.
• Marfan’s syndrome 3. Increased endothelial shining reflex at the central
• Ehlers-Danlos syndrome portion of the cornea at the peak of the cone due
• Osteogenesis imperfecta to increased concavity of the posterior surface.
• Congenital hip dysplasia 4. Increased visibility of corneal nerve fibers
• Oculodento digital syndrome forming a network of gray line with gray dots.
• Rieger’s syndrome 5. Brown ring of iron pigment deep in the
• Crouzon’s syndrome epithelium (Fleisher’s ring) at the base of the cone,
• Floppy eyelid syndrome seen in red-free light in 50 percent of cases.
6. Ruptures in Descemet’s membrane producing
Other Systemic Associations hydrops and linear scars on healing.
• Down syndrome 7. Ruptures in the Bowman’s membrane produce
• Turner’s syndrome reticular, subepithelial, and anterior stromal scars.
• Hypothyroidism 8. Double cones, i.e. one small acute protrusion with
a large peripheral protrusion in the area of the
Associated Ocular Disorders cone.
9. Scarring in the center of the cone leads to opacity.
• Retinitis pigmentosa 10. Inferior corneal steepening is an early sign of
• Leber’s congenital amaurosis keratoconus
• Blue sclerae
• Congenital cataract Keratometry
• Aniridia
• Retinopathy of prematurity There is a lack of parallelism of the mires in Javal
• Fuchs’ dystrophy keratometer. In Bausch & Lomb keratometer,
• Posterior polymorphous dystrophy inclination of the plus mires that cannot be corrected
• Granular and lattice dystrophy by rotation of the axis is a feature. The plus mires jump
from one side to other when alignment is attempted.
Allergic Conditions Irregular astigmatism is manifested by blurring of
the mires that cannot be eliminated by focusing.
• Spring catarrh
• Asthma
Ophthalmoscopy
• Atopic dermatitis.
There is a dark round shadow in the corneal midperi-
CLINICAL FEATURES phery due to total internal reflection of the light
surrounding the central bright red fundus reflex and
S y m p t o m s Gradual decrease in vision; photophobia;
separating it from the normal red peripheral reflex.
monocular diplopia or monocular polyopia. No
chromatic aberration is seen. Severe photophobia and
Retinoscopy
watering is seen in cases of hydrops. Particularly
adolescent females are affected. There is conical Due to high myopic irregular astigmatism, there is a
protrusion of the cornea with central thinning. The scissors motion of the shadow. A round dark rim is
apex of the cone is usually directed inferonasally. visible at the base of the cone.
Keratoscopy Differential Diagnosis

Handheld keratoscope or Placido’s disk shows qualita- Keratoglobus
tive topographic changes. Closer ring spacing in
This is due to thinning of periphery of the cornea
inferior quadrant indicates corneal steepening.
which gradually progresses toward the center. It is
Photokeratoscope or corneocope can show the
present at or soon after birth. So it is thought to be a
earliest changes in keratoconus.
developmental anomaly.
Perforation can occur in this condition with
Computer- assisted Video Keratoscopy
minimal ocular trauma. Acute hydrops can also occur.
It is one of the most important diagnostic aids for very Management is the same as in keratoconus. It is more
early as well as abortive forms of keratoconus in the likely to become vascularized when it heals.
other eye of the patients with unilateral keratoconus
or in the family members. Data of videokeratoscopic Posterior Keratoconus
image are analyzed by computers and depicted as
It is a nonprogressive, dome-shaped posterior
color coded maps. Red color indicates myopic refrac-
excavation in the cornea which may be small and
tion or ectasia and blue color indicates hypermetropic
circumscribed (keratoconus posticus circumscriptus)
refraction or flattening of the cornea. Very early cases,
or may be diffuse (keratoconus posticus totalis). It is
suspicious cases, atypical cases which are otherwise
considered to be a congenital defect. Origin is prior to
subclinical and cannot be diagnosed on slit lamp
5th or 6th month of gestation. A traumatic etiology is
examination, can be detected by this technique. A new
also reported.
terminology of keratoconus “suspects” has come into
The condition is typically bilateral, vision is not
existence and the criteria for diagnosis of keratoconus
affected. LASIK surgery is contraindicated in posterior
have changed with the development of this technique.
keratoconus.
Pachymetry (Pachometry)
Pellucid Marginal Degeneration
Slit lamp pachymetry shows thinning in the center of
It is a bilateral peripheral corneal ectatic disorder
the apex. Ultrasonic pachymetry shows exact thickness
characterized by a band of thinning of 1-2 mm width
of cornea at different places. Thinning in the inferior
typically in the inferior cornea. Maximum corneal
quadrant can be diagnostic of keratoconus. Central
protrusion occurs superior to the area of thinning.
or paracentral corneal thickness of less than 450 μm is
There is no other abnormality and it occurs in 2nd to
abnormal. If the reading decreases by nearly 20 μ
5th decade.
towards the inferior periphery on successive
pachymetric readings, it is suspicious of keratoconus.
Increase in the progressive thinning of the cornea is a MANAGEMENT
true index of keratoconus.
Management of keratoconus begins with spectacles.
Once the vision cannot be improved with glasses,
HISTOPATHOLOGY
contact lenses may be tried. Combination of hard over
Decreased number of collagen fibers particularly in soft contact lenses known as “Piggyback” contact
the cone area is observed during histological lenses may be tried. These days, contact lenses of
examination. Amyloid deposition in the sclera is seen double curve and fitting are made specially for
suggestive of secondary amyloidosis of cornea. keratoconus patients.
Breaks, holes, and gaps in the Bowman’s In the early stages of the classification, contact lens
membrane are seen. The gaps are filled with fibroblasts is recommended and the patient feels comfortable. As
and connective tissue. The primary defect is thought the corneal curvature goes on changing, irregular/
to be in the basal layer of epithelium. Corneal hydrops mixed astigmatism develops and high power contact
develop as a result of breaks in Descemet’s membrane lens is required. It may be necessary to prescribe hard-
and overlying epithelium. over-soft piggyback contact lens. After further
Endothelial cell pleomorphism and polymega- progress of the disease, stable lens fit is impossible
thism can occur near the cone area. and the contact lens falls off. Simultaneously,
Chapter 29: Keratoconus 225
transparency of the cornea is decreased due to corneal cornea.7-9 It appears to be a viable method for treating
hydrops and scarring of the cornea which leads to clear cornea keratoconus in patients who are intolerant
gross visual defect. to contact lens wear.
In cases of contact lens failure and apical scarring, As the cornea in keratoconus is generally thin and
penetrating keratoplasty (PK) is the usual treatment.2,3 more so at the apex, excimer laser photoablative
Usually, graft rejection rate is comparatively rare and procedures are contraindicated. However, if corneal
postoperative best-corrected-vision of 6/9 or better is nebulae at or near the tip of the cone appears to be the
common. Of course, myopia with astigmatism is often cause of low vision, then phototherapeutic keratecto-
seen after PK for keratoconus. However, continuous my may be considered.
endothelial cell loss and recurrence of keratoconus in
the graft may deteriorate the visual prognosis REFERENCES
further.4,5 1. Kumeich JH, Daniel J, Knutte A. Live epikeratophakia for
keratoconus. J Cataract Refract Surg 1998;24,329.
2. Brierly, Izguierdo LJ, Marnis MJ et al. The success of
Phakic Intraocular Lens penetrating keratoplasty for keratoconus. Eye 1990;4:673.
3. Kirkness CM, Friker LA, Streak AD et al. Penetrating
High myopia of keratoconus is usually associated with keratoplasty for keratoconus. Cornea 2000;19:329.
fragile cornea and keratoplasty may not be a suitable 4. Ableson MB, Colin UB, Gillette TE et al. Recurrent
surgical procedure. Phakic intraocular lens in high keratoconus after keratoplasty. Am J Ophthalmol 1980;90:672.
myopia is becoming a popular procedure. This 5. Kremer J, Eagle RC, Repuano CJ et al. Histologic evidence of
recurrent keratoconus several years after keratoplasty. Am J
operation can be considered to avoid the postoperative
complications of keratoplasty. Another innovative 6. Schanzin DJ, Asbell PA, Buris TE et al. Intracorneal ring
surgical procedure for treatment of keratoconus in segment Phase II results for correction of myopia.
patients intolerant to contact lens is to flatten the Ophthalmology 1997;104,1067.
cornea by intrastromal insertion of stromal ring.6 7. Colins J, CochenerB, Savary J et al. INTACs inserts for treating
keratoconus. One year result. Ophthalmology 2001;108,1409.
These rings are 0.25 to 0.45 mm thick inserted
8. Colins J, Cochener B, Savary J et al. Correcting keratoconus
intrastromally in the corneal periphery act as passive with intracorneal ring. J Cataract Refract Surg 2003;29,279.
spacing element that shorten the arc length of the 9. Colin J, Velou S. Current surgical options for keratoconus. J
anterior corneal surface and thereby flatten the central Cataract Refract Surg 2003;29, 279.
Chapter 30
Peripheral Corneal Ulcers

J Ram, SK Pandey
The periphery of the cornea may be affected by a nosis of the diseases. Aggressive systemic treatment
number of ocular infections or hypersensitivity is required specially in patients of collagen vascular
reactions to products of various infectious agents. A diseases to stop progression of corneal destruction.
number of systemic diseases can lead to peripheral
corneal ulceration, and it may be a presenting feature Etiological Factors
of systematic disorders such as rheumatoid arthritis,
A number of disorders can lead to development of
polyarteritis nodosa, and Wegener’s granulomatosis.
peripheral corneal ulceration. It can occur following
The peripheral corneal ulcer is usually defined as a
infections, postinfectious disorders, abnormalities of
crescent-shaped lesion of juxtalimbal corneal stroma
the eyelids or lashes, dermatological conditions, dry
usually located in the peripheral 3-4 mm of cornea
eyes, collagen vascular disease, and other autoimmune
and associated with epithelial defect and stromal
disorders. Classification of peripheral corneal
infiltrate. Pain, photophobia, foreign body sensation
ulceration is summarized in Table 30.1.
or decrease in visual acuity are common symptoms.
A careful history about ocular and systemic illness is
Clinical Features
mandatory. Comprehensive ocular examination com-
bined with general physical examination must be done Typical presentation of patients with peripheral
in all cases to find out the cause. Laboratory studies ulcerative keratitis (PUK) includes decreased vision
are frequently necessary to confirm the systemic diag- (secondary to induced irregular astigmatism), redness,
Table 30.1. Classification of peripheral corneal ulcers
Infective Noninfective
Local Systemic Local Systemic
Bacterial Tuberculosis Hypersensitivity and Vasculitis
Viral Syphilis autoimmune disorders Rheumatoid arthritis
Fungal Varicella zoster Marginal keratitis Sjögren’s syndrome
Chlamydial Gonorrhea Vernal keratoconjunctivitis Relapsing polychondritis
Parasitic HIV Immune corneal ring Junvenile rheumatoid arthritis
Bacillary dysentery Mooren’s ulcer Systemic lupus erythromatosis
Blepharitis Polyarteritis nodosa
Wegener’s granulomatosis
Giant cell arteritis
Miscellaneous Dermatological
Exposure keratitis Ectodermal dysplasia
Neurotrophic keratitis Benign mucous membrane pemphigoid
Superior limbic keratitis Acne
Keratoconjunctivitis sicca Psoriasis
Leukemia.
Chapter 30: Peripheral Corneal Ulcers 227
irritation, and pain. Usually, varying degrees of vasoconstrictors as well as systemic antihistamines
corneal stromal loss adjacent to the limbus occurs have also been recommended. Use of topical
independent of etiology. An infiltrate of inflammatory cyclosporine 1 percent eyedrops is reported with
cells in stroma with conjunctival, episcleral and scleral variable results. 8 Other reported therapeutic
inflammation usually occurs in these cases. modalities for VKC include conjunctival cryosurgery,
systemic aspirin administration 9 and supratarsal
MARGINAL KERATITIS injection or steroids.10
It is most common form of peripheral ulcerative
MOOREN’S ULCER
keratitis usually seen in middle-aged patients.1 The
lesions are typically benign as one or more gray-white, It is an idiopathic condition characterized by pro-
peripheral stromal infiltrates having their long axis gressive inflammatory thinning and ectasia of
parallel to the limbus. Symptoms include pain, foreign cornea.11 It initially involves the peripheral cornea and
body sensation, and a marked photophobia. If left eventually spread both circumferentially and
untreated, healing generally occurs in two to four centrally. Typical cases are unilateral, limited type and
weeks without vascularization. Recurrences are quite occur mostly in older patients and respond well to
common. Treatment includes low doses of topical therapy.12 The atypical type occurs in younger patients
corticosteroids.2 Antigenic load should be reduced particularly in blacks, usually bilateral in up to 75
from eyelid margins and conjunctiva by eradicating percent of cases. The course is more aggressive with
pathogenic organisms. Oral doxycycline 100 mg twice poor response to all forms of therapy.
a day for a week can be given in cases of marginal Clinical features include unilateral or bilateral
keratitis associated with clinical meibomian gland painful ulcerations and ectasia of peripheral cornea.13
disease. The anterior one third to one half of the stroma is
involved characteristically with a steep overhanging
VERNAL KERATOCONJUNCTIVITIS (VKC) edge (Figs 30.1 and 30.2). Healing with vascularization
(Detail in Chapter 15) follows with recurrence in a period of 4 to 18 months.
Foster14 has devised diagnostic criteria for Mooren’s
A recurrent, bilateral inflammation of the tarsal and
ulcer, which include: (a) crescent-shaped peripheral
limbal conjunctiva can also involve the peripheral and
ulcer, (b) undermining central edge with overhanging
paracentral cornea. It is a disease of warm climates
lip, (c) intrastromal yellowish white infiltrate at
usually affects children prior to age of 14 years.3,4 Most
spreading ulcer edge, (d) circumferential and central
of the patients have a characteristic of conjunctival dis-
progression of ulcer, (e) re-epithelialized, vascularized
charge which is yellowish, mucoid, and ropy. Papillary
thinned corneal scar in the way of advancing ulcer,
hypertrophy of tarsal conjunctiva begins as diffuse,
and (f) absence of scleral involvement. Mooren’s ulcers
small papilla which progresses to form a large flat
can be associated with previous ocular trauma,15
topped “cobble stone papilla”. Limbal form is
chemical burns,16 surgical procedures,17 helminthiasis,
characterized by gelatinous thickening and
chronic hepatitis,18 herpes simplex,19 herpes zoster,20
opacification of the superior limbus. Whitish Horner-
syphilis, tuberculosis, and autoimmune disease of
Tranta’s dots may be seen in superior limbus. These
unknown etiology.21
are considered as pathognomonic for VKC. Corneal
Treatment of Mooren’s ulcer is difficult and
involvement may be seen both in punctate keratitis
frequently unsatisfactory. The prime therapeutic
and ulcerative keratitis.4,5 Punctate keratitis generally
concern in Mooren’s ulcer is arresting the inflam-
involves superior third of cornea. Ulcerative keratitis
matory process, thereby preserving the integrity of the
usually presents as solitary, shield-like ulcer involving
eye. A stepwise approach for the management of
the superior cornea.6 VKC is an atopic disease and its
Mooren’s ulcer recently reported by Chow and
clinical manifestations are usually result of type 1
Foster22 include the following.
(immediate) hypersensitivity response. It can be asso-
ciated with eczema, hay fever or asthma. Currently,
Step I Topical Steroids
typical mast cell stabilizers (e.g. cromolyn sodium) is
the mainstay of treatment in mild VKC.7 Topical Topical prednisolone acetate 1 percent or beta-
corticosteroids, mucolytics, tear substitutes and methasone 0.1 percent one hourly along with topical
Step III Systemic Immunosuppressive

It is usually indicated in bilateral or progressive cases
to limit the progressive corneal destruction. Most
commonly used agents include cyclophosphamide
(200 mg/kg/day), methotrexate (7.5 to 15 mg once
weekly), and cyclosporine A (10 mg/kg/day).
Step IV Other Surgical Procedure

Brown et al24 reported the role of superficial lamellar
keratectomy to arrest inflammatory process and allow
healing. Despite treatment, perforation may occur in
some cases. Application of tissue adhesives and
bandage contact lens is preferred for small perforation,
Fig. 30.1: The right eye close up of a 40-year-old female with
while patch graft or conjunctival flaps are usually
characteristic of Mooren’s ulcer, showing crescent-shaped
corneal ulcer from 8 o’clock to 2 o’clock
necessary for management of large perforation.
Step V Rehabilitation
Once healing is complete, penetrating keratoplasty
may be required. Foster25 recommended, the use of
large tectonic corneal graft. Later on, 7.5 to 8 mm
optical graft can be performed.
RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is the most common
collagen vascular disorder affecting the peripheral
cornea.26 Ocular involvement is characterized by
keratoconjunctivitis sicca (Sjögren’s syndrome),
scleritis, episcleritis, and corneal changes. 27 The
Fig. 30.2: The left eye of a 40-year-old female patient with peripheral cornea is most commonly involved usually
characteristic Mooren’s ulcer, overhanging edge and
as a direct extension of the scleral inflammatory pro-
undermining of central edge
cess (Fig. 30.3). Four patterns of involvement include:28
(a) sclerosing keratitis, (b) acute stromal keratitis,
cycloplegics and prophylactic antibiotics. Frequency
(c) limbal guttering and (d) keratolysis.
of topical steroids can be increased to half hourly if
Sclerosing keratitis is the most common corneal
epithelial healing does not occur within 2 or 3 days.
complication associated with scleritis. Acute stromal
Oral pulse therapy (60 to 100 mg of prednisolone) can
keratitis may present as superficial or midstromal
be added if topical therapy is ineffective after 7 to 10
peripheral infiltrates in association with nodular or
days.
diffuse non-necrotizing scleritis.29 These may coalesce
to form diffuse peripheral opacification that may result
Step II Conjunctival Resection
in vascularization, epithelial breakdown, and stromal
It is usually indicated if ulcer progresses despite melting. Peripheral corneal furrowing, usually begins
steroid regimens. Conjunctival resection is usually in an area of sclerosing keratitis, progressing circum-
done 4 mm posterior to limbus and parallel to ulcer ferentially to involve entire periphery.30 Severe corneal
at least 2 clock hours to either side of the peripheral thinning is associated with necrotizing scleritis
ulcer. Cryotherapy of limbal conjunctiva can be done. (Figs 30.3 and 30.4). Keratolysis is associated with
Stilma et al23 reported 52 percent recurrence in a series marked necrotizing scleritis or scleromalacia per-
of 38 Mooren’s corneal ulcer with conjunctival forans.31 Rapid destruction of stroma resulting in
excision. descemetocele formation can occur in less than a week
Chapter 30: Peripheral Corneal Ulcers 229
respiratory tract and a focal glomerulonephritis.35
Ocular involvement may be seen in up to 58 percent
of cases, including proptosis (due to orbital
involvement) with or without peripheral ulcerative
keratitis.36 Initiation of immunosuppressive therapy
(e.g. cyclophosphamide 2 mg/kg/day) can be both
sight and life saving. Impending or actual corneal
perforation can be managed with cyanoacrylate
adhesive, conjunctival flap, or lamellar and or
penetrating keratoplasty.
Polyarteritis Nodosa (PAN)

Fig. 30.3: This is right eye of a 46-year-old male with rheumatoid
Peripheral corneal ulcer, conjunctival lesions, scleritis,
arthritis showing extensive necrotizing scleritis with peripheral
corneal ulcer choroiditis, retinal vasculitis, optic atrophy, disc
edema, exudative retinal detachment, central retinal
period. Therapy consists of aggressive control of
artery occlusion are ocular findings in PAN. The
scleral inflammation with systemic corticosteroids or
clinical characteristic of PUK associated with PAN are
immunosuppressive agents.32 Cyanoacrylate glue,
topical collagenase inhibitors, and therapeutic soft
contact lenses are useful to seal corneal perforations
of less than 2 mm. Penetrating keratoplasty may be
needed in order to seal larger perforation or restore
visual acuity.
Systemic Lupus Erythematosis (SLE)
Scleritis, keratitis, corneal furrowing and retinal
vasculitis are reported ocular complications of SLE.
Punctate epithelial keratitis is a major corneal
manifestation seen in up to 88 percent of cases.33
Diagnosis for SLE can be made by skin biopsy.
Systemic chloroquine can be used for treatment of
keratitis associated with SLE.
Fig. 30.4: The same eye (Fig. 30.3) showing vascularization
Sjögren’s Syndrome
This chronic multisystem autoimmune disorder is
characterized by keratoconjunctivitis sicca and
xerostomia. The patient usually presents with
intolerance to air, reading, difficulty in opening eyes,
foreign body sensation, and watering. Slit lamp
biomicroscopic examination reveals low tear
meniscus, floaters, and mucous strands. Tear film
break-up time is usually less than 10 seconds. Frequent
use of topical lubricants is the mainstay of
management for the corneal complications of Sjögren’s
syndrome (Fig. 30.5). Therapeutic contact lens,
cyanoacrylate glue or penetrating keratoplasty are
treatment modalities for corneal perforation cases.34
Wegener’s Granulomatosis
Fig. 30.5: Left eye of 25-year old man with Sjögren’s syndrome
Wegener’s granulomatosis is necrotizing granulo- showing 4.0 × 2.5 mm peripheral corneal with stained with
matous inflammation of upper as well as lower fluorescein at 8 o’clock position
similar to Mooren’s ulcer. Therapy with local medical 15. Frangieh T, Kenyon K. Mooren’s ulcer. In Brightbill FS (Ed):
and surgical strategies may temporarily retard Corneal Surgery: Theory, Techniques and Tissue, 2nd edn.
St. Louis: Mosby 1993;328-35.
progression of ulcer until control with systemic 16. Evans PJ. A case of Mooren’s ulcer. Trans Ophthalmol Soc
prednisolone and cyclophosphamide is achieved. UK 1950;70:94-95.
17. Mondino BJ, Hofbauer JD, Foos RY. Mooren’s ulcer after
penetrating keratoplasty. Am J Ophthalmol 1987;103:53-56.
Relapsing Polychondritis 18. Moazami G, Aurar J, Florakis G et al. Interferon treatment of
Mooren’s ulcer associated with hepatitis C. Am J Ophthalmol
It is an autoimmune inflammatory condition consis- 1995;119:365-66.
ting of nose and ear chondritis, ocular inflammation, 19. Brown Sl, Mondino BJ. Therapy of Mooren’s ulcer. Am J
arthritis with cochlear and vestibular damage. Its Ophthalmol 1984;98:116.
treatment consists of nonsteroidal anti-inflammatory 20. Mondino BJ, Brown SI, Mondzelewski JP. Peripheral corneal
ulcer with herpes zoster opththalmicus. Am J Ophthalmol
drugs, systemic corticosteroids, and immuno-
1978;86:611-14.
suppressants. 21. Foster CS, Kenyon K, Greiner G et al. The immunopathology
of Mooren’s ulcer. Am J Ophthalmol 1979;88:149-59.
REFERENCES 22. Chow CYC, Foster CS. Mooren’s ulcer. Int Ophthalmol Clin
1996;36:1-19.
1. Chignell AH, Easty DL, Chesterton JR et al. Marginal 23. Stilma J. Conjunctival excision or lameller scleral autograft
ulceration of cornea. Br J Ophthalmol 1970;54:433-40. in 38 Mooren’s ulcers from Sierre Leone. Br J Ophthalmol
2. Aronson SB, Elliot JH, Moore TF, O’Day DM. Pathogenetic 1993;67:465-78.
approach to therapy of peripheral corneal inflammatory 24. Brown S, Mondino B. Penetrating keratoplasty in Mooren’s
disease. Am J Ophthalmol 1970;70:65-90. ulcer. Am J Ophthalmol 1980;89:255-58.
3. Neumann E, Gutmann MJ, Blumentkrantz N et al. A review 25. Foster CS. Immunologic disorders of conjunctiva cornea and
of four hundred cases of vernal conjunctivitis. Am J sclera. In Albert Da, Jakobiec FA (Eds): Principles and Practice
Ophthalmol 1959;47:166-72. of Ophthalmology. Philadelphia: Saunders 1994;200-03.
4. Buciley RJ. Vernal keratoconjunctivitis. Int Ophthalmol Clin 26. Tauber J, Sainz dela Maza M, Hoang-Xuan T et al. An analysis
1988;28:303-08. of therapeutic decision making regarding immuno-
5. Abelson MB, Udell IJ, Allansmith MR et al. Allergic and toxic suppressive chemotherapy for peripheral ulcerative keratitis.
reactions. In Albert DM, Jakobiec FA (Eds): Principles and Cornea 1990;9:66-73.
Practice of Ophthalmology. Philadelphia: Saunders 1994;1: 27. Jayson MIV, Jones DED. Scleritis and rheumatoid arthritis.
77,100. Ann Rheum Dis 1971;30:343-47.
6. Trocme SD, Kephardt GM, Bourne WM et al. Eosinophilic 28. Watson PG. Diseases of the epislcera and sclera. In Duane
granule major basic protein deposition in corneal ulcers TD (Ed): Clinical Ophthalmology. Philadelphia: Harper &
associated with vernal keratoconjunctivitis. Am J Ophthalmol Row Publishers 1984;23(4).
1993;115:640-43. 29. Smith RE, Schanzlin DJ. Rheumatoid diseases. In Smolin G,
7. Allansmith MR, Ross RN. Ocular allergy and mast cell Thoft RA (Eds): The Conrea: Scientific Foundations and
stabilizers. Surv Ophthalmol 1986;30:229-44. Clinical Practice. Boston: Little Brown, 1983;249-63.
8. Secchi AG, Tognon MS, Leonardi A. Topical use of 30. Lyne AJ. Contact lens cornea in rheumatoid arthritis. Br J
cyclosporine in the treatment of vernal keratoconjunctivitis. Ophthalmol 1970;54:410-15.
Am J Ophthalmol 1990;110:641-45. 31. Watson PG, Hayreh SS. Scleritis and episcleritis. Br J
9. Abelson MB, Butrus SI, Weston JH. Aspirin therapy in vernal Ophthalmol 1976;60:163-91.
conjunctivitis. Am J Ophthalmol 1983;95:502-05. 32. Jampol LW, West C, Goldberg MF. Therapy of scleritis with
10. Holschaw DS, Whitcher JP, Wong IG et al. Supratarsal cytotoxic agents. Am J Ophthalmol 1978;86:266-71.
injection of corticosteroid in the treatment of resistant vernal 33. Gold DH, Morris DA, Henkind P. Ocular finding in systemic
keratoconjuctivitis. Am J Ophthalmol 1996;121:243-49. lupus erythematosus. Br J Ophthalmol 1972;56:800-04.
11. Tabbara KF. Mooren’s ulcer. Int Ophthalmol Clin 1986;26:91. 34. Pfister RR, Murphy GE. Corneal ulceration and perforation
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1971;71: 417-21. 1980;98:89-94.
13. Watson PG. Management of Mooren’s ulceration. Eye 35. Robin JB, Schanzlin DJ, Meisler DM et al. Occular involvement
1997;11:349-56. in respiratory vasculitides. Surv Ophthalmol 1985;30:127-40.
14. Foster CS. Systemic immunosuppressive therapy for 36. Bullen CL, Liesegang TJ, McDonald TJ et al. Occular complica-
progressive bilateral Mooren’s ulcer. Ophthalmology tions of Wegener’s granulomatosis. Ophthalmology
1985;92:1436-39. 1983;90:270-90.
Chapter 31
Ocular Chemical Burns

JS Saini, A Gupta
Chemical trauma to the eye forms a small but Table 31.1: Various types of chemicals
significant part of ocular trauma. Most chemical
I. Alkalis
injuries are minor and heal without any serious Ammonium hydroxide Sodium hydroxide
sequel. Sometimes the chemical nature of injury is Potassium hydroxide Calcium hydroxide
available from the circumstantial clinical history. Magnesium hydroxide Barium hydroxide
However, it is important to recognize a potential Tetraethylammonium Strontium
chemical component of any ocular injury that can hydroxide hydroxide
provide for appropriate emergency treatment. Acids Lithium hydroxide
and alkalis form the major chunk of ocular chemical II. Acids
burns. Alkali injuries are more commonly a. Inorganic acids
encountered. They are extensively used in industries Sulphuric acid Hydrochloric acid
Nitric acid Chromic acid
and in various household as cleansing agents.1 Alkali
Hydrofluoric acid
injuries tend to be more severe than acid injuries b. Organic acids
because of the quick penetration into the eyes. Acid Acetic acid Citric acid
burns are often confined to the ocular surface and Formic acid Oxalic acid
tend to produce superficial damage. Trichloracetic acid Glycol and thio-
glycolic acid
EPIDEMIOLOGY (hair perm)
Maleic acid Caprice acid
Chemical ocular trauma constitutes 7 to 9.9 percent III. Miscellaneous
of reported ocular trauma. 2-4 The frequency of Organic solvents
bilateral ocular involvement has been reported from Alcohols: Methyl alcohol, ethyl alcohol, butyl alcohol,
23 to 42 percent.5,6 Most victims are young males and ethylene glycol (coolant)
the exposure to chemicals occurs in industrial Aldehydes: Formaldehyde, acetaldehyde
accidents, at home, and in association with criminal Halogenated hydrocarbons: Methylene chloride,
carbon tetrachloride, dichloro-diphenyl-trichloro-
assaults. The frequency of bilateral involvement is ethane (DDT), dichloro-difluoro-methane (Feron gas)
higher in assault victims. Approximately two-thirds Hydrocarbons: Petroleum, kerosene, benzene,
of the injuries are minor (Grades I and II). Various naphthalene
categories of chemical burn are shown in Table 31.1. Ketones
Ethers
SOURCES OF COMMON INJURIOUS Metallic corrosives
Iron, copper, mercury, lead, zinc
CHEMICALS (Table 31.2) Others
Alkalis Detergents, preservatives in topical solutions, contact
lens cleaning solutions, tear gas, insecticides, adhesives,
Ammonia and ammonium hydroxide These are com- topical drugs, mouthwashes, air fresheners and
monly used in fertilizers, as refrigerant and in perfumes, chilli powder.
Table 31.2: Common causes of chemical injuries Calcium hydroxide It is found in lime, quick lime,
slaked lime, mortar, plaster, cement or whitewash.
Agents Common sources/uses
It has a relatively poor ocular penetration. It reacts
Alkalis with the epithelial cell membrane and leads to the
Ammonia and ammonium Fertilizers, refrigerants, formation of calcium soaps, which limits its further
hydroxide household cleansing agents tissue penetration. Early corneal opacification is a
(7%). Manufacture of other
chemicals
prominent feature because of a reaction with the
Sodium hydroxide Drain cleaner proteoglycans leading to formation of a precipitant.
Potassium hydroxide Caustic potash Retention of lime particles in the superior fornix may
Magnesium hydroxide Sparklers and fireworks act as a reservoir of alkali leading to severe chemical
Lime Mortar, cement, plaster, injury.
whitewash, quicklime,
slaked lime Magnesium hydroxide It is a constituent of flares,
Acids sparklers, and firecrackers. The presence of mag-
Sulphuric acid Industrial cleaners, battery nesium hydroxide leads to a more severe injury than
acid accompanying thermal and mechanical trauma alone
Sulphurous acid Fruit and vegetable would warrant.10
preservatives, bleach,
refrigerants Acids
Hydrofluoric acid Etching and polishing glass,
glass frosting, silicone Most acid injuries are minor and heal with little or
production, mineral no ocular damage. Trauma mostly occurs from contact
(uranium, beryllium, with weak acids or dilute strong acid.
tantalum) refining,
chemical treatment of Sulphuric acid Known as oil of vitriol is one of the
metals, gasoline alkylation more common agents causing chemical injury amongst
Acetic acid Vinegar (4-10%), essence of acids. Injuries caused by sulphuric acid are more
vinegar (80%), glacial acetic severe than that can be accounted for on the basis of
acid (90%) hydrogen ion alone. This additional damage occurs
Chromic acid Chrome-plating industry. due to an exothermic reaction, which occurs when
sulphuric acid combines with water, leading to a
laboratories. Exposure to ammonia gas leads to charring effect on the tissue (thermal component of
protective lacrimation and hence ocular injury is the injury). Sulphuric acid is also used as battery acid.
uncommon unless a direct blast of the gas occurs. Battery explosions occur when hydrogen and oxygen,
When combined with water, ammonia forms ammo- which are produced by electrolysis during charging
nium hydroxide. This is most commonly encountered of a battery, come in contact with a spark or a flame.
in 7 percent concentration as household cleansing These injuries are becoming increasingly common and
agents.7 Ammonium hydroxide is soluble in both result in combined chemical, thermal, and mechanical
lipids and water and, therefore, passes easily through trauma, often associated with contusions, lacerations
both the lipophilic corneal epithelium and hydrophilic and retained intraocular foreign bodies.11
stroma. It reaches the anterior chamber within 5 Hydrofluoric acid It is a weak inorganic acid but a
seconds of exposure. It causes less initial stromal strong solvent. Strong solutions are either of 49 or
opacification which, along with the white eye 70 percent concentration. It is used chiefly in etching
produced by limbal ischemia, may lead to the and polishing of glass and in semiconductor industry.
mistaken conclusion that the ocular damage is mild. It is also used for frosting glass, in chemical treatment
Sodium hydroxide It is also known as lye or caustic of metals, refining of uranium, tantalum, and
soda or sodium hydrate. It is commonly used as drain beryllium and in alkylation of high octave (aviation)
cleaner. It penetrates into anterior chamber within 1 gasoline. Hydrofluoric acid causes exceptionally
minute with peak concentration occurring within 3-5 severe injuries due to rapid penetration unlike most
minutes.8,9 Potassium hydroxide is similar to sodium other acids. Typically, following even severe hydro-
hydroxide in penetrability and severity of injury. fluoric acid injury, the epithelium is only minimally
Chapter 31: Ocular Chemical Burns 233
opaque. Ulceration is uncommon because of the collagen fibrils and loss of the protective glycos-
binding of divalent ions like calcium by fluoride. aminoglycans, contribute to acute rise of intraocular
Subconjunctival hemorrhages are also common as the pressure and increased susceptibility of collagen to
binding effect on calcium may act as an anti- enzymatic degradation.14,15 In severely affected eyes,
coagulant.12 due to deeper penetration of chemicals, ciliary body
is damaged resulting in low levels of glucose and
Hydrochloric acid and nitric acid They produce similar
ascorbate in the anterior chamber. Ascorbic acid is
injuries. Nitric acid burns are generally tinted yellow.
essential for the conversion of proline and lysine into
The area of corneal opacification and necrosis is
hydroxyproline and hydroxylysine, respectively for
generally limited to the area of contact. Hydrochloric
collagen synthesis. Also, ascorbate aids in the
acid is more lipid soluble than other acids which
conversion of monocytes into fibroblasts and in the
accounts for a more severe injury.
formation of rough endoplasm reticulum and
Chromic acid It is a water-soluble compound that glycosaminoglycans. All these activities are compro-
combines with Water to form a strong caustic acid. It mised in such eyes.16
is used in chrome-plating industry. Repeated Compared to alkalis, acids lack penetrability. This
exposure to acid droplets is common, leading to is due to the precipitation and coagulative necrosis
chronic inflammation and a brown discoloration of of the corneal epithelium, which forms a protective
conjunctiva. barrier to further penetration. Removal of the necrotic
epithelium may reveal a clear stroma underneath. In
Acetic acid Known as vinegar (4-10%) or glacial acetic
severe penetrating burns, iris, lens, and ciliary body
acid (90%), it is a weak acid and tends to produce
may be affected in a manner similar to alkalis.17,18
minor damage. Concentrations less than 10 percent
are thought to be incapable of producing any severe
Inflammation
trauma. Exposure induces reflex lacrimation that is
protective. The initial damage to the corneal epithelium and
Other chemicals used in various industries may stroma chemotactically attracts polymorphonuclear
not be well known for ocular toxicity but assume and mononuclear leukocyte within the first 24 hours.
special significance in industrial disasters. During the Corneal stromal inflammation persists as long as
Bhopal Gas Tragedy in India, exposure to methyl- epithelial defect exists. Retardation of epithelial
isocyanate gas caused acute severe burning, foreign recovery and stromal collagenolysis due to products
body sensation, lacrimation, and subsequently of inflammation contribute toward ocular damage.
blurred vision, chronic conjunctivitis, dry eye, and Therapeutic measures to reduce or prevent further
persistent corneal opacities.13 accumulation of inflammatory cells during the acute
phase help in reducing further damage.
PATHOMECHANISM OF CHEMICAL INJURY
Ocular Surface Damage
Acute inflammatory response, ocular surface damage,
and stromal collagen lysis are the three components Following chemical injury to the surface epithelium,
of chemical injury contributing to the severity of the rate of recovery and functional competence of
ocular chemical burns and clinical outcomes. the regenerating surface depend largely on the extent
The mechanism of damage due to the hydroxyl of the residual pool of limbal stem cells. If the stem
ion (OH) remains the same for all alkalis. What cell loss area is extensive, denuded cornea surface is
determines the varying severity of different alkalis resurfaced by conjunctival cells. Migration of epithelial
is the nature of the cation and the ‘inherent toxicity’ cells is slowed by persistence of inflammation and
of the chemical. In general, hydroxyl ions saponify epithelial basement membrane damage. Resurfacing
fatty acid component of cell membranes, resulting in from peripheral cornea cells or limbal stem cells is
cell death, disruption of the epithelial barrier, and not only more rapid but also the resulting surface is
deeper penetration of alkali into the stroma. Cations functionally more competent. Conjunctiva like epithe-
of alkali react with carboxyl (COOH) in the collagen lium on the corneal surface initially demonstrates
and stromal glycosaminoglycans. The consequent large number of goblet cells, relatively poor
swelling and thickening as well as shortening of adhesibility to the stroma and incomplete barrier
function. Over a variable period of years conjunctiva more severe injuries, conjunctival goblet cells are also
like epithelium tends to transdifferentiate to a more lost. Ocular penetration of the chemical leads to
cornea like surface. Transdifferentiation of the corneal stromal clouding and edema, ischemic necrosis of
surface is adversely affected by deficiency of vitamin perilimbal tissue, iris, and ciliary body. A fibrinous
A and presence of blood vessels. Although iritis and cataract formation may occur in severe
corticosteroids help reduce the initial inflammation, injuries. Thrombosis of vessels may be seen clinically
they do not influence the degree of vascularization as cattle trucking, ghost vessels, and limbal ischemia
that is determined by the conjunctiva like corneal giving rise to appearance of white looking eye.
surface. Regardless of the source of regenerating Subconjunctival hemorrhages may be seen. Intra-
epithelium, intact surface prevents microbial and nonocular pressure (IOP) is affected in a bimodal fashion.
microbial sterile stromal ulceration. Corneal Within a few seconds after the injury, an increase in
epithelium secretes a cytokine to inhibit keratocyte IOP occurs due to shrinkage of collagen fibrils and
type I collagenase production. When the epithelium resultant distortion of trabecular meshwork. The
is disrupted, the inhibitory role is lost resulting in second peak occurs within a few hours and is due to
enhanced collagenolysis. Incompletely aqueous outflow obstruction and increased episcleral
transdifferentiated corneal epithelium is prone to venous pressure, trabecular meshwork damage and
persistent epithelial defects and easy susceptibility inflammatory debris obstruct outflow channels. Pros-
to abrasions.19 taglandin release also contribute to this phase.25-27 In
eyes with severe ciliary body damage, hypotony may
Stromal Ulceration result. Corneal clouding may occur within minutes
Following chemical burns, sterile stromal ulceration due to stromal edema and also due to changes in the
is generally seen 2-3 weeks or more after chemical stromal proteoglycans. Within a few hours, poly-
injury. Collagenolytic and proteolytic enzymes are morphonuclear cells, monocytes and fibroblasts start
released from infiltrating polymorphonuclear cells, invading the ocular structures. 23 In acid burns
regenerating epithelium, fibroblasts and keratocytes. opacification and charring of conjunctiva and corneal
Several closely related enzymes (called matrix epithelium may be apparent within a few seconds of
metaloproteinases) are involved. Type I collagenase exposure. Hydrofluoric acid is an exception, however.
has been found as early as 9 hours after chemical
trauma and usually peaks at 14-21 days coinciding Early Reparative Phase (1 to 3 Weeks after Injury)
with the clinical onset of sterile ulceration.20,21 Type After the first week, the corneal and conjunctival
I collagenase cleaves Type I, II, and III collagen which epithelium migration continues and in all but the most
are the predominant collagen types in the corneal severe cases completely covers the ocular surface.
stroma. Normally, collagenase is not found in the Corneal neovascularization, and invasion by infla-
cornea in either active or inactive form. Calcium acts mmatory cells parallel epithelial regrowth. Corneal
by stabilizing the enzyme structure, while zinc plays opacity begins to clear and in milder cases it may
a vital role in the enzymatic activity of hydrolysis.22,23 resolve completely. Collagen synthesis and glyco-
A relative deficiency of superoxide dismutase also saminoglycans synthesis peak by 14 days. Formation
occurs in association with corneal epithelial loss, of retrocorneal membrane occurs in cases with severe
which potentiates damage to the cornea.24 endothelial injury. Iritis disappears in milder cases
EVOLUTION OF TISSUE INJURY AND with recanalization of iris and ciliary body vessels.
CLINICAL PRESENTATION In more severe cases, severe fibrosis of iris and ciliary
body occur due to formation of granulation tissue.
Acute Phase (Immediately 1 Week after Injury) Corneal ulceration is also most commonly developed
Immediately after exposure to a chemical, there is by second to third week as collagenase activity peaks
disruption of cell membranes leading to loss of corneal during this period.
and/or conjunctival epithelium, keratocytes, corneal
Late Reparative Phase
nerves, endothelium, blood vessels, cellular and
(3 Weeks to Several Months after Injury)
vascular components of iris, and ciliary body and lens
epithelium. In milder injuries this may be restricted The balance between collagen synthesis and collagen
to merely corneal and conjunctival epithelial loss. In breakdown, which determines the presence or
absence of stromal ulceration, ultimately decides the to progression of symblepharon and to the develop-
outcome of chemical injury. Progressive or recurrent ment of entropion, trichiasis, and exposure with
corneal stromal ulceration leading to descemetocele associated further damage to ocular surface. Cataracts
formation, melting and perforation of the cornea is may develop early as a result of direct alkali damage
the most serious complication of chemical burns. to lens epithelium or due to inflammatory process.
Progressive ulceration is the main cause of loss of
eye in such injuries. Recurrent less severe ulceration
Grading of Ocular Chemical Burns Severity
leads to significant visual loss due to irregular corneal
surface. Corneal ulceration usually stops when the Hughes29 in 1946 first classified chemical burns into
cornea is totally vascularized. Blood vessels bring in mild, moderate, and severe depending on the clarity
nutrients and precursors of protein and proteoglycan of iris details and blanching of the conjunctiva. Roper
synthesis along with serum collagenase inhibitors, Hall30 and Ballens31 later modified this classification
which aid in healing. Progressive corneal vascu- to include the extent of corneal epithelial loss and
larization occurs after more severe alkali burn and the area of limbal damage and correlated the clinical
often does not subside till entire cornea is findings with the prognosis and treatment strategy.
vascularized. A fibrovascular pannus may overgrow The assessment of limbal ischemia provides inputs
the cornea in moderately severe injuries. When for an initial presumptive grading of the injury based
corneal endothelium is destroyed beyond its on the extent of assumed stem cell loss. Clinical
compensatory reserve, persistent corneal edema observation of the evolution of the healing pattern
results along with development of retrocorneal, then allows a precise determination of extent of limbal
cyclitic or iris fibrous membranes.28 Permanent loss
stem cell damage. This facilitates final classification
of corneal innervation may occur with resultant
into a confirmed grading of the injury (Table 31.3).
neuroparalytic or neurotrophic keratitis.
This use of grading system helps in making
Abnormalities of tear film are also common. Aqueous
appropriate therapeutic decisions.
and mucin components are affected adversely.
Scarring with loss of accessory lacrimal glands and/ Poor prognosis factors relate to the area of
or obstruction of ductule openings of major lacrimal chemical exposure (i.e. extent of corneal epithelial loss,
gland may lead to aqueous deficiency. Mucin extent of conjunctiva, episcleral and scleral ischemia)
deficiency occurs due to diffuse loss of goblet cells. and to the degree of chemical penetration (i.e. degree
Mucin deficiency promotes keratinization of corneal of corneal clouding, presence of hypotony, cataract,
and conjunctival epithelium. Intraocular pressure may and iritis).
range from hypotony to glaucoma due to primary In clinical evaluations, assessment of limbal
outflow obstruction, extensive peripheral anterior ischemia patterns forms the acceptable basis for
synechia, trabecular meshwork obstruction or very estimated stem cell loss. The area of conjunctival
rarely due to increased episcleral venous pressure. fluorescein staining corresponds roughly to the area
Presence of hypopyon or fibrinous iritis is an ominous of limbal ischemia. As limbal ischemia may not be
indicator of the possibility of secondary glaucoma prominent immediately after a chemical injury this
due to synechia formation or fibrous proliferation in area of staining also helps to grade the severity of
anterior chamber. Contraction of fibrovascular tissues presumptive stem cell damage. In severe cases, it is
of substantia propria of the conjunctiva may contribute prudent to re-examine after 48-72 hours to grade the
Table 31.3: Ocular chemical burns: Clinical severity grades

Grades Cornea Conjunctiva Prognosis
Grade I Epithelial loss only No ischemia Good: Full recovery
Grade II Some stromal haze but Ischemia less than one Good: Some scarring
iris visible third of limbus
Grade III Widespread stromal Ischemia affecting one Guarded: Vision impaired,
haze, iris details obscured third to one half of limbus perforation rare
Grade IV Opaque, no view of iris Ischemia greater than Poor: Expect perforation.
or pupil one half of limbus
Table 31.4: Therapy of ocular chemical burns

Therapeutic measures Medical Surgical
Control Topical antibiotics/ Debridement of tissues
inflammation steroids/NSAIDs
Promote Mucomimetic tear Punctal occlusion
re-epithelialization substitutes Primary artificial epithelium
Vitamin A analogs
Topical fibronectin Combined surgical
Topical EGF procedures—Tenonplasty
Bandage contact lens Conjunctiva—Tenon flap
Keratoepithelioplasty
Correction of trichiasis,
entropion, symblepharon
Support healing and Collagenase inhibitors Limbal autotransplant
rehabilitation Protease inhibitors Conjunctival flap
Ascorbic acid Glue application
supplementation Therapeutic keratoplasty
Vitamin A analogs Optical keratoplasty
Tetracyclines Keratoprosthesis.
injury as good clinical examination may not be possible thoroughly examined for small particulate matter.
immediately after the injury. When there is no evident Calcium hydroxide embed-ded in the tissue may not
limbal ischemia, the eye can be presumed to have a irrigate out freely. A 0.01-0.05 molar EDTA
grade I stem cell injury. (ethylenediaminetetra-acetic acid) solution can be
used as an irrigant to dissolve it. A cotton bud soaked
Treatment of Ocular Chemical Burn in sodium EDTA can also be used. Other methods of
irrigation are implantation of a T-tube and use of
Management of ocular burns aims to help promote
irrigating scleral lenses. All necrotic tissue contain-
re-epithelialization and transdifferentiation of
ing particulate matter should be removed as this can
denuded ocular surface, support repair processes and
prolong inflammation and lead to delayed healing.
minimize ulceration, and control inflammation (Table
31.4).
Acute Phase Treatment
The most important component of treatment of
ocular chemical burns is the initiation of irrigation— Topical antibiotics are started to prevent secondary
the sooner the better (Table 31.5). infection. Mydriatic-cycloplegics prevent the forma-
Any available bland nontoxic liquid like water, tion of posterior synechia and also relieve discomfort
ionic solutions or buffer solutions can be used. Sterile due to ciliary spasm. Attempt should be made to
solutions like normal saline, Ringer’s lactate or buffer record the intraocular pressure (usually best deter-
solutions are preferred, as water may cause minor mined by Mackay-Marg or pneumotonometer) and
cellular damage owing to its hypotonicity. Use of appropriate antiglaucoma medication should be
acidic solutions to neutralize alkali and vice versa administered. In case intraocular pressure estimation
may compound the injury and is contraindicated.28 is not possible, oral carbonic anhydrase inhibitors
pH of the lower fornix should preferably be should be administered. Efficacy and adverse effects
measured before initiation of irrigation. This also of topical antiglaucoma medication have not been
helps to identify whether injury is due to an acid or established in such situations. In case of minor injuries,
alkali. Irrigation should be carried out for about half simple irrigation along with topical cycloplegic-
an hour or more. Five minutes after irrigation, pH Table 31.5: Initiation of immediate primary therapy
should again be measured and further irrigation • Irrigation
performed if pH is not neutral. In case particular • Removal of particulate matter
matter is embedded in the cornea and conjunctiva, it • Debridement of devitalized tissue
should be gently removed with the help of a cotton • Topical antibiotics
swab. Lower and upper fornices should be • Topical anti-inflammatory agents.
mydriatic combination and application of pressure then left in place for 6-8 weeks. Soft contact lenses
patch may suffice. Topical steroids are useful at this and collagen shields are, however, often poorly
stage to reduce inflammation and the flux of tolerated in acute stage of chemical burns and may
inflammatory cells into the cornea. Studies indicate32 in fact be harmful.37,38
that steroids can be used safely in the first 10 days, Sweeping of the fornices with glass rods coated
even if epithelium is not intact. In fact, corneal re- with ointment to lyse adhesions or the use of scleral
epithelialization may be hastened with steroids at rings and symblepharon rings can be done to prevent
this stage due to decreased inflammation. If re- symblepharon formation due to apposition of raw
epithelialization is not completed by 10 days, steroids bulbar and tarsal conjunctiva surfaces. Frequent tear
should be rapidly tapered and discontinued as the substitutes with ointment used at this stage promote
risk of potentiating ulceration outweighs the potential re-epithelialization, ameliorate superficial punctate
benefit. Medroxyprogesterone acetate has proved keratopathy and reduce the risk of recurrent erosion.
useful at this stage. Although it is a weaker anti-
inflammatory than topical steroids, it has been shown Intermediate Phase Treatment
(Treatment of Reparative Phase)
to inhibit collagenase and reduce corneal ulceration
with minimal suppression of wound repair. Non- Eyes in which re-epithelialization is nearly or totally
steroidal anti-inflammatory drugs (NSAIDs) such as complete without significant vascularization need only
diclofenac sodium and ketorolac tromethamine have optical rehabilitation. In the eyes demonstrating
significant effect in reducing inflammation and have extensive stem cell damage the risk of stromal
a potential role when steroids are contraindicated. ulceration and perforation is high. Even if healing
Collagenase inhibitors (chelating agents) are also occurs, it is accompanied by severe corneal vascu-
useful at this stage. Both calcium and zinc are larization, conjunctival and corneal scarring, goblet
necessary for collagenases activity. These agents bind cell and mucin deficiency, and recurrent or persistent
calcium and zinc leading to reduced enzymatic epithelial defect. Progressive lid deformities, symble-
activity. A 0.2 molar solution of sodium EDTA can pharon formation, and neurotrophic keratitis may
be used.33 Cysteine (0.02 M solution) also acts by occur in these eyes. Mucomimetic tear substitutes help
chelating divalent ions and disrupting the disulphide stabilize the tear secretions and prevent repeated
bonds. Use of this drug is still experimental, as it is epithelial defects. If exposure keratitis is a signifi-
cant problem, median temporary tarsorrhaphy should
difficult to prepare.33
be done or a soft contact lens can be used, especially
Topical Aprotinin, a protease inhibitor, is found
if trichiasis is a problem. Bandage contact lens
to have limited plasminogen activity. 34 Systemic
promotes epithelial migration, basement membrane
doxycycline and other derivatives which chelate zinc
regeneration, and epithelial-stromal adhesion by
and inhibit PMN leukocyte activity are powerful
protecting the ocular surface from the windshield
anticollagenases.35
wiper effect of the lid.
Oral ascorbic acid 2 gm qid and topical 10 percent The control of intraocular inflammation may
ascorbate in methylcellulose can be given 1 hourly. It secondarily improve aqueous outflow and lower the
is important that ascorbate is administrated early as intraocular pressure. At this stage, topical vitamin A
late supplementation does not halt ulceration. Topical analogs for treating ocular surface disorders
epidermal growth factor acts by stimulating RNA, associated with abnormal keratinization and goblet
DNA, and protein synthesis. Studies have shown that cell abnormality are useful. In case where re-epi-
topical EGF (0.05 mg/ml in phosphate buffer solution) thelialization has taken place, retinoic acid could play
resulted in faster healing rates. However, this drug a role in promoting goblet cell recovery and corneal
is still in experimental stage.36 epithelial differentiation during the late reparative
Soft contact lens should be used where corneal period.39
re-epithelialization is delayed. This protects the Topical fibronectin has been shown to promote
epithelium from the shearing effect of the lids and cell to cell adhesions. It has no effect on cell mitosis
also promotes epithelial adhesions leading to faster or cell migration. Fibronectin is the multimeric
and better healing. Ideally, it should be fitted a few glycoprotein present in the extracellular matrix. After
days after the injury using lenses of moderate to high corneal injury, fibronectin is produced by epithelial
hydration and high oxygen permeability. These are cells 40 and keratocytes within 8 hours and is
distributed on the bare basement membrane ahead surrounding area of corneal thinning and necrosis
of and under the advancing epithelial edge, where it which is often seen in such eyes. Almost invariably
persists till the wound closure is complete. corneal grafts become opaque and vascularized.
Other complications of LK include persistent epithelial
Surgical Treatment including Rehabilitation defect, ulceration of donor graft, ‘cheese-wiring’ of
the sutures, wound dehiscence, and rapid loss of graft
In the acute and intermediate stages of severe
clarity.
chemical burns surgical intervention may be required
In the early reparative phase (within 3-4 months),
to help support repair process and minimize
once sufficient revascularization to support the
ulceration. Tissue adhesives (isobutyl-cyanoacrylate)
autograft has occurred, limbal autotransplant helps
can be used for sealing small impending or actual
prevent or reduce permanent ocular morbidity sequel
perforations. This has a tectonic effect on the cornea,
(Fig 31.1B). Ocular surface replacement is an effective
and retards further ulceration. Tissue adhesives have
way of restoring surface integrity in patients with
also been shown to have antimicrobial properties.41
monocular chemical injury. This can be performed
Less than 1.5 mm perforation may be successfully
using either conjunctiva or limbal autotransplants.
closed using tissue adhesives42 and this may eliminate
The use of conjunctiva transplantation was initially
the need for therapeutic keratoplasty.
described by Thoft in 197745 who recommended
Surgical procedures (conjunctiva-tenon flap and
conjunctiva transplantation for corneal
tenonplasty) are performed in eyes with more
vascularization and scarring after chronic monocular
extended burns of cornea, limbus and conjunctiva
chemical burns more than one year after injury (Fig
(Fig 31.1A). Initially, the necrotic conjunctiva and the
31.1C). The transplanted conjunctiva tissue migrates
underlying tissue are excised down to the ischemic
over the stromal tissue and adheres firmly and
sclera. These procedures are performed, with the aim
eventually assumes biochemical and morphologic
of covering the denuded sclera and to prevent
features similar to normal corneal epithelium, a
keratolysis.43 A thick conjunctiva-tenon advancement
process termed as conjunctiva transdifferentiation.46
flap is made, pulled to the limbus and tightly sutured
with mattress sutures. Tenonplasty is indicated when This may be effective in rehabilitation of the ocular
no conjunctiva is left in the fornices which can be surface and in selected circumstances may prove to
moved. Here, the Tenon’s tissue is bluntly separated benefit the vision as well. However, some studies
from the deep orbital tissue near the equatorial region have shown that the resurfaced cornea demonstrates
of the eyeball, pulled forward and moved to the poor cell adhesibility and the surface does not really
limbus, and sutured tightly. The advantage of these completely transdifferentiate as evidenced by the
procedures is that immediately after surgery, the persistence of goblet cells in such corneas.45 This is
sclera tissue is covered, and healthy conjunctival also supported by studies of glycolytic enzymes and
epithelium touches the limbus. At the same time glycogen content, 47 tensile strength, 48 keratin
artificial epithelium should be used to cover the profile,49 epithelial protein profile,50 and paracellular
denuded corneal stroma. Artificial epithelium is also permeability51 of the transdifferentiated conjunctiva,
useful to cover denuded corneal stroma in burns all of which indicate that the morphologic
limited to cornea only. Rigid gas-permeable (RGP) transformation is accompanied by only incomplete
contact lenses (diameter 10 mm and radius of biochemical and physiological transformation. In
curvature of 6.5-7 mm), are glued to the corneal severe chemical injuries, a significant proportion of
surface with isobutyl-cyanoacrylate glue. The aim is limbal stem cells may be destroyed causing poor
to halt progressive keratolysis in acute stage by healing. A valuable procedure for rehabilitation of
protecting the cornea from exposure to collagenolytic such eyes is limbal autotransplantation. It also
enzymes. This procedure decreases patients’ prepares the eye for sight restoring procedures like
discomfort, reduces incidence of scarring, optical penetrating keratoplasty. The operative
vascularization and ulceration.44 procedure involves the transfer of two free grafts
Tectonic penetrating keratoplasty is indicated for from the uninjured or less injured (grade I) eye to
globe-threatening perforations that are too large to the severely injured eye. Superficial keratectomy is
be managed by glue application alone. Lamellar performed, to remove superficial vascularized scar
keratoplasty (LK) is less successful because of the tissue, along with a complete conjunctival peritectomy
for approximately 2 mm posterior to the limbus. Deep
stromal dissection is avoided to decrease the risk of
inadvertent corneal perforation. Sector grafts of
limbal tissue which extend approximately 0.5 mm into
the clear cornea and 2.0 mm into bulbar conjunctiva
are then harvested from the 12 and 6 o’clock position
of the healthy eye. Each graft extends
circumferentially about 4 clock hours and measures
3 × 10 mm. Partial thickness corneal groove incision
is made and carried back towards limbus in a lamellar
fashion. The limbal autografts are then secured with
10-0 nylon sutures to the recipient cornea.
Postoperatively, moderate doses of topical steroids
and antibiotics are given along with cycloplegics and
A
unpreserved lubricants. Complications of this
procedure include inadvertent donor cornea
microperforation during the procedure. Also, if donor
tissue is taken from an eye whose limbus is
compromised, it is potentially possible to induce a
state of ocular surface failure in the donor eye.51,52
Recently, the use of fresh unmatched donor limbal
allograft transplantation has been reported.
However, this procedure, besides being difficult to
perform introduces the potential of epithelial
rejection.
Keratoepithelioplasty is a newer surgical proce-
dure for treatment of persistent epithelial defects in
patients without healthy donor tissue in the fellow
B eye. Persistent epithelial defects are characterized by
their chronic course, central location, and
accompanying inflammation. Use of soft contact
lenses, patching, and tarsorrhaphy may lead to
healing of these defects, but there always remains a
tendency to recur. The procedure involves
performing total superficial keratectomy and then
placing lenticules of donor cornea at corneoscleral
limbus. The donor eyes should be as fresh as possible.
Approximately 4 × 6 mm size lenticules (corneal
epithelium with minimal stroma) are removed. These
are then sutured at the limbus using 10-0 nylon
sutures. Topical steroids are given to minimize
chances of immunological rejection. It is
recommended that this procedure be used only for
C those epithelial defects that occur relatively long after
the initial traumatic event. Its use in acutely inflamed
Figs 31.1A to C: (A) Conjunctiva-tenonplasty procedure
eyes has not been established.53
involves bringing conjunctiva-tenon to the limbus. (B) Limbal Punctal occlusion either temporary (using either
conjunctiva autotransplant involves anchoring limbal collagen plugs or canalicular sutures), or permanent
conjunctiva at the limbus. (C) Conjunctiva transplant involves (using cautery) can be done for dry eye state. A
placing free conjunctiva on the cornea
temporary or permanent paracentral or lateral center ophthalmic casualty department during a 24-week
tarsorrhaphy can dramatically facilitate re-epitheliali- period. JR Soc Med 1989;76:279-82.
4. Pfister RR. Chemical injuries of the eye. Ophthalmology
zation. This also facilitates the use and retention of 1983;90:1246-53.
bandage contact lenses. 5. Morgan SJ. Chemical burns of the eye: Causes and manage-
Optical penetrating keratoplasty should be ment. Br J Ophthalmol 1987;71:854-57.
delayed for at least 1 year, when all corneal repair 6. Sainai JS, Sharma A. Ocular chemical burns: Clinical and
processes and inflammation have been inactive for demographic profile. Burns 1993;19:67-69.
7. Stanley JA. Strong alkali burns of the eye. N Eng J Med
some time. Keratoplasty in such eyes carries a poor 1965;273:1265-66.
prognosis because of presence of tear deficiency, 8. Paterson CA, Pfister RR, Levinson RA. Aqueous humor pH
abnormalities of lids and lashes, conjunctiva scarring after experimental alkali burns. Am J Ophthalmol 1975; 79:414-
corneal epithelial defects, stromal vascularization, 19.
presence of glaucoma, anterior segment fibrosis and 9. Grant WM. Experimental investigation of paracenteses in the
treatment of ocular ammonia burns. Arch Ophthalmol
retrocorneal membrane formation. The most
1950;44:399-404.
important factor influencing the visual outcome is the 10. Harris LS, Cohn K, Galin MA. Alkali injury from fireworks.
re-establishment of normal cornea like ocular surface. Ophthalmol 1971;3:849-51.
Normal lid anatomy should be re-established by 11. Holekamp TIR, Becker B. Ocular injuries from automobile
symblepharon lysis, expansion of fornices if required batteries. Trans Am Acad Ophthalmol Otolaryngol 1977;
83:805.
and treatment of trichiasis, entropion or ectropion.
12. McCulley JP, Whiting DW, Lauber S. Experimental ocular
Prior control of glaucoma is an important hydrofluoric acid burns. Invest Ophthalmol Vis Sci 1979;18:195.
consideration. Eyes with an unstable ocular surface 13. Khurrum MA, Ahmad S Hafeez. Long-term follow up of ocular
should undergo conjunctiva or limbal autograft lesion of methyl-isocyanate gas disaster in Bhopal. Ind J
transplantation at least 6 months before keratoplasty. Ophthalmol 1987;35:136-37.
Overall prognosis for this procedure is enhanced by 14. Cejkova J, Lojda Z, Obenberger J. Alkali burns of rabbit cornea
II: A histochemical study of glycosaminoglycans. Histo-
employing fresh donor tissue with intact and firm chemistry 1975;45:71.
epithelium. Postoperative complications include 15. Grant WM, Kern HL. Action of alkalis on the corneal stroma.
increased risk of graft rejection, glaucoma and Arch Ophthalmol 1955;54:931-34.
phthisis bulbi. 16. Pfister RR, Paterson CA. Additional clinical and morphological
Keratoprosthesis is done as a last resort for visual observations on the favorable effect of ascorbate in
experimental ocular alkali burns. Invest Ophthalmol Vis Sci
rehabilitation. The only indication now is repeated 1977;16:478-87.
graft failure after keratoplasty. Through and through 17. Friedenwald JS, Hughes WF, Hermann H. Acid burns of the
prosthesis offers the best results. However, the eye. Arch Ophthalmol 1946;35:98-108.
benefit is generally temporary due to the high 18. Schutz G, Henkind P, Gross EM. Acid burns of the eye. Am J
incidence of complications such as extrusion, Ophthalmol 1968;6:654-57.
19. Wagoner MD. Chemical injuries of the eye: Current concepts in
retroprosthetic membrane, glaucoma, retinal pathophysiology and therapy. Surv Ophthalmol 1997; 41:275-
detachment and infection.54 312.
Some other surgical procedures which are yet in 20. Brown SI, Weller CA, Akiya S. Pathogenesis of ulcers of the
experimental stages include limbal transplants from alkali burned corneas. Arch Ophthalmol 1970;83:205-08.
a heterologous donor combined with systemic 21. Brown SI, Weller CA, Wasserman H. Collagenolytic activity of
alkali burned corneas. Arch Ophthalmol 1969;81:370-73.
immunosuppressants, limbal transplants combined
22. Berman MB, Manabe R. Corneal collagenase: Evidence for zinc
with large aperture excimer laser photoablation, and metallozymes. Ann Ophthalmol 1973;5:1193-1209.
transplantation of ‘harvested’ stem cells which are 23. Berman MB et al. Characterization of collagenolytic activity in
propagated on biodegradable membranes.55 ulcerated cornea. Exp Eye Res 1971;11:225-27.
24. Nirankari VS et al. Superoxide radical scavenging agents in
treatment of alkali burns. Arch Ophthalmol 1981;99:886.
REFERENCES
25. Paterson CA, Pfister RR. Intraocular pressure changes after
1. Morgan SJ. Chemical injuries of the eye: Causes and alkali burns. Arch Ophthalmol 1974;91:211-18.
management. Br J Ophthalmol 1987;71: 854-57. 26. Paterson CA, Eakins KE, Paterson E, Jenkins RM et al. The
2. Jones NP, Hayward JM, Khaw PT et al. Function of an ocular hypertensive response following experimental acid burns
ophthalmic ‘accident and emergency’ department: Results of in the rabbit eye. Invest Ophthal Vis Sci 1979;18:67-74.
a six-month survey. Br Med J 1986;92:18-90. 27. Chiang TS, Moorman LR, Thomas RP. Ocular hypertensive
3. Vermon SA. Analysis of all new cases seen in a busy regional response following acid and alkali burns in rabbits. Inv
Ophthalmol 1971;10:270-73. glue. Arch Ophthalmo 1983;101:958-60.
28. Matsuda H, Smelser GK. Endothelial cells in alkali burned 42. Weiss JL et al. The use of tissue adhesive in corneal perforations.
corneas. Arch Ophthalmol 1973;89:402-09. Ophthalmol 1983;90:610-15.
29. Hughes WF. Alkali burns of the eye 2 clinical and pathological 43. Reim M, Teping C. Surgical procedures in the treatment of
course. Arch Ophthalmol 1946;36:189-214. most severe eye burns. Acta Ophthalmol 1989;67:47-54.
30. Roper-Hall MJ. Thermal and chemical burns. Trans Ophthal 44. Dohlman CH et al. Further experience with glued on contact
Soc UK. 1965;85:631-53. lenses (artificial epithelium). Arch Ophthalmol 1970;83:10.
31. Ballen PH. Treatment of chemical burns of the eye. Eye Ear 45. Thoft RA, Friend J. Biological transformation of regenerating
Nose Throat Monthly 1964;43:57. ocular surface epithelium. Inves Ophthal Vis Sci 1977;16:
32. Donshik PC, Berman MB, Dohlman CH et al. Effect of topical 14-20.
steroids on ulceration in alkali burned corneas. Arch 46. Thoft RA. Conjunctival transplantation. Arch Ophthalmol
Ophthalmol 1978;96:2117-20. 1977;95:1424-27.
33. Brown SI, Weller CA. Collagenase inhibitors in prevention of 47. Friend J, Thoft RA. Functional competence of regenerating ocular
ulceration in alkali burned cornea. Arch Ophthalmol surface epithelium. Inves Ophthal Vis Sci 1978;17:
1970;83:352-53. 134-39.
34. Brion M, Lambs L, Berthon G. Metal ion-tetracycline interactions 48. Kinoshita S, Friend J, Thoft RA. Keratin like proteins in corneal
in biological fluids: Part 5. Agents Actions 1985;17:229-42. and conjunctival epithelium are different. Inves Ophthal Vis
35. Cejkova J et al. Histochemical study of alkali burned rabbit Sci 1983;24:577-81.
anterior segment in which severe lesions were prevented by 49. Harris TM et al. Biochemical transformation of bulbar
aprotinin treatment. Histochemistry 1989;92:441. conjunctiva into corneal epithelium: An electrophoretic analysis.
36. Singh G, Foster S. Epidermal growth factor in alkali burned Exp Eye Res 1985;41:597-606.
corneal epithelial wound healing. Am J Ophthalmol 50. Huang AJW et al. Modulation of paracellular permeability
1987;103:802-07. during corneal epithelial wound healing. ARVO Abstracts Inves
37. Aronson SB, Elliot JH, Moore TE et al. Pathogenetic approach Ophthal Vis Sci 1986;27(suppl):54.
to therapy of peripheral corneal inflammatory disease. Am J 51. Kenyon KR, Tseng SCG. Limbal autotransplantation for ocular
Ophthalmol 1970;70:65. surface disorders. Ophthalmology 1989;96:709-23.
38. Cavanagh HD, Pihlaja D, Thoft RA. The pathogenesis and 52. Morgan SJ, Murray A. Limbal autotransplantation in acute
treatment of persistent epithelial defects. Trans Am Acad and chronic phases of severe chemical injuries. Eye 1996;10:349-
Ophthalmol Otolaryngol 1976;81:754-69. 54.
39. Soong HK et al: Topical retinoid therapy for squamous 53. Thoft RA. Keratoepithelioplasty. Am J Ophthalmol 1984;97:
metaplasia of various ocular surface disorders. Ophthalmology 1-6.
1988;95:1444-46. 54. Rao GN, Blatt HL, Aquavella JV. Results of keratoprosthesis.
40. Phan TM et al. Topical fibronectin in an alkali burn model of Am J Ophthalmol 1979;88:190-96.
corneal ulceration in rabbits. Arch Ophthalmol 1991;103: 55. Dua HS. Stem cells of ocular surface: Scientific principles and
414-19. clinical applications. Br J Ophthalmol 1995;79:970-71.
41. Eiferman RA, Synder JW. Antibacterial effect of cyanoacrylate
Chapter 32
Eye Banking
JS Saini, SK Gupta
Eye banks are conceived to provide for procurement, responsible for the day-to-day running of the entire
processing, and distribution of safe quality donor eyes eye bank services.3 He should be a trained senior
for therapeutic use and research.1 corneal surgeon of repute so as to inspire confidence
Eye banks undertake comprehensive work in staff and public. Technical in-charge maintains good
including promotional public relation activities and communication with the regulatory council, enucleators,
enhancement of public awareness, tissue harvesting, eye bank personnel, eye procurement coordinators
tissue evaluation, tissue preservation, and tissue and public. The other key managerial person in the
distribution. Eye bank training centers provide for eye bank is the eye bank manager. The Eye Bank
training of personnel in procedures for eye banking Association has recommended that there should be
in addition to the activities of an eye bank. There is no at least three technicians and grief counselors.
utility for promotional publicity without providing
for tissue harvesting mechanism. To be reasonably cost ORGANIZATION OF AN EYE BANK
effective, an eye donation center should be able to
Each eye bank should have a policy manual with
procure 20 pairs of eyes annually from an operative
details of all the policies and functions. 4,5 These
area population of 2-3 lakhs. An eye bank could serve
policies should include the job description of the
4-8 eye donation centers covering operative area
personnel employed by the eye bank. A technical
population of 8-15 lakhs. Each eye bank training center
manual should be prepared or adapted which
can be equipped to meet the training related needs of
describes the technical operations of the eye bank. The
4-8 eye banks.
eye bank Technician reports to the Medical Director
and is responsible for performing the day-to-day
EYE BANK STRUCTURE AND FUNCTION
operation. The technician must be familiar with the
Eye banks are structured as relative autonomous, procedures and policies of the eye bank, aseptic
largely voluntary community based and networked techniques of enucleation, tissue handling, corneal
set-up with in-built mechanism for equitable excision, and preservation procedures. Most
distribution of harvested tissue for human use and importantly, the person must be fully aware of the
research. Depending upon the local requirements, eye biohazards of the profession and should take all safety
bank are most suitably located either in a large hospital measures to protect oneself and other staff from
set-up or a central neutral nonprofit organization. possible contagious diseases. Certified and trained
Regardless of the location, each eye bank should have technicians preferably with medical laboratory work
a broad Regulatory Council of people from other background are suitable. At the eye bank, additional
specialties and walks of life to ensure a wider input assistant technicians, volunteers and community
for efficiency and community participation.2 program specialists for grief counseling, public liaison,
The Eye Bank Association of India has recommen- and soliciting eye donations participate. Similarly, a
ded that each eye bank should be under the charge of driver and a vehicle should remain available at the
a Medical Director/Technical In-charge who will be disposal of eye bank round the clock. If the eye bank
Chapter 32: Eye Banking 243
is situated within the premises of a hospital, the Table 32.1: Equipment for an eye bank
general reception and the ambulance services of the Mandatory Desirable
hospital could be utilized. Paging system currently
available are extremely useful to save time. • Refrigerator with temperature • Incubator
recording device • Specular microscope
• Biological safety cabinet or • Ultrasonic cleaner
EQUIPMENT FOR AN EYE BANK operation theatre • Ice machine
The equipment needed for an eye bank are listed in • Slit lamp • Microbiology facilities
(Table 32.1). It is desirable to install equipment • Sterilization facilities • Centrifuge
• Enucleation and corneal
dedicated for eye bank use.2,4,5
excision instruments
REGULATORY LAWS FOR EYE BANKING

when solicited this way, about 8 percent of the families
Eye bank staff should remain familiar with the local
consent to donate.1
operational legal framework. Procurement of eyes for
therapeutic use is legal in almost all countries of the
Publicity
world including India.6 Some forms of consent are
required under the law. Legal system either employs Public awareness plays a very crucial role in
an opt-in option wherein an affirmative consent has facilitating eye donation. Several publicity modes of
to be documented, and/or the consent is presumed the print media, audio-visual aids, and lectures have
unless specifically barred by the individual. been exploited to disseminate information about eye
In India, central government has enacted donation. Collecting pledge cards from the public for
legislation in 1994 that becomes applicable to the union potential eye donations works more toward
territories administered by the central government.7 popularizing the concept of eye donation than actually
Over a period of time, states are expected to adopt resulting in immediate eye donation. Publicity should
state legislation on the lines of central government. take care of also informing the community about the
However, till the time states enacted a uniform law operational steps of actual donation of eyes.
that eye banking continues to be governed by the Community pledges of 50 per thousand population is
existing legal system of each state. It is possible to a reasonable index of community support and
obtain a copy of the local state law relevant to eye publicity.
banking from the state secretariat.
Operational Efficiency
STRATEGIES TO ENHANCE EYE COLLECTION
Eye banking demands a very efficient round-the-clock
As of now, there is acute shortage of donor eyes in operational system in receiving a donor call and
most of the developing world.8-10 In India, estimated executing a response for eye collection to that call
corneal blindness is, 1.5 lakhs unilateral blind and 5.9 preferably within 20-30 minutes. These help to enthuse
lakh bilateral blind (NPCB-WHO, 1986-89).11 Against the community and meet the time constrains for
this huge demand for donor eyes in India, eye harvesting viable donor eyes. Modern eye banking
collections numbered 12,000 in 1995, of which only 50 demands assistance of dedicated state of the art
percent were assessed to be of usable grade.12 communication facilities.
Grief Counseling Legal Improvement

There is a general reluctance about eye donation at Enacted laws governing organ or tissue procurement
the time of a family member’s death resulting in low all over the world, have incorporated one of the two
voluntary eye donations. Family members need general approaches. One, voluntary affirmative
assistance to overcome the moments of grief and a consent by the descendent before death of the
tactful reminder that a timely eye donation is possible survivors in legal possession of the body after death.
for the human good.13-15 This strategy works best in The second approach presumes consent and allows
areas where large numbers of emergencies are treated tissue removal in the absence of prior objections. The
and there are concentrations of daily deaths because approach in each country is to a large extent deter-
of the nature of hospital work. On an estimated basis, mined by its need for organs, legal and social heritage,
and the public support for such laws.8,16,17 The choice In situ excision of the corneoscleral button is also in
of law and its enthusiastic application by the health practice. Both these procedures should be carried out
care workers in turn, influences the success of efforts meticulously with utmost respect to the donor.
to develop a sufficient supply of corneas.
There are 160 countries in the world where it is Preliminary Procedures
legal to procure cadaver eyes. 6 Countries with
Before starting any preparation for tissue collection,
“voluntary consent” or “opt-in” structure depend
legal permission should be obtained from the next kin
heavily on the surviving family consent to facilitate
of the deceased for eye donation.4,5 It is necessary to
eye donation (Uniform Anatomical Gift Act 1968, USA
go through the donor’s medical records and check for
or its variants).18-20 Most Asian countries including
the ocular and medical contraindications (Table 32.2).
India have legal “opt-in” system. Even within this
Wash hands with alcohol or similar disinfectant
“opt-in” system to facilitate consenting, some
solution. Put on protective clothing—surgical gown,
countries including the USA have refined “mandated
cap, mask, eye protection and nonsterile or prep
choice consent”17 and “routine inquiry laws.”21 State
gloves. Identify the donor either by a toe tag or some
is obligated to elicit premortem consent to donate eyes
other form of identification label on the body of the
upon death along with one of the mandated state
donor. Elevate and position the head so that it is
requirements like driver license, ration card, income
tax return, etc. Each individual has an option to refuse
eye donation by choice; but the experience has been Table 32.2: Contraindication to the procurement or use
that this practice helps the individual to think of of donor cornea1,4,5,25
donation at a time when there are no emotional upsets
and other pressures. Under the provision of the I. Systemic
“required request law”, health care workers are 1. Conditions potentially hazardous to eye bank
personnel and fatal, if transmitted:
obligated to request the family of the deceased for eye
a. Acquired immunodeficiency syndrome or HIV
donation upon death and offer further information seropositivity
about eye donation (Routine Inquiry Law, 1986, USA). b. Rabies
Legal requirements also help overcome apathy of c. Active viral hepatitis
health professionals to the process of obtaining consent d. Creutzfeldt-Jakob disease.
for eye donation. These legal provisions have helped 2. Other contraindications:
improve procurement of donor eyes. 22 In many a. Subacute sclerosing panencephalitis
countries, there are separate legal provisions b. Progressive multifocal leukoencephalopathy
authorizing eye donations by forensic pathologists c. Reye’s syndrome
without the requirement of obtaining consent.6 To d. Death from unknown cause including unknown
facilitate easier operational procedures, legal encephalitis
e. Congenital rubella
provisions permit removal of the cadaver eyes by non-
f. Active septicemia including endocarditis
ophthalmologists also (Cornea Tissue Act, 1986, UK).23 g. Acquired immunodeficiency high risk
behavioral features including homosexuals,
TISSUE RETRIEVAL intravenous drug abusers, prostitutes and
hemophilics
Tissue can be retrieved for transplantation either by h. Leukemia (blast form)
performing an enucleation, or by an in situ i. Lymphoma and lymphosarcoma.
corneoscleral excision.24 Donor eye enucleation is
technically easier and requires less time to perform II. Ocular
a. Intrinsic eye disease—retinoblastoma, active
than in situ corneoscleral excision. While enucleating inflammatory disease (conjunctivitis, iritis, uveitis,
donor eyes, however, there may be occasional vitreitis, retinitis), congenital abnormalities
significant blood ooze. Corneal endothelium quality (keratoconus, keratoglobus), central opacities and
deteriorates in enucleated eyes in 24-36 hr, which can pterygium.
be prolonged only on preservation of the corneoscleral b. Prior refractive procedures—radial keratotomy scars,
buttons in tissue culture medium. Many eye banks lamellar inserts, laser photoablation.
now recommend enucleation of the whole donor eyes c. Anterior segment surgical procedures (cataract,
glaucoma).
and corneoscleral excision in the eye bank laboratory.
straight and in one line with rest of the body. Elevation
of head allows minimal seepage of fluids into orbital
region and positioning helps during the cleaning and
surgical procedure thereafter. Discard used gloves into
biohazard bag. Open a clean drape to cover an area
close to the donor for supplies and equipment. Prior
to draping, if possible, decontaminate the area with
alcohol or similar solutions.
Collection of Blood
The best sites for postmortem blood collection are the
femoral vein, subclavian vein, heart or the jugular
vein. Use a 10 ml syringe and a spinal needle for
collection of blood from the heart, or a 10 ml syringe
and a 1½ × 18 G needle for other sites. Choose the site
for collection and clean the area with 70 percent
alcohol. Collect 5-10 ml of blood. Keep the tube upright
from the time of collection till the blood sample is
delivered to the eye bank and serum is separated.
Preparation
Prepare the donor as per operating room standards.
Open the right eye with the help of a sterile cotton
tipped applicator or sterile hemostat and copiously
irrigate the conjunctiva sac with sterile saline. Repeat
the same procedure on the left eye using a new cotton
tipped applicator or hemostat. After irrigation, clean
both sides of orbital area with alcohol swab/alcohol
gauze held in a sterile hemostat. Make sure alcohol
does not enter the eyes.
Enucleation
Insert the eyelid speculum and put 5 to 10 drops of
antibiotic solution on the cornea and keep the cornea
moist during enucleation (Figs 32.1A to F). Cut the
conjunctiva from the limbus 360 degrees around the
cornea. Isolate and clamp the lateral rectus muscle
with a hemostat. Cut the muscle distal to the eye. Figs 32.1A to F: Donor eye enucleation procedure. Following
Leave the hemostat in place so that at the end of the 360 degree peritomy (A), ocular muscles are cut (B), eyeball is
procedure, it can be used to lift the eye out of the then lifted (C), and optic nerve (D), as well as oblique muscles
are cut (E). Finally, harvested eyeball is placed in a glass vial
socket. Isolate and cut the superior, inferior, and
(F)
medial rectus muscles close to their point of
attachment to the eye. Isolate the inferior and superior
obliques and cut them. The hemostat rotates the eye to secure it firmly in socket with sterile cotton ball or
to check that all muscles have been cut and gently raise gauze. All disposables should be discarded in an
the eyeball and cut the optic nerve. Gently dissect appropriate biohazard bag and carried back to the eye
away the adherent tissue and put the eyeball in the bank to be disposed off properly. Corneoscleral button
eye cage so that the optic nerve passes through the can then be excised from the whole globe for
hole in the bottom of the cage and the cornea facing preservation in tissue preservation media (Figs 32.2A
upwards. Pull the optic nerve with the Allis forceps to D).
Figs 32.2A to D: Corneoscleral button excision procedure. Scleral incision 4-5 mm in length at 2-3 mm behind limbus
(A) is made, scleral incision is extended for 360 degrees (B), iris is pulled away from the cornea (C, D)
In Situ Corneoscleral Excision Gently put the cornea into the medium. The
epithelial side should touch the bottom of the vial.
Open the right eye and without touching the cornea
Without touching the donor, remove the speculum
insert the eyelid speculum. With the help of the
and proceed similarly with the left eye.
toothed forceps, grasp the conjunctiva close to the
limbus and make a small cut with the conjunctiva
Donor Cornea Viability
scissors. Introduce the scissors with their blades closed
Evaluation Methods
into the space between the conjunctiva. Cut the
conjunctiva from the limbus 360 degrees around the Donor corneal tissue may be available either as whole
cornea. Put 5 to 10 drops of antibiotic solution on the globes stored in a moist chamber or corneoscleral disk
cornea. Make an incision through the sclera, 2 to 3 mm in storage media.
from the limbus, and 4 to 5 mm in length into the The donor eyes are to be examined with a bright
suprachoroidal space with 15-blade. Using the right torch and preferably a portable slit lamp before
and left Castroviejo corneoscleral scissors, cut the enucleation or corneoscleral excisions (Table 32.3).
sclera 360 degrees evenly with blades of the scissors.
If excision has been performed correctly, the cornea Gross Examination
will be attached to the ciliary body-choroid (uvea) only Once the whole globes arrive at the eye bank, the
at the scleral spur. With toothed forceps, hold the condition of packing and the presence of ice in the
cornea by its scleral rim and with the iris forceps, styrofoam container is to be noted to know whether
gently pull away the iris. If excision has been the cold chain is broken. Sometimes the jar containing
performed correctly, an air bubble will appear in the eyes may be filled with water causing excessive
anterior chamber. stromal hydration. Such eyes are to be discarded
Table 32.3: Examination of donor eyes before in situ corneoscleral rim excision
A. Adnexa Dacryocystitis, styes, pustules, discharge (conjunctivitis)
B. Cornea Epithelium edema, exposure, trauma and foreign bodies.
Stroma Arcus senilis, corneal scars—central/limbal (evidence of prior
surgery), corneal infiltrates, abnormal corneal shape/size,
e.g. keratoconus, edema.
Endothelium Keratic precipitates, central guttata
C. Anterior chamber Shallow/flat, blood in anterior chamber, abnormal anatomy
congenital and acquired due to prior intraocular surgery.
unless a specular microscopy can be done to prove applicators. A low magnification is to be used initially
the presence of adequate endothelium. The jar and the to scan the globe for gross abnormalities with a wide
cap are to be examined for organic debris. The globe slit beam held at 45°.
is to be examined for scleral lacerations. In an eye bank,
Corneal epithelium Epithelial microcystic edema,
initial examination similar to that indicated in (Table
defects and debris are to be looked for. Epithelial
32.4), should be carried out on a slit lamp bio-
edema is an indicative of poor endothelial function.
microscope.2,4,26 The sclera is to be examined for any
Epithelial edema has to be carefully differentiated
yellow discoloration indicating a jaundiced donor.
from surface irregularity of the epithelium by oblique
When corneoscleral buttons are received, the color
illumination or retroillumination techniques.
of the tissue storage media is to be noted. If contents
are colorless or yellowish in color, it indicates an acidic Corneal stroma The corneal stroma is screened for
pH which could be due to microbial contamination. opacities, infiltration, edema and Descemet’s folds.
The expiry date of the storage media mentioned on
Corneal endothelium The specular endothelial reflection
the vial is to be noted.
provides a gross estimate of the endothelium in terms
of cell density, pleomorphism and presence of guttata.
Biomicroscopic Examination
A drop or two of antibiotic solution on the surface of
Whole globe examination The moist chamber stored the cornea will improve endothelial viewing.
tissue is to be examined as early as possible before the Frequently, linear markings similar to snail tracks are
corneal edema increases. The tissue is to be thawed to seen on the endothelium. These are stress fractures of
room temperature for the endothelium to function and the endothelial sheet from the trauma of excision.
deturgescence the cornea. All handling of the glove Crystals in the anterior chamber may indicate prior
should be done with sterile instruments/cotton tipped freezing of the eye and such globes are to be rejected.6
Table 32.4: Cornea viability rating scale2,4,5

Parameter Not present 1 2 3 4
Clarity crystal clear slight haze moderate haze heavy haze
Epithelial defects none not in center 50-90% of center > 90%
Epithelial edema none slight overall moderate marked
Scars 0 none peripheral peripheral central
Foreign bodies none none peripheral central
Stromal edema nonapparent slight peripheral mild entire thick
Opaque infiltrate 0 none none none none
Keratic none peripheral few central dense
precipitates
Arcus senilis none light, >8 mm >6 mm clear < 6 mm clear
clear cornea
Folds none peripheral central central
Guttata none 3-4 spots >4, central > 4, central
Jaundice 0 none light yellow moderate yellow orange
Endothelial count 2500/mm2 2000/mm2
Corneoscleral button examination The glass vials may Table 32.5: Cornea with specular endothelial patterns
be placed in a special holder and viewed conveniently unfit for transplantation
in a mirror placed below the vial or a special corneal
storage viewing chamber provides a good view of the 1. An endothelial cell density less than 1500 cells/mm2
excised rim. 2. Severe polymegathism or pleomorphism of the
The tissue is allowed to be warmed to room endothelial cells
3. Presence of central cornea guttata
temperature. As the corneal becomes compact due to
4. Abnormally shaped cells such as fused cells (these cells
the presence of dextran in the storage media, the
are seen in stressed endothelium)
presence of corneal edema cannot be assessed 5. Abnormal single cell defects
correctly; hence, the examination of whole globes 6. Severe edema of endothelium
before processing the tissue for media storage is very 7. Presence of inflammatory cells or bacteria on endothelium
important.
Table 32.6: Final cornea evaluation criteria
Specular Microscopy
Excellent = rating 1 a. no epithelial defects
A careful slit lamp examination provides an overall b. crystal clear stroma
status of the endothelium. The normal endothelium c. no arcus senilis
shows a pattern of cells of similar size and shape with d. no folds in Descemet’s membrane
no abnormal dark or bright structures being apparent e. excellent endothelium—no defects.
(Table 32.5). The cell density is between 2000 and 3500 Very good = rating 2 a. slight epithelial haze or defects
b. clear stroma
cells per sq mm.27
c. very slight arcus
Documentation d. few light folds
e. very good to excellent endothelium—
The details regarding a particular donor and the no defects.
donated tissue should be recorded meticulously and Good = rating 3 a. obvious moderate epithelial defects
in detail on a form for the transplanting surgeon to b. light-to-moderate cloudiness
evaluate the overall quality of the tissue. Tissue is c. moderate arcus senilis < 2.5 mm
d. obvious folds (numerous but shallow)
graded and labeled as excellent, very good, fair, and
e. few vacuolated cells.
poor2,4,5 (Table 32.6). Fair = rating 4 a. obvious epithelial defects (>60%)
b. moderate-to-heavy stromal cloudiness
CORNEA PRESERVATION c. heavy folds (numerous, deep, central)
d. heavy arcus senilis >2.5 mm
Moist Chamber Storage e. fair-to-good endothelium—moderate
This method is used for the storage of whole globe for endothelial defects, vacuolated cells,
a short period of time. The whole globe is stored in a low cell density.
Poor a. moderate vacuolated cells (some
sealed container at 4°C after applying topical central)
antibiotics. The major advantages of this method are b. severe stromal cloudiness
its simplicity, requiring little expertise, and a c. marked folds (heavy, numerous,
minimum manipulation. The major disadvantages are central)
that the storage time is limited to approximately 48 d. fair endothelium—marked defects,
hours and endothelium remains in contact with low cell density, numerous central
aqueous which is surrounded by tissues undergoing vacuolated cells
e. technical problems in removal.
postmortem autolysis.28
1. Position the eye jars so that they are immediately
Technique
adjacent to the edge of sterile field formed when
Moist chamber consists of a closed container with sterile instrument pack is opened.
cotton gauze moistened with sterile saline or other 2. Open a sterile moisture impermeable barrier drape.
sterile ophthalmic solution to provide a moist 3. Scrub three to five minutes and dry hands with a
environment. The container is never completely filled sterile towel.
with liquid so that entire eye is immersed. The 4. Soak or irrigate the eye using a povidone-iodine
procedure includes the following steps: or antibiotic solution for 3 to 5 times in a sterile
medicine cup. Avoid contaminating the sterile field tration of 2.5 percent the effect on corneal thickness is
by wetting of a cloth drape, if one is used. adequate without deleterious effect on the endothe-
5. Transfer the whole eye with sterile forceps from lium. Chondroitin sulfate is available from whale
antibiotic/antiseptic soaking solution to sterile eye (Type A, 38000 mw), wine (Type B, 2700 mw), and
jars for storage. shark (Type C, 73200 mw). Most newer media employ
6. Store whole globes for penetrating keratoplasty a 99 percent pure mixed source chondroitin sulfate of
(PK) in a moist chamber at 4°C maximum for 24- 6750 mw.29 Both high and low molecular weight chon-
48 hours. droitin sulfate is required. Low molecular weight
chondroitin sulfate helps retain viability of endothe-
Tissue Media Preservation lium in addition to the deturegence effect of higher
molecular weight chondroitin sulfate. Chondroitin
The prevailing practice today is to excise corneoscleral
sulfate also acts as an antioxidant. It is not as effective
button and place it in the tissue culture media. The
as dextran for thinning of the cornea. Most currently
storage media offers the following advantages:
preferred media contain both dextran and chondroitin
1. Provides a chemically defined and stable environ-
sulfate.32-34
ment at 4°C.
Electrolytes concentration in tissue preservation
2. Helps support and enhance metabolic activities.
media have generally been kept closer to that found
3. Helps reduce stromal swelling due to presence of
in the aqueous humor (Table 32.7). pH buffer system
colloidal active ingredients which render the tissue
employed in most of the media is the hepes buffer.
surgically manageable.
Most of the media contain Gentamicin at 65.5 to 99
4. Keeps the tissue under sterile conditions till use.
mg/ml concentration although new evidence has
5. Provides time for the eye bank to serologically
suggested that vancomcin may be a safer and more
screen the donor for communicable diseases.
efficacious antibiotic. Newer media also contain
The main ingredients of cornea preservation media
nonessential amino acids, ATP precursors vitamin B12
include the following:
and ascorbic acid for supporting the viability of
1. Dextran
endothelium. Insulin at 10 microgram/ml and HEGF
2. Chondroitin sulfate
(human epidermal growth factor) at 10 mg/ml are
3. Electrolytes
used to help sustain metabolic activity and mitogenic
4. pH buffer system
potential of corneal endothelium in newer media.29
5. Antibiotics
Although not as yet commercially available new
6. Essential amino acids
evidence is emerging that new antioxidant purpuro-
7. Antioxidants, ATP precursors
guallin, antiproteases, anticollagenases, and low
8. Insulin
concentrations of hydrocortisone may be beneficial to
9. Epidermal growth factor
preserved corneal endothelium34 (Table 32.8).
10. Antiproteases, anticollagenases.
Dextran helps to keep preserved cornea thin.29
Generally, the effectiveness of cornea is proportionate Table 32.7: Electrolyte composition of tissue
to the concentration of dextran. At concentration of 8 storage media
percent, dextran produces a significant damage to the Constituents Aqueous mM/L MK K-SOL CSM CSM-
endothelium; and at concentrations above 5 percent, DEXTRAN
it precipitates in the solution. Initially, tissue preserva- Sodium 163 147 206 189 180
tion media contained 5 percent concentration of
Potassium 2.2-3.9 5.5 4.2 4.8 4.6
500,000 mw dextran. 30 Subsequently, it has been
determined that 1 percent concentration of 40,000 mw Calcium 1.8 1.8 1.1 1.8 1.8
dextran is equally effective and the newer media are Chloride 132 133 108 117 110
based on this observation.29 Glucose 2.7-3.7, 5.2 3.9 4.7 4.7 4.7
Chondroitin sulfate is akin to naturally occurring Bicarbonate 30.2 13 nil 4.7 4.7
glycosoaminoglycans in the corneal stroma. It also
Osmolality 304 320 322 325 309
helps to keep the preserved cornea thin. 31 Dose
response studies had demonstrated that at concen- pH 7.38 7.3 7.31 7.1 7.24
Table 32.8: Cornea storage media

Constituents MK K-SOL CSM DEXSOL OPTISOL PROCELL
Base medium TC-199 TC-199 MEM MEM MEM,TC-199 MEM
Chondroitin nil 2.5 % 1.35 % 1.35 % 2.5 % 1.35 %
sulfate
Dextran 5% nil nil 1% 1% 1%
Hepes buffer yes yes yes yes yes yes
Nonessential nil nil yes yes yes yes
aminoacids
Sodium nil yes yes yes yes yes
bicarbonate
Sodium pyruvate nil nil yes yes yes
Antioxidants nil nil nil yes yes yes
Gentamicin 65.5 69.6 67.3 98 99 98
sulfate mg/ml
Ascorbic acid nil nil nil nil yes nil
Vitamin B12 nil nil nil nil yes
Insulin nil nil nil nil nil 10 μg/ml
HEGF nil nil nil nil nil 10 ng/ml
Storage time 4 days 7 days 7 days 10 days 14 days 14 days
Table 32.9: Organ culture medium composition 5. Tissue Banks International, Eye Banking Manual of Technical
Policies and Procedures, 1994.
Constituents Concentration 6. Lee PP, Yang JC, McDonnel. Worldwide legal requirements
MEM media for obtaining corneas—1990. Cornea 1992;11:102-07.
Defined fetal bovine serum 10 percent 7. The Transplantation of Human Organs Act. 1994,
Chondroitin sulfate 1.35 percent Government of India.
L-glutamine 2.0 mm 8. Lim ASM, Balakrishnan V. Corneal blindness and corneal
Sodium pyruvate 1.0 mm grafting in Asia. Asia-Pacific J Ophthalmol 1992;4:23-28.
Nonessential amino acids 0.1 mm 9. Coster DJ, Wiliams KA. Donor cornea procurement: Some
2-mercaptoethanol 0.44 mm problems in Asia. Asia-Pacific J Ophthalmol 1992;4(2):7-13.
Gentamicin sulfate 100 mg/ml 10. Griffith NF. The promise of “international eye banking”.
Ophthalmology 1990;14:205-10.
11. National plan for control of blindness—WHO Survey.
Long-term organ culture storage system involves Government of India, 1986-89.
placing the corneoscleral button in the special storage 12. Eye Bank Association of India. Eye donation statistics, 1995.
organ culture medium in a Petri dish initially for two 13. Diamond GA, Campion M, Mussoline JF. Obtaining consent
to three days at 34°C in 5 percent CO2 in water jacketed for eye donation. Am J Ophthalmol 1987;103:198-203.
incubators.35 After two media changes, the cornea are 14. Mannieu DV, Evans RW. Public attitudes and behavior
regarding organ donation. JAMA 1995;253:3111-15.
suspended in 130 ml of medium by a spinal needle
15. Basu PK, Hazariwala KM, Chipman ML. Public attitudes
hook inserted through the scleral rim and then stored toward donation of body parts, particularly the eye. Can J
at 34°C. Organ culture method enables a preservation Ophthalmol 1989;24:216-20.
period of 35 days (Table 32.9). 16. Veriana JR, Nora LM, Bone RC. Issues in biomedical ethics.
In: Disease-a-Month. 1993;39:884-89.
REFERENCES 17. Strategies for cadaveric organ donation-Council on Ethical
and Judicial Affairs of American Medical Association.
1. Proceedings of seminar on hospital cornea retreival Council Report. JAMA 1994;272:809-12.
programme, Hyderabad. 1997. Ministry of Health, 18. Eye Bank Association of India Medical standards, 1996.
Government of India and Eye Bank Association of India. 19. The Punjab Anatomy Act, 1963, Government of Punjab State,
2. Saini JS, Reddy MK, Jain A et al. Perspectives in eye banking. India.
Indian J Ophthalmol 1996;44: 47-55. 20. The Goa, Daman and Diu (Authority for use of eyes for
3. Proceedings of workshop on eye banking in India, therapeutic purposes) Act, 1980.
Hyderabad. Ministry of Health, Government of India, 1996. 21. Andersen KS, Fox KM. The impact of routine inquiry law on
4. Minnesota Eye Bank Manual revised, 1995. organ donation. Health Att 1988;7:65-78.
22. Farge EJ, Silverman LM, Khan MM. The impact of State 29. Lindstrom RL. Advances in corneal preservation. Trans Am
legislation on eye banking. Arch Ophthalmol 1994;112:180- Ophthalmol Soc 1990;88:555-48.
85. 30. McCarey BE, Kaufman HE. Improved cornea storage. Invest
23. Armitage WJ, Moss SJ, Easty DLB. Supply of corneal tissue Ophthalmol 1974;13:165-73.
in the United Kingdom. Br J Ophthalmol 1990;74:685-87. 31. Kaufman HE, Varnell ED, Kaufman S. Chondroitin sulphate
in a new cornea preservation medium. Am J Ophthalmol
24. Lane SS et al. Whole globe enucleation versus in situ corneal 1984;98:112-14.
excision. Cornea 1994;13:305-9. 32. Steinemann TL, Kaufman HE, Lindstrom RL. Intermediate
25. Uniform Anatomical Gift Act. 8a ULA 16, (Suppl) USA, 1989. term storage media (K-sol, Dexsol, Optisol). In Brightbill F
26. Reinhart WJ. Gross and slit lamp examination of donor (Ed): Corneal Surgery: Theory, Technique and Tissue. St
cornea. In Brightbill FS (Ed): Corneal surgery: Theory, Louis: CV Mosby Co 1993;609-13.
technique and tissue. St. Louis: CV Mosby co 1993;570-75. 33. Kaufman HE, Beuerman RW, Stenemann TL et al. Optisol
corneal storage medium. Arch Ophthalmol 1991;109:864-68.
27. Hoffer KJ, Kraff MC. Normal endothelial cell count range.
34. Vila J, Hasany SM, Parker JA, Rootman DR. In vitro
comparative study of a locally prepared corneal storage
28. Friedland BR, Froster RK. Comparison of corneal storage in medium and optisol. Can J Ophthalmol 1996;31:221-27.
Mc Carey-Kaufman medium, moist chamber, or standard eye 35. Lindstrom RL. Minnesota system cornea preservation. Br J
bank conditions. Invest Ophthalmol 1976;15:143-47. Ophthalmol 1986;70:47-54.
Chapter 33
Penetrating Corneal
Transplantation
AK Bansal, GN Rao
Modern methods of eye banking, corneal preservation, successful penetrating keratoplasty was done by Zirm
surgical techniques with exquisite precision, early in 1906, where the graft remained clear for 18 months.
recognition, and prompt treatment of complications The 8 principles enunciated by Zirm for a successful
have made corneal grafting the most successful form keratoplasty are still true today, albeit, with few
of organ transplantation. modifications. These principles are:
1. Exclusive use of human donor material—young
BACKGROUND and healthy, if possible
2. Use of Von Hippel’s trephine and Eserine
The idea of replacement of a diseased cornea
3. Adequate anesthesia
originated in the eighteenth century in the mind of a
4. Strict asepsis
Frenchman named GP De Quengsy. Although he
5. Avoidance of contact of antiseptics with cornea
never actually performed a corneal transplant, he
6. Protection of graft between layers of moistened
outlined in detail the instruments, the technique,
gauze pieces
postoperative management, and possible compli-
7. Adequate retention of graft with overlay sutures
cations following such a procedure. Erasmus Darwin
8. Careful selection of cases.
also suggested trephining of a corneal graft to replace
Over the last century corneal transplant surgery
a scarred cornea in 1797.
has evolved from a crude, mostly unsuccessful experi-
In the nineteenth century Reisinger was the first
ment to a highly sophisticated, refined and delicate
person to give the idea of replacement of a scarred
procedure with a high success rate. Much of the
cornea with living tissue and coined the term
progress over this period has been in the fields of
“Keratoplasty.” Since the results of most of his
corneal physiology, pathology, and improved storage
experimental work were poor, his idea of keratoplasty
techniques. Better surgical instrumentation,
was thought to be one of the most audacious fantasies.
microsurgical techniques, and better understanding
The first attempt at keratoplasty in a human being
of the behavior of corneal graft following trans-
was made by Kissam in 1844 using pig’s cornea in
plantation are main contributory factors.
human eye. The graft remained clear for 2 weeks. Von
Hippel in 1886 transplanted a lamellar graft from a
INDICATIONS
rabbit’s cornea into a young girl’s eye, resulting in
visual improvement from hand movement to 20/40. i. Optical: Where the graft is done for visual rehabili-
A very significant contribution from him was the tation.
invention of a circular trephine with a clockwork ii. Tectonic: For restoring the altered corneal struc-
mechanism which simplified cutting the corneal ture.
button. The circular trephine has become the mainstay iii. Therapeutic: Tissue substitution for refractory
of surgical instruments used in keratoplasty. The first corneal diseases.
Chapter 33: Penetrating Corneal Transplantation 253
Indications for penetrating keratoplasty (PK) have The prognosis for visual improvement after
changed drastically over the last 25 years or so. In the penetrating keratoplasty for keratoconus is excellent.
mid twentieth century in developed countries, the Success rate in various studies ranges from 90 to 93.6
most common indications for corneal grafting were percent. A vision of 20.40 or better is usually achieved
scars following herpes simplex keratitis, regrafts and in 73 to 92.1 percent of the eyes. Occasionally, lamellar
keratoconus. Transplants for cataract extraction keratoplasty has been suggested as an alternative to
related bullous keratopathy were almost nonexistent. penetrating keratoplasty for the treatment of
About ten to fifteen years ago, the main indications keratoconus, but the visual results with it are not good
for transplants were regrafts and keratoconus with as with penetrating keratoplasty and wrinkling of
aphakic bullous keratopathy becoming a fairly Descemet’s membrane and scarring at donor host
common indication.1 More recent data indicated that interface often reduces the optical clarity.
cataract extraction related bullous keratopathy was
the leading indication for corneal transplants till 1980s. Corneal Edema
In a retrospective analysis of keratoplasties performed
In pseudophakic or aphakic edema if the vision
over a nine-year period (1980-1988) at a leading
becomes unacceptable or the eye becomes painful, a
corneal center, the seven most common indications
penetrating keratoplasty is the only treatment. About
for penetrating keratoplasty were found to be
85 percent of the transplants done for aphakic and
keratoconus (24.0%), pseudophakic or aphakic bullous
pseudophakic corneal edema remain clear.6-9 The
keratopathy (21.2%), corneal scarring (13.9%), Fuchs’
chances of getting a vision of 20/40 or better range
dystrophy (12.5), regrafts (8.1%), and herpetic keratitis
from 42 to 70 percent.
(5.3%). It was seen in this study that while keratoconus
was the leading indication from 1980 to 1985, in the
Failed Graft
latter period, pseudophakic bullous keratopathy
became the predominant indication accounting for Regrafting may be done for a variety of reasons includ-
24.4 percent of the cases. 2 Other less common ing primary graft failure, graft rejection, glaucoma,
indications were infectious (nonviral) keratitis (3.5%), graft infection, etc. Sometimes regraft has to be done
trauma (1.5%), other dystrophies (1.4%), congenital for high astigmatism not correctable with contact
opacities (0.8%), and chemical burns (0.5%). Various lenses. Another indication for regraft is recurrence of
other studies3,4,5 have also shown the emergence of corneal dystrophy in the graft.
pseudophakic bullous keratopathy as the most Failed graft is a frequent indication for corneal
common indication for penetrating keratoplasty which transplantation. In a large study, regrafts accounted
correlates well with the dramatic increase in the for 22.7 percent of all keratoplasties while in recent
number of intraocular lens implantations over this study regrafts accounted for only 8.1 percent of
period. In the undeveloped or developing countries keratoplasties.2 The refinement of surgical technique
the picture is somewhat different. Our experience has and suture materials and instruments coupled with
indicated corneal scars to be the most common early recognition and management of graft rejection
indication for penetrating keratoplasty followed by has significantly enhanced the success rate of kera-
pseudophakic/aphakic bullous keratopathy, toplasty. The use of HLA matched donor corneas and
keratoconus, corneal infections, dystrophies, and the prevention/suppression of graft rejection with
failed grafts in that order. drugs like Cyclosporine-A may further reduce the
need for regrafts.
Some Specific Indications for
Penetrating Keratoplasty Herpes Simplex Keratitis
Herpetic keratopathy requires PK when stromal
Keratoconus
necrosis and recurrent geographical and trophic ulcers
Penetrating keratoplasty in keratoconus is indicated develop. Herpetic keratitis accounts for 5 to 9.8 percent
in situations of contact lens intolerance, contact lens of PK. Clear grafts can be obtained in approximately
failure, apical scarring and rapid progression toward 80 percent of the cases when the herpes simplex is
periphery. inactive and the eye is quiet10 but the chances for
success fall to 40 to 50 percent in eyes with active like Peter’s anomaly, Sclerocornea or CHED. In such
disease with extensive neovascularization. cases prognosis is usually poor due to amblyopia
unless surgical intervention is undertaken early.
Corneal Infections (Non-viral) The probability of obtaining clear graft at the age
of one year has been shown to be maximum (73%) in
Microbial corneal ulcer still remains a significant
case of acquired nontraumatic opacities, less (70%) in
problem. A therapeutic penetrating keratoplasty is
trauma and least (60%) in cases of congenital anoma-
required if: (a) ulcer is not responding to medical
lies.14
treatment, (b) impending perforation, (c) recent
perforation of the cornea. Due to nonavailability of
PROGNOSIS
effective antifungal ocular preparations, management
of fungal corneal ulcers is a problem. Therapeutic The prognosis for graft clarity depends upon initial
keratoplasty is indicated in most of the fungal ulcers. pathological condition of the recipient cornea apart
from other factors such as quality of donor tissue,
Corneal Dystrophies surgical technique, timing of surgery, postoperative
care, etc. The various prognostic groups are as follows:
Corneal dystrophies are one of the major indications
for penetrating keratoplasty. In the West, Fuchs’
Gr I Excellent Prognosis
dystrophy has been found to be the most common
indication of keratoplasty.2,4,11 In Asian population • Keratoconus
macular stromal corneal dystrophy is common among • Traumatic leucoma
all the dystrophies followed by Fuchs’ and congenital • Lattice and granular dystrophy
hereditary endothelial dystrophy (CHED).12 Recent • Superficial stromal scars.
study shows macular stromal dystrophy to be the most
common indication (23.1%) followed by CHED Gr II Good Prognosis
(13.2%), Reis Buckler’s Lattice and Granular (9.9%
• Small vascularized scars
each), and Fuchs’ (6.6%).
• Bullous keratopathy
• Fuchs’ dystrophy
Keratoplasty in Children
• Failed grafts from group I which have not been
Grafts in infants and children can often be difficult as vascularized
the cornea and sclera are more elastic and are difficult • Macular stromal dystrophy
to handle, the iris more adhesive, vitreous more • Interstitial keratitis.
tenacious and the eyes mount a more severe inflamma-
tory response. Follow-up care is another problem in Gr III Fair Prognosis
children. • Moderately vascularized cornea
Indications in pediatric age group include: • Failed Gr/II grafts
i. Congenital corneal opacities as in • Active stromal herpes simplex keratitis
• Peter’s anomaly • Congenital hereditary endothelial dystrophy
• Sclerocornea • Scars following bacterial corneal ulcers.
• Glaucoma with corneal edema
• Corneal dystrophies. Gr IV Guarded Prognosis
ii. Acquired nontraumatic causes like • Mild dry eye
• Infection • Active fungal keratitis
• Steven-Johnson’s syndrome • Failed or rejected Gr/III grafts
• Keratoconus. • Anterior chamber cleavage syndrome
iii. Trauma It is one of the most important indications • Corneal staphyloma
of keratoplasty in children. The prognosis tends • Epithelial downgrowth
to be worse in children in traumatic cases as • Corneal blood staining
compared to adults.13 • Mild chemical burns
The second most frequent indications for corneal • Congenital glaucoma
transplantation in children are congenital conditions • Most pediatric keratoplasties.
Gr V Poor Prognosis
• Severe dry eye—pemphigoid
• Steven-Johnson’s syndrome
• Chemical burns.
DONOR CORNEA
Role of eye bank for supply of donor material along
with its retrieval, selection and storage is described in
Fig. 33.2: Specular microscopic picture of corneal endothelium
Chapter 46.
showing abnormal cells of various shapes joining at abnormal
angles
Specular Microscopy
Specular microscopy is an important method for
evaluation of the donor cornea before penetrating
keratoplasty. It is employed to note the following
features of endothelial cells.
i. Cell density
ii. Cell shape, size, uniformity, pleomorphism, and
polymegathism (Figs 33.1 and 33.2).
iii. Presence of corneal guttata (Fig. 33.3).
iv. Evidence of any old intraocular inflammation and
endothelial insult (Fig. 33.4).
The higher the endothelial cell density, greater
would be the success of transplantation. If the cell Fig. 33.3: Specular microscopic picture showing corneal
density is appreciably less than what might be expected endothelium with moderate guttate changes
from a donor of similar age, then that tissue should
be excluded. Corneas with considerable polymega-
thism or pleomorphism have an increased incidence
of postsurgical decompensation15 and have a reduced
functional reserve.16 Similarly, presence of cornea
guttata also leads to reduced endothelial functional
reserve.
The criteria to consider a cornea unsatisfactory are:
i. Very low endothelial cell count (< 1500 cells/
mm2).
ii. Extreme polymegathism or pleomorphism.
Fig. 33.4: Specular microscopic picture of corneal

endothelium showing multiple keratic precipitates
iii. Presence of significant corneal guttata.

iv. Presence of extensive areas with severe edema.
v. Presence of inflammatory cells on the endo-
thelium.
Donor Corneal Preservation
Fig. 33.1: Specular microscopic picture showing corneal During the past ten years there has been an increase
endothelial cells of normal shape, size, and density. Such a in understanding in corneal preservation techniques.
cornea is ideal for transplantation The father of modern eye banking was Filatov of the
USSR who reported his 35 years experience of corneal Specular microscopy It is with morphometric analysis
transplants obtained from human cadavers within a can be used to determine corneal endothelial cell
few hours after death and stored in an ice chest at 4°C density and morphology in an intact eye as well as in
for 20 to 56 hours prior to transplantation. This method a corneoscleral rim.
is essentially the same as the moist chamber technique. Enzyme release This technique involves monitoring the
Then, cryopreservation was thought of as a method release of cytoplasmic or lysosomal enzymes into the
of preserving the donor tissue because of its potential aqueous humor which is related to organelle and
for prolonged preservation. Although the method has plasma membrane disruption and hence tissue
proven clinically successful, its complexity and less viability. Various enzymes which can be studied
than optimal endothelial cell preservation have include lactate dehydrogenase and acid phosphatase.
discouraged its use. The major breakthrough in
Magnetic resonance imaging This method allows
corneal preservation came with the introduction of
noninvasive measurement of intracorneal pH and
MK medium (McCarey and Kaufman), in 1974. It is
determination of the levels of adenosine triphosphate,
one of most commonly used methods of corneal
inorganic phosphate and other energy related
preservation today. For the first time this medium
phosphate metabolites.
allowed the surgeon to perform keratoplasty as a
planned procedure rather than an emergency surgery. Redox fluorometry It was originally developed as a
More recently media containing chondroitin sulfate technique for noninvasively determining the
have been introduced in which corneas can be stored metabolic status of the corneal tissue by measuring
up to 2 weeks at 4°C. the relative concentration of reduced pyridine
nucleotides and oxidized flavoproteins. Recent
Methods of Assessing Corneal modifications allow the imaging of individual
Endothelial Viability endothelial cell as well.
Intracellular glutathione Intracellular glutathione
In order to analyze the effectiveness of corneal
oxidation-reduction profile can be used as a method
preservation method, it is necessary to assess the
of assessing the capability of fluid transport by the
capacity of the technique for maintaining endothelial
corneal endothelium.
viability. Each method for assessing viability attempts
to evaluate changes in a specific functional process or Radioactive isotope studies Ability of corneal endothelial
alterations in cellular morphology. Various methods cells to incorporate tritiated uridine into RNA can be
of assessing corneal endothelial viability include: taken as a measure of their viability
Oxygen consumption Several investigations have
Staining method The method utilizes the capacity of
monitored oxygen consumption as a measure of
various dyes to stain the devitalized or viable
endothelial cell viability.
endothelial cells which can then be counted. Various
dyes that can be used include Trypan Blue, Nitro Blue Endothelial tissue culture This method takes into
Tetrazolium, Acridine Orange, Rose Bengal, Evans account the availability of endothelial cells to prolife-
Blue and Alizarine Red. rate in tissue culture as a measure of endothelial cell
viability.
Temperature reversal This process gives a direct
demonstration on corneal endothelial function by Methods of Corneal Preservation
showing the reversal corneal thickening after warning
the cooled cornea. An ideal method for corneal preservation is yet to be
developed. The requirement for optimal corneal
Bicarbonate flux This method monitors maintenance preservation include indefinite period of preservation
of endothelial bicarbonate flux as a measure of endo- while maintaining structural and functional viability
thelial viability. It is based on the fact that net bicarbo- of the tissue, sterility, easy availability, technical
nate flux is related to endothelial pump function. simplicity, easy transportability, and inexpensiveness.
Electron microscopy Transmission electron microscopy None of the presently available media fulfill all these
allows the examination of morphology of cells and requirements.
the structural damage, if present, while by scanning This various corneal preservation methods can be
electron microscopy plasma membrane integrity may classified on the basis of their ability to enhance the
also may be ascertained. viability of cornea in terms of duration.
These are: stabilization of the pH and added phenol red as a pH
i. Short-term storage methods indicator. The osmolarity of the medium is 290
ii. Intermediate-term storage methods mOsm/kg and the pH is 7.4. This is known as modi-
iii. Long-term storage methods. fied MK medium. In this medium the cornea can be
stored at 4°C for upto 4 days.
Short-term Storage It is generally accepted that storage time in MK
medium should not exceed 4 days. MK medium has a
Moist chamber method Whole globe preservation at 4°C
protective effect on the endothelium compared to
with saline humidification for upto 48 hours was the
moist chamber storage when corneal tissue is warmed
standard method of the corneal storage in countries
to room temperature.19
like USA until 25 years ago and it is still the most
popular method in the third world countries.
Chondroitin Sulfate Enriched Media
Major advantages of this method are that it is
simple, inexpensive, easily transportable, and requires K-Sol medium K-Sol was initially used for inter-
minimum manipulation. mediate-term storage of corneal tissue for at least 2
• Storage time is limited to 48 hours, which makes it weeks at 4°C.20 K-Sol medium consists of the following
necessary that the surgery be performed as an constituents:
emergency. During this time it is difficult to • TC99
perform HLA matching and screening of donor for • Chondroitin sulfate 2.5 percent24
AIDS and hepatitis virus. • Hepes buffer 0.025 M
• Endothelium remains in the rapidly changing • Gentamicin sulfate 100 μg/ml.
aqueous environment surrounded by tissues In earlier clinical studies, K-Sol storage for up to 2
undergoing autolysis. weeks gave identical results with those found with
• A 25 to 30 percent decrease in endothelial viability MK medium storage for only 2-3 days.21 Endothelial
is seen in moist chamber stored eyes after 48 hours cell loss was found to be 6 percent 2 months after
in rabbits. corneal transplants in corneas stored in K-Sol for a
Factors of significance in assuring endothelial mean of 6.8 days at 4°C and in MK medium for a mean
viability are: of 39 hours at 4°C.22,23
a. Enucleation within six hours after death. Though some reports suggest that K-Sol preserved
b. Maintenance of cool environment until enucleation cornea shows better endothelial stability other
by placing ice bags on closed lids. reports25 suggest that there is no difference of activity
c. Maintenance of 4°C temperature during transpor- between modified MK medium and K-Sol medium.
tation, and
Corneal storage medium (CSM) CSM is another
d. Careful slit lamp examination of donor eye by a
potential medium for use in intermediate-term corneal
qualified person.
preservation. It was introduced in 1986.26 It consists
of the following:
Intermediate-term Storage
• Minimum essential medium
McCarey-Kaufman medium • 1.35 percent chondroitin sulfate
• 0.025M herpes buffer
Original formulation of the MK medium consisted of
• Mercaptoethanol
the following:17
• Nonessential amino acids.
• TC 199
• Gentamicin 100 μg/ml.
• 5 percent Dextran (Mol wt. 40,000)
• Bicarbonate buffer Dexol medium Dexsol was introduced in 198827 for
• Penicillin and streptomycin (100 unit/ml) which intermediate term corneal storage and is now used in
was later substituted by gentamicin in concentra- eye banks allover the world. Its composition is similar
tions of 50-200 μg/ml. to that of CSM, with 1 percent dextran added to
This medium was modified by Waltman and increase colloidal osmotic activity. It is composed of
Plamberg in 1978.18 They substituted 0.025 M HEPES the following:
(N’-2-hydroxyethylpiperazine-N-ethane-sulphonic • Minimum essential medium
acid) buffer for bicarbonate buffer for better • 1.35 percent chondroitin sulfate
• 1 percent Dextran, mol wt 40,000 examined daily for evidence of contamination. If after
• Hepes buffer 10 days, no growth is noted in any of the microbiologic
• Gentamicin sulfate 100 μg/ml media and the media in the closed bottles containing
• Nonessential amino acids 0.1 m mol/l the corneas are clear and without any pH change, the
• Sodium pyruvate 1 m mol/l system is considered sterile and cornea is considered
• Additional oxidants. fit to be transplanted.
Dexsol is significantly superior to other media in Addition of chondroitin sulfate has been shown to
retaining energy dependent ion transport at storage affect marked decrease in endothelial cell loss. In a
times through 6 days.28 study it was noted that endothelial cell loss 2 months
Optisol medium This medium was described in 1991 after keratoplasty was 7.9 percent in corneas cultured
by Kaufman and associates.29 It contains both dextran in medium containing 1.35 percent chondroitin sulfate
and chondroitin sulfate to enhance corneal dehydra- as compared to corneas cultured in identical media
tion during storage. Its constituents are the following: without chondroitin sulfate where the endothelial cell
• TC 199 + minimum essential medium loss was to the tune of 28.7 percent. An additional
• 2.5 percent chondroitin sulfate advantage of adding chondroitin sulfate is that the
• 1 percent Dextran, mol wt 40,000 corneas remain thin which leads to greater ease during
• Herpes buffer the surgery.
• Gentamicin sulfate 100 μg/ml Transmission and scanning electron microscopy
• Nonessential amino acids 0.1 m mol/l have shown maintenance of endothelial morphology
• Sodium bicarbonate for up to 120 days in organ cultured corneas. Epithelial
• Sodium pyruvate l m mol/l intercellular and intracellular edema develops and a
• Additional antioxidants. decrease in the number of epithelial cells occurs, but
This medium combines advantages of two the general epithelial structure is maintained for at
previously developed media K-Sol and Dexol. least 35 days.31,32
Cryopreservation It can be regarded as the only true
Long-term Storage
preservation method that can preserve the corneas for
This includes organ culture method and cryopreserva- an indefinite period of time.
tion. Capella and Kaufman developed the basic
Organ-culture method It is a method for long-term method of cryopreservation which, with slight modifi-
preservation of donor cornea up to 35 days without cation, is still used in some of the eye banks. In this
any remarkable loss of endothelial cells and ultrastruc- technique, the corneoscleral rim is passed through a
tural defects. series of solutions containing increasing concen-
The method of organ culture30 is as follows: trations of dimethyl sulfoxide (DMSO) upto 7.5
The corneoscleral segment is placed in Petri dish percent. The tissue is placed in each solution for 10
containing 15 ml of medium. The organ culture minutes. Next the tissue is frozen at a controlled rate
medium consists of the following: upto –80°C and subsequently stored at –160°C indefi-
• Engle’s minimum essential medium nitely.
• Earle’s salts without L-glutamine The constant availability of excellent quality donor
• L-glutamine tissue is an advantage in dealing with emergency
• Decomplemented calf serum situations like corneal trauma and perforation.
• 1.5 percent chondroitin sulfate (Mol wt 50,000). Besides, there is enough time available for performing
The corneas are maintained in the Petri dishes with bacteriological studies on donor tissue and also the
endothelial side up for 2 to 3 days for one or two HLA compatibility studies.
medium changes and stored at 34°C in 5 percent Despite its advantages, cryopreservation has not
carbon dioxide in water jacketed incubators. The been a popular method for corneal preservation
corneas are then suspended in 130 ml of the medium because it needs expensive equipment and highly
by a special needle hook inserted through the scleral trained technical persons. A slight error in the
rim and then stored at 34°C. The bottle containing the procedure can lead to tissue damage rendering it
cornea, as well as the plates and the media are unsuitable for use.
The mechanisms of damage to tissue during too loose nor too tight and they must be equidistant,
freezing include increased solute concentration, otherwise it will lead to irregularity in recipient rim
intracellular micro-ice crystal formation, changes in and will result in astigmatism.
pH and osmolarity, etc. Cryoprotective agent like
DMSO, glycerol, and polyvinylpyrolidone are used Trephining of Recipient Button
to minimize the damage to the tissue by modulating
The globe at this point is well stabilized by fixation
these factors. DMSO acts as a membrane stabilizer.
sutures and with small toothed forceps fixed with mild
Removal of water from the tissue by passing it through
pressure to the sclera near the limbus. The cornea is
solutions containing DMSO and sucrose prior to
blotted dry and if epithelium is loose and edematous
freezing reduces the free water available for crystal
it is removed with a cellulose sponge, since it interferes
formation. There have been many modifications of the
in proper visualization of the trephine mark. A corneal
Capella-Kaufman preservation technique.
trephine of appropriate size is selected so as to
At present because of its complexity and the
encompass whole or most of the diseased portion and
endothelial damage it produces, cryopreservation is
yet not large enough to reach the limbus. In most cases
not a favored method for corneal preservation.
a trephine of 7.5 to 8.5 mm size is required. The tre-
phine is placed vertically over the cornea and the
SURGICAL TECHNIQUES
surgeon looks through and around the trephine to
Anesthesia ensure its proper centering. Proper centering of
trephine on the recipient cornea is a very critical step
Local anesthesia is preferred because of its greater
in the procedure. The trephine is then given rotating
convenience and rapid postoperative mobilization
movements, ensuring to apply equal pressure over the
that it allows. Adequate anesthesia and akinesia of
cornea throughout the movement and a cut of approxi-
both eyelids and the globe are extremely essential.
mately 80 percent depth of the cornea is made.
A peribulbar block is preferred over a retrobulbar
Several manual and automated trephines are
one. The eye is rendered hypotonic by digital massage,
available for this purpose. The following criteria are
by using a Honnan’s balloon or Pinki pressure balls.
desirable in corneal trephine.
i. Should be available in various sizes.
Field Preparation and Draping
ii. Should be comfortable to use and stable during
The operative field is prepared and draped in a cutting.
manner that it provides a sterile field that is well iii. Surgeon should have a clear view of the whole
protected from surrounding nonsterile areas. The cornea within and around the trephine while
anterior segment is protected from possible cutting.
contamination from eyelashes and surrounding iv. The trephine should be able to be rotated in a
structure by a plastic drape that isolates both eyelashes direction perpendicular to the axis of the trephine.
and meibomian gland orifices. The conjunctival sac is The problems with the ordinary circular trephine
then rinsed with BSS and then swabbed with a sterile are the following:
cotton-tipped applicator. i. The corneal button gets ballooned inside the tre-
phine mouth leading to cutting of a graft larger
Eye Exposure, Fixation, than trephine size,
and Scleral Support ii. Due to variability in elasticity of the corneal tissue,
an oval or irregular cut may be produced particu-
A wire speculum (e.g. Barraquer’s) is used.
larly in firm to hard eyes,
If the eye is not in a vertical position, a superior
iii. In very soft eyes owing to collapse of cornea extre-
and/or inferior rectus suture can be passed and fixed
mely beveled and irregular cut is produced, and
to head towel for rotating and stabilizing the globe.
iv. Trephine tilting can result in oval button.
A Flieringa scleral ring can be used if the sclera is
expected to collapse on removing the corneal button,
Motorized Trephines
particularly in cases of aphakes and children. Scleral
ring can be sutured to the sclera with four 6-0 silk or These trephines have a common electric motor in the
Merselene sutures taking shallow scleral bites 3 to main body and a circular trephine at the motor shaft
4 mm behind the limbus. Sutures should neither be end. The ‘Microkeratrome’ unit not only allows for
variation of rotation velocity but also has rapid Management of Vitreous

braking within a tenth of a second. It also causes less
An intact vitreous face should always be preserved. If
stromal disruption and a smoother interface.33
vitreous is present in front of iris then it can be
removed with cellulose sponges and Vannas scissors.
Suction-Fixation Trephines
Alternatively, vitreous can be aspirated with a wide
Hessburg-Baron trephine34 is a suction-fixation type bore cannula. Any strand of vitreous in front of iris
of trephine. This trephine consists of an outer corneal should be removed and the host-graft junction should
suction ring for fixation and an inner circular cutting be totally free of vitreous. When available, application
blade which is exceedingly sharp. This trephine allows of mechanized vitrectomy technique is preferred.
for penetration of the stroma to a measured depth.
Each full revolution of the trephine advances the blade IOL Insertion
by 250 micron.
IOL can be inserted in an aphakic eye if the eye has a
potential for good vision. IOL may also be inserted as
Chamber Entry and Corneal Button Removal
a part of triple procedures. In cases where posterior
Anterior chamber may be entered using the trephine capsule is intact, the implant is held with a McPherson’s
while cutting the recipient bed. This leads to a very forceps and inferior haptic is inserted in the capsular
perpendicular cut and easy removal of host cornea. bag. The superior haptic is then inserted holding it
Chances of iris and lens injury are high with this and with a forceps or can be dialed into the capsular bag.
therefore most of the surgeons prefer to make a In cases where posterior capsule break is present,
controlled entry into anterior chamber with a knife. posterior chamber IOL can still be tried, if there is only
The chamber is entered with a sharp blade (B.P.No.11) a small break and peripheral capsule is present. In case
inserted vertically avoiding the iris. The cut is where there is no posterior capsular support, the lens
extended to 3 to 4 mm to allow the insertion of the can be sutured to the iris or to the sclera.
corneal scissors. Then the corneal button is removed
with curved corneal scissors. The tip of the lower blade Trephination of Donor Material
is inserted and directed slightly upward to avoid iris
The eyeball (in case of Moist chamber technique of
touch. While cutting care is taken to keep the blades
storage) is immersed in preservative free freshly
of the scissors perpendicular, the outer blade should
prepared gentamicin eye drops 0.3 percent (15-20 ml)
cut in the groove made by trephine.35 Sometimes
in a bowl for 20 minutes prior to surgery. Then the
posterior tags of stroma or Descemet’s are left behind
eyeball is placed over a piece of gauze and a
leading to an uneven posterior lip which leads to
transscleral perforation is made with a knife 2 to 3 mm
tilting of the graft with resultant astigmatism.
behind the limbus. The incision is circumferentially
Therefore, all the posterior tags should be removed
completed with a curved scissors. The anterior scleral
perpendicularly with a Vannas scissors.
lip is next caught with a toothed forceps and elevated
at one end, and the ciliary body is gently teased free
Management of the Lens
from the scleral spur and the entire iris lens diaphragm
If a cataract is present it should be removed using is thus freed from the back of cornea. Care should be
extracapsular cataract extraction technique. It is taken to avoid the collapse of anterior chamber. The
advisable to remove even an early cataract at the time entire corneoscleral button is then transferred to a
of keratoplasty, since after the surgery this cataract is teflon block with endothelial surface up. The button
bound to progress more rapidly and later on removal is well-centered over the block and kept under a punch
of cataract can lead to significant damage to the graft containing a trephine. Firm steady pressure is applied
endothelium. Anterior capsulotomy can be done with to the punch allowing it to pass through the donor
a blade and nucleus is expressed out by applying tissue into the teflon block. If a clean through and
pressure over sclera. The cortical matter is aspirated through cut is made, the corneal button should remain
using a two-way cannula of an automated system. on the teflon block when the trephine is removed. A
Cortical matter aspiration is always tedious as it is drop of BSS is placed gently over the endothelial
done in an open chamber and hence suction is not very surface and a moistened tumbler or bowl is placed
effective. inverted over the button to prevent it from drying.
Very few surgeons cut the donor button from suture with removal of initial 4 sutures. 10-0 nylon is
epithelial side these days. The method, however, is used while in case of double running sutures one 10-
commonly used in our country. Brightbill and Polack 0 and for the other 11-0 nylon is used.
showed that punching the donor material from endo- The orientation for each suture has to be radial as
thelial side against a firm surface leads to less if originating from an imaginary point in the center of
endothelial damage and give a cleaner cut. pupil. The needle is made to pass through the
It is widely accepted that the donor button should Descemet’s and once the needle emerges through the
be slightly larger than the recipient corneal hole. Descemet’s and once the needle emerges through the
Troutman demonstrated that a larger trephine is margin of the graft, the recipient bed is caught with a
necessary to prepare tissue from the posterior surface forceps and needle is passed through it at the same
than is needed to prepare the recipient bed.36 The level. In general, each bite is approximately 1.0 mm
donor button can be of the same size in very high long in the donor and 1.5 mm long on the recipient
myopes, 0.2 mm larger in phakic eyes and 0.5 mm side.
larger in aphakic eyes, pseudophakic eyes, triple As stated above, suture pattern can be interrupted
procedures, and in lens exchanges. (Fig. 33.5) or continues (Fig. 33.6). Interrupted sutures
Many types of punches and cutting blocks are are preferred in case of children, in vascularized
available for cutting the donor button but some corneas, corneas of uneven thickness, corneas with
surgeons prefer to use a hand held disposable trephine localized areas of inflammation or corneas in which
for this purpose.37 The present day cutting blocks the bites on the recipient side end too close to or in
attempt to approximate the corneal shape and reduce the sclera.38 Main drawback of interrupted suture is
tissue distortion. The Brightbill teflon cutting block
utilizes three walls, each with a different radius of
curvature and diameter along with an 8 mm red
centering dot. The Taune cutting block has a single
well with multiple radii of curvature and a central air
escape hole.
Graft Placement and Chamber Maintenance

Next step is to place the donor cornea onto the
recipient bed. A viscoelastic material is placed over
the iris and anterior lens capsule to keep the iris and
lens back and avoid their coming in contact with
endothelium. The donor button is transferred to
recipient bed with a corneal spatula or with a fine-
toothed forceps. The viscoelastic material placed in Fig. 33.5: Clear graft showing 16 interrupted suture
anterior chamber need not to be removed after
suturing.
Suturing the Corneal Button

Suturing is the most crucial step in keratoplasty. The
first four sutures known as the cardinal sutures are
most crucial in orienting the graft evenly in the bed.
The first suture is placed at 12 o’clock position
followed by a suture at 6 o’clock. In placing the 6
o’clock suture it is important to ascertain that there is
equal distribution of tissue to both sides of the suture.
Two sutures are then placed at 3 and 9 o’clock
positions, respectively. Subsequent suturing consists
of placement of 12 or more interrupted sutures, 4 or 8
interrupted and a running suture, or a double running Fig. 33.6: Clear graft showing a single continuous suture
that they stimulate more inflammation and

vascularization. Advantages of interrupted sutures lie
in technically less difficulty in their application and
removal, rapid wound healing and inability to adjust
individual suture bites. The advantage of burning the
knot is that it incites lesser inflammation but are
difficult to remove while reverse is the case with
exposed knots.38
Continuous sutures are used when there is no
vascularization, the thickness of the graft and peri-
pheral rim is even and there are no inflammatory
signs. Continuous sutures have the advantage of
inciting lesser inflammation, uniform wound healing,
and greater ease of intraoperative suture loop tension
adjustment. But the disadvantage is that they cannot
be selectively removed and if one suture breaks or is Fig. 33.7: Slit lamp photograph of a case of primary graft
left loose, the entire suture may be affected. failure showing marked stromal edema and folds
Final Evaluation changes or thickening of Descemet’s membrane have

Once suturing a complete, the suture ends are also been shown to be a cause of primary graft
trimmed and the knots may be buried in the anterior failure.39
stroma. Anterior chamber is deepened with BSS and Faulty technique of corneoscleral button excision Improper
wound margins are checked for any wound leak by technique in removing the corneoscleral button can
applying gentle pressure over the graft. At the end of damage the endothelial cells. The factors which can
procedure, a subconjunctival injection of gentamicin cause endothelial damage during this procedure are
20 mg and dexamethasone 2 mg is given and a patch the following:
and shield is applied. i. Excessive folds and stretching or cornea
ii. Shallowing of anterior chamber leading to irido-
COMPLICATIONS corneal touch
The complications after penetrating keratoplasty can iii. Instrumental touch to the endothelium.
be divided into early, intermediate, and late. Improper corneal preservation Prolonged preservation
of the donor tissue may lead to endothelial cell loss
Complications Early
and an increased incidence of primary graft failure.
Primary Graft Failure Moist chamber stored corneas should be used within
Primary graft failure (Fig. 33.7) is defined as an irrever- 48 hours. Corneas stored in MK medium can be used
sible graft edema occurring in the immediate postope- upto 4 days, those stored in K-Sol and Dexol media
rative period. The incidence of primary graft failure can be used upto 10 days while those stored in Optisol
varies from 0 to 5 percent. Irrespective of the cause, medium are viable till 2 weeks. Successful corneal
all cases of primary graft failure show donor corneal grafting with corneas preserved in organ culture
damage with markedly decreased endothelial cell medium upto 35 days and with cryopreservation upto
count. The factors responsible for the primary graft 1 year have been reported.
failure are: Surgical trauma Surgical trauma and resulting exces-
Selection of donor tissue Donor corneas with endothelial sive intraocular inflammation may result in primary
cell counts less than 1500/mm2 should be rejected. donor failure. Care should be taken to avoid any
Donor corneas showing excessive polymegathism and contact between the endothelium and instruments.
pleomorphism of endothelial cells are likely to Chamber should be kept formed during suturing and
undergo primary graft failure and indicate compro- viscoelastic agents must be used to protect endothe-
mised endothelial function and hence should be lium from contact with other intraocular structures
rejected. Donor corneas showing evidence of guttate and intraocular lens implant, when present.
Glaucoma
Postkeratoplasty glaucoma is defined as an acute
elevation of intraocular pressure after penetrating
keratoplasty with or without optic nerve and visual
field changes.40
Although the elevated pressure usually resolves
spontaneously by the end of first postoperative week,
sometime it can become a chronic problem. It is an
important cause of graft failure following penetrating
keratoplasty:40
Mechanism Causes of high IOP following keratoplasty
include the following:
Fig. 33.8: Photograph showing a postkeratoplasty epithelial
i. Pre-existing glaucoma
defect (stained with fluorescein)
ii. Postoperative inflammation
iii. Distortion of trabecular meshwork stores within the epithelium. Survival of epithelium
iv. Angle closure during storage is dependent upon maintenance of
v. Retention of viscoelastic material metabolic requirements of the epithelium. Therefore,
vi. Malignant glaucoma epithelial cell survival is directly related to the method
vii. Steroid induced glaucoma. of donor storage. Storage in moist chamber at 4°C
The incidence of glaucoma after keratoplasty stabilizes cellular glycogen levels for 48 hours. In MK
ranges from 13 to 38 percent in phakic eyes and 42 to medium41 intact epithelium can be maintained for 79
89 percent in aphakic eyes. hours at 4°C.41 However, 35 percent of corneas stored
Collapse of trabecular meshwork is the main cause in this manner will have 5 to 100 percent area of
of aqueous outflow obstruction. Through and through epithelial defect before keratoplasty. Epithelium of
sutures might alleviate the loss of posterior support corneas stored in organ culture medium maintains a
to the trabecular meshwork. The use of oversized normal ultrastructure for at least 35 days.
grafts in aphakic or pseudophakic eyes is thought to
Intraoperative causes Various causes in this group are
decrease the incidence of glaucoma by reducing angle
purposeful removal of epithelium by surgeon, cutting
distortion and collapse of the trabecular meshwork.
of donor button on a Teflon block from endothelial
side and intraoperative trauma from manipulation of
Epithelial Defects
the corneal button during suturing. The drying effect
The integrity of the corneal epithelium is vital for graft of the microscope light can also lead to desiccation of
survival. Presence of an epithelial defect (Fig 33.8) epithelium.
increases the risk of rejection, infection, stromal
Postoperative causes Following are the causes of
opacification, ulceration, vascularization, poor stromal
postoperative epithelial defect:
healing, thinning and even perforation apart from
a. Due to movement of the lids the epithelium is
interfering with vision. Ultimately these complications
loosened.
may lead to graft failure. Epithelial defects have been
b. Local abnormalities such as trichiasis, entropion,
shown to occur on the first postoperative day in
blepharitis or loose or exposed knots.
approximately 70 percent of donor cornea stored in
c. Topical medication and preservatives.
MK medium41 and in approximately 80 percent of
d. Tear film abnormalities, lagophthalmos and poor
corneas stored in organ culture medium.42
lid movement.
These causes of epithelial defects can be divided
e. Local primary ocular surface disorders caused by
into three categories:
pemphigoid, Steven-Johnson syndrome or chemi-
i. Those occurring during storage of cornea
cal burns.
ii. Intraoperative
In the postoperative period, denervation of donor
iii. Postoperative.
cornea itself may retard epithelial healing as corneal
Cell loss during storage The energy source for corneal nerves are required for corneal mitotic activity and
epithelial cell maintenance is provided by glycogen healing.44
Intermediate Complications
Graft Rejection
Immunologic graft rejection (Figs 33.9 and 33.10) is
the most common cause of late graft failure. Almost
18 percent of the grafts show immunologic reaction/
rejection and 12 percent of the grafts fail because of
rejection. The first description of corneal allograft rejec-
tion was published in 1948. By transplanting indi-
vidual corneal layers in rabbits, Khodadoust and
Silverstein demonstrated that epithelium, stroma and
endothelium could separately undergo immunologic
rejection.
Following are the four types of corneal graft
rejection:
Epithelial rejection It is characterized by the appearance
of an elevated rejection line that stains with fluorescein Fig. 33.9: Photograph of a case of immunologic graft
rejection showing the presence of endothelial rejection line
or rose bengal.
Subepithelial infiltrates Subepithelial white infiltrates
0.2 to 0.5 mm in diameter, randomly distributed imme-
diately below the Bowman’s membrane in the donor
tissue is a sign of allograft rejection. Average time of
onset is 10 months after keratoplasty and frequency
is 15 percent.
Stromal rejection These consist of a sudden onset of
peripheral full thickness haze in a previously clear
graft associated with a circumcorneal injection. It
commonly occurs in association with endothelial
rejection.
Endothelial rejection It presents in one of the two ways, Fig. 33.10: Another case of graft rejection showing
viz either in the form of diffuse keratic precipitates endothelial rejection line
scattered across the donor endothelium or in the form
of a Khodadoust line which originates at a vasculari- Graft Infection
zed area of the peripheral donor cornea or at a point
of junction of an anterior synechia with the endo- Infection is a common cause of graft failure. Patients
thelium. Rejection line consists of lymphoid cells with corneal transplants are specially prone to
associated with a moderate anterior chamber reaction. infection because of the frequent use of corticosteroids
Potential risk factors for corneal allograft rejection and contact lenses. The incidence of graft infection in
include the following: our cases has been about 5 percent.
• Vascularization Bacterial and fungal infection Bacterial and fungal
• Previous graft failure keratitis (Fig. 33.11) following penetrating kerato-
• Bilateral grafts plasty can be often lead to graft failure.45,46
• Intact donor epithelium There are three common sources for bacterial and
• Eccentric graft fungal infections following penetrating keratoplasty:
• Large graft i. Contamination of donor tissue with micro-
• Recipient’s age less than 50 years organisms.
• Non HLA matched grafts. ii. Incomplete excision of recipient infected tissue.
Fig. 33.12: Picture showing development of dendritic ulcer in

Fig. 33.11: Picture showing graft infiltrate the graft due to herpes simplex
iii. Infection from organisms acquired from ambient dehiscence. The rupture almost always occurs at the
air. host-graft junction.
The ambient air is the most common source of
bacterial and fungal infections after keratoplasty. Late Complications
Factors associated with development of late bacterial
Recurrence of Disease
and fungal infections include topical corticosteroid
usage, loose or broken sutures, persistent epithelial Dystrophies A well known but uncommon complica-
defects, dry eye, and suture removal. tion of keratoplasty is the recurrence of corneal disease
Herpes simplex Epithelial herpes simplex virus within the donor tissue. Recurrence of the host disease
in the grafts are most evident in cases of dystrophies
activation may occur following keratoplasty for
(Fig. 33.13). Recurrences have been noted for Reis
corneal disorders other than herpes (Fig. 33.12).
Buckler’s dystrophy,43 Granular dystrophy,44 Lattice
Secondly, there may be a recurrence of herpes in
dystrophy,45 and Macular dystrophy.46
patients who had undergone keratoplasty for herpetic
keratitis. Graft survival is better if patients with Herpes simplex keratitis In cases undergoing kerato-
herpetic keratitis undergo keratoplasty when the plasty for herpes simplex, recurrence of herpetic
disease inactive. disease in grafted cornea has been shown to occur in
Acanthameba keratitis Primary Acanthameba infection 12 percent of cases followed up to 3 years and in 47
of a corneal graft is not common. It must be considered percent of the cases followed up to 5 years. 48
in cases where a graft infection is unresponsive to Fortunately, half of these corneas maintained clear
grafts with treatment of recurrent herpetic disease.
conventional antimicrobial treatment.
Acanthameba keratitis frequently encountered as a
recurrence following penetrating keratoplasty. Results
in recurrent cases have been poor. Many cases
progress despite aggressive medical treatment and
surgical intervention during an active stage.
Wound Dehiscence
Would dehiscence is a common and sometimes
preventable risk factor for graft failure. Incidence of
wound gape, separation and override may be high.
Trauma remains an important cause of wound
dehiscence after keratoplasty. The corneal wound
never appears to attain a strength of unoperated Fig. 33.13: Picture showing recurrence of granular stromal
cornea42 and seemingly trivial blows may result in a dystrophy in the graft
Late Graft Failure of Unknown Etiology developed into a highly sophisticated and successful
technique. However, a lot of shortcomings remain. An
Occasionally, a graft that has remained clear for many
ideal corneal storage medium which would store the
years opacified without any obvious cause. In many
donor tissue over a long period without compromising
cases, late decompensation may be secondary to a
its quality is yet to be developed. Postoperative
decrease in the endothelial cell density below that is
complications particularly immunologic rejection and
necessary to maintain corneal dehydration.49
astigmatism continue to nullify to a great extent the
extensive work by the corneal surgeons in this line.
Postkeratoplasty Astigmatism
Shortage of good quality donor tissues as well as quali-
Postoperative astigmatism results primarily from fied corneal surgeons is another problem in the
deformation of the cornea by surgery. High developing world.
postoperative astigmatism has primarily been a Nevertheless, the future seems to hold a lot of
problem following penetrating keratoplasty with 10 promise for the millions of people affected by corneal
percent of grafts resulting in at least 5-6 D of blindness allover the world. Research going on in the
astigmatism. field of corneal physiology, corneal preservative
Various factors that determine the postoperative media, growth factors for corneal wound healing,
astigmatism are: immunomodulator drugs, newer suture materials,
Recipient pathology Higher astigmatism has been seen viscoelastic substances coupled with availability of
in case of aphakic patients.50 The higher astigmatism better instrumentation and better trained corneal
in these cases has been attributed to an unstable surgeons is bound to improve the outlook of corneal
corneolimbal ring. In one study, a comparison was transplantation in the coming years. The twenty-first
made on astigmatism following keratoplasty in cases century, indeed, is going to be a very exciting period
of pseudophakic bullous keratopathy and cases for the corneal surgeon.
undergoing a triple procedure. It was found that
significantly greater astigmatism was present in the ACKNOWLEDGEMENTS
former group.51 The authors wish to convey their sincere thanks to Dr
Donor-Recipient disparity Most of the studies have Sharadini Vyas, Dr Swadesh Acharjee and Dr Brijesh
found no significant difference in the final astigmatic Pawar for the invaluable help that they provided in
error when an oversized donor button was used.52 But the preparation of this article.
one study, 53 did find a significant increase in
astigmatism when 0.5 mm oversized donor buttons REFERENCES
were used.
1. Smith EE, McDonald HR, Nesburn AB, Minckler DS.
Graft diameter Most surgeons use a graft size of 7.0- Penetrating keratoplasty, changing indications—1947 to 1978.
8.5 mm although smaller or larger diameter grafts are Arch Ophthalmol 1980;98:1226.
2. Lindquist TD, McGlothan JS, Rotkis WM, Chandler JW.
occasionally used. There has been no difference in Indications for penetrating keratoplasty—1980-1988. Cornea
astigmatism in patients receiving grafts of small or 1991;10:210.
large diameters. 3. Buxton JN, Norden RA. Indications and contraindications of
PK In: Corneal Surgery: Theory, Technique and Tissue.
Suturing technique Different techniques of suturing Brightbill FS (Ed). CV Mosby Co, 1986;130.
like interrupted sutures, interrupted combined with 4. Robin JB, Gindi JJ, Koh K et al. An update of the indications
for penetrating keratoplasty. Arch Opthalmol 1986;104:87.
a single running suture, or a double running suture 5. Hymazn L, Susel R, Lance B. The keratoplasty evaluation
have got no relation to postkeratoplasty astigmatism. project. Presented at May 1985 meeting or ARVO, Sarasota.
Although the suture induced astigmatism may be 6. Kramer SG. Cystoid macular edema after aphakic penetrating
reduced significantly during the postoperative course keratoplasty. Ophthalmol 1981;88:782.
7. Charlton KH, Binder PS, Parl T. Visual prognosis in
by selective suture removal, the final astigmatism after pseudophakic corneal transplants. Ophthalmic Surg
all sutures are out may not be altered significantly. 1981;12:411.
8. Samples JR, Binder RS. Visual acuity, refractive error and
EPILOGUE astigmatism following corneal transplantation for
pseudophakic bullous keratopathy. Ophthalmol 1985;92:1554.
Corneal transplantation, which in the beginning was 9. Meyer RF and Sugar A. Penetrating keratoplasty in pseudo-
considered to be more than an absurd idea, has now phakic bullous keratopathy. Am J Ophthalmol 1980;90:677.
10. Cohen EJ, Laibson PR, Arensten JJ. Corneal transplantation 32. Bourne WM, Doughman DJ, Lindstorm RL. Decreased
for herpes simplex keratitis. Am J Ophthalmol 1983;95:645. endothelial cell survival after transplantation of corneal
11. Brady SE, Rapuano CJ, Arensten JJ. Clinical indications and preserved by three modifications of corneal organ culture
procedures associated with penetrating keratoplasty—1983- technique. Ophthalmology 1985;92:1538.
1988. Am J Ophthalmol 1983;108:118. 33. Schanzlin DJ, Robin JB and Spence DJ. Clinical and ultra-
12. AI Faran MF, Tabbara KF. Corneal dystrophies among structural analysis of variable speed corneal trephination.
patients undergoing keratoplasty in Saudi Arabia. Cornea Ophthalmol Surg 1983;14:755.
1991;10:13. 34. Hessburg PC and Barron M. A disposable corneal trephine.
13. Doren GS, Cohen EJ, Brady SE. Penetrating keratoplasty after Ophthalmol Surg 1980;11:730.
ocular trauma. Am J Ophthalmol 1990;110:408. 35. Brightbill FS, Palac, FM and Slappey T. A comparison of two
14. Stulting RD, Sumers KD, Cavanagh HD. Penetrating methods for cutting donor corneal button. Am J Ophthalmol
keratoplasty in children. Ophthalmol 1984;91:1222. 1973;75:500.
15. Rao GN, Shaw EL, Arthur EJ, Aquavella JV. Endothelial cell 36. Troutman RC. Astigmatic consideration in corneal graft.
morphology and corneal deturgescence. Ann Ophthalmol Ophthalmol Surg 1979;10:21.
1979;11:885. 37. Sugar J. Phakic keratoplasty surgery: Theroy technique and
16. Yee RW, Geroski DH, Matsuda M, Correction of corneal Tissue. CV Mosby Co, 1986;194-200.
endothelial pump site density area, function, morphology in 38. McCulley JP, Eliason JA. Rationale for selection of suturing
wound repair. Invest Ophthalmol Vis Sci 1985;26:1191. technique in penetrating keratoplasty. In Leibowitz HM (Ed):
17. McCarey BE, Kaufman HE. Improved corneal storage. Invest Corneal Disorders. Saunders, 1984;547.
Ophthalmol 1974;13:165. 39. Buxton JN, Seedor JA, Perry HD. Donor failure after corneal
18. Waltman SR, Palmberg PF. Human penetrating keratoplasty transplantation surgery. Cornea 1988;7:89.
using modified MK medium. Opthalmol Surg 1978;9:48. 40. Karesh JW, Nirankari VS. Factors associated with glaucoma
19. Sachs R, Goldman K, Valenti J, Kaufman HE. Corneal storage after penetrating keratoplasty. Am J Ophthalmol 1983;96:160.
at room temperature. Arch Ophthalmol 1978;96:1075. 41. Meyer RF and Bobb KC. Corneal epithelium in penetrating
20. Kaufman HE, Vernett ED, Kaufman S. Chondroitin sulfate keratoplasty. Am J Ophthalmol 1982;90:142.
in a new cornea preservation medium. Am J Ophthalmol 42. Miller RA, Richard IL, Lindstrom L et al. Healon use for the
1984;98:112. preservation of donor epithelial cell loss during keratoplasty.
21. Bourne WM. Endothelial cell survival on transplanted human Invest Ophthalmol 1984;25(Suppl):171,(ARVO ABSTRACTS).
cornea preserved at 4°C in 2.5 percent chondroitin sulfate in 43. Nork TM, Holley FJ, Hayes Wntlandt T et al. Timolol inhibits
one to 13 days. Am J Ophthalmol 1986;102:382. corneal epithelial wound healing in monkeys and rabbits.
22. Bourne WM. Endothelial cell survival on transplanted human Arch Opthalmol 1984;102:1224.
cornea preserved at 4°C in 25 percent chondroitin sulfate in 44. Beuerman RW, Klyce SD, Vigo MC et al. Modulations of
one to 13 days. Am J Ophthalmol 1986;102:382. latency and velocity in corneal epithelial wound healing.
23. Busin M, Yau C, Avni I, Kaufman HE. Comparison of K-Sol Invest Ophthalmol 1985;26(Suppl):91, (ARVO ABSTRACTS).
and MK medium for cornea storage: Results of penetrating 45. Fong LP, Ormerod LD, Kenyon KR, Foster CS. Microbial
keratoplasty in rabbits. Br J Ophthalmol 1986;70:860. keratitis complicating penetrating keratoplasty. Ophthalmol
24. Stein RM, Bourne WN, Campbell RJ. Chondroitin sulfate for 1988;95:1269.
corneal preservation at 4°C. Arch Ophthalmol 1986;104:1358. 46. AL-Hazza SA and Tabbara KF. Bacterial keratitis after
25. Stein RM, Liabson PR. Comparison of chondroitin sulfate to penetrating keratoplasty. Ophthalmol 1988;95:1504.
MK medium for corneal storage. Am J Ophthalmol 47. Topping TM, Stark WJ, Maumenee E, Kenyon KR. Traumatic
1987;104:490. wound dehiscence following penetrating keratoplasty. Br J
26. Lindstorm RL, Doughman DJ, Skelink DL, Mindrup EA. Ophthalmol 1988;66:174.
Minnesota system corneal preservation. Br J Ophthalmol 48. Fine M, Cignetti FE. Penetrating keratoplasty in herpes
1986;70:47. simplex keratitis. Arch Ophthalmol 1977;95:613.
27. Skelnik DL, Pearlstein CS, Mindrup EA. Corneal preservation 49. Wilson SE, Kaufman HE. Graft failure after penetrating
at 4°C with chondroitin sulfate containing medium supple- keratoplasty. Survey Ophthalmol 1990;34:325.
mented with dextran and epidermal growth factors. Invest 50. Pearlman EM. An analysis and interpretation of refractive
Ophthalmol 1988;29(Suppl.):111. errors after penetrating keratoplasty. Ophthalmology
28. Walkenbach RJ. Corneal function after storage in commercial 1981;88:39.
eye bank media. Invest Ophthalmol 1991;32:551. 51. Samples JR, Binder PS. Visual acuity, refractive error and
29. Kaufman HE, Beuerman RW, Steineman TL et al. Optisol astigmatism following corneal tranplantation for
corneal storage medium. Arch Ophthalmol 1991;109:864. pseudophakic bullous keratopathy. Ophthalmology
30. Doughman DJ, Lindstorm RL and Singh G. Long-term organ 1985;92:1554.
culture for corneal storage: Minnesota system. In Brightbill 52. Bourne WM, Davison JA, O’Fallon WM. The effects of over
FS (Ed): Corneal Surgery: Theory, Technique and Tissue. CV size donor buttons on postoperative intraocular pressure and
Mosby Co, 1986;84-93. corneal curvature in aphakic penetrating keratoplasty.
31. Pels E and Schuchard Y. Organ culture and endothelial Ophthalmology 1982;89:242.
evaluation as a preservation medium for human corneas. In 53. Perl T, Charlton KM, Binder PS. Disparate diameter grafting
Brightbill (Ed): Corneal Surgery: Theory, Technique and astigmatism intraocular diameter grafting astigmatism
Tissue, Mosby CS, 1986;93-102. intraocular pressure, visual acuity. Ophthalmol 1981;88:774.
Chapter 34
Current Status of Lamellar

Keratoplasty
Anita Panda
HISTORICAL BACKGROUND iii. A large graft can be performed,

iv. Minimal incidence of rejection,
Cornea was the first solid tissue to be transplanted
v. Does not require viable corneal endothelium, thus
and having less rejection rate than other transplanted
preserved cornea can be used,
tissues. Though history dates back as early as 1824
vi. Requires less period of hospitalization and less
when Franz Reisinger introduced the concept of
follow up visits. If the procedure fails it does not
corneal transplantation; experimentally, the procedure
had not become popular as all his grafts were preclude a lamellar or penetrating keratoplasty
opacified. at a later date.1,2
LAMELLAR KERATOPLASTY (LK) Problems of LK

This is a procedure where a partial thickness of the Besides perforation and irregular bed preparation the
pathological host cornea is removed and replaced with problems during lamellar keratoplasty are mal-
donor tissue of similar size and thickness. The central apposition and remnants debris of foreign bodies at
inlay lamellar keratoplasty is optical whereas the interface. There may be delayed healing since the
peripheral is mainly done for the stem cell re- healing occurs at two areas one at graft-host junction
population, as these cells are situated at the limbus and the other at the interface, persistent epithelial
and 1 mm within the peripheral cornea. The onlay defect, graft vascularization, recurrence of the disease
lamellar graft provides a tectonic support and it also and occasionally rejection.1,3
negates the irregular astigmatism by flattening the
cornea as seen in cases of keratoconus. Keyhole pattern Terminology
has a composite action. It provides stem cells to the
diseased cornea and also provides optical function as The terminology of lamellar keratoplasty has been
seen in cases of recurrent pterygium. Though lamellar designated as:
keratoplasty is not a solution for all corneal disorders, i. Inlay lamellar keratoplasty, where a partial
a wide variety of the cases can be benefited by this thickness of the recipient cornea is removed by
procedure.1,2 lamellar dissection and replaced by a partial
thickness donor cornea,
Advantages of LK ii. Onlay lamellar keratoplasty, where a partial
The advantages of LK over conventional PK are the thickness donor cornea is placed over a de-epithe-
following: lialized recipient cornea in which either a small
i. An extraocular procedure, peripheral keratectomy and/or lamellar dis-
ii. Devoid of any intraocular complications, section has been done.2
Chapter 34: Current Status of Lamellar Keratoplasty 269
Indications In case of sclerocorneal graft, care should be taken
that both recipient and donor tissue should match
The time old classification of indications are:
anatomically.
i. Tectonic grafts
ii. Optical grafts
Methods of Lamellar Dissection4-6
iii. Therapeutic grafts, and
iv. Cosmetic grafts. It can be performed by lamellar dissector, or
These grafts include all types of inlay lamellar and microkeratome. To avoid perforation and to obtain a
onlay grafting including stem cell transplantation as smooth plane, which is the most desirable aspect of
per the newer classification.1,2 lamellar keratoplasty, intrastromal injection of air,
viscoelastic and saline (hydrodelamination) prior to
Tectonic Grafts dissection followed by lamellar separation with
lamellar dissector are beneficial.
These grafts are performed to strengthen the thinned-
Other sources from where only the limbal tissues
cornea as in cases of corneal opacity of any etiology
are obtained for stem cells transplant, include:
with irregular thinning, large descemetocele, peri-
i. Cadaver eye (in situ removal of the lenticule
pheral marginal degeneration and keratoconus.
without removing eyeball),
ii. Blood-related donor, and
Optical Grafts
iii. Normal fellow eye.
It is performed to rehabilitate a patient visually. This
is indicated in the superficial, noninflammatory and INDICATIONS OF LK1,2,7-12
stable corneal opacities, epithelial dystrophies, corneal
The present day indications of LK in order of
degeneration affecting the anterior half-thickness of
frequency are (Table 34.1):
the cornea.
1. Degenerative
2. Post-inflammatory
Therapeutic Grafts
3. Congenital
This is indicated in eyes where a deep lamellar 4. Post-traumatic
keratectomy is performed to remove total corneal 5. Dystrophies
pathology like pterygium, benign corneal tumors such 6. Neoplastic.
as dermoids and malignant corneal tumors such as
squamous cell carcinoma of cornea. It is also Revolution of Surgical Techniques
considered in cases of bullous keratopathy and 1. Conventional LK
epithelial corneal dystrophies. Further, it is performed — Inlay conventional
as a patch graft in eyes having perforation after corneal 2. Modified inlay
ulcer. a. Inlay segmental
b. Inlay keyhole
Sources of Donor Tissue for LK c. Inlay annular.
Sources from which the corneal tissue are obtained 3. Advanced LK
for LK include: a. Onlay advanced LK13-15
i. Eyeball preserved in moist chamber, b. Onlay limbal transplantation16-20
ii. Media preserved corneoscleral disk, and Table 34.1: Lamellar keratoplasty (1977-1997)
iii. Glycerine preserved corneoscleral tissue.1,2 (N=1222)
Precision on Graft Cutting Types No of Eyes Percentage

Degenerative 530 43.37
For conventional inlay and onlay the graft size of the
Post-inflammatory 220 10.00
donor disk should be the same for segmental, keyhole Congenital 183 14.97
and annular inlay lamellar keratoplasty. While the Post-traumatic 122 9.98
thickness of the graft should be uniform it should be Dystrophies 93 7.61
slightly thicker than the recipient bed. Neoplastic 74 6.05
c. Keratoepithelioplasty procedure is also adopted for donor button pre-

d. Double chamber technique paration and the corneal button is fixed to the recipient
e. Inlay sclerokeratoplasty as an adjunctive bed (Figs 34.2A and B). In cases having peripheral
procedure to PK. corneal lesion a tectonic graft can be done followed
by future central optical graft.
Surgical Steps
Conventional Inlay LK Inlay Keyhole Lamellar Keratoplasty
The indication of this procedure is for all types of This technique is indicated when there is peripheral
corneal lesions involving the central partial thickness corneal involvement including the visual axis.
of the cornea. By this a required size and depth Surgical steps consist of a mark on the central
recipient’s diseased cornea is removed and replaced cornea upto the superior and inferior border of the
by identical size and thickness of donor cornea lesion. The ends are extended to the limbus and the
(Figs 34.1A and B). For total superficial corneal 0.3 mm thick corneal tissue along with the mass is
destruction a large corneoscleral lamellar graft can be separated and fixed at the medial canthus. Identical
performed (Figs 34.1 C and D). size and thick donor tissue is obtained by similar
manner and fixed to the recipient bed (Fig. 34.3A to D).
Inlay Modified Segmental LK
This is indicated when the corneal lesion invades the Inlay Annular LK
partial thickness of the cornea but eccentric and not This is indicated when the corneal lesion is peripheral
involving the visual axis. and involves the entire 360 degree. The whole
Procedures The surgical steps are similar to inlay LK procedure is similar to conventional inlay LK except
except that the preliminary mark is either with two that two required sized trephines are used peri-
different sized trephines or free mad hand method pherally in an annular fashion both for recipient and
depending upon the size of involvement. Similar donor (Figs 34.4 A and B).
Figs 34.1A to D: Conventional—inlay LK. (1) Host cornea, (2) Trephine mark,
(3) Host stroma, and (4) Donor lenticule
Figs 34.2A and B: Modified inlay—segment. (1) Corneal lesion, (2) Segmental LK
Figs 34.3A to D: Modified inlay—key hole. (A) Corneal lesion, (B) Partial thickness dissection,
(C) Recipient cornea, (D) Key hole LK
Figs 34.4A and B: Modified inlay—annular. (1)

Corneal lesion, (2) Annular LK
Onlay Lamellar Keratoplasty (Epikeratoplasty)13-15

This is indicated in cases of keratoconus having no
apical scarring and aids in flattening the cornea
thereby reducing irregular astigmatism.
The basis of the surgical steps includes removal of
a 0.5 mm annular peripheral rim of the corneal
epithelium and stroma along with central epithelium.
A 0.5 mm larger partial thickness donor corneal tissue
is fixed to the recipient bed (Figs 34.5A and B).
Onlay Limbal Transplantation

(Stem Cell Transplant)
This is indicated in a large number of cases with
corneal damage which includes post-chemical burns,
post-radiation, Stevens-Johnson syndrome, chronic
contact lens use, multiple limbal surgeries, benign and Figs 34.5A and B: Onlay LK—epikeratoplasty. (1) Host cornea,
malignant limbal tumors, ocular cicatricial pemphi- (2) 0.5 mm annular dissection, (3) De-epithelialized host cornea,
goid, extensive symblepharon of any etiology, and and (4) Epikeratoplasty done
aniridia. Though there are variations in conjunctival
management the limbal and corneal management are
similar in each of the above indications.
Procedure After recessing conjunctiva from the
limbus and sclera, the undermined tissue is scraped
with blunt dissector. The area is irrigated to remove
any tissue debris.
Two trephines, 9 mm and 11 mm in size, are used
to make 2 marks 0.1 mm deep on the cornea and
limbus, respectively. The encompassed tissue is
removed. Similar limbal lenticules are removed either
from the cadaver eye (in situ removal) or from freshly
enucleated eyeballs. The annular lenticules are
bisected into two halves. The length of each lenticule
depends upon the extent of the limbal involvement.
While removing the donor lenticules, if removed in
piecemeal, care is taken to retain both superior and
Figs 34.6A and B: Onlay limbal transplantation. (1) Diseased
inferior pallisade of Vogt of the donor in the prepared cornea, (2) Debrided host cornea, (3) Limbal transplant
lenticules, as these sites inhabit the maximum
population of the stem cells. Two circumferential Keratoepithelioplasty
sutures with 10-0 monofilament nylon at the extreme This technique is used in cases of persistent epithelial
ends of each lenticule are applied separately and the defect after keratoplasty following chemical injury to
knots are buried. One to three extra sutures are applied eliminate the superficial scarring and vascularization.
at the scleral end of each lenticule depending upon The only difference from onlay limbal transplantation
the length of the lenticule. No sutures are applied at is use of a thin corneal stromal lenticule rather than
the corneal side. The eyes are patched after instillation limbal lenticule and fixing to the recipient bed in a
of antibiotic drops. The procedure can be combined reverse pattern, so that the limbal portion of the
with conventional inlay LK for immediate visual gain lenticule faces toward the cornea and the corneal side
(Figs 34.6A and B). is toward the limbus (Fig. 34.7A).
Procedure The whole procedure is similar to limbal viscoelastic cushion with 16, 10-0 monofilament nylon
transplantation except that instead of limbal tissue the sutures. Three to four small peripheral holes are made
midperipheral donor corneal tissue is selected. Three at the Descemet’s membrane and endothelium with
to five such lenticules are obtained and properly the help of a 27 gauze bent needle (Figs 34.8A to D).
oriented. These lenticules are secured to the host bed
while keeping the limbal side of the lenticules towards Inlay Sclerokeratoplasty as an Adjuvant to PK
the cornea. Care is taken to pass two 10-0 nylon sutures
circumferentially, not radially. A bandage contact lens This technique is indicated in cases with total corneal
is applied to cover inner half to three fourth of involvement specially when the whole corneal
pathology extends from limbus to limbus (Figs 34.9A to
lenticules (Fig. 34.7B).
D).
This procedure is also combined with central
lamellar keratoplasty. To perform this, first, the central Procedure Following 360 degrees peritomy, two hori-
LK is carried out followed by the fixation of the zontal cuts are made at 3 and 9’O clock position of the
lenticules. Bandage soft contact lens, however, is conjunctiva. Stay sutures are applied at the conjunctiva
applied in every case. for better scleral exposure besides superior and
inferior rectii bridle sutures. The episcleral tissue
including any other extra tissue are removed and the
sclera is exposed 5 mm from the limbus. With the help
of a 14 mm trephine, 0.2 mm deep mark is made on
the sclera.
The partial thickness scleral dissection is carried
out upto 0.5 mm inside the peripheral cornea. The
scleral flange made in this way is held together and
with the help of a 9.5 mm trephine a half-thickness
corneal groove is made outside the encompassed
scleral flange. The anterior chamber entry is made with
a blade. Viscoelastic is injected into the anterior
chamber to prevent intraocular tissue damage and also
to help in separation of iris from the cornea. The
corneal section is completed with the help of corneal
scissors. Other associated surgical procedures such as
pupilloplasty, lens removal and vitrectomy are
undertaken wherever indicated.
Figs 34.7A and B: Keratoepitheoplasty with conventional inlay
LK. (1) Recipient’s diseased cornea, (2) Donor lenticules with Donor Tissue Preparation and Fixation
scleral side towards central cornea, (3) Central LK
Using 14 mm trephine blade an annular 0.2 mm deep
groove is made on an enucleated donor eyeball. Partial
Inlay Deep LK with Descemetoendotheliotomy thickness scleral flange is dissected upto the limbus.
(Double Chamber Technique) Using a 10 mm trephine blade an annular partial
thickness groove is made. The anterior chamber is
This procedure is indicated in cases of complicated
entered with a blade breaker. After injecting the
aphakic or pseudophakic painful bullous keratopathy
viscoelastic into the anterior chamber the corneal
where opening of the chamber is hazardous.
section is completed with a corneal scissors. The full
Procedure The surgical steps are exactly similar to thickness cornea with partial thickness scleral tissue
conventional inlay lamellar keratoplasty except that is then fixed to the recipient bed with 4 limbal mattress
the bed is formed by Descemet’s membrane and endo- 10-0 monofilament nylon sutures. Four more scleral
thelium of the recipient. A full thickness same size sutures are passed alternating to each corneal suture
donor corneal button is fixed to the recipient bed over (Figs 34.10A to D).
Figs 34.8A to D: Deep LK with descemetoendotheliotomy. (1) Host cornea, (2) Trephine mark, (3) Descemet’s
membrane, (4) Donor lenticule (5) 26 gauze needle (6) Perforation in Descemet’s membrane (I) Anterio-
anterior chamber, (II) Postero-anterior chamber
Figs 34.9A to D: Sclerokeratoplasty recipient. (A) Total diseased cornea, (B) Partial thickness scleral dissection
(C) Recipient sclerocorneal bed, (D) Donor sclerocorneal button fixed to recipient
Figs 34.10A to D: Sclerokeratoplasty (Donor tissue preparation). (A) 14 mm trephine mark, (B) Partial thickness
scleral dissection, (C) 10 mm limbal trephine mark, (D) Sclerocorneal button
REFERENCES 11. Wood TO, Fleming JC, Dotson RS, Cotton MS. Treatment of
Reis Buckler’s corneal dystrophy by removal of subepithelial
1. Cassey TA. Corneal grafting: Principle and Practice. fibrous tissue. Am J Ophthalmol 1978;85:360.
2. Marguerite B McDonald: Onlay Lamellar Keratoplasty in the 12. Richard JM, Paton D, Gasset AR. A comparison of PK and
Cornea. In HE Kaufman (Ed): Churchil Livingstone, 1988;697. LK in Keratoconus. Am J Ophthalmol 1978;86:807.
3. Smirmaul H, Casey TA. A clearview trepine and lamellar 13. Kaufman HE, Werblin TP. Epikeratophakia for keratoconus.
dissector for corneal grafting. Am J Ophthalmol 1980;90:92. Am J Ophthalmol 1982;93:342.
4. Anwer M. Dissection technique in L K. Br J Ophthalmol 14. McDonald MB, Kaufman HE, Durrie DS et al. Epikera-
1972;56:711. tophakia for keratoconus. Arch Ophthalmol 1986;104:1294.
5. Barrquer JI. Lamellar keratopasty. Ann Ophthalmol 1972;4:437.
15. Panda A. Epikeratoplasty. Ocular Surg News 1994;5:2.
6. Polack FM. Lamellar keratoplasty. Arch Ophthalmol
16. Kenyon K, Seng T. Limbal autograft transplantation.
1971;86:293.
Ophthalmol 1989;(96)5:701.
7. Malbran E, Stefani C. Lamellar keratoplasty in corneal
17. Stephen Morgan, Aidan Murray. Limbal transplant in
ectasias. Ophthalmogica 1972;164:59.
8. Reech MJ. Corneoscleral lamellar transplant for recurrent chemical injury. Eye 1996;10:349.
pterygium. Arch Ophthalmol 1971;86:296. 18. Michael D. Wagoner: Chemical injuries of the eye. Surv
9. Laughera PA, Arensten JJ. Lamellar keratoplasty in the Ophthalmol 1997;(41)4:275.
management of recurrent pterygium. Ophthalmic Surg 19. Copeland RR Jr, Char DH. Limbal autograft reconstruction
1986;17:106. after conj Sq cell carcinoma. Am J Ophthalmol 1990;110:412.
10. Wood TO, Walker GG. Treatment of BSK. Am J Ophthalmo 20. Tseng, Tsai: Human allograft limbal transplant. Cornea
1975;l80:553. 1994;(13)5:389.
Chapter 35
Evolution of Refractive
Keratoplasty
Cornea contributes to more than 80 percent of the total Following contractions, the central optical zone of
dioptric power in non-accommodated state of the eye. cornea flattens resulting in reduction of refractive
In 1949 Jose Barraquer of Autonomous University of power in myopic eyes. Application of heat at the apex
Barcelona, Spain defined Refractive Keratoplasty as of keratoconus also flattens the central cornea;
“modification of the refraction of the eye by plastic however resultant loss of corneal transparency causes
surgical intervention in the cornea’. This is also known further diminution of visual acuity. Laser beam may
as “Keratorefractive Surgery”. Characteristically it also be applied in thermokeratoplasty.
may be autoplastic or homoplastic. It is said to be
physiological in the sense that only human cornea is Epikeratophakia
used. It is also called non-invasive, as the globe is not
entered to perform the optical modification. Though Epikeratophakia is a form of refractive surgery on the
it was conceived in 1949, it was not until 1958 that cornea for correction of keratoconus,4 aphakia and
Barraquer started to use interlaminar graft for optical high myopia. It is a form of living contact lens. It was
modification for removal of astigmatism. During the the most widely practiced lamellar keratoplasty
following years a number of ophthalmic surgeons technique. The concept of epikeratophakia originated
including Aimslie in UK, Krosnov in USSR, Troutman from a procedure known as epikeratoprosthesis or
in US and Hoffmann in Germany followed Barraquer adhesive prosthesis tried by Gasset and Kaufman in
to further develop the technique. 1968 where a plastic lens was glued down on the
The various procedures in refractive surgery corneal surface, after removing the epithelial cells, by
practiced in the past include application of heat on using various types of adhesives; most of the cases
the cornea known as thermokeratoplasty, incisions on were successful with Isobutyl glues. Unfortunately in
the anterior and/or posterior surface of the cornea: course of time the prostheses and the glue made the
Radial keratotomy introduced by Sato (1894) 1 for cornea opaque and hence the practice was abandoned.
myopia, corneal lathing techniques of keratomileusis, Werblin and Kaufman5 devised epikeratophakia
keratophakia and epikeratophakia.2,3 These proce- by using lathe cut donor corneal lenticules which had
dures are obsolete now. been used mainly in pediatric aphakic eyes. Other
methods of correction available at that time were
Thermokeratoplasty spectacle lens, contact lens; and could not be used in
Thermokeratoplasty involves application of heat in the babies due to obvious reasons. It was tried in adult
corneal stroma. The principle of this procedure is aphakia, myopia and phakic hyperopia. Epikeratopha-
coagulation of the collagen fibers leading to fibrosis kia with planopower lenticules was developed to treat
and contraction. In myopia the heat is applied radially keratoconus like onlay lamellar keratoplasty as re-
leaving the central 4 to 5 mm of cornea unaffected. enforcement of the cone in keratoconus.
Chapter 35: Evolution of Refractive Keratoplasty 277
In the operative procedure the visual axis of the Keratophakia
patient’s eye is identified first. Commercially available
Using microkeratome devised by Barraquer, a
prelathed lenticule from biological lens having
planostromal lamellar disk is removed from donor
predetermined power is placed into an antibiotic
solution for about 20 minutes. Corneal lenticules also cornea and allowed to thaw to lathe cut a lenticule of
may be prepared from unfrozen corneas by using predetermined power. The lenticule is placed over the
excimer laser. The paracentral corneal epithelium is host prepared stroma with the convex surface
thoroughly denuded by rubbing with a cellulose anteriorly. Then the previously removed host stromal
sponge. A 7 mm or 7.5 mm trephine is used to incise disk is sutured over the lenticule.
the patient’s cornea partially to a depth of 0.2 to 0.3 During application of the microkeratome, the
mm. Then a thin annular keratectomy is performed intraocular pressure is kept raised by application of a
immediately central to the trephination mark in order pneumatic suction ring around the limbus. The
to provide a seat for securing the edge of the lenticule. optimum diameter and thickness of the lenticule are
The rehydrated epikeratophakia lenticule is then 8mm and 0.3 mm respectively.
sutured into the annular keratectomy host cornea with Though keratophakia is an extraocular procedure
interrupted nylon sutures. The main drawback of the there may be some corneal complications during
operation is that it takes a long time before optimum surgery or during the post-operative period which
visual acuity is achieved; but the advantage is that may cause deterioration of vision instead of improve-
when occasion arises it can easily be removed without ment. Corneal decompensation may lead to
leaving any scar. opacification which require penetrating keratoplasty.
Operative complications are perforation and flattening
Alloplastic Refractive Keratoplasty of the anterior chamber. Due to improper placement
of the lenticule, severe degree of astigmatism may
This technique involves the intrastromal implantation
result.
of hydrogel materials that have been manufactured
with specific curvature. Like the biological lenticule:
Radial Keratotomy (RK)
such lenses help to increase the anterior corneal
curvature. Another alloplastic material, polysulfone, The concept of modifying the surface of the cornea is
has been developed which when placed in between not new; suggestions for an operation for correction
the epikeratophakia graft and the Bowman’s memb- of astigmatism was made as early as 1894.8 Radial
rane alters the refractive power, not by changing the incisions on the anterior and/or posterior corneal
anterior corneal curvature but by modifying the surface were made to modify the surface of the cornea
intrastromal refractive index. by Sato and his associates 6 for treatment of high
Keratophakia and keratomileusis are two types of myopia, astigmatism and keratoconus. However, most
kerato-refractive procedures initially conceptualized of the cases where posterior keratotomy was done,
by Barraquer in 1965.4 The main principle of this proce- developed bullous keratopathy necessitating penetra-
dure is to lathe cut the biological cornea according to ting keratoplasty. Due to development of these
the power to be incorporated. In keratomileusis a complications the operation was abandoned. By this
lamellar button of the anterior half of corneal stroma operation Fyodorov of Russia was able to accomplish
of the patient is removed and after freeze drying a
reduction of myopia of 2 to 6.5 diopters. In the United
predetermined power is introduced in the posterior
States also several investigators after extensive study
surface of the button. For correction of myopia a con-
had confirmed the effectiveness of radial keratotomy
vex portion is removed and for correction of hyperopia
in reducing myopia. 7 Until the recent past this
a concave portion is removed. The button is again
sutured back onto the cornea. The principle of operation was performed with much success all over
keratophakia is to lathe cut a lenticule of required the world.
power from homologous cornea and insert it in the
corneal stroma. A convex and a concave lenticule is Operative Procedure
used in the correction of hyperopia (aphakia) and The operation was done under surface anesthesia but
myopia respectively. to avoid the risk of operative complications, retrobulbar
anesthesia is used for absolute akinesia. It is essential Keratomileusis

to determine the thickness of the cornea with a
It is another cryosurgical procedure for correction of
ultrasonic pachymeter and to locate the optical (not
refractive error. This is an autokeratoplasty technique;
the anatomical) center of the cornea by an optical
in which the power is lathed into the host’s own
centering device attached to the operating microscope;
stromal lenticule. This procedure is more popular for
a 3mm to 4 mm round optical zone is marked with a
correction of myopia than for aphakia.
trephine blade around the optical center. The ring is
Initial operative technique is almost the same as in
the starting point of the radial incisions over the
keratophakia. A lenticule is obtained from the host
cornea. The depth of the incision should involve the
cornea by lamellar keratectomy with microtome. The
outer two-thirds of the thickness of the cornea.
desired power is cryolathed in the posterior surface
Maximal flattening of the optical zone of the cornea
of the lenticule. The lenticule is then placed on the
can be achieved with approximately 8 incisions; Sato
bare stromal bed and secured in place with 10-0 nylon
made 80 (40 anterior and 40 posterior) incisions and
sutures. For hyperopic keratomileusis, the majority of
Fyodorov started with 32, but found 16 to be as
tissue lathing is made at the peripheral part of the
effective; but most of the surgeons get satisfactory
lenticule to shape a positive power lens.
results with 8 incisions. Clear zone diameters of less
than 3 mm are liable to produce intolerable post-
operative glare and greater than 4.5 mm will have REFERENCES
minimal effect. Razor blade should not be used; 1. West C. Corneal disease in Peyman GA; Saurens DL,
sophisticated guarded diamond knives are used for Goldberg MF (Eds). Principles and Practice of Ophthalmology.
accurate incisions.9 WB Saunders 1980;1:405.
2. Barraquer J. Special methods in corneal surgery in King JH
Though the result of the operation is unpredictable, Jr. McTiguel W (Eds). The Cornea, Butterworths 1965.
good results were claimed in expert hands. The 3. Kaufman HE, McDonald MB. Refractive Surgery for aphakia
operation is not free from operative, early post- and myopia. Trans Ophthalmol Soc UK 1984;104:43.
operative and late post-operative complications. 4. McDonald MB, Koenig SB, Safir A et al: Onlay lamellar kerato-
Perforation of the cornea may occur during the plasty for the treatment of keractoconus. Br J Ophthalmol
1983;67:615.
operation; though spontaneous healing may occur; 5. Werlin TP, Kaufman HE, Friedman MH et al: Epikeratophakia
occasionally it might require stitching. Post-operative III. Preliminary results of a prospective clinical trial. Arch
pain, photophobia, corneal edema, epithelial erosions, Ophthalmol 1981;99:1957.
stromal overgrowth and corneal dystrophy are some 6. Sato T, Akiyama K, Shibata H. A new surgical approach to
of the complications reported by various workers. myopia. Am J Ophthalmol 1953;36:823.
7. Waring G, Lynn M, Geiender H (PERK Study group). Results
Bacterial infection even leading to endophthalmitis9,10 of prospective evaluation of radial keratotomy one year after
and corneal erosions with vascular and epithelial surgery. Ophthalmology 1985;92:177.
ingrowth have been reported. The main drawback of 8. Waring GO. Evolution of radial keratotomy for myopia. Trans
the operation is that the result is unpredictable and a Ophthalmol Soc UK 1984;104:28.
physiologically and anatomically normal cornea is 9. Rowsay JJ, Balycat HD, Yeisky KB. Diamond knife.
Ophthalmol Surg 1982;13:279.
converted into a pathological one. Moreover myopics 10. Rowsay JJ, Hays JC. Radial Keratotomy in Davidson JJ,
of more than 4 diopters are not benefited much by Fraundufelder FC (Eds.) Recent Advances in Ophthalmology,
this operation. Churchill Livingstone 1985.
Chapter 36
Photorefractive Keratectomy
Technique and
Postoperative Regimen
MS Sachdev, Namrata Sharma
The first excimer photorefractive keratectomy (PRK) manifest and cycloplegic refractions, no matter what
for myopia on a “normally sighted” human eye was the patient’s age may be. The cornea should be
performed at the LSU Eye Center in July 1987, by carefully scrutinized for any sign of pathologic
McDonald and colleagues. Excimer lasers are gas conditions that might affect the surgical outcome.
lasers in which the lasing medium inside the resonator Other measurements that are not part of the routine
consists of a gas mixture that is excited by special ophthalmic examination, including pachymetry, glare
pretreatments.1 It is important to use videotapes and testing, evaluation of visual fields, corneal sensitivity,
printed information in educating patients. The last and endothelial cell counts, may also be done
step in a full informed consent is a discussion between routinely. Corneal topography measurements as base-
the patient and the surgeon, during which the patient line, and at least one more time postoperatively
must be given an opportunity to ask questions. (usually at 6 or 12 months) should be done. During
the preoperative evaluation, the informed consent
PREOPERATIVE EVALUATION form can be presented to the patient and discussed as
The preoperative evaluation should be performed as needed.
close to the date of surgery as possible. A preoperative The accuracy of the manifest refraction cannot be
examination within 45 days of the scheduled surgery overemphasized; it should correspond very closely to
should be undertaken. All previously evaluated the cycloplegic refraction, and it is by far the most
contact lens-wearing patients must discontinue their important measurement taken prior to undergoing
use at least 2 weeks prior to their presurgical excimer PRK.
evaluation in the case of soft or rigid gas-permeable
contact lenses and 3 weeks in the case of polymethyl- Preparation of the Patient
methacrylate (PMMA) lenses. It is desirable, that at The patient is placed under the excimer laser and
least two identical K-readings and baseline refractions topical proparacaine hydrochloride 0.5 percent is
be obtained prior to the procedure in the case of all instilled into the eye. The patient is instructed to fix
contact lens wearers, particularly those who have been with the operative eye on the red coaxial fixation light,
wearing PMMA lenses. and the surgeon centers the laser over the entrance
Preoperative evaluation should include a complete pupil. Because of the possibility of cyclotorsion of the
ophthalmic examination of both eyes. An extremely globe, the orientation of the patient’s cylinder is
careful uncorrected and best corrected visual acuity confirmed immediately prior to surgery using the axis
measurements should be taken, along with both measurement device (VISX, Inc). The VISX axis
measurement system project a parallel line pattern pupillary distance for the surgeon, and the prescrip-
through the camera port of the microscope onto the tion is dialed into the eyepiece, unless the surgeon
patient’s eye. The patient’s spherical error is first intends to wear his or her correction during surgery.
corrected by a slide’s lens to focus the line pattern at The preoperative keratometry readings and
the patient’s far point. Then the pattern is rotated by refraction are entered into the computer which
the patient until the lines are as short as possible. This controls the laser, and the patient is seated in the chair,
identifies the axis of the myopic cylinder (negative so that eye to be treated will be directly under the
notation) of the patient to within a few degrees. The operating microscope. A drop of proparacaine is
distinctness and accuracy of the endpoint is better for placed in each eye, and the nontreated eye is patched
larger amounts of refractive cylinder. This is repeated so that the patient cannot crossfixate during the
several times to get an average and to test consistency procedure.
before treatment. A lid speculum is placed between the upper and
A few pulses of laser energy are then applied with lower lids, and an annular sponge, soaked in
the slit maximally narrowed in order to confirm proparacaine, is dropped onto the limbus. The patient
proper orientation of the slit relative to the corneal is asked to look directly at the fixation light, and a
cylinder and to acquaint the patient with visual, Sinskey hook is used to mark the center of the pupil.
auditory, and olfactory sensations associated with the Some investigators do this under three different levels
laser ablation. The patient’s preoperative topographic of room illumination, in order to be absolutely certain
corneal map is placed upside down above the oculars that the center of the pupil has been located correctly.
of the operating microscope, matching the surgeon’s Others prefer to pilocarpinize the pupil. The patient
view, so that the surgeon can readily double-check is instructed to fixate on an annular target inside the
that the laser slit is properly oriented. The corneal laser delivery system. When the patient is fixating on
epithelium is then removed with a blunt spatula, or the target and the He-Ne beams are centered on the
by performing a 6.0 mm diameter ablation through cornea and the pupillary axis, the patient is in precise
the epithelium, and then using the blunt spatula to focus with the laser. It is of note that after the He-Ne
ascertain that no residual islands of epithelium remain beams are brought to a pinpoint focus on the cornea,
they diverge and are seen as 2 spots equally spaced at
on Bowman’s layer. This latter technique minimizes
the 3 and 9’o clock positions in the midperiphery of
the time required for epithelial removal, and thus the
the iris.
likelihood dehydration of the laser over the entrance
During the clinical evolution of PRK in years 1988
pupil is confirmed while the patient fixates on the
to 1994, ablation zone diameters have progressively
flashing centration light.6
increased from 3.5 mm3 to 6.5 mm or more.1 The major
One avoids intraoperative corneal hydration
reason for the increase was the high incidence of
changes by minimizing the interval between epithelial
symptomatic halos under night driving conditions
removal and corneal ablation.
when small ablation zones were used.3
Surgical Technique We use a 193 nm argon fluoride excimer laser. To
correct myopia, this laser uses a computer-controller
A checklist includes a laser energy reading and beam iris diaphragm to vary the diameter of the ablation
alignment, as well as a check of the uniformity and beam so as to ablate more tissue centrally than
diameter of the beam with PMMA test blocks. Before peripherally, thereby flattening the cornea.4
each surgical procedure, one or more test ablation is Creation of a circular optical zone mark is done
performed on PMMA blocks, and are read in a with a large radial keratotomy (RK) optical zone (OZ)
lensometer to be certain in order that the amount of marker. Some surgeons use a marker that is exactly
ablation is consistent with that needed for the the same size as the intended ablation zone, while
individual patient. When the PMMA test lens is others use a marker 0.5 to 1.0 mm larger. Next, the
consistent with the desired correction, a calibration central epithelium within the mark is removed with a
table supplied by the laser company, is checked to be spatula. The more common clinically used methods
sure that the appropriate depth per pulse is used for of deepithelialization include mechanical debridement
entry into the computer. The patient’s name, the date, with a bent spatula or a sharp blade, 4 chemical
eye to be treated, and study or protocol designation deepithelization by means of topical anesthetics,
are recorded on the videotape. The eyepieces of the cocaine1 or alcohol 5, and photoablative deepithe-
operating microscope are adjusted to the proper lialization.1
Chapter 36: Photorefractive Keratectomy Technique and Postoperative Regimen 281
At this point training session is performed to Follow-up examinations are scheduled at 24-hour
familiarize the patient with the upcoming PRK intervals until reepithelialization is documented.
procedure. Patient using a bandage contact lens can instill
First, the laser is programmed for a 3-diopter medication directly into their own eyes (generally an
correction. One percent HPMC is applied on the entire antibiotic, a dilating agent, and diclofenac are applied);
corneal surface. This layer of liquid will block any laser if the patient is being patched, the surgeon instills the
ablation on the surface of the cornea. The goal of this medications once a day at the time of the examination.
is 3-fold, i.e. (1) to allow the patient to hear the louder, Reepithelialization is usually complete within 3 to 5
snapping noise made when the laser is hitting the days, after which the patient is placed on an artificial-
tissue, (2) to mark the epithelium over the visual axis tear regimen. Unpreserved artificial tears are best for
so that adequacy of concentration can be checked, and the delicate new epithelial layer that has just covered
(3) to determine the size of the optical zone and extent the ablated area; many of these patients have dry eyes
of corneal epithelial removal for laser keratectomy and require extra-lubrication to prevent recurrent
directly under the Bowman’s membrane. epithelial defects.
It is important that stromal hydration be uniformed Patients routinely do not require a topical steroid;
just prior to ablation; some investigators believe that this regimen is reserved only for those patients who
a quick wipe with a cellulose sponge is all that is appear to be regressing rapidly. It is important to
needed, while others feel that artificial tears, followed prepare the patient for a moderate amount of
by a squeegee maneuver with a blunt instrument, such postoperative pain. After re-epithelialization is
as a cyclodialysis spatula, suffices. complete, the patient can be discharged from daily
With the VISX microscope, a magnification setting care; patients return for a 1-month check-up. It should
of 12/14 is needed for the ablation to be aligned be explained, however, that the eye will be quite
properly with the reticle of the eyepiece. The large blurry, somewhere between 20/200 and 20/50, for the
debris aspirator is attached to the VISX 20/40 unit so first 1 to 2 postoperative weeks, but that is possible
that it hovers over the patient’s lower lid, in a position for the patient to resume all normal physical activities
to remove debris effectively. Next, the position of the and a normal work schedule (except swimming, which
patient’s iris plane is checked to be certain that it is is best delayed for at least 3 weeks postoperatively
perpendicular to the path of the laser beam. The until the epithelial layer is of normal thickness, to
position of the iris is verified by two surgical assistants, protect against invasive microorganisms (that may be
one on each side of the surgeon. found in swimming pools).
Most ablations take approximately 11 to 45 seconds Overcorrection is extremely common in the first
for the treatment of 1 to 6 D myopia; it is important few weeks; if one is attempting to achieve full distance
that the surgeon concentrates to maintain the position correction, it is desirable. People near 40 years of age
of the eye with the fixation device, or to stop the will notice decreased distance vision and near vision
ablation if, during patient self-fixation, the surgeon for the ensuing weeks or months; the length of their
notices that the eye is beginning to drift. If a “drifting” poor vision is age-dependent and outcome-dependent
ablation is performed, irregular astigmatism and and patients will take longer to come out of their
unpredictable diopter outcome can result. hyperopic stage.
At the completion of the ablation, the assistant
irrigates the eye and postoperative medications are PRK FOR ASTIGMATISM
instilled. Many surgeons use one drop of homatropine Candidates for photorefractive keratectomy (PRK) for
5 percent, and a drop of ciprofloxacin. A semipressure astigmatism should have healthy corneas and stable
patch is applied to the eye, or, as more recently, a refractive errors. Patients with postsurgical astigma-
bandage contact lens. Many surgeons also instill a tism should have had all sutures removed, with stable
drop of diclofenac sodium. topography and refraction documented by repeat
Printout for the patient’s chart, including all the examinations performed at least 1 month apart. Just
laser parameters, the attempted change in diopters, as with photorefractive keratectomy for myopia,
the depth per pulse in the stroma, and the number of underlying eye disease, such as dry eye or chronic
shots at each step in the opening of the iris diaphragm blepharitis, are contraindications to the surgery and
are available. should be looked for carefully and treated
preoperatively. The preoperative examination a flattening of the cornea will occur in the vertical (90
consists of measurements of visual acuity with and degree) meridian. Primarily, this technique is designed
without correction, refraction, keratometry, to eliminate myopic astigmatism. The slit mechanism
biomicroscopic evaluation, pachometry, funduscopy, can be rotated, also under computer control, such that
tonometry, measurement of pupil diameter, and the mechanical axis can be aligned with the astigmatic
computer-assisted corneal topographic analysis. axis of the patient. The blades are oriented by the
Despite their protestations, patients who initially computer to be parallel to axis of refractive cylinder,
present with the contact lenses in place should be expressed in minus cylinder form, thereby flattening
required to return for repeat examination, as both soft the cornea in the appropriate (steep) meridian. With
and rigid contact lenses (especially the latter) can this approach, a vertical “wall” equal to the astigmatic
substantially alter the corneal topography and ablation depth would appear at two ends of the
measured refractive error. resultant rectangular ablation, along the mechanical
The refraction and topography should be followed axis. For this reason, a “transition zone” of 0.3 mm is
until they are stable. Patients who start out with generated at the ends of the slit to form a sigmoidal
asymmetric inferior steepening that is replaced by a transition between unoperated and ablated cornea.
more spherical and symmetric cornea probably have
Elliptic Ablation
contact lens-induced corneal warpage. Patients who
develop progressively greater inferior corneal steepen- Modification of the diaphragm hardware allows
ing may have mild keratoconus, and should be production of an elliptical area of ablation. The
examined repeatedly and carefully before deciding to flattening of the cornea will occur along the meridian
do surgery. We currently decline to operate on patient of the slit expansion, as described for the cylindrical
with even mild keratoconus that can be appreciated ablations. In myopia surgery, a series of concentric
only by topographic examination. circular ablations is performed, while this technique
The amount of correction desired is based on the for astigmatism creates a series of concentric elliptic
patient’s preoperative refraction. The computer is ablations. This technique can be used when the
programmed to perform cylindrical or elliptic magnitude of the cylindrical error is less than or equal
ablations designed to correct the patient’s cylindrical to the magnitude of the spherical myopia, where the
error, and the desired refractive change is refractive error is expressed in minus cylinder form.
programmed into the computer in minus cylinder The width of the narrow dimension of the ellipse is
form. If the patient has compound myopic astigma- dependent on the ratio of the spherical error to the
tism, we can correct the myopia and astigmatism cylindrical error. When the cylindrical error is small
sequentially by performing a cylindrical ablation (for compared to the spherical error, the ellipse is nearly
astigmatism) and a spherical ablation (for myopia), circular. When the cylindrical refractive error
approaches the magnitude of the spherical component
or we can correct them simultaneously with an elliptic
of the refractive error, the narrow dimension of the
ablation. In general, we are on the side of undercorrec-
ellipse becomes progressively shorter, with the
ting any coexisting myopia, with the understanding
smallest acceptable width being 4.8 mm. The elliptic
that residual myopia can be addressed, if necessary,
ablation has the theoretical advantages of producing
with a subsequent spherical ablation.
a transition at the edge of the ablation in the flat
Cylindrical Ablation meridian of the cornea, and it produces simultaneous
correction of the spherical refractive error, thereby
To correct astigmatism, the large-diameter excimer shortening the duration of the procedure and conse-
beam is passed through a set of parallel blades. The quently the likelihood that the corneal surface will
separation of the blades is under computer control, become dry or that the patient will lose fixation during
and the resultant variable slit is used to control the the surgery.
laser delivery, the iris diaphragm used for myopic
ablations.6 In case of the slit, however, the cornea PRE AND POSTOPERATIVE
should be flattened only in the meridian perpendicular MEDICAL TREATMENT
to the long axis of the slit (termed the mechanical axis);
no refractive change is intended along the mechanical Corticosteroids
axis (long axis of the slit). Thus, if the mechanical axis There is no consensus on the benefits, if any, of
is oriented horizontally (in the 180 degree meridian), preoperative corticosteroid therapy on outcome after
wide area excimer laser ablation in humans. The In a separate study13 of 86 patients randomized to
appropriate role, if any, for corticosteroids in the fluorometholone, plasmin inhibitor (aprotinin) or
postoperative management of photorefractive keratec- nothing, the steroid-treated eyes had greater refractive
tomy remains uncertain as well. The use of changes at three and six months, but the differences
postoperative corticosteroids has been common since became nonsignificant three months after the steroids
initial small animal studies suggested that they limit were discontinued. Aprotinin did not affect the
subepithelial deposition of new collagen and ground refractive error, but was associated with greater haze
substance7 and initial clinical observations of the at nine weeks and 2 months, postoperatively.
effects of topical steroids in blind and sighted human Although these two prospective trials failed to
eyes.3 Seiler et al3 reported that discontinuation of provide evidence of a beneficial role of the routine
topical dexamethasone caused a myopic shift of 0.5 to use of a several-month course of corticosteroids after
1.0 D within days (postulated due to epithelial photorefractive keratectomy, steroid use remains
hyperplasia), with a subsequent drift of 0.25 to 0.5 D routine among the majority of surgeons performing
over one month due to production of subepithelial this procedure. There are several potential limitations
extracellular matrix. At one year, noncompliance with of the trials that have been performed to date. Use of
steroid usage was a risk factor in half of his patients small ablation zone diameters (as small as 4.0 mm),
who developed severe haze (grade 2.5 or more) and and therefore quite shallow ablation depths, weaken
regression.8 Sher et al similarly described a patient who the apparent relevance of these trials of current clinical
developed severe haze and almost total regression of practice in which ablation diameters of 6.0 mm are
the corneal flattening after failing to comply with their common. Relatively small sample sizes in these trials
recommended course of corticosteroid therapy. The limit the power to detect a significant difference,
patient had previously undergone myopic epikerato- reducing confidence that lack of statistical significance
phakia without success, so the relationship between means there is no important effect of the steroids. In
the regression and steroid therapy is unclear. In a the second study,13 for example, the authors report
retrospective study, Tengroth et al10 compared patients that after 6.00 D treatments, the refractive change was
who received a five-week course of steroids with those significantly greater at six weeks and at three and six
taking steroids for three months; the longer duration months (p>0.01) in the steroid-treated patients.
therapy was associated with less early regression, but However, within three months of discontinuing
the shorter duration group was closer to emmetropia steroids this difference again fell below statistical
with a smaller standard deviation at one year. In significance (p>0.07). Considering that there were only
another retrospective study, Tengroth et al11 compared 13 eyes treated with steroids and 14 controls, the
results with topical dexamethasone 0.1 percent for narrow margin by which statistical analysis failed to
three months with eyes that received no steroids; at prove significance cannot allow one to conclude with
three months, there was statistically significant less confidence that no difference exists. The study also
regression in the steroid treated group. reports that four patients treated with steroids were
Few controlled prospective studies have examined overcorrected by more than 2 less D at 12 months,
the value of corticosteroid therapy after photorefrac- while similar overcorrections were not noted in the
tive keratectomy. Gartry et al12 performed a double- other groups. This observation weakens the assertion
blind placebo-controlled trial involving 113 patients that corticosteroids do not influence the outcome of
treated with ablations to correct either 3.00 or 6.00 less surgery, and raises the possibility that at least a subset
D of myopia. Patients were randomized to either a of patients (that cannot be identified preoperatively)
three-month course of topical dexamethasone 0.1 are very responsive to such therapy. In addition, the
percent or vehicle. At three months, dexamethasone- control eyes were not treated with vehicle in these
treated eyes had greater refractive changes, on studies. Since many patients interested in PRK are
average, than did eyes not given steroids, but the contact lens-intolerant (and tear deficiency is an
difference was statistically significant only for the 6.00 important contributor to this problem), differences in
D corrections. At six and 12 months postoperatively, the frequency with which drops are applied could
there were no statistically significant differences affect surgical outcome. Also, these studies did not
attributable to the steroids in refractive change or sue nonsteroidal antiinflammatory drugs and
corneal haze. Steroid-related pressure rise occurred therapeutic soft contact lenses to control postoperative
in 11 percent of the eyes receiving dexamethasone. pain. The use of contact lenses and nonsteroidal
antiinflammatory drugs is widespread and may alter decrease postoperative pain, which appears to result
the postoperative inflammatory response, and from the ability of these drugs to limit elevations in
therefore impact on the need for corticosteroids14 in certain arachidonic acid metabolites. A randomized,
the routine management of patients after PRK remains double-masked study compared postoperative pain
unresolved. in patients treated with diclofenac sodium 0.1 percent
Two other possible uses of corticosteroids after ophthalmic solution or its placebo vehicle.18 Compa-
photorefractive keratectomy are the control of imme- red to the control group, diclofenac-treated patients
diate postoperative corneal inflammation and to treat rarely experienced the early peak in pain, had less pain
eyes that have experienced regression of the initial overall until 72 hours postoperatively, and experien-
refractive change. Campos et al15 in the rabbit model, ced significantly less photophobia and burning/
showed that superficial stromal infiltration by leuko- stinging; significantly fewer patients treated with
cytes could be substantial, 24 hours after photo- diclofenac required oral narcotics. These authors
refractive keratectomy; this accumulation of concluded that epithelial healing over the ablated
inflammatory cell was dramatically reduced with cornea was not delayed in response to the diclofenac
topical fluorometholone. Although the relationship sodium. Other nonsteroidal agents appear to
between the severity of early postoperative corneal significantly reduce postoperative pain, but similar
inflammation and eventual outcome (refractive controlled trials have not yet been published.
change and haze) after wide area excimer ablation is The use of therapeutic soft contact lenses is
not clearly established,16 there is reason to think that common in conjunction with nonsteroidal anti-
a short course (a few days) of a week topical cortico- inflammatory drug.18 The relative contributions of the
steroid might limit inflammation and improve patient drug and the contact lens to control pain are not
comfort. In eyes that have received steroids post- completely understood. Also, the use of a soft contact
operatively, only to regress after the steroids are lens introduces new variables and potential
discontinued, there is the common clinical experience complications, including tight lens syndrome and, at
that at least some of these eyes will respond to a second least, a theoretically increased risk of infectious
course of corticosteroids by regaining some of the keratitis.
initial flattening.10 The mechanism for this steroid- In mammalian cell cultures, ultraviolet light stimu-
induced corneal flattening is undetermined, and there lates cyclooxygenase metabolism and produces high
is currently no method for determining which subject level of prostaglandin E2 (PGE2). Levine et al19 have
of patients who undergo photorefractive keratectomy shown that PGE2 leukotriene B4 and bradykinin act
might benefit from postoperative corticosteroid as chemoattractants for polymorphonuclear leukocytes
therapy. (PMNs) and can cause hyperalgesia. Nonsteroidal
If corticosteroids are to be used for an extended anti-inflammatory agents have been found to
period of time after PRK, an important consideration dramatically reduce pain after excimer laser PRK.18
is the possibility of steroid-induced rises in intraocular In rabbits, excimer laser PRK has been found to result
pressure. Because all wound healing activity after in a prompt elevation of corneal levels of PGE2, and
wide-area ablation occurs within the superficial this increase in PGE2 can be limited with topical
cornea, it is probably preferable to minimize the application of diclofenac sodium, a cyclooxygenase
amount of corticosteroid within the aqueous humor. inhibitor. PGE2 elevation also occurs with mechanical
There are no satisfactory data to address the issue of superficial lamellar keratectomy of equal depth to
whether penetrating corticosteroids and non- excimer wide area ablation,19 but the elevation is much
penetrating corticosteroids differ in their effects on less with the mechanical technique, indicating a
postoperative healing. In one pair of identical twins, specific effect of the ultraviolet radiation on PGE2
one was treated with fluorometholone 0.1 percent and synthesis. Pretreatment of the cornea with diclofenac
the other with dexamethasone 0.1 percent after photo- sodium begining two hours prior to ablation did not
refractive keratectomy; the results were identical in further limit PGE2 synthesis19 suggesting that pretreat-
the two eyes.17 ment with such nonsteroidal anti-inflammatory agent
is unlikely to be of benefit clinically.
Nonsteroidal Anti-inflammatory Agents Whether nonsteroidal anti-inflammatory drugs
Nonsteroidal anti-inflammatory drugs have been used have a role in the long-term postoperative manage-
after photorefractive keratectomy primarily to ment of eyes after photorefractive keratectomy is
undetermined. In the rabbit model, prolonged therapy 5. Campos M, Raman S, Lee M, McDonnell PJ. Keratocyte loss
with diclofenac sodium decreased corneal haze after after different methods of deepithelization. Ophthalmology
1994;101:890-94.
photorefractive keratectomy.20 In one limited clinical 6. Marshall J, Trokel S, Rothery S et al. Photoablative reprofiling
study 16 the two eyes of a patient with myopic of the cornea using an excimer laser: Photorefractive
regression after PRK were treated topically, one with keratectomy. Lasers Ophthalmol 1986;1:21-48.
a corticosteroid and the other with diclofenac sodium, 7. Tuft SJ, Zabel RW, Marshall J. Corneal repair following
in an attempt to regain refractive effect. The eye treated keratectomy: A comparsion between conventional surgery
and laser photoblation. Invest Ophthalmol Vis Sci
with the steroid experienced further corneal flattening,
1989;30:1769-77.
while the diclofenac-treated eye did not respond to 8. Seiler T, Wollenask J. Myopic photorefractive keratectomy
therapy. Further laboratory and clinical investigations with the excimer laser: One year follow-up. Ophthalmology
are needed to define the appropriate role of 1991;98:1156-63.
nonsteroidal anti-inflammatory drugs in the acute and 9. Sher N, Chen V, Bowers RA et al. The use of the 193 nm
excimer laser for myopic photorefractive keratectomy in
long-term medical management of patients after
sighted eyes: A multicenter study. Arch Ophthalmol
photorefractive keratectomy. 1991;109:1525-30.
10. Tengroth B, Epstein D, Fagerholm P et al. Excimer laser
Other Wound Healing Modulators photorefractive keratectomy for myopia: Clinical results in
sighted eyes. Ophthalmology 1993;100:739-45.
A focus of recent research efforts has been control of 11. Tengroth B, Fagerholm P, Soderberg P et al. Effect of cortico-
the postoperative corneal cellular response to steroids in postoperative care following photorefractive
photorefractive keratectomy using drugs that may be keratectomisis. Refract Corneal Surg 1993;(Suppl)9:61-64.
related fibroblast activity. Use of the cytotoxic agent, 12. Gartry DS, Kerr Muir MG, Marahsall J. The effect to topical
corticosteroids on refraction and corneal haze following
mitomycin was reported to reduce the corneal haze
excimer laser treatment of myopia. An update. A prospective,
in rabbits after PRK, with a reduction in the amount randomised double-masked study Eye 7: 584-90.
of newly synthesized collagen and ground substance 13. O’ Brart DPS, Lohman CP, Klonos G et al. The effects of topical
at the epithelial-stromal interface. 21 Subsequent corticosteroids and plasmin inhibitors on refractive outcome,
studies showed the postoperative use of mitomycin haze, and visual performance after photorefractive
keratectomy. A prospective, randomized, observermasked
to be associated with substantial toxicity, however,
study. Ophthalmology 1992;101.
including inhibition of epithelial wound healing, 14. Piebenga LW, Matta CS, Deitz MR et al. Excimer photorefrac-
without dramatic improvement in corneal clarity. tive keratectomy for myopia. Ophthalmology 1993;100:1335-
Another study examined the efficacies of idoxuridine 45.
and two collagen cross-linkage inhibitors, beta- 15. Campos M, Abed HM, McDonnell PJ. Topical fluorometha-
lone reduces stromal inflammation after photorefractive
aminoproprionitrile and D-penicillamine, in rabbits
keratectomy. Ophthalmic Surg 11994;0:626-30.
after excimer ablation, but reports of reduced haze 16. Ramirez-Florez S, Maurice D. Inflammatory cells, refractive
have not been confirmed.20 Finally, topical interferon regression, and haze after PRK (abstract). Invest Ophthalmol
alpha 2b, known to inhibit fibroblast glycosamino- Vis Sci 1993;(Suppl)34:704.
glycan production, has also been reported to reduce 17. Machat JJ. Double-blind corticosteroid trial in identical twins
corneal haze in rabbits, and to have an effect additive following photorefractive keratectomy. Refract Corneal Surg
1993;(Suppl)9:105-7.
to that of topical dexamethasone. 18. Sher N, Frantz JM, Talley A et al. Topical diclofenac in the
treatment of ocular pain after excimer photorefractive
REFERENCES keratectomy. Refract Corneal Surg 1993;9:425-36.
19. Levine JD, Gooding J, Donatoni P et al. The role of the
1. Seiler T, McDonnell PJ. Excimer laser photorefractive keratec- polymorphonuclear leukocyte in hyperalgesia. J Neurosci
tomy. Surv Ophthaolmol 1995;40(2):89-118. 1985;5:3025-29.
2. Uozato H, Guyton DL. Centering corneal surgical procedures. 20. Tamamo JH, Gollamudi S, Green WR et al. Modulation of
Am J Ophthalmol 1987;103:264-75. corneal wound hearing after excimer laser keratomileusis
3. Seiler T, Kahle G, Kriegerowski M. Excimer laser (193 nm) using topical mitomycin C and steroids. Arch Ophthalmol
myopic kertomileusis in sighted and blind eyes. Refract 1991;109:1141-46.
Corneal Surg 1990;6:165-73. 21. Yamaguchi T, Sekiya Y, Noyori K. Effect of β-methasone,
4. Campos M, Hertzog L, Wand XW et al. Corneal surface after idoxuridine, and two collagen cross-linkage inhibitors on
deepithelization using sharp and a dull instrument. rabbit corneas after excimer laser photoblation (abstract).
Ophthalmic Surg 1992;23:618-21. Invest Ophthalmol Vis Sci 1991;(Suppl)32:1248.
Chapter 37
Laser-Assisted In Situ
Keratomileusis (LASIK)
Dipak Bhuyan
INTRODUCTION disorder.
• Independence from use of correcting glasses
LASIK stands for laser assisted in-situ
• Intolerance to contact lens due to difficulty in daily
Keratomileusis. Any discussion about LASIK must
manipulation, hypersensitivity to contact lens
begin with the “Father of modern refractive surgery”,
cleaning solution, dry eye, giant papillary conjunc-
Jose Ignatio Barraquer, MD, of Bagota, Columbia.
tivitis and Keratitis
Dr Barraquer’s premise was to add or remove
• Professional reasons where access to some profes-
sufficient tissue from the cornea to modify the
sion is determined by the level of uncorrected
refraction of the eye (cornea is responsible for 2/3rd
visual acuity
of the total unaccommodated power of the eye. He
• Aesthetic and social reasons
began his work on the instrumentation shortly before
• Sport related reasons
1949. Using the microkeratome designed by him,
• To correct residual low vision after Radial Kerato-
Barraquer developed “keratomileusis”.1 Reasonably
tomy (RK), Penetrating Keratoplasty (PKP) and
good results were achieved in the hands of a skilled
cataract operation.
ophthalmic surgeon using this technique. Dr Stephen
Trokel published the landmark paper in the American
Age
Journal of Ophthalmology in 1983,2 outlining the
potential of using excimer laser, which had been Refractive surgery is performed usually after the age
developed 10 years earlier for creation of computer of 18 years, as this assures certain refractive stability.
chips, for reshaping the cornea and correcting vision.
By combining the reproducibility of patient wound Refraction
healing of lamellar surgery with the accuracy and
Stability of refraction is required for long term post
extreme precision of the excimer laser, a new hybrid
LASIK stable correction. A change in refraction within
procedure was born. Ioannis Pallikaris, coined the
+ 0.50 D over one year is considered stable.
term LASIK. He performed the first surgery on a
The wearing of hard or gas permeable contact
seeing eye in 1990.3,4
lenses should be discontinued for four weeks and
soft lenses 1 week prior to LASIK.
PREOPERATIVE EVALUATION
Motivation CONTRAINDICATIONS
The main objective which motivates a patient to
Motivation
undergo refractive surgery is to achieve partial or
total independence from his or her refractive Patients who do not understand the reality of the
Chapter 37: Laser-Assisted In Situ Keratomileusis (LASIK) 287
outcome of refractive surgery. • Fundoscopy
• Corneal topography
Age • Pachymetry (corneal thickness)
• Pupil size
Age below 18 years.
• Glaze and contrast sensitivity
• Specular Bio-microscopy
Refraction
Unstable refraction during 12 months prior to surgery STABILITY OF REFRACTION
The change in spherical equivalent should not be more
Ocular Pathology
than 0.50 D over preceding 12 months. It can be
• Infection of lid, conjunctiva, cornea, etc. evaluated from his or her history of earlier refractive
• Keratoconus status.
• Corneal dystrophy
• Central corneal thickness less than 450 micron CONTACT LENS
• Dry eye
Contact Lens wear may cause alteration of the corneal
• Cataract, glaucoma, iritis, retinopathy, optic
surface, resulting into reversible change in refractive
atrophy, etc.
status and corneal warpage. Soft lenses should be
• Herpes virus infection
discontinued a week before evaluation and treatment
and hard/RGP lenses should be discontinued for 4
Systemic Pathology
weeks or until the refractive status stabilizes. In case
• Pacemaker, it may be affected by the laser’s of corneal warpage, lenses may have to be disconti-
electric field nued for several months.
• Pregnancy
• Diabetes mellitus, Rheumatoid arthritis, AIDS are MEDICAL AND OPHTHALMIC PROBLEMS
relative contra-indications
Following conditions should be ruled out as they may
increase the risk of complication or result in unsatis-
Pre LASIK Examination
factory outcome after LASIK. Ocular conditions are
Patient selection in any refractive procedure is of vital blepharitis, narrow palpebral fissure, sunken eye, one
importance. After considering the facts of indications eyed, dry eye, active ocular infection, filtration bleb,
and extra-indications, when the patient is selected, poor BSCVA, diabetic or vascular retinal disease
following are the steps to be followed: requiring laser treatment, keratoconus, thin cornea
• The patient should be educated about the (< 450 μ). History of systemic conditions to be recor-
procedure by brochures, video presentation or by ded are—pacemaker, pregnancy, diabetes, arthritis,
consultation with the surgeon vascular and autoimmune diseases and drug allergy).
• The patient should be explained the risks / benefits
of the alternative procedures available EXPECTATION
• To obtain an informed consent signed by the
The patient should understand that no refractive
patient
surgery is perfect. It cannot give 20/20 unaided visual
• Thorough history taken regarding stability of
acuity to all the patients. The aim is to reduce depen-
refraction, contact lens, general health and
dency on spectacle or contact lens. Need for a reading
ophthalmic problem
glass for the presbyopic patients need to be explained.
CLINICAL EXAMINATION
REFRACTION
• Uncorrected visual acuity (UCVA) and best
spectacle corrected visual acuity (BSCVA) Both cycloplegic and manifest refractions are
• Manifest and Cycloplegic refraction performed. Cycloplegic refraction helps to prevent
• Slit-lamp Bio-microscopy overcorrection in myopia and under-correction in
• Intraocular pressure (IOP) recording hyperopia. Cylinder should be expressed in the minus
cylinder form. It is the manifest refraction that is used

for correction into the computer for LASIK.
FUNDOSCOPY
Indirect ophthalmoscopy is performed to evaluate
the peripheral retina as the vitreous base is under
high stress during application of the suction plate of
the microkeratome and may predispose to retinal
detachment. If any degenerative patch is present, they
should be treated by cryopexy 6 weeks before and
by Laser12 2 weeks before LASIK.
CORNEAL TOPOGRAPHY
Videokeratography provides information on the
corneal topography e.g. radius of curvature, dioptric
power of the cornea at any given location and the
axis of astigmatism. It helps to detect, steep or flat
cornea, early or established keratoconus, corneal
surface disorders due to disease or contact lens wear
in follow up of post LASIK cases by use of ‘difference’
or ‘subtraction’ maps. It is also used in Topography-
assisted LASIK (TA LASIK) or Topography-linked
LASIK (TOPOLINK), where topographic data is
electronically transmitted to the computer of the
LASIK machine and by special software it is converted
into light value based on which amount of ablation is
calculated. This is useful to treat irregular astigmatism
following keratoplasty, radial keratotomy, corneal
injuries, etc.
Figs 37.1A and B: Pachometry samples
PACHOMETRY (Figs 37.1A and B)
Pachometry, ultrasonic measurement of the thickness PUPIL SIZE
of the central cornea or the thinnest area, is essential
Measurement of the pupil size is important to decide
before LASIK. It is important to design the treatment
the diameter of the optical zone. The zone diameter
algorithm to preserve adequate residual stromal
should be bigger than the mesopic pupil diameter.
thickness of 250 μm after the ablation. Some surgeons
Ideally pupil diameter is measured by infra-red
use pachometer intra-operatively to ensure the
pupillometer, but can be measured by simple pupil
measurement of the flap thickness and the residual
gauge also. The Orbscan-II gives the diameter of the
thickness. Orbscan-II uses the Placido’s reflex with
pupil by scanning technology.
scanning slit technology combined to analyze the
anterior as well as the posterior surface of the cornea
LASER-TISSUE INTERACTION (Figs 37.2 and 37.3)
enabling to detect fore-clinical early posterior
keratoconus, for which LASIK is contraindicated. Laser (Light Amplification by Stimulated Emission
Orbscan performs pachometry at 5000 points and of Radiation) is a strong beam of light, in which all
provides the thickness of the thinnest point. Special the rays are of same wavelength and they are in phase
pachometer has been developed to measure the or coherent. The atom has a nucleus and electrons
thickness of the corneal epithelium. This helps to more in circular paths in a defined distance around
measure and follow up epithelial hyperplasia after it. This distance of the electron path to the nucleus
LASIK, which is an important cause of regression. defines the energy level of the electrons. It is possible
to add energy to one electron to lift it to a higher
which corresponds energy level at 6.4 eV.5 Excimer
means ‘excited dimer’, that is, excited atom of a
mixture of two rare Halogen gases. In LASIK they
are Argon and Fluorine. It has a wavelength of 193
nm. It is highly absorbed by water in corneal tissue.
Interaction time is short, from nanoseconds (10-9 Sec)
to microseconds (10-6 Sec). It has no thermal effect or
shockwave, but breaks molecules to result ‘photo-
ablation’. The energy of a single photo (6.4 eV/
193 nm) is about twice as high as the binding energy
of the molecules of the cornea (3.5 eV).6 The photo-
ablation is achieved within a reasonable energy
density range of 50 mJ/cm 2 to 300 mJ /cm 2. A
Fig. 37.2: Movement of photons of laser beam thickness of 0.25 μm of corneal tissue is ablated per
shot. Therefore to remove 1 μ corneal tissue it requires
4 shots.
orbit by electricity or flash light. This is the excited
In LASIK, the flap thickness is about 160 μm and
state of the atom and is unstable. When the atom
the minimum thickness at the base to be left is 250 μm.
returns to the stable state, the electron returns back
Therefore, minimum of 410 μm (160 + 250 μm)
to the orbit and the extra energy is emitted as light
thickness of the cornea is preserved at the center.
i.e. photon. This photon stimulates another atom and
Therefore, tissue that can be ablated is equal to
the process continues to produce more photons.
minimum corneal thickness minus 410 μm. Tissue
These photons leave the laser medium through one
thickness (T) that is to be ablated for a given power
of the two mirrors, which is partly reflecting.
(D = Diopter) and optical zone (H in mm) is calculated
Shorter the wavelength means higher photon
by Munnerlyn formula, T = (DH2)/3.7 Here, T is
energy. The energy of photon is measured in atomic
limited by pachometry reading and H is limited by
units. The energy of 1 eV (Electron Volt) corresponds
pupil diameter.
to 1239 nm (Infra-red). Therefore, the Excimer Laser
with Argon and Fluorine emits light at 193 nm (UV)
Fig. 37.3: Action of photon energy on the corneal tissue

Fig. 37.4: Lasik optics
FLUENCE TEST
Fluence test is a safety procedure to check the energy
and homogeneity of the laser delivery system of the
machine before every case. Under a given room
condition (temperature between 15 and 25°C and
humidity between 25 and 50%) and energy level
(120 mJ/cm2), the excimer will cut or ablate a thickness
of 0.25 μm of the corneal stroma. The Chiron—
Technolas fluence plate has an orange plastic plate
with an aluminium foil of thickness of 10 μm. The
laser must perforate the foil by 65 shots. If number
of shot required is more than 65, then the energy
level is low and is to be increased by the right shift
key of the computer. It is so precise that 65 shots Fig. 37.5: Laser Delivery
perforating aluminum foil to expose orange color of
the plate confirms energy density of 120 mJ/cm2. The moves away from a predefined range. The system
color change shows the homogeneity of the entire consists of infra-red illumination system, which
beam diameter. The present double spot fluence test projects on the cornea after lifting the flap. An infra-
also checks the scanning ability of the machine (Figs red camera takes the picture of the eye and calculates
37.4 and 37.5). the center of the pupil, utilizing the contrast between
the iris and the pupil. Once the image and center is
EYE TRACKING locked in the computer, the camera takes a number
The laser beam must hit the corneal surface of photographs of the eye per second (120 shots/min
perpendicularly at the center. During laser delivery in Technnolas 217°C). Whenever the eye moves, the
inadvertent movement of the eye by a non- image data received by the camera controls the
cooperative patient may result into decentration and movement of the scanning mirror to maintain laser
induced astigmatism. An eye tracking prevents these delivery in the center of the cornea. In Technolas
complications. In active Eye Tracker, the laser beam 217°C the beam follows the eye movement upto 3
follows the eye-movement and in passive Eye mm and beyond which the laser is blocked.
Tracker, the laser beam is blocked when the eye
LASER DELIVERY SYSTEM
The three major laser delivery systems used are:
1 Broad beam or wide field ablation
2 Scanning slit ablation
3 Flying spot or scanning spot ablation
BROAD BEAM (Fig. 37.6)

Broad beam laser uses beam of reducing diameter to
remove different layers. Advantages are—short
duration, forgiving on decentration and eye tracker
is not necessary. Disadvantages are—results central
island (dia), only used for myopia, high shockwave
and higher maintenance.
SCANNING SLIT
It uses a diaphragm to produce a rectangular beam
with changeable dimensions. This is then used on
the cornea by means of linear or rotational movement
to treat several areas of it, without overheating.
Advantages are— no central island, smoother ablation
surface, and lower shockwave. Disadvantages are— Fig. 37.6: Broad beam—central Island
it is a slower process and requires an eye-tracker.
FLYING SPOT
The flying spot technique utilizes a small beam of 1.2
nm diameter to ablate a small tile of tissue per pulse
randomly to avoid overheating. Advantages are—
no central island (Fig. 37.7), low shockwave, low
maintenance, can treat myopia, hypermetropia and
astigmatism and no optical zone limitation.
Disadvantages are—slowest, eye-tracker is required
and high repetition rate is necessary.
MICROKERATOME (Table 37.1)

The Microkeratome is required to make a corneal
flap to facilitate intra-stromal corneal ablation in
LASIK. It creates a uniform and smooth flap of precise
thickness and diameter, by cutting through the Fig. 37.7: No central Island
corneal stromal lamellae. It consists of a powered
blade driven by electromechanical system and
activated by a fool pedal. The newer keratomes under LASIK PROCEDURE
development are Medjet Hydroblade Keratome Operating Room Preparation
which utilizes water jet technology and ‘Laser
Microkeratomes’, e.g. ‘Femtosecond Laser An optimal operating room environment and practice
Microkeratome’ and ‘Novatec Laser Microkeratome’ of aseptic surgical technique are extremely important
which utilizes picosecond infra-red laser to result for Lasik. The room temperature should be between
intra-stromal photo-disruption, eliminating the need 15 and 25 degree Celsius (round the clock OT air-
of a suction ring and a blade. conditioning), humidity should be between 25 and
50 percent (use of dehumidifier) and the air should
be particle free (use of filtration unit). Uninterrupted
Table 37.1: Microkeratomes for LASIK
292
Microkeratome Function Cutting Blade Oscillations Advance rate Flap Flap
mechanism angle per minute diameter Depth
Conventional Automatic Stainless steel 26º 8,000 3.7 mm/sec Variable 160 μm
Bausch and Lomb blade up to 9.0 mm
Surgical
Automated
corneal shaper
Bausch and Lomb Automatic Stainless steel 25º NS NS Fixed at 160 μm or 180 mm
Surgical Hansatome blade 8.5 or 9.5 mm
Microkeratome
Herbert Schwind Both Stainless steel 30º 11,000 16.6º/sec 7.0-10.0 mm 160 mm or 180 mm
Supratome blade
Innovative Automatic Stainless steel NS 24,000 1.0-4.0 mm/sec 8.9-9.2 mm 130,160 or 190 mm
Optics blade (myopia) or
Innovatome 9.4-9.6 mm
(hyperopic)
Mastel Precision Surgical Manual Crystal diamond >50º 0 Adjustable 9.1 mm (myopia) Fixed at 160 μm
Instruments Buzard automatic 10.0 mm (hyperopic)
diamond Barraqueratome
Med-logics ML Automatic Stainless steel 24º 9,000-15,000 3.5-5.0 mm/sec 8.0-10.0 mm 160 μm, 180 μm
Microkeratome A blade
Micra micratome Manula Stainless steel 25º Variable NA Up to 130 μm,160 μm,
Advanced Corneal/ blade cartridge up to 15,000 10.0 mm 200 μm
Refractive Instru-
mentation (ACRI)
Modal 7000
Section 3: Diseases of Cornea
Moria LSK one Manual Stainless steel 25º 14,000 NA 7.0-10.0 mm Precalibrated:
blade 130 μm, 160 μm, 180 μm
Moria LSK Manual or Stainless steel 30º 14,000 3.7 mm/sec 7.0-10.5 mm Precalibrated: 160,180 mm
Carriazo Barraquer Automatic blade (automatic)
New United Manual Stainless steel 25º 15,000 NA Variable 130-150 μm
Development Corp blade up to 10.0 mm
Turbokeratome
(SCMD)
Summit Krumeich- Automatic Steel blade 26º 1-20,000 rpm 0.1-3.0 mm/sec 8.0-10.0 mm 130,160,180 μm
Barraquer
Microkeratome
Contd...
Contd...
Microkeratome Function Cutting Blade Oscillations Advance Flap Flap
Mechanism angle per minute rate diameter Depth
Disposable
Katena Products Inc. Manual Stainless steel 25° 20,000 NA 8.5 or 9.5 mm 160 μm
Barron Microkeratome blade
Laser sight- Automatic Stainless steel 26° 10,000 4.5 mm 8.5-9.5 mm 130 or 160 μm
Automated blade
disposable Keratome
Moria LSK one Manual Stainless steel 25° 14,000 NA 7.0-10.0 mm Precalibrated: 160,180 μm
disposable blade
Solan ophthalmic Automatic Stainless steel 26° 12,500 6.8 mm/sec 8.5 mm or 130-220 μm
products Flapmaker blade 10.5 mm
Water jet
Medjet hydroblade Automatic Circular water NA NA NA Adjustable Adjustable
keratome beam up to 9.0 mm
Visijet Automatic Water beam NA NA 6.7 mm/sec 7.0-11.0 mm 120-200 μm

hydrokeratome
Laser
Intralase femtoecond Automatic Laser NA NA NA 10.0 mm Variable
laser Microkeratome photodisruption
Novatec laser Automatic Transmissive NA NA NA Creates Infinitely

Chapter 37: Laser-Assisted In Situ Keratomileusis (LASIK)
microkeratome wavelength Laser intrastromal adjustable

bubbles and flaps
NA-Not applicable
NS-Not supplied by
company
293
power supply system (UPS) should be available.
Laser Machine Preparation

After electrical connection, the machine is switched
on. Fluence test is performed to assess laser energy.
If it is low, gas exchange from reservoir to the
activation chamber is done by the computer and
fluence test is performed again as described earlier.
The patient’s filial data and treatment parameters like
refractive power, optical zone, flap thickness, flap
diameter, etc. are fed to the computer, which then
calculates the residual thickness, number of shots and
time in second required. If the residual thickness is
below 250 microns, the optical zone diameter is to be Fig. 37.8: Hansatome Power console
reduced, which again is restricted by the pupillary
diameter. Thus, the laser machine remains ready to
deliver adequate laser during the surgery on pressing
the foot-pedal.
Surgeon Preparation
Surgeon preparation for LASIK is the same as for
any intraocular procedure: surgical scrubbing, using
of mask, cap, gown and powder-free gloves.
Instrument Preparation (Figs 37.8 to 37.12)

The Microkeratome console is switched on. The
Fig. 37.9: Suction ring handle
suction tube is connected to the console on one end.
The other end is connected to the handle of the suction
ring (it comes in 8.5 and 9.5 mm diameter). Suction is
tested by switching the foot-pedal of the console for
vacuum build-up and tested by the holding of a
sterilized rubber ball. A disposable metallic blade is
taken out from its plastic container by blade handling
pin and engaged into the slot of the metallic motor
head (three heads in Hansatome, with different plates
to create a flap thickness of 160, 180 and 200 microns).
The blade is moved side-wise to ensure freeness in
its movement as it oscillates while advancing through
the cornea. The right or left adapter is fitted to the
head according to the eye to be operated. The head
is then connected to the handle and the console. The Fig. 37.10: Blade being loaded onto head
microkeratome is run dry and in absolute alcohol
forward and backward free as well as on the track
Ringer Lactate and distilled water.
of the suction ring by foot-pedal. The power required
can be read on the console during the trial. Other Patient Preparation
instruments required in LASIK are, lid speculum,
corneal marker, gentian violet, cellulose sponge, Preoperative broad-spectrum antibiotics are used
corneal spatula, flap protector, irrigation cannula, topically into the eye 2 to 3 days prior to the surgery.
Barraquer tonometer, temperature and humidity On the day of the surgery face and the eyes are
gauze, steridrape, disposable syringe with BSS or washed with soap-water. 5 to 10 minutes before
head. No salt solution should be used, as the crystals
on the track may obstruct the movement of the
microkeratome. Intra-operative tonometry is
performed with Barraquer’s tonometer. The
applanated area should be within the mire inscribed
on it. It indicates that, the IOP is above 65 mm of Hg.
A good suction and a high IOP are pre-requisites for
the cut with the microkeratome to give a smooth and
precise corneal flap. The head of the microkeratome
is engaged to the suction plate and it is moved
forward and backward pressing the proper foot-
pedal switches. After the complete reverse cut, the
vacuum of the suction ring is released and the
Fig. 37.11: Hansatome head with R/L adapter microkeratome is disengaged. The flap, thus created,
is flipped over the perilimbal conjunctiva using a blunt
spatula or a forceps. The exposed corneal stromal
surface is wiped dry with a cellulose sponge. Then,
the infra-red illuminator is pulled near the cornea
and the eye tracker14 is switched on to lock the aiming
beam of the laser to the center of the pupil by the x,
y, z movement of the patient’s table and the
computer. Pre-programmed laser is delivered by
pressing the foot-pedal. Too dry a cornea will result
over-correction and too wet a cornea will result
under-correction. Care must be taken during ablation
to protect the hinge of the flap. After completion of
ablation, the stromal bed is wet with a drop of BSS
Fig. 37.12: Hansatome head connected to motor handle or Ringer lactate and the flap is repositioned with a
firm stroke away from the hinge. The interface is
irrigated to remove all the debris. The flap is
surgery, one drop of 0.5% Proparacaine or 4% smoothened by sweeping the cornea away from the
lidocaine is instilled into the eye to be operated. The hinge with a cellulose sponge. The edge is aligned
patient wears a cap and a gown in the OT. The patient following the proper alignment of the pre-placed
lies on the bed with the head under the laser head of
the machine. The chin and the forehead should be in
the same level i.e. the laser beam should be
perpendicular to the cornea. The skin of the lids and
the conjunctival sac be sterilized with 5% Povidone
iodine and draped. Just before the application of the
speculum one more drop of topical anesthesia is
instilled. The cornea is marked in the mid periphery
by a corneal marker using gentian violet or methylene
blue.
This helps in proper repositioning of the corneal
flap at the end of surgery or in case of accidental
free-cap. The suction ring is applied centering the
visual axis (center of the pupil) and the foot-pedal is
pressed to allow vacuum to build up and fix the globe.
The patient is informed about pressure sensation and
blurring of vision. A drop of distilled water is applied
on the cornea before engaging the microkeratome Fig. 37.13: Corneal marking
marks. The peripheral gutter is dried with a dry

cellulose sponge to facilitate adhesion of the flap to
the stromal bed. After 1-2 minutes peripheral cornea
is depressed and the translation of the resultant striae
onto the flap is taken as evidence of optimal adhesion
(striae test). The speculum and drape are carefully
removed. The patient is asked to blink to reconfirm
correct repositioning of the flap. A drop of antibiotic,
NSAID and artificial tear are instilled.
Complications of LASIK
LASIK is a surgical art demanding meticulous
attention, high order of surgical skill and strict
adherence to surgical protocol to achieve a high rate
Fig. 37.14: Application of corneal suction ring of success and to avoid all possible complications.
The complications of LASIK may be related to
i. Laser ablation
ii. The microkeratome
iii. Handling of the flap
iv. Healing
These complications can best be grouped into Pre-
operative, intra- and post operative.
PREOPERATIVE
1. Excessive application of topical anesthetic can
cause epithelial edema and sloughing.
2. Application of drape and/or speculum may cause
abrasion to the corneal epithelium
3. Corneal marking with gentian violet may cause
corneal epithelial toxicity
4. Inadequate exposure may lead to inadequate
Fig. 37.15: Barraquer Tonometer
suction resulting in various intra-operative
complications.
INTRAOPERATIVE
1. Incomplete flap is formed due to incomplete pass
of the keratome blade. It can occur due to
inadequate intra-ocular pressure buildup,
premature release of foot-pedal of the hansatome
or release of suction. Surgery can be performed
after 3 months with a thicker footplate.
2. Irregular flap is formed due to inadequate suction.
In steep cornea, there may be formation of ‘central
buttonhole’. In steep cornea (> 46D) a deeper
depth plate should be used.
3. Free cap is encountered if LASIK is performed on
Fig. 37.16: Intraoperative tonometry a flat cornea (<41D).
4. Bleeding from limbal vessels in a large diameter ethylene oxide, cleaning solution residue,
flap or due to corneal neovascularization in long blepharitis, meibomian gland secretion, tissue
term contact lens wearer can occur. Merocel debris, gentian violet, RBC, sponge residue to oil
sponges are used to tamponade the bleeding. It from the motor head of the microkeratome.13
may cause flap staining. 5. Optical complications may be:
5. Other intraoperative flap related complications • Decentration
are- • Irregular or induced astigmatism
• Flap damage by handling or instrumentation • Over/under correction
• Flap wrinkling due to drying • Regression
• Flap dislocation. • Central island
6. Inadequate irrigation under the flap may result • Glare and Halos11
in interface debris 6. Corneal ectasia is a progressive regression with
7. Complications related to inadequate laser delivery steepening of the corneal curvature resulting from
may occur due to mechanical problems of the the removal of a large chunk of stromal tissue by
machine. ablation. It is prevented by maintaining a residual
stromal bed thickness of > 250 μm.
POSTOPERATIVE COMPLICATIONS REFERENCES
1. Flap displacement can occur post-operatively 1. Barraquer JJ. Results of myopic keratomileusis. J Refract Surg
induced by trauma. It should be lifted, irrigated 1987;3:98.
and repositioned. 2. Trockel S, Srinivasan R, Braren B. Excimer laser surgery of the
2. Epithelial ingrowth is due to seeding of epithelium cornea. Am J Ophthalmol 1983;94,125.
3. Pallikaris IG, Papatzanaki ME, Siganos DS et al. A corneal
in the interface or due to irregularity or folded
flap technique for laser in situ keratomileusis. Arch Ophthalmol
edge of the flap. It may manifest as an island or a 1991;109:1699.
cyst or a translucent sheet. 4. Signos DS, Pallikaris IG. Laser in situ keratomileusis in partially
3. Infection or infective keratitis is a rare sighted eye. Invest Ophthalmol Vis Sci 34: 800, 1993.
complication of LASIK, but should be treated 5. Chiron Technolas/Application. 1996;1/1-1/3.
adequately. The flap must be lifted, irrigated and 6. Chiron Technolas / Application. 1996;3/1-2/3.
7. Rasik B Vajpayee. Handbook of Lasik Surgery. Jaypee Brothers
materials sent for staining, culture and sensitivity
Medical Publishers: New Delhi. 2000;39.
test. 8. Smith JR, Maloney RK. Diffuse lamellar keratitis – a new
4. Diffuse lamellar keratitis reported first by Smith syndrome in lamellar refractive surgery. Ophthalmology
and Maloney8 is also called “Sands of Sahara” 1998;105,1721.
syndrome. It is characterized by diffuse, 9. Hoffman RS, Fine IH, Packer M. Incidence and outcome of
multifocal, non-infectious infiltrates in the LASIK with diffuse lamellar keratitis treated with topical and
oral corticosteroids. J Cataract Refract Surg 2003;29,451.
interface. Hatsis classified it into four grades.
10. Lackner B, Pich S, Schmidinger. Glare and halo phenomena
Grade I localized superior infiltrate; Grade II the after laser in situ keratomileusis. J Cataract Refract Surg
infiltrate spreads to involve the entire interface; 2003;29, 444.
Grade III dense opaque infiltrate with flap edema 11. Arevaldo JF, Ramirez E, Suarez E. Rhegmatogenous retinal
and in Grade IV there is flap melting with lid detachment in myopic eyes after laser in situ keratomileusis. J
edema and anterior chamber reaction. It appears Cataract Refract Surg 2001;27,674.
12. Peraz – Gomrez, Efran N. Confocal microscopic evaluation of
within 2 to 6 days after LASIK. Grade I and II are
patients at the corneal flap interface after myopic laser in situ
treated with hourly topical steroids. In Grade II keratomioleusis. J Cataract Refract Surg 2003;29,1373.
and IV the flap should be lifted and irrigated and 13. Chitkara DK, Rosen E, Gore C et al. Tracker assisted laser in
brushed with Merocel sponge to remove the situ keratomileusis for myopics using autonomous scanning
infiltrates. It’s exact etiology is not known; but and Tracking. Ophthalmology 2002;109,965.
may be due to any cause like thermal injury,
Chapter 38
Limbal Transplantation
of Stem Cells
Anita Panda, Namrata Sharma
The corneal epithelium is a renewing tissue that loses the source of stem cells generating the renewing
its surface cells to the tear film, maintaining a five to corneal epithelium.
six layered cellular structure. The origin of these cells, The stem cell population is broadest at the upper
however, has been poorly understood. There are other and lower limbal poles and gradually narrowed
renewing cell populations of the body that have been around the limbus to the horizontal. Based on the
investigated much more extensively; in particular, the observation of vortex patterns of the corneal
epidermis, intestinal epithelium, blood-forming epithelium in conditions like toxic keratopathy, striate
organs of the body, and spermatogenesis.1,2 In each melanokeratosis, Fabry’s disease, and superfical iron
of these tissues, stem cells are believed to generate lines of the cornea, it was postulated to be a radial,
their own kind and transient amplifying cell (TAC). centripetal slide of epithelial cells, the limbal
TACs give rise to post-mitotic cells (PMC), which epithelium.
terminally differentiate into the mature cell type. Using monoclonal antibodies AE-5, Schirmer 4
showed that a 64K keratin, typical for the corneal
epithelial phenotype, labeled all of the corneal
ABOUT THE STEM CELLS
epithelium except the superficial layers of the limbal
Stem cells have certain characteristics that are common epithelium. The deep limbal epithelial layer did not
to all of the tissues. They are quite primitive, showing stain, indicating that these cells were not typically
no differentiation products within their cytoplasm. differentiated epithelial cells. Cotsarelis5 subsequently
They manifest very low mitotic activity and therefore, established a relatively slow-cycling period for these
slow cycling of the cell. Their infrequent divisions can basal limbal epithelial cells by showing retained
give rise to TAC or duplication. The TACs are the thymidine over a long period of time. Eboto6 has
mitotic factories of the tissue, producing as many as demonstrated that there is enhanced growth of
1000 terminally differentiated cells (TDC) from one epithelial cells derived from limbus compared to the
TAC. Stem cells can also be induced to proliferate by central cornea. If all of the limbal tissue is excised,
tumor-promoting agents. The exact anatomical including the peripheral edge of corneal epithelial
positions of the stem cells and their progeny as they cells, persistent epithelial defects and corneal
enter the cornea are unknown. vascularization will develop when the cornea is
The clinical anatomy of the limbus was observed subsequently subjected to trauma.7 There is no direct
in 1921 by Vogt3 who described ridges present in the histologic proof that stem cells exist. There are,
perilimbal conjunctiva perpendicular to the cornea. however, compelling immunohistologic findings by
The significance of this observation did not become Zieske8 who was able to produce a monoclonal
evident until 1971 when studies by Davanger and antibody to the 50K keratin believed to be specific for
Evanson suggested that these perilimbal arrays were stem cells. The fluorescent marker of this reaction
Chapter 38: Limbal Transplantation of Stem Cells 299
stains the basal epithelial cells straddling the limbus Table 38.1: Categories of corneal stem cell diseases
0.5 mm on the cornea and about 1.0 mm on to the I. Unequivocal corneal stem cell loss
perilimbal conjunctiva. The absence of stain of a. Alkali injuries
postmitotic and terminally differentiated corneal and b. Other chemical injuries
conjunctival epithelial cells confirms the conviction c. Dry eye
that stem cells reside only in basal layers of the d. Excision of neoplasia
e. Extensive limbal surgery.
perilimbal epithelium.
The half-life (time needed for replacing half of all II. Probable stem cell disease
A. Naturally occurring
pre-existing cells) for the corneal epithelium is
a. Ocular cicatricial pemphigoid
predicted at about 9 weeks. Also, the normal corneal b. Aniridia
epithelium of rabbit is expected to undergo an almost B. Environmentally induced
complete (95 to 99%) renewal by the progeny of the a. Erythema multiforme
limbal stem cells in about a 9 to 12-month period. This b. Vitamin A deficiency
is in agreement with the relative absence of corneal c. Nitrogen mustard
epithelial graft rejections more than 13 months after d. Herpes simplex
e. Pterygium
keratoplasty, indicating its complete replacement by
C. Iatrogenically induced
the host tissue. a. Radiation keratopathy
b. Contact lens keratopathy
CATEGORIES OF CORNEAL STEM
c. Drugs.
CELL DISEASES
III. Possible stem cell dysfunction
The recognition of the fact that there is a specific cell a. Neurotrophic keratitis
source for corneal epithelial cells, and that its function b. Cyclocryotherapy
could become damaged or deranged, it permits the c. Peritomy
identification, elucidation, and treatment of a variety
underlying stroma is preserved because acid will
of seemingly unrelated disease processes (Table 38.1).
precipitate the protein within the epithelial cells,
Unequivocal Corneal Stem Cell Loss thereby acting as a barrier to further penetration into
the eye. If the limbus is injured, corneal stem cells
Aklali-injured Eye
located in the base of 10 layers of epithelium might be
Dua and Forrester 9 reported epithelial healing protected from damage and be capable of producing
progress of 17 alkali-injured human eyes. They a perfectly normal phenotype of corneal cells when it
observed that when some viable epithelium was replicates.
present, healing was initiated from both sides of the
uninjured limbal epithelium, extending circumferen- Dry Eye
tially around the denuded limbus, until the two
Any ocular surface disorder which leads to pro-
proliferating tongue-like projections met. The central
gressive corneal scarring, vascularization, persistent
corneal epithelial defect was the last to heal; careful
epithelial breakdown like dry eye or Stevens-Johnson
observation of these patients during the healing phase
syndrome can be treated by limbal transplantation.
is extremely important and that it is probably wise to
remove any conjunctival epithelium that attempts to Excision of Neoplasia
bridge the limbus on to the cornea. This will ensure
There is substantial circumstantial evidence that
that the phenotype of the epithelium covering the
limbal neoplasms are derived from the pluripotential
cornea is entirely corneal.
stem cells located in the deep limbal epithelium.
Prolonged environmental injury from ultraviolet light
Other Chemical Injuries
or other sources induce DNA damage to corneal cells,
There are other chemical injuries that can produce an causing their neoplastic proliferation.10,11 When the
injury as severe as alkali does, for example high lesion does not entirely encompass the limbus,
concentrations of acid. Yet, most other chemical excisional biopsy eliminates the tumor but leaves
injuries, such as weak acids, might opacify the residual limbal stem cells behind to grow and renew
epithelium and cause it to be lost as a sheet while the this population. A neoplasm that encircles the cornea
underlying stroma remains clear. In these cases, the requires complete excision, removing all stem cells,
even those that might still be producing normal Herpes simplex Herpes keratitis causes a variety of
corneal epithelial cells. The result of such a complete epithelial defects which are persistent and fail to
excision is persistent corneal epithelial defects and respond to any form of treatment. Although
vascularization with an irritable, non-seeing eye. unproved, there appears to be a fatigue of the corneal
stem cell system, explaining the intractability of these
Extensive Limbal Surgery ulcers.
Extensive limbal surgery that may be undertaken for Pterygium Ultraviolet14 rays and other environmental
benign tumors like limbal dermoid or cataract surgery injuries are likely to damage the narrow band of limbal
may produce limbal stem cell deficiency. stem cells present temporally and nasally. One recent
theory suggests that when that barrier is broken,
Probable Stem Cell Diseases conjunctival epithelial cells are allowed to stream on
to the adjacent cornea, encouraging blood vessel
Naturally Occurring
ingrowths.15 A second point of view holds that
Ocular cicatricial pemphigoid: The autoimmune process “altered” stem cells proliferate at the limbus and spill
associated with ocular cicatricial pemphigoid (OCP) out onto the cornea, releasing vasoproliferative agents
is directed at the basement membrane zone of the and encouraging pannus ingrowths.
ocular epithelium, resulting in a separation within the
lamina lucida between the plasma membrane of the Iatrogenically Induced
basal cells and the electron-dense lamina densa.12
Radiation keratopathy Damage to the lacrimal and
Subconjunctival scarring progresses with
accessory lacrimal glands and conjunctiva have
symblepharon formation. In this disease process, it is
adverse effects on the production and stability of the
probable that the stem cells of the corneal epithelium
tear film. It is difficult to discriminate radiation
are eventually destroyed. It is likely that stem cell of
damage to corneal stem cells when damage to other
conjunctiva located within the fornices might also be
tissues strongly influences the outcome. Radiation
destroyed, creating a loss in the replicative capacity
exposure16 primarily damages cells during their
of the conjunctival epithelium.13
mitotic phases and is least damaging to these cells at
higher levels of differentiation. Relatively mild to
Environmentally Induced
moderate degrees of radiation of the eye will probably
Erythema multiforme: The major form of this disease reduce the rapid turnover of the corneal TACs causing
and its extreme, toxic epidermal necrosis, have been a temporary epithelial defect on the corneal surface
strongly associated with exposure to drugs or until corneal stem cells generate enough TAC to
infections. Extensive subepithelial microvasculitis and repopulate the cornea.17
bullae are believed to contain toxic products causing
Contact lens keratopathy Defects of the corneal epithe-
massive exfoliation of the epidermis and the mucous
lium, vascularization, and scarring are reported in this
membranes of the mouth and eyes.12 Lifelong ocular
condition.
disease is not uncommonly associated with persistent
epithelial defects, ulceration, vascularization, scarring, Drugs Various topically applied and systemic medica-
and, occasionally, perforation of the eye. tions have been shown to have an unfavorable effect
on corneal epithelium: Anesthetics like practolol, are
Vitamin A deficiency: Deficiency of vitamin A is likely
associated with an idiopathic response of irritated
to have a widespread effect on many processes of
eyes, persistent epithelial defects, scarring, and
epithelium, including an inhibitory effect on mitotic
vascularization in 0.2 percent of users.18,19
activity of the corneal stem cells and/or the TAC.
Nitrogen mustard: The more severe injuries showed Possible Stem Cells Diseases
porcelain-like conjunctival ischemia at the limbus,
Neurotrophic Keratitis
epithelial defects, infiltration of inflammatory cells and
ulceration. Repeated corneal ulcers resulted in Loss of corneal sensation often results in chronic
progressively vascularized corneal scars. When the defects of the corneal epithelium.20 The corneal epithe-
injury was severe, a prolonged period of healing was lium is believed to require neurogenic stimulation for
required. the normal renewal process, possibly by the release
Chapter 38: Limbal Transplantation of Stem Cells 301
of substance P. Corneal denervation might deprive the conjunctival and hence, probably did not include
corneal epithelium, and particularly the corneal stem corneal stem cells.
cells, of a required stimulatory agent.20,21
Autogenous Stem Cell Transplantation
Cyclocryotherapy
To treat pterygium, Kenyon and colleagues have
When cyclodestructive procedures are used to treat advocated limbal autografts from the superior
glaucoma, the overlapping freeze zones subject the quadrant of the same eye, transplanted into their
corneal stem cells to repeated freeze-thaw, potentially anatomically corrected position, to cover the bare
damaging or destroying a substantial number of cells. sclera of the excised pterygium base.23 Using the
technique in 57 eyes of 54 patients (of which 16 were
Peritomy primary and 41 were recurrences) the recurrence rate
was only 5 percent. An autograft was repeated in two
When diabetics undergo retinal detachment proce-
of the unsuccessful cases, with no recurrence making
dures, a peritomy is commonly performed, and, where
the final outcome virtually 100 percent successful. In
necessary, intraoperative removal of the corneal
these cases, it was thought that the barrier to
epithelium when it becomes edematous to allow
conjunctival cell invasion of the cornea was reinstated
visualization of the posterior pole. Postoperative
with a limbal stem cell transplant.
persistent epithelial defects are common in such
Kenyon et al24 also performed limbal autografts in
conditions.
20 chemically injured eyes, two thermal injuries, three
keratopathies induced by contact lenses, and one
TREATMENT OF STEM CELL DISEASE
surface failure. Of 21 patients followed over a 6-month
Treatment of stem cell disease must begin with period, 17 showed improved vision, 19 rapid healing,
removal of any noxious elements that might further 20 with stable adhesion, 5 with arrested vessels, and a
damage this tissue. Subsidence of any unnecessary subsequent successful penetrating keratoplasty in
drug treatment, contact lenses, and waiting for eight.
quiescence of inflammatory disease processes, such
as alkali injury, are reasonable approaches. Specific Corneal Stem Cell Autotransplantation
treatment of stem cell disease at this time is achievable
The extent of the lesion is demarcated with cautery
only by transplantation of corneal stem cells into the
and then excised completely. Three stem cell
limbus of the deficient eye. There are the following
transplants may be obtained from the limbus of the
possible sources of tissue, i.e. bulbar conjunctiva or
other eye and sutured equidistant around the limbus
limbal stem cells obtained autologously,
of the recipient eye. Postoperatively, these autografts
homologously, or cultured:
grow a normal donor epithelium on to the recipient
cornea with an intact and clear epithelium lacking
Bulbar Conjunctival Transplantation
vascularization, scarring, or epithelial breakdown.
To remove the vascular scar resulting from alkali
injury, Thoft performed a complete superifical Corneal Stem Cell Homotransplantation
keratectomy followed by bulbar conjunctival
There are patients in whom the disease affects both
transplants into the limbal area.22 In the series of 12
eyes so that no autologous corneal stem cells are
chemical or thermal burns, followed for a period of 2
available. These patients have few other alternatives
to 5 years he was able to achieve improved vision in
to homotransplantation of limbal stem cells.
eight eyes while vision was unchanged in one and
Homologous tissue containing corneal stem cells
decreased in three. In the same report, persistent
persists and gives rise to viable stem cells on the
epithelial defects were treated with limbal transplants
recipient cornea.
in three eyes with chemical injuries and two with
chronic herpetic infections. In all five eyes, a stable Surgical technique A button hole is fashioned in the
epithelial surface resulted with improved vision in conjunctiva which is then undermined beyond the
three. Our current knowledge of stem cell disease limbus. This allows maximal retention of conjunctiva,
makes it difficult to explain how he achieved such which is allowed to slip out to a position 3 to 4 mm
success, given that his autotransplants were beyond the limbus. This process is assisted with
strategically located relaxing incisions. When the culture suggests limbal location of corneal epithelial stem
vascularized surface tissue is strongly adherent to the cells. J Cell Biol 1986;103:49-62.
5. Cotsarelis G et al. Existence of slow-cycling limbal epithelial
underlying tissues and cannot be elevated, it is scraped basal cells that can be preferentially stimulated to proliferate:
off with a surgical blade. The corneal and conjunctival implications on epithelial stem cells. Cell 1989;57:201-09.
resection sites are kept moistened while the donor 6. Ebto B, Friend J, Thoft RA. Comparison of central and
tissue is obtained. peripheral human corneal epithelium in tissue culture. Invest
The conjunctiva is obtained from a donor in whom Ophthalmol Vis Sci 1988;28:1450-56.
7. Huang AJW, Tseng SCG. Corneal epithelial wound healing
the cornea had been used in the preceding case. The in the absence of limbal epithelium. Invest Ophthalmol Vis
donor conjunctiva is thinned by reflecting the Sci 1991;32:96-105.
conjunctiva over the cornea and excising the tenon’s 8. Zieske JD, Bukusoglu G. Characterization of a potential
capsule. The conjunctiva is then incised as close to the marker of corneal epithelial stem cells. Invest Ophthalmol
Vis Sci 1991;33(1):143-52.
limbus as possible and cut from its insertion into the
9. Dua HS, Forrester JV. The corneoscleral limbus in human
cornea. The specimen is spread out on to a moistened corneal epithelial wound healing. Am J Ophthalmol 1990;110:
paper and transported to the surgical site where it is 646-56.
draped around the limbus. It is sutured in its 10. Applegate LA, Ley RD. DNA damage is involved in the
anatomically correct position at the limbus using a induction in opacification and neovascularization of the
cornea by ultraviolet radiation. Exp Eye Res 1991;52:493-97.
vertical mattress 9-0 nylon suture encircling the 11. Ley RD et al. Photoreactivation of ultraviolet radiation-
limbus. It is tied in one position to create a single induced skin and eye tumors of Monodelphis domestics.
continuous suture. Cancer Res 1991;51:6539-42.
12. Mondino BJ. Cicatricial pemphigoid and erythema
Transplantation of Cultured multiforme. Ophthalmology 1990;97:939-52.
13. Wei ZG et al. In vitro growth and differentiation of rabbit
Corneal Limbal Stem Cells bulbar, fornix, and palpebral conjunctival epithelia. Invest
Ophthalmol Vis Sci 1993;34:1814-28.
There is some controversy whether stem cells might
14. Taylor HR et al. Corneal changes associated with chronic UV
be cultured on a transplantable substrate, in an irradiation. Arch Ophthalmol 1993;107:1481-84.
artificial medium, and then transplanted into the 15. Tseng SCG. Concept and application of limbal stem cells. Eye
deficient eye. Human limbal stem cells have been 1989;3:421-57.
shown to survive in a subdermal mouse model, produ- 16. Fowler J, Denekamp J. Regulation of epidermal stem cells. In
Carnie A, Lala P, Osmond D (Wds): Stem Cells of Renewing
cing cells that are immunologically of stem cell type. Cell Populations. Academia Press, New York, 1989;117-34.
Another study showing the inhibition of rabbit corneal 17. Ching SV et al. Radiation-induced ocular injury in the dog: A
stem cells by hydrocortisone in vitro suggest that these histological study. Int J Radiat Oncol Bio Phys 1990;19:321-
cells might not retain their stemness and only perform 28.
as stem cells in their limbal niche.25 Indeed, if stemness 18. Wright P, Fraunfelder FT. Practolol-induced oculomucocuta-
neous syndrome. In Leopold IH, Burns RP (Eds): Symposium
is not possible to retain in vitro then animals might be on Ocular Therapy, John Wiley and Sons, New York, 1990;97-
considered as temporary vehicles for tissue transfer. 110.
These proposals are well within existing technology 19. Yang JS et al. Biphasic effects of hydrocortisone of the stem
and merit research attention. cells and transient amplifying cells of rabbit corneal
epithelium. Invest Ophthalmol Vis Sci 1993;34(4):1012.
20. Duke-Elder S. System of Ophthalmology. Diseases of the
REFERENCES Outer Eye. 2, (Volume 8), CV Mosby: St Louis, 1965;803-10.
21. Butler JM, Hammond BR. The effects of sensory denervation
1. Hall PA, Watt FM. Stem cells. The generation and of the response of the rabbit eye to prostaglandin EI.
maintenance, of cellular activity. Development 1989;106:619- Bradykinin and substance P. Br J Pharmacol 1980;89:335-39.
33. 22. Thoft R. Indications for conjunctival transplantation. Ophthal-
2. Potten CS, Schofield R, Lajtha LG. A comparison of cell mology 1982;89:335-39.
replacement in bone marrow, testis, and three regions of 23. Kenyon Kr, Tseng SCG. Limbal autograft transplantation for
surface epithelium. Biochemica et Biophysica Acta ocular surface disorders. Ophthalmology 1989;96:709-23.
1979;560:281-99. 24. Kenyon KR. Conjunctival autograft transplantation for
3. Vogt A. Textbook and Atlas of Slit Lamp Microscopy of the advanced and recurrent pterygium. Ophthalmology
Living Eye. 3 ed (Volume I). Bonn-Bad Godesberg, Germany: 1989;92:1461-70.
Wayenborgh, 1921;52-53. 25. Lindberg K et al. In vitro propagation of human ocular surface
4. Schirmer A, Gavlin S, Sun TT. Differentiation-related epithelial cells for transplantation. Invest Ophthalmol Vis Sci
expression of a major 64K corneal keratin in vivo and in 1993;34:2672-79.
Chapter 40
Scleritis and Episcleritis

JS Saini
Episcleritis and scleritis are common diseases and Table 40.1: Classification of episcleritis and scleritis
present all age groups.1 The incidence is estimated at
Episcleritis
about 0.08%.2 Clinicians have often a difficulty in
• Diffuse
confirming involvement of sclera when overlying • Nodular
tissues are also inflamed. Posterior sclera inflamma-
tion is particularly difficult to diagnose because there Scleritis (Anterior, posterior or both)
• Diffuse
may be no characteristic visible signs in the retina or
• Nodular
choroid and all that the patient is complaining of is • Nectrotizing
loss of vision; for, although severe pain is usually a — With inflammation
feature of posterior scleritis, the condition can occur — Without inflammation
without any pain at all.
or diffuse episcleritis and nodular episcleritis.

CLINICAL DEFINITIONS AND CLASSIFICATION
Clinically, inflammation, which involves episclera and CLINICAL FEATURES
Tenon’s capsule without underlying oedema of the Episcleritis is a transient periodic inflammation of
sclera, is termed episcleritis. The inflammation may the episclera. It is much more commonly seen in
be diffuse (simple episcleritis), in which it affects part young women than men, is rarely uncomfortable and
or the whole of the outer covering, or it may become is never damaging to the eye. The appearance and
aggregated into nodules in which the exudate remains the prickly sensation it produces do however, cause
localized to one area (nodular episcleritis) (Table considerable distress to some patients who demand
40.1). The milder forms of scleritis follow a similar some form of treatment. Unless the inflammation is
pattern, except that there is some involvement of the very severe or prolonged, there is little point in
underlying sclera and the inflammation is more undertaking any investigations, as these are almost
intense. universally negative.3 However, a careful history
Necrotizing scleritis is quite different. In this sometimes reveals a precipitating factor, which if
condition the sclera and all its coats including the eliminated may be successful in preventing
overlying conjunctiva, become involved in a destruc- recurrences. If the attacks are prolonged beyond 21
tive granulomatous process, which if inadequately days they should be investigated in the same way as
treated will lead to the destruction of the eye and for patients with scleritis, as many of these will be
the inevitable loss of vision. One form of episcleritis found to have some underlying systemic disorder.
or scleritis does not change to another. The disease Clinically, although the redness may be very
found at presentation is the condition, which will be intense, examination reveals that the inflammation is
present in all recurrences. confined to the episcleral tissue (the conjunctival
There are two major types of episcleritis: simple vessels remain normal or are only slightly dilated).
There is no distortion of the vascular pattern, scleritis can occur without pain, particularly in sclero-
although rate of flow of blood through the vessels is malacia perforans and in some patients with posterior
increased and the vessels are more permeable. There scleritis. It is, therefore, important to consider
is no discharge or pain, only discomfort (Table 40.2). posterior scleritis as a diagnosis when faced with
In nodular episcleritis the vessels in one area of patients with loss of vision, a slightly swollen disc or
the episclera become much more permeable, allowing exudative retinal detachments.
a localized aggregation of inflammatory cells and Scleritis, like episcleritis, is a recurrent condition
exudate. As in simple episcleritis there is no undue and is usually bilateral eventually. Untreated, scleritis
discomfort, and there is no discharge from the eye. may progress destructively to cause uveitis, cataract,
A normal vascular pattern is maintained although the glaucoma, optic neuritis and even perforation of the
vessels in the area of the episcleral nodule is dilated, globe. In addition, scleritis may be a manifestation
are freely permeable and the blood flows very rapidly of potential life threatening systemic disorder. It
through them. The underlying scleral tissue is not follows, therefore, that the correct early diagnosis is
involved. Clinically the course is much the same as essential.4
with simple episcleritis but because of the localized This is done by taking a careful history to
oedema the resolution tends to be slower. Only those ascertain: the type of onset; symptoms, such as the
with very persistent disease should be fully investi- type of pain and its distribution; the presence of
gated. photophobia and watering of the eye; and symptoms
Scleritis is a painful manifestation. However, suggestive of underlying connective tissue disease.
Table 40.2: Cardinal features for differentiating scleritis from episcleritis

Episcleritis Anterior Scleritis Posterior
Simple Nodular Nodular Diffuse Necrotising Scleromalacia

Perforans
Onset Sudden Usually Gradual Gradual Gradual Insidious Gradual

Sudden
Redness Bright red Red slight Dusky red Bluish red Bluish red Very slight Variable
Pain Slight Slight Moderate Moderate Severe Slight, if any Severe localised
localised localised localised localised localised and referred
and referred and referred and referred
Photophobia Occasionally Occasionally Occasionally Occasionally Common None Unusual

and
lacrimation
Vascular Superficial Superficial Superficial Superficial Superficial Avascular Superficial

changes episcleral and deep and deep and deep episcleral area and deep
episcleral episcleral episcleral and episcleral
occasionally
avascular patch
Chemosis Occasional Rare Rare Common Variable Absent Common
Scleral Rare Rare Common Common Common Always Rare

thinning or
transparency
Visual Acuity Normal Normal Normal Occasionally Commonly Commonly Very

lost lost lost commonly lost
Chapter 40: Scleritis and Episcleritis 309
If there is any doubt, the opinion of a rheumatologist the inflammatory process. The overlying inflam-
or other interested physician should be sought. mation is much more intense than in episcleritis. This
Routine investigation of the haemoglobin levels, a sometimes causes conjunctival chemosis, so in order
differential white cell count, erythrocyte to observe the contour of the underlying sclera it
sedimentation rate, ‘C’ reactive protein, serum uric may be necessary to blanche the vessels using 10%
acid, serology for syphilis and an immunological phenylephrine drops. Having observed that the sclera
survey should be undertaken. The immunological is edematous the next important decision is whether
survey should include immunoglobulin levels, the this lesion is destructive or potentially so. This
autoantibodies, Rheumatoid Factor (RhF), antinuclear requires careful examination of the vessels as scleritis
antibodies (ANA) (DNA binding). If the physical is caused by a T-cell mediated granulomatous change
signs suggest a systemic vasculitis, anti-nuclear accompanied by a vasculitis that is sometimes the
cytoplasmic antibody tests (pANCA and cANCA) primary lesion. Initially this appears to be a venulitis,
should be performed. These investigations will reveal the arterial tree becoming involved later. The
the presence or absence of severe underlying systemic vascular changes caused by the inflammation can be
disease, which may not be apparent even on the most detected by anterior segment fluorescein
careful examination, so determining whether the angiography, as can the non-perfusion,
patient is likely to need immunosuppressive therapy vasoobliteration and re-routing of blood which
rather than treatment with anti-inflammatory agents. indicates the onset or presence of necrotizing scleritis.
Ocular examination has to be directed at deciding Anterior uveitis accompanying scleritis is extre-
whether the sclera itself, rather than just the coats of mely rare and, if cells are present in the anterior or
the eye, is involved; and if so, whether this inflam- posterior chamber, this indicates either serious disease
matory process is leading, or is likely to lead, to or the wrong diagnosis.
destruction of that tissue and those around it. The
presence of anterior scleritis can usually be deduced Diffuse Anterior Scleritis
by physical examination, but the diagnosis of
Diffuse anterior scleritis is the most benign type of
posterior scleritis is difficult because its presence can
scleritis but it is also frequently misdiagnosed leading
only be implied from its effect on the surrounding
to unnecessary pain and discomfort to the patient
tissues. Even then, severe posterior scleritis may be
and occasionally a permanent reduction in visual
present without any visible signs in the retina or
acuity.
choroid. It is only possible to examine the posterior
The main differentiating feature from episcleritis
sclera with B-scan ultrasonography, although the
is the intense pain, which radiates from the eye to
methods are not yet sophisticated enough to decide
the temple or unto the face. The pain commonly wakes
whether the choroid or sclera are involved together
the patient in the early hours of the morning,
or separately. If B-scan ultrasonography is not
gradually fading as the day progresses. The redness
available, CT scanning or MRI scanning with an orbital
can be intense and may be associated with chemosis
coil will identify the swollen tissue.
of the conjunctiva, but more commonly there is a
redness of the anterior segment. The condition is
Anterior Scleritis
usually unilateral in each attack but may affect both
Clinically, scleritis presents as a diffuse, nodular or eyes from time to time and is accompanied by some
necrotizing scleritis. It is very unusual for a condition photophobia and watering which is worse if the pain
to progress from one form to another, although some is intense.
patients in the course of this disease will have a It is often difficult to tell whether the underlying
nodular attack on one occasion and a diffuse one on sclera is swollen even after the superficial vessels
another, and the occasional person will develop have been blanched. If in doubt, the configuration of
necrosis within a large scleral nodule. Nodules can the vessels themselves should be examined with care.
sometimes be multiple but each small nodule shows In episcleritis the vessels, although dilated, retain
the same characteristics as the larger ones. their normal pattern and the capillary nets are readily
The diagnosis of anterior scleritis, which accounts visible and patent. In scleritis, however, areas of capil-
for at least 75% of all patients with scleritis, depends lary closure occur, and the venules leak and become
on the observation that the sclera itself is involved in partially or totally occluded. As a consequence the
vascular pattern becomes distorted and abnormal. the patient is inadequately treated, the sclera and
The easiest place to see these changes is the limbus, overlying episclera and conjunctiva become necrotic
where the normally completely regular capillary within a very short time. This process will rapidly
arcade becomes distorted, irregular and degenerate. extend from the site of the original lesion, especially
As these changes are permanent, an abnormality of if the vascular tree is affected. However, intensive
this network suggests a current or old attack of scleral and adequate systemic therapy will reverse the
inflammation. situation and allow healing to occur. This healing is
usually completed with fibrous tissue, but if the
Nodular Scleritis defect is too large the underlying choroid may be
exposed.
Nodular scleritis is different from nodular episcleritis.
In the early stages, low-dose anterior segment
Not only are the nodules fixed, but they are extremely
fluorescein angiography can be very helpful in decid-
painful and tender to the touch.
ing whether necrosis might occur. In necrotizing
Nodular scleritis tends to be bilateral, although
scleritis, as well as a deep leakage of dye, there are
commonly only one eye is affected at a time. The
also vaso-occlusive changes in the overlying vessels
nodules often recur at the same site and are accompa-
and a gross abnormality of the adjacent limbal. If
nied by referred pain to the head, lacrimation and
these changes are seen, urgent systemic treatment is
photophobia. They may be solitary or multiple. If
required.
the multiple nodules occur close to the limbus, they
can be accompanied by sharp rise in intraocular
pressure. Necrotizing Scleritis without Inflammation
Many patients with nodular scleritis have no (Scleromalacia Perforans)
associated systemic disease, but some who are in the The term scleromalacia perforans should be used
late extraarticular stages of rheumatoid arthritis can solely for patients who present with a necrosis of the
develop painless scleral rheumatoid nodules which sclera which is not accompanied by pain or severe
rarely require treatment and which fade sponta- ocular inflammation. Almost all patients with this
neously. If left alone, the nodule will be replaced by condition have long-standing inactive rheumatoid
fibrous tissue after treatment; but if it is removed, it arthritis. The changes in the sclera are almost always
will leave bare choroid. due to arteriolar occlusive changes, which result in
death and sequestration of the affected tissue. As
Necrotizing Scleritis the changes are irreversible, patients with this
Necrotizing scleritis is the most severe form of scleral condition do not need treatment unless the disease
disease and is almost always associated with some is seen in its very early stages or there are other
systemic disease. If misdiagnosed or left untreated, changes in the eye which call for treatment.
the patient will soon become blind, either because of
perforation of the globe or the associated compli- Posterior Scleritis
cations of keratitis, cataract or retinal edema.
Posterior scleritis is very under-diagnosed. It is not
If uveitis is present it is certain that there is serious
uncommon, but it presents in such a variety of ways
significant disease at or behind the equator of the
that it is often not considered in the differential
globe.
diagnosis of visual loss, particularly if pain is not a
prominent feature. There appear to be two major sub-
Necrotizing Scleritis with Inflammation
groupings of posterior scleritis:
The commonest form of necrotizing scleritis is 1. In young people who complain of rapidly decreas-
accompanied by severe inflammation. The onset may ing visual acuity and a variable amount of pain
be gradual, but inflammation often rises to a peak of which is often referred outside the eye. The
intensity within a week of onset. It may be either commonest physical sign is choroidal folds and/
unilateral or bilateral. The pain, which wakes the or swelling of the optic nerve head. No anterior
patient at night, occurs at the same time as the scleritis or systemic disease can be found.
redness, but at this stage the physical signs may be 2. Other patients present in a similar way to those
minimal even though the patient is obviously ill. If who have anterior scleritis. In some instances the
disease spreads from the anterior segment; in the normal limbal architecture and cytokines are also
others it starts in the posterior segment and can released into the cornea as well as cells. The cytokines
be, nodular or necrotizing. As in anterior scleritis, penetrate the cornea, widely affecting the corneal
many patients have associated systemic disease. fibrocytes. If their concentration is very high, as in
Posterior scleritis has become much more frequen- necrotizing scleritis, then the corneal tissue becomes
tly recognized since the advent of the 90D lens, damaged and resorbed leading to various and often
fluorescein angiography, B-Scan ultrasonography and characteristic peripheral and central corneal changes.
CT scanning. Also ophthalmologists have become Corneal infiltration to the extent of opacification
much more aware of the possibility of posterior scle- is most commonly seen in patients who have had
ritis being the cause in unusual cases of loss of vision, scleritis following an attack of herpes zoster, and
exudative detachments, choroidal effusion peripheral corneal tissue is most often lost as a result
syndrome, swollen disks and choroidal folds. of a granuloma or vasculitis affecting the limbus. The
B-scan ultrasonography is by far the most useful limbal vasculitis and vascular occlusion may lead
investigation in this condition. The features which either to the gradual loss of the peripheral corneal
need to be looked for on ultrasonography are: tissue or an active destruction of tissue. In the diffuse
1. The thickness of the posterior, coats of the eye and nodular forms the cornea becomes infiltrated and
beyond the normal range of 1.2 to 1.9 mm. It is sometimes vascularized in regions adjacent to the
not possible to distinguish retina, sclera and inflamed sclera. These changes are much more likely
choroid from each other unless they are detached. to occur if the attacks are recurrent, severe or inade-
2. Separation of the posterior surface of the sclera quately treated. In necrotizing disease the changes
from the episclera. are more intense. Some are related only to the
3. Presence or absence of retinal or choroidal adjacent necrotizing scleritis. In this situation, the
detachments, or swelling of the disk. cornea becomes damaged as a result of the cellular
and cytokine activity associated with the original
Corneal Changes in Scleritis disease. Other patients may develop localized or
The cornea may become involved at any stage during circumferential corneal changes. The destructive
the course of episcleral or scleral inflammatory change once initiated in the cornea can sometimes
disease. The corneal changes are more commonly progress separately from the scleral diseases and can
seen when the inflammation is severe and they are become so severe that perforation can result. Finally,
always preceded by easily identifiable changes to the the cornea can be invaded by a granuloma arising in
limbal vasculature in which the vessels leak, become the episcleral tissue. Such a granuloma destroys both
occluded or sprout new vessel complexes. As these the sclera and cornea around it by degrading the
changes are characteristic of the various conditions, collagenous tissue.
careful observations of these vessels in the early
stages of the scleral inflammation may give a clue as Etiology
to the probable severity and possible progression of
Scleritis is found in patients who have some underly-
the disease. If there is excessive leakage, particularly
ing autoimmune disorder. The precipitating cause in
from new vessels, this will lead to corneal
the eye is damage to the ocular tissue from
opacification. It will also lead to lipid deposition and
mechanical, surgical, bacterial or viral trauma.
corneal infiltration as it interferes with the normal
Sclerokeratitis is commonly associated with the
flow of metabolites within the corneal tissue. If on
the other hand there are vasculitic changes within sero-positive connective tissue disorders, usually
the limbal vessels, then changes occur within the occurring in the vasculitic phase of these diseases. It
circulation which may become totally or partially is therefore, most commonly seen in association with:
occluded as well as incompetent. These changes if rheumatoid arthritis, systemic lupus erythematosus
prolonged lead to the formation of new vessels and the systemic vasculitides, such as polyarteritis
around the limbus and if there is an appropriate nodosa, Wegener’s granulomatosis and relapsing
stimulus they will invade the cornea itself. Any of polychondritis.
the vascular networks at the limbus, whether deep
Rheumatoid Arthritis
or superficial, can give rise to these new vessels.
Inflammation adjacent to the limbus always disrupts Although vasculitis is a constant feature of the
disorders connected with scleritis and its associated Relapsing Polychondritis

corneal changes, it is by no means certain that it is
the primary change in the development of the disease. Patients with relapsing polychondritis almost always
The inflammatory joint changes of rheumatoid develop scleral disease during the course of their
arthritis are typically seen in the early stages of the illness. Although the exact etiology is unknown, it is
disease and if any eye signs occur at this stage they assumed to be an autoimmune vasculitis associated
tend to involve the episclera only. The pattern only with specific antibodies which attack cartilage, Type
changes late in the disease, corresponding to the VI collagen and similar connective tissues. When the
period in which the joint changes are quiescent and eye is involved, the patients develop a particularly
burnt out and the extra-articular manifestations of severe and intractable scleritis which can involve the
rheumatoid nodules, skin ulceration and vasculitic anterior and posterior segments of the eye. This
rash appear. At this stage, all the manifestations of condition is not as uncommon as previously
sclerokeratitis, includ-ing scleromalacia perforans, supposed.
become apparent; the severity depends on the
intensity of the immune response. Other Associated Systemic Diseases
Uveitis and scleritis are almost mutually exclusive
Wegener’s Granulomatosis and conditions. If cells are found in the anterior or
Polyarteritis Nodosa posterior chambers in patients with scleritis this
In those conditions in which vasculitis plays a promi- indicates that either they have severe disease
nent part in the systemic disease, such as Wegener’s involving the ciliary body or that they have mixed
granulomatosis and polyarteritis nodosa, the eye connective tissue disease. It is well known that
condition has a characteristic appearance, Patients Crohn’s disease and ulcerative colitis have joint
usually present with an elevated irregular granuloma, manifestations, and if there is eye involvement this
which if treated effectively leads to loss of tissue but takes the form of an acute anterior uveitis. However,
not loss of integrity of the globe. If these granulo- some patients with these conditions will present with
matous changes are at the limbus, the peripheral a scleritis indistinguishable from those seen with the
corneal destructive changes transgress the limbus, seropositive arthritides whilst others present with a
affecting both cornea and sclera. This does not happen migratory scleral, corneal or episcleral disease very
in other melting or destructive disorders where the similar to conjunctival phlycte-nular disease. Other
changes remain either within the sclera or within the clinical conditions in which scleritis may develop as
cornea. When associated with a systemic vasculitis, systemic lupus erythematosis, Reiter’s syndrome,
corneal gutters are always preceded by corneal Polyarteritis nodosa, Ankylosing spondylosis and
infiltration deep to Bowman’s membrane which Behcet’s disease.
disappears as soon as adequate therapy is given. It is Apart from the pathological and serological
important to detect this group of diseases early, findings, there is good clinical evidence that scleritis
because even the mildest scleritis can be associated is an autoimmune disorder. Quite apart from its
with severe systemic disease. This is of particular appearance in patients who have single or multiple
importance where the renal tract is involved, as the autoimmune disorders, there is a group of patients,
patient may be unaware that anything is amiss until who may or may not show surgical evidence of
very late in the disease. The anti-nuclear cytoplasmic connective tissue disorders, who develop a particu-
antibody test (ANCA) is crucial to the diagnosis of larly severe and intractable form of diffuse anterior
these diseases, and specific immunosuppressive or necrotizing scleritis when they have an eye
therapy is now available for them. Patients require operation. The acronym SINS (surgically induced
long and continued medical supervision, because even necrotizing scleritis) has been used for this not
after a period of remission the disease can become uncommon problem.5 This can follow ocular surgery
reactivated and need further intensive active of any kind, including cataract, glaucoma,
treatment. strabismus, and retinal detachment. Although the
latent period from surgery to the onset of scleritis
varies from the first postoperative day in a previously
sensitized patient to 40 years, the commonest story as most will have some underlying systemic, vascular
is of a patient whose eye does not completely settle or connective tissue disorder. The underlying
after surgery and after 3 to 4 months the eye gradually systemic disorder must be treated and this may in
becomes more red and painful and is not helped by itself be sufficient to control the ocular disease.
local medication. Some patients have had squint However, because of the unusual immunological
surgery in childhood and have responded to cataract situation in the eye, adjunctive therapy is almost
extraction by developing a scleritis at the site of the always required.
original squint surgery. Scleritis is largely associated with the seropositive
Whilst almost all the acute inflammatory diseases connective tissue disorders, and is immunologically
affect the sclera or episclera, there are other induced and perpetuated. It is also often associated
conditions which can affect this tissue. with a systemic autoimmune vasculitis. These
disorders must be specifically looked for and excluded.
Infections Anterior diffuse and nodular scleritis, although
found in patients with connective tissue disorders,
Infection of the sclera is rare partly because the scleral are rarely sight threatening and often respond to
fibers are tightly bound together and the tissue itself systemic non-steroidal anti-inflammatory drugs
has no blood supply. This is the reason why in the (NSAIDs). However, necrotizing scleritis is rapidly
pre-antibiotic era, evisceration was recommended for destructive and requires urgent treatment with
endophthalmitis. However, infection can occur, espe- immunosuppressive therapy. Posterior scleritis is
cially in an immunosuppressed or immunodeficient more difficult to manage because of the difficulties
patient, either from a blood-borne infection or from in the differential diagnosis, but the same principles
a localized abscess in the tissues on either side, such apply and control of pain is by far the best indicator
as an infected scleral plomb following retinal of success of treatment. Patients with diffuse, nodular
detachment surgery.6-8 All scleral abscesses present anterior scleritis and their counterparts in the
in a similar manner. There is an appearance of a posterior segment will usually respond to an NSAID
localized tender swelling on the globe; the conjunctiva such as flurbiprofen. As soon as the eye is quiet, the
and episclera are extremely congested, but unlike drug may be withdrawn, as it is unusual for the
scleritis the pain does not radiate to the face in the disease to recur immediately. Some patients may
early stages of the disease. In untreated or develop side effects.
inappropriately treated cases the abscess can extend Control can be reliably measured by the presence
into the cornea, into the eye to give rise to or absence of pain and by the degree of swelling and
endophthalmitis or into the orbit to create an orbital vascular congestion. The presence or absence of pain
abscess. may also be used to titrate the dosage of medication.
Failure to control diffuse or nodular scleritis with an
Granulomatous Lesions NSAID should make one suspect the presence of an
Granulomas occasionally occur as a result of foreign early necrotizing scleritis. Also, if fluorescein
body. However, they are most commonly seen as angiogra-phy reveals an area of non-perfusion, this
part of ophthalmia nodosa in which the hairs of the patient must be considered to have early necrotizing
various varieties of hairy caterpillars become scleritis. If there is no immediate response to NSAIDs,
embedded in the eye. Because of the shape of the the patient must be treated with
spine of the hair it will migrate inwards into the eye immunosuppressants. In patients with intractable
exciting a granulomatous reaction en route. disease, and those with necrotizing scleritis, systemic
steroids should be given. These must be given in
immunosuppressive dosages in order to control the
Therapeutic Regimes for Scleral Disease disease, i.e. oral prednisolone 60-80 mg daily. As soon
Topical non steroidals or steroidal anti-inflammatory as the disease is under control (i.e. when the pain
drugs are clearly insufficient.9 Subconjunctival steroids disappears), the dose can rapidly be reduced to an
are contraindicated. Unlike episcleritis, scleritis is a anti-inflammatory dose of 20 mg within 4 to 6 days,
potentially destructive disease.10 Patients with this and then gradually withdrawn. There are a few
condition must always be thoroughly investigated, patients who will require additional therapy because
the disease recurs when the steroids are reduced local therapy, or if local therapy is contraindicated a
below 20 mg prednisolone. These patients require systemic non-steroidal anti-inflammatory agent may
additional non-steroidal medication, so that the have to be given. This can be stopped as soon as the
steroid requirement can be reduced. The combination inflammation is suppressed.
therapy will often reduce the steroid requirement to
5 mg prednisolone or less. If this fails, cyclosporin Surgery in Necrotizing Keratitis
should be considered. Azathioprine is often Surgery should only be undertaken when the
advocated as a steroid-sparing agent as well as an systemic disease has been brought under control, and
immunosuppressive agent. Unfortunately, this is not continued supervision of both the eye and the
very effective in the treatment of scleritis. In patients systemic disease must be continued. Surgery may be
with a systemic vasculitis, systemic cyclophosphamide required if the eye becomes perforated. The disease
will have to be given, the maintenance dosage being cannot be controlled when there is excess antigen
related to the lymphocyte count. There is always a load or if the patient is unable to take medication.
delay in the therapeutic effect of this type of Systemic intravenous pulsed steroid and
immunosuppressive agent. During this period, which immunosuppression must be given at the time of
lasts 2-3 weeks, high steroid dosage will have to be surgery.
continued. In a further few cases, the disease is so
severe and the eye so much at risk that pulsed therapy REFRENCES
with intravenous predniso-lone and cyclo-
1. Watson P, Ortiz JM. Color Atlas of Scleritis. CV Mosby. Spain,
phosphamide should be considered. These regimes 1995.
are potentially hazardous,and treatment should be 2. Williamson J. Incidence of eye disease in cases of connective
undertaken with a physician or rheumatologist tissue disease. Trans Ophthalmol Soc UK 1974;94:742.
conversant with their use. 3. Akpek EK, Uy HS, Christen W, Gurdal C, Foster CS. Severity
of episcleritis and systemic disease association.
Episcleritis Therapy 4. Foster CS. Immunosuppressive therapy for external ocular
inflammatory disease. Ophthalmology 1980;87:140.
Episcleritis is a superficial disorder rarely associated 5. O’Donoghue E, Lighman S, Tuft S, Watson P. Surgically
with any systemic disease. It is self-limiting although induced necrotising sclerokeratitis (SINS)-precipitating factors
recurrent and unless it causes acute discomfort, and treatment. Br J Ophthalmol 1992;76:17.
6. Saini, JS, Sharma A, Pillai P. Scleral tuberculosis. J Trop and
requires no treatment. If treatment is necessary and
Geographic Med 1988; 40: 350.
non-steroidal anti-inflammatory agents are available 7. Carlson AN, Foulks GN, Perfect JR, Kim KH. Fungal scleritis
for local use, one of these should be given. Local after cataract surgery. Cornea 1992;11:151.
steroids will reduce the inflammatory response and 8. Hamady R, Sainz M, Raizman MB, Foster CS. Six cases of
scleritis associated with systemic infection. Am J Ophthalmol
increase the patient’s comfort but should not be used
1992;114:55.
on a continuing basis because they can induce glaucama 9. Watson PG. Doyne memorial lecture 1982. The nature and
and cataract. Steroids do not change or shorten the treatment of scleral inflammation. Trans Ophthalmol Soc UK
course of the disease. Very occasionally if there is 1982;102:257.
10. Watson PG. The diagnosis and management of scleritis.
persistent and painful inflammation unresponsive to
SECTION 4: DISEASES OF THE LENS
Chapter 41
Anatomy-Histology of the
Human Crystalline Lens
Suresh K Pandey, Liliana Werner, David J Apple, Vidushi Sharma
The adult crystalline lens measures approximately The anterior and posterior poles form the optical and
9.6 ± 0.4 mm in diameter with an approximate geometrical axis of the lens. Although the normal lens
anterior-posterior diameter (thickness) of 4.2 ± is transparent and clear in vivo, it is seldom completely
0.5 mm.1,3,11 Figures 41.1A and B show the empty colorless; even in childhood a slight yellowish tint is
capsular bag after removal of the crystalline lens. The present that tends to intensify with age.
diameter of ciliary sulcus 11.1 ± 0.5 mm, according to The crystalline lens is a unique transparent, bicon-
studies performed at the Center for Research on Ocular vex intraocular structure, which lies in the anterior
Therapeutics and Biodevices, Storm Eye Institute, segment of the eye suspended radially at its equator
Charleston, SC, USA (now renamed as David J Apple, by the zonular fibers and the ciliary body, between
MD, Laboratory for Ophthalmic Devices Research, the iris and the vitreous body. Enclosed in an elastic
John A Moran Eye Center, Salt Lake City, Utah, USA).3 capsule, the lens has no innervation or blood supply
Figs 41.1A and B: Gross photographs of the pediatric and adult human eyes obtained post-mortem showing the capsular bag,
zonules shape, and status after phacoaspiration/phacoemulsification of the lens substance. Both pictures were taken from an
anterior (surgeon’s) view; cornea and iris were excised to allow better visualization: (A) Empty capsular bag of a pediatric (aged
24 months) human eye obtained postmortem stained with 0.1% trypan blue. The diameter of the crystalline lens and empty
capsular bag were 9.2 mm and 9.6 mm, respectively. The anterior and posterior capsulorhexis are also visible, (B) Empty
capsular bag of a adult (aged 44 years) human eye obtained postmortem stained with 0.5% indocyanine green dye. The diameter
of human crystalline lens and empty capsular bag were 9.9 mm and 10.4 mm, respectively. Note the zonules are stained green
and clearly visible
316 Section 4: Diseases of the Lens
after fetal development. Its nourishment must be Growth of the Human Crystalline Lens
obtained from the surrounding aqueous and vitreous, The pediatric ocular structures, including the crystal-
and the same media must also remove metabolic waste line lens, are significantly smaller than in the adult,
products. Therefore, disturbances in circulation of especially in the first 1-3 years of life.9,10,11-13,16,17 the
these fluids, or inflammatory processes in these mean axial length of a newborn’s eye is 17.0 mm
chambers, play a large role in the pathogenesis of lens compared to 23-24 mm in an adult. The human crystal-
abnormalities. The aqueous humor continuously flows line lens grows throughout life by the deposition of
from the ciliary body to the anterior chamber, bathing new fibers. Figures 41.2A to F show the growth of the
the anterior surface of the lens. Disturbances in human crystalline lens. The most rapid lens-growth
permeability of the lens capsule and epithelium can occurs from birth to 2 years-of-age. The mean diameter
occur, leading to the formation of cataracts. of the capsular bag is about 7.0-7.5 mm at birth, which
Posteriorly, the crystalline lens is supported by the increases to about 9.0-9.5 mm by the age of 2
vitreous (hyaloid) face and lies in a small depression years.9,10,11-13,17 Human crystalline lens growth is
called the “patellar fossa.” In younger eyes, the slower after the second decade. The lens does not
vitreous comes in contact with the posterior capsule increase much in size thereafter because of a relative
in a circular area of thickened vitreous, the loss of hydration and shrinkage of the lens nucleus,
ligamentum hyaloideocapsulare. The potential space which offsets some of the increase from new fiber
between the capsule and the circle of condensed deposition. Nuclear opacities (nuclear sclerosis) is the
vitreous is called Berger’s space. The peripheral border physiologic change that occur as the result of the above
of the lens is the equator, formed from the joining of changes in hydration and nuclear size. The lens
the anterior and posterior capsules, and is the site of nucleus may become sufficiently opaque to cause
insertion of the zonules. visual difficulties. Also, the lens capsule thickens with
The lens consists of three components capsule, age and loses some of the inherent elasticity, which
epithelium, and lens substance. The lens substance is further decreasing the capacity for accommodation
a product of the continuous growth of the epithelium and helping to lead to presbyopia.5,6
and consists of the cortex and nucleus. The transition
between the cortex and nucleus is gradual. It does not
Lens Capsule
reveal a concise line of demarcation when observed
in histological sections. The lines of demarcation are The lens capsule is a basement membrane elaborated
often better visualized by slit-lamp microscopy. by the lens epithelium anteriorly and by superficial
Fig. 41.2A: Gross photographs of human crystalline lens taken Fig. 41.2B: Gross pictures of a pediatric human lens obtained
from a child aged 4 months (left side). On the right side postmortem, 20 months, showing human crystalline, zonules
photographs human crystalline lens from the adult aged 70 and ciliary body (anterior or surgeon’s view). The diameter of
years human crystalline lens was 8.5 mm
Chapter 41: Anatomy-Histology of the Human Crystalline Lens 317
Fig. 41.2C: Gross pictures of a pediatric human lens obtained Fig. 41.2D: Gross photographs of pediatric human eyes
postmortem, 20 months, showing human crystalline, zonules obtained postmortem aged 3 years showing crystalline lens
and ciliary body (Miyake-Apple posterior view) zonules and ciliary body. Anterior (surgeon’s view): The
diameter of human crystalline lens was 9.3 mm
Fig. 41.2E: Gross photographs of pediatric human eyes Fig. 41.2F: Gross photographs of an adult human eye obtained
obtained postmortem aged 3 years showing crystalline lens postmortem (aged 60 years) showing crystalline lens, zonules
zonules and ciliary body (Miyake-Apple posterior view) and ciliary body (Miyake-Apple posterior view). The diameter
of human crystalline lens was 9.8 mm
Figs 41.2A to F: Growth of the human crystalline lens
fibers posteriorly. By light microscopy the lens thickness of the anterior capsule compared with the
capsule appears as a structureless, elastic membrane, much thinner posterior capsule, may result from the
which completely surrounds the lens. It is a true fact that the former lies directly adjacent to and is
periodic acid-Schiff (PAS) positive basement actively secreted by the epithelium, whereas the lens
membrane, a secretory product of the lens epithe- epithelium is not present on the posterior surface.
lium.1,15 Figures 41.3A and B demonstrate histology Local differences in capsular thickness are important
of the anterior, equatorial, and posterior lens capsule surgically, particularly because of the danger of tears
using 2 different staining techniques. The capsule or rupture of the thin posterior capsule during
functions as a metabolic barrier and may play a role cataract surgery. Remnants of the tunica vasculosa
in lens shaping during accommodation. The lens lentis are common and appear as light-gray opacities
capsule is of variable thickness in various zones. At (Mittendorf dots) at or near the posterior pole. These
its thickest regions the lens capsule represents the opacities are rarely responsible for significant visual
thickest basement membrane in the body. The relative loss.
Figs 41.3A and B: Histological section of human crystalline lens showing anterior, equatorial and posterior lens capsules:
(A) Anterior lens surface stained by the PAS stain, which imparts a brilliant red hue to the basement membranes. The anterior
lens epithelium lays down a basement membrane, which is thick anteriorly; it is the thickest basement membrane in the body.
(Original magnification X 100), (B) Masson’s Trichome stain. (Original magnification X 100)
Lens Epithelial Cells anterior capsular thickening following implan-

tation of a phakic PC IOL in close proximity (or
It is pertinent to discuss some details about the lens
on) the anterior surface of the crystalline lens.
epithelial cells and their behavior after cataract
3. E-cells are located in the second zone, as a conti-
surgery. Postoperative proliferation of these cells may
nuation of the anterior lens epithelial cells around
lead to opacification of the posterior lens capsule,
the equator, forming the equatorial lens bow, with
which in-turn may contribute to decrease vision after
the germinal cells. These cells normally show
the cataract surgery and implantation of the intrao-
mitotic capability, and new lens fibers are continu-
cular lenses.12-15 The lens epithelium is confined to the
ously produced at this site. Because cell production
anterior surface and the equatorial lens bow (Fig. 41.4).
It consists of a single row of cuboidal-cylindrical cells,
which can biologically be divided into two different
zones with two different types of cells:
1. A-cells are located in the anterior—central zone,
(corresponding to the central zone of the anterior
lens capsule). They consist of relatively quiescent
epithelial cells with minimal mitotic activity. When
disturbed, they tend to remain in place and not
migrate. However, in a variety of disorders (e.g.
inflammation, trauma), an anterior subcapsular
epithelial plaque may form. The primary type of
response of the anterior epithelial cells is to
proliferate and form fibrous tissue by undergoing
fibrous metaplasia.
2. Recently, a new potential complication of A-cell
proliferation has emerged in the field of refractive
Fig. 41.4: Schematic illustration of the microscopic anatomy of
surgery. The anterior subcapsular opacities that
the lens, showing the “A” cells of the anterior epithelium and
have been described with various phakic posterior the “E” cells, the important germinal epithelial cells of the
chamber (PC) IOLs are based on A-cell prolife- equatorial lens bow. These lens epithelial cells plays
ration. The fibrotic response of the anterior lens predominant role in the pathogenesis of various complication
epithelium is what determines the degree of as postoperative opacification of anterior and posteior capsule
in this region is relatively active, the cells are rich and are bound together by ground substance. After
in enzymes and have extensive protein formation, the cellular nuclei of the lens fibers are
metabolism. E-cells are responsible for the continu- present only temporarily. Subsequently they disapp-
ous formation of all cortical fibers, and they account ear, leaving the lens center devoid of cell nuclei except
for the continuous growth in size and weight of in certain pathologic situations, (e.g. the maternal
the lens throughout life. During lens enlargement rubella syndrome).
the location of older fibers becomes more central The original lens vesicle represents the primary
as new fibers are formed at the periphery. embryonic nucleus; in later stages of gestation the fetal
In pathologic states, the E-cells tend to migrate nucleus encircles the embryonic nucleus. The various
posteriorly along the posterior capsule; instead of layers surrounding the fetal nucleus are designated
undergoing a fibrotic transformation, they tend to according to stages of growth. The most peripherally
form large, balloon-like bladder cells (i.e. Wedl cells). located fibers, which underlie the lens capsule, form
These are the cells that are clinically visible as “pearls” the lens cortex. The designation of cortex is actually
(Elschnig’s pearls). These equatorial cells are the an arbitrary term signifying a peripheral location
primary source of classic secondary cataract, especially within the lens, rather than specific fibers.
the pearl-form of posterior capsule opacification The relationship between sclerosis and hardness
(PCO). E-cells are responsible for the formation of a is uncertain. Traditionally the word “sclerosis” has
Soemmering’s ring, which is a donut-shaped lesion, been associated with decreased water content of the
composed of retained/regenerated lens cortex and crystalline lens. Although there is no consensus in the
cells that may form following any type of disruption past literature about the extent to which the lens
of the anterior lens capsule. This lesion was initially hardens; recent evidence has demonstrated more
described in connection with ocular trauma. It is the consistently that increased hardness of the crystalline
basic precursor of classic PCO. The E-cells have also lens occurs with age. Emery-Little proposed a classifi-
been implicated in the pathogenesis of opacification cation of lens nuclei depending on varying degree of
between piggyback IOLs, also termed interlenticular hardness.4 Using postmortem human eyes, we have
opacification.14 developed a model of inducing cataract of varying
degree of hardness in a laboratory setting using the
Lens Substance (Cortex and Nucleus) Miyake-Apple posterior video technique and this is
The lens substance consists of the lens fibers themsel- shown in Figures 41.5A to E.2,7,8 Figure 41.6A to C
ves, which are derived from the equatorial lens summarizes the anatomical relationship of the human
epithelium. On cross-section these cells are hexagonal, crystalline lens, ciliary body and zonules.
Fig. 41.5A Fig. 41.5B

Figs 41.5A to E: Aging of the lens substance (nuclear sclerosis). Emery-

Little’s classification was proposed for the hardness of nuclear cataract
(varying from soft, semi-soft, medium hard, hard and rock-hard), in
clinical setting. We have presented posterior view of the postmortem
phakic human eye showing an experimental example of induction of
different degrees of nuclear sclerotic cataract after injection of
Karnovsky’s solution in the lens substance.8 (A) Miyake-Apple posterior
view of a human eye obtained post-mortem from a 79-year-old male,
showing the crystalline lens. There is a grade 1 of nuclear hardness
(soft cataract, according to the Emery-Little classification). B, C, D and
E) Same eye 5, 15, 20 and 30 minutes after the injection of Karnovsky’s
solution within the nucleus, with the creation of grades 2, 3, 4 and 5 of
nuclear hardness, respectively
Figs 41.6A to C: Parasagittal section of the phakic human eye obtained postmortem. Note the crystalline lens suspended by the
ciliary zonule: (A) Crystalline lens and zonules, (B) Higher magnification of crystalline lens, ciliary body and zonules from another
case, (C) Higher magnification of ciliary body and zonules from another case. Miyake-Apple posterior view
In summary, the crystalline lens is a unique trans- 8. Pandey SK, Werner L, Escobar-Gomez M, Apple DJ, et al.
parent, biconvex intraocular structure, which lies in Creating cataracts of varying hardness to practice extracapsu-
lar cataract extraction and phacoemulsification. J Cataract
the anterior segment of the eye suspended radially at Refract Surg 2000;26,322.
its equator by the zonular fibers and the ciliary body, 9. Pandey SK, Wilson ME, Trivedi RH, Werner L, Apple DJ, et
between the iris and the vitreous body. The lens al. Pediatric cataract surgery and intraocular lens implanta-
consists of three components: capsule, epithelium, and tion: Current techniques, complications and management. Int
lens substance. The lens substance is a product of the Ophthalmol Clin 2001;41,175.
10. Pandey SK, Wilson ME, Apple DJ et al. Childhood cataract
continuous growth of the epithelium and consists of
surgical technique, complications and management. In: Garg
the cortex and nucleus. A, Pandey SK, eds., Textbook of Ocular Therapeutics. Jaypee
Brothers, New Delhi, India, 2002.
11. Pandey SK, Thakur J, Werner L et al. The Human Crystalline
ACKNOWLEDGEMENT Lens, Ciliary Body and Zonules: Their Relevance to
The authors gratefully acknowledge the partial Presbyopia. In: Agarwal A, ed., Presbyopia: A Surgical Text.
Slack Inc., Thorofare, NJ, USA, 2002;2,15-25.
support of an unrestricted grant from Research to 12. Pandey SK, Werner L, Apple DJ. Posterior capsule
Prevent Blindness, Inc. New York, NY, USA. opacification: Etiopathogenesis, clinical manifestations, and
management. In: Garg A, Pandey SK, eds., Textbook of Ocular
Therapeutics. Jaypee Brothers, New Delhi, India 2002;408-25.
REFERENCES 13. Vargas LG, Peng Q, Escobar-Gomez M, Apple DJ. Overview
1. Apple DJ, Auffarth GU, Peng Q, Visessook N. Foldable of modern foldable intraocular lenses and clinically relevant
Intraocular Lenses. Evolution, Clinicopathologic Correlations, anatomy and histology of the crystalline lens. Int Ophthalmol
Clin 2001;41,1.
Complications. Thorofare, NJ:Slack, Inc., 2000.
14. Werner L, Apple DJ, Pandey SK. Postoperative proliferation
2. Apple DJ, Lim E, Morgan R, et al. Preparation and study of
of anterior and equatorial lens epithelial cells: A comparison
human eyes obtained postmortem with the Miyake posterior
between various foldable IOL designs. In Buratto L, Osher R,
photographic technique. Ophthalmology 1990;97:810.
Masket S (Eds): Cataract surgery in complicated cases.
3. Assia EI, Castaneda VE, Legler UFC, et al. Studies on cataract
Thorofare, NJ: Slack 2000;399-417.
surgery and intraocular lenses at the Center for Intraocular
15. Werner L, Pandey SK, Escobar-Gomez M, Apple DJ, et al.
Lens Research. Ophthal Clin North Am 1991;4:251.
Anterior capsule opacification: A histopathological study
4. Emery JM, Little JH. Phacoemulsification and Aspiration of comparing different IOL styles. Ophthalmology 2000;107,463.
Cataracts; Surgical Techniques, Complications, and Results. 16. Wilson ME, Apple DJ, Bluestein EC, Wang XH. Intraocular
St Louis:CV Mosby 1979;45-8. lenses for pediatric implantation: biomaterials, designs and
5. Glasser A, Croft MA, Kaufman P. Aging of the human sizing. J Cataract Refract Surg 1994;20,584.
crystalline lens and presbyopia. Int Ophthalmol Clin 2001;41,1. 17. Wilson ME, Pandey SK, Werner L et al. Pediatric Cataract
6. Glasser A, Kaufman PL. The mechanism of accommodation Surgery: Current Techniques, Complications and Manage-
in primates. Ophthalmology 1999;106,863. ment. In: Agarwal S, Agarwal A, Sachdev MS, Mehta KR,
7. Miyake K, Miyake C. Intraoperative posterior chamber lens Fine IH, Agarwal A, eds., Phacoemulsification, Laser Cataract
haptic fixation in the human cadaver eye. Ophthalmic Surg Surgery and Foldable IOLs. Jaypee Brothers Medical
1985;16,230. Publishers, New Delhi, India, 2000;369-88.
Chapter 42
Displacement of the Lens:

Etiology and Management
YR Sharma, Nikhil Pal, D Mittal, Deepender V Singh
Normally the crystalline lens is present in patellar ii. Simple microspherophakia.

fossa, and remains suspended by zonule of Zinn with b. With associated ocular anomalies
its center corresponding to the visual axis. Displace- i. Ectopia lentis et pupillae
ment of the lens may be classified topographically ii. Aniridia.
as: (1) subluxated, and (2) luxated or dislocated (Fig. c. With associated systemic anomalies
42.1). i. Marfan’s syndrome
ii. Homocystinuria
SUBLUXATION iii. Weil-Marchesani syndrome
Zonular dialysis and partial lens displacement occur, iv. Rieger’s anomaly
but the displaced lens remains partially in the patellar v. Hyperlysinemia
fossa. vi. Sulfite oxidase deficiency
vii. Sturge-Weber syndrome
DISLOCATION OR LUXATION viii. Crouzon’s diseases
ix. Sprengel’s anomaly
Lens is completely displaced from the patellar fossa;
x. Oxycephaly.
it may appear in one of the following areas:
xi. Ehler-Danloss syndrome
1. Incarcerated in the pupil
2. Secondary to other ocular conditions
2. In the anterior chamber
i. Mature or hypermature cataract
3. In the vitreous
ii. Uveitis, endophthalmitis
4. Subretinal space
iii. Congenital glaucoma
5. Remain as wandering lens
iv. High myopia
6. In very rare cases of trauma, it may be extruded
v. Megalocornea
out of the globe partially (lenticele) or completely.
vi. Cornea plana
First description of a dislocated lens is attributed
vii. Intraocular tumors
to Berryat in 1749. Stellawag introduced the term
viii. Persistent hyperplastic primary vitreous
ectopia lentis to describe congenital dislocations.
ix. Retinitis pigmentosa
x. Retinal detachment
ETIOLOGY OF DISLOCATED LENS
xi. Iris Coloboma
Displacement of the lens may be classified 3. Traumatic subluxation/dislocation and couching:
etiologically into three broad groups: Of the above three groups, traumatic displacement
1. Inheritable forms of the lens is most common, constituting more
a. Isolated forms than half the cases. Next in order of frequency
i. Simple ectopia lentis are Marfan’s syndrome, hypermature cataract,
Chapter 42: Displacement of the Lens: Etiology and Management 323
and Weil-Marchesani syndrome. Couching is also be associated. Muscular underdevelopment
seldom practiced now, but surgical posterior may lead to hernia formation.
dislocation of lens in cataract surgery especially 2. Ocular features3
in phacoemulsification has become all too 1. Lens subluxation: Bilateral, symmetrical, non-
common. progressive, upward and temporal displacement
occurs in 80 percent cases. Microspherophakia is
occasionally seen.
Simple Ectopia Lentis
2. Angle anomalies: prominent iris processes in 75
This may be congenital or spontaneous. Congenital percent cases.
type, resembling that of Marfan’s syndrome, occurs 3. Glaucoma in 8 percent cases
early in life, and is bilateral and symmetrical. 4. Hypoplasia of dilator pupillae.
Displacement is upward and temporally. It is 5. Cornea plana
transmitted by autosomal dominant inheritance. 6. Axial Myopia
Spontaneous type occurs at any time during adult 7. Retinal detachment
life. Displacement is often downward. Hereditary 8. Useful vision may be present either through
influence on spontaneous dislocations was reported aphakic or phakic area of the pupil.
by Vogt.1 9. Cataract formation
10. Accommodation is not affected if the crystalline
lens is clear.
Ectopia Lentis et Pupillae
Here ectopia lentis is associated with pupillary Homocystinuria
anomalies. Pupils are oval or slit like and are usually 1. It is an inborn error of metabolism due to lack of
ectopic. The pupillary displacement is in the opposite enzyme cystathione synthetase, which is
direction to that of the ectopia lentis. It is usually responsible for converting essential amino acid
bilateral and symmetrical and recessive in methionine to cystine and its end products.
transmission; cataract, glaucoma, and retinal 2. Hereditary disease with autosomal recessive
detachment may be other associated anomalies. inheritance.
3. Characteristic facies with fair hair, fair
complexion, mental retardation, spastic gait,
Microspherophakia
muscular weakness, and erythematous patches on
Microspherophakia is an isolated entity and is the skin of the face.
transmitted by autosomal recessive manner. It has 4. Ocular features include the following:
been attributed to arrest of development at 5th and a. Bilateral subluxation of the lens downward and
6th month of the intrauterine life. Pupillary block nasally.
glaucoma is a common complication.2 Repeated IOP b. Accommodative power of the eye is lost due
measurements are indicated even in the presence of to disintegration of the zonules.
excellent vision. Microspherophakia in Weil- c. Glaucoma may be present in one-fourth of the
Marchesani syndrome has associated systemic patients.
features. 5. Diagnosis is made by the following tests:
a. Urine examination with sodium nitroprusside
test.
Marfan’s Syndrome
b. Estimation of homocystine in urine, and homo-
First described completely by Marfan in 1896, cystine methionine in plasma by using amino
Marfan’s syndrome is transmitted by autosomal acid analyzer.
dominant inheritance and is characterized by c. Enzyme assay of cystathionine synthetase
following systemic and local features: activity in extracts of liver obtained by fine
1. Systemic features Cardiac and skeletal anomalies needle aspiration biopsy.
are present. Aneurysm of ascending aorta may 6. Systemic complications are as follow:
be present. Limbs are unproportionately long a. Markedly increased tendency for platelets
compared to trunk. Arachnodactily, pectus aggregation, may lead to myocardial and
deformity, joint laxity, and high arched palate may cerebrovascular occlusive disorder.
Fig. 42.1: Displacement of lens
b. Increased risk for fatal complications during humor through the pupil, hence called glau-
general anesthesia. coma inversus.
d. Angle anomaly due to mesodermal dysgenesis.
Weil-Marchesani Syndrome7,8 Ectopia lentis may also be associated with the
following conditions:
This recessively inherited syndrome is characterized
by the following: 1. Aniridia This is due to arrest of differentiation of
the ectoderm of the optic cup. In addition to ectopia
A. Systemic features Short stature, short and stubby lentis, it may be associated with spherophakia,
fingers and mental retardation. congenital glaucoma, and macular dysplasia.
B. Ocular features include the following: 2. Ehler-Danlos syndrome (Fibrodysplasia hyperelastica)
a. Microspherophakia This is an autosomal dominant hereditary disease.
b. Forward subluxation of the lens The ocular features include subluxation of lens,
c. Secondary glaucoma due to blockage of the blue sclera, angioid streaks, keratoconus,
pupil by spherical lens. This glaucoma needs epicanthus, ptosis, and strabismus. Laxity of the
mydriatic to open up the passage for aqueous palpebral tissue shows unusual ease of everting
Chapter 42: Displacement of the Lens: Etiology and Management 325
the upper lid (Meterier’s sign). The other important findings associated with
3. Rieger’s syndrome Basically this is autosomal domi- traumatic dislocations are commotio retine, choroidal
nant hereditary mesodermal dysgenesis of iris and tear, and retinal detachment. Management of a case
cornea. Lental anomalies include ectopia lentis and of anterior dislocation of the lens is an ocular
coloboma of the lens. Hypoplasia of the anterior emergency. After lowering the intraocular pressure
iris stroma, posterior embryotoxon, aniridia, and by intravenous mannitol, the lens should be removed
pupillary abnormalities are common. as early as possible. The intrasurgical posterior
dislocation of lens or lens pieces, during phaco-
Ocular Diseases Causing emulsification, present different set of problems, and
Displacement of the Lens require special management techniques and a
a. Hypermature cataract is the most common ocular considered approach.
cause of spontaneous dislocation of the lens in
adults. Displacements owing to stretching of Management
zonules are seen in conditions such as congenital The management of ectopia lentis is challenging
glaucoma, high myopia, and megalocornea. especially in children, who are at risk of amblyopia.
b. Degeneration of zonules occurs in cases of retinal In addition to the optical and visual challenges
detachment, retinitis pigmentosa, and uveitis. presented by subluxation of the lens, the physician
c. Displacement of lens in cases of intraocular tumor must be concerned about the potential associated
is mainly due to mechanical pressure. systemic conditions, the diagnosis of which may be
life saving. Homocystinuria and Marfan’s syndrome
Traumatic Displacement of the Lens
should be especially ruled out. Patients with
Injury to the suspensory mechanism is common in homocystinuria are predisposed to life threatening
concussion injury of the eye. Minimal subluxation of thrombotic complications, especially during general
the lens, whether clinically manifested or not, occurs anesthesia. Recognized modalities of treatment include
after almost all concussion injuries of the eye. The pyridoxine, in combination with folic acid and
following forces are involved in concussion injury: vitamin B12; methionine – restricted and cystine
a. Backward thrust and rebounding of the lens. supplemented diet and betaine. Patients with
b. Pressure wave of aqueous that forces root of the Marfan’s syndrome should be investigated for
iris backward cardiovascular system abnormalities. The importance
c. Forcible recoil of vitreous body. of careful refraction through both aphakic and phakic
d. Compensatory sudden enlargement of portions of the visual axis before concluding that
corneoscleral ring. optical correction is inadequate cannot be overstated.
As a rule zonules are torn easily at their However, if visual acuity does not improve
attachment to the lens. Once the zonular attachment sufficiently with optical correction, or the magnitude
is ruptured, the lens may be retained in the patellar or asymmetry of required correction is not tolerated,
fossa by its attachments to the anterior vitreous face. other alternatives should be considered.
The lens may be subluxated laterally (lateral
subluxation) or there may be anteroposterior rotatory Subluxated Crystalline Lens
displacement (axial subluxation). Clear Lens
Complete traumatic luxation (dislocation) of the
lens may follow different routes, i.e. into anterior A minimal subluxated clear crystalline lens that is
chamber, vitreous, subretinal, space, subscleral region, asymptomatic may simply be observed. For a
subconjunctival or may extrude through scleral substantially subluxated clear crystalline lens, one
rupture. Most dreaded complication of dislocation may have to give spectacle6 rehabilitation either
of lens is secondary glaucoma, which occurs in about through the phakic or aphakic pupil. Sometimes
one-third of the cases. In anterior dislocation onset special type of contact lens has to be used, which
of glaucoma is sudden, and in posterior dislocation occlude a specific part of pupil. Miotics or mydriatics6
it is insidious. It may be stated, that in anterior can be tried. Nd: YAG laser has also been used to do
dislocation glaucoma develops in hours, and in optical iridotomy and zonulolysis. The goal of laser
posterior dislocation it develops in years. procedures is to enlarge the aphakic portion of
pupil.7,8 If these techniques are not successful, then
one may have to resort to surgical removal of as possible. If a posteriorly dislocated lens is fixed to
subluxated lens either through limbal approach or retina and is not causing any complication, then it is
pars plana approach. Pars plana approach involves best, left alone. If posteriorly dislocated lens is freely
making 3 sclerotomies; one for infusion cannula, moving, coming in way of visual axis, causing
others for placement of vitrectomy probe, inflammation and/or glaucoma, then it has got to be
phacofragmentor, fiber optic light source or MVR removed through pars plana approach.
blade. After placing the infusion port, MVR blade is After doing complete pars plana vitrectomy, lens
put from one superior sclerotomy to stabilize the lens, can be removed either through limbal route or
and lens is removed either by vitrectomy probe or sclerotomy. Lens can be removed through the limbus
phacofragmentome depending upon the density of by MVR blade, endocryo or perfluoro carbon liquids
nucleus, which depends upon age of the patient. For (PFCL).10 The other option is to float the lens away
limbus approach we make two port entries; one for from retina after putting PFCL. When the lens has
infusion cannula and one for vitrectomy probe. Pars floated in the mid vitreous, then it is crushed with
plana approach has the advantage of better visibility the endoilluminator and vitrectomy probe. Then the
during the entire procedure, and if any piece of lens is removed either by vitrectomy probe or
nucleus falls back, it can be easily removed. But if phacofragmentome depending upon the density of
this complication happens in limbal approach, then the cataract. This approach is superior, as chances of
one has to convert to pars plana approach. Wire vectis damage to retina is less, as the lens is removed in
and cryoprobe can also be used for limbal route mid vitreous and anterior chamber route is not taken.
removal. Visual rehabilitation can be achieved either by
Thus, within-the-bag lensectomy for the removal contact lens or intraocular lens (IOL). Because of
of subluxated lenses, is a relatively safe surgical absence of capsule support, ciliary fixated or in the
procedure with beneficial visual outcome. Correction bag PC IOL can not be put. Anterior chamber intra-
of the aphakia with glasses or contact lenses, as ocular lenses can be used. If there is anterior chamber
routinely practiced is far from ideal, but certainly angle damage, then scleral fixated PC IOL can be used.
safer than the presently available alternatives, like
scleral fixated IOLs, anterior IOLs or refractive REFERENCES
surgery. 1. Vogtl Z. Angeleik 1905;14:53.
2. Kwsitko ML. Secondary Congenital Glaucoma: Diagnosis and
Cataractous Lens Therapy, In: Glaucoma (Ed): Cairens. London: Grune and
A minimally subluxated cataractous lens (less than Stratton Co, 1986.
3. Cross HE, Jensen AD. Ocular manifestations in Marfan’s
one quadrant of zonulodialysis) can be removed with syndrome and homocystinuria. Am J Ophthalmol 1973;75:405.
phacoemulsification, and sometimes an intraocular 4. Jerret WH. Dislocation of the lens. Arch Ophthalmol
lens can be placed. Capsular tension rings (CTR) have 1967;78:289.
recently been advocated for centration of the capsular 5. Jensen AD, Cross HE, Paton D. Ocular complication in the
bag and PC IOL in such cases.9 Weil-Marchesani syndrome. Am J Ophthalmol 1974;77:262.
6. Nelson LB, Szmyel SM. Aphakic correction in ectopia lentis.
For substantially subluxated cataractous lens,
Ann Ophthalmol 1985;17: 445.
management is surgical removal. Pars plana approach 7. Straatsma BR, Allen RA, Pettet TH et al. Subluxation of the
is preferable over limbal approach. The lens can be lens treated with iris photocoagulation. Am J Ophthalmol
removed either with a vitrectomy probe or 1966;61:1312.
phacofragmentome, depending upon density of 8. Tchaki H, Larson RS, Nichols BD et al. Neodymium: YAG
laser zonulolysis for treatment of lens subluxation.
nucleus. Through limbal route, it can be extracted by
cryoprobe or wire, vectis. Vectis should be introduced 9. Buckley EG. Scleral fixated (sutured) posterior chamber
from the region, in which there are no zonules. intraocular lens implantation in children. J AAPPOS
1999;3,289.
DISLOCATED LENS 10. Lin KR, Peyman GA, Chen MS et al. Use of high density vitreous
substitutes in the removal of posteriorly dislocated lenses or
Lens dislocated anteriorly has to be removed as early intraocular lenses. Ophthalmic Surg 1991;22:503.
Chapter 43
Etiopathogenesis of Senile
Cataract: Prospects of
Medical Therapy
YR Sharma, Nikhil Pal, Kamal Kishore, Deepender V Singh
FORMATION OF CATARACT leakage of the liquid lens matter without producing

glaucoma.
The human lens continues to increase in thickness
throughout life, as new fibers are formed by the
DEFINITION OF CATARACT
proliferation of anterior subcapsular epithelial cells
in the pre-equatorial and equatorial regions.1 These Cataract may be defined, as any type of opacity of
newly formed fibers extend beneath the capsule in the lens. Small congenital or punctate opacities may
an arcuate manner toward the posterior pole be observed in 10 to 20 percent of the individuals
compressing the central fibers in the center of the without any adverse effect on vision.
lens. Over the years, central fibers become sclerosed, Framingham Eye Study 2, Indo-US Study 3 and
and acquire a yellowish-brown color. These factors American National Studies4 defined senile cataract
increase the overall refractive index of the lens, as “the presence of lens opacities (excluding early
producing a myopic shift in the refraction. Nuclear cortical changes), which could not be ascribed to
cataract is formed by compactness, and dehydration congenital, secondary or other specific causes with
of the central lens fibers along with pigment visual acuity of 6/9 or worse”.
accumulation. Terms like, brown cataract (cataract
brunescence) and black cataract (cataract nigra) have CLASSIFICATION OF CATARACT
been used to denote advanced nuclear cataracts.
Duke-Elder6 classified immature cataracts into the
Cortical cataract, on the other hand, is preceded
following groups:
by development of water clefts in the lens cortex,
1. Nuclear
which continue to increase in size leading to
2. Cortical
formation of wedge like opacities. In advanced stages,
a. Cuneiform
cataract may become pearly white and intumescent
b. Perinuclear
hypermature cataract. If left untreated, the cortical
c. Cupuliform
material undergoes liquefaction, causing the hard
brown nucleus to appear in the lower part if the Cuneiform opacities These are the earliest features of
capsular bag. Still later, due to increased permeability cortical cataract. These are wedged shaped opacities,
of the capsule, the lens protein leaks out to produce with their apex towards the center of the lens,
lens induced glaucoma. Sometimes a shrunken extending in a radial direction toward the anterior
cataract may develop (membranous cataract) due to pole of the lens. These opacities increase in size, as
Fig. 43.1: Diagram of the scheme used in the CCRG classification system, showing the various
anatomical zones of the lens in the sagittal (Fig. 43.1A) and en face (Fig. 43.1B)
well as in extent to finally involve most of the lens f. Supranuclear (SN)

cortex. Intumescent immature cataract, is an g. Nuclear (N).
intermediate stage in the development of cortical Extent of subcapsular cataracts is graded by
cataract, in which the lens swells up due to relating the opacity to a series of concentric circles,
accumulation of fluid. the outermost representing the equatorial circle of
the lens. Each circle indicates a predetermined area
Perinuclear variety of cortical cataract It is characterized
of the lens shown in percentage of total area (Fig.
by multiple dot like opacities in the deeper cortex,
43.2). The enface view of the lens is divided into 100
which surrounds the adult nucleus like a ring.
equal segments (Fig. 43.3). By counting the number
Cupuliform cataract It is the term used to describe of segments involved, the extent of opacities is
localized posterior subcapsular opacity. Such cataracts immediately calculated.
are usually associated with nuclear sclerosis. Classification schemes such as the Lens Opacities
For epidemiology study and follow-up, classifi- Classification System II6 and III7 (LOCS II and LOCS
cation of cataract has been made after taking photo- III), and the Age Related Eye Diseases study (AREDS
graphs, and studying the color change and position Manual of Operations, 1994) use photographic
of the opacity inside the lens. standards to subdivide each major type into grades.
The American Cooperative Cataract Research
Group (CCRG) has proposed a classification based
on the stereoscopic color photographs of excised
human lenses. Six stereoscopic views of the lens are
usually taken, and the color transparencies are
utilized in a marked manner for classification. Extent
of opacities are described semiquantitatively.
Accordingly, the following classification has evolved:
1. Hypermature (H) A totally opaque lens, that has
undergone a marked anteroposterior swelling.
2. Mature (M) A totally opaque lens with no recogniz-
able anatomical zone swelling.
3. Immature cataracts These possess some amount of
normal lens anatomy. This group may further be
subclassified into the following (Figs 43.1A and
B):
a. Anterior subcapsular (SCA)
Fig. 43.2: Estimation of the area involved by a subcapsular
b. Posterior subcapsular (SCP) cataract (SCA or SCP) in the CCRG system. The smaller circles
c. Anterior cortex (CXA) are designated with a number representing the percentage of
d. Equatorial cortex (CXE) the area of the equatorial (outermost) circle occupied by the
e. Posterior cortex (CXP) designated circle
Chapter 43: Etiopathogenesis of Senile Cataract: Prospects of Medical Therapy 329
Protein and amino acids Since the earliest reports of
cataract in tryptophan deficiency, numerous accounts
confirming this observation, have been published and
the effect is ascribed to the resultant protein
deficiency. Epidemiological studies showed an
association of cataract and less intake of protein food.
Vitamins Riboflavin, vitamin E, and vitamin C are
involved in lens metabolism. Riboflavin modifies
action of the enzyme glutathione reductase. Vitamins
E and C probably act as deoxidant.
Essential elements Calcium deficiency due to any cause
leading to hypocalcemia has long been known to
cause zonular cataract. Lower plasma levels of calcium
Fig. 43.3: En face view of the lens dividing it into one hundred has been found in patients with senile cataract as
equal segments. The largest circle represents equator of the compared to controls. The role of deficiency of other
lens essential elements such as copper, zinc, and selenium
in the development of cataract has also been
These grades are based either on density and color postulated.10 Though, the recently conducted Age-
(in case of the nucleus or according to the anatomic Related Eye Disease Study ( AREDS) sponsored by
area of the cataract (in the case of the cortical and the National Eye Institute (NEI of USA),7 in which
posterior subcapsular areas). One may directly nutritional supplements were given in the dose of
compare the patients’ lens as seen by the slit lamp Vitamin C 500 mg, Vitamin E 400 IU, Beta-Carotene
with a photographic copy of the various standard 15 mg, Zinc Oxide 80 mg, Cupric Oxide 2mg showed
grades, as set up in the various classification schemes that nutritional supplements do not seem to prevent
(clinical grading), or one may take photographs of
cataracts or to keep them from getting worse over
the lens being studied, and later grade the
time.
photographs according to the classification scheme
used (photographic grading).
Medical Factors
ETIOPATHOGENESIS OF CATARACT Diabetes When blood sugar levels are elevated
Though exact etiopathogenesis of senile cataract is beyond 200 mg per ml, the enzyme hexokinase is
not known, age-related cataract may have saturated and remaining glucose is converted by
multifactorial and synergistic causes. 8 Nuclear aldose reductase to sorbitol, which accumulates in
sclerosis and nuclear cataract seem to be an age related the lens fibers and causes cataract by causing osmotic
phenomenon.5 stress. Thus, diabetics have a greater risk of cataract
Epidemiological studies have shown that incidence formation at an early age.11
and type of cataract vary in different parts of the
world. For example, in India visual disability from Dehydration An association between prior episodes
cataracts tends to occur on an average, 14 years earlier of dehydration crises resulting from severe diarrhea,
than in the West,9 and cortical or soft cataract is the cholera or heat stroke and senile cataract has been
predominant type as compared to the posterior suggested. 12,13 During dehydration episodes, the
subcapsular and nuclear varieties. Following osmotic imbalance secondary to malnutrition and the
aetiopathogenic factors to be considered: rise of blood urea and ammonium cyanide levels are
A. Personal factors responsible for cataract formation; ammonium cyanide
B. Environmental factors is believed to denature crystalline proteins of the lens
C. Other related factors. by carbamylation.13-15
Personal Factors Environmental Factors

Personal factors are (a) Dietary factors, and (b)
Role of Sunlight, UV Radiation, and Thermal
Medical factors.
Effect
Dietary Factors
Exposure to radiation from almost the entire range minoids).

of the electromagnetic spectrum has a cataractogenic 3. Increase in protein aggregates.
potential. Single dose of 200 rads radiation has been 4. Retention of sodium with loss of potassium and
shown to be cataractogenic. Clinical, experimental, inositol.
and epidemiological studies have emphasized 5. Decrease in the concentration of reduced gluta-
cataractogenic influence of sunlight, but the exact thione.
mechanism is yet unknown. The photo-perioxidation 6. Increase in protein disulfide bonds and oxidized
of lens constituents including amino acid residues, cystein residues.
lipid moieties, and other membrane components 7. Formation of high molecular weight (HMW)
brought about by near UV light, infrared, and proteins resulting from abnormal products of
microwaves via generation of free radicals, may play protein glycosylation/ketolysation.
an important role.16,17,18 8. Malonaldehyde formation resulting from lipid
In addition to its UV component, sunlight can perioxidation.21
initiate cataractogenesis by a thermal mechanism. 9. Formation of lipid-protein aggregates.
Infrared and microwave components of the solar 10. Formation of disulfide cross links, leading to
radiation are absorbed by the iris stroma, raising the aggregation of proteins resulting in opacity.
temperature of the posterior chamber and lens.
Experimental animals exposed to high ambient PROSPECTS OF MEDICAL THERAPY OF
temperatures, are seen to develop cortical opacities; CATARACT
on the other hand, increase in the temperature of the
The search for an effective medical therapy for senile
posterior chamber, and lens in animals exposed to
cataract has eluded researchers because the actual
bright sunlight in the tropical climate has been
cause of senile cataract formation is not yet fully
demonstrated. Glassblowers exposed to high
understood. Based on the currently accepted
infrared radiation have shown increased prevalence
hypotheses of human cataract formation, various
of cortical opacities in their 5th and 6th decades. This
drugs have been evaluated for their potential
shows that the damage caused by the infrared
anticataract effect, but none has scientifically proved
radiation might be cumulative.
to be effective.
Studies also show that bright sunlight and high
environmental temperature, and total amount of
Anticataract Drugs
annual exposure to sunlight have a direct relation to
high incidence of senile cataract in the hot and dry 1. Antioxidants
areas of the world. Epidemiological studies reveal Glutathione
that cortical opacities were seldom seen in the 10 to Beta carotene
12 o’clock segment of the lens. This may be attributed Twin 80
to the protective effect of the upper lid against light Ansam C
induced thermal damage to the lens.19 Benzyl alcohol
Vitamin E
Other Factors 2. Aldose reductase inhibitors
Sulindac
Epidemiological studies indicate that:20
Sorbinil
a. Dark colored people have higher risk of
3. Inhibitor of nonenzymatic glycosylation
developing cataract
Aspirin
b. Prevalence of cataract is more in short persons
4. Miscellaneous
c. Cataract is common in people of rural origin with
Bendazac
poor socioeconomic status.
Antioxidants
BIOCHEMICAL CHANGES IN CATARACT Glutathione It is a tripeptide consisting of glutamic
The following biochemical alterations take place in acid, cysteine, and glycine. The high concentration
cataractous lens: of its reduced form in the normal lens, and decreased
1. Reduced level of soluble proteins (crystallins). concentration in all types of cataract has led to several
2. Increased level of insoluble proteins (albu- hypotheses of its role in lens metabolism.
Chapter 43: Etiopathogenesis of Senile Cataract: Prospects of Medical Therapy 331
Prevention and reversal of lens opacities by gluta- 1981;277.
thione has been reported in experimental animals. 2. Mohan M, Sperduto RD, Angra SK. Indo-US case control study
of age related cataracts. Arch Ophthalmol 1989;107:670.
However, in a prospective study, 2 percent reduced 3. Hiller R, Sperduto RD and Ederer F. Epidemiologic associations
glutathione eye drops q.i.d. did not show any effect.21 with cataract in 1971-1972: National Health and Nutritional
Examination Survey. Am J Epidemiol 1983;118:239.
Beta carotene and Twin 80 Beta carotene and Twin 80 4. Duke-Elder S. Cataract. In: Duke-Elder S (Ed). Diseases of the
prevented light injury to the lens in experimental Lens and Vitreous, Glaucoma and Hypotony. St. Louis, Mosby
animals. 1969;155.
5. Chylack LT Jr, Leske MC, McCarthy D et al. Lens opacities
Ansam C An alcoholic metabolite of the nonsteroid Classification System ( LOCS II) Arch Ophthalmol
antiinflammatory drug (NSAID) diclofenac, having 1989;107,991.
antioxidant properties has got protective effect 6. Chylack LT Jr, Wolfe JK, Singer DM et al. The Lens Opacities
Classification System III. Arch Ophthalmol 1993;111,831.
against lipid perioxidation of the lens. It prevents
7. Stratasma BR, Horwit J, Takemoto L et al. Clinicobiochemical
oxidation of reduced thiol (-SH) groups, and correlations in ageing-related human cataract. Am J
maintains glutathione in reduced form. Ophthalmol 1984;97:457.
8. Javitt J, Sommer A and Venkataswamy G. The economic and
Benzyl alcohol It is a strong antioxidant. It has physio- social impact of restoring sight. In: Henkind P (Ed) Acta XXIV
chemical properties similar to the breakdown metabo- International Congress of Ophthalmology. Philadelphia: JB
lites of NSAID. Lippincot, 1983;1308-12.
9. Simoons FJ. A geographic approach to senile cataracts: Possible
Vitamin E Vitamin E, a naturally occurring antioxi- links with milk consumption, lactase activity, and galactose
dant, has been shown to prevent photoperioxidation metabolism. Dig Dis Sci 1982;27:257.
of lens lipids. Though in experimental animals 10. Ederer F, Hiller R and Taylor HR. Senile lens changes and
diabetes in two population studies. Am J Ophthalmol
cataract progression is slowed down, in clinical studies 1981;91:361.
there is no statistically significant effect. 11. Minassian D, Mehra V, Jones B. Dehydration crisis from severe
diarrhea or heat stroke and risk of cataract. Lancet 1984;1:751.
Aldose Reductase Inhibitors 12. Minassian D, Mehra V, Verry J. Dehydration crisis: A major
risk factor in blinding cataract. Br J Ophthalmol 1989;73:100.
Sulindac Sulindac, an NSAID is a potent inhibitor of 13. Harding J, Rixon K. Carbamylation of lens proteins: A possible
the an enzyme aldose reductase, which converts factor in cataractogenesis in some tropical countries. Exp Eye
glucose to sorbitol via the polyol pathway. Sugar Res 1981;31:567.
14. Harding J and Rixon K. Is diarrhea a major cause of cataract in
cataract could be prevented and slowed down by
some tropical countries. Metabolic Pediatr Syst Ophthalmol
aldose reductase inhibitors.22 1981;5,161.
15. Bhatnagar R, West KP Jr and Vitale S. Risk of cataract and
Sorbinil Sorbinil, 5-6 fluorospirochroman 4-5 imida-
history of severe diarrheal disease in Southern India. Arch
zoline 2, 4' dione, is also a potent aldose reductase Ophthalmol 1991;109:696.
inhibitor. Its oral administration has prevented experi- 16. Varma SO, Chand D and Sharma YR. Oxidative stress on lens
mental sugar cataract formation, induced by diabetes and cataract formation: Role of light and oxygen. Current Ete
or diet containing 50 percent galactose, and topical Res 1984;3:35.
17. Al-Ghadyan AA, Cotlier E. Rise in lens temperature on exposure
application of 1 percent drops prevented galactose
to sunlight or high ambient temperature. Br J Ophthalmol
induced cataract in rats. 1986;70:421.
18. Mohan M, Sharma YR, Vaypayee RB et al. Clinical evidence for
Nonenzymatic Reductase Inhibitors In patients of light induced thermal damage in cortical cataract. In: Kockwin
rheumatoid arthritis, long-term use of aspirin is asso- O, Saaki K, Keske MC (Eds). Risk Factors for Cataract
ciated with a decreased rate of cataract progression.23 Development. Dev Ophthalmol Basel, Karger 1986;17:114.
The mode of anticataractous action of aspirin is 19. Leske MC and Sperduto RD. The epidemiology of senile
considered to be reduction of serum tryptophan cataract. A review. Am J Ophthalmol 1983;118:152.
20. Bhuyan KC, Bhuyan DK and Podos SM. Evidence of increased
levels, inhibition of the enzyme aldose reductase, and lipid perioxidation in cataracts. IRCS 1981;9:126.
prevention of nonenzymatic glycosylation of lens 21. Sharma YR, Vaypayee RB, Bhatnagar R et al. Topical sulindac
proteins. therapy in diabetic senile cataracts: Cataract IV. Indian J
REFERENCES 22. Sharma YR, Vajpayee RB, Bhatnagar R et al. Tropical sulindac
1. Cotlier E. The lens. In Moses RA (Ed). Adler’s Physiology of therapy in diabetic senile cataracts: Cataract IV. In J Ophthalmol
the Ete: Clinical Applications, 7th Edn, St. Louis, Mosby 1989;37:127.
23. Cotlier E, Sharma YR. Aspirin and senile cataracts in rheumatoid
arthritis. Lancet 1981;7:338.
Chapter 44
Work-up for Cataract Surgery

Sudha Sutaria
Evaluation of patients for cataract surgery is operation. The presence of trachoma, especially healed
absolutely essential. Systematic evaluation of the trachoma is not a contraindication but complications
health of the patient and an evaluation of the eye under such as trichiasis or entropion are looked for and
consideration, as well as of the opposite eye is of prime corrected. The lid margins are carefully examined for
importance. chronic infections of the meibomian glands.
GENERAL PHYSICAL STATUS Visual Status

The assessment of general physical status starts with It is imperative to assess the functional health of the
the cardiovascular system. An evaluation of the retina before undertaking cataract surgery, especially
cardiovascular status is essential to rule out so as to enable a prognosis to be made with reasonable
hypertension, ischemic heart disease, and congenital accuracy. History of probable intercurrent ophthalmic
cardiac problems. An assessment of the respiratory diseases may have some deleterious effect on the
system for chronic bronchitis, tuberculosis, or any outcome of cataract operation. Slit lamp
other respiratory condition such as asthma, which may biomicroscopic examination to exclude mainly any
lead to spasm or coughing are made note of. Patients sign of past anterior uveitis; tonometry to rule out
with significant cardiac problems should be referred undiagnosed ocular hypertension
to a cardiologist for relevant investigations to get
clearance for cataract surgery. Diabetes mellitus must Sensitivity to Light
particularly be ruled out, and if detected be thoroughly
In a fully matured cataract the perception of light and
controlled. A special search must be made for condi-
an accurate assessment of the direction from which
tions such as leprosy, sexually transmitted disease,
light is projected ensures good peripheral retinal
skin ailments, and chronic fungus infections. Children
function and a favorable visual prognosis.
with congenital cataracts require a very thorough
The devices which allow images to fall upon the
assessment by a pediatrician. Many disease conditions
macula with not so mature a cataract, can be used to
are associated with congenital cataracts and may pose
assess central vision. A simple method is to perforate
risks in general anesthesia.
a piece of cardboard with five or six holes and hold a
torch light behind it. If the patient can judge the
EVALUATION OF THE EYE
number of holes in the cardboard, the macular
Not only the eye to be operated on, but the opposite function can be taken as normal.
eye also should be thoroughly examined with special
attention to the following: Potential Acuity Meter (PAM)
This is s special attachment for a slit lamp which
External Eye and Adnexa
projects Snellen’s images through a light beam which
Blepharitis, conjunctivitis and dacyocystitis should be narrows to a diameter of 0.1 mm. This beam simulates
excluded and if present should be treated prior to an aerial pinhole aperture, which diverges after it
Chapter 44: Work-up for Cataract Surgery 333
passes through the eye, thus projecting the letters onto ERG, EOG, and VER may also be possible to assess
the central retina as though the lens were not opaque. retinal function.
Ability to read projected letters correctly ensures good
macular function. Another similar device is the Lotmar Examination of the Anterior Segment
visometer, which can be attached to Haag Streit slit
Cornea
lamps.
A detailed examination of the cornea with oblique
Laser Interferometry illumination, and with a biomicroscope is made.
Opacities of the lightest nature, irregularities in the
In case of early cataract with macular lesions, the post-
thickness of the cornea, vascularization and
operative expected visual result is assessed by using
endothelial status are made note of. This is particularly
a Helium-Neon laser generated interference fringes,
necessary as we have a lot of corneal diseases, some
which are focused on the eye from two sources, which
of which may be quiescent and the trauma of surgery
will overlap behind the lens. By changing the size of
may excite a flare up, e.g. herpetic keratitis. Specular
the fringes, visual acuity can be ascertained.
microscopy when possible is made to study the corneal
endothelial status.
Contrast Sensitivity and Glare
The density of the endothelial cells is about 4000
These may be tested in not very dense cataracts, where to 5000 per sq mm. In the elderly and in disease
a more accurate functional status of the retina is to be conditions, the density decreases with persistent
made. These are sophisticated tests, and require a corneal pathology, such as with a high intraocular
sensitive and intelligent patient for accurate results. pressure or cornea guttata, the endothelial density
may fall below 1500 per sq mm thus compromising
Pupillary Reaction to Light corneal health and function. A good assessment of the
corneal endothelium can also be made without a
Reaction of the pupil to light thrown into the eye may
specular microscope by examining the endothelium
sometimes be the only test possible, when the patient
on slit lamp in the zone of specular reflection.
is not too sensitive, perhaps too old and has other
general problems, such as deafness or lack of
Anterior Chamber
comprehension.
The depth of the anterior chamber and uniformity is
B-scan Ultra Sonography a good indication of previous uveal disease. The angle
of the anterior chamber must always be examined in
When the fundus cannot be visualized either with a
cases suspected to glaucoma as also of trauma. Normal
direct or indirect ophthalmoscope, and when the
gonioscopic findings lend to a good prognosis.
response to projected light is either slow or not reliably
Glaucoma, wherever present or suspected must be
accurate, an examination of the eye with ultrasound
confirmed and controlled before embarking on lens
of 8 to 10 MHz must be carried out. This absolutely
implantation. If necessary, the two surgeries for
necessary to rule out vitreous hemorrhage, retinal
glaucoma and IOL may be performed at the same
detachment and intraocular tumor.
time.
Sound waves as they pass through various media
in the eye travel at variable frequencies and produce
Indications for lens implantation
opaque images as they meet the more highly dense
choroid and sclera. Vitreous is sonolucent and outline In general, any eye that can undergo a cataract
image of the posterior segment indicates attached extraction may have a lens implanted. Infants and
choroid and retina. A further mobile sonographic children may pose certain problems for the
probe in various directions may elicit turbulence of inexperienced surgeons but as surgical experience
the posterior layer or the presence of echogenic mounts, the list of contraindications diminish.
membranes indicating previous disease or hemor- In children, one may not be able to assess the future
rhage. Color Doppler B-scans bring out contrasting growth of the eye and a lens inserted in early
images even better. Thus a more accurate prognosis childhood may not provide the necessary visual
is made possible. Electrophysiological tests such as correction. Little children also tend to develop
posterior capsular opacification and may require a no surgery should be begun unless adequate hypotony
secondary interference. However, to prevent ambly- has been achieved.
opia, it is incumbent to operate early enough,
especially in case of bilateral cataracts. A tendency for Various Method of Sterilization
the eyes to diverge indicates that amblyopia may be of Instruments
setting in. 1. Autoclaving It is the commonest widely used
method, and inexpensive and bacteriologically
PREOPERATIVE PREPARATION most acceptable. However sharp instruments tend
to loose their edge.
Preoperative preparation consists of the following 2. Hot air sterilization This is dry and acceptable.
steps: 3. Ethylene oxide (ETO) also called gas sterilization It is
1. Trimming of the eyelashes (some surgeons prefer cost effective for mass work and hospital practice.
only upper lashes). Gamma ray sterilization available for commercial
2. Thorough washing with soap and water of the eye products tends to leave behind some radioactivity.
and skin around must be done and the skin painted 4. Acetone Medical grade acetone is excellent for
at least three times with betadine. Before beginning sharp instruments which are dipped in an acetone
surgery, eyelids, lid margin, and surrounding skin container for 2-10 minutes. Rubber and plastics
of the forehead, nose, cheek, and temple must be dissolve in acetone. Therefore, protective caps must
covered by a sterile drape or thin plastic skin (steri be removed before the instruments are dipped in
drape) available commercially or home made may acetone. The instruments must be rinsed
also be applied. This ensures that the surgeon’s thoroughly in sterile distilled water before use.
hands, instruments, an suture material do not Acetone evaporates quickly. Therefore, the
touch the patient’s skin but only this sterile drape. container preferably of glass or aluminum should
3. A thoroughly dilated pupil, as wide as possible be covered.
must be achieved with tropicamide 1 percent, 5. Formalin vapor sterilization It is useful for equip-
phenylephrine hydrochloride 5 percent, and in ment which cannot be sterilized chemically or by
resistant pupils, drops of flurbiprofen 0.03 percent heat or steam. Equipment must however be left
is instilled until a full dilatation of the pupil is overnight in formalin vapor.
obtained. 6. Sterilization of fluids and IOLs Commercially avail-
4. A good hypotony and a soft eyeball ensure trouble able irrigating fluids are supposed to be sterile; it
free surgery. Hypotony is best achieved by is safe to autoclave them before use.
compressing the eyeball with a rubber ball (super It is good practice to label all the bottles (glass in
pinkie) secured in position over the eye by elastic preference to plastic containers which may have micro
bands and held by Velcro. punctures not easily detected) with the patient’s name,
Measurement of the intraocular pressure before date and use, and any addition to the fluid such as
and after the pressure reducing maneuver is a good gentamicin or adrenaline. These containers should be
indication of hypotony having been achieved. A fall kept in storage for about one month. Should the
of 10 to 14 mm on the Schiotz tonometer indicates a patient develop endophthalmitis of any severity, the
satisfactory low pressure. Mannitol given intraven- fluid used is available for bacteriological study.
ously induces an urgent need to micturate and adds
to problems of patient management on the table. In IOL Power
case of intraoperative positive pressure, a deep The last important consideration for lens implantation
intravenous sedation of the patient with diazepam is estimation of power of the lens that is to be
often helps to lower the pressure. As a cardinal rule, implanted.
Chapter 45
Evolution of Modern
Intraocular Lens Surgery
Suresh K Pandey, Liliana Werner, David J Apple
Age-related cataracts represent the most common Table 45.1: Evolution of techniques for cataract surgery
cause of blindness in the world. At present there are
Technique Year Author/ Surgeon
about 2.0 million cataract operations per year.
Worldwide, 14,000 new patients with cataract appear Couching 800 Susutra
everyday. At the beginning of the 21st century, ECCE* (Inferior incision) 1745 Daviel
modern cataract-intraocular lens (IOL) surgery has ECCE (superior incision) 1860 von Graefe
become one of the safest, most successful, and most ICCE** (tumbling) 1880 Smith
frequently performed outpatient surgeries in the
ECCE with PC-IOL*** 1949 Haroid Ridley
industrialized world including North America. 1,2
Approximately 6,000,000 implants being done ECCE with AC-IOL**** 1951 Strampelli
worldwide each year. Phacoemulsification 1967 Charies Kelman
Ophthalmic surgeons have witnessed a significant Folbable IOLs 1984 Mazzocco
evolution in surgical techniques for cataract extraction Capsular Surgery 1992 D J Apple
in the 20th century. The most remarkable advance is, Accommodating IOLs 1997 Cummings/Kamman
of course, the considerable decrease in the size of
Phakonit/Microphaco/ 1998 A Agrwal/RJ Olson/
the wound incision. Small-incision cataract surgery MICS+ J Allo
using phacoemulsification through clear corneal self-
Dye-enhanced Cataract 2000 SK Pandey/L Werner/
sealing incisions avoids cauterization and suturing. Surgery DJ Apple
Moreover, this is faster, more controlled, and less
traumatic, when compared with conventional large- *ECCE: extra capsular cataract extraction;
incision extracapsular cataract extraction (ECCE). **ICCE: Intracapsular cataract extraction.
With the advent of the Ultra small incision cataract ***PC-IOL: posterior chamber intraocular lens
surgery technique today it is possible to remove the **** AC-IOL: anterior chamber intraocular lens
cataract through a 0.9 mm incision.3,4 The evolution + MICS: Microincision cataract surgery.
in surgical techniques for cataract extraction is
summarized in Table 45.1. tival anesthesia. Due to marked improvements in
Anesthetic techniques for cataract surgery have surgical techniques, it is no longer essential to ensure
also advanced significantly (Table 45.2).5 General complete akinesia of the eye and as a consequence,
anesthesia was preferred in past years, followed by the technique of topical anesthesia has been
various techniques of injectable anesthesia including popularized as “phaco anesthesia”.This includes eye
retrobulbar, peribulbar, sub-tenon, and subconjunc- drops application, sponge anesthesia, eye drops plus
intracameral injection, and most recently gel
Table 45.2: Evolution of anesthetic techniques (couching) (Fig. 45.1). Sir Harold Ridley’s cataract
for cataract surgery extraction and implantation of an IOL marked the
Technique Year Author
beginning of a major change in the practice of
ophthalmology (Fig. 45.4). The first operation for IOL
General anesthesia 1846 — implantation was done at St. Thomas’s Hospital,
Topical Cocaine 1884 Koller London. The extracapsular removal of the cataract
Injectable Cocaine 1884 Knapp took place on November 29, 1949. Ridley selected
Orbicularis 1914 -Van Lint, O’Briens acrylic as the initial biomaterial based on the experi-
-Atkinson ence of ophthalmologists who dealt with World War
Hyaluronidase 1948 Atkinson II injuries involving Perspex plastic (Fig. 45.2).1,2 On
Retrobulbar (4% cocaine) 1884 Knapp postoperative refraction, it was revealed that the eye
Posterior Peribulbar 1985 Davis and Mandel had become myopic (-14.0 D). On February 8, 1950,
Limbal 1990 Furata and IOL of the correct power was inserted.6
coworkers
Anterior peribulbar 1991 Bloomberg SMALL INCISION CATARACT SURGERY
Pinpoint anesthesia 1992 Fukasawa AND IMPLANTATION OF FOLDABLE LENSES
Topical 1992 Fichman
Topical plus intracameral 1995 J Gills Charles D Kelman, believed that cataracts could
No anesthesia 1998 A. Agarwal theoretically be removed through a 2 or 3 mm incision
Cryoanalgesia 1999 F Gutierrez- by using vibrational energy to fragment the lens
Carmona inside the eye. Dr Kelman garnered the idea
Xylocaine jelly 1999 P Koch, EI Assia reportedly after a visit to the dentist, where he found
Hypothesis, No anesthesia 2001 SK Pandey, an ultrasonic device being used to help remove plaque
A Agarwal and debris from teeth. Phacoemulsification, invented
and pioneered by Dr Kelman, has become the most
application (Table 45.2). preferred method of cataract surgery in USA and
the industrialized world (Table 45.1).
LARGE INCISION CATARACT SURGERY
AND IMPLANTATION OF RIGID LENSES Foldable Lenses Manufactured from Hydrophobic
and Hydrophilic Acrylic and Silicone Biomaterials
In former times, when anesthesia and fine surgical
instrumentation were beyond conception, the A variety of foldable IOL designs manufactured from
cataractous lens was dislocated into the vitreous hydrophobic or hydrophilic acrylics, as well as
Fig. 45.1: Illustration from a 1966 facsimile of a 1583 German atlas of a renaissance eye surgery, showing the
ancient technique of couching. Left: Frontal view. Right: An example of ornamental couching needles (From: Bartisch,
G.: Augendienst, Dresden, Germany, 1583)
Chapter 45: Evolution of Modern Intraocular Lens Surgery 337
Fig. 45.2: Photographs of Ridley’s 8th implant operation, on May 10, 1951. These pictures were
taken from the original film. The clips range from the von Graefe incision of approximately 10-11
mm in length (upper left) to the lens removal (lower left) and the IOL insertion (low center and right)
Figs 45.3A to C: Illustrate characteristics of the single-piece

AcrySof™ lens (Alcon Labs., Fort Worth, TX, USA). A: Gross
photograph of a human eye obtained postmortem implanted
with this lens design, showing optimal centration of the lens
and clear capsular bag. B: Scanning electron photomicrograph,
showing the “velvet” finishing of the lens edge. C: Gross
photograph, showing the yellow color of the AcrySof™ Natural
lens (under investigation)
Figs 45.4A and B: present features of the Sensar™ lens with the OptiEdge™ technology (Allergan
Inc., Irvine, CA, USA). This design is stated to combine the advantage of truncated optics and at the
same time eliminate the drawbacks such as glare, etc. A: Clinical picture of a patient implanted with
this lens design (courtesy: Allergan Surgical). B: Scanning electron photomicrograph showing the 3
components of the OptiEdge™
silicone biomaterials are available to the anterior September 2001. Subsequently, another surgeon, Dr.
segment surgeon (Figs 45.3 to 45.5). 3 Choice of Amar Agarwal implanted the first Phakonit
foldable lens design varies from surgeon to surgeon. ThinOptX® rollable IOL on October 2, 2001 in
Foldable lenses with truncated optics manufactured Chennai, India. Figures 45.7A to 45.7D illustrate the
from hydrophobic acrylic lenses are preferred by the Phakonit technique with implantation of the
surgeons because of reduced incidence of posterior ThinOptX™ rollable IOL (Abingdon, VA, USA).
capsule opacification (PCO). Silicone polymer was the As IOL technology becomes available that enables
first biomaterial used for foldable lenses. Figures insertion through very small surgical wounds, it is
45.6A to C illustrate some of the newly available clear that ultra-small incision cataract surgery will
silicone lenses. become more commonplace. The first lens available
for implantation in sub-2 mm incisions was a one-
piece acrylic lens manufactured by Acritec (Munich,
ULTRA-SMALL INCISION CATARACT SURGERY Germany).
AND IMPLANTATION OF ROLLABLE LENSES The ThinOptX® IOL is manufactured from off-
Bimanual phacoemulsification can now be performed the-shelf hydrophilic acrylic materials. The dioptric
through an ultra-small (0.9 mm) incision using the powers of this IOL range from –25 to +30, and the
“Phakonit” technique.3,4 The acronym “Phakonit” lens thickness ranges from a 30 μm up to 350 μm. The
stands for phacoemulsification (PHAKO) being ultrathin properties of the lens are attributable to its
performed with a Needle opening (N) via an ultra- design based upon some optical principle.
small incision (I) and with the sleeveless ultrasound At present new technologies are being developed
tip (T). to accommodate various foldable IOLs suitable for
Ongoing research for the development of laser smaller incisions. Phakonit ThinOptX® rollable IOL
probes, cold phaco, microphaco, and micro-incision is the first prototype IOL that can be inserted through
cataract surgery (MICS) confirm the interest of sub-1.4 mm incisions. Further modifications regarding
leading ophthalmologists and manufacturers in the the design and optic sizing of this IOL are in progress.
direction of ultra-small incisional cataract surgery. IOL using hydrophobic acrylic biomaterials combined
The first case of cataract surgery with implantation with square-edged optics to minimize the incidence
of the ThinOptX® (UltraChoice) IOL was performed of posterior capsule opacification are also available
by Dr. Jairo E. Hoyos in Barcelona, Spain in now. Preliminary development of an instrument to
roll the lens and a lens injector has been carried out.
Figs 45.5A to F: summarize some of the hydrophilic acrylic lenses being used today. A: Gross photograph showing the Rayner
Centerflex™ lens. B: Clinical picture of a patient implanted with this lens design (courtesy: Dr. Michael Amon, Vienna, Austria).
C: Scanning electron photomicrograph showing the square edge of the Centerflex™ lens. D: Gross photograph of a human eye
obtained postmortem implanted with the Ciba Vision MemoryLens™, showing good centration of the lens and clear capsular
bag, with the exception of the presence of Soemmering’s ring formation limited to one quadrant. E: Gross photograph showing
the Bausch and Lomb Hydroview™ lens. F: Clinical picture of a patient implanted with this lens design (courtesy: Dr. Manfred
Tetz, Berlin, Germany)
Figs 45.6A to C: illustrate the newly available silicone lenses. A: Clinical picture of a patient implanted with the CeeOn Edge™
(Pharmacia Inc., Peapack, NJ, USA) lens (courtesy: Dr. K. D. Solomon, Charleston, SC, USA). B: Gross photograph showing an
experimental implantation of the same lens design in a human eye obtained postmortem, prepared according to the Miyake-
Apple posterior video-photographic technique. C: Gross photograph showing the ClariFlex™ 3-piece silicone lens with the
OptiEdge™ technology (Allergan Inc., Irvine, CA, USA)
Figs 45.7A to D: illustrate the Phakonit technique with implantation of the ThinOptX™ rollable IOL (Abingdon, VA, USA). A:
Photograph showing the ThinOptX™ rollable IOL. B: The cataract was removed through a 0.9 mm incision using the phakonit
technique. The ThinOptX™ IOL was gently rolled between the thumb and index fingers of the surgeon and inserted through a
sub-1.5 mm incision. C: The ThinOptX™ IOL is unfolding inside the capsular bag, upon normal body temperature. D: Note the
well-centered ThinOptX™ IOL in the capsular bag. Viscoelastic solution is being removed using bimanual irrigation/aspiration
probes. AcrySmart™ is another IOL design that can be inserted through ultra-small incision as shown in Figures 8A-8D. (Courtesy:
Amar garwal, MS, FRCS, Chennai, India)
Fig. 45.8A to D: illustrate the AcrySmart™ IOL design. The pre-folded dehydrated IOL unfolds in balanced salt
solution (model H44-IC-1). B: Later stage in the unfolding process. C: The pre-folded dehydrated IOL was
inserted in the capsular bag. D: Gross photograph showing the AcrySmart™ model 48 S.
Such instrumentation will probably make it possible Table 45.3: Six factors to eradicate PCO
to insert this IOL through a sub-1 mm incision.
Three surgery-related factors Three IOL-related factors
(“capsular” surgery) (“Ideal” ICL)
The Future Challenges
1. Hydrodisection- 1. Bioconpatible IOL to reduce
Despite of considerable advancement surgeons need enhanced cortical stimulation of cellular
to overcome two important challenges. These include: clean-up proliferation
A. Eradication of posterior capsule opacification
2. In the bag fixation. 2. Maximal Iol optic-posterior
B. Restoration of accommodation.
3. Small CCC diameter capsule contact, angulated
ERADICATION OF POSTERIOR slightly smaller than that haptic, “bioadhesive”
CAPSULE OPACIFICATION of IOL optic. This places biomaterial to creat a
We have proposed 6 factors to eradicate PCO the CCC edge on the “shrinkwarp”
(Table 45.3).7 Efforts are in progress to eradicate PCO, anterior surface of the 3. IOL optic geometry
optic and helps square, truncated edge
a nagging complication of cataract-IOL surgery. sequeter the capsular
Eradication of PCO is critical for success of multifocal bag. This creates a
and accommodative lenses. “shrinkwrap” of the
capsule around the IOL
New Concept for PCO Eradication: optic.
Sealed Capsule Irrigation (SCI)
PCO is the major cause for vision loss following

cataract surgery, and a major problem in pediatric
cataract surgery where the incidence approaches
100%. Reducing or eliminating PCO relies on
removing cells from the anterior and equatorial
regions of the lens capsule after cataract removal.
Dr Anthony Maloof has developed a new concept
in irrigation of the human lens capsule following lens
surgery called Sealed Capsule Irrigation (SCI), which
may also allow the isolated safe delivery of
pharmacologic agents into the capsular bag following
cataract surgery (Fig. 45.9). Sealed Capsule Irrigation
is a form of Sealed Irrigation System applied to the
internal eye, and may be applied elsewhere to the
body. In the eye, the technique of capsular bag
irrigation may be used with pharmacologic agents to
target lens epithelial cells and reduce PCO. The SCI
should meet the following requirements: it should
be minimally invasive, be easy to use, fit through a
small incision, be relatively inexpensive, provide a
repeatable seal with the lens capsule, and be not add
significantly to the duration of routine cataract
surgery.
RESTORATION OF ACCOMMODATION
Accommodative Intraocular Lenses
The stellar success and perfected results of modern
small-incision cataract-IOL surgery after phaco-
emulsification has provided motivation to cataract
surgeons to restore accommodation. Several manufac-
turers, ophthalmologists and vision research scientists
are in the process to design and evaluate the
accommodative IOL for placement in the capsular bag
of the human and animal eyes to assess some degree
of functional accommodation. These approaches are
based on replacing the presbyopic crystalline lens with
an artificial IOL of fixed focal length that could,
theoretically, be translated forward in the eye with
an accommodative effort. One possible approach that
has been explored experimentally in animals is
injection of a polymer lens into the capsular bag
through a small capsulorhexis after
phacoemulsification. Some researchers have explored
the surgical techniques required to inject a polymer
into the capsular bag and the efficacy of these
procedures to restore accommodation in monkeys.
Some of the currently available accommodative IOLs
Fig. 45.9: Illustrate the concept of a sealed capsule irrigation include hinged-plate haptics IOL, BioCom Fold IOL,
device (SCID) or perfect capsule™ being developed by Dr. manufactured by the Morcher® GmbH, Germany,
Anthony Maloof. (Courtesy: Anthony Maloof, MD). akkoomodative 1 CU, manufactured by
Fig. 45.10A to D: Efforts are in progress to restore accommodation after cataract-IOL surgery using accommodative lenses. A:
Gross photograph showing the Morcher BioComFold™ lens. B: Schematic drawing representing the HumanOptics Akkommodative
1 CU lens implanted in the capsular bag of a human eye. C: Schematic drawing representing the C and C CrystaLens™. D:
Gross photograph showing an experimental implantation of the Visiogen Inc. (Irvine, CA, USA) intraocular accommodating
system in a human eye obtained postmortem, prepared according to the Miyake-Apple posterior video-photographic technique.
The capsular bag of the eye was stained with trypan blue, to enhance visualization of the lens. The picture was taken from an
anterior view with retroillumination.
HumanOptics, Erlangen, Germany, and AT-45 IOL 1. Apple DJ, Ram J, Foster A, Peng Q. Elimination of cataract
manufactured by C and C (Figs 47.10A to 10D). blindness: A global perspective entering the new millennium.
Surv Ophthalmol 2000;45:S1.
2. Werner L, Izak AM, Isaacs RT, Pandey SK, Apple DJ. Evolution
SUMMARY AND CONCLUSIONS and pathology of intraocular lens implantation. In: Yanoff M,
Ducker JS (Eds): Ophthalmology. St Louis, Mosby-Yearbook,
Intraocular lens implantation, introduced in England
2002 (in press).
by Sir Harold Ridley in 1949, has emerged as a supre- 3. Agarwal A, Agarwal S, Pandey SK, Agarwal A, Bagmar A,
mely successful procedure in the 21st century. Inven- Shah SP. Phakonit: Lens removal through 0.9 mm incision. J
tion and development of phacoemulsification tech- Cataract Refract Surg 2001;27:1531.
nique by Dr Charles Kelman, facilitated “small-inci- 4. Pandey SK, Werner L, Agarwal A, Agarwal S, Agarwal A, Lal
V, Patel N, Hoyos JE, Callahan W, Callahan JS, Callahan JD.
sion cataract surgery” allowing a reduction in size of
Phakonit: Cataract removal through a sub-1mm incision and
the incision from approximately 10-3 mm. Recent implantation of ThinOptX® rollable intraocular lens. J Cataract
development of bimanual phacoemulsification Refract Surg 2002;28:1710.
technique allowed ophthalmic surgeons to perform 5. 9. Pandey SK, Werner L, Apple DJ, Agarwal A, Agarwal A,
“ultra small-incision cataract surgery” using a sub Agarwal S. No anesthesia clear corneal phacoemulsification
1 mm incision. New IOL lens designs, improved versus topical and topical plus intracameral anesthesia:
Randomized clinical trial. J Cataract Refract Surg 2001;27:1643.
manufacturing techniques, and quality controls, 6. Trivedi RH, Apple DJ, Pandey SK et al. Sir Nicholas Harold
coupled with improved microsurgical techniques and Ridley, He changed the world so that we might see it better. In
viscosurgery have contributed and will contribute J Ophthalmol 2003;51, 211.
to this acceptance. 7. Pandey SK, Werner L, Apple DJ. Posterior capsule opacification:
Etiopathogenesis, clinical manifestations, and management.
REFERENCES In: Garg A, Pandey SK. Textbook of Ocular Therapeutics.
Jaypee Brothers, New Delhi, India 2002, 408-425.
Chapter 46
History of IOL
Neha Charan, R Charan, H Charan
Sir Harold Ridley inserted the first posterior chamber Second Generation (Development of Anterior
IOL in the left eye of a 45-year-old lady after an Chamber Lenses) (Figs 46.1 to 46.4)
extracapsular cataract extraction (ECCE) at St Thomas
The second generation lenses were the anterior
Hospital, London on 29th November, 1949. Ridley
chamber angle fixated lenses. They had a few advan-
was not aware of the earlier attempts of Tadini and
tages over the Ridley’s lenses, viz:
Casaamata. Ridley first got the idea when a medical
1. Implantation could be performed after an intracap-
student observing him operating a cataract case asked
sular or extracapsular extraction.
why he did not replace the cataractous lens which he
2. Secondary implantation could be performed.
had removed, with a new one. As an Air Force
3. Dislocation of the lens would be minimized.
ophthalmologist, Ridley had observed that retained
However, two major complications of these angle
foreign bodies of aeroplane canopies made of
fixated AC-IOLs were: (1) Corneal decompensation,
polymethyl methacrylate (PMMA) were tolerated
and (2) Glaucoma. In most of the cases, the lens had
well by the eyes. Thus, he chose this material for
to be removed.
making the intraocular lens.1
Third Generation IOLs
PROGRESS OF IOL DEVELOPMENT
(Iris Supported, Iris Clip)
First Generation
Binkhorst in 1957 developed his iris clip lens to
The first generation lenses experimented by Ridley circumvent the major problems of the preceding
in 1948 were of the following specifications:2,3 lenses, viz dislocation in Ridley’s lenses and corneal
Type : Biconvex decompensation in anterior chamber angle fixated
Diameter : 8.35 mm lens. Binkhorst’s lens was clipped to the iris with two
Weight : 17.4 mg in water (modern lens anterior loops and two posterior loops extending
weighs 1 mg in water) behind the iris through the pupil (Figs 46.5 to 46.8).
Refractive : + 24.0 D
power Other Advantages of Iris Clip Lens
The drawbacks of Ridley’s posterior chamber IOLs
a. Foreign body reaction at the angles was
were the following:
eliminated.
i. Severe postoperative reactions due not only to
the retained lens matter but also due to the b. Lens was accurately centered.6-8
remnants of the sterilizing solution on the lens.
ii. A high incidence of dislocation which was about Disadvantages of the Iris Clip Lens
13 percent. a. Weight of the lens was to be borne by the iris
iii. Glaucoma in about 10 percent of cases. leading to iris atrophy
iv. Iris atrophy. b. Pupillary block glaucoma could develop if
The implant had to be removed in approximately peripheral iridectomy or iridotomy was not
15 percent of the cases.4 adequate
Chapter 46: History of IOL 345
Figs 46.1A and B: Baron’s anterior chamber IOL 1952 Fig. 46.2: Strampelli rigid tripod anterior chamber IOL, 1953
Fig. 46.3: Dannheim flexible closed-loop Fig. 46.4: Barraquer J-loop anterior chamber IOL, 1962
anterior chamber IOL, 1952
Fig. 46.5: Binkhorst iris clip IOL, 1957, 1958

Fig. 46.6: Fyodorov Type II “Sputnik” iris-clip IOL, 1968 Fig. 46.7: Worst platina IOL, 1973
Fig. 46.8: Copeland iris-plane IOL Figs 46.9A and B: (A) Choyce Mark VIII rigid anterior
chamber IOL, 1956. (B) Strampelli angle supported ACIOL
Fig. 46.10: Shearing J-loop posterior chamber IOL, 1973

c. Lens was far in front of the nodal point of the 4. Lack of inflammatory reaction
eye. 5. Lack of antigenicity
6. Lack of carcinogenicity.
Fourth Generation
Types of IOLs
Choyce’s anterior chamber one piece lens emerged
as the fourth generation IOL in 1956.5 There have Basically there are of two types:
been as many as nine modifications of Choyce’s a. Three piece lens—optic and the haptic made of
anterior chamber angle supported lens.9 These lenses different or the same material.
are excellent for ease of insertion and stability of b. One piece lens—optic and haptic made of the same
fixation (Fig. 46.9). material.
Fifth Generation Materials for the Optics of the Lens

These are posterior chamber lenses initially modified PMMA
by removing the posterior two loops of Binkhorst’s
Ithas:
four-loop iris clip lens and placing retroiridially after
• Superior consistency
ECCE.10-12 Subsequently, posterior chamber IOLs
• Not fragile
primarily intended for placement in the capsular bag
• Optimum transparency
have been designed (Fig. 46.10).
• Suitable for injection molding, lathing, and
polishing
Advantages of Posterior Chamber Lens
• Easily sterilizable with gas
a. It lies close to the nodal point thereby reducing • Transmits broader light spectrum than the human
image magnification and aniseikonia. lens.
b. Glare is eliminated because the lens is covered by
the iris. Other Optic Materials
c. It provides good pupil mobility.
Foldable IOLs made of silicones, acrylics, and
d. The fundus view is superior.
hydrogels.
e. Damage to the corneal endothelium, trabecular
meshwork iris erosion, as well as late dislocation
Materials for Haptics
are practically nil.
Polyamides—Perlon, Supramid, Nylon 66
FURTHER ADVANCES AND FUTURE OF IOL
The strength, flexibility, and manufacturing properties
After trials undertaken by lens implant surgeons for of this material are suitable for IOL haptics. However,
further development of design and technology of IOL they tend to undergo disintegration when in contact
implantation, following designs have come up. with biologically active tissue13 (not a significant
a. Bifocal or multifocal lens. problem when placed in the biologically inactive
b. Foldable lens which may be implanted through a capsular bag). This coupled with the possible inferior
3 mm incision after phacoemulsification. loop memory has led to abandon this material for
c. Injectable lens by introducing a liquid biomaterial making IOL haptics.
into the intact lens capsule after removing the
cataractous lens matter. This lens would probably Polyethylene Terephthelate (Dacron) and
have the accommodative capability. Polyethylene Glycolterephthelate (Mersiline)
These materials are resistant to hydrolysis and to
MATERIALS
UV irradiation and at the same time well tolerated
The ideal implant material should have the following by ocular tissue. Since 1975, several hundred
properties: Medallion lenses have been implanted by Fechner
1. High optical quality using mersiline sutures.
2. Light weight
3. Resistant to biodegradation Polypropylene (Prolene)
The chief advantage of prolene over the polyamide Optional Features

is its hydrophobic nature, making it highly resistant 1. Multifocal optic modification.
to hydrolysis. This material has been used in 2. Surface modification (such as heparin modifi-
cardiovascular surgery for a long time. However, full cation).
spectrum UV light may lead to a significant loss of 3. Positioning holes and notches (best kept to a
its tensile strength. minimum).
PMMA Clinical Features
One piece PMMA IOLs with PMMA loops are superior 1. Designed for in-the-bag implantation.
to 3 pieces polypropylene loop IOL in that it has a 2. Good permanent centration, best suited for
superior loop memory. Polypropylene loops not only potential use with multifocal IOL optics and
tend to re-expand completely, but they are also more obviates the need for large (6.5-7.0 mm) optics.
subjected to compression and distortion by fibrous 3. Amenable for use with planned ECCE with hydro-
contraction of the capsular bag. Thus, they prevent a (visco) dissection and extraction or preferably
snug fit when placed in the bag. PMMA loops, on the with phacoemulsification.
other hand, symmetrically stretch the posterior 4. Optimal use is with continuous curvilinear
capsule and make possible a close uniform contact of capsulorhexis and hydrodissection.
the posterior surface of the IOL and posterior capsule. 5. Appropriate stretch on posterior capsule will
This close contact is supposed to provide a barrier reduce the incidence of posterior capsular opacifi-
effect to prolification and migration of cells leading cation.
to posterior capsular opacification— “No space no 6. Retains many of the advantages of completely,
cells” effect. Biconvex or posteriorly convex IOLs, circular or disk IOLs without the impracticablities
and posterior angulation of the IOL optic with respect of requiring a large incision and being difficult to
to the haptics up to 10 percent enhance this effect. implant.
IOL Design Features STERILIZATION
1. One piece all PMMA IOLs because of their superior Chemical Sterilization
loop memory as mentioned above.
2. Modified (short) C-loop configuration (easy i. Ridley sterilized the lenses by immersion in 1
insertion, optimal loop conformity to capsular percent solution of quaternary ammonium base
bag). with tetradecyl-trimethylammonium bromide
3. 12.0-12.5 mm tip to tip total diameter (as opposed (Cetrimide). It often gave rise to postoperative
to conventional 13.5-14 mm IOLs). These iridocyclitis, sometimes with hypopyon, hence
downsized IOLs confirm best to the size and shape this method was soon abandoned.
of the capsular bag, (10.5 mm in diameter) and ii. Soaking the lens in 10 percent sodium hydroxide
are easier to insert. Downsizing applies mainly to solution at 35°C for at least 3 hours to destroy
one piece PMMA IOLs, less critical with three piece all the spores and nuclei.12 Shortly before use,
polypropylene loop IOLs. the lens is washed with sterile distilled water
4. Biconvex optic (optically favorable and maximizes and residual sodium hydroxide is neutralized
contact of optic to posterior capsule). by 1 percent sodium bicarbonate.
5. Optic size 5.0 or 6.0 mm diameter or ovoid (5.0 ×
6.0 mm). This represents a compromise to small Gas Sterilization
incision surgery with foldable IOLs. If surgeon’s In this method the IOL is placed in a low pressure
rate of achieving good IOL centration is high, chamber (22-25 mm Hg) with a relative humidity
larger optics are not necessary. level of 45 to 65 percent and exposed to ethylene
Angulation of the loop optic in anterior posterior oxide in a mixture of 12 percent ethylene oxide and
plane to about 10° (again to maximize contact with 88 percent dichlorodifluoromethane (Freon) for 4
posterior capsule). Larger angulation would make hours at 50°C.
insertion difficult, especially through small tunnel Ethylene oxide kills microorganisms by its
incisions. chemical activity. The gas is not supposed to react
with PMMA but supposed to maintain the physical b. Axial length of the eye (by A-scan ultra-
and chemical properties of PMMA. Certain amount sonography).
of ethylene oxide penetrates into the plastic resulting c. Keratometry reading in terms of dioptric power
in formation of toxic material. To purge this material, of the eye or in terms of radius of curvature with
it is advocated to air the lenses in vacuum at higher keratometer.
temperature. It is also recommended that the gas The values of the above parameters are inserted
sterilized lens should be soaked for several minutes into the computer which is programmed in most of
in balanced salt solution (BSS) immediately before the A-scan machines for calculating power by using
they are implanted. Balanced salt solution, however, different formulae.
does not remove the monomers and contaminants as
sodium hydroxide does. Postoperative inflammation SRK Formula
has been observed with ethylene oxide sterilized lens
Simplest and most commonly used dependable
caused either by the strong toxic effect of residual
formula used is SRK formula (Sanders DA Retzleff J
ethylene oxide or their derivatives. This is the only
and Kraff MC). The following equation is used for
sterilization method permitted in the United States
this formula:
at present.14,15
P = A–2.5 L – 0.9 K
where
Radiation Sterilization
P = IOL power to produce emmetropia
Gamma ray sterilization is effective. PMMA can be (in diopter).
exposed up to 2.5 M rad without any significant L = Axial length of the eye (in mm).
alteration of its optical, chemical or physical K = Average of horizontal and vertical power
properties; but radiation more than 2.5 M rad alters of cornea in diopter measured by
the polymer structure of PMMA making it brittle and keratometry.
yellow. Lenses with polypropylene loops cannot be A = Specific constant for each lens type and
sterilized with gamma rays, because it alters the manufacturer.
molecular structure of polypropylene.
Theoretical Formulae
POWER CALCULATION
a. Fyodorov
Three methods may be used to find out the power of b. Colenbrander
the intraocular lens to be implanted in a particular c. Binkhorst.
eye: For calculation of lens power by the above
1. Empirical, formulae, the following additional parameters are
2. Clinical, and essential:
3. Biometry. N = Aqueous and vitreous refractive index.
F = Postoperative anterior chamber depth in
Empirical mm (estimated).
R = Radius of curvature in mm.
In the early days of IOL implant surgery (before 1975)
a standard power of plus 19.0 D was used in all cases.
Holladay Formula16
The argument was that about 80 percent of the
patients have only a small primary refractive error This is an improvement over the other theoretical
and so majority of patients will be satisfied. formulae and said to be a second generation of
theoretical formula. The number of parameters for
Calculating IOL Power by Biometry this formula is much more than in other formula, viz
retinal thickness factor, anterior chamber diameter
Three basic parameters are necessary to calculate the
from angle to angle, surgeon factor, refractive index
power by using various formulae:
of cornea and aqueous, and many more. Though it is
a. Anterior chamber depth (by A-scan ultrasono-
a lengthy procedure, it is considered as the most
graphy).
accurate formula for power calculation.
Sources of Error in IOL Power Calculation by a group of surgeons which are dependent on the
surgical technique adopted by those particular
Perfect predictability of IOL power is probably
surgeons. These values may not be accurate for
unattainable due to inherent limitations either in the
another surgeon using IOL of the same design by
instrument used or in its operation.
the same manufacturer. On the other hand, if the A-
constant for a lens is specific for “in-the-bag” place-
Error in Determination of Axial Length of the Eye
ment and one or both the haptics are inadvertently
a. Ultrasonic axial length measurements, however, placed in the ciliary sulcus, this will lead to some
electronically controlled or computerized have to error in postimplant refraction. In-the-bag fixated lens
make assumptions about the speed of sound in needs to be of a higher power (by about 0.5 to 1.50
the normal and pathological ocular issues. D) as compared to sulcus fixated lens. If the
b. Method of coupling the ultrasound probe is postoperative refraction is consistently found to be
important: incorrect, then the surgeon should find his own A-
i. Immersion technique wherein a sclera cup is constant for a particular lens type and use this in SRK
placed between the lids and is filled with formula for calculation of lens power.
methylcellulose. The A-scan probe is immersed Lens power calculations have been shown to be
in the methylcellulose. The probe does not touch accurate within an error of ± 1.0 D; therefore, it is
the cornea. better to error on the side of mild myopia rather
ii. In applanation or contact method the probe is than hypermetropia. In spite of appropriate lens
either attached to a forward projecting applana- power calculation, there may be some other optical
tion cone from or replaces the tonometer prism errors which are beyond the reach of the surgeon.
of Goldmann applanation or is directly placed Lens power determination may differ between
on the cornea with a coupling fluid. Indentation manufacturers, defect in the manufacture and
of the cornea in this method will give a lower pathology of the lens. There may be difference of
axial length reading. 0.1 mm error in axial effective power up to 1 D or more.
length results in about 0.25 D error is A few points to be remembered while doing
postoperative refraction. biometry are:
c. True axiality of the measurement is subject to i. IOL power calculation should ideally be done
observer error. for both the eyes though the operation is planned
for one eye in the first instance.
Error in Keratometry ii. Measurement should be repeated if :
a. axial length is found to be less than 22 mm or
If applanation is done before keratometry, the
more than 25 mm.
corneal mires may be hazy and difficult to evaluate.
b. Difference between the 2 eyes is:
On the other hand, if the eyepiece of the keratometer
— mean corneal power more than 1 D
is not calibrated properly for the observer, then an
— Axial length more than 0.3 mm.
error of measurement may occur.
c. Resultant emmetropic implant power more
Keratometry is also subject to observer error. The
than ID.
increasing use of autokeratometry obviates this
iii. Patients with contact lens should not wear the
problem.
lens for 24 hours prior to power calculation.
To a certain extent, the error may sometimes be
due to defect in the instrument itself. A 0.25 D error
REFERENCES
in keratometry corresponds to about 0.25 D error in
postoperative refraction. 1. Ridley H. Intraocular acrylic lenses. Trans Ophthalmol Soc UK
1951;71:617.
2. Ridley H. Demonstration of 4 patients at the Joint Clinical
A-Constant Error Meeting. Trans Ophthalmol Soc UK 1952;72:669.
3. Ridley H. Intraocular acrylic lenses. Brit J Ophthalmol
A-constant error in SRK formula may also be a source
1960;44:705.
of error. 4. Jaffe N. S Pseudophakos. St Louis: RV Mosby, 1978.
Published A-constants represent averages of A- 5. Choyce DP. Long term tolerance of Choyce Mark I and Mark
constants for a particular design of IOL determined VIII: Anterior chamber implants. Proc R Soc Med 1970;61:310.
6. Binkhorst CD. Ridley’s intraocular lens prosthesis: The
postoperative reaction, results obtained in 12 cases. Ophthal- 10. Simcoe CW. Iris suture fixation of intraocular lenses. Am
mologica (Basel) 1957;133:384. Intraocular Implant Soc J 1977;3:217.
7. Binkhorst CD. Use of the pupillary lens (iris clip lens) in aphakia: 11. Pearce JL. Experience with 194 posterior chamber lenses in 20
Our experiences based on the first fifty implantations. Br J months. Trans Ophthalmol Soc UK 1977;97:258.
Ophthalmol 1962;46:343. 12. Hobbs BC, Wilson GS. The disinfectant activity of caustic soda.
8. Binkhorst CD et al. The pupillary lens: A substitute for the J Hyg 1942;42:436.
cataractous crystalline lens. Med Radiogr Photogr 1966;42:16. 13. Jaffe NS, Layman HM, Jaffe MS. Cystoid macular edema after
9. Choyce DP. The evolution of the anterior chamber implant up intracapsular and extracapsular cataract extraction with and
to and including the Choyce Mark IX. Ophthalmology without an intraocular lens. Ophthalmology 1982;89:25.
1979;86:197. 14. Stark WJ, Rosenblam P, Maumance AE et al. Postoperative
inflammatory reactions to intraocular lenses sterilized with
ethylene oxide. Ophthalmology 1980;87:385.
15. Stark WJ, Brunner WE, Martin NF. Management of sublaxated
posterior chamber intraocular lenses. Ophthalmic Surg 1982;13:
130.
16. Holladay JT, Praeger TC, Chandler TY et al. Cataract Refract
Surg 1988;13:4.
Chapter 47
Foldable IOLs
Tanuj Dada, Harinder S Sethi
The evolution of the cataract surgery with the ages and the refractive error changes.5 The Intraocular
introduction of intraocular lens implantation has been Contact Lens (ICL) from STAAR surgical and the
one of the major achievements of modern medicine. Phakic Refractive Lens (PRL) Ciba Vision are both
The intraocular lenses provide a precise pseudophakic posterior chamber phakic IOLs that vault over the
optical rehabilitation with minimal magnification and crystalline lens and do not require sulcus fixation.6
excellent optical properties. The advent of small inci- However, ultrasound biomicroscopic studies have
sion surgery made possible by phacoemulsification documented an IOL-crystalline lens touch leading to
and foldable IOLs represents another major milestone cataract formation with these IOLs.
in cataract surgery.1-3 Recently, the era of Phakic
foldable IOLs for refractive surgery has also started. SMART LENS: A NEW IOL TECHNOLOGY
It is important for the ophthalmologists to have an
The lens has been developed by Medennium Inc.,
in-depth knowledge of the basic design and optical
Irvine, California. The Smart lens uses a thermodyna-
features of the various foldable IOLs currently in use.
mic hydrophobic acrylic material that is packaged as
a solid rod 30 mm long and 2 mm wide. When
PHAKIC IOLs
Phakic IOLs are increasingly being used for correction
of high myopic errors (—8 to —20D). These IOLs are
of three main types:3,4
1. Iris fixated, e.g. Artisan/Verisyse IOLs (Fig. 47.1)
2. Angle fixated, e.g. Kelman Duet/Vivarte IOLs and
(Figs 47.2 to 47.4)
3. Posterior chamber IOLs, e.g. ICL /PRL.
The iris and angle fixated lenses require a laser
iridotomy to be performed prior to the lens insertion.4
The Artisan lens requires a 6 mm incision and thus
may be associated with significant astigmatism. The
Vivarte IOL from Ciba Vision is a foldable phakic
IOL which has three angle supports. 5 It is now
available in a multifocal form also for presbyopic
patients with a +2.5 D add for near correction. The
Kelman Duet is a unique IOL in that it is inserted
through a 1-1.5 mm incision as a two phase
procedure. The haptics are inserted separate from
the optics and are attached to the optic within the
anterior chamber. An additional advantage of this
lens is that one can change the optic as the patient Fig. 47.1: Iris Claw Phakic IOL
Chapter 47: Foldable IOLs 353
implanted into the eye via a small incision, the rod is
transformed at body temperature into a soft gel-like
material that has the shape of a full sized biconvex
lens that completely fills the capsular bag. The entire
transformation takes less than 30 seconds. The
material is entirely cohesive and does not leak out of
the capsular bag through the capsulorhexis. The main
advantage of the lens is that it can restore accommo-
dation.
IOL WITH ENDOCAPSULAR RING DESIGN

The Concept 360 is a single-piece hydrophilic acrylic
Fig. 47.2: Angle supported Phakic IOL IOL (Corneal Inc.), with 10% posterior angulation of
the haptics, to guarantee consistent IOL placement,
posterior capsular contact and capsular bending.7 The
main distinguishing feature of this lens is the presence
of six identical loops, which together form a circular,
closed capsular tension ring after it is placed in the
bag. The ring is formed from open loops and can
adapt to different bag diameters. Less lens material
is accumulated since the haptics also occupy the space
between the equator of the lens and the periphery of
the IOL optic, thereby reducing the chance of
epithelial cell proliferation.
SUTURE-FREE IOL FIXATION

IN CAPSULELESS EYES
A sulcus-fixated, sutureless IOL has been developed
to offer an alternative for eyes lacking capsular
support. The lens allowed stable fixation against
dislocation and tilting without the support of the
capsule or trans-scleral sutures. The innovative lens
design has two IOL haptics which run along and
Fig. 47.3: Kelman Duet IOl become embedded within almost the entire
circumference of the ciliary sulcus, providing
increased stability in all plains.8 The haptics end in
two peripheral iris anchors that ‘button’ onto the iris
surface through peripheral iridectomies to prevent
backward sliding of the IOL.
COLLAMER IOL
The collamer IOL from Staar Surgical Inc (USA) is a
pure polymer of collagen and is the most biocompa-
tible IOL (Fig. 47.5). The collagen attracts a mono-
layer of fibronectin on the surface of the lens, which
in turn inhibits deposition of other proteins on the
surface of the lens. Once the monolayer is formed,
Fig. 47.4: Vivarte IOL the lens is not recognized as a foreign body inside
the eye. The material has a refractive index of 1.44
capacity for the near eye. It has a 2 mm near zone in

the center of a 5.5 mm optic which provides 4.0 D of
added power.
Three-zone MIOL
A variety of three-zone MIOLs providing distance
and near vision by using a near annulus at various
distance from the central distance component have
been popular. The Storz True Vista TM and the
Domilens Progress ThreeTM are examples of this style.
Patients with normal pupils do enjoy both near and
distance vision but smaller pupils can obstruct the
Fig. 47.5: The Staar Collamer IOL near component with some three-zone MIOLs. One
advantage of this lens design is that even though
there is pupil dependency, distance vision is always
and is available both as a single piece and multipiece
preserved despite the loss of near acuity with miosis.
IOL.9
The Storz True VistaTM IOL has a 1.5 mm central zone,
2.6 mm midperipheral zone and an overall diameter
MULTIFOCAL INTRAOCULAR LENSES
of 6 mm. Thus, these lenses have three concentric
The intraocular lenses commonly in use have a fixed refractive zones. Central and peripheral zones
focus which can be adjusted by adjusting the IOL provide distance power, while the midperipheral
power to serve for near, intermediate or distance zone provides near add power.
vision. It is not possible to see near and distant objects
clearly with these lenses and thus patients are always Five-zone Spherical Curve MIOL
dependent on spectacles.10 Over the past decade, a
The AMO ArrayTM SA40N is a lens designed with
variety of multifocal intraocular lenses (MIOLs) have
five zones of near and distance powers on the anterior
been introduced and enjoyed a widespread clinical
surface of the optic. These power rings help to reduce
use. Both refractive and diffractive models have been
pupillary dependency. The ArrayTM is considered a
shown to be effective in allowing each eye to achieve
“distance dominant” lens and provides near acuities
quality, uncorrected distance and near acuity after
without correction in the J-3 range or better, offering
cataract surgery. The major concerns with the use of
good midrange and near acuity for most tasks. The
these lenses are the loss of contrast sensitivity and
lens has a 4.7 mm central zone with 5 annular
the inducement of glare and halos from light sources
refractive zones. Some patients will prefer the
during night vision. 11 All MIOLs require careful
addition of a bifocal add for finer print and especially
attention to IOL power calculations and the creation
under low-light conditions. The AMO ArrayTM is
of a relatively planospherical result after surgery. The
available in a foldable silicone material with PMMA
multifocal intraocular lenses can be classified into
haptics. A new injectable delivery system allows for
following types.1-3
greater ease of insertion. The AMO ArrayTM lens is
the most popular multifocal IOL in current use.
Refractive MIOLs
Two-Zone/Target or Center Surround MIOL Diffractive MIOLs
TM Diffractive optics multifocal technology is slowly
The Iolab NuVue is an example of an MIOL with
the central near add in the middle of the optic gaining wide acceptance. The major advantage of this
surrounded by a distance optical power. A new lens is less pupil dependency and the ability to
model made of silicone with PMMA haptics has provide an even distribution of near and distance
shown surprisingly good clinical results despite the vision. However, manufacturing techniques are more
potential for visual blur with pupillary miosis. The difficult and critical with these lenses due to
NuVue TM is considered to be a “near dominant” difficulties with making of the diffractive plate. The
MIOL and some surgeons use it in a monovision
Alcon ReSTOR diffractive multifocal IOL is one such
IOL, which has an anterior conventional refractive
surface, which provides the distant power and a
posterior concentric diffractive plate, which provides
additional power ranging from 2.5 to 4.5 D. Pharmacia
has also developed a diffractive MIOL, the CeeonTM
811E. Addition of a diffractive component to the
popular Acrysof TM acrylic IOL is also under
consideration.
ACCOMMODATING INTRAOCULAR LENS

The ability to implant a new lens within the original
capsular bag of the crystalline lens and restore the
physiologic accommodation is a concept being
investigated by many research workers all over the
globe. Kamman and Cumming have modified the
traditional plate haptic silicone IOL to allow for
movement of the IOL within the capsular bag after Fig. 47.6: Staar Toric intraocular lens
insertion. This intriguing design has demonstrated
initial success in restoring presbyopic accommodation.
Accommodative amplitudes of approximately 2 to 3 TORIC INTRAOCULAR LENSES
diopters have been observed. However, long-term The plate haptic IOL (Fig. 47.6) design has been
studies have to be done before the clinical efficacy of modified to produce a toric IOL with the correction
these lenses is established. C&C Vision crysalens cylinder added along the long axis of the IOL. This
model AT-45 accommodating IOL has been shown is marked on the surface of the lens optic . For the
in initial studies to provide 2.5 to 2.75 D of toric design to be effective, the lens should not rotate
accommodation. The lens flexes back and forth and within the eye after implantation. Rotation is
moves up to 1.5 mm with contraction of the ciliary relatively unusual but can occur during the first 4 to
muscle.12 6 weeks after implantation, prior to fibrosis around
the lens and through the large positioning holes. After
LASER ADJUSTABLE IOL this 4 to 6 week period, the lens fixates in the capsular
Calhoun Vision (Sanfrancisco, USA) is developing a bag via the fibrosis through the positioning holes and
new IOL whose power can be adjusted fusion of the anterior and posterior capsules. This
postoperatively with laser energy. It is a foldable helps to prevent long-term rotation as well as
silicone IOL embedded with photosensitive silicone decentration and dislocation of the IOL.14,15
macromers. These macromers polymerize after being
hit by a low energy laser. The power adjustments
PIGGYBACK INTRAOCULAR LENSES
can be made by causing a polymerization of these
macromers in different regions of the lens. If the laser This concept involves the use of two intraocular lenses
is fired in the center of the lens, then polymerization placed one on top of the other (piggyback). This may
at the center leads to an increase in the IOL power. be done as a primary procedure to obtain an optimal
Polymerization in the periphery decreases the power refractive result in highly ametropic eyes (e.g. high
of the lens, while polymerization in one meridian can hypermetropia) where sufficiently high power in a
be used to treat residual astigmatism after cataract single IOL may not be available. The second IOL can
surgery. After the surgeon has achieved a satisfactory also be implanted at a later date as a secondary
refractive result, the remaining photosensitive procedure to correct for a poor refractive result of
polymers are destroyed, thereby “locking” the lens the previous cataract surgery. Both the lenses can be
at the desired refraction.13 placed in the capsular bag or one can be placed in the
bag and the second IOL in the ciliary sulcus. The main
complication with use of piggyback lenses is
interlenticular opacification or interpseudophakic
opacification of polypseudophakia (opacification
between the two IOLs) which may require both IOLs
to be explanted.16,17
IMPLANTABLE MINIATURIZED TELESCOPE (IMT)

Vision Care ophthalmic technologies has developed
the IMT device which is basically a miniature
implantable Galilean telescope which can restore
central vision in patients with age-related macular
degeneration (ARMD). It contains a number of
microlenses which magnify objects in the central visual
field and allow the patient to see without external
low vision aids. It is implanted in the posterior Fig. 47.8: Aniridia IOLs
chamber after routine cataract surgery and held in
position by haptic loops similar to ordinary IOLs18
(Fig. 47.7).
ANIRIDIA IOL
Morcher has developed special IOLs for use in
patients with aniridia or a severe post-traumatic
deficiency of the iris (Fig. 47.8). These IOLs are
available in various designs with an overall length
ranging from 12.5 mm to 14 mm and an optic
diameter of 3.5 mm to 5 mm. There is a central optic
made up of clear PMMA surrounded by an aperture
of black PMMA material with a size ranging from 3.5
to 10 mm. These IOLs have an A constant of 118.1
Figs 47.9 and 47.10: Thinoptx Rollable IOL

Fig. 47.7: Implantable Miniaturized Telescope (IMT) (Courtesy Dr Amar Agarwal)
and are available in a dioptric range of 10-30
dioptres.19,20
THINOPTX ROLLABLE IOL

The Thinoptx IOL (Figs 47.9 and 47.10) can be
inserted through a 0.9 mm incision. It is the latest
advancement in small incision surgery that allows
for complete phaco surgery via the two side ports.
These IOLs have a thickness of 100 microns and can
be manufactured in powers ranging from +30 D to –
30 D. These ultra-thin lenses are made up of
hydrophilic material and used along with the
Phakonit surgery. The front surface of the lens is a
curve that resembles a radius and the back surface
has a series of steps with concentric rings. The back
surface can be concave, convex or plano. The lens is
taken out of its container and placed in a bowl of BSS
to make it pliable. It is then taken into the surgeon’s
hand between the index finger and the thumb. The
lens is then rolled in a rubbing motion and held with
a forceps for insertion through the side port incision.
Once inside the bag, the lens opens up gradually as it
warms up to the body temperature.1,3
NEGATIVE SPHERICAL IOL

The Tecnis intraocular lens from Pharmacia is the first
IOL designed to reduce spherical aberration.
Investigators have demonstrated improvement in
contrast sensitivity under mesopic and photopic
conditions with this technology. Recent advances in
wavefront measurement of total ocular aberrations
and corneal aberrations have demonstrated that the
Figs 47.11 and 47.12: AcrySof Natural IOL
asphericity of the cornea remains constant throughout
life, while the refractive gradient of the lens changes
and produces increasing spherical aberration. The This is the new AcrySof single-piece blue-blocking
decline in contrast sensitivity with age parallels an IOL (SB30AL or AcrySof Natural IOL). This IOL has
increase in spherical aberration. The Tecnis IOL is transmission characteristics similar to those of the
designed to reproduce the compensatory negative natural crystalline lens of a 53-year-old human. A
spherical aberration of the youthful crystalline lens yellow chromophore (Figs 47.11 and 47.12) has been
and increase pseudophakic contrast sensitivity. The added in the IOL which absorbs the blue light.
6-mm optic polysiloxane lens is equiconvex with a Therefore, in addition to blocking ultraviolet light,
prolate anterior surface and a refractive index of 1.46. wavelengths between 400 and 450 nm are only
The posterior and anterior edges are sharp and the partially transmitted. The high-frequency blue
polyvinylidine fluoride haptics have a capsular C wavelength light may be more likely to damage the
design. Clinical trials have shown a uniform improve- retina through release of free radicals. The AcrySof
ment of contrast sensitivity over a variety of spherical Natural IOL blocks the unnatural transmission of this
IOLs in intra- and inter-individual studies.21 blue light and thereby may protect the retina better
than standard UV-blocking IOLs. The yellow colored
BLUE LIGHT-FILTERING IOL lens is also more easily visible inside the cartridge
and thus easier to load and implant.
COMPLICATIONS OF FOLDABLE Bag Sulcus Fixation

INTRAOCULAR LENSES
During insertion of the IOL, the lower haptic may be
Descemet’s Membrane Detachment caused by placed in the bag and the upper haptic may lie in the
IOL during Insertion ciliary sulcus. This can lead to IOL decentration and
the haptic may also cause a chronic uveitis/pigment
When inserting an IOL, the lower edge of the optic dispersion by rubbing on the iris tissue. Asymmetric
can cause a Descemet’s membrane detachment. This loop placement can also cause the windshield wiper
Descemet’s membrane detachment is likely to occur syndrome with the superior loop and optic shifting
if IOL is inserted just parallel to the scleral tunnel position with eye movements and causing damage
incision and where a detached scroll of membrane is to the corneal endothelium. To avoid this
already present. In such cases, the membrane can be complication, the upper loop of the IOL should be
repositioned through the injection of air or expanding carefully dialed in the bag and the surgeon should
gas into the anterior chamber.1-3 check that both haptics are in the bag before
concluding the surgery.1-3
Posterior Capsular Rupture during IOL Insertion
The posterior capsule can be ruptured during IOL IOL Decentration
insertion; and if there is a pre-existing tear in the
posterior capsule, it can extend. Such a complication Implanting a small diameter IOL (which is meant to
can occur if adequate quantity of viscoelastic has not go in the capsular bag) in the ciliary sulcus can lead
been inserted in the bag or there is considerable to a severe decentration of the IOL. This is especially
leakage of viscoelastic substance during IOL insertion. seen when a rent in the posterior capsule occurs and
The use of a passport system with plate haptic lenses the small diameter IOL is placed over the margin of
is more likely to cause this problem. If there is a tear the capsulorhexis by the surgeon. It is important to
in the posterior capsule prior to IOL insertion, the remember that plate haptic lenses which do not have
injector/passport system should not be used at all. If open loops should never be placed over the
a tear occurs during IOL insertion, the IOL may be capsulorhexis. The surgeon should always have a
left in the bag if the tear is small and the viscoelastic large diameter (6.5 mm optic, overall diameter 13
removed manually with a Simcoe cannula or using mm) IOL available for implanting in the ciliary sulcus
bimanual irrigation-aspiration. However, if there is in the event of a large posterior capsular rupture. In
a large tear, then the IOL should be placed on the cases of zonular dehiscence, a PMMA endocapsular
margin of the capsulorhexis.1-3,22,23 ring should be implanted within the capsular bag and
then the IOL inserted, to prevent decentration of
IOL Damage during Insertion the IOL.1-3,24,25
The haptics may be damaged during IOL insertion Lens Dislocation

through a small wound and one of the haptics may
be broken. In such cases, it is essential to remove Complete lens dislocation into the vitreous is a rare
and replace the IOL. During insertion, care should complication. It may occur due to the presence of an
be taken to adequately extend the incision so as not unrecognized zonular dialysis during surgery or the
to force the IOL through a small and tight wound. presence of pre-existing zonular deficiency such as
Special caution is warranted when a high power IOL in post-traumatic eyes or eyes that have undergone
is injected. Use of a wrong forceps for holding the previous vitreoretinal surgery. Such a complication
IOL may cause compression marks on the IOL optic has also been reported after YAG capsulotomy,
and may even crack the IOL requiring explantation especially with plate haptic lenses. A pars plana
of the IOL. Special IOL cutters are available (Osher vitrectomy is necessary for removal of lenses
IOL cutter, Utrata foldable lens cutter) to cut the optic dislocated into the vitreous and the intraocular lens
and explant the IOL through an unenlarged incision. may then be repositioned with iris or scleral suturing
If these are not available it is better to enlarge the or substituted with an anterior chamber IOL.1,2,23,24
incision and remove the IOL.1-3
Silicone Oil Adherence to IOL
Irreversible silicone oil adhesion to the optic of a creates an anterior shift of the IOL and progressive
silicone foldable IOL may occur during vitreoretinal myopia. The condition can be prevented by
surgery. The silicone oil droplets condense onto the performing a large capsulorhexis. The treatment of
optic of the IOL and lead to a severe degradation of this capsular distension syndrome is done by doing
the optics of the IOL. This condition can be avoided a Nd-YAG laser capsulotomy of the anterior capsule.
by not implanting silicone IOLs in eyes with present A nick is created at the edge of the capsulorhexis at
or potential vitreoretinal disease2,3 2/3rd locations which allows fluid trapped within
the capsular bag to escape into the anterior chamber.
IOL Discoloration
CAPSULAR CONTRACTURE SYNDROME
IOL discoloration has been reported with the first
generation silicone IOLs. The discoloration of the The anterior capsulorhexis can undergo a progressive
optic varies from light tan to a brown color and contracture leading to a capsular phimosis with
appears from 15 months to 5 years after implantation. obscuration of the visual axis and decentration of the
It can also be seen in the IOLs in vitro if the lenses IOL. This occurs due to a fibrous metaplasia of the
have not been used for a long time. Although this residual lens epithelial cells and is aggravated if the
coloration does not affect the visual acuity, it can original capsulorhexis is small. This complication is
cause a fall in the contrast sensitivity.1,2,26,27 most frequently seen with the silicone plate haptic
lenses. The contracture can be relieved by performing
IOL Glistenings a YAG capsulotomy at the margin of the anterior
capsule.30,31
This complication has been reported with the AcrySof
IOL, especially if AcryPak packaging has been used Posterior Capsule Opacification
instead of the traditional wagon wheel packaging.
These glistenings are basically microvacuole Posterior capsular opacification (PCO) is currently the
formation within the lens optic and are influenced most important issue in modern-day cataract surgery.
by temperature changes. They can cause a significant Residual lens epithelial cells at the equator and the
decrease in the contrast sensitivity and induce glare.1,2 anterior capsule proliferate and cause an opacification
of the posterior capsule after cataract surgery. This
Glare leads to a decrease in the visual acuity, contrast
sensitivity and causes glare. Silicone and PMMA
Use of small optics (< 5.5 mm) can cause an edge lenses have higher rates of PCO as compared to acrylic
glare, especially during conditions of decreased lenses.1,2,32
illumination, which cause a pupillary dilatation. This A YAG laser capsulotomy has to be performed in
is a serious problem with square edge lenses such as such cases, but it can cause damage to the optic of
the AcrySof with a 5.5 mm optic. It can cause a the IOL and opening up of the posterior capsule
significant visual disability to the patients, especially increases the risk of a subsequent retinal detachment.
during night driving. A trial of 0.5-1% pilocarpine This can be reduced by the following factors:
may be done to decrease the symptoms in such 1. Adequate hydrodissection for facilitating a
patients, although the IOL may even have to be complete cortical clean up.
explanted due to this problem.2,28 2. An in-the-bag fixation of the IOL.
3. Diameter of the capsulorhexis slightly smaller than
Capsular Bag Distension Syndrome
the optic (seals the bag).
This problem arises when a small capsulorhexis 4. High biocompatibility of the IOL.
completely covers the optic and thereby seals the 5. Maximal IOL optic-posterior capsule contact.
capsular bag.29 There is sequestration of fluid secreted 6. Square truncated edge of the IOL optic.
from the remnant epithelial cells within the capsular Primary posterior capsulorhexis with optic
bag and a progressive inflation of the capsular bag. capture in pediatric cases.
Retained viscoelastic material behind the IOL can also
lead to this condition by creating an osmotic gradient Endophthalmitis
and drawing more fluid from across the capsule. This Delayed onset endophthalmitis, which has a delayed
onset and an indolent course, has been described in 14. Schwartz DM, Jethmalani JM, Sandstedt CA et al. Post-
eyes with intraocular lenses. The most common implantation adjustable intraocular lenses. Ophthalmol Clin
North Am 2001;14: 339.
responsible organism is Staphylococcus epidermidis. A 15. Nichamin LD. Treating astigmatism at the time of cataract
more idolent form caused by Propionibacterium acnes surgery. Curr Opin Ophthalmol 2003;14:35.
may present as chronic granulomatous uveitis with 16. Gills JP, Van der Karr MA. Correcting high astigmatism with
white plaques on the posterior capsule. This infection piggyback toric intraocular lens implantation. J Cataract Refract
appears to be enhanced by localized entrapment of Surg 2002;28:547.
organisms within the capsule and has been reported 17. Gills JP, Fenzl RE. Minus-power intraocular lenses to correct
refractive errors in myopic pseudophakia. J Cataract Refract
only in eyes with intraocular lenses. Adherence of Surg 1999;25:1205.
organisms to lenses may play some role. If Propionibac- 18. Till JS. Piggyback silicone intraocular lenses of opposite power.
terium is suspected, vancomycin is the treatment of J Cataract Refract Surg 2001; 27:165.
choice, although some cases may not respond to 19. Kaskaloglu M, Uretmen O, Yagci A. Medium-term results of
medical management and require an IOL explantation implantable miniaturized telescopes in eyes with age-related
with excision of the involved capsule.1-3 macular degeneration. J Cataract Refract Surg 2001;27:1751.
20. Tanzer DJ, Smith RE. Black iris-diaphragm intraocular lens for
aniridia and aphakia. J Cataract Refract Surg. 1999;25:1548.
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9. Sutureless capsular fixation of intraocular lens. Eurotimes humans. Arch Ophthalmol 1991;109:913.
2003;10:16. 28. Mester U, Dillinger P, Anterist N. Impact of a modified optic
10. Brown DC, Ziemba SL. Collamer IOL FDA Study Group. design on visual function: Clinical comparative study. J
Collamer intraocular lens: Clinical results from the US FDA Cataract Refract Surg 2003;29:652.
core study. J Cataract Refract Surg 2001;27:833. 29. Theng JT, Jap A, Chee SP. Capsular block syndrome: A case
11. Leyland M, Zinicola E. Multifocal versus monofocal intraocular series. J Cataract Refract Surg 2000;26:462.
lenses in cataract surgery: A systematic review. Ophthalmology 30. Davison JA. Capsule contraction syndrome. J Cataract Refract
2003;110:1789. Surg 1993;19:582.
12. Montes-Mico R, Alio JL. Distance and near contrast sensitivity 31. Elies Amat D, Coret Moreno A, Mauricio Casanovas J et al.
function after multifocal intraocular lens implantation. Surgical management of the capsular contraction syndrome.
J Cataract Refract Surg 2003;29:703. Arch Soc Esp Oftalmol 2002;77:377.
13. Accomodating intraocular lenses. Eurotimes 2002;7:13.
Chapter 48
Anesthesia for Cataract Surgery

J Ram, SK Pandey
Anesthesia for cataract surgery aims at in making modifications of both retrobulbar and peribulbar
both the patient and the surgeon comfortable and injection techniques. Techniques of subconjunctival
the surgical procedure safe. Preoperative counseling anesthetic injection were reintroduced by Furata et
may create confidence in the patient and make the al8 and Fukasawa9 with the advent of small incision
anesthesia more effective. Trends have shown a swing cataract surgery. Finally, Fichman10 reported the use
from general anesthesia to retrobulbar, then of topical tetracaine anesthesia for
peribulbar, and now recently to topical anesthesia. phacoemulsification.
HISTORICAL BACKGROUND CATARACT SURGERY ANESTHESIA

In 1884, Koller for the first time used cocaine for The objective of cataract surgery anesthesia is to
topical anesthesia in Austria. Herman Knapp 1 assure safe surgical procedure by achieving akinesia,
successfully performed enucleation by using anesthesia, and appropriate hypotony.11
retrobulbar cocaine in the same year. Van Lint2 in
1914 introduced orbicularis akinesia by local injection REGIONAL ANESTHESIA
to supplement topical and subconjunctival anesthesia.
The choice of the local anesthetic agent for each
In 1930 procaine was used for retrobulbar anesthesia
procedure is a matter of personal preference.12 The
by O’Brien.3 Atkinson,4 in 1948 reported that larger
onset of action, duration of action, and safe dosage
volumes of local anesthetic can be injected without
of regional anesthetic agents are summarized in
much increasing the orbital pressure by addition of
Table 48.1.
hyaluronidase. Subsequently, retrobulbar anesthesia
gained rapid favor and became the anesthetic route
Role of Hyaluronidase
of choice. Davis and Mandel 5 reported their
experience with posterior peribulbar injection. When added to local anesthetic solutions, hyaluroni-
Bloomberg,6 Weiss, and Deichman7 reported further dase allows rapid and consistent blocks. In patients
Table 48.1: Regional anesthetic agents
Agents Chemical Conc Max dose Relative Onset of Duration of
(Trade name) classes (mg/kg) potency action (min) action
Procaine (novocaine) Ester 1-4 percent 12 1 7-8 30-45 min
Mepivacaine (Carbocaine) Amide 1-2 percent 7 2 3-5 120 min
*Lidocaine (Xylocaine) Amide 1-2 percent 7 2 4-5 40-60 min
*Bupivacaine (marcaine, Amide 0.25-0.75 percent 3 8 5-11 4-12 hrs
sensocaine)
Etidocaine (Duranest) Amide 1-1.5 percent 400 8 3-5 5-10 hrs
*Preferred regional anesthetic agent by most of the ophthalmic surgeons.
for cataract surgery the extent of the block and its

effects on intraocular pressure (IOP) can be evaluated
with minimal waiting. Hyaluronidase also helps to
limit the rise of IOP that may occur transiently with
retrobulbar injection.13
Preparation of Local Anesthetic Solution

Local anesthetic solution for various blocks is
prepared by adding 1500 units of hyaluronidase and
0.3 ml of adrenaline to 30 ml 2 percent lidocaine
hydrochloride solution. Addition of adrenaline to
xylocaine is contraindicated in patients of ischemic
heart disease, cardiac arrhythmias or hypertension.
SEVENTH NERVE BLOCK

The techniques used to achieve facial blocks are
VanLint,2 O’Brien’s block,7 Atkinson’s block,4 and
Nadbath Ellis akinesia.14,15 The aim of the facial block
is to achieve paralysis of orbicularis oculi muscle to Fig. 48.1: Diagram of O’Brien and Atkinson techniques: (A)
prevent blepharospasm which causes rise of Classic O’Brien technique, (B) Modified O’Brien technique, and
intraocular pressure. (C) Atkinson technique
O’Brien’s Block
Five ml of mixture of 2 percent lidocaine with 0.75
percent bupivacaine is injected using a sharp 25 gauge
5/8 inch (16 mm) needle (passed to its full depth)
anterior to the tragus of the ear over the head of the
condyle (Fig. 48.1). Infiltration of lid skin is also
indicated for those using lid sutures.
Injection into temporomandibular joint or external
auditory meatus may occur accidentally with the
O’Brien’s technique.
Retrobulbar Block
The retrobulbar block produces akinesia of the extra-
ocular muscles and anesthesia of the orbital contents.
The route most commonly used is through lower eye
lid. A small skin wheal is made at the junction of
lateral and middle one third of the inferior orbital
margin. The patient should not asked be to look
superiorly during the injection, as this moves the optic Fig. 48.2: Retrobulbar injection of anesthetic agent at
nerve inferiorly and closer to the inserted retrobulbar junction of medial two-third and lateral one-third of the orbit
needle.16 A 45 mm, 25 gauge needle with a blunt point superior and nasal to the original direction (Fig. 48.2).
is introduced through the wheal and directed Slight resistance or pop is felt as the needle penetrates
backward along the orbital floor until the tip of the the intermuscular fascia. Aspiration should be
needle passes the equatorial region of the globe, attempted to test if any blood vessel is penetrated; if
approximately 15 to 20 mm from skin surface. The this does not occur, 2 to 3 ml of anesthetic solution is
direction of the needle is then changed so that it is then injected. After the injection is made intermittent
directed toward the apex of the orbit which is slightly firm digital pressure on the eye is applied for 20 to
Chapter 48: Anesthesia for Cataract Surgery 363
30 seconds and off for 5 to 10 seconds, to
prevent occlusion of the retinal circulation and carried
out for approximately five minutes in order to
produce both hypotony of the eye and diffusion of
anesthetic agent. Eye is then examined for adequate
akinesia and hypotony: when the patient is asked to
look in all directions, there should be minimal or no
movements. It is important to put two drops of 5
percent povidone iodine into the conjunctival sac to
sterilize it before commencing surgery.
PERIBULBAR (PERIOCULAR) INJECTION

Peribulbar injection is given at the junction of lateral
one third and medial two-thirds of lower lid using
26 gauge needle with bevel toward the globe; 1 ml
of solution is injected in the orbicularis muscle. The
needle is angled slightly laterally and 3 ml of solution
injected slowly at equator, then needle is bit advanced
just past the equator and 4 ml of solution in injected
Fig. 48.3: Peribulbar anesthesia—superior and inferior site
(Fig. 48.3). Mild proptosis and bulging of superior
showing deposition of anesthetic just past to equator
nasal lid fold are indicators of good block. Ocular
compression can be achieved using digital massage, technique of topical anesthesia in 1992, since then it
superpinkie or Honan balloon at least for ten minutes. is rapidly gaining popularity for clear cornea phaco-
Evaluation of ocular motility should be done; in case emulsification. The prerequisites of this technique
of incomplete block it can be repeated either in include well informed and cooperative patient, and
superonasal quadrant or through nasal conjunctival skilled surgeon.
cul-de-sac.
Technique
SUBTENON ANESTHESIA
Several drops of 0.5 percent cetakaine (Tetracaine)
In this technique 2 percent lidocaine is injected into or 0.75 percent bupivacaine or 4 percent lidocaine
subTenon space under the effect of topical anesthetics instilled at 5 to 10 minutes interval before surgery.
with a 27 gauge needle. Alternatively, delivery of The microscope is set on the lowest illumination and
anesthetic agent can also be done using curved/ the patient is advised to fixate on microscope light
flexible cannula after incising the conjunctiva and during the procedure. Frequent dialogue is main-
Tenon’s capsule under topical anesthesia. Advantages tained with the patient during the procedure and
of subTenon anesthesia are lack of elevation of blood continued reassurance is offered. An anesthesiologist
pressure and transitory cardiac arrhythmia. Additio- is required to monitor patient’s discomfort.
nally no postoperative rise of IOP (as seen with Recently, use of preservative free intracameral
peribulbar injection) is seen with this technique.18 lidocaine is getting popularity. Masket’s technique
of topical anesthesia includes use of 4 percent
COMFORTABLE REGIONAL ANESTHESIA
lidocaine topical drops, 0.5 percent tetracaine swab
Regional anesthesia can be made comfortable for to limbus and 0.5 ml of 1 percent nonpreserved
patients by warming it to near body temperature, lidocaine into anterior chamber after paracentesis.19
instillation of topical anesthetic into conjunctival sac Transient reduced but reversible contrast sensitivity
and avoiding epinephrine which is potentially painful and visual acuity were reported for first few
due to its acidity. postoperative hours in those who received topical
plus intracameral lidocaine.
TOPICAL ANESTHESIA
In the 1880s cocaine was used as topical anesthetic. Advantages of Topical Anesthesia
Koller 18 reported that cocaine was an effective Beside it is cost effective, immediate visual recovery,
conjunctival anesthetic agent. Fichman10 reported the avoidance of postoperative ptosis and sight threate-
ning complications (e.g. globe perforation, optic nerve needle with resulting optic atrophy or secondary
damage) are special advantages of topical anesthesia. intraocular hemorrhage due to presumed damage to
The major limitations and drawbacks of topical retinal artery or vein have been reported.24,25 The
anesthesia are a proficient experienced surgeons, well position of the globe may influence the rate of injury.
informed and motivated patient, inability to handle Placing the eye in the primary position reduces the
intraoperative complications, if occurs, unsuitability danger of nerve or vessel damage. Penetration of
for anxious, deaf and those having dense cataract. globe can occur with both retrobulbar and peribulbar
blocks.26
LOCAL ANESTHESIA The risk factor for globe penetration is more in
high myopes having axial length of more than 26 mm.
Local anesthesia is preferred over general anesthesia
Rate of scleral penetration reported by Hamilton et
for cataract as well as other intraocular surgeries. It
al27 is one out of 5235 retrobulbar injections and not
is cost effective and lowers risks of serious systemic
a single perforation out of 6705 peribulbar injections.
complications. Elderly patients and those with
Davis and Mandel 17 reported the rate of globe
significant, medical problems undergoing surgery
perforation in one out of 16224 cases (0.006 percent).
under local anesthesia should be monitored by an
The perforation of the globe is not uncommon in high
anesthesiologist.
myopes who have large eyes with thin sclera but can
Premedication also occur in otherwise normal eyes.28 The signs of
perforation may include sudden pain, loss of vision,
Apprehensive and anxious patients must receive an
most commonly hypotony, or rarely increased IOP.
intramuscular injection of a combination of meperi-
If a penetrating or perforating wound is suspected,
dine (pethidine) with promethazine (phenergan) as
it is not advisable to explore the sclera since needle
a premedication. Alternatively, diazepam 5 mg orally
entry site is small and self-sealing. The common
2 hours preoperatively is also effective.
complications resulting from globe perforation are
retinal detachment and intraocular hemorrhage.
Side Effects and Complications
Retrobulbar hemorrhage following retrobulbar
of Local Anesthesia injection has been reported between 0.074 percent to
Pain and ecchymosis during administration of local 2 percent.16,17,23 Jaffe et al29 recommended postponing
anesthesia are usually caused by large gauge needles the surgery till one week. Raised IOP should be
with blunted points, poorly finished needles with controlled with oral acetazolamide. General
microscopic barbs, penetration of needle through anesthesia is considered in patients having repeated
rectus muscle, too rapid injection of anesthetic and retrobulbar hemorrhage.29
cold nonbuffered anesthetic solution.17 Amaurosis is Central retinal artery occlusion (CRAO) is another
constant with true retrobulbar anesthesia and only sight threatening complication of retrobulbar
rarely seen after periocular anesthesia. Non-sight hemorrhage after retrobulbar injection of anesthetic
threatening complications include ptosis, diplopia, solution.30,31 Increasing proptosis in an eye with retro-
and retrobulbar hemorrhage. Incidence of post- bulbar hemorrhage should alert the surgeons, when
operative ptosis (of 2 mm or more) after cataract retinal circulation cannot be visualized as in cataract
surgery were reported between 0 to 20 percent.20-22 surgery. A lateral canthotomy should be performed
Incidence of diplopia is less than 1 percent reported to maintain retinal circulation and to prevent retinal
by Davis and Mandel. 17 The cause of prolonged hypoxia. Intraocular pressure should be lowered by
muscle malfunction is probably intramuscular injec- using intravenous mannitol or oral acetazolamide.
tion as reported by Rinkoff and associates.23 Eyelid Life threatening complications include cardiac
speculum, bridle suture, pressure on the globe and arrest, respiratory depression, central nervous
upper lid and prolonged upper lid patching are other system (CNS) depression, and seizures. The incidence
factors incriminated in the production of of CNS complications following retrobulbar
postoperative ptosis and diplopia.20-22 Optic nerve anesthesia ranges from 0.09 percent to 1.5 percent.27
damage, globe penetration, retrobulbar hemorrhage, Petty et al32 noted incidence of cardiovascular collapse
and central retinal artery occlusion are important sight in 2 out of 910 cases of retrobulbar injection (0.22
threatening complications. Direct injury to the optic percent), respiratory arrest in 2 cases, and CNS
nerve or central retinal vessels by the retrobulbar symptoms in 3 cases (0.33 percent). Studies have
Chapter 48: Anesthesia for Cataract Surgery 365
implicated direct injection into the sheaths of the A preoperative visit by the anesthesiologist to the
optic nerve and subsequent travel to the CNS via patient is especially important, both to assess the
subdural or subarachnoid space is responsible for medical history, physical and mental state of the
these complications.33 As stated previously, “up and patient and to allay any fears of operation and
in” position of globe should be avoided and the eye anesthesia. In elderly persons sedation under local
is maintained in the primary position to avoid optic anesthesia is usually achieved by midazolam and
nerve sheath injection34 (Fig. 48.4). Ocular side effects fentanyl combination or sedation can also be
of topical anesthetic agents include,18 stinging, super- accomplished by midazolam propafol infusion.
ficial punctate keratitis, corneal erosion, persistent
epithelial defect and allergic reactions. Induction of Anesthesia
Peribulbar anesthesia avoids some of the complica-
tions of retrobulbar injections including injection into Induction of anesthesia usually done by using
the nerve sheaths. Subconjunctival injection of thiopental or propafol since onset is smooth and safe,
anesthetic agent is safest method but does not and none of them causes rise in IOP. Ketamine is not
produce akinesia of the eye lids and globe. suitable for use as an induction agent in intraocular
surgery because of the high incidence of blepharo-
GENERAL ANESTHESIA spam, eyeball movements or hallucination following
its use in adults. It also causes a rise in IOP which is
Local anesthesia is preferred method for most of the more sustained than transient rise, occurring during
procedure but general anesthesia is specially indicated intubation and following the use of suxamethonium.
for35 the following:
1. Pediatric cataract surgery
Intubation
2. Mentally retarded patients
3. Patients with painful arthritis, epilepsy for Endotracheal intubation and controlled ventilation
frequent coughing is good technique since it permits the surgeon to
4. Anxious, apprehensive and psychiatric patients. operate in a clean sterile field with adequate
relaxation. It gives complete control of an otherwise
Technique for General Anesthesia inaccessible airway and avoids coughing movements
which increases IOP. Suxamethonium (1-1.5 mg/kg
Premedication
body weight) should be given intravenously to
ensure adequate conditions for intubation and to
allow sufficient time for establishment of adequate
general anesthesia.
Maintenance of Anesthesia
Anesthesia maintenance is achieved by using oxygen
nitrous oxide (33-66%) with intermittent pancuro-
nium and halothane (0.5-1.5%). Halothane is most
suitable anesthetic agent since it offers rapid induction
to sufficient depth, which causes small fall in IOP,
and is not irritating to trachea. It provides good
operating conditions and is associated with a low
incidence of postoperative nausea and vomiting and
acquire return of consciousness when the anesthetic
is withdrawn. Many other agents have been used,
e.g. Isofluorene, serofluorene, are of current interest.
While under anesthesia, the patient should be put on
Fig. 48.4: Penetration of optic nerve during retrobulbar injection intermittent positive pressure ventilation in order to
by standard 1½ inch needle, if eye is in an elevated and achieve good hypotony. This is particularly important
adducted position for conventional surgery with IOL implantation. At
the conclusion of surgery the relaxant is reversed with 1989;44-63.

intravenous neostigmine (50 mg/kg) preceded by 12. Wilson RD. Complications associated with local and general
anesthesia. Int Ophthalmol Clin 1992;32:1-22.
atropine (20 mg/kg) and spontaneous ventilation is 13. Mindel JS. Value of hyaluronidase in ocular surgical akinesia.
reestablished. Am J Ophthalmol 1978;85:643.
14. Nadbath RP, Rehman I. Facial nerve block: Am J Ophthalmol
Extubation and Recovery 1968;55:143-46.
15. Ellis GS. Akinesia of the facial nerve: A laboratory investigation
To prevent coughing during extubation, an adequate of surgical anatomy. Trans Am Ophthalmol Soc 1968;66:746-
halothane concentration should be maintained until 87.
the close of surgery. The pharynx is suctioned and 16. Ellis PP. Retrobulbar injections. Surv Ophthalmol 1974;18:425.
17. Kirsch RE. Further studies on the use of digital pressure in
the patient is given a few breaths of oxygen and the
cataract surgery. Arch Ophthalmol 1957;58,641.
tube is removed. Oxygen via a disposable facemask 18. Koller C. Preliminary report on topical anesthetic of the eye.
should be administered to all elderly patients until Arch ophthalmol 1934;12,473.
they are fully awakened. 19. Sabbagh L. Intracameral lidocaine spurs acceptance or topical
approach. Eye World 1997;1:28-29.
20. Stasion OG. Postoperative ptosis: Etiology, diagnosis,
CONCLUSIONS treatment, informed consent. Presented at the fourth Annual
Scientific meeting of the Ophthalmic Anesthesia Society, San
Anesthesia for cataract surgery is safe. Local Antonio, 1990;6 Oct.
anesthesia is preferred over general anesthesia. On 21. Kaplan LJ, Jaffe NS, Clayman HM. Ptosis and cataract surgery.
account of several advantages and lower incidence Ophthalmology 198592:237-42.
22. Deady JP, Price NJ, Sutton GA. Ptosis following cataract and
of complications peribulbar block is preferred to trabeculectomy surgery. Br J Ophthalmol 198972:283-85.
retrobulbar block. Topical anesthesia completely 23. Rinkoff JS, Doft BH, Lobes LA. Management of ocular
eliminates life-threatening complications and is penetration for injection of local anesthesia preceding cataract
suitable in hands of skilled surgeon for motivated surgery. Arch Ophthalmol 199198:1421-25.
and cooperative patient to perform clear corneal 24. Morgan CM, Schatz H, Vine AK et al. Ocular complications
associated with retrobulbar injections. Ophthalmology
phacoemulsification. General anesthesia is reserved 1988;95(5):660-65, .
for children, mentally retarded, and apprehensive 25. Pautler SE, Grizzard WS, Thompson LN et al. Blindness from
patients. retrobulbar injection into the optic nerve. Ophthalmic Surg
1991;17(6):334-37.
26. Duker JS, Belmont JB, Benson WE et al. Inadvertent globe
REFERENCES perforation during retrobulbar and peribulbar anesthesia.
1. Knapp H. On cocaine and its use in ophthalmic and general 27. Hamilton RC, Gimbel HV, Strunin L. Regional anesthesia for
surgery. Arch Ophthalmol 1884;13:402. 12000 cataract extraction and intraocular lens implantation
2. VanLint A. A paralysis palpebrale temporarie provoquee dans procedures. Can J Anesth 1988;35:615-23.
l’operation de la cataract. Ann Ocul (Paris) 1914;151:420. 28. Hay A, Flynn HW Jr, Hoffman JI et al. Needle perforation of
3. O’Brien CS. Local anesthesia. Arch Ophthalmol 1948;12:241- the globe during retrobulbar and peribulbar injections.
53. Ophthalmology 1991;98(7):1017-24.
4. Atkinson WS. Local anesthesia in ophthalmology. Am J 29. Jaffe NS: Surgical technique. In Cataract Surgery and its
Ophthalmol 1948;31:1607-18. Complications. CV Mosby Co. St. Louis, Missouri, USA
5. Davis DB, Mandel MR. Posterior peribulbar anesthesia: An 1990;34-108.
alternative to retrobulbar anesthesia. J Cataract Refract Surg 30. Kraushar MF, Seelanfraund, Freillch DB. Central retinal artery
1991;12:182-84. closure during orbital hemorrhage from retrobulbar injection.
6. Bloomberg C. Anterior peribulbar anesthesia: Five years Trans Am Acad Ophthalmol Otolaryngol 1974;78:65-70.
experience. J Cataract Refract Surg 1991;17:508-11. 31. Goldsmith MO. Occlusion of central retinal artery following
7. Weiss JL, Deichman CB. A comprison of retrobulbar periocular retrobulbar hemorrhage. Ophthalmologica 1967;53:191-96.
anesthesia for cataract surgery. Arch Ophthalmol 1989;107:96. 32. Petty JM, Davis JM, Strunin L. Retrobulbar block for cataract
8. Furata M, Tomoko T et al. Limbal anesthesia for cataract surgery: Retrospective review of 910 patients (Abstract). Anesth
surgery. Ophthalmic Surg 1990;21:22-25. Intensive Care 1984;13:95-100.
9. Fukasawa H. Pinpoint anesthesia: Presented at the ophthalmic 33. Drysdale DB. Experimental subdural retrobulbar injection of
anesthesia society meeting, Dallas, 1992;7 Nov. anesthetic. Ann Ophthalmol 1984;16(8):716-18.
10. Fichman RA. Topical anesthesia. In: Gills JP, Hustead RD, 34. Peterson WC, Yanoff M. Complications of local anesthesia. Int
Sanders DR (eds). Ophthalmic Anesthesia. Thorofare, NJ: Slack Ophthalmol Clin 1992;32:23-30.
1993;1661-72. 35. Donlon JV. Anesthesia and Eye, Ear, Nose and Throat. Surgery
11. Ropar-Hall MJ. Anesthesia and akinesia for eye operations. In: in Miller’s Anesthesia. Churchill Livingstone, Inc NY 1994;2176-
Stallard’s Eye Surgery. Butterworth International Edition 83.
Chapter 49
Extracapsular Cataract
Extraction and IOL Implantation
Alpesh R Shah, Abhay R Vasavada
Extracapsular cataract extraction (ECCE) with PCIOL Intraocular Lens Implantation

in the bag is accepted as a well-established technique a. Implantation site
and increasingly used as a preferred procedure by b. Configuration of IOL
most cataract surgeons. This technique needs appro- c. IOL material
priate surgical training and a good operating
microscope. ECCE involves removal of nucleus and PREOPERATIVE EVALUATION
residual cortex, leaving behind capsular support. The
Patient counseling on procedures and expectations is
three options involving ECCE are:
a vital part of the preoperative workup. Any patient
Conventional ECCE: Nucleus is expressed after who needs to undergo cataract surgery should have
anterior capsulotomy through pressure and counter- a general and an ophthalmologic workup. A complete
pressure technique. medical history including diabetes mellitus, hyper-
tension, ischemic heart disease, chronic obstructive
Manual small incision non-phaco: Nucleus is pulmonary disease, bleeding disorders, connective
expressed through tunnel after prolapsing in anterior tissue (collagen) disorders, history of drug intake,
chamber by increasing IOP with the use of ACM drug allergy, etc. should be elicited and conditions
(anterior chamber maintainer) or viscoelastic. should be treated with the help of a physician (usually
an anesthesiologist). The ophthalmologist should be
Phaco: This technique utilizes the ultrasonically aware of medication or drug sensitivities that may
vibrating needle to emulsify the nucleus and aspirated alter the outcome of surgery. The ocular history is
it through the same needle. important to identify conditions that could affect
This chapter deals with conventional ECCE. either the surgical approach or the visual prognosis.
A history of trauma, inflammation, amblyopia, optic
Preoperative Evaluation nerve disease, retinal pathology can affect visual
prognosis.
Surgical Techniques
• Anesthesia Ophthalmic Examination
• Incision It is important to establish whether, apart from
• Anterior capsulotomy cataract, there are coexistent ophthalmic conditions
• Hydroprocedures that may influence surgery or postoperative recovery
• Nucleus removal and outcome. Both eyes are assessed fully by routine
• Cortex removal ophthalmic workup which includes slit lamp biomi-
• IOL implantation and wound closure croscope examination, posterior segment
• Postoperative treatment and refraction observations under mydriasis.
Slit-lamp Biomicroscope Examination and type of the capsulotomy. The lens position
must be evaluated for presence of subluxation,
a. Examination of orbit and ocular adnexa includes:
pseudoexfoliation syndrome to plan appro-
1. Presence of meibomian dysfunction
priate surgical strategy. The lens should also
2. Abnormal tear dynamics
be examined for the presence of any capsular
The surgeon should also note the potency of
changes like plaque on anterior and posterior
nasolacrimal duct to find out the presence or absence
capsules.
of acute dacryocystitis. Deep seated eyes and narrow
palpebral fissure should warn the surgeon about
Refraction and Visual Acuity
difficulties that may be encountered during surgery.
b. Examination of anterior segment Snellen’s acuity is one test for visual performance. It
1. Cornea The cornea is examined carefully for is also important to test distance and near visual
corneal guttate on the endothelium. It has an acuity. In mature cataract projection and perception
important prognostic value for the outcome of of rays should be checked.
surgery. In the presence of guttate, the surgeon
should discuss with the patient the use of diffe- Tonometry
rent types of viscoelastics and should tailor the
IOP should be checked for Glaucoma.
surgery to minimization of trauma to the
endothelium. Fundus Evaluation
2. Anterior chamber The anterior chamber depth
Direct and indirect ophthalmoscopy should be
should be measured with Haag Streit anterior
undertaken to evaluate the anatomical and functional
chamber pachymetry. Central depth of the
integrity of the posterior segment. A full fundus
anterior chamber and size of the nucleus help
examination is necessary to evaluate macula, optic
in planning the appropriate surgical strategy,
nerve, retinal vessels and retinal periphery, paying
especially with reference to the wound size.
particular attention to early macular degeneration
3. Iris Iris examination should include color
which may limit visual rehabilitation after surgery.
and pattern. Abnormalities like iris atrophic
Diabetic patients should be examined carefully for
patches, rubeosis iridis, iris nodules, presence
the presence of macular edema or retinal ischemia
of dandruff-like material at the papillary
with or without neovascularization. The retinal
border and ectropion uvea should be noted.
periphery should be carefully examined to detect the
Abnormalities like peripheral anterior and
presence of vitreo-retinal traction or preexisting
posterior synechiae should also be noted.
retinal holes which may warrant preoperative
4. Examination of pupil Pupillary reactions should
treatment. Optic nerve should be examined for pallor,
be elicited before cataract surgery. Pupillary
cup-disc ratio or other abnormalities.
abnormalities like afferent pupillary defect
(APD) should be noted. A swinging flashlight IOL Power Calculation
test should rule out an afferent pupillary defect
from serious retinal (typically retinal detach- Keratometry for corneal curvature and ‘A’ scan
ment in mature cataract) or optic nerve ultrasonography should be performed to determine
dysfunction (advanced glaucomatous cupping) axial length and calculate appropriate IOL power.
that may indicate a poor visual potential.
5. Examination of crystalline lens The appearance Special Tests
of the lens should be carefully noted. The a. Specular microscopy As corneal endothelium is
cataract should be noted in terms of its type vulnerable during cataract surgery, it may be
[Type I: Nuclear; Type II: Anterior cortical; necessary to examine and record the status of
Type III: Posterior cortical; Type IV: Posterior endothelium before surgery using specular
subcapsular] and density [G1-2: Soft; G3: Firm microscopy. The assessment has a prognostic value
to hard; G4: Hard (Red Brown); G5: Very hard for corneal survival.
(Black or brunescent)]. Awareness of the b. Corneal pachymetry Measurement of central corneal
presence of a brunescent cataract helps in thickness is useful in assessing the function of
planning the size of incision and also the size endothelium.
Chapter 49: Extracapsular Cataract Extraction and IOL Implantation 369
c. ‘B’ scan ultrasonography In eyes that have mature has inherent ability to appose well. The
cataracts it is not possible to make a visual assess- incision is placed just anterior to the limbal
ment of the posterior segment of the eye. It is insertion of conjunctiva. The first step of
necessary to rule out retinal detachment, vitreous incision is perpendicular to the corneal
hemorrhage or vitreo-retinopathy which may surface. About ¾th of the thickness should
complicate cataract surgery. It is necessary to be achieved. The length of the incision is
investigate the eye by B scan to forewarn the about 9 to 10 mm, which can be titrated
surgeon and to advise the patient regarding the depending upon the density of the nucleus.
prospective surgical outcome. The second plane of incision for entry is
d. Conjunctival swab Conjunctival swab should be made with stab knife obliquely. The incision
taken two days prior to surgery. Culture and can be enlarged after injecting viscoelastic
sensitivity tests is done when necessary. Usual either with Bark-Parker’s (BP) knife or with
practice is to give local antibiotic drops (Quinolone corneal scissors. A 2 to 3 mm opening just
group) two-hourly on previous day and four times right side of
at half-hour interval before surgery. 12 o’ clock position is made for initiating
capsulotomy. Enlargement of incision is
SURGICAL TECHNIQUES done after completion of capsulotomy.
Irrigating cystotome can also be used to
Anesthesia
enter the anterior chamber and later for
Peribulbar and fascial block should be given in capsulotomy.
presence of an anesthetist. Intracath should be ready
in all patients to deal with any emergency during Corneoscleral Incision
surgery. Peribulbar injection is a mixture of 5 ml Inj.
A fornix-based conjunctival flap is made and the
xylocaine 2 percent with adrenaline and 5 ml Inj.
bleeding is cauterized. The incision is made using BP
bupivacaine 0.5 percent with Inj. hyaluronidase to
knife starting approximately 1 mm behind the limbus.
aid diffusion within the orbital tissues. Adrenaline
The dissection is carried out in the same plane
should be avoided in hypertensive and ischemic heart
forward till the limbus. The procedure for entry in
patients. Hypotony can be achieved by super pinkie
to anterior chamber and enlargement of incision is
ball or Honan balloon for 10 minutes with intermittent
similar to that of corneal incision.
release of pressure.
Anterior Capsulotomy
Incision
Anterior capsulotomy is probably the vital step in
The cataract incision may proceed from the outer
ECCE. It determines the ultimate outcome of the
surface of the globe to the anterior chamber in a single
extracapsular surgery and also helps in the
plane (perpendicular or beveled) or double plane
implantation of intraocular lens in safe posterior
(combination of both) either positioning superiorly
chamber. Currently the most popular techniques
or temporaly.
practiced for anterior capsulotomy are:
a. Corneal incision: We prefer corneal incision because
A. Multipuncture capsulotomy
of the following advantages:
B. Continuous curvilinear capsulorhexis (CCC).
1. Intraocular maneuvers are easy because of
better access to the cataract.
Multipuncture Capsulotomy
2. Chances of intraoperative iris prolapse are less
compared to corneoscleral incision. This type of capsulotomy creates a ‘ragged’ but
3. There is no bleeding, so the eye remains quiet approximately circular opening. Multiple punctures
in early postoperative period. are made in a circular fashion. The cystotome can be
• Disadvantage of corneal incision. Relatively created by bending a 27 gauge needle or can be
high postoperative astigmatism. selected from innumerable customized styles. The
• Construction of corneal incision: The cystotome for making a puncture on the anterior
corneal incision can be single or two-plane. capsule is directed towards the optic nerve. The first
Two-plane incision is preferred because it puncture starts at 6 o’ clock position and gradually
proceeds clockwise to 12 o’ clock position. A similar

procedure is carried out in the anti-clockwise
direction from 6 o’ clock position to 12 o’ clock
position thus completing the capsulotomy. The
punctures are made adjacent to each other and each
puncture is joined to the previous puncture. On an
average 50 similar punctures may be required to
achieve a complete capsulotomy. During the process
of entire capsulotomy care should be taken not to
disturb cortical fibers. We prefer a circular anterior
capsulotomy of approximately 5 to 7 mm diameter
(Fig. 49.1). The entire procedure can be performed
with the irrigating cystotome entering the unopened,
completely opened or semiclosed anterior chamber.
Fig. 49.1: Multipuncture capsulotomy
A viscoelastic material is used to maintain a constant
anterior chamber depth. The high viscosity
viscoelastic like Inj. Sodium Hyaluronate helps in
maintaining anterior chamber depth better. However,
methyl cellulose also serves the same purpose with
repeated injections. This style of capsulotomy is easy
to learn and perform, universally practiced and
applicable to all kinds of cataract. Radial anterior
capsular splits (Fig. 49.2) occur almost universally
when the nucleus is delivered or with IOL
implantation. In general, tears do not extend to the
posterior capsule due to the firm attachment of the
zonular fibres on the anterior capsule. These radial
anterior tears, however, produce uncertainties
pertaining to the stability of the capsular bag and the
position of the intraocular lens. A part of the free Fig. 49.2: Anterior capsule tear in multipuncture capsulotomy
loop of the IOL may come out of the bag through the
radial tears thus making it difficult to achieve proper
placement of implant in the bag. This may not have a
favorable effect on posterior capsule opacification.
Moreover, the anterior capsule flap is invariably
aspirated or pulled during the process of cortex
removal with Simcoe’s cannula.
Continuous Curvilinear Capsulorhexis

This is a controlled tearing of the anterior capsule
producing a strong, smooth, regular and circular
opening (Fig. 49.3). Although circular opening is pre-
ferred, it could be of any shape. This style of anterior
capsulotomy does not give anterior capsule tears
encountered in other types of capsulotomies. The
integrity of the capsular bag is maintained with CCC
and in-the-bag implantation of an IOL is achieved. It Fig. 49.3: Continuous curvilinear capsulorhexis
allows safe and effective hydrodissection and hydro-
delineation and endocapsular phacoemulsification. with controlled phacoemulsification by ensuring-in-
Capsulorhexis has revolutionized cataract surgery the bag IOL implantation. Capsulorhexis makes
removal of residual cortex easy and also allows prefer the forceps technique in white mature and
cleaning of the anterior capsule. This technique is pediatric cataracts.
compatible with all types of surgery including ECCE.
Disadvantage Anterior chamber depth maintenance is
Capsulorhexis is elastic distortion. It can be stretched
difficult.
up to 125 percent of its size and it withstands large
degree of disparity during nucleus delivery and also Relaxing cuts The aim is to achieve rhexis in all patients.
with IOL implantation. If the size of the rhexis is small and nucleus is relatively
large, relaxing incisions are placed. Most commonly,
Cystotome technique We prefer this technique. The most
2 relaxing incisions are made—one at 10 o’ clock and
important step in CCC is creating a flap and everting
the other at 2 o’ clock positions.
it with cystotome. A puncture is created with tip in
the center and extended horizontally to the left side
Hydroprocedure
for about 2 mm with side of cystotome. The flap
created is now everted by giving it a push with the Hydrodissection and hydrodelineation help in
front of the cystotome (Fig. 49.4). Care should be reducing the size of the nucleus. This helps the
taken to keep the flap everted throughout the surgeon to deliver the nucleus through a small rhexis
procedure. The viscoelastic is injected to form the and a small incision.
anterior chamber when necessary. Once the full circle
is almost completed, the end will reach the beginning. Hydrodissection
Joining of capsulorhexis should encompass the • Conventional This involves injection of fluid into
beginning to eliminate potential weak point in rhexis the cortical layer of the lens under the anterior
margin. Alternatively, the whole procedure can be capsule to separate the nucleus from the cortex
performed in reverse fashion with anticlockwise and capsule. A cannula of 26 or 27 gauge needle
direction. mounted on 2 ml syringe is used for
hydrodissection.. The tip of the cannula is directed
Advantage of cystotome technique
in the superficial cortex and the irrigating fluid is
i. A small needle allows very little leak of viscoelastic
injected rapidly to create a wave. This fluid wave
ii. Rhexis extension can be prevented, as travel with
dissects the superficial cortex and passes finally
cystotome is small.
between the posterior cortex and the rest of the
Forceps technique Technique is compatible with Inj. lens mass. Hydrodissection is completed by
Sodium Hyaluronate. The principle of the forceps noticing a fluid wave, nucleus bulge and
technique corresponds to the principle of the needle symmetric shallowing of the anterior chamber.
technique. The forceps can be used either directly to • Cortical cleaving This is a technique designed to
create a puncture and tear the flap or after creating a cleave the cortex from the lens capsule. The
flap with needle. To create a circular tear grasping anterior capsular flap is tented with the tip of
and regrasping of the flap with forceps is vital. We cannula before injecting fluid. Once the cannula
elevates the anterior capsule with continuous
irrigation it creates a fluid wave which passes
circumferentially in the zone just under the
anterior capsule, cleaving the cortex from the
posterior capsule (Fig. 49.5). The advantage of this
technique of hydrodissection is that it leaves
behind only a few residual cortical fibres after
cataract removal.
• Hydrodelineation Hydrodelineation is a term used
by Anis to describe the act of separating an outer
epinuclear shell or multiple shells from the central
compact mass of inner nuclear material, the endo-
nucleus, by a forceful irrigation of BSS fluid into
the mass of the nucleus. The blunt-tipped cannula
is advanced as deeply as possible, thereby riding
Fig. 49.4: Cystotome
across the top of the firm nucleus. Then the
good hydrodissection. In trying to deliver the nucleus

through small rhexis, if excessive pressure is applied,
the whole capsular bag can be dislocated resulting in
ICCE. To prevent this, relieving cuts should be
applied.
Nucleus slide technique involves the sliding of the
nucleus on a vectis which is fitted with an irrigation
device. First a cleavage is created between nucleus
and posterior capsule by injecting methyl cellulose.
The vectis is passed underneath the nucleus. The
pressure from the scleral lip of the incision is
transmitted to cause the lower pole of the nucleus to
slide out of the eye. In this technique it is important
to ensure an appropriate plane of cleavage. Sometimes
it becomes essential to retract the anterior capsule to
Fig. 49.5: Hydrodissection introduce the instrument behind the nucleus which
can be quite tricky. In the process of expression if the
cannula is advanced inferiorly to create a tract to
nucleus is hard it can rub against the endothelium. If
allow a cleavage plane for the fluid. The cannula
the nucleus is fully prolapsed in front of the iris,
is then partially withdrawn within the tract,
irrigating vectis is placed underneath and the nucleus
still embedding sufficient length of cannula in the
slides out.
lens material to trap the fluid to be injected. The
pressure of fluid seeks out the natural cleavage
Cortex Removal
plane between the inner nucleus and the middle
epinuclear layer because the path is of least After the removal of nucleus the residual cortex is
resistance. Usually, a circumferential golden ring aspirated thoroughly from the capsular bag. The
is seen outlining the cleavage between the hydrodissection and hydrodelineation processes
epinucleus and endonucleus. Circumferential reduce the size of the nucleus leaving behind the
division by hydrodelineation reduces the size of epinuclear and peripheral cortex. To a beginner, the
nucleus. This allows the nucleus to be delivered mass of residual cortex may appear nerve racking.
from small, intact rhexis. Moreover, this epinucleus Aspiration of residual cortex is apparently easy since
creates a protective cushion, which is very impor- it is already separated from the surrounding capsule.
tant in posterior polar cataracts during phaco- Aspiration is relatively safer with CCC (with or
emulsification which can have a preexisting without relaxing incisions) than with multipuncture
posterior capsule defect. Since hydrodelineation capsulotomy. The major drawback of multipuncture
leaves behind a thick epinucleus, most surgeons capsulotomy is that free flaps of anterior capsule may
prefer to perform hydrodissection. interfere with cortex aspiration. The art of aspiration
of cortical material is fascinating. A good end result
Nucleus Removal requires controlled aspiration with a well-formed
anterior chamber and the posterior capsule retained
Manual expression of the nucleus with pressure and
backwards throughout the procedure. The following
counter pressure is the easiest and most popular
factors contribute to a sustained backward positioning
method employed till today. Initial pressure is
of the posterior capsule.
applied at 12 o’ clock position to subluxate the nucleus
1. Infusion should be adjusted by changing bottle
forward. Continuous pressure is then applied at 6
height or flow rate.
and 12 o’ clock positions. A suture tying forceps or a
2. Semi-closed anterior chamber can be achieved by
lens expressor is used to express the nucleus at 6 o’
3 to 4 interrupted sutures. The placement of
clock position. The pressure created at 6 o’ clock
sutures is determined by the diameter of the IOL
position is on the clear cornea but not on the scleral
optic.
side of the limbus. For 12 o’ clock position a bent
3. A gentle pressure on the superior iris with the
cystotome or a vectis may be safely used by increasing
base of Simcoe’s cannula prevents iris prolapse as
pressure to express the nucleus. Amount of pressure
well as forward bulging of the posterior capsule.
needed to express the nucleus can be reduced by
Irrigating Fluids cortex at the periphery is engaged initially with gentle
suction and later it is stripped by pulling the port
Irrigating fluids have undergone a considerable
towards the center of the anterior chamber. It is
improvement during the two decades. Many of the
sometimes necessary to move the cannula sideways
refinements have been made possible by better
for bringing cortical fibers to the center of the anterior
understanding of physiology and anterior segment
chamber. Finally, the residual central cortex is
dynamics. The evolution of intraocular irrigation
aspirated by increasing suction (many a times, the
solution has been from normal saline through various
stripped cortex is not aspirated inside the syringe
modifications of lactate Ringer’s solution, balanced
and the cannula is brought out of the eye along with
salt solution (BSS®) and finally Glutathione Bicarbo-
the stripped cortex).
nate Ringer’s (GBR) which evolved commercially into
balanced salt solution PLUS (BSS PLUS®). The major
Removal of Cortex by Simcoe’s Method
problems with lactate Ringer’s solution are a variable
pH and lack of ingredients necessary for normal The principles of removal of the cortex with Simcoe’s
endothelium function. BSS offers a stable pH with method remain the same. Irrigation is performed
citrate acetate buffer but still lacks the energy with the bulb held in the right hand or through
yielding substance. BSS PLUS is chemically similar to suspended bottle with infusion set. Aspiration is done
aqueous and vitreous. BSS PLUS should be with a larger syringe—either 2 ml or 5 ml—held in
considered the solution of choice as an irrigating fluid the left hand. The superior cortex is aspirated through
during cataract surgery. a separate inferior incision.
• Removal of subincisional cortex Sometimes it is very
Manual Irrigation and Aspiration Cannula difficult to engage the subincisional cortex. In such
cases; a small quantity of methyl cellulose is injected
Manual irrigation and aspiration system comprises in subincisional area to create space which allows
of single or double cannula. The most popular cannula the surgeon to engage the cortex easily. Repeating
has double irrigation and aspiration systems. hydroprocedure with hockey canulla is helpful.
Irrigation is either through gravity dependent with • Removal of cortex by automated irrigation and aspira-
infusion bottle (drip) or through a non-gravity system tion (I/A) The procedure of the automated I/A is
where the surgeon holds a collapsible bulb or syringe similar to the procedure described above. It is fast
to control infusion. Aspiration is performed through but lacks fine control. This can be improved by
a 0.3 mm size port mounted on the tip of the cannula. doing I/A through a closed anterior chamber and
The most popular cannula used in India are those by titrating irrigation flow rate. The rapid infusion
developed by Dr Daljit Singh and Dr Simcoe. pushes the posterior capsule backwards and a
We have designed a variant of Simcoe’s cannula space is created between anterior and posterior
incorporating some features of Dr Daljit Singh’s capsules. This makes access to the cortex easy and
cannula. A 22-gauge cannula which is slightly larger the entire procedure safe and rapid. Repeated
than Simcoe’s cannula with overall curve similar to entries of the probe into the eye are avoided as
Daljit Singh’s model. The irrigation and aspiration stripping and aspiration of cortex are merged into
ports are closer to each other and the latter is at the one and completed in a fraction of time. Removing
tip which is bent forward. This bend at the tip the superior cortex is also comparatively easy with
prevents posterior capsule aspiration. Lastly, two automated I/A by tilting the probe towards
additional holes at the bottom of the irrigating cannula vertical position and directing aspiration port
keep the posterior capsule away during cortex towards the cortex. (In bimanual I/A system,
aspiration. irrigation and aspiration materials are held
separately in the hands and the procedure is
Technique
performed through two separate ports). Residual
A small syringe gives fine control with plunger and cortical fiber on central posterior capsule may
better manipulation. We prefer to use 1 ml disposable obstruct the visual axis. These can be tackled by
insulin syringe for aspiration. Alternatively a 2 ml or scraping or vacuum cleaning.
5 ml syringe can also be used (with a very smooth
movement of the plunger). A bottle of 500 ml Posterior Capsule Cleaning
balanced salt solution (BSS) is suspended at a height
The capsule cleaning techniques require a good coaxial
of about 60 to 70 cm above the level of the eye. The
microscope and are performed better with good predisposed to retinovitreal complications like
viscoelastic materials. With some expertise, the high myopia, history of retinal detachment in
chances of damaging or rupturing the capsule are the fellow eye and availability of only one
negligible. functional eye. Posterior capsule may be
1. Posterior capsule scraping The capsule can be scraped scrapped behind a PCIOL with a fine polishing
with a mechanical device. This removes the instrument like sand blasted polisher. This
cortical fibers and debris adherent to the capsule. procedure ensures the integrity of the capsular
Several instruments are available. Most of them barrier. It is most useful in cases of true prolife-
have a rough surface (sand blasted) or a ring-like rative type of PCO formation.
edge. • The need for peripheral iridectomy The aim of this
2. Vacuum cleaning It is a controlled aspiration of procedure is to prevent pupillary block. With
residual fine cortical fibers and debris with the close chamber technique which gives good
help of a fine cannula. In automated I/A the control to surgeon, pupillary block is infre-
capsule vacuum cleaning can be done in a quent. As a rule iridectomy is avoided.
controlled way which removes the adherent However, it can be considered in the event of
fibers. Cleaning techniques are not effective for vitreous loss in complicated eyes.
the removal of plaque as plaque is an integral part
of the capsule. Cleaning should not be done IOL Implantation and Wound Closure
vigorously in an attempt to remove plaque. After cortex wash anterior chamber and capsular bag
• Surgery when posterior capsule (PC) rupture occurs are inflated with viscoelastic.
Early recognition, a light surgical touch and
application of viscoelastic techniques may Techniques of Implantation
minimize the damage caused by PC rupture.
One should try to maintain the capsule integrity a. Dialing technique This is our preferred technique.
continuously while removing residual cortical Here first inferior haptic is placed underneath the
and nuclear matter. anterior capsule then the haptic-optic junction is
• Posterior capsulorhexis Posterior capsulorhexis is engaged by a Sinsky’s or Lester’s hook. The IOL
indicated in pediatric patients and in adults is pushed inferiorly towards 6 o’ clock, the optic
when posterior capsule rupture is small. The is pressed posteriorly towards the optic nerve and
rupture can be converted by this technique then it is dialed to place the superior haptic
into a smooth and strong opening. Viscoelastic, underneath the anterior capsule (Fig. 49.6). The
trailing haptic can also be grasped with forceps
Inj. Sodium Hyaluronate is mandatory. The
and placed inside the bag. Dialing technique does
edge of the tear is picked up by the
not depend on the size of the pupil and any IOL
capsulorhexis forceps and a small posterior
can be placed with ease through a small pupil.
capsulorhexis is performed. This technique has
completely changed the management of
anterior vitreous. The rhexis opening will not
let vitreous to prolapse forward. The entire
posterior capsule will act as if it is one
continuous membrane. “In-the-bag”
implantation can safely be done. Anterior
vitrectomy, then is no longer necessary.
However, it requires a lot of experience and
excellent skill to perform this procedure.
• Posterior capsule scraping at a later stage Opening
of the posterior capsule with Nd-YAG capsulo-
tomy may predispose the eye to posterior
segment complications. Although the post-
laser complication rate is very low, it could be
of serious concern in eyes which are already Fig. 49.6: Postoperative picture
b. Looping technique Here the inferior or leading INTRAOCULAR LENS IMPLANTATION
haptic is placed underneath the inferior anterior
Better manufacture of intraocular lenses and their
capsule. Then the tip of superior haptic is flexed
improved designs and quality, with advances in
or looped until the highest convexity comes
surgical techniques, have resulted in a new approach
underneath the upper papillary margin. The
to IOL implantation and quality of cataract surgery.
forceps still holding the tip of the haptic is
a. Implantation site:
retracted upwards to ensure that most of the
A. Ciliary sulcus
superior haptic is underneath the iris. Then the
B. In the bag
superior haptic is released. Many a times, the upper
C. Asymmetrical
loop may go in front instead of going underneath
b. Configuration of IOL
the anterior capsule.
A. One piece—Looped and plate haptic design
B. Three piece —Looped design
Suturing
c. IOL material
After IOL implantation, wound is closed either with A. Rigid—PMMA
interrupted or continuous suturing. Before tying last B. Foldable—Hydrophobic Acrylic, Hydrophilic
suture viscoelastic is removed thoroughly. Enough Acrylic, Silicone.
time should be spent to remove dispersive type
(methyl cellulose) of viscoelastic. IOL optic should Implantation Site (Figs 49. 7A and 49.7B)
be tapped with the tip of cannula to bring out
Ciliary Sulcus Fixation
viscoelastic from the bag. Rotate knot of suture to
bury inside them. The ciliary sulcus is the area bounded anteriorly by
peripheral iris, laterally by uveal tissue in apposition
Constriction of Pupil with the scleral wall and posteriorly by ciliary
processes. Clinical experience and histopathological
Pupil is constricted at the end with intracameral
examination have shown that this type of fixation
injection of Pilocarpine. It reduces posterior synechia
may lead to erosion of uveal tissue. This leads to
formation and subsequent pupil distortion.
recurrent inflammation, pigment dispersion,
hemorrhage and glaucoma.
Subconjunctival injection or
Intracameral Vancomycin Indications
At the end of surgery a mixture of 0.5 ml. Dexametha-
sone and 0.5 ml. Gentamycin is injected subconjunc-
tivally. Alternatively, 1 mg of Injection Vancomycin
can be injected in the anterior chamber.
Postoperative Treatment and Refraction

Steroid and antibiotic combination drops are prescri-
bed four times a day for one month and then tapered
every weekly for three weeks. Non-steroidal
antiinfla-mmatory drops can be given thrice a day
when there is more postoperative inflammation.
Mydriatic drops Tropicamide once at night is
prescribed for one or two weeks. Systemic antibiotic
(Quinolone group) is given for five to seven days.
Major limitation of ECCE is stability of refraction
in early postoperative period. The refraction
stabilizes usually at 8 weeks. Interrupted suturing
has advantage of selective suture removal at 8 weeks
to reduce surgically induced astigmatism. Residual
Figs 49.7A and B: Implantation site
correction can be given after that.
• Rupture of posterior capsule but retention of during the postoperative period.

sufficient peripheral capsular support. This • Technique for implantation in the bag Viscoelastic is
condition is particularly useful when anterior injected in the capsular bag to inflate the bag and
capsulorhexis has been performed. create space between anterior and posterior
• Secondary implantation following ECCE. The capsules. Leading haptic is placed inside the
capsular fornices may get obliterated after a few inferior portion of bag. The trailing haptic is dialed
weeks of primary ECCE procedure. in the bag with dialing hook. Alternatively, it is
• Size of IOL for ciliary fixation: The minimum flexed with forceps and placed in subincisional
length of the lens for implantation in sulcus must capsular bag. IOL haptic is placed in 90° meridian
be about 13 to 13.5 mm. A shorter (12-12 mm) to the relaxing incision in the capsulorhexis.
IOL is likely to get decentered.
• Technique for implantation in ciliary sulcus: Asymmetric Fixation
Viscoelastic is injected in the posterior chamber.
In asymmetric fixation one loop is outside the bag
This increases the space between peripheral
and another is inside the bag. This occurs after in the
capsule and posterior surface iris. Leading haptic
bag implantation in multipuncture capsulotomy.
is placed in the posterior chamber very close to
Because loop may slip out of the bag from anterior
posterior surface of iris. Haptic-optic junction is
capsule tear which are commonly associated with
engaged with dialing hook and trailing haptic is
multipuncture capsulotomy. Decentration is
placed in the same manner in the posterior
frequently seen in asymmetric fixation of IOL.
chamber. Alternatively, after placing leading
haptic, trailing haptic is grasped with forceps,
Configuration
haptic is flexed and is placed underneath the iris.
Care should be taken to place both the haptics One piece construction improves the IOL’s ability to
anterior to the capsular support to achieve symme- resist capsular bag shrinkage and maintain centration.
trical fixation. Three piece construction promotes foreign body
reaction more than one piece. The joints in three piece
In the Bag Fixation lenses act as a nidus for cellular deposition.
It is desirable to achieve IOL fixation in the bag.

Looped Design
Anatomically, fixation within the bag appears very
logical. Optically also the IOL is placed at or very This group of IOL comprises of modified J or C loop
close to the nodal point. Using an aqueous fluoro- design. They are most commonly used implants.
photometric technique and laser cell—flare photo- • Loop Loops could be made up of PMMA, poly-
metric studies to compare the sequelae of various propylene or PVDF, poly HEMA or acrylic copo-
IOL fixation sites have demonstrated that in the bag lymer. Polypropyline and poly HEMA haptic
fixation is least disturbing to the blood aqueous material lead to comparatively more decentration
barrier. The safety of in the bag fixation has been because their resistance to capsule contraction is
documented by observing intraoperative behavior smaller. Angulation of haptic pushes the optic
of the haptic and optic using Miyake posterior video posterior to the pupillary plane and hence reduces
technique in human cadaver eyes. Apple and his possibility of pupil capture. It also increases
colleagues have shown on histopathological contact of posterior surface of optic with capsule.
examinations that in the bag fixation of lenses is more This can reduce migration of proliferative PCO to
secure and is less likely to create biodegradation of the visual axis.
haptics than sulcus fixation. They have also shown • Optic Optic could be convex plano, plano convex
that decentration of IOL is least (0.2 mm) with intact or biconvex. Biconvex optic produces smaller
rhexis, moderate (0.22 mm) with 1 relaxing incision distortion of image on decentration. The size of
and significantly high with 2 relaxing incisions (0.38 the optic may vary from 5.0 to 7.0 mm. Larger
mm). size lenses are difficult to insert. On the other hand,
• Size of IOL for in-the-bag fixation Capsular bag the smaller the optic size, more the glare arising
diameter is around 10.5 mm. The overall size of from the lens edge. The most commonly used IOL
an IOL should be 12.0 to12.5 mm. Slightly larger size is 6.0 mm.
IOL than bag diameter (e.g. 12-12.5 mm) adapts • Plate haptic design: Commonly used plate haptic
well to the shrinkage of the bag which is common IOL is made of silicone material. This construction
makes the IOL rigid and theoretically reduces
decentration as a result of capsule fibrosis. In
clinical practice looped lenses are more popular
than plate haptic.
IOL Material
PMMA
This is the most time tested material (Fig. 49.8). Many
of IOL properties are tested against this material in
clinical use. Mechanically, it is very strong and has
good optical properties. However, it is hard and
hydrophobic.
HSM lens The surface is changed through a unique
process of end point attachment of heparin molecule. Fig. 49.9: Acrysof® IOL
This makes PMMA hydrophilic. It is known to
produce less uveal inflammation and cellular deposits.
rhexis and minimal astigmatism.
Foldable 3. Toric IOL: This demands accurate IOL power
Typically, foldable IOL implantation is a part of small calculation.
incision cataract surgery. However, it can be consi- 4. Accomodative IOL: This demands accurate
dered along with conventional ECCE to take the refractive outcome and well-centered rhexis with
advantage of certain IOL material (e.g. Acrysof®) in in the bag implantation of IOL.
reducing PCO (Fig. 49.9). Foldable lens in particular 5. Aspheric IOL: This reduces spherical aberration. It
silicone IOL should be avoided in eyes where compli- demands in the bag fixation and minimal
cated vitreoretinal surgery is anticipated. astigmatism.
Newer IOL’s SUMMARY

1. Blue light blocking IOL: It is postulated that retinal
toxicity to pigment epithelium and photoreceptor A well-performed conventional ECCE and in the bag
resulting from blue light (400-450 mm) wavelength implantation of PMMA IOL remains a leading
can be prevented with the use of such lens. strategy in cataract management in developing
2. Multifocal IOL: This IOL needs a well-centered countries.
BIBLIOGRAPHY
1. Daljit Singh et al. Cataract and IOL (1993 edition, Jaypee
Brothers).
2. David J Apple et al. Intraocular Lenses: Evolution, Designs,
Complications and Pathology (1989 edition—William &
Wilkins).
3. Emanuel S Rosen. Intraocular lens implantation (1984 edition,
The CV Mosby company).
4. Lucio Burrato et al. Phacoemulsification Principles and
Techniques. Chapter (4)—Capsulorhexis (Page 83-92), Chapter
(5)—Hydrodissection (Page 93-96) (2003 edition – Slack
incorporated).
5. Norman S Jaffe. Cataract Surgery and Its Complications.
Fourth edition (1989) Chapter (3) – Surgical Technique( Page
33-111).
6. Roger F Steinert. Cataract Surgery: Technique, Complications
Fig. 49.8: PMMA IOL and Management (1995 edition—WB Saunders Company)
Chapter (4 to7)—Preparation (Page-35-103), Chapter 8 –
Extracapsular Cataract Surgery (Page 107-118).
Chapter 50
Techniques of Nonphaco Small

Incision Cataract Surgery (SICS)
KPS Malik, Ruchi Goel
There have been great refinements in cataract surgery The incision size varies mostly from 5.5 to 7 mm.
in recent years. Reduction in size of the wound has The nucleus is delivered as a whole in all the tech-
led to achievement of early visual and functional niques except phacofracture/ phacosection where it
recovery. Nonphaco SICS has emerged as a popular is broken into two or three fragments allowing
technique which offers all the merits of phaco- extraction through a smaller incision size. Side pocket
emulsification with added advantages of wider dissection and larger internal opening are mandatory
applicability, safety, easier learning curve, low cost in techniques using ACM and microvectis. The
and machine independence.1 The landmark step in demerit of phacosandwich and phacofragmentation
development of this surgery has been the concept of techniques is greater instrumentation inside the
anterior chamber jeopardizing the safety of corneal
sclero-pocket tunnel, introduced by Dr Richard Kratz.
endothelium. The various steps of surgery shall now
It made nucleus delivery possible through a small
be discussed briefly followed by nucleus management
external incision producing lesser postoperative
in detail.
astigmatism, faster stabilization of final refraction and
greater postoperative comfort. ANESTHESIA
The procedure comprises of local or general anes-
thesia, sclerocorneal pocket tunnel dissection, capsulo- Local or general anesthesia is used. Any form of local
tomy, hydroprocedures, nucleus prolapse out of the anesthesia is used depending upon the experience of
bag, nucleus exit out of the tunnel, cortical wash, IOL the surgeon and the anticipated problems. The local
placement and wound closure. Various techniques of anesthesia can be peribulbar/retrobulbar/sub-
nucleus delivery are being practiced by different conjunctival/subtenon/topical/intracameral preser-
vative free xylocaine injection with or without facial
surgeons all over the world. These are as follows:2
block.
1. Technique using anterior chamber maintainer
No attempt is made to lower the intraocular
(ACM)
pressure preoperatively. Preoperative or intraopera-
2. Irrigating microvectis technique tive administration of mannitol or Acetazolamide is
3. Fish hook technique not necessary. Super pinky should not be tied. The
4. Phacosandwich need is for normotensive or hypertensive eyeball.3
5. Phacofracture/phacosection Physiologically a normotensive eyeball is the best
• Bisector because there is minimal disturbance of retinal and
• Trisector phacosalute and fracture uveal tissue.
• Wire loop technique A hypertonic state of eyeball also facilitates:
• Phacofracture at the exit • Introduction of MVR knife for creation of side
• Multiphacofragmentation ports
Chapter 50: Techniques of Nonphaco Small Incision Cataract Surgery (SICS) 379
• Dissection of corneoscleral tunnel The frown and inverted ‘V’ lie within the incisional
• Performing capsulorhexis funnel and are astigmatically neutral.
• Hydroexpression of nucleus
Method of Tunnel Dissection
SCLEROCORNEAL POCKET TUNNEL INCISION
A superior rectus bridle suture is optional depending
The success of SICS depends on efficient, smooth and on the surgeon’s choice. The incision area is prepared
functional construction of a clean sclerocorneal pocket by detaching the conjunctiva from the limbus from 11
tunnel of suitable dimensions. It has now been o’clock to 2 o’clock position. After undermining the
recognized that the incision is more than a port of conjunctiva, minimal cautery is applied.
access to the anterior segment. A poorly constructed The site of external incision (scleral groove)
wound regardless of how well it is closed, can be a depends on the anterior chamber depth. In hyper-
source of astigmatism, filtration, iris trauma and metropic small eye, groove should not be made too
endophthalmitis. 4 There are two incisions: the far away from the limbus. The incision is usually made
external, which is the scleral groove and the internal, on the steep axis of ‘K’ for cylinder 1D or greater. A
which is the site of entry into the anterior chamber guarded diamond knife/ 11 number blade on BP
(AC). These are joined by a tunnel. The internal handle or a 15° angled keratome can be used. The
incision permits the cornea to change shape and leads initial groove is approximately 0.3 mm deep. Begin-
to corneal instability.5 An unstable external incision ners can start with a straight incision (Fig. 50.2) and
or suture manipulation of the external incision can then gradually shift to frown incision.
disturb the alignment of the internal incision, which Presently the authors use the frown shaped incision
can result in induced astigmatism. with two backward radial extensions at each end of
the frown (Fig. 50.3). A parabolic groove convex
The External Incision towards limbus is made 1.5 to 2 mm behind the limbus
with a chord length of 5.5 mm. 1mm long vertical
Gills and Sanders concluded that corneal astigmatism
backwards cuts are made from each end of the
is directly proportional to the cube of length of the
parabolic groove. The incision is analogous to the
incision and is inversely proportional to the distance
central cable of a suspension bridge, the entire anterior
the incision is placed from the limbus.5 Koch described
edge of the incision cannot slide, limiting the potential
the incisional funnel as an imaginary area of safety in
for corneal flattening.4
which external incisions can be placed with minimal
induced astigmatism (Fig. 50.1). Short incisions can
be made close to the limbus and longer ones away, all
having an equivalent effect on corneal curvature. The
external incision can be straight, frown or inverted ‘V’.
Fig. 50.1: Incisional funnel Fig. 50.2: The straight external incision
backward extensions are useful especially in a very

large nucleus where side pockets can be further
enlarged and external opening can be made bigger
without extending the incision in the astigmatic zone.
Constructing the Side Ports

MVR knife is used to create valvular openings at the
10 o’clock and 6 o’clock positions. The side port at 10
o’clock can be used for performing capsulotomy,
hydrodissection, nucleus manipulation, bimanual
irrigation-aspiration and dialing of IOL in the bag. The
6 o’clock port is used for insertion of ACM.
CAPSULOTOMY
There are three types of capsular openings:
• Capsulorhexis (CCC)
• Can-op-rhexis
Fig. 50.3: The frown external incision with • Envelope
backward extensions Although nonphaco SICS can be performed in
Can opener capsulotomy also but CCC is the
In the groove made earlier, a 2.4 mm crescent knife
procedure of choice due to its inherent advantages.
or diamond knife, is engaged and its tip is tilted
Use of Trypan blue dye has made CCC possible in all
anteriorly to follow the curve of the limbus and the
kinds of cataract. The size of the CCC should be kept
dome of the cornea. While maintaining uniform depth,
more than or equal to 6mm. If there is disproportion
tunneling is performed anteriorly upto 2mm of clear
between the size of the nucleus and the size of CCC,
cornea. The blade is tilted 90° medially and laterally
relaxing cuts should be given and CCC can be
to dissect the side pockets in the cornea and sclera
converted to Can-op-rhexis. The shape of the CCC
from limbus to limbus (Fig. 50.4).
should preferably be oval with a thin rim at the 12
Thus the tunnel is like a funnel with internal
o’clock. This facilitates nuclear manipulation and
opening of about 8 mm and external opening of 5.5
aspiration of cortex. Some surgeons prefer to perform
mm. It is 4mm wide at its center. The large internal
envelope capsulotomy especially in a camp setting
opening allows engagement of the nucleus. The
because it is easier and faster to perform.
COMPLETING THE TUNNEL

In the predissected tunnel, 3.2 mm angled keratome
is introduced. After traversing the full extent of the
tunnel it is dipped into the anterior chamber. Subsequ-
ent cuts are made during forward movement of the
knife. Cutting while moving backwards leads to
irregular cuts in Descemet’s membrane.
HYDROPROCEDURES (Figs 50.5 and 50.6)

This comprises of hydrodissection and hydro-
delineation. In hydrodissection, the nucleus is
separated from the cortex and the capsular bag. In
hydrodelineation the hard core nucleus is separated
from the epinucleus resulting in debulking of the
Fig. 50.4: Tunneling forward with the crescent knife nucleus.
Fig. 50.5: Hydrodissection in progress Fig. 50.7: Nuclear prolapse out of the bag: Sinskey‘s hook is
used to nudge the nucleus slightly downwards
Fig. 50.6: Hydrodelineation
Adequacy of hydrodissection can be confirmed by Fig. 50.8: Nuclear prolapse out of the bag: Superior pole is
bimanual rotation of the nucleus within the capsular lifted up using Sinskey‘s hook as a crowbar
bag by using two Sinskey’s hooks. One hook is passed
from the main port and one through the side port. NUCLEAR DELIVERY USING ANTERIOR
While the nucleus is impaled by one of the hook’s the CHAMBER MAINTAINER (Fig. 50.9)
other rotates it clockwise or anti-clockwise. Michael Blumenthal, initially described this technique.
He performs all the maneuvers under fluid and does
NUCLEUS PROLAPSE OUT OF THE BAG
not use viscoelastics. We have modified his technique
The anterior chamber is deepened with viscoelastics. and use viscoelastic.13
Sinskey’s hook is introduced into the anterior The anterior chamber maintainer is a hollow steel
chamber, after retracting the CCC margin, it is placed tube with a 0.9 mm outer diameter and 0.65 mm inner
behind the superior pole of the nucleus, a slight diameter. The ACM is inserted at 6 o’clock position
downward nudge is given followed by an upward lift through a valvular opening made by MVR knife from
(Figs 50.7 and 50.8). Once a portion of the nucleus the temporal side. The tube of ACM is attached to BSS
comes out of the bag, rest can be cart wheeled out bottle suspended 50 to 60 cm above the patient’s eye.
using a dialer. Injection of viscoelastic while keeping Viscoelastic is injected both in front and behind the
the cannula pressed on the anterior surface of the iris, nucleus. A lens glide or an iris repositor is positioned
further pushes the nucleus out. Once the nucleus behind the nucleus. ACM is opened and slight
comes in the anterior chamber, viscoelastic is again pressure is applied on the lens glide on the scleral side
injected in front of it to provide endothelial protection. to engage the nucleus. Intermittent pressure on the
MICROVECTIS TECHNIQUE (Fig. 50.10)

A 4 mm or 5 mm wide microvectis with three 0.3 mm
forward irrigating ports and a gentle superior
concavity is preferred.
Nucleus extraction with an irrigating vectis was
first described by Steinert. Both hydroexpression as
well as viscoexpression can be used. Irrigating wire
vectis is available in various sizes. Depending on the
mode of expression, the microvectis is attached to a
syringe containing BSS or low molecular weight
viscoelastic.
Copious amounts of viscoelastic is injected both in
front and behind the nucleus. The superior rectus
suture is held in the left hand and the vectis is
positioned beneath the nucleus. The irrigating vectis
is withdrawn slowly without irrigating till the superior
pole of the nucleus is engaged. The irrigation is then
Fig. 50.9: Assisted delivery: Modified Blumenthal started and the vectis is slowly withdrawn while
technique pressing down the scleral lip. The force of irrigation
has to be reduced when the maximum diameter of
lens glide or iris repositor helps in the outward the nucleus clears the tunnel to prevent forceful
movement of the nucleus. If the nucleus engages in throwing out of the nucleus.
the section but further progress is stalled, one can
PHACOSANDWICH TECHNIQUE
make use of assisted delivery. A 23 G needle is held
in left hand and the nucleus is engaged at right angle This technique was introduced in 1985 by Luther Fry.7
to its axis. The needle assists by pulling it and It involves sandwiching the nucleus between lens loop
intermittent pressure on the lens glide or iris repositor and spatula. He uses a 7mm frown incision for the
guides the nucleus out. In case of a large and hard purpose. The lens loop is placed beneath the nucleus
nucleus, a bit of it may be sheared off, remaining and the spatula on top, and the nucleus is taken out
nucleus is then pushed back into the anterior chamber as two-handed technique (Fig. 50.11).
and smaller diameter is engaged and flown out. If the Phacosandwich can be modified and performed
nucleus does not engage in the tunnel, despite full flow through a 6.5 mm incision. Viscoelastic is injected both
of ACM, the reason can be as follows: in front and behind the nucleus. Wire vectis 4 × 9 mm
• Small tunnel is placed behind the nucleus holding it in left hand
and viscoelastic cannula in front of the nucleus in right
• Irregular tunnel
hand. The nucleus is sandwiched between the two
• Incomplete dissection of tunnel
instruments and extracted. Viscoelastic is injected
• Hypotony
while the nucleus is brought out.
• Premature entry into the anterior chamber with
prolapsed iris obstructing the outlet
• Vitreous in AC
Whenever such a situation is faced, the chamber is
filled with viscoelastics and the tunnel is revisited with
3.2mm slit knife. If hypotony is suspected, viscoelastic
can be injected through the ACM by the assistant,
while the surgeon keeps a close watch. Once the
nucleus engages in the section it can be delivered either
by hydroexpression or the viscoexpression can be
continued. If the nucleus engages but fails to deliver
due to hypotony, raising the bottle height may
facilitate the nuclear delivery.8 Fig. 50.10: Nuclear delivery using Microvectis
the vectis. Gentle lifting pressure with the vectis and
steady pressure with the nucleotome splits the nucleus
into two halves. The vectis is then removed leaving
the nucleotome in position. Then, with another
instrument, either a straight spatula or Kuglen and
the nucleotome, the two halves are separated.
Viscoelastic is injected between the anterior surface
of the nuclear fragments and the endothelium as well
as the cleavage plane of the two fragments. The nuclear
forceps, which has 9mm long jaws (each having a
double row of teeth) is introduced into the anterior
chamber. One jaw goes in between the two fragments
and the other jaw to the outside and the nuclear
fragment is brought out by downward pressure on
the posterior lip. The anterior chamber is reestablished
with viscoelastic and the second fragment is extracted
in a similar way.
Fig. 50.11: Phacosandwich
The procedure can be accomplished with a wire
vectis and Sinskey’s hook. The wire vectis occupies
PHACOFRACTURE/PHACOSECTION TECHNIQUE lesser space and conforms to the shape of the nucleus.
The advantage of this technique is removing a large The wire vectis is placed beneath the nucleus and the
nucleus through a small incision size. Sinskey’s hook is placed diagonally on the anterior
As early as 1983, Gerald T Keener9 designed a surface of nucleus. The nucleus is crushed into two
nucleus snare or divider. He used an 18 or 19 G, blunt by approximation of the two instruments. Sinskey’s
tipped needle or cannula and a 32 G monofilament hook is brought out and wire vectis is left in place.
stainless steel wire. The ends of the suture were The two halves are separated after injecting viscoe-
threaded backward through the flattened tip of the lastic. Each half is brought out sandwiching it between
cannula so that an elliptical loop, 11 × 5 mm protruded. the vectis and the viscoelastic cannula. Viscoelastic is
The two ends of the suture are extended through the injected as the nuclear pieces are extracted.
hub of the cannula; they were twisted into a flattened In the Bisector technique, the nucleus is broken
coil. After the nucleus prolapse into the anterior against a 4 mm × 8 mm solid curved vectis and a
chamber, it is suspended in sodium hyaluronate. The bisector (Fig. 50.12). Trisector technique involves a
wire is then positioned around the nucleus and the trisector which has two longitudinal limbs, sharp
loop is shortened by pulling it back. This causes the posteriorly. The nucleus is broken into three fragments
loop to cheese wire through the nucleus dividing it by pressure against the trisector and the solid vectis
into two. The two halves are separated completely. (Fig. 50.13).
The corneal lip of the wound is held with the forceps, Phacosalute and fracture is a technique in which
lens loop is positioned beneath the nuclear fragments the nucleus is prolapsed anteriorly either at 3 or 9
and each fragment is slipped out. o’clock mechanically by applying counter pressure at
Peter Kansas, 10 popularized the technique of the opposite quadrants. The nucleus is then aligned
phacofracture. He used two modified Kuglen vertically in 12-6 o’clock meridian, part of it within the
instruments to prolapse the nucleus out of the bag. bag part within the AC. The superior portion of the
The anterior chamber is filled with viscoelastic. A solid nucleus is amputated or pinched off using a capsule
curved vectis, 3 mm wide and 9mm long is used. The forceps and expressed using an irrigating vectis.
vectis is insinuated under the nucleus without Nucleus can also be fractured in the tunnel while
applying much force. Once the solid vectis is in it is being delivered with the irrigating wire vectis.
position, nucleotome is positioned on the anterior The Manual multifragmentation was described by
surface of the nucleus and the two instruments are Francisco J Gutierrez Carmona.11 It involves fragmen-
maneuvered towards each other. The nucleotome tation of nucleus into multiple tiny pieces of 2 × 2 mm.
gradually cleaves its way through the nuclear It can be performed through 3.2 mm clear corneal or
substance and stops when it comes in contact with 3.5 mm scleral tunnel incisions.
Once the nucleus has been prolapsed into the

anterior chamber, high density viscoelastic is injected
into the surrounding area to fill the anterior chamber.
The spatula is placed beneath and the nucleotome on
the top of the nucleus. The two instruments are pressed
against each other and the nucleus is fragmented into
four pieces which remain within the nucleotome. The
fragments of the nucleus are extracted from the
anterior chamber using a sandwhich technique
(Fig. 50.14).
Fig. 50.14: Phacofragmentation: Taking out the

nuclear pieces
ROLE OF ACM IN PHACOSANDWHICH AND

PHACOSECTION TECHNIQUES
In both these techniques there is too much instru-
mentation inside the chamber. This increases the
chance of endothelial damage. The authors observed
Fig. 50.12: Phacofracture: Bisector technique that the chamber collapse could be prevented during
the nuclear extraction by injection of viscoelastic
through the ACM by the assistant. This little modifica-
tion makes these techniques safe in the hands of a
beginner also (Figs 50.15 and 50.16).
THE FISH HOOK TECHNIQUE

This was introduced by Albrecht Hennig.12 He uses a
30G ½ inch needle, bending it with fine pliers or a
needle holders. The hook is mounted on a 1ml
tuberculin syringe and can be re-autoclaved. After
placing some viscoelastic between nucleus and
posterior capsule and into the anterior chamber, the
bent 30G needle hook is inserted between nucleus and
posterior capsule with the sharp needle tip pointing
to the right side. Then the hook is turned and slightly
pulled back, so that the needle tip is engaged into the
central lower portion of the nucleus. Without lifting,
the nucleus is pulled out of the capsular bag and
Fig. 50.13: Phacofracture: Trisector technique through the tunnel (Fig. 50.17).
Cortex, Aspiration, Intraocular Lens Implantation
and Wound Closure
With almost universal practice of CCC, cortical
aspiration has become much easier and safer.
Hydrodissection aids in loosening the cortex.
Advantage of using ACM is continuous wash out of
sludge formed by viscoelastic and cortex. While
performing irrigation aspiration with Simcoe cannula,
the tip of the cannula is placed close to the rhexis
margin, cortex is engaged, dragged to the center from
the periphery and then aspirated. The authors
routinely perform bimanual irrigation-aspiration
using an olive tipped cannula with a rounded tip and
a superior opening. It is attached to a syringe.
Irrigation is provided by ACM. The olive-tipped
cannula is introduced into the anterior chamber from
Fig. 50.15: Phacosandwich using an Anterior 10 o’clock side port or the main port and the aspiration
Chamber Maintainer is performed. It is especially useful for aspirating the
12 o’clock cortex (Fig. 50.18).
IOL Implantation
The optic size varies according to the size of the
incision. If a rigid PMMA IOL is to be implanted, the
capsular bag is inflated with viscoelastic, the IOL is
held with a lens holding forceps, at the upper one-
third of the optic. The inferior haptic is slipped into
the bag at 6 o’clock position. The IOL is released and
regrasped at the trailing haptic and rotated clockwise
or anticlockwise till the trailing haptic-optic junction
reaches 3 o’clock position. The dialer is introduced
Fig. 50.16: Phacofracture using an Anterior

Chamber Maintainer
Fig. 50.18: Aspiration of 12 o‘clock cortex using ACM and

Fig. 50.17: Nuclear delivery by fish hook technique olive-tipped cannula
through the side port and placed either in the hole in Fine’s infinity suture. The authors use an ‘infinity’
the optic or at the haptic-optic junction and dialed shaped suture (Fig. 50.19) but it differs from Fine’s
clockwise with a gentle push backwards(towards the infinity suture. The first bite is taken from inner lip of
posterior capsule) and towards the periphery. the sclera to exit at the outer lip on the left side of the
incision; suture is then crossed over to the cornea on
Wound Closure the right extreme of the incision. Next bite is taken
from outer lip of the cornea to the section to exit at the
After IOL implantation, the chamber is evacuated of
sclera. The suture is then crossed over again to the
viscoelastics. The side ports are hydrated. The internal
left side to take the corneal bite. The knot is tied and
corneal lip sits back in perfect apposition to produce
buried in the section itself to avoid postoperative
watertight self-sealing valvular effect only after return
irritation.
of normal intraocular pressure. Therefore for optimal
wound apposition it is important to rebuild the
CONCLUSION
intraocular pressure after completion of surgery. The
wound is then covered by conjunctiva and its ends There are various methods of SICS practiced by
are cauterized using a wet field cautery. different surgeons. Each has its own merits and
Suturing of the tunnel may be required in case demerits. In skilled hands all the procedures give good
integrity of the tunnel is not good or the incision is results irrespective of the type of cataract.
more than 6.5 mm in size to avoid against the rule
astigmatism. The various suturing techniques emplo- REFERENCES
yed are vertical sutures (radial), horizontal sutures and
1. Natchiar G. Manual SICS in comparison with Phaco-
emulsification. In Manual Small Incision Cataract Surgery.
Arvind Publications: India 2000;7.
2. Goel R, Malik KPS. Techniques of Nuclear Delivery in Non
Phaco Small Incision Cataract. Ophthalmology Today
2003;4;92.
3. Malik KPS, Goel R. Our Technique of SICS using Anterior
Chamber Maintainer: Modified Blumenthal Technique. In
Manual of Small Incision Cataract Surgery: CBS Publications.
India 2003;125.
4. Singer JA. The scleral approach to cataract incisions.
Ophthalmology Clinics of North America 1995;8;429.
5. Koch PS. Structural analysis of cataract incision construction.
J Cataract Refract Surg 1991;17;661.
6. Gills JP, Saunders DR (Eds). Small Incision Cataract Surgery:
Foldable lenses, one stich surgery, sutureless surgery,
astigmatic keratotomy. Thorofare, NJ: Slacks. 1990;147.
7. Fry LL.Small Incision Planned Extra. In Ashok Garg (Ed):
Clinical Practice in Small Incision Cataract Surgery (Phaco
manual): Jaypee Brothers Medical Publishers, New Delhi,
India. 2004;258.
8. Malik KPS, Goel R. Nuclear Management: In Manual of Small
Incision Cataract Surgery, CBS Publications, New Delhi,
India. 2003;39.
9. Keener GT Jr. The Nuclear Division for Small Incision cataract
Extraction. In Rozakis GW(Ed): Cataract Surgery: Alternative
Small Incision Techniques. Thorofare NJ, Slack 1990;163-91.
10. Kansas PG, Sax R. Small incision cataract surgery using
manual phacofragmentation technique. J Cataract Refract
Surgery 1998;14:328.
11. Ashok Garg. Carmona FJG: Manual Multifragmentation
(MPF) Allows for Small Incision Cataract Surgery (Phaco
Manual). Jaypee Brothers Medical Publishers P (Ltd), New
Fig. 50.19: Infinity suture used by the authors Delhi 2004;356.
Chapter 51
Concept and Principles of

Phacomachine
Jagat Ram, Suresh K Pandey
The goal of phacoemulsification is to remove cataract A second form of energy generated by the
through a small incision so as to achieve rapid visual ultrasound is termed as cavitation, i.e. the formation
rehabilitation. Three important factors which help in of a cavity. 5 Cavitation can be considered as a
achieving this goal are accurate biometry, perfect sonological effect of the ultrasound. This effect is
craftsmanship, and application of principles of phaco- produced by the physical process that creates,
dynamics. Understanding fundamental principles of enlarges, and ultimately implodes gas and air cavities
phacomachine and their utilization is of utmost in a liquid. The sonological effect occurs because all
importance to achieve the perfect surgical results.1 The sound waves, including ultrasound emit cycles of
basic functions of the phacomachine are ultrasonic compression and decompression.6 Each cycle of sound
emulsification, irrigation and aspiration. Following are waves causes the cavity to grow greater than it shrinks,
the essential components of a phaco unit: thus the cavity continues to grow. When the cavity
can no longer maintain itself, it implodes. The heat is
ULTRASONIC HANDPIECE
generated5 but the region is so small that the heat
Phaco or ultrasonic power is produced by piezoelectric dissipates quickly. The implosion also creates a
crystal that converts electric energy into mechanical
vibration in the phaco handpiece (Fig. 51.1). This phaco
power is transmitted along ultrasonic handpiece into
the phaco tip. 1mm titanium phaco needle is hollow
with distal opening functioning as the aspirating port
and irrigation fluid flows through two ports located
180° apart on the silicone sleeve. The needle vibrates
at the rate of 30,000 to 60,000 cycles per second to
emulsify the nucleus.3
Mechanism of Phacoemulsification
The basic mechanism of phacoemulsification is the
emulsification of cataractous lens by the process of
mechanical cutting. Mechanical cutting, in turn is
determined by stroke length. The phaco tip’s high
acceleration breaks the frictional bonds within the lens
material. This effect of solid on solid produces
mechanical cutting and this is the major part of Fig. 51.1: Phacoemulsification handpiece with power line,
ultrasound energy produced by phacoemulsification.4 irrigation, and aspiration tubing
tremendous negative pressure (up to 70,000 negative

PSI) which results in ultrafine emulsification of lens
particles. The ultrasound plays an important role in
cavitation. The cavitation also causes air bubble
formation in the tubing and in the anterior chamber.
PHACO TIPS/NEEDLES
The phaco needle is made of titanium and has hollow
distal opening which act as an aspirating port. Phaco
tips have variable beveled angle varying between 0°
to 60°. The 0° flat tip has minimum sculpting power
but has strong holding power. This tip is occluded
most easily and is used for phaco chop techniques.
The 45° tip has a sharp cutting power but poor holding
power and is used mainly for sculpting. The 30° tip is
most commonly used by the beginner as it has Fig. 51.3: Irrigation and aspiration handpiece
balanced sculpting and holding power (Fig. 51.2). holding or attracting the materials toward the phaco
or IA port. The rise time is the measure of rapidity
IRRIGATION ASPIRATION HANDPIECE with which the vacuum builds on occlusion of the
The irrigation and aspiration (IA) tip is smooth and aspirating port. The flow rate is an important factor
rounded with single aspirating port on the side of the in the rise time.
tip (Fig. 51.3). The irrigation ports are placed most
commonly 90° away from the aspirating port. The PERISTALTIC PUMPS
silicone sleeve fits around the IA tip. Most commonly This is a simple design popularized by the heart-lung
used IA tip is of 0.3 mm. In addition to the straight IA machines used in open heart surgery. The incoming
tip, 45° and 90° tips also are available. The 45° and 90° aspirating tubing pinches against the pump roller as
IA tips allow access to cortical matter present at 12 the pump head rotates (Fig. 51.4). The continued
o’clock position. rotation creates a pressure differential and as the
aspirating port is occluded by the nucleus, vacuum is
ASPIRATION PUMP produced in the aspirating tubing. At higher flow rate,
Aspiration pumps are used primarily to control the vacuum is produced in the lining even without an
aspiration and vacuum. The most commonly used are occlusion of the aspirating port.
(i) peristaltic pump, and (ii) venturi pump.
It is essential to understand the terms flow rate,
vacuum, and rise time. The flow rate is the amount of
the fluid pulled out of the eye per minute from the
irrigation tubing or instrument tip. The flow rate is
measured in ml/minute. The vacuum is a negative
suction force created by the pump which helps in
Fig. 51.2: Commonly used phaco tips with different

bevel angles Fig. 51.4: Peristaltic pump with rotating roller and tubing
Chapter 51: Concept and Principles of Phacomachine 389
The vacuum build up is slow in peristaltic compa- similar to venturi pump in both sharing relatively
red to the rapid vacuum rise in venturi pump. In fast flow rates and rapid rise in vacuum.
peristaltic system, one has to approach the nuclear
fragments to produce occlusion and then vacuum will FOOT PEDAL
rise in contrast to venturi pump where rapid rise in The foot pedal has four positions. The position 0 is
spontaneously created vacuum pulls the nuclear the resting, and this is fully upright point of the
material toward the phaco tip on pressing the foot foot pedal. In this position no fluid flows. All the
pedal. The peristaltic pump allows zero and high other positions refer to the travel of the foot pedal
vacuum phaco. The peristaltic pump has higher safety to a particular range. In the position 1, the plunger
margin and is safe for use by the beginners. slides away from the tubing and only irrigation
fluids flow. As the position 2 is entered, the pump
VENTURI PUMP head begins to rotate and irrigation and aspiration
The venturi pump is driven by the compressed gas occur simultaneously. The position 3 of the foot
which generates vacuum. The production of vacuum pedal represents a point in which ultrasonic power
is related to the flow of gas which is regulated by a is active. In this position, all the irrigation, aspira-
valve (Fig. 51.5). The vacuum built up is almost tion, and ultrasonic modes are present (Fig. 51.7).
instantaneous from zero to preset level on pressing Most of the modern phacomachines have a foot
the foot pedal and does not depend on the occlusion pedal reflux control in which the fluid is pushed
of the aspirating port. This provides good followability from the aspiration line to the eye to push back the
of the tissue. As a result of rapid rise in vacuum with engaged iris or capsule. Some phacomachines have
this pump, there is an increased risk of posterior similar pedal setup for both phaco and IA mode
capsular rupture and iris trauma, particularly by the while others combine the travel of the position 2
beginner. and 3 into a single longer excursions for position 2
in IA mode.1,2
DIAPHRAGMATIC PUMP Specification of a Phacomachine
In this pump, a flexible membrane within the cassette An ideal phacomachine should have the following
is used to generate the vacuum (Fig. 51.6). This is specifications:
Fig. 51.5: Venturi pump and compressed gas regulation

Fig. 51.6: Diagram showing working of diaphragmatic pump
1. It should have preset linear and pulse modes in

phaco mode.
2. It should have facility for preset vacuum, flow
rate.
3. It should have a multifunction foot switch.
4. A minimum vacuum range between 0-201 mm Hg
(desirable 0-400 mm Hg) in the ultrasonic (US
mode) provides sufficient vacuum for phaco chop
techniques.
5. Reflux facility should be present in the foot pedal
to disengage capsule or iris from the aspiration
tubing.
6. The monitor should be provided with a panel
display of parameters such as phaco power,
Fig. 51.7: Foot pedal working in phaco and irrigation and
irrigation, aspiration, IA minimum, IA maximum,
aspiration mode
vacuum, flow rate, bottle height, etc.
7. Phacomachine should ideally have accessories for
wet field diathermy and anterior vitrectomy. It is the primary responsibility of the surgeon to
8. The monitor should display total phaco power have full knowledge of the functioning of the machine.1
and effective phaco power used to emulsify The knowledge of proper machine setup is essential
cataract. for its functioning and also to get the maximum
9. The surgeon should be able to feed the memory advantages of its capabilities.
with the parameters of at least phaco power,
vacuum, and flow rate to emulsify different REFERENCES
density of cataracts. 1. Seibel BS. Phacodynamics. Mastering the Tools and Tech-
10. The machine should have the scope for reusable niques of Phacoemulsification Surgery. Thorofare: NJ Slack,
1992.
tubing and cassettes.
2. Sachdev MS. Phacoemulsification: A Practical Guide. New
11. It is desirable to have an auditory feedback in Age International Limited, New Delhi: 1996.
phacomachine. It may indicate the different 3. Kelman CD. Phacoemulsification and aspiration. Am J
functions by auditory electronic sound. Ophthalmol 1967;64:23.
12. It is desirable to have a remote control which can 4. Gooberman GL. Ultrasonic Theory and Application. Hart
Publishing, New York: 1968.
be kept in a sterile area to change the parameter
5. Frederick JR. Ultrasonic Engineering. John Wiley and Sons,
during phacoemulsification. New York: 1965;71-115.
13. Monitor panel should display the error or any 6. Suslick KS. Ultrasound: Its Chemical, Physical, and Biological
fault arising in phacomachine. Effects. VCH Publishers, New York: 1988.
Chapter 52
Removal of Subincisional
Cortex in Small Incision
Cataract Surgery
Vilas A Bidaye, SV Bidaye
INTRODUCTION increases. The handle is then brought into a vertical

position (which is normally kept almost parallel to the
The major problem in small incision cataract surgery
iris plane). The aspiration port is brought into contact
is the removal of cortical material from below and
with cortex material and capture with low aspiration.
around the incision. This is particularly difficult with
Now the handle is rotated to 30 to 40 degree to move
a corneal or scleral tunnel especially if the rhexis is
the aspiration port away from the posterior capsule.
smaller or decentered distally.
The vacuum is increased slightly (120 to 150 mm Hg),
One approach to the 12 O’clock cortex is aspiration
and the tip is rotated through a further 120 to 150
through a separate side port incision usually at 7
degrees to direct the aspirating orifice towards the
O’clock and using the coaxial Simcoe Cannula to
surgeon. Then the vacuum is increased again (300 to
remove the cortical matter at 12 O’clock. But to
500 mm Hg) to completely aspirate the cortical mass
manipulate the Simcoe Cannula, the incision has to captured in the port.
be slightly larger than the other techniques. There are It stands to reason that with this verticalization,
various other techniques used to remove the sub- abnormal pressure is exerted on both edges of the
incisional cortex and we will examine them one by incisions—upward on the anterior edge and down-
one for their advantages and drawbacks. ward on the posterior edge. The former causes the
Various methods described by Lucio Buratto are: formation of corneal folds with consequent reduction
1. Verticalization of the coaxial tip. in visibility; the latter can exert abnormal pressure on
2. Extension of the Incision. the iris tissue. The maneuver also causes distortion of
3. Mobilization of the cortex with viscoelastic subs- the incision with a consequent increase in BSS loss,
tance (VES). reduction in the chamber depth, rising of the posterior
4. Mobilization of the cortex with IOL. capsules, and an increased risk that the I/A tip will
5. Technique using curved coaxial cannulas. capture and rupture the posterior capsule.
6. Mobilization of the cortex with manual aspiration. If the I/A tip is inside the tunnel, scleral or corneal,
7. Bi-manual technique. and if there is poor mydriasis and a small rhexis, it is
almost impossible to use this method successfully.
VERTICALIZATION OF THE COAXIAL TIP
To correctly perform an operation with an anterior EXTENSION OF THE INCISION
limbal incision, the bottle of BSS is raised so that the The technique involves extending the incision to the
depth of the anterior chamber and the capsular space size suitable for the IOL and first inserting the I/A tip
at the extreme right to aspirate the cortex situated in TECHNIQUE WITH A CURVED COAXIAL CANNULA
the sector on the left, and then on the extreme left to
One huge step forward was the invention and produc-
aspirate the cortex on the right.
tion of angled or curved coaxial cannulas. They are
The technique is difficult. As the incision is wide,
generally angled between 45 and 90 degree with a
a considerable amount of BSS will escape and the
slight gentle curve of the body of the tip, which allows
chamber will flatten. It is therefore difficult to capture
the surgeon to reach the cortex present at the equator
the material, particularly if there is poor mydriasis or
of the capsular bag close to the main incision.
small rhexis, or even if the surgeon uses a spatula,
introduced through the side port incision, to retract
MOBILIZATION OF THE CORTEX WITH MANUAL
the iris.
ASPIRATION, SUCK AND SPIT TECHNIQUE
TECHNIQUE OF USING VISCOELASTIC One more technique consists of capturing the cortical
material by aspiration exerted by a thin U-shape
Another technique involves the use of viscoelastic
cannula with olive tip, connected to a syringe
substance (VES) to mobilize and capture the cortex.
containing BSS (manual I/A). The cannula has an
The viscoelastic must be a hyaluronic acid-based
orifice in front of the olive tip. The olive tip creates
material—Provisc or Healon would be a logical choice.
space between the anterior and the posterior capsule
Substances like Viscoat or Methylcellulose, are not
and helps to dislodge by rubbing the cannula on the
suitable. The product is injected gradually where there
cortical mass trapped between the two. The loosened
is residual material to try detaching the adhesions
cortex can be caught in the aspiration port by sucking
between the cortex and the posterior capsule.
it in. The caught mass in the aspiration port is then
The surgeon enters the anterior chamber with the
held with minimum suction and the cannula is now
coaxial cannula (without irrigation) and brings the
used as a forceps to pull the mass in the centre of the
aspiration orifice into contact with the material to be
pupil. BSS and VES is also sucked in and the chamber
aspirated (the maneuver is simple because VES has
becomes shallow. This makes it difficult to take the
created space and widened the pupil, improving visi-
bent cannula out of the eye. Hence the loosened
bility). Aspiration is then activated and both the cortex
cortical mass in the cannula is pushed back in the
and VES are removed. The maneuver can be repeated
anterior chamber by pressing the plunger of the
if necessary. The disadvantage of this technique is that
syringe (Spitting) This reforms the chamber and now
several injections of VES are required.
the cannula can be moved out of the eye. The mass is
then aspirated with a coaxial I/A cannula.
MOBILIZATION CORTEX USING AN IOL
This technique involves the insertion of an IOL in the SYSTEM USING TWO SEPARATE CANNULAS:
capsular bag, even when sub-incisional cortical mass (BIMANUAL I/A)
persists. Do not remove the VES that was injected for
the implant. The lens is rotated in a clockwise direction Technical Features of the Two Cannulas
and the surgeon takes advantage of the mechanical Handles
friction exerted first by one loop and then by the other
which mobilize the masses. They are finally aspirated Titanium proved to be the best material and it is also
together with VES using a coaxial I/A cannula. The the lightest. However, stainless steel and aluminum
presence of IOL will provide safety to posterior are valid alternatives.
capsule. The internal lumen of the handle must be greater
This procedure will sometimes reach the objectives than that of the cannulas; this will facilitate the
rapidly. In other cases, rotating the IOL is difficult aspiration of the cortex with the aspirating cannulas,
because of the presence of the cortex or because mobili- and BSS irrigation with the irrigating cannulas. It will
zing the cortical mass is difficult. This technique causes also make cleaning the handles easier.
zonular stress through the repeated rotation of the
IOL, which is not always, a smooth procedure. In Cannulas
addition, it does not always completely remove the • The two cannulas must be slightly curved. This
residual cortex. facilitates the access to the equatorial material,
Chapter 52: Removal of Subincisional Cortex in Small Incision Cataract Surgery 393
reduces the movement in the chamber, and avoids limbus. The incision must be almost tangential to the
exerting excessive pressure on the two side port iris plane and be trapezoidal in shape. The external
incisions. opening (1.6 to 1.8 mm) must be slightly wider than
• The two cannulas must have exactly the same the internal incision (1.0 to 1.2 mm) facilitating the
diameter so that they can be used alternately penetration of the cannula. The internal opening must
through the two side port incisions. The optimal be just slightly larger than the diameter of the cannula
diameter for the cannula is 23 G. to reduce the BSS leakage and avoid the formation of
• The two terminals must be closed (so the orifices corneal folds.
must be positioned along the shaft). This limits the An incision, which is too small, will cause the
risk of descemet’s membrane detachment when formation of corneal folds, with reduction in visibility,
entering the chamber, but above all reduces the particularly when the aspiration cannula is angled to
risk of rupturing the posterior capsule when one reach fragments close to the entrance incision. A larger
of the cannulas enters a flattened anterior chamber. incision will cause the chamber to become shallow
• The end of the aspiration cannula may be slightly because of the leakage.
sanded. This will allow the surgeon to use the
cannula to clean the posterior capsule or to clean
Technique
the internal surface of the anterior capsule follow-
ing capsulorhexis. The handle fitted with the irrigation cannula is attach-
• There should be just one aspiration orifice of ed to the irrigation tube (a mistake cannot be made,
0.3 mm size, situated on the concave side of the as the aspiration cannula will not fit); the same applies
cannula, about 1.5 mm from the end of the cannula. to the aspiration handle.
To clean the posterior capsule with the vacuum Prior to entering the chamber, the surgeon pushes
technique, the cannula must have an orifice on the the foot pedal into position 1 to remove air from the
convex side. aspiration handle. Do not move into position 2 because
• The optimal diameter of the irrigation orifices is if air enters the aspiration line, the aspiration proce-
0.5 mm. One of the two orifices must be on the dure will be radically changed. The tip of the irrigation
convex side and the other on the concave side. In cannula is therefore, introduced through the side port
this way, the irrigation flow is directed toward the incision on the left of the main incision with irrigation
chamber angle. open.
Principles for Use of Two Cannulas As BSS enters the anterior chamber it will deepen
the spaces immediately, distend the chamber and the
The two cannulas are used alternately through the two capsular bag, and facilitate the entrance of the aspira-
side port incisions, so the aspiration of the cortex will tion cannula through the other side port incision.
be performed in two steps.
At this point, the irrigation cannula can remain
In the first phase, the aspiration cannula is intro-
immobile inside the incision while the aspiration
duced through the side port incision positioned on
cannula is brought to the equator, opposite to the
the right of the main opening (while the aspiration
entrance point. The cannula approaches a fragment
cannula enters the incision on the left) and the entire
cortex in the 180 degree opposite the entrance point of cortex and when contact is made, the surgeon
of the cannula is aspirated. Next, two cannulas are activates the aspiration by pushing the pedal about
simultaneously extracted and inverted so that the halfway down.
aspirating cannula can remove the residual material The cortical material occludes the orifice, vacuum
in the capsular bag in the remaining half. In this way, increases along the aspiration line, and the material
the surgeon can easily reach the entire 360 degree of sticks more firmly to the orifice. Slowly and gradually,
the capsular equator and removal of the cortex can be a sector of the cortex detaches from the capsular bag.
complete even in the sectors below the primary inci- At this point, the surgeon moves the cannula toward
sion.(There is no 12 O’clock concept in the Bimanual the center of the chamber. In this way the cortex is
Technique) caught from behind the anterior capsule and then
pulled to the center.
Incisions for Two Cannulas When the fragment has been freed and the cannula
The two side port incisions must have their entrance is positioned with the orifice roughly at the center of
in clear cornea in front of the vascular arches of the the anterior chamber, the pedal is pushed down
completely so that the vacuum reaches its maximum this will help avoid accidental capture of the
preset value. This allows rapid aspiration of the anterior or posterior capsules.
captured cortex. • To avoid traction or tension on the incisions
This manoeuvre is repeated as often as is necessary because this may cause the formation of corneal
to remove all the material within the reach of the 180 folds, which will interfere with visibility.
degrees opposite the entrance point of the aspiration • To wet the cornea frequently so that visibility is
cannula. always optimal for observing within the anterior
Then the aspiration cannula and the irrigation chamber.
cannula are withdrawn and then reversed. The • To realize that rubbing the irrigation cannula
irrigation cannula is now introduced through the against the mass may assist the aspiration of
incision which was previously used for aspiration and
particularly hard masses, which occludes the
the aspiration cannula is introduced through the
aspiration orifice.
opposite side port and will be used to aspirate the
• To use the cannula, if there is poor mydriasis, as
cortex from the remaining 180 degree. Both the side
though it was a spatula to move the iris laterally
port entries usually close spontaneously at the end of
the procedure. and to give a better view of the cortex, aspirating
Parameters used for this technique are very simple. it with aspiration cannula.
Normally the flow rate is set at 18 ml/min and the • To remember that if one of the incisions is too wide
maximum vacuum is 400 mm of Hg with linear control and allows too much fluid to escape, edematizing
of the aspiration. In practice maximum vacuum set at one or both of the incisions can rectify the problem.
250 mm of Hg is usually sufficient. Appropriate use Alternately, the tip can be placed obliquely inside
of the pedal, flow rate, vacuum, and bottle height will the incision in order to partially close the incision.
also help reduce fluctuations in the anterior chamber
to a minimum. CONCLUSION
Advantages of Bimanual Technique This Bimanual method is safe and rapid, and gives
1. The entire 360 degree of capsular bag can be surgeon great freedom of movement in the anterior
thoroughly cleaned. chamber and inside the capsular bag. This system
2. It’s a close chamber technique. allows the surgeon to clean 360 degree of the equator
3. It’s a positive pressure technique. and work in a completely closed chamber. It is the
elective procedure for any situation in which it is
Useful Hints difficult to remove the sub-incisional cortex, but it is
During the procedure, the surgeon may find it useful also recommended as a routine procedure to remove
• To keep aspiration under direct visual control as the cortex completely from the capsular bag.
Chapter 53
Phacoemulsification in
Difficult Situations
K Ravishankar, Deepak Garg
Today, phacoemulsification is the preferred method ting defect in the PC. Forceful hydrodissection can
of performing cataract surgery. As more and more result in rupture of the PC and vitreous loss and even
cataracts are being treated by phacoemulsification, the dropping of the dense plaque into the vitreous.
surgeons are faced with new problems and challenges. In these cases a hydrodelineation should be carried
Fortunately, there are also ways in which these situa- out before the hydrodissection (Fig. 53.1).
tions can be tackled skillfully. In this way the posterior capsule can totally be
We have divided these difficult situations into the avoided and the nucleus can be removed safely above
following groups: the protecting posterior cortex.
1. Types of cataracts The cortex is stripped from the periphery toward
a. Posterior polar cataract, the center from all around. It is important that the
b. White cataract central cortex be removed last, lest there may be a
c. Hard cataract posterior capsular dehiscence.
d. Intumescent cataract
e. Pediatric cataracts White Cataract
f. Subluxated cataracts
In a white cataract there is no red reflex and doing the
2. Cataracts in colobomatous eyes
capsulorhexis is the difficult step. There is a high
3. Cataracts in postsurgical eyes
a. Post vitrectomy
b. Post trabeculectomy
4. Cataracts in patients with small pupils
5. Cataracts in patients with pseudoexfoliation
PHACOEMULSIFICATION IN DIFFERENT TYPE

OF CATARACTS
A phacoemulsification surgeon could face a challenge
in the following conditions:
Posterior Polar Cataract

This type of cataract has a dense plaque in the posterior
capsule (PC), which is associated with a relatively soft
nucleus. There is usually a weak PC or even a preexis- Fig. 53.1: Hydrodelineation before hydrodissection
chance of loosing the edge of the capsulorhexis and Modification of standard phaco technique may help
thus converting to a beer can opening or causing an to minimize the risk of these complications.
extension of the rhexis. Today we have different stains More highly retentive viscoelastics with longer
that can be used to stain the anterior capsule. Because retaining power should be used to deepen the AC for
of these stains the need for the red reflex no longer capsulorhexis and to protect corneal endothelium
exists and one can safely perform a capsulorhexis. The during phaco. The capsulorhexis should be made large
most commonly used stain is trypan blue. It is enough to allow for generous grooving and sculpting
available in 0.3% concentration. The other stains that of the nucleus [6.0-6.5 mm]. The larger capsulotomy
one could use are indocyanine green (ICG) and also makes nuclear manipulation easier, with less
fluorescein. likelihood of ‘nicking’ the anterior capsular edge with
the phaco tip or a second instrument. Hydrodissection
Technique of Staining the Anterior Capsule and hydrodelineation should be attempted; however
a large, dense nucleus and compact cortex are often
These stains when used in the anterior chamber can encountered. If hydrodelineation is successful, mani-
also stain the corneal endothelium. Therefore, the stain pulation of the smaller portion of the nucleus will be
is injected into the anterior chamber under an air far easier than manipulation of the entire nucleus.
bubble. A paracentesis is made and air is injected in A curved phaco tip, such as the Kelman tip will
the anterior chamber such that a single large bubble deliver power more directly to the hard nucleus.
is formed in the anterior chamber. Next, through the Exposure of more of the titanium tip by retraction of
same paracentesis the anterior chamber is entered with the silicone sleeve back further than normal will also
a 2 ml syringe filled with trypan blue and a 23 G increase the cutting efficiency of the tip. The use of
cannula (Fig. 53.2). higher vacuum levels will increase the phaco-
The tip of the cannula is advanced till it lies below efficiency and hold nuclear chips more firmly. High
the air bubble and above the anterior capsule and then vacuum tubing and Mackool style phaco systems are
0.5 to 1 ml of the dye is injected. This is left in the designed to decrease the risk from high vacuum. The
anterior chamber for about 45 seconds to one minute following are the techniques that one can use in very
and the anterior chamber is washed out through the hard nuclei:
same paracentesis opening. Now as the anterior • Crack and flip
capsule is stained a capsulorhexis is performed in the • Phaco chop
usual manner. • Crater divide and conquer.
Hard Nucleus Intumescent Cataract

Dense, brunescent cataract presents a great threat for In this type there are a few considerations that one
intraoperative and postoperative complications like has to keep in mind while performing cataract surgery.
zonular dialysis, posterior capsule rupture, vitreous Main difficulties arise in visualization of the anterior
loss and posteriorly dislocated lens fragments. capsule, the presence of milky cortex, fibrosed capsule,
Prolonged phaco times at higher power levels can lead a small, dense nucleus and increased intralenticular
to scleral or corneal burns and corneal decom- pressure.
pensation due to higher endothelial cell damage. The difficulty here lies in making of the rhexis.
When the rhexis is initiated there is a high chance of
extension of the rhexis posteriorly because of the
sudden egress of the milk. To improve visibility in
these cases, higher magnification as well as elimination
of extraneous operating room light is essential.
Oblique lighting with a secondary light source may
enhance visualization when there is diminished red
reflex.
A 2-stage technique is adopted. The first is to
Fig. 53.2: Cannula under the air bubble injecting trypan blue puncture the central anterior capsule with a needle
on the anterior lens capsule and aspiration of the liquefied contents thus
Chapter 53: Phacoemulsification in Difficult Situations 397
decompressing the bag. In the second stage the patient or in other words, whether the child is old
capsulorhexis is completed. One should aim for a enough to cooperate for a Nd-Yag capsulotomy if
small capsular opening. The rhexis is completed under necessary.
high viscosity viscoelastic material after washing away
the milky material with BSS (if some of it has entered Subluxated or Dislocated Cataract
the anterior chamber) and filling the anterior chamber Normal zonules can withstand a mechanical stretch
with viscoelastics. This may also be done under an air of about 3.4 to 3.8 mm and a negative pressure of about
bubble to aid in visualization of the torn out anterior 200 mmHg. The preoperative features of a cataract
capsule. The surgeon can also inject fluorescein with zonular weakness are asymmetry of anterior
(0.05 ml) under the anterior capsule to stain it. Because chamber depth (ACD), irregularity of ACD, phaco-
there is no counter pressure provided by the lens donesis or iridodonesis, flattening of equator of lens
material it is a better option to use forceps for and vitreous in the anterior chamber.
capsulorhexis rather than the tip of the bent needle. One must assess preoperatively the amount of
One must also remember not to attempt hydro phacodonesis that exists in a patient. An ultrasound
procedures after the capsulorhexis is over. biomicroscopy is the investigation of choice to accura-
tely document the clock hours of zonular dehiscence.
Pediatric Cataracts In the presence of mild zonular dehiscence (less than
There are many considerations that one has to take 3 hours) a conventional phaco surgery can be
into account when deciding to operate on pediatric performed. In the presence of moderate zonular
cataracts. Whether one should do a pars plana lensec- disinsertion (3-5 hours), insertion of a capsular tension
tomy or a regular phacoemulsification with IOL ring (CTR) is essential for safe phaco surgery. In the
implantation, what is the size and power of the IOL presence of major zonular disinsertion (upto 7 hours)
to be implanted, at what age to operate upon a pedia- scleral fixation of the capsular bag or insertion of the
tric cataract and whether to do a primary posterior capsular ring along with in-the-bag capsule IOL
capsulorhexis or not. Addressing all of these issues fixation can be tried.
are beyond the scope of this chapter. What we will
Surgical Technique
concentrate upon is the actual procedure of perfor-
ming phacoemulsification. The surgery can be performed under GA or LA. One
The incision as in adult phacoemulsification should must not use the super-pinky. The incision is away
be a posterior limbal 3 planar incision. The advantage from the area of zonular weakness. The CCC is done
of this incision is that the wound is a self-sealing one in the zonule free zone of the anterior capsule and
and children often rub their eyes after the surgery. while performing the rhexis a shearing rather than
The self-sealing nature of the incision provides safety tearing force should be used. Forceps can be used
in this situation. After the anterior chamber is filled instead of the bent needle to further reduce the stress
with viscoelastic material the capsulorhexis is on the remaining zonules. The CCC can also be made
attempted. The capsule in these patients is known to slightly eccentric away from the zonular weakness.
extend easily. Thus after creating the flap of the The hydro-procedures should be minimal and gentle.
anterior capsule the edge is held with an utrata forceps There are other surgical precautions that one must take
and the flap further extended. With frequent regras- while performing the surgery. The bottle height
ping of the capsular edge and directing the edge should be low. One must use a low aspiration flow
towards the center of the capsule, extension of the rate and a low vacuum. High cavitation tips should
capsulorhexis is prevented and one can achieve a good be used and the phaco chop is the preferred technique.
continuous curvilinear capsulorhexis (CCC). Since the The cortical dissection should be done with visco-
nucleus is soft, hydro procedures are not required. The elastics. Manual tangential aspiration should be done
lens nucleus and cortex can be removed using the and bimanual irrigation aspiration will prevent any
ultrasound probe in the aspiration mode. However, extra strain on the zonules.
ultrasound energy is rarely required. The remainder
of the cortex is aspirated with the irrigation aspiration IOL Insertion
port. The decision whether to perform a primary This is an important step because, due to the zonular
posterior capsulorhexis depends on the age of the weakness there is a less zonular support for the lens
and this may cause complications like decentration of Sizes of CTR

the IOL, tilting or even posterior dislocation of the IOL
Capsular rings of 12/10 mm diameter are most
with the bag. A standard capsular bag IOL is used. A
commonly used in patients of normal axial length.
single piece with capsular ‘C’ haptics is preferred. One
13/11 mm diameter rings are used in mild to moderate
must avoid plate haptics. The IOL can be placed along
myopia. 14/12 mm diameter rings are used for high
or perpendicular to the axis of the dialysis. Placing
myopic patients. 10.5/9 mm diameter rings are used
the IOL along the axis expands the bag to its natural
for pediatric patients (Fig. 53.3).
contour. There is better centration of the IOL. However,
there is zonular support for one haptic only. On the
PHACO IN COLOBOMATOUS EYES
other hand if the IOL is placed perpendicular to the
axis of weakness then there is ovalization of bag, Patients with coloboma of the iris have other impor-
decentration due to postoperative contracture of bag tant factors that are surgically important like low
but there is zonular support for both haptics. scleral rigidity, poor mydriasis, microphthalmia and
zonular weakness. It is very important not to disturb
Capsular Tension Ring (Endocapsular Ring) the vitreous because these patients usually have an
associated coloboma of the choroid and thus an
Using a CTR re-establishes the contour of capsule. It increased chance of developing retinal detachment in
protects the capsular fornix and avoids extension of the future. Other surgical considerations are the role
dialysis. While performing the surgery it prevents of CTR in these cases. They prevent intraoperative
misdirection of irrigating fluid and tamponades the extension of the rhexis and reduce postoperative
vitreous. Finally it stabilizes the IOL once inserted.1 contracture of the bag. One also has to consider the
There are two important prerequisites before higher incidence of development of postoperative
inserting the CTR. One is to have done a good hydro monocular Diplopia. Both IOLs and contact lenses are
and the other is to have a complete CCC. Timing of available to reduce this diplopia.
insertion of the CTR can vary. It can be inserted after
rhexis, after nucleus phacoemulsification or even after PHACOEMULSIFICATION IN POST-
Irrigation/Aspiration (I/A). Inserting it after rhexis SURGICAL EYES
provides full advantage of CTR. There is safer nucleus
removal; however, insertion is difficult at this stage. Phacoemulsification in a Vitrectomized Eye
Inserting the CTR after nucleus removal offers better Before one discusses the problems likely to be faced
visualization for the insertion but removing the in these types of cases, there are a few other important
nucleus could have damaged the zonules. Also the considerations like the type of posterior segment
cortex can get entrapped between the CTR and the surgery that the patient has undergone, the number
capsular equator. Inserting the CTR after I/A is the of surgeries and the indication or type of surgery
easiest. However, at such a late stage there is a limited performed. For example diabetics should have their
role of CTR. retinopathy controlled preoperatively, and they
should be informed about the risk of progression of
Implantation Technique retinopathy after the surgery.
The ring is introduced through the cataract incision
with convexity to the side of the paracentesis. Once
the ring is introduced in the bag, a buttonhole spatula
is placed through the paracentesis guiding the ring
and preventing the CCC from getting deformed.
Another spatula through the phaco tunnel is intro-
duced to help in guiding the ring into the bag. IOL
insertion should be performed as gently and carefully
as possible to avoid further zonular disinsertion or a
capsular tear caused by the suture in scleral fixation
of the capsule alone or capsule–IOL technique. Fig. 53.3: Sizes of CTR
There are two important considerations regarding the volume and forcing the anterior chamber to
the IOL to be used. One must expect a higher tendency shallow. Raising the height of the infusion bottle only
for the blood aqueous barrier to be broken down in worsens the problem. The phaco technique depends
these cases, and thus higher levels of postoperative on the individual surgeon’s preference. Since there is
inflammation. More hydrophilic biomaterials are a high chance of loose zonules, a non-rotational
better suited than surface treated IOL’s. The second technique such as Fine’s chip and flip or Gimbel’s
important consideration is postoperative visualization phaco sweep may be more useful. While sculpting, it
of the posterior segment. Thus one should use IOL is advisable to use the angled Kelman phaco needle
with large optic diameters so that postoperative to make the ‘angle of attack’ more efficient. Sufficient
fundus visualization is not hampered by the edge of phaco power should be used to prevent pushing and
the IOL. chattering of the nucleus. Hydrodelineation will
Intraoperatively, taking a superior rectus suture further help the surgeon in performing endocapsular
greatly helps because of the low scleral rigidity in manipulations. As mentioned earlier in the chapter
vitrectomized eyes. For the same reason one may also one may also employ the use of an endocapsular ring
use a fleringa’s ring to stabilize the globe. The depending on the zonular integrity. Again to reduce
conjunctive should be opened very carefully because the stress on zonules it is important that the fluid
there may be buttonholing of the conjunctiva with inflow and aspiration are reduced and more stress
chances of conjunctival scarring during the healing should be on manual removal of the cortical matter.
process. Also the patient may need further surgeries One may face a patient who has undergone a
in the future, most important of which is a trabecu- posterior segment surgery in the past with silicone oil
lectomy wherein the presence of good conjunctival present in the eye. These patients may undergo
tissue is of paramount importance. Prior to making silicone oil removal and a cataract surgery at the same
the incision, it is advisable to make a side port and time. The oil removal is done after the phaco-
exchange the aqueous for viscoelastic material. This emulsification of the cataract. There are two ways in
will make the globe firm and thus prevent the creation which one can remove silicone oil. In one the eye is
of a superficial tunnel, which is likely to occur if entered through the pars plana and the oil is removed.
attempted in a soft eye. To prevent intraoperative The other way is to make a posterior capsulorhexis
softening of the eye, the side ports should be well after removal of the cataract and start injecting BSS.
constructed to prevent leakage of fluid through them. The oil will float up and flow out of the section. After
A small pupil is a common finding in these cases and making sure that the oil is removed, the IOL is inserted
as explained later pupilloplasty techniques may be in the posterior chamber.
employed. The next step is the capsulorhexis. One
should not inject too much of viscoelastic in the Cataract in Post-Trabeculectomy Eyes
anterior chamber. As mentioned previously, the Performing a cataract surgery in an eye that has
anterior chamber is already deep, and filling it with previously undergone a successful filtering surgery
excess viscoelastics will only deepen it further making carries the risk of failure of the filtration surgery. The
CCC procedure difficult. A large rhexis should be failure of the initial filtering surgery could be due to
attempted so that postoperative opacification of the many reasons. Inadvertent trauma may occur to the
remnant of the anterior capsule does not cause bleb during the surgery, prolonged hypotony during
obstruction to fundus examination. Because the the surgery may cause adhesion of the bleb walls,
patient has undergone previous posterior segment inflammatory components of the aqueous may seal
surgery, there is a high chance of presence of a the bleb or remnants of lens material or capsule may
posterior capsular defect. Thus the hydrodissection block the fistula.
should be very gentle and followed by frequent Preoperatively, it is important to assess the filtering
decompression of the bag to prevent “blowout.” The surgery and plan the site of incision. Because the
bottle height should be lowered because the anterior patient has undergone a previous filtering surgery,
chamber depth in these cases is on the higher side. massage after the local anesthesia should be avoided.
Also these patients are more prone to develop the The incision site should be away from the bleb. A clear
infusion deviation syndrome wherein the fluid is corneal temporal section is the ideal site because of its
directed posteriorly into the vitreous cavity increasing distance from the bleb. The smaller the incision the
less the inflammation post operatively and this is what about 10 to 20 seconds. Of course there is possibility
the surgeon must aim for. It is very important to avoid of causing microsphincterotomies during the
inadvertent trauma to the bleb during the surgery. The maneuver and should not be done in Rubeosis
surgeon may encounter a small pupil in these cases. iridis.
The ways to deal with this small pupil are discussed b. By using self-retaining flexible nylon iris retractors
later in the chapter. After completing the capsulorhexis, introduced through limbal paracentesis, the pupil
it is important to remove the capsule through the is enlarged about 5 to 5.5 mm diameter to complete
incision and not leave it behind as it may cause the phaco procedure and insertion of IOL
blockage of the trabeculectomy site later. It is also
important during phacoemulsification, and irrigation PHACOEMULSIFICATION IN PATIENTS WITH
and aspiration to keep the sclerostomy site free from PSEUDOEXFOLIATION
nuclear and cortical matter and to keep an eye on the
Cataracts in patients with pseudoexfoliation pose
anterior chamber depth and the height of the bottle
multiple challenges to a surgeon. These patients have
because more dynamic changes will be observed in
poorly dilating pupils and chances of zonular
these cases. The viscoelastic material is removed
dehiscence. How to deal with a small pupil has already
completely by using the irrigation and aspiration
been explained (vide supra). While performing the
probe for about 20 to 25 seconds in each of the four
capsulorhexis, it is important not to exert force on the
quadrants. Then the anterior chamber is filled with
zonules. The rhexis is done with a forceps rather than
balanced salt solution. The bleb should form by this
a cystitome. Also unlike in other cataracts the rhexis
time and if it does not form an internal revision of the
should be at least 6 mm. This will reduce the amount
bleb is necessary. The anterior chamber is reformed
of anterior capsular epithelial cells, which in turn will
with viscoelastic material. A cyclodialysis spatula is
reduce the postoperative capsular fibrosis. In these
inserted through the wound and advanced through
cases due to the lack of strong zonules, there is a chance
the sclerostomy site and moved in an arc like fashion
of shrinkage of the rhexis postoperatively. Next comes
in the space to break any adhesions in the space.
the hydroprocedures, which should also be performed
Further it is important to remove all the viscoelastic
very carefully to prevent zonular stress. It is important
material from the eye. It is not a must that the surgery
to repeatedly decompress the capsular bag and
must be sutureless.
maintain a slight pressure on the posterior lip of the
PHACOEMULSIFICATION WITH SMALL PUPIL incision to prevent inadvertent build up of the eye
pressure. Grooving should be done with high
Usually a pupil of about 5 mm diameter is enough for
cavitation tips to prevent pushing of the nucleus.
an experienced surgeon to perform the cataract
Rotations should be two handed so that the forces are
surgery. A small pupil will pose a challenge to the
truly tangential and again zonular stresses are reduced
surgeon. Pupils may not dilate due to hyalinization
to a minimum. Cracking is done by the non-rotation
of iris stroma and posterior synechia. In eyes which
technique. Cortical aspiration is probably the most
do not dilate properly, a cocktail of 1% tropicamide,
important threat to causing zonular weakening. One
2% cyclopentolate hydrochloride and 2.5% pheny-
lephrine drops are instilled at 5 to 10 mins interval for
2-3 times. In addition, Flurbiprofen sodium 0.03%
should be administered every 10 minutes for 3 doses
one hour before surgery.
If the pupil cannot be dilated by the above methods
then the following non-surgical procedures are tried.
a. By two soft iris hooks introduced into the anterior
chamber through the incision, the iris is stretched
at 12 o’clock and 6 o’clock position, the former pulls
the pupillary border and the latter pushes the
pupillary border. The same procedure is repeated
by putting the hooks at 3 o’clock and 9 o’ clock
position. Each maneuver is performed slowly for Fig. 53.4: Iris hook dilating the pupil
can implant the IOL and then try removing the cortex. to do a peripheral iridectomy in such cases specially
Another option would be to insert an ECR, which has if one expects postoperative inflammation and
been described earlier. formation of posterior synechia. Heparin coated IOLs
are indicated in such cases. These lenses decrease the
PHACOEMULSIFICATION IN UVEITIC EYES deposits on the IOL. They however do not decrease
The challenge in performing a phacoemulsification in the postoperative inflammation in any way. Post-
an uveitic eye, is to prevent intraoperative compli- operatively the patient should be on topical steroids
cations and to reduce the postoperative inflammation. for a longer duration and may even receive systemic
Thus prior to performing the cataract surgery, it is very steroids depending on the need of the patient.
important to control the ocular inflammation. The eye
should be quiet for at least three months before a BIBLIOGRAPHY
decision to perform cataract surgery is taken. Topical 1. Cionni RJ, Osher RH. Endocapsular ring approach to the
steroids and NSAIDS, periocular steroids and even subluxated cataractous lens. J Cataract Refract Surg
systemic steroids or immusuppressives if required, 1995;21:245.
can bring about this control of inflammation. 2. Fine HI. Phacoemulsification in presence of a small pupil. In
As regards performing the cataract surgery, one Cataract Surgery, Techniques, complications and manage-
ment by Steinert: Saunders, 1995.
could take a limbal incision like in the other cases. The 3. Graether JM. Graether pupil expander for managing the small
pupil may be bound down and one will have to use pupil during surgery. J Cataract Refract Surg 1996;22:530.
an iris spatula to separate the posterior synechae. One 4. Masket S. Avoiding complications associated with iris
may also resort to the various ways of tackling small retractors in small pupil cataract extraction. J Cataract Refract
pupil as described earlier. Surg 1996;22:168.
5. Nichaminin LD. Enlargement of the pupil for cataract
It is important to perform an intensive cortical clean
extractionusing flexible nyloniris retractors. J. Cataract Refract
up in such cases. Leaving any cortical matter will Surg 1993;19:793.
increase the chances of postoperative inflammation 6. Shephard DM. The pupil stretch technique for miotic pupil
which are in any case high in such cases. It is advisable in cataract surgery. Ophthalmol Surg 1993;24:451.
Chapter 54
Phacoemulsification for
Surgeons in Transition
Jagat Ram
Phacoemulsification has become the procedure of controls the operating microscope foot pedal, right
choice for cataract surgery. The main problem with foot controls the phaco foot pedal, eyes judge the
this technique, however, is that surgeons need more phacoemulsification technique, and brain coordinates
time to master this procedure due to its longer learning the whole process. The coordination is difficult in the
curve.1-6 There are several factors which contribute to beginning and is achieved with the time and expe-
the learning of phacoemulsification and their rience. Best way to learn phacoemulsification is to
knowledge is important to reduce the learning curve. form the strategies and then proceed gradually with
The common problems faced by a surgeon in firm determination.
transition are listed below. The factors contributing to safe transition from
extracapsular cataract surgery to phacoemulsification
MENTAL BLOCK are described below:
What mainly contribute to the relatively longer 1. Surgeons ability
learning curve in phacoemulsification is the mental 2. Selection of initial cases
block or fear in conversion from large incision, manual, 3. Selection of eye
extracapsular cataract surgery to small incision, 4. Use of operating microscope
automated, sutureless, phacoemulsification due to 5. Phacomachine selection
apprehension of more initial complications. This fear 6. Role of phaco skill transfer courses
is similar to what was present while we converted 7. Understanding phaco settings
from intracapsular cataract surgery to extracapsular 8. Problems faced by the surgeons in transition and
cataract surgery. The results of experienced phaco their management
surgeons are excellent. It would be unfair to compare 9. When to convert to conventional extracapsular
the results of experienced extracapsular surgeon with cataract surgery.
a surgeon in transition to phacoemulsification.6 But
once the technique of phacoemulsification is mastered, Surgeons Ability
results of phacoemulsification become gratifying and The surgeons should have firm determination and
reproducible. must keep positive mental aptitude toward the new
surgical technique. Although it is not a must for
PROBLEM OF COORDINATION surgeon in transition to perform routine extracapsular
In the beginning while performing phacoemul- surgery to acquire the skill of phacoemulsification, the
sification, a surgeon in transition is faced with the experience of surgeon performing extracapsular
problem of coordination. Right hand holds phaco surgery under operating microscope is additionally
handpiece, left hand uses second instrument, left foot helpful in safe transition to this technique.
Chapter 54: Phacoemulsification for Surgeons in Transition 403
Selection of Initial Patients irrigation and aspiration tubing. Irrigating fluid
should be on and priming must be done in the U/S
It is important to recognize and select cooperative
(Ultrasonic) mode. The aims of the priming is to charge
patients for initial surgery. The patient should be
the phaco handpiece and remove the air bubble from
between 40-50 years of age. The patient should be able
the tubing. If electricity interruption occurs during
to lie down quietly for a long time. The patients who
surgery, priming of the phaco handpiece should be
are obese, nervous, suspicious, and over enthusiastic
repeated.
and intellectual are not suitable for initial phaco
The phaco needles most commonly used are 0°,
surgery. There should be no systemic contraindication
15°, 30°, 45° and 60°. Zero degree flat tip has minimum
for use of adrenaline in the irrigation fluid. Patients
cutting power but occlude most readily thus has
with associated bronchial asthma, bronchitis, ischemic
strong holding power and is used for phaco chop
heart disease, hypertension, diabetes mellitus,
technique. 60° tip has very sharp cutting power but
Parkinsonism are not suitable for the beginner.
has minimum holding power. Phaco tip with 30° has
Selection of Eye good holding and cutting power and is suitable for
surgeon in transition for use.7
One should evaluate clarity of the cornea, pupillary
dilatation, and hardness and maturity of cataract in Role of Phaco Skill Transfer Courses
the preoperative examination. The cataract for initial
surgery should be relatively soft. Posterior sub- It is useful to participate in a skill transfer course, as it
capsular cataracts are easy for phacoemulsification. It will provide encouragement and feeling of handling
is important to select immature cataract with good red of the equipment. Performing phacoemulsification on
glow. The cornea must be clear with normal anterior few animal eyes or on cadaver eyes will provide
chamber depth. The endothelial cells count should be confidence to perform the surgery in the clinical
adequate (over 2,500 cells/mm2). Pupillary dilatation setting and it also helps to reduce the learning curve.4
should be more than 8 mm. Cataract in eyes which A new approach to reduce the learning curve in
are deep seated, highly myopic, and hypermetropic phacoemulsification is use of open sky8 or modern
or with associated ocular diseases such as glaucoma closed system in Miyake posterior video view
and uveitis are not suitable for beginner. Hard and technique.9
intumescent cataracts are also difficult for the surgeon Assisting a phacoemulsification surgeon, setting
in transition. The other eye of the patient should have of phacoemulsification equipment and observing live
good vision. surgery, video and reading of books on the subject
definitely help in acquiring skill of the art of phaco-
Use of Operating Microscope emulsification.7,10-17 Mastering of the vital steps of
The surgeon performing conventional cataract surgery phacoemulsification such as capsulorhexis, hydro-
under operating microscope is of great help. The dissection, and automated irrigation and aspiration
operating microscope should have red reflex facility during conventional extracapsular cataract surgery
which helps in performing continuous curvilinear will help in safe and rapid transition.
capsulorhexis and also in judging the nuclear groove
depth. Understanding Phaco Setting for
Phacoemulsification
Phaco Machine Specification Phacoemulsification settings will depend on many
Phaco machine should have preset linear and pulse factors. One of the important parameters is hardness
modes, aspiration, vacuum, flow rate and a multi- of nucleus. Soft cataract needs low phaco power 40-
function foot switch. Vacuum range between 0-400 50 percent to emulsify whereas hard cataracts require
mm Hg is sufficient for phaco chop techniques. Phaco phaco power between 60-80 percent. The sculpting
machine with peristaltic pump system are safer for needs low flow rate (10-20 ml/min) and low vacuum
surgeons in transition. Phaco machine should have (5-15 mm Hg). Quadrants emulsification requires high
facility for wet field cautery and anterior vitrectomy. flow rate (20-25 ml/min) and high vacuum (60-100
Priming of the phaco handpiece should be done after mm Hg). No phaco power is required for aspiration
fixing the phaco tip in position and attaching the of cortex, it only needs high vacuum (Table 54.1).
Table 54.1: Setting of phaco power, vacuum, and flow narrow tunnel will lead to incision burn and through
rate for phacoemulsification a wide tunnel fluid will flow out (Fig. 54.2) during
Steps Phaco power* Vacuum Flow rate phacoemulsification. Remember to place the phaco
(%) (mm Hg) (ml/min) incision in the steepest meridian as it will produce
flattening of the meridian.
Sculpting 50-60* 005 - 15 15-20
Phaco chop 50-60 100 - 200 15-20
Quadrant 50-60 100 25-30 Continuous Curvilinear Capsulorhexis (CCC)
emulsification
Cortex aspiration nil 065 - 400+ 15-20 Capsulorhexis is most vital step for performing
phacoemulsification.18,19 Capsulorhexis is performed
*
Depending on the hardness of the cataract with needle cystitome or capsulorhexis forceps after
filling the anterior chamber with viscoelastic substance
Problems Faced by the Surgeons in preferably sodium hyluronate. It is important to
Transition and their Management fashion a flap on the anterior capsule and evert it and
then move the flap in a circular manner, applying the
Phaco Incisions forces centripetally to prevent radial capsular tear
It is advised for surgeons in transition to perform (Fig. 54.3). The capsulorhexis is completed by moving
scleral incision. Scleral incision is constructed straight the flap outside inward. Most common problem faced
or frown shaped about 1.5 to 2 mm from the limbus. is the development of radial capsular tear. It is
It is performed with blade fragment or Bard Parker essential to maintain a deep anterior chamber during
knife blade or diamond knife. The scleral tunnel is capsulorhexis procedure as shallowing of anterior
constructed with crescent blade 1.5 mm into the chamber most often lead to radial capsular tear
corneal stroma and then anterior chamber is reached (Fig. 54.4). It is equally important to perform the
with 3.2 mm keratome, making 1.5 mm corneal valve. capsulorhexis with patience as hurry most often lead
Side port incisions is made with 15° blade. It is to radial capsular tear.
important to use sharp instruments to construct a
water tight scleral tunnel with a corneal valve. Hydrodissection and Hydrodelineation
Surgeons in transition should properly cauterize the The aim of hyrodissection is to achieve rotation of the
vessels and avoid perforating vessels in the scleral nucleus.20 Hydrodissection is performed by injecting
tunnel area to prevent bleeding. It is vital to construct the fluid with 27 G cannula between lens capsule and
an appropriate size scleral tunnel (Fig. 54.1) as a nucleus (Fig. 54.5). Adequate hydrodissection is
Fig. 54.1: In appropriate size incision, phaco tip is passed into Fig. 54.2: Fluid flow out of the anterior chamber during
the anterior chamber easily and it does not produce incision phacoemulsification through wide phaco incision leading to
burn during phacoemulsification shallowing of anterior chamber
observed as spreading of fluid wave between lens
capsule and nucleus all around. It is confirmed by
rotation of the nucleus with cannula or Sinskey hook.
In the beginning, inadequate hydrodissection is
common, and more vigorous rotation in this situation
leads to zonular dehiscence. Hydrodelineation is
performed by injecting the fluid between epinucleus
and nucleus (Fig. 54.5). The aim of the hydro-
Fig. 54.5: Hydrodissection is performed by injecting the fluid

between capsule and cortex and hydrodelineation by injecting
fluid between epinucleus and nucleus
delineation is to demarcate the safe zone for phaco-

emulsification.
Phacoemulsification Techniques
The beginner should perform divide and conquer,21
or four quadrants cracking or spring surgery or chip
and flip techniques.15 He may perform phaco chop22,23
technique only after gaining some experience
(Fig. 54.6). Problems faced by surgeons in transition
during phacoemulsification of the nucleus are as
follows:
i. Shallow and narrow groove Phaco surgeon in tran-
sition have fear of sculpting too deeply and
inadvertently rupturing capsule. More common-
ly, beginner (phaco surgeon) prepares shallow
and narrow groove which makes subsequent
Fig. 54.3: It is essential to fashion and evert a capsular flap

and move it in a circular manner, applying the forces
centripetally to complete capsulorhexis
Fig. 54.4: Maintenance of deep anterior chamber with Fig. 54.6: Grooved nucleus is fractured into two halves, applying
viscoelastic helps to keep lens capsule flat and thus prevent the forces in the opposite direction, using phaco tip and phaco
radial capsular tear formation during capsulorhexis formation chop or second instrument
steps of phacoemulsification difficult. Fracturing iv. Iris prolapse Iris prolapse usually occurs in eyes
of groove with inadequate depth is difficult and with improper wound construction related either
most often leads to zonular dehiscence or even to placement of width of the incision. An incision
posterior dislocation of nucleus. One should make too wide allows outward flow of fluid and may
a deep groove involving a three-needle thickness carry portion of iris toward the wound. Too wide
centrally and two-needle thickness in the incision should be closed with the application of
peripheral nucleus (Fig. 54.7), at this stage red a vicryl 7-0 suture and anterior chamber should
reflex becomes more clear in comparison to the be filled with viscoelastic agent to continue the
adjacent nucleus. phacoemulsification.
ii. Problem of air bubbles formation Air bubbles are v. Posterior capsular rupture Use of high phaco
produced as a result of cavitational effect during power for relatively soft cataract may lead to
phacoemulsification. Use of high phaco power for posterior capsular rupture. Radial capsular tear
emulsification of hard nucleus produces more air in the capsulorhexis margin may extend to
bubbles. It may also occur as a result of use of re- involve posterior capsule during phacoemul-
autoclavable tubing and cassette. Use of Ringer’s sification. Posterior capsular tear may develop
lactate in glass bottle or avoiding excessive use particularly during aspiration of lens matter
of re-autoclavable cassette also helps to decrease around 12 O’clock. If the rent in the capsule is
small without presence of vitreous in the anterior
air bubbles formation. Adequate priming also
chamber, beginner may convert to conventional
helps to remove the problem of air present in the
extracapsular surgery. If vitreous is present in the
tubing.
anterior chamber, vitrectomy is required.
iii. Problem of focusing Surgeon in transition often
Vitrectomy and lensectomy is performed using
experiences focusing problem during grooving
vitreous cutter with aspiration and separate
and phacoemulsification. This problem occurs as
irrigation.15 It is important to lower the bottle
a result of change in the depth of anterior height or one may preferably perform cortex
chamber. The shallowing results more often due removal with manual two-way cannula.
to outflow of fluid through wide incision. vi. Posterior nucleus dislocation This is a rare compli-
Focusing of operating microscope should be cation and occurs if one proceeds with phaco-
changed accordingly. Use of lower magnification emulsification in presence of radial or posterior
also helps to decrease the focusing problem. Haze capsular tear. Pressure of phaco tip and second
in the anterior chamber is troublesome and is instrument on the nuclear quadrants in presence
produced as a result of emulsification of hard of radial tear in the capsulorhexis margin result
nucleus; once the emulsified lens matter is in trap door formation resulting in nucleus or
drained out anterior chamber haze disappears. nuclear fragments dislocation. Fracturing of
Assistant should keep watch on the irrigating nuclear groove with inadequate depth groove
bottle fluid as anterior chamber may suddenly may also lead to zonular dehiscence and dis-
collapse once fluid is finished. location of nucleus. If nucleus or nuclear fragment
dislocation occurs one should perform anterior
vitrectomy and after enlarging the section, place
6-6.5 mm optic diameter polymethyl metha-
crylate posterior chamber intraocular lens on the
posterior capsule if it is adequate. Placement of
small diameter phaco IOLs may lead to decen-
tration. The nucleus removal is done by the retinal
surgeon later on. One should not try to follow
the dropped nucleus or remove unseen nucleus
with wire vectis as it more often leads to more
complications like retinal detachment or retinal
Fig. 54.7: Deep grooving (approximately 3/4 of the nucleus tear.
thickness) is essential, this helps in producing easy fracture of vii. Constriction of pupil Constriction of pupil may
the nucleus occur during phacoemulsification. Adrenaline
(1:1,000) 0.5 ml, should be added to the irrigating When to Convert to Conventional
fluid if the patient does not suffer from ischemic Extracapsular Cataract Surgery
heart disease or hypertension. Manipulation of Surgeon in transition should convert to extracapsular
iris should be avoided with phaco tip or second cataract surgery without discouragement if the
instrument. Use of viscoelastic also helps to situation is so warranted. In phacoemulsification each
mechanically dilate the pupil. Adequate dila- step is vital, if one step goes wrong, there are more
tation in the preoperative period with cyclo- chances of developing complications in the subsequent
pentolate 1 percent, phenylephrine 5 percent, and steps. The surgeon in transition should convert to
tropicamide 1 percent should be achieved. conventional extracapsular cataract surgery keeping
Preoperatively, use of flurbiprofen 0.03 percent in view the safety of patient. The beginner should
three times at the interval of half an hour may convert to conventional extracapsular cataract surgery
help to maintain pupillary dilatation. by enlarging the section in the following situations:
viii. Problem of 12 o’clock lens matter Posterior capsule a. In case of failure to prepare a proper phaco
tear most commonly occurs while aspirating incision.
12 o’clock lens matter. It is convenient to aspirate b. If radial capsular tear develops during capsulor-
12 o’clock lens matter with 27 G cannula making hexis.
side port incision at 7 o’clock position in addition c. If surgeon fails to achieve complete hydro-
to 2 o’clock. It is also useful to use 45° and 90° IA dissection.
tip for aspiration of 12 o’clock lens matter d. Occurrence of zonular dehiscence.
(Fig. 54.8). A characteristic star shaped pattern is e. Posterior capsular tear or dislocation of nuclear
observed (Fig. 54.9) when the posterior capsule fragment.
is engaged in the IA tip; at this stage use the foot f. Before excessive endothelial cell damage occurs.
to activate the reflux facility to disengage the The surgeons in transition should explain all the
posterior capsule. possible complications to the patient which may occur
during the phacoemulsification procedure. He must
also explain possibilities of conversion to extracapsular
cataract surgery before operation. This makes both the
surgeon and patient more conformable in the event
of operative complications.
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14. Apple DJ, Mamalis N, Olson RJ, et al. Intraocular Lenses: 21. Gimbel HV. Divide and conquer nucleofractis phacoemulsi-
Evolution, Designs, Complications, and Pathology. Baltimore: fication: Development and variations. J Cataract Refract Surg
Williams and Wilkins, 1989. 1991;17:281.
15. Koch PS. Mastering Phacoemulsification: A Simplified 22. Nagahara K. Video presentation. ASCRS Film Festival, Seattle,
Manual Strategies for the Spring, Crack, and Stop and Chop 1993.
Techniques. New Delhi: Jaypee Brothers, First Indian Edition, 23. Koch PS, Katzen LE. Stop and chop phacoemulsification. J
1995. Cataract Refract Surg 1994;20:566-70.
Chapter 55
Complications of
Phacoemulsification
Mary Abraham
Complications from phacoemulsification may be those avoided by using sharp instruments to enter the
that are common to manual extracapsular cataract anterior chamber, ensuring that subsequent instru-
extraction but with different implications, or related ments follow the correct plane of entry. Tear of the
specifically to the approach and actual process of Descemet’s membrane by the phaco tip or other
phacoemulsification. They could be intraoperative or instruments may occur. To prevent such complication,
postoperative and as with any other surgical proce- the tip is coated well with viscoelastic material. If
dure, be influenced by the knowledge, training, skill, the tear is large then corneal edema may result. Large
and makeup of the surgeon. The complications could tears may need repositioning by viscoelastic and even
be trivial or serious, and the trivial occasionally a stitch may be necessary. Endothelial damage can
leading to more serious ones. Anticipation of certain result from instrument touch, preservatives in drugs
problems, quick analyses of their consequences once such as pilocarpine and adrenaline used
they set in and effective management of an intracamerally, and high phaco energy. Careful
established complication will help in salvaging the handling of instruments, washing out drugs used
maximum possible structural and functional integrity intracamerally, and avoidance of high phaco energy
of the eye. It would be useful to distinguish difficulties will help avoiding endothelial damage. Specular
from complications for purposes of learning and microscopy in eyes suspected to be at risk will help
effective intraoperative management, though both in determining the prognosis and in planning the
may be interrelated. Surgeons starting their training surgery. Corneal edema could develop intra-
with phacoemulsification, those switching over to operatively when there is direct extensive trauma to
phacoemulsification from manual techniques and the endothelium from surgical instruments or
those trying out newer manipulations are all likely irrigating fluids and is best prevented by meticulous
to face different but specific difficulties that need to technique. Pupils that become miotic after
be overcome. Difficulties and complications commencement of surgery, prior to or during
associated with one’s learning curve gradually phacoemulsification would need dilatation by
decrease in frequency, and good visual outcomes adrenaline. Opening the capsule with a continuous
have been reported during the learning or transition tear and nuclear fracturing have been recommended
period.1-6 when the pupil remains small.7 Posterior displacement
OPERATIVE COMPLICATIONS of the lens-iris diaphragm, deepening of the anterior
chamber, and pupillary dilatation have been observed
Complications in General in highly myopic eyes, vitrectomized eyes and in eyes
Blunt instruments introduced to enter the anterior with pseudoexfoliation.8,9 This is managed by early
chamber may tear Descemet’s membrane; this is best delivery of the nucleus from the capsular bag and
performing phacoemulsification at the pupillary
plane8 or by the use of a special chamber-maintainer.9 the capsulotomy is parallel to the pupil at all times.
Complications Related to Incision CAPSULAR BAG SYNDROME
A faulty incision may need sutures to approximate Capsular bag syndrome is caused by entrapment of
the wound, resulting in greater astigmatism. There- the anterior rim of the capsulorhexis to the anterior
fore, incisions whether scleral or corneal have to be surface of the implant. During the early postoperative
half-thickness. Scleral tunnel incisions that are more period the capsular bag becomes more distended and
than 3 mm, posterior to the limbus could be the cause the IOL is pushed anteriorly; this results in myopic
of troublesome bleeding and by virtue of its greater change of refraction. If proper care is not taken to
length create difficulties in maneuvering the phaco remove the viscoelastic agent from the capsular bag
tip. A suture placed anterior to the bleeder will before putting the IOL into the bag, this phenomenon
effectively seal the wound, stop further bleeding and is likely to occur. The treatment consists of creating
prevent the blood from entering the anterior a laser hole in the peripheral part of the capsular bag.
chamber. If the suture is posterior to the bleeder, the
entrapped blood will trickle into the anterior Complications Related to Hydro Procedures
chamber. Anteriorly placed non-beveled incisions that Forcible spurts of large volume fluids can induce peri-
are less than 2 mm, posterior to the limbus may, due pheral extension of small radial tears and zonular
to a smaller area of contact, prevent adequate ruptures with resultant posterior capsule rupture,
approximation of the wound. Thin sclera predisposes vitreous loss and posterior dislocation of the lens.
to button-holing and a steep one can result in The predilection for eyes with pseudoexfoliation or
premature entry into the anterior chamber causing a increased axial length to develop some of these
tear in Descemet’s membrane or iris prolapse. complications is debated.10,11 Slow and deliberate
Placement of the scleral incision 2-3 mm from the injection of fluid under the capsule with a close watch
limbus avoids most of these problems. Clear corneal on the fluid wave, and identifying high risk eyes
incisions are ideally 1.75 mm in length and placed preoperatively should minimize this complication.
temporally as a shorter tunnel will cause wound leak The surgeon should be alert to the extension of radial
and a longer one will impair visualization. tears if more serious sequelae such as posterior capsule
rupture and lens subluxation are to be avoided.
Complications Related to Anterior Capsulotomy
Chamber Collapse
Too small a capsulotomy can result in inadvertent
inferior tears during trenching. These tears could Chamber collapse may be due to insufficient inflow
extend posteriorly during subsequent nucleus and/or excessive outflow. Chamber collapse may lead
cracking procedures. Moreover, as with nonphaco to damage to the iris and posterior capsule as well as
procedures, there could be difficulty in introducing to the corneal endothelial cells.
the intraocular lens, increased risk of posterior
capsular opacification and late shrinkage of the CORNEAL COMPLICATIONS
anterior capsular rim. Too large a capsulotomy can Corneal complications could be mild or severe and
result in premature and persistent luxation of the lens can occur intra- or postoperatively, and are generally
into the anterior chamber making nucleus related related to preoperative corneal status, intraoperative
procedures difficult. Capsular margins that are irrigating fluids, and surgical manipulations.
irregular are more likely to be engaged at the phaco Generally, the corneal endothelium remains
tip leading to radial tears. The size of anterior unaltered after uncomplicated phacoemulsification.
capsulotomies have therefore to be 0.25 mm less than Corneal endothelial cell loss one year after routine
that of the optic of the intraocular lens. Smooth, phacoemulsification was reported to be 9 percent12
controlled capsulotomies are best obtained through and no difference in endothelial cell counts were seen
a separate stab incision placed to the right of the phaco in eyes that underwent phacoemulsification or
wound. Bent capsulotomy needles or the Utrata planned extracapsular surgery.13 In a multivariate ana-
forceps are well suited for the purpose and frequent lysis, firmness of the nucleus was the most significant
repositioning of the needle tip should ensure that
Chapter 55: Complications of Phacoemulsification 411
risk factor for endothelial cell loss and mechanical provides the infusion and a vitreous cutter without
contact with nuclear fragments thought to be the the irrigation sleeve should be used to perform the
principal cause.14 Viscoelastic substances protect the anterior vitrectomy. The anterior chamber maintainer
endothelium from surgical trauma. A comparative helps to keep the vitreous back as the cutter clears
study on the protective effects of hydroxypropyl the vitreous. Irrigating sleeves are avoided because
methylcellulose and sodium hyaluronate on corneal they hydrate the vitreous further and tend to expel
swelling following phacoemulsification showed that it. If the capsular support is judged to be inadequate,
though the mean increase in central corneal thickness a sulcus fixated lens with a diameter larger than the
measured by ultrasonic pachymetry a day after capsulorhexis can be then placed in front of the
surgery was significantly higher in eyes where anterior capsule. Clear cortex that is not identified
methylcellulose was used, no difference in corneal and removed during surgery may make itself obvious
thickness could be observed at 5 weeks. 15 Post- postoperatively by swelling up and turning white.
operative corneal edema due to lens matter that is The cortex may lie in the anterior chamber, at the
either retained in the anterior chamber or dropped pupillary area, or in the posterior chamber. Cortical
into the vitreous is invariably associated with a remnants from otherwise uncomplicated surgery but
considerable rise in intraocular pressure. Removal of resulting in postoperative corneal edema, glaucoma,
lens matter with pars plana vitrectomy if necessary inflam-mation or reduced vision, need to be irrigated
results in restoration of corneal clarity, normalization and aspirated. Small portions of the cortex that occupy
of intraocular pressure, and improvement in the pupil without signs of spontaneous absorption
vision.16-19 and obstructing vision may be disrupted by using
Anti-inflammatory medications alone do not help. the Nd:YAG laser taking care to avoid the intraocular
Severe complications such as progressive corneal lens. Admixture of lens remnants and vitreous in the
opacification, bullous keratopathy, and retrocorneal anterior segment will need anterior vitrectomy.
membranes have been reported in the past20,21 and Of more serious consequence is the retention of
should be exceedingly rare today with the refinement nuclear fragments and dislocation of the nucleus or
of surgical instrumentation and technique. However, its fragments into the vitreous as the ocular fluids
if corneal decompensation sets in, penetrating cannot effectively dissolve them. The incidence of
keratoplasty would be required with concurrent lens matter dislocation during phacoemulsification
attention to any associated inflammation or raised is reported to be 1.1 percent. Lens fragments in the
intraocular pressure. vitreous need pars plana vitrectomy. This is to be
performed by a vitreoretinal surgeon as soon as the
Complications from Retained Lens Matter complication has occurred or the wound can be closed
and vitrectomy performed at a later date. It is best
Lens constituents such as anterior capsule, portions
that the surgeon promptly recognizes this compli-
of the cortex, nuclear fragments or the entire nucleus
cation and refrains from attempting removal of lens
may be unwittingly left behind in the eye or the
material through the limbal route. Serious compli-
surgeon may have been forced to close the eye before
cations such as the formation of giant retinal breaks
he had removed all these material completely. Nuclear
have been reported after such attempts. Appropriate
or cortical fragments that are roughly 25 percent of
management by pars plana vitrectomy using liquid
the entire lens tend to absorb spontaneously without
perfluorocarbons, if necessary, is compatible with
much sequelae. Larger fragments tend to produce
good visual function and results have not been
uveitis, 19,20 corneal edema, 19 glaucoma 19 cystoid
influenced by immediate or deferred vitrectomy.17
macular edema, 19 or retinal detachment with
The task of explaining the problem to the patient and
resultant impairment or loss of vision. They may
the need for further surgery by another surgeon is
manifest as marked intraocular inflammation with
part of the management and should not be
hypopyon.19 Such fragments in the anterior segment
considered an embarrassment.
should therefore be removed, preserving as much of
the capsular bag as possible. If vitreous had gained
Posterior Capsular Tear
access into the anterior segment, anterior vitrectomy
is mandatory. An anterior chamber maintainer which This is one of the most significant complication of
phacoemulsification. It is a common complication met different from eyes that have had manual
by the surgeons in transition. If capsular tear is extracapsular surgery.19 The incidence is also less
noticed early in the process of emulsification, then it when the posterior capsule is intact. Uncomplicated
is better to complete the surgery by the extarcapsular cystoid macular edema that impairs vision and shows
method after widening the incision. However, if most no sign of spontaneous resolution can be treated by
of the nucleus is emulsified then the rest of the 500 mg acetazolamide administered orally daily for
nucleus may be removed by phaco with the help of a period of 2 weeks if patients are compliant and
some instrument to push the nuclear remnant through tolerant to the side effects.19 Cystoid macular edema
the already made tunnel incision. Capsule tear is associated with anterior segment disorganization or
followed by vitreous coming to the anterior chamber. vitreous traction will need anterior segment
Nucleus fragments as well as the lens cortical matter reconstruction or vitrectomy.
drop into the vitreous cavity. Help from posterior Uncomplicated phacoemulsification should not
segment surgeon is urgently required to deal with generally result in increased incidence of retinal
such complication by pars plana vitrectomy and breaks or detachment. High risk eyes such as those
scleral fixated IOL is the only solution. with myopia, or retinal detachment in the fellow eye
must be identified. One should look for retinal breaks
Endophthalmitis pre- and postoperatively and treat breaks with high
risk characteristics. Though the incidence of these
Preoperative attention to the ocular adnexa, proper
problems is no higher than that associated with
sterilization of instruments, ensuring the sterility of
manual extracapsular extractions, the incidence rises
intraocular irrigating solutions and meticulous
once complications such as posterior capsule rupture,
surgical practice will go a long way in minimizing if
vitreous loss, retention or dislocation of lens
not eliminating this complication. The role of pre,
fragments occur. Scleral buckling procedures are
intra or postoperative antibiotics has not been proved
effective in retinal detachments without
to prevent endophthalmitis and should never be
complications, and vitreous surgery will be needed
considered to cover lapses in sterilization techniques.
for those complicated by proliferative
Symptoms vary in degree and include pain, redness,
vitreoretinopathy and retained or dislocated lens
watering, and reduced vision in varying degrees.
matter. The retinal reattachment rate following
Diagnosis must be prompt and a differentiation made
retinal or vitreous surgery is good and comparable
from an acute uveal reaction that may or may not be
to series where phaco was not done.
associated with retained lens material and from
vitreous hemorrhage. Culture and sensitivity tests
GLAUCOMA DUE TO VISCOELASTIC
from anterior chamber and vitreous taps are man-
datory for diagnosis and subsequent management. Viscoelastic agents are freely used during phaco
Once diagnosis is established, appropriate intravitreal surgery to protect the endothelium and to prevent
antibiotics or vitrectomy must be considered. This damage to the iris during the surgery. Commonly
could be performed by the phaco surgeon if he is used viscoelastic substances are methylcellulose,
trained in such techniques, or else, the management chondroitin sulphate and sodium hyalunorate. If the
must be entrusted to a trained vitreous surgeon. viscoelastic substances are not completely removed,
Results from intravitreal antibiotics are comparable intraocular pressure rise is a common complication.
to vitrectomy. Oral and intravenous administration The IOP rises between 4 to 7 hours after the operation
of drugs are of no use. Good visual results are possible and spontaneously returns to normal after 24 to 72
after prompt vitrectomy. hours. Usually some amount of viscoelastic substance
is drained out through the trabecular spaces. Eyes
RETINAL COMPLICATIONS with decompensated trabecular meshwork function
prior to surgery have more tendencies to develop
The true incidence of cystoid macular edema is
raised intraocular pressure.
difficult to determine as it depends on the manner of
documentation and the interval between surgery and
POSTERIOR CAPSULE OPACIFICATION
its detection. However, it does not appear to be a
major problem after phaco and the incidence is no This is a common sequelae, rather than a complication
Chapter 55: Complications of Phacoemulsification 413
of cataract surgery.22 IOL size23 is a common factor 10. Fine IH, Hoffman RS. Phacoemulsification in the presence of
attributed to opacification of the posterior capsule pseudoexfoliation: Challenges and options. J Cataract Refract
Surg 1997;23:160-65.
and is most commonly seen within 3 years after the 11. Dosso AA, Bonvin ER, Levenberger PM. Exfoliation syndrome
surgery. Polishing the posterior capsule at surgery and phacoemulsification. J Cataract Refract Surg 1997;23:122-
does not prevent its occurrence. An adequate Yag 25.
laser capsulotomy improves the vision in eyes where 12. Werblin TP. Long-term endothelial cell loss following
vision is impaired and refraction has not helped. Yag phacoemulsification: Model for evaluating endothelial damage
capsulotomy is however deferred for at least a year after intraocular surgery. Refract Corneal Surg 1993;9:29-35.
13. Ohrloff C, Zubcou AA. Comparison of phacoemulsification
after phaco in order to minimize the subsequent and planned extracapsular extraction. Ophthalmologica
chances of cystoid macular edema, retinal breaks, and 1997;211:8-12.
retinal detachment. 14. Hayashi K, Hayashi H, Nakao F et al. Risk factors for corneal
endothelial injury during phacoemulsification. J Cataract
REFERENCES Refract Surg 1996;22:1079-84.
15. Pederson OO. Comparison of the protective effect of methyl-
1. Hara T, Hara T. Clinical results of endocapsular phacoemulsi- cellulose and sodium hyaluronate on corneal swelling following
fication and complete in-the-bag intraocular lens fixation. J
phacoemulsification of senile cataracts. J Cataract Refract Surg
Cataract Refract Surgery 1987;13:279-86.
1990;16:594-96.
2. Prince RB, Tax RC, Miller DH. Conversion to small incision
16. Ross WH. Management of dislocated lens fragments following
phacoemulsification: Experience with the first 50 eyes. J
phacoemulsification surgery. Can J Ophthalmol 1993;28:163-
Cataract Refract Surg 1993;19:246-50.
66.
3. Francis IC, Irvine S, O’Brien DP et al. Prospective evaluation of
one surgeon’s first 100 cases of endocapsular phaco- 17. Kim JE, Flynn HW Jr. Smiddy WE et al: Retained lens fragments
emulsification cataract surgery. Aust NZJ Ophthalmol after phacoemulsification. Ophthalmology 1994;101:1827-32.
1993;21:147-52. 18. Tommila P, Immonen I. Dislocated nuclear fragments after
4. Thomas R, Braganza A, Raju R et al. Phacoemulsification: A cataract surgery. Eye 1995;9:437-41.
senior surgeon’s learning curve. Ophthalmic Surg 1994; 25:504- 19. Bohigian GM, Wexler SA. Complications of retained nuclear
09. fragments in the anterior chamber after phacoemulsification
5. Tarbet KJ, Mamalis N, Theurer J et al. Complications and with posterior chamber lens implant. Am J Ophthalmol
results of phacoemulsification performed by residents. J 1997;123:546-47.
Cataract Refract Surg 1995;21:661-65. 20. Arentsen JJ, Rodrigues MM, Laibson PR. Corneal opacification
6. Smith JH, Seiff SR. Outcomes of cataract surgery by residents occurring after phacoemulsification and phacofragmentation.
at a public county hospital. Am J Ophthalmol 1997;123:448- Am J Ophthalmol 1977;83:794-804.
54. 21. Polack FM, Sugar A. The phacoemulsification procedure. 111.
7. Gimbell HV. Nucleofractis phacoemulsification through a small Corneal complications. Invest Ophthalmol Vis Sci 1977;16:
pupil. Can J Ophthalmol 1992;27:115-19. 39-46.
8. Zauberman H. Extreme deepening of the anterior chamber 22. Mamalis N, Crandall AS, Linebarger E et al. Effect of intraocular
during phacoemulsification. Ophthalmic Surg 1992;23:555- lens size on PCO after phacoemulsification. J Cataract Refract
56. Surg 1995;21:99-102.
9. Wilbrandt HR, Wilbrandt TH. Pathogenesis and management 23. Wilhelmus KR, Emery JM. Posterior capsule opacification
of the lens-iris diaphragm retropulsion syndrome during phaco- following phacoemulsification. Ophthalmic Surg 1980;11:
emulsification. J Cataract Refract Surg 1994;20:48-53. 264-67.
Chapter 56
Posterior Capsule Opacification:

Pathogenesis, Management
and Prevention
Jagat Ram, Gagandeep S Brar, Supratik Bandopadhyay
Posterior capsule opacification (PCO) and posterior unacceptably high—still over 25% during the 5-year
chamber intraocular lens (PCIOL) decentration are the postoperative period.1 Furthermore, adverse clinical
two remaining major complications of extracapsular sequelae may be associated with Nd: YAG laser
cataract extraction (ECCE) or phacoemulsification.1-6 posterior capsulotomy. Last but not least, there are
Ridley performed first intraocular lens implantation very significant and compelling financial reasons to
in 1949, himself noted these complications in his eliminate the necessity to do the Nd: YAG laser
earliest patients.7 In his publications, he described lens capsulotomy. Nd: YAG laser posterior capsulotomy
decentration, remarking that apparently, the most now ranks as the second most expensive surgical cost
difficult problem was to retain the lens in position. to the US health care system, the cost of the original
He also recognized the problem of PCO and desig- cataract operation being the first.13
nated it as “the principal complication” that is not easy The reported Nd: YAG laser posterior capsulotomy
to treat, which requires division of posterior capsule, rate ranged from 30 to 50% in the 1980s.2,3,11 More
i.e. surgical posterior capsulotomy. 8,9 Control of
decentration and PCO is becoming more necessary
now that IOL implantation is emerging as a refractive
procedure that mandate almost a perfect optical
rehabilitation—as opposed to the former goal of
simply removing the opaque lens material and
achieving safe but less than optimal visual rehabili-
tation.2-5 As the cataract operation continued to be per-
fected, major goal is to eliminate this complication.
Clinical studies have noted the varying incidence
between 10-50% of posterior capsule opacification
following ECCE (Fig. 56.1) or phacoemulsification
(Figs 56.2 and 56.3) with PC IOL implantation.1-3,12-15
Schaumberg et al. a conducted an important meta-
analysis of published articles on PCO and generated
Fig. 56.1: Slit lamp photograph of an eye, status postimplan-
pooled estimate of eyes developing PCO over three tation of rigid PMMA IOL one haptic in the capsular bag and
postoperative points viz. 1, 3 and 5 years. They noted the other in the sulcus. Note posterior capsule opacification in
that the rate of PCO remains unexpectedly and the visual axis at 1 year postoperatively
Chapter 56: Posterior Capsule Opacification: Pathogenesis, Management and Prevention 415
virtual eradication of secondary cataract, the second
most common cause of visual loss after cataract
surgery worldwide.
Why to Eliminate Posterior Capsule Opacification?

Posterior capsule opacification is nagging compli-
cation of ECCE/phaco with PCIOL surgery. There are
several reasons why posterior capsule opacification
need to be eliminated, including the following:
1. The main treatment of posterior capsule opacifi-
cation is Nd: YAG laser capsulotomy, which may
produce several complications such as IOL optic
damage, intraocular pressure rise, cystoid macular
Fig. 56.2: Slit lamp photograph of an eye, status post- edema and increased risk of retinal detachment
implantation of rigid PMMA IOL in the capsular bag. Note particularly in high myopes.
posterior capsule opacification in the visual axis at 2 years post- 2. Expectation of patients receiving modern cataract
operatively surgery is similar to those receiving refractive
surgery. Patients almost expect perfect result.
Satisfactory results of multifocal IOLs also require
decrease in the posterior capsule opacification rate.
3. Posterior capsule opacification causes a significant
financial burden to health care system. Until
recently, Nd : YAG laser posterior capsulotomy is,
most costly procedure the second only to cataract
surgery in USA. In the developing countries, the
facility of Nd:YAG laser posterior capsulotomy for
management of posterior capsule opacification is
not available at all places and all secondary cataract
patients cannot afford the treatment.
4. Posterior capsule opacification is the most common
complication in pediatric IOL implantation and its
reduction will help to improve the safety and
efficacy of IOL implantation in children. 24,25
Fig. 56.3: Post-implantation of Alcon AcrySof IOL in the capsular Posterior capsule opacification is one of the main
bag. Note visually significant posterior capsule opacification at causes of amblyopia after pediatric cataract
1 year postoperatively surgery.
5. Finally, the posterior capsule opacification has
significantly impeded the delivery of successful
recent reports document an additional decrease in
cataract surgery with IOL implantation to 25
PCO and Nd: YAG laser capsulotomy rates.5,11,14-17
million people blind from cataract worldwide.26
With the use of modern surgical techniques and IOLs,
the posterior capsule opacification and Nd: YAG laser
Pathogenesis of Posterior Capsule Opacification
posterior capsulotomy rate is decreasing to less than
10%.18-23 In a recent study by Apple et al24 comparing Most secondary cataracts are caused by proliferation
foldable versus rigid designs, the foldable IOLs were of equatorial lens epithelial cells, forming the pearl
associated with a much lower Nd : YAG laser posterior form of posterior capsule opacification.26 Posterior
capsulotomy rate (14.1% vs 31.1%). Surgical tools and capsule plaque or fibrous plaque detected in patients
IOLs are now available to bring these rates down to after ECCE are not uncommon in the developing
single digits. Careful application and use of these tools countries27 and such plaques are rarely seen in the
by surgeons can genuinely lead in the direction of industrialized world.
The epithelium of the lens consists of anterior corrected visual acuity after surgery. Visually
epithelial cells known as A-cells, which is single significant posterior capsular opacification is defined
continuous cell line. These cells are continuous with as a decrease in the best-corrected postoperative vision
the cells of the equatorial lens bow. The cells of by two Snellen’s lines. Tetz described a photographic
equatorial lens bow are the E-cells, which comprise of image analysis system that can morphologically score
the germinal cells undergoing mitosis as they peel off posterior capsule opacification without dependence
from the equator. They continuously form the peri- on visual acuity testing. 31 Standardized slit lamp retro-
pheral cortical fibers. A-cell tends to remain in place illumination photographs are analyzed. Posterior
and not migrate and is prone to change toward fibrous capsule opacification score is calculated by multi-
tissue (fibrous tissue metaplasia) when disturbed. In plying the density of opacification and graded from
contrast, E-cells of equatorial lens bow tend to migrate 1-4 by the fraction of capsule area behind the IOL optic
along the posterior capsule and form pearls to form that is opacified. This technique shows good inter-and
posterior capsule opacification. These equatorial cells intra-individual reliability. Pandey et al reported a
are primary sources of classical secondary cataract, more sophisticated system of retroillumination
especially the pearls form of posterior capsule imaging of the posterior capsule using a computerized
opacification.26 Fibrous form of posterior capsule high resolution digital system that can produce
opacification occurs as result of either posterior excellent images for objective documentation and
proliferation of A-cells or may result from a fibrous quantitative measurement of posterior capsule
metaplasia of posteriorly migrating E-cells. opacification.32 Apple et al utilized Miyake-Apple
Clinical appearance of PCO may be caused by a posterior photographic technique for analyzing
postoperative localized endophthalmitis, a condition commonly used IOL model in eyes obtained postmor-
that has been recognized as a cause of persistent, tem to evaluate PCO and whether or not an eye had
usually low-grade uveitis. Meisler and associates28 an Nd : YAG laser capsulotomy.15
were first to recognize the role of Propionibacterium
acnes as an offending organism. Piest and associates27 Prevention of Posterior Capsule Opacification
and Apple and associates28 were the first to emphasise
the concept of a post-ECCE localized infectious Although all the steps of cataract surgery are impor-
process caused by sequestrated organism within the tant in reducing this entry, six factors are particularly
capsular bag. Clinically, it is important to be aware of important in relation to eliminating or at least delaying
the fact that clinical picture of PCO may be produced posterior capsule opacification.
by localized endophthalmitis. The use of Nd: YAG First, very essential step in reducing PCO is the
laser capsulotomy to treat the posterior capsule reduction of formation of postoperative Soemmering’s
thickening in this condition may lead to precipitation ring, which is precursor of PCO. This can be reduced
of severe inflammation. not only by excellent hydrodissection-enhanced
cortical clean-up but also use of a highly biocompatible
EVALUATION TECHNIQUES FOR IOL that reduces stimulation of cellular prolife-
POSTERIOR CAPSULE OPACIFICATION ration. 2,3,5,13,26 The six factors influencing PCO
formation are described below.
Precise methods of evaluation are important to
measure the progress of posterior capsule opacifi-
Hydrodissection-enhanced Cortical Clean-up
cation. Most of the studies evaluate posterior capsule
opacification in patients after ECCE/30 phacoemulsifi- First formal publication on this procedure was coined
cation after full dilatation of pupil using slit lamp by Faust30 in 1984; and later on, in 1992 Howard Fine31
biomicroscopy. PCO is defined as opacification of the perfected the technique of subcapsular fluid injection
posterior capsule in the visual axis that is observed and coined the term cortical cleavage hydrodissection.
on silt lamp biomicroscopy, which includes Soemme- The cortical clean-up hydrodissection is used by many
ring’s ring (PCO peripheral to the IOL optic) and surgeons to facilitate lens substance removal and
Elschnig’s pearls and fibrous opacification behind the enhance the safety of the surgery. The goal of
IOL optic. The degree of opacification is assessed using hydrodissection is to remove equatorial cells and
distant direct ophthalmoscopy, direct visualization by cortex, as opposed to single layer of anterior epith-
slit lamp biomicroscopy, and decrease in best- elium that does not migrate.13,26
In-the-Bag Fixation of IOL
The obvious advantage of the in-the-bag fixation is
accomplishment of good centration and more
important advantages that is not often appreciated is
reduction in incidence of PCO.2,3,5,13,26,35,36 The hydro-
dissection-enhanced cortical clean-up and in-the-bag
fixation of IOL are the two most important surgical
factors in reducing PCO. In-the-bag fixation of IOL
functions primarily to enhance the IOL-optic barrier
effect. When the IOL optic is fully in the capsular bag,
its contact is maximum with the posterior capsule and
the barrier effect is functional (Fig. 56.4). When one or
both of the haptics are out-of-the bag, a potential space
exists that allows ingrowth of cells towards visual axis.
Fig 56.4: Post implantation of Pharmacia 911 foldable IOL in
the capsular bag. Note clear visual axis at 3 year postoperatively
Capsulorhexis Edge on the IOL Surface
A significant factor which helps in reducing PCO is
creation of capsulorhexis with a diameter slightly
smaller than that of IOL optic. This helps to provide a
tight fit (analogous to a “shrink-wrap”) of the capsule
around the optic.26,37-39
Biocompatibility of IOL
In general, the amount of PCO depends in part on the
biocompatibility of the IOL. The less the cell
proliferation, the less the chance of posterior capsule
thickening. The amount of PCO depends on many
factors such as the quality of surgery, duration of
implant in the eye and biocompatibility of IOL
material. It has been reported that AcrySof IOL
displays the lowest amount of cell proliferation, Fig. 56.5: Clear visual axis at 2 year postoperatively in an
(Fig. 56.5) and hence is most biocompatible.40-43 eye implanted with AcrySof foldable IOL in the capsular bag
Maximum IOL Optic Posterior Capsule Contact haptics are available which reduce PCO rate; examples
In-the-bag fixation of IOL helps to maintain a tight are S140NB, Pharmacia 911A, Technis IOLs.
contact between the IOL optic and posterior capsule
Barrier Effect of IOL Optic
and helps to inhibit the migration of cells across the
visual axis.10,14,44-48 Posterior angulation of IOL haptics The IOL-optic barrier effect comes into play as a
and a posterior convexity of IOL optic also contribute second line of defense against PCO.49-53 Implanting
significantly in maintaining this maximum posterior IOL in the capsular bag enhances the barrier effect (Fig.
capsule contact. Still another factor, which appears to 56.6). It has been shown that optic with round edges
contribute in, is related to stickiness of IOL bioma- might have negative influence by allowing some of
terial, which in turn might create an adhesion of the the cells to migrate under the tapered edge of the optic
capsule of IOL optic. onto the posterior capsule. A truncated optic edge
Capsule bag implanted IOL provides barrier effect appears to create an abrupt and effective block to cells
for preventing migration of lens epithelial cells onto growing onto the posterior capsule. Examples of
posterior capsule. Presently, foldable IOLs with optic square edge optic IOLs are Alcon AcrySof(R), Cee On
of superior silicone material with PMMA or PVDF 911, etc. (Fig. 56.7).
studying immunological agents such as monoclonal

antibodies targeted to lens epithelial cells.
Management of Posterior Capsule Opacification

In the past invasive surgical posterior capsulotomy
was the primary treatment of posterior capsule
opacification and it is still performed where the Nd:
YAG laser facility is not available or in cases with very
dense or fibrotic membrane particularly in children.61
The treatment of choice for clinically significant
posterior capsule opacification is Nd: YAG laser
posterior capsulotomy.62,63 It is an effective modality
in the management of posterior capsule opacification.
There are several disadvantages of Nd: YAG laser
Fig 56.6: Miyake-Apple view of an eye obtained postmortem
demonstrating capsule bag implanted IOL with silicone optic capsulotomy. There are several vision-threatening
and prolene haptics (S13NB IOL) complications such as damage to IOL optic, postopera-
tive intraocular pressure elevation, cystoid macular
edema, retinal detachment, IOL subluxation or
dislocation and exacerbation of localized endophthal-
mitis. Nd: YAG laser posterior capsulotomy signifi-
cantly increases the overall cost of cataract surgery
beside burden on the health care.
Keeping in view several vision-threatening compli-
cation of Nd: YAG laser capsulotomy or surgical
capsulotomy, peeling or removal of epithelial cells
from the posterior capsule in eyes with pearls type of
PCO with automated irrigation mode or capsule
vacuuming mode or using two-way Simcoe cannula
is recommended particularly for high myopic patients
where incidence of retinal detachment increases
several folds after Nd: YAG laser or surgical posterior
capsulotomy.
Fig. 56.7: Diagrammatic representation of a capsular bag
fixated truncated edge IOL optic. The abrupt edge prevents A New Entity: Interlenticular Opacification (ILO) or
migration of the lens epithelial cells onto the posterior capsule Opacification of Piggyback IOL
The use of piggyback IOL, i.e. use of paired IOLs in
Pharmacological Techniques one eye is becoming more and more common for
and Immunological Inhibitors for PCO correcting residual refractive error after IOL surgery
or as primary procedure in high refractive error. 64-70
Pharmacological techniques which would accomplish Opacification between two-implanted IOLs, has been
the reduction or destruction of lens epithelial cells termed as “Interlenticular opacification” or “inter-
would be perhaps effective in reducing PCO.2,54-60 The pseudophakos Elschnig’s pearls”. In contrast to PCO,
various pharmacological studied are caffeic acid this entity occurs as a result of pearls formation or
phenethyl ester in a rabbit model, hypo-osmolar drugs opacification between the two IOLs undoubtedly due
(sterile water), and metabolites. Antimetabolites that to ingrowths of cells from the equatorial lens bow.
have been studied are daunomycin, methotrexate, 5- Werner et al68 have suggested implanting the posterior
fluorcil and colchicine. The rationale for using is to IOL in the capsular bag and anterior IOL in the sulcus
inhibit lens epithelial cell mitosis while avoiding toxic to reduce this complication beside all the factors listed
effects to non-mitotic cells. Some investigators are for preventing PCO.
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Chapter 57
Multifocal IOLs
Gagandeep S Brar, Jagat Ram
INTRODUCTION b. When viewing a distant object, the multifocal IOL

patient, or even a patient without a pseudophakos,
Cataract surgery today has evolved into a highly
will not allow an image to encroach on the macula-
sophisticated and technically near perfect procedure
object line, since this would block the view of the
which has done away with hospital stay, long-term
distant object.
refractive instability and need to suture the section.
In distance vision, the near focusing point of the
The standard of care for cataract surgery today is lens
multifocal IOL causes the object to be focused as a
extraction and replacement with a monofocal
large, blurry image that cannot complete with the
intraocular lens. However, these monofocal lenses
sharp image on the macula. The same phenomenon
have a single focus, which does not allow good spec-
occurs in reverse for near vision.
tacle free vision for both distance and near. Various
Most monofocal IOL patients, when corrected for
attempts have been made to establish some degree of
distance, cannot comfortably read 20/50 at near. To
pseudoaccommodation such as aiming for myopic
be a valuable asset, multifocal IOLs must not signifi-
astigmatism, targeting one eye for distance and the
cantly compromise distance vision and must provide
fellow eye for near (monovision concept) or multifocal
comfortable 20/40 or better uncorrected near vision.
intraocular lenses (Fig. 57.1). Monovision does not
allow full advantages of binocularity, including
stereopsis at near and bilateral stimulation of visual
cortex for enhancement of distance visual acuity.
Multifocal IOLs are today an increasingly viable
option available to cataract and refractive surgeons
for providing patients with freedom from spectacles
after cataract surgery.
PRINCIPLE OF MULTIFOCALITY
Multifocal IOLs in general provide both far and near
vision by splitting light to two or more focal points.
Some portion of a multifocal IOL that does not change
shape must be capable of focusing a distant object on
the macula and another portion must be capable of
focusing a near object on the macula. Macular confu-
sion, a state of having two discrete images focused on
the macula simultaneously, does not occur for two
reasons.
a. Reading material or other near objects are opaque
and no image from a distant object can be focused Fig. 57.1: Design characteristics of the AMO Array refractive
through the reading material to fall on the macula. accommodative type of multifocal intraocular lens
This 20/40 or better uncorrected near vision provided Exclusion Criteria

by a multifocal IOL allows a patient to perform
1. Patients with a monofocal lens in the other eye.
without spectacles many up-close tasks that cannot
Adaptation may be difficult, and patients may be
be performed well with a monofocal IOL, which is
unhappy with the slightly decreased contrast of
emmetropic for distance and allows 20/80 uncorrected
the multifocal eye.
near vision. When using a monofocal IOL, most
2. A patient with high ametropia as it is more difficult
surgeons aim for a residual refractive error of -0.50 D
to calculate accurate IOL power.
to -1.00 D, which allows for a reasonable compromise
3. Patients with unrealistic expectations, who, during
between uncorrected distance and near vision. A mild
counseling, focus too much on potential side
degree of astigmatism may provide “pseudo-
effects.
accommodation”, but postoperative astigmatism
4. Patients with history of retinal detachments, or
> 1.75 D significantly reduces the quality of vision.
potential for future retinal laser treatments
(diabetes mellitus, AMD, etc.) . This is because the
PATIENT SELECTION multifocal optics may interfere with fine focusing
of the laser.
At the XIII European Society of Cataract and Refrac-
5. Patients having undergone previous glaucoma
tive Surgery (ESCRS) Congress in Amsterdam, 1995,
filtering surgery or corneal transplantation
several exclusion criteria for multifocal IOL implan-
surgery.
tation were agreed upon:
6. Pediatric patients because of unreliability of IOL
1. Because age reduces contrast sensitivity, 83 years
power calculations.
of age was considered to be the upper age limit,
7. Patients with moderate to severe macular degene-
with no lower age limitations.
ration. These subjects may require low-vision
2. Patients with endocrine disorders that might affect
devices to read small print, and thus, the advantage
behavior were excluded. Also, worrying, deman-
of the multifocal IOL may not be fully appreciated.
ding and impatient persons were excluded. Brain
Also reduction of the proportion of light from a
plasticity is considered important because of the
single focal plane potentially may reduce the
longer adaptation period to multifocal
performance of the low vision device.
pseudophakia.
8. Cases where there is doubt about the stability of
3. Possible side effects of multifocal IOLs such as
IOL centration (zonular weakness or dehiscence,
halos, glare and blurred vision should be consi-
posterior capsule rupture or an incomplete
dered with regard to patient profession e.g., long
capsulorhexis.
distance driving.
9. Unilateral cataract in a young patient with a normal
4. Exclude patients with low tolerance to glare and
opposite eye is a contraindication.
brightness.
5. Patients with pre-existing pathology or eye
BIOMETRIC CONSIDERATIONS2-4
abnormality that would affect postoperative visual
results should be excluded. Also exclude patients The key to multifocal success is very careful IOL power
with very small or fixed dilated pupils. calculation. It is recommended that the surgeon be
6. Exclude patients with irregular astigmatism or personally involved and might even do it himself. The
high degrees of regular astigmatism unless intra- instructions must be properly calibrated. Use a third
operative keratotomy or incisional axis modifi- generation formula such as the SRK-T, Holladay or
cation is performed. It is probably best to avoid Hoffer Q. Before beginning to implant multifocal IOLs,
more than 1.5 D against-the-rule astigmatism if a it is recommended to establish a personalized surgeon
12 o’clock incision is planned and a 1.0 D with- constant. This consists of the A-constant for the SRK
the-rule astigmatism if a temporal incision is made. formula, anterior chamber depth in the Hoffer formula
The image distortion caused by the astigmatism and/or “surgeon” factor in the Holladay formula.
(1.6% for every 1 D of cylinder) will superimpose These personalized power constants are best
on top of the underlying contrast acuity loss. For developed following implantation of at least 20 similar
similar reasons, these eyes are more sensitive to IOLs. Patients with a residual refractive error of 0.5 D
subtle amounts of PCO and require a laser or less and a cylinder error of less than 0.75 D will be
capsulotomy earlier than a monofocal IOL. less dependent on glasses. Higher levels of post-op
Chapter 57: Multifocal IOLs 423
myopia tend to create too much of distance blur MULTIFOCAL IOL STYLES 1, 5, 6
without any appreciable benefit for near vision.
Refractive
Higher levels of post-op hyperopia will cause distance
and near blur. For most patients, it is best to err on the These IOL obtain multifocality from a change in
side of low hyperopia, preferably +0.1 D to +0.5 D. optical refractive power in different areas of the IOL
Slightly hyperopic patients tend to be more satisfied optic. This type of IOL is designed to direct light to a
than those who are slightly myopic. This is probably broad range of foci from near to far.
related to unwanted visual problems such as haloes
and night glare that slightly myopic patients might AMO ARRAY Refractive IOL (Fig. 57.2)
experience under scotopic conditions with point
sources of light. Small amounts of post-op hyperopia This IOL has provided new interest because of its
will create minimum blur for the distance image foldability. It is a three-piece biconvex posterior
without appreciably affecting the near image while at chamber mod-C IOL with silicone optic and PMMA
the same time minimizing the size of out-of-focus blur haptics. It has an optic diameter of 6.0 mm and overall
circle created by the near producing portions of the diameter of 13.0 mm. The optic has a series of
lens. If the distance refraction is between +0.1 D to repeatable, continual aspheric power distribution on
+0.5D, uncorrected visual acuity will be minimally the anterior surface of the lens, and a constant
affected and the +3.5 D add in the IOL translates into thickness of 0.9 to 1.1 mm. This IOL is designed to
an effective spectacle add of approximately 3D. In the utilize 100% of available light. Approximately 50% of
real world, near acuity at the preferred working the available light is allocated to distance dominant
distance is more important than near acuity at fixed performance; approximately 37% is allocated to near;
distances because we all tend to choose our preferred and approx. 13% is for intermediate foci depending
distance when we read. Adding more plus power to on pupil size. The lens optic within the central 4.7 mm
the IOL might make reading uncomfortable because diameter has a zonal progressive design with a central
of the shorter working distance. 2.1 mm distance zone followed by five annular zones
with a reading add of 3.5 D alternating with distance:
POSTOPERATIVE OUTCOME ANALYSIS • Zones 1,3, and 5 are distance dominant
The current standard of care maintenance that at least • Zone 2 and 4 are near dominant
50% of patients be within 0.5 D of predicted refraction, • Each of the five zones has ability to refract distance,
90% within + 1.0 D and 99.9% within + 2.0 D.4,5 To intermediate and near focal points, each zone
maximize successful outcome: repeats the entire refractive surface. As the step is
• Discourage patients from using glasses for a while going up and down, we get intermediate powers
after the multifocal is implanted. This allows for on the way to the near peak. The intermediate is
patients to adapt and discover that they can see actually available in every zone (Fig. 57.3).
without additional correction. Patients often report
a gradual decrease in multiple haloes and night
time glare.
• Don’t wait for more than a few weeks to implant
in the second eye in patients with bilateral cataract.
This facilitates adaptation.
• Reassure the patients that it might take a few weeks
to adapt to the new imagery.
If glasses are required, the following steps are
recommended:
• Manually refract (Most autorefractors do not give
an accurate reading with multifocal lenses). Start
by over-plussing.
• Prescribe the minimum amount of cylinder that
provides the best acuity.
• Evaluate near acuity with distance correction and
prescribe add only if necessary. Fig. 57.2: A well-centered capsular bag fixated Array IOL
distance zone. It therefore, resembles the AMO Array

distant dominant lens.
Morcher Refractive Bifocal Lens

These are asymmetrical multifocal IOLs that require
bilateral implantation. The master eye IOL (83S). This
concept is based on the hypothesis that the image in
the dominant focus of both eyes will be additive, thus
allowing a binocular contrast sensitivity and distance
and near acuity that are superior to that in bilateral
multifocal IOLs with symmetric light distribution.
Domilens Progressive Multifocal IOL

Fig. 57.3: A capsular fixation Array IOL with an eccentric This is a near dominant progressive lens of 7.7 mm
continuous curvilinear capsulorhexis. Note the visually with 13.5 mm haptics. The central aspheric zone of
significant posterior capsule opacification 4.7 mm progresses from a + 3.75 D central reading
The IOL is distant dominant for safety because far add to an intermediate area with the rest of the IOL
image quality is considered most crucial to spherical for distance. It is, therefore, similar to the
uncontrollability of light and inability to change object Lobal Nuvue near-dominant lens.
position. The near add of 3.5 D is equivalent to 3.0 D
in the spectacle plane. Diffractive Multifocal Lenses
The AMO array, by having less abrupt transitions These IOLs function by focusing light on the macula
between zones, is designed to lower the potential for by diffraction. Diffraction is the phenomenon of light
haloes and rings around lights and to allow for a range bending as it passes near an edge. The shape of the
of foci from near to distance. The multiple zones and edge determines the amount of bending. The waves
continuous curves are designed to make the lens of light can be made to augment or suppress each other
relatively forgiving to decentration and tilt and allow by constructive or destructive interference,
more compensation than gently expected for astig- respectively. With these IOLs diffraction is caused by
matic error. circular microridges on its posterior surface that create
constructive interference of light rays to direct rays at
Iolab Nuvue Refractive IOL either near or far foci. Thus, most diffractive IOLs are
The Iolab Nuvue 8191 refractive IOL is a single piece bifocal, with approx. 41% of light directed to the far
PMMA with blue haptics and 5.5 mm round biconvex image and 41% to the near image. Approx. 18% of the
optic with a central 1.5 mm diameter reading add of remaining incident light is lost to higher-order
+ 4.0 D (equivalent to + 2.9 D in the spectacle plane). diffraction and is unfocusable. This is in contrast to
The blue haptics are 12.5 mm in diameter; this lens refractive IOLs that focus 100% of the available light.
comes within the category of small incision lenses. This Although success of refractive multifocal IOLs
design is sensitive to pupil size since the distance depends on good centration, no tilt and a normal pupil
vision may be compromised when the pupil becomes size, the diffractive IOL function is almost
miotic. Therefore, this IOL functions better when the independent of pupil size and movement.
lens is decentred relative to the pupil axis. The
transition zone between the two segments may be 3 M Multifocal IOL
responsible for glare and, also, for an improved depth This lens works on the diffractive principles but is no
of field due to it’s variable refractive surface. longer in production being a large optic lens with
manufacturing problems.
Storz True Refractive Multifocal IOL
It has a one piece PMMA 5.5 biconvex optic with Pharmacia CeeOn 808X and
12.5 mm haptics. There are 3 segments: a central 811E Diffractive Bifocal IOL
distance zone of 1.5 mm diameter, a near annular zone The 808 X has a 6.5 mm biconvex optic, and the 811 E
of 1.1 mm width of 4.0 D add, and a peripheral has a heparin sulfate surface modified 6.0 mm optic
with two-micron high diffractive rings on the posterior
optic surface (Fig. 57.4). Both lenses are biconvex
single-piece PMMA with 12.0mm diameter haptics
and +4.0 D reading addition. It is essentially a bifocal
IOL without any intermediate foci.
New Accommodating Lens

Kamman7,8 et al reported on a foldable, hinged plate-
haptic silicone lens. The optic is 4.5 mm in diameter
and the overall diameter 11.5 mm. The groove between
the optic and haptic allows forward and backward
optic movement with constriction and relaxation of
the ciliary muscle. At 26 months post-op, the 5 eyes
has accommodative amplitudes ranging from + 1.75
D to 3.5 D. This lens would not reduce contrast sensi-
tivity.
VISUAL OUTCOMES Fig. 57.4: The diffractive type of multifocal IOL.

Note the Nd: YAG laser capsulotomy
The visual outcomes of the use of various multifocal
IOLs 9-14 shall be discussed under the following
headings: clinically similar, with a mean of 20/25 for multifocal
1. Visual acuity eyes and 20/23 for monofocal eyes. Uncorrected
2. Depth of focus distance V/A of 20/20 or better was achieved by 18%
3. Contrast sensitivity (18 of 102) of multifocal and monofocal eyes
4. Visual symptoms respectively.
5. Driving ability For near V/A, the study found statistically
6. Spectacle use and patient satisfaction significant differences in favor of multifocal IOLs.
Mean uncorrected near V/A was 20/33 for multifocal
Visual Acuity eyes and 20/54 for monofocal eyes, with a mean
difference of 2 lines. 86% (87 of 101) of multifocal but
A recent meta-analysis of all published randomized only 49% (49 of 101) of monofocal eyes achieved J3
controlled trials10 reported better unaided near acuity (20/40) or better uncorrected VA. The proportion of
with multifocal intraocular lenses compared to eyes achieving J1 or better was 47% for multifocal eyes
monofocal IOLs. The largest evaluation of refractive and 12% for monofocal eyes. Results of near acuity
accommodative type of multifocal IOL is the Array with distance correction were similar to uncorrected
multifocal safety and efficacy study11 (n = 456). This near vision with a difference between mean values of
prospective, nonrandomized, fellow eye comparative two lines in favor of multifocal eyes. In the monofocal-
trial included a subset of subjects (n = 102) who multifocal subset (n = 101), a higher percentage of
received a monofocal in one eye and a multifocal in multifocal eyes achieved the combined distance and
the other. This subset for interocular comparisons near visual acuity criteria with 77% of multifocal eyes
without the issues of inter-patient variability. For the and 46% of monofocal eyes achieving 20/40 or better
remaining subjects, the fellow eye was either and J3 or better. Using best distance correction, the
multifocal, monofocal or phakic. The 1 -year post-op proportion of eyes achieving both acuity levels was
results of the monofocal-multifocal subset were the 81% for multifocal eyes and 48% for monofocal eyes.
primary focus of this report. The above VA results demonstrated that the Array
In this subset, uncorrected distance V/A was IOL provided significantly better uncorrected and
similar between groups with a mean of 20/32 for corrected V/A, but distance V/A was clinically similar
multifocal eyes and 20/30 for monofocal eyes. between the lens groups.
Although a statistically significant difference was Visual acuity results for the Array lens have also
found for best-corrected V/A, the results were been reported by Arens et al.12 In this retrospective
study, visual function was evaluated in 21 patients In the Array lens safety efficacy study, depth of
with bilateral Array implants and 15 patients with focus was defined as the total range of defocus
bilateral monofocal implants. The objective of this between distance and near where the visual acuity was
study was to find out whether a multifocal IOL affects 20/40 or better. Multifocal eyes demonstrated a
binocularity. No significant difference was found significantly greater depth of focus compared with
between monofocal and multifocal IOLs for monofocal eyes, with a mean depth of focus increase
uncorrected and corrected distance V/A, but when of 0.94 D for multifocal eyes. The additional depth of
uncorrected distance V/A was measured mono- focus provided by the multifocal IOL was most
cularly, subjects with multifocal lenses achieved better pronounced at near, where an approximately three-
distance acuity than those with monofocal lenses. line visual increase occurred.
Liekfeld et al 13 compared visual acuity of the Vaquero-Ruano et al15 compared the Array lens
diffractive CeeOn 811E lenses (n = 26) and refractive and a monofocal IOL by determining the distance
Array multifocal IOLs (n = 24). At 4 to 6 weeks post- depth of focus by defocusing from + 3 D to -4 D using
op, the CeeOn group achieved significantly better near a 96% contrast Regan chart. The Array lens was found
V/A than the Array group. Mean uncorrected near to have a significantly broader depth of focus than
V/A was 20/20 Snellen for the CeeOn group and 20/ the monofocal IOL, especially in the near vision range
30 for the Array group. Near visual acuity with from-1 D to -3 D.
distance correction was also significantly different
between the groups, with mean values of 20/20 for Contrast Sensitivity
the CeeOn group and 20/25-20/30 for the Array
The best acuity possible for a given contrast is known
group. No between-group differences for distance V/
as contrast sensitivity. Contrast sensitivity is defined
A were found. The better near V/A scores for the
as the reciprocal of the contrast that barely allows a
CeeOn lenses are partially caused by this lens having
certain acuity.
a higher add of +4.0 D, compared with the Array with
The main drawback of multifocal IOLs is a loss of
an add of +3.5 D. Although increasing the add power
contrast sensitivity at low spatial frequencies. This is
of a lens improves near acuity values by increasing
because multifocal optics function to distribute light
magnification, the working distance at which the
through several foci, so contrast sensitivity is reduced
reading material must be held is decreased with
and glare disability increased when the image of a
increasing add power. Also, the size of the out of focus
distant focus is overlapped by the out-of-focus images
blur circle created by the add when viewing distant
generated from the multifocal design. So the increased
point sources of light is increased, which may possibly
depth of focus provided by a multifocal IOL is usually
exacerbate the perception of halos. Thus, higher
provided at the expense of image clarity. Patients with
diopter add lenses are a trade-off in the overall facility
diffractive and refractive lenses have been reported
of visual function.
to experience a reduction in contrast sensitivity,
Avitable et al14 have also evaluated the CeeOn 811
although the issue has traditionally been more
E multifocal in a group of 35 patients that were all
strongly associated with diffractive IOLs.
unilaterally implanted. At the final examination (mean
The Array lens safety and efficacy study evaluated
20 months post-op), the mean UCVA and BCVA
contrast acuity in 67 of the subjects with multifocal -
values were 0.79 and 1.00 respectively. UCVA of 20/
monofocal lenses. Regan contrast acuity letter charts
40 or better was achieved by 34 of the 35 patients (97%).
were used for distance, and the Holladay Contrast
Acuity tests for near. In a group of 43 subjects with
Depth of Focus
monofocal-multifocal IOLs with medium sized pupils
The goal of a multifocal IOL is to imitate physiologic (>2.5 mm to < 4 mm), the monofocal lenses achieved
accommodation, which provides high visual acuity better acuity than did the multifocal IOLs at low-
from distance to near. With a monofocal IOL, V/A is contrast levels with the Brightness Acuity Tester (BAT)
maximum at a distinct distance and decreases with off (mean difference, -0.6 Regan line at 25% and -0.9
increasing defocus. The depth of focus increase regan line at 11%; P < 0.007), but visual function and
provided by multifocal IOLs as compared to patient satisfaction results demonstrated that no
monofocal IOLs results in a tradeoff with decreased perceived disadvantages are associated with reduced
image clarity resulting from multifocal vision. low contrast acuity. Low contrast acuity loss was
apparently an acceptable compromise for the that the slightly reduced contrast sensitivity in the
enhanced near and functional vision that patients were group with diffractive lenses might result from the
able to experience across a range of distances. differences in light distribution produced by
Contrast acuity results from Vaquero-Ruano et al15 diffractive and refractive principles. With the 3M
were similar to those of the Array lens safety and diffractive IOL, 41% of incoming light is allocated to
efficacy study. In their evaluation of binocular vision distance focus, 41% to near focus and 18% to higher
with a multifocal IOL, Arens et al12 measured mono- orders of diffraction that remains unfocussed by the
cular and binocular contrast sensitivity in patients eye at all times. All available light is used with the
with bilateral monofocal or bilateral Array IOLs. refractive ARRAY lens. Depending upon pupil size,
Contrast acuity was measured by using Regan Low 50-60% is allocated to the distance focus, and the
Contrast Acuity Charts of 96%, 50%, 25%, and 11%. remaining 40-50% to near and intermediate foci. Thus
The test was performed with distance correction at the distance focus of the diffractive 3M IOL is
3 m and with maximum room luminescence. The ultimately generated by a smaller amount of the
results show at high and moderate contrast, but at 11% incoming light than in the refractive IOL. Leikfeld et
contrast, the sensitivity level was significantly lower al13 compared contrast sensitivity afforded by the
monocularly in the group with multifocal lenses (0.41 refractive ARRAY lens versus the diffractive CeeOn
monofocal vs. 0.33 multifocal; P <0.05). Binocularly at 811E lens. They found both the groups to be
11% contrast the groups exhibited similar levels of comparable with regard to contrast sensitivity and low
sensitivity. In general, both groups had slightly better contrast visual acuity and concluded that both the
acuity binocularly and monocularly, but the difference IOLs function well.
was less than one line of visual acuity. Although not
statistically significant, the test showed some
Visual Symptoms
improvement in binocular contrast acuity at higher
contrast levels compared with monocular values. This As a part of the Array lens safety and efficacy study11
might result from neural summation of two monocular subjects with multifocal IOLs completed a question-
responses. Such responses correspond to normal naire at one year postoperatively to subjectively
observers, in whom binocular contrast acuity is typi- evaluate their visual performance and level of
cally higher than monocular sensitivity. The investi- difficulty regarding visual symptoms. Multifocal
gators therefore, recommended bilateral implantation patients reported significantly more difficulty than did
of the Array lens to maximize contrast sensitivity and patients with monofocal IOLs for just 3 of 11
stereopsis. They also suggest that bilateral implan- symptoms: (1) haloes (P = 0.001), (2) glare/flare (P =
tation may reduce the occurrence of optical symptoms. 0.014), and (3) blurred (P = 0.011). The percentage of
Pieh et al16 evaluated contrast sensitivity and glare patients with multifocal versus monofocal lenses
disability with diffractive 3M and the refractive Array reporting severe difficulty with these symptoms was
multifunctional IOLs. Contrast sensitivity was 15% versus 6% for haloes, 11% versus 1% for glare/
determined at best corrected distance with a series of flare, and 4% versus 1% for blurred far vision.
stationery, vertical, sinusoidal gratings generated on Although the differences were significant, the mean
a television monitor. The spatial frequencies were 0.5, scores were generally low, thereby indicating most
1.0, 3.0, 6.0, 11.4 and 22.8 cycles per degree (cpd), and patients experienced relatively no limitation with the
testing took place under mesopic conditions. A ARRAY IOL. Most patients in both groups reported
reference range for contrast acuity was established no difficulty for all other optical symptoms, which
using a group of phakic patients to accurately rate the included night vision, blurred near vision, distorted
performance of multifocal IOLs. They found that both far vision, depth perception, double vision had color
the groups were in the lower part of the reference distortion.
range, but the group with diffractive IOLs was slightly Vaquero-Ruano et al15 found that the occurrence
less sensitive to contrast (90-94% of refractive level) of ghosting and glare were similar in groups with
from 3.0 cpd to 11.4 cpd, although the difference in Array and monofocal IOLs. All patients found the
the two groups was only statistically significant at 6.0 visual symptoms tolerable, and no patient requested
cpd. At 22.8 cpd, no significant difference was found to have their IOLs removed. Peih et al16 used BAT as
between the two groups. The investigators suggested the glare source while measuring contrast acuity of
subjects with a diffractive 3M or the refractive Array CeeOn 811E and the refractive Array lens, Liekfeld et
IOL. The BAT is a hand held instrument used to al13 found no significant difference between groups
simulate 3 bright light conditions. The low brightness with respect to V/A under glare at 4 to 6 weeks post-
setting is comparable with bright overhead operative.
commercial lighting, medium brightness, to a partly
cloudy day and high brightness, to direct overhead Driving Ability
sunlight. For the group with the diffractive 3M lenses,
Given that the primary disadvantage of multi-
contrast sensitivity under glare conditions was in the
functional IOLs is visual performance in low-contrast
lower limit of the reference range (based on phakic
situations, some investigators have questioned the
subject results) and dipped below the reference range
effect of multifocal IOLs on night-driving ability.
at 3 and 6 cpd. The group with Array lenses also
Featherstone et al17 conducted a driving simulation
performed within the lower portion of reference range
study as part of the Array Lens safety and efficacy
but only dipped below the reference range at 3 cpd.
study. This study was a test operator -masked,
At 6 cpd, the difference between the two groups was
parallel-group comparison between 33 patients with
statistically in favor of Array lenses. The investigators
bilaterally implanted Array IOLs and 33 control
suggest that this difference may suggest that the 3 M
subjects with bilaterally implanted monofocal IOLs.
IOL is more sensitive to glare than the Array lens, but
Subjects were evaluated with respect to their
they discussed the possibility that smaller pupil size
recognition rates and recognition distances for traffic
in the presence of glare may enhance contrast
signs. The same criteria plus avoidance behaviors were
sensitivity for patients with Array lenses. Pupil size
evaluated in the presence of hazards. The results
has no effect on the diffractive IOL. With the refractive
showed that the 2 groups performed similarly in 26
IOL, a smaller pupil causes as much as 60% of
to 30 comparisons. In the 4 groups with statistically
incoming light to be directed at the distant focus
significant differences, the monofocal group
leading to higher levels of contrast acuity.
performed better, but on average, multifocal patients
Dick et al3 found that halo size in patients with
still performed within safety guidelines. This study
Multifocal IOLs was significantly larger than that of
demonstrated that the multifocal lens does not
monofocal or zonal-progressive refractive IOLs. One
preclude driving safely. Grosskopf et al 18 also
explanation for this is that the zonal-progressive
investigated night driving safety in patients with
multifocal IOL is a distance dominated IOL, whereas
multifocal IOLs and found that both patients with
in a refractive IOL, light is distributed in equal parts
monofocal and multifocal IOLs are likely to experience
for distance and near in addition to 18% stray light.
visual impairment during night time driving.
Another reason is that the zonal progressive multifocal
IOL’s aspheric surface and continuous step-free curves
seem to be less sensitive to produce stray light than Spectacle use and Patient Satisfaction
diffractive IOL, which have numerous rings with a This aspect is important because many patients with
step height of 2 mm. multifocal IOLs expect a certain level of spectacle
Arens et al also used the BAT as a glare light source independence.
during visual acuity tests of patients with Array and Spectacle use was determined in the Array lens
monofocal lenses. Testing was performed with best safety and efficacy study at one year following
distance correction for a projected acuity chart at 5m surgery. Eighty one percent of subjects with bilateral
in a darkened room. At each brightness of the BAT, array lenses reported that they could function
the best V/A was recorded. For binocular testing, a comfortably at near without the use of spectacles. For
BAT was held for each eye. In all three lighting intermediate vision, 93% of them could function
conditions, patients with binocularly implanted Array comfortably without spectacles. Similarly, 93% could
lenses exhibited slightly better visual acuity than function comfortably without glasses for distance. The
patients with monofocal IOLs, but the differences were study also found that the full benefit of multifocal IOLs
not statistically significant. Monocularly, the results are more likely to be realized with bilateral than
were similar between groups. These results suggest unilateral implantation as the proportion of spectacle
that glare produced by this method was not a independent subjects with unilateral Array
significant issue for patients with multifocal Array implantation was generally less than with bifocal
IOLs. In a 50-patient comparison study of diffractive Array implantation.
Patient satisfaction at one year postoperative was chemically remove cataracts through a needle incision,
evaluated in the Array lens safety and efficacy study will we move to an injectable liquid lens implant that
with two questions: (1) Were you satisfied with your restores accommodation ?
surgery? and (2) Would you elect a multifocal lens
again? In all groups with multifocal lenses with in the REFERENCES
1. Pearce JL. Multifocal intraocular lenses, Curr Opin
study (unilateral, bilateral, and monofacal -multifocal),
more than 90% were moderately or very satisfied, and 2. Steinert RF. How to use the new multifocal IOL. Review of
more than 90% would effect the same lens again. Those Ophthalmology, 1998.
of Vaquero-Ruano et al support these results. All 50 3. Dick BH, Krummenauer F, Schwen C, Krist R, Pfeffer N,
patients with Array lenses in their study stated that objective and subjective evaluation of photic phenomena after
they were satisfied with the Array multifocal and monofocal and Multifocal intraocular lens implantation.
Ophthalmology 1999;1187.
appreciated their improved range in functional vision, 4. Holladay JT, Prager TC, Ruiz RS, et al. Improving the
even if they were not completely free of spectacle use. predictability of intraocular lens power calculations. Arch
Avitabile et al14 evaluated satisfaction levels of Ophthalmol 1986;104:539.
patients implanted unilaterally with CeeOn 811 E 5. Holladay JT, Musgrove KH, Prager Tc et al. A three part
diffractive multifocal IOLs. 31% of the patients were system of refining intraocular lens power calculations. J
Cataract Refract Surg 1988;14:17.
dissatisfied with their uncorrected near and distance 6. Pearce JL. Multifocal intraocular lenses. Cur Opin
vision, whereas 43% were satisfied and 26% were Ophthalmol 1997;8;1:2.
highly satisfied. The investigators suggested that the 7. Kamman J, Cumming JS. New accommodating IOL looks
high dissatisfaction rate (31%) is related to unilateral promising in first European trials. Euro Times 1996;1:14.
implantation in this study. With best distance 8. Kamman J. Vitreous stabilizing, single piece, mini-loop, plate-
haptic silicone intraocular lens. J Cataract Refract Surg
correction, satisfaction levels improved: only 6% were
1998;24:98.
dissatisfied, 57% were satisfied, and 37% b were highly 9. Steinert RF, Visual outcomes with multifocal intraocular
satisfied. 89% of the subjects elected to have the same lenses. Curr Opin Ophthalmol 2000;11:12-21.
IOL implanted in the other eye also. 10. Leyland M, Zinicola E. Multifocal versus Monofocal
With the asymmetric multifocal system,19 80% Intraocular Lenses in Cataract Surgery. A Systematic Review.
reported never using spectacles, whereas 20% used
11. Steinert RF, Aker BL, Trentacost DJ, Smith Taratino N. A pros-
spectacles for distance. This study suggests that this pective comparative study of the AMO ARRAY zonal pro-
system may provide patients with an ability to gressive multifocal silicone intraocular lens and a monofocal
function without spectacles that is similar to that intraocular lens. Ophthalmology 1999;106;1243-55.
experienced with Array lenses. 12. Arens B, Freudeenthaler N, Queentin CD. Binocular function
after bilateral implantation of monofocal and refractive
CONCLUSIONS multifocal intraocular lenses. J Cataract Refract Surg
1999;25:399.
Multifocal IOLs enhance near vision performance 13. Liekfeld A, Walkow T, Anders N, et al. Prospective evaluation
without spectacles compared with monofocal IOLs. of two multifocal lens models. Ophthalmologe 1998;95:253.
The “spread” of focus inherently results in some loss 14. Avitabile T, Marano F, Canino EG, et al. Long-term visual
of contrast sensitivity, but most patients seem to results of bifocal intraocular lens implantation. J Cataract
function well without difficulty caused by loss of Refract Surg 1999;25;1263.
15. Vaquero-Ruano M, Encinas JL, Milan I, et al. Array multifocal
contrast. “Ghost images” or haloes occur because of versus monofocal intraocular lenses; long-term follow-up. J
the out-of-focus portion of the image in the multifocal Cataract Refract Surg 1998;24;118.
IOL, and these are perceived as a problem by a few 16. Pieh S, Weghaupt H, Skorpik S. contrast sensitivity and glare
patients. Perception of glare and contrast sensitivity disability with diffractive and refractive multifocal intraocular
loss is perhaps greater with diffractive optics lenses. J Cataract Refract Surg 1998;24:659.
17. Featherstone KA, Bloomfield JR, Lang AJ, et al. Driving
compared with refractive optics. Future refinements
simulation study : bilateral Array multifocal versus bilateral
to multifocal IOLs may include varying the add power AMO monofocal intraocular lenses. J Cataract Refract Surg
in the second eye and varying the distribution of light 1999;25:1254.
energy between distance and near for both eyes. 18. Grosskopf U, Wagner R, Jacobi FK, et al. Twilight vision and
Finding a drug that will breakdown cortical lens glare sensitivity in monofocal and multifocal pseudophakia.
Opthalmologe 1998;95:432.
matter but would have no toxic effect on other
19. Jacobi FK, Kammann J, Jacobi KW, et al. Bilateral implantation
intraocular lens may be the harbinger of chemical of asymmetric diffractive multifocal lenses, Arch Ophthalmol
cataract removal. When the day comes that we can 1999;117:17.
Chapter 58
Piggyback IOLs
Sushismita Kaushik, Jagat Ram, Supratik Bandopadhyay
Piggyback intraocular lens implantation is a new atraumatic procedure. An IOL exchange involves
modality which is fast emerging as a viable option removing the existing IOL before implanting a new
for the refractive correction of high hyperopes. As a one. The additional manipulation required for the
secondary procedure, it is useful to correct pos- removal process, particularly if the IOL is strongly
tpseudophakic refractive errors. An overview of fixated, increases the risks of complications such as
these lenses is presented, with a brief description of retinal tears, cystoid macular edema, cyclodialysis,
early experiences with its implantation. and posterior or anterior capsular raptures.
Achieving emmetropia in extremely short eyes The power of a secondary piggyback IOL is also
after cataract surgery is a difficult challenge clinically more predictable than an IOL exchange because it is
for following reasons. challenged purely on the basis of the patient’s
1. Ultrasound biometers are calibrated with average postoperative refraction.
measurements for normal sized eyes (22-24 mm)
that are incorrect for small eyes causing significant PRIMARY PIGGYBACK IOL IMPLANTATION
measurement errors. Eye proportions in small eyes
High Hyperopes
are usually different due to relatively normal
anterior segments and short posterior segments. Primary piggyback implantation for high hyperopia
2. Any measurement error in a short eye will have a or even hyperopia requiring lens power close to the
much greater effect on the final refraction, because higher side of the available inventories is now
a given deviation would be a much greater increasingly used as a viable option for those patients
percentage in a small eye. with cataract. The highly hyperopic patient with
3. Lenses above 34.0 D are not readily available, cataract presents with two potential problems. The
must be custom manufactured, and suffer from first is the possibility of surgical complications which
the severe spherical aberration caused by the steep may arise from the structural nature of the eye. These
radii render these high power lenses nearly include higher chances of choroidal effusions,
spherical. malignant glaucoma, expulsive hemorrhage, repeated
In 1993, Gayton and Sanders 1 attempted to iris prolapse during surgery and increased chances
overcome this problem by implanting two IOLs in of secondary angle closure glaucoma. The second
one eye to provide adequate power in a case of micro- problem is implanting adequate power while
phthalmos. The required IOL power was 46.0 D. maintaining good optical quality and accurate
Necessity became the mother of invention. Since refraction.
Gayton was unable to get any manufacturer to make Even if the surgeon is fairly confident of the IOL
a 46.0 D lens posteriorly and a 20.0 D lens anteriorly power, lenses of powers greater than 34.0 D are not
in the capsular bag. available with most manufacturers. A practical
This idea has since been extended to include solution to the problem of providing accurate power
secondary corrections of pseudophakic refractive for the patient with the short eye is to implant two
errors. Implanting a secondary IOL anterior to the IOLs “piggyback” style which together provide
one already in place is an easy and relatively adequate power with satisfactory image quality.
Chapter 58: Piggyback IOLs 431
Minus Power Piggyback Lenses POWER CALCULATION FOR A PIGGYBACK IOL
(GILLS’ NOMOGRAM FOR POWER
Primary minus-power piggyback implantation is rare,
though it has been reported in a cataract patient with CALCULATION)6
keratoconus with severe myopia. 2 The patient
required a - 14.0 D intraocular lens. Two negative- Primary Implantations
power IOLs were implanted to optimize visual
Optimizing axial length measurements does not
results. Fifteen weeks later uncorrected visual acuity
guarantee the desired refractive outcome in small
was 20/80 at distance and 20/50 at near. Best-
eyes. Holladat et al 7 examined several hyperopic
corrected distance vision was 20/40 with -0.75 D.
patients and took detailed anatomic measurements.
In most cases, he found that these eyes had normal
Toric Piggyback IOLs
anterior segment dimensions. The abnormality was
Gills et al 3 reported implantation of two toric haptic a short axial length due to a shortened posterior
IOLs in a patient with 5.12 D corneal astigmatism segment. Therefore, most formulas were found to
with good results, and a post-operative refractive be underestimating the required power in these short
astigmatism of 1.0 D. They later4 implanted a pair of eyes since they assumed a proportional anatomy
piggyback IOLs which sutured together to combat similar to normal eyes.
high corneal astigmatism. They reported that suturing The first case of piggyback IOL implantation by
toric lenses together allows greater correction of Gayton1 resulted in a hyperopic refractive surprise
astigmatism without concern about counter rotation of +8.0 D, requiring an exchange of the anterior IOL
of the lenses. of 20.0 D with a 30.0 D lens. These results of
postoperative hyperopia were echoed by Holladay
Multifocal Piggyback IOL et al 7 in their series of piggyback IOL implantation.
By combining a piggyback technique with the use of Several theories for this postoperative hyperopia
a multifocal IOL, it is possible to obtain the optical have been postulated:
advantages of both, achieving high-quality visual Since all the current formulas shorten the expected
acuity for distance and near vision and reducing the anterior chamber depth as a function of the axial
optical aberrations of extremely high-powered single length, they would all predict the position of the lens
IOLs. Donoso et al 5 reported 5 hyperopic patients (6 to be too anterior, which results in a hyperopic error.
eyes) who had phacoemulsification and in-the-bag a. Another factor is the actual position of the
implantation of 2 foldable IOLs in the bag, a silicone piggyback lenses in the bag. It was earlier assumed
multifocal IOL placed in front of a silicone monofocal that the anterior lens would be anterior in the
IOL. Good results were obtained in near and distance posterior chamber than the normal lens. However,
uncorrected visual acuities, and patient satisfaction Holladay’s postoperative measurements revealed
was excellent in all cases. that due to the elasticity of the posterior capsule
the anterior lens was in the normal position and
Secondary Piggyback Implantation the posterior lens was one lens deeper than normal.
b. A significant problem with indentation biometry
Secondary piggyback implantation are now used in is that the cornea is easily indented even by the
conditions of: most skilled hands. Even the slightest indentation
a. Postoperative refractive surprises - with the can cause significant measurement errors which
advent of minus power lenses, even myopic are magnified when the eye is short.
pseudophakes can benefit. A new Holladay power formula, the Holladay
b. Pseudophakic patients who have undergone a II, 8,9 has been developed using additonal
penetrating keratoplasty and develop significant measurements like the white-white corneal diameter,
visually disabling refractive errors. lens thickness and anterior chamber depth, and takes
c. Pseudophakic children with IOL power changes. into account the lens power shift caused by piggyback
d. Patients who have undergone a corneal refractive IOL implantation.
procedure and are thus more likely to have a The total power required is divided in half
postcataract surgery refractive error. between the two lenses.
Secondary Implantation central refractive power must be lower than the

surrounding zone. Therefore, the patient must be
a. Hyperopic pseudophake
using the central zone for distance vision and the
Power required (< 21 mm)
surrounding zone for near vision, thus accounting
= (1.5 × spherical equivalent)
for the clinical evidence increased depth of focus.
+ 1.
(22-26 mm) = (1.4 × spherical equivalent) + 1.
COMPLICATIONS
(> 27.0 mm)= (1.3 × spherical equivalent) + 1.
b. Myopic pseudophake A recent cause of concern with the piggyback IOL is
Power required (< 21 mm) the cellular growth between the lenses. 14-20 Shugar
= (1.5 × spherical equivalent) and Schwartz15 were the first to report Elschnig pearl
- 1. formation in the peripheral interface between
(22-26 mm) = (1.4 × spherical equivalent) - 1. piggybacked acrylic lenses. They noted a late
(> 27.0 mm)= (1.3 × spherical equivalent) - 1. hyperopic shift in refraction as a result of this inter-
Fenzl et al 10 studied a cohort of 51 myopic pseudo- lenticular opacification (ILO). Shugar and Keeler16
phakes where a mean residual myopia of -3.05 D was followed it up with a report of interlenticular opacifi-
reduced to -0.38 D. All patients were within 1.0 D of cation as a late late complication of piggybacked IOLs.
desired refraction. Best-corrected vision was 20/40 Gayton et al 17 studied the clinicopathological
or better in 96% of cases. correlation of IOL in piggyback IOLs. They found
that it was caused by lens epithelial cell migration
IMAGE QUALITY and proliferation in the space between two piggyback
IOLs. They suggested the following measures to
At high diopteric powers (> 40.0 D), image quality
reduce the development of this complication.
of a piggyback lens is superior to that of a single
1. Careful cortical clean up during surgery to remove
lens. At such high dioptres, significant spherical
most residual cells from the equatorial bow.
aberrations occur in single lenses. Very steep radii
2. Placement of the posterior IOL in the bag and the
are required causing the lens to be shaped like a
anterior IOL in the sulcus. The bioadhesion of the
sphere. Thus resolution is compromised, resulting in
posterior lens to the cut edge of the capsulorhexis
a severely distorted image quality.
isolates the lens epithelial cells from the
Hull et al11 have studied various lens shapes for
interlenticular space.
very short eyes that would minimize spherical
3. Perform a CCC larger than the IOL optic. The cut
aberration. The optimum shape for maximizing image
anterior edge of the CCC then adheres to the
quality was found to be a piggyback system using
posterior capsule and sequesters the lens epithelial
two convexo-plane surfaces with both the convex
cells in the periphery.
surfaces facing the cornea.
This complication is now widely known, and may
require explanation of the pair of lenses. Eleftheriadis
DEPTH OF FOCUS USING A PIGGY BACK SYSTEM
et al 18 observed that careful separation of the IOL
Fenzl et al10 have clinically noticed an increased depth complex from the capsule, meticulous clean up of the
of focus in many eyes receiving multiple implants. proliferating material, and implantation of single or
Overall increased depth of focus was observed in dual in-the-bag PMMA IOLs through a large incision
46% of eyes with a single IOL and in 54% of eyes with capsulorhexis enlargement may help in the
with piggyback IOLs. prevention of recurrence of interface opacification.
Findl et al12,13 have hypothesized a possible expla- Jackson et al 21 described the occurrence of inter-
nation for this phenomenon. They observed a central lenticular opacification in association with asymmetric
contact zone between two piggyback acrylic lenses haptic fixation of the anterior intraocular lens. They
using specular microscopy. This contained a central found that interlenticular opacification was localized
dark zone surrounded by Newton rings. They to the interlenticular area near the anterior lens haptic
probably represent a thin gap between the lenses fixation in the ciliary sulcus, which supported the idea
which causes interference. that sulcus placement of the anterior IOL helps to
It was postulated that within the contact zone the prevent interlenticular opacification.
lens curvatures must be flatter and therefore the The technique of piggyback IOL implantation is
Chapter 58: Piggyback IOLs 433
used relatively infrequently now but is likely to 10. Fenzl RE, Gills JP III, Gills JP. Piggyback intraocular lens
increase in the coming decades. Though it is applicable implantation. Curr Opin Ophthalmol 2000;11:73.
11. Hull CC, Liu CS, Sciscio A. Image quality in polypseudo-
as a primary procedure in cases of extreme refractive
phakia for extremely short eyes. Br J Ophthalmol 1999;83:656.
errors, it is slowly gaining a place in the secondary 12. Findl O, Menapace R, Rainer G, Georgopoulos M. Contact
correction of postpseudophakie refractive surprises. zone of acrylic piggyback intraocular lenses. J Cataract Refract
Awareness regarding power calculations, techniques Surg 1999;2:860.
of implantation and complications like ILO is 13. Findl O, Menapace R. Piggyback intraocular lenses. J Cataract
imperative before using these lenses fruitfully. Refract Surg 2000;26:308.
14. Rosen ES. Face to face with IOLs. J Cataract Refract Surg
REFERENCES 1999;26:729.
1. Gayton JL, Sanders VN. Implanting two posterior chamber 15. Shugar JK, Schwartz T. Interpseudophakos Elschnig pearls
intraocular lens in a case of microphthalmos. J Cataract Refract associated with a late hyperopic shif: a complication of
Surg 1993;19:776. piggyback posterior chamber intraocular lens implantation. J
2. Gills JP. Piggyback minus power lens implantation in Cataract Refract Surg 1999;25:860.
keratoconus. J Cataract Refract Surg 1998;24:666. 16. Shugar JK, Keeler S. Interpseudophakos intraocular lens surface
3. Gills JP, Van der Karr MA. Correcting high astigmatism with opacification as a late complication of piggyback acrylic
piggyback toric intraocular lens implantation. J Cataract Refract osterior chamber lens implantation. J Cataract Refract Surg
Surg 2002;28(3):547. 2000;26:448.
4. Gills JP Sutured piggyback toric intraocular lenses to correct 17. Gayton JL, Apple DJ, Peng Q, et al. Interlenticular opacification
high astigmatism. J Cataract Refract Surg 2003;292:402.
: Clinicopathological correlation of a complication of posterior
5. Donoso R, Rodriguez A. Piggyback implantation using the
chamber piggyback intraocular lenses. J Cataract Refract Surg
AMO array multifocal intraocular lens. J Cataract Refract Surg
2000;26:330.
2001;27(9):1506.
6. Gills JP. Multiple intraocular lens implantation. In Gills JP, 18. Eleftheriadis H, Marcantonio J, Duncan G, Liu C. Interlenticular
Fenzl R, Martin RG, (Eds): Cataract Surgery : The State of the opacification in piggyback AcryS of intraocular lenses :
Art. Thorofare, NJ: Slack, 1998. explanation technique and laboratory investigations. Br J
7. Holladay JR, Gills JP, Leidlein JL, Cherchio M. Achieving Ophthalmol 2001;85(7):830.
emmetropia in extremely short eyes with two piggyback 19. Apple DJ. Trans Am Ophthalmol Soc. Influence of intraocular
posterior chamber intraocular lenses. Ophthalmology lens material and design on postoperative intracapsular cellular
1996;03:1118. reactivity. 2000;98;257.
8. Fenzl RE, Gills JP, Cherchio M. Refractive and visual outcome 20. Werner L, Shugar JK, Apple DJ, Pandey SK, Escobar-Gomez
of hyperopic cataract cases operated on before and after the M, Visessook N, Evans BB. Opacification of piggyback IOLs
implementation of the Holladay II formula. Ophthalmology associated with an amorphous material attached to
1998;105:1759. interlenticular surfaces. J Cataract Refract Surg
9. Gayton JL, Sanders V, Van der Karr M, Raanan M. Piggy- 2000;2611:1612.
backing intraocular implants to correct pseudophakic refractive
21. Jackson DW, Koch DD. Interlenticular opacification associated
error, Ophthalmology 1999;106:56.
with asymmetric haptic fixation of the anterior intraocular
lens. Am J Ophthalmol 2003;135(1):106.
Chapter 59
Secondary Intraocular Lens

Implantation
DEFINITION Monocular aphakia or contralateral pseudophakia

comprises the most common indication for secondary
Secondary intraocular lens implantation (IOL) is
implant. Over a period of 4 to 7 years, up to 50 percent
defined as insertion of an IOL into an eye which is
aphakia-contact lens users gave up or had to
rendered aphakic by prior cataract extraction by any
discontinue the contact lens wearing due to intolerance
method, or by an exchange IOL, which is a special
or physical disability.1-5
case of secondary IOL implantation.1
Monocular aphakia with contralateral
Common type of secondary IOL is anterior
pseudophakia forms the major groups of patient who
chamber or a posterior chamber lens; secondary
undergo secondary IOL implantation and it is well
implantation of posterior chamber lenses in the
established with successful clinical reports.6
absence of a posterior capsular support is by fixing
the haptic to the ciliary sulcus and suturing it to the Aborted Primary Lens Implantation
iris or by transscleral suture.
Due to some intraoperative technical difficulties,
sometimes primary implantation is difficult and
INDICATIONS
hazardous, and it had to be abandoned. If
a. Monoocular aphakia. complications are properly managed and good
i. Spectacle or contact lens intolerance. anatomical and functional result ensured, planned
ii. Old and disabled persons with tremor, secondary IOLI may be persuaded if other means of
Parkinsonism and other physical disability correction are unsatisfactory.7
which makes handling and using of spectacle
or contact lens difficult. Bilateral Aphakia with or without Macular Diseases
iii. Occupational and circumstantial situations In aphakia patients with bilateral senile macular
where spectacle or contact lens is not suitable degeneration who are deprived of central vision,
or cumbersome, e.g. athletes, dancers, etc. secondary implantation may restore some useful
b. Contralateral pseudophakia. peripheral vision.
c. Aborted primary IOL implantation.
Though various reports have emphasized that Relative Contraindications
secondary implantation can be successfully carried out
of Secondary IOLI
in these situations, it should only be taken after careful
evaluation of the patients’ needs and the risks a. One-eyed patient Though secondary posterior
involved. It is important for both the patient and the chamber IOLI is considered as a contraindication
surgeon to realize that secondary implantation carries in one-eyed aphakic, it is not hazardous in a case
all the risks and hazards of an intraocular surgery. with intact posterior capsule and endothelial cell
Chapter 59: Secondary Intraocular Lens Implantation 435
density of 1200 to 1500 mm2 in persons below the that of other secondary IOLI because significant
age of 45 to 50 years. Anterior chamber secondary preexisting pathology remains in most cases who need
IOLI also can be done in cases with intact anterior an exchange.12
vitreous face after round pupil intracapsular Options for IOLI are (a) ACIOL (b) PCIOL (in the
extraction.8 bag or sulcus fixated) (c) Iris clipped / sutured.
b. Patients with filtration bleb These patients are not Iris clip/suture lens is associated with a variety of
generally considered unless absolutely needed complications including corneal decompensation,
because second surgical procedure may lead to CME, posterior synechiae formation, excessive iris
closure of the filtration bleb. damage, sphincter damage and uveitis. Worst iris clip
lens has better results than the iris sutured lens.
IOL Exchange: Explantation
Preoperative Preparation
It may not be possible to reposition the posteriorly for Secondary IOLI
dislocated posterior chamber IOL. However, the PC
Preparation of the patient is almost the same as
IOL may need to be explanted due to causes like
primary implant with special emphasis on the
decentration, implant optic opacification or incorrect
following points:
power. Causes of anterior chamber IOL explantation
1. A soft eye is mandatory
include excessive corneal decompensation leading to
2. Status of pupil, depending on the type of implant
pseudophakic bullous keratopathy, Uveitis-glaucoma-
(anterior chamber or posterior chamber).
hyphema (UGH) syndrome and cystoid macular
To attain the desired “soft eye”, the following
edema. Therefore, after anterior chamber lens
measures are taken:
exchange visual recovery is poor, whereas after PCIOL
1. Peribulbar anesthesia with 2 percent xylocaine with
exchange in 90% of cases potential for visual recovery
hyaluronidase without or with adrenaline.
is good.
2. A proper digital or instrumental massage.
When there is some complication of IOL and if the
3. Hyperosmotic agent (20% mannitol) in proper
particular design of lens is considered to be the cause
body weight dosage unless otherwise contra-
of the untoward effects then after thorough
indicated.
investigation and due consideration a different design
4. Preoperative oral Acetazolamide (250-500 mg).
of lens may be implanted.
In secondary anterior chamber IOLI a constricted
Indications for IOL exchange are:9
pupil is desirable and it is obtained by frequent instilla-
a. Corneal decompensation (with anterior chamber
tion of 2 percent pilocarpine, whereas in secondary
and iris clip lens).
posterior chamber implant, a widely dilated pupil is
b. Spontaneous or traumatic dislocation of IOL.
acquired with mydriatics.
c. Residual refractive error of 6 diopters or more.
d. Chronic irritating eye with low grade iridocyclitis
Associated Surgical Procedures
(sterile hypopyon).
e. UGH syndrome (uveitis-glaucoma-hyphema synd- Depending on the type and quality of previous
rome). surgery (ICCE or ECCE), and choice of the secondary
f. Optical distortion with glare, halo, etc. due to implant, the associated procedures may be:
decentration. 1. Cleaning of the posterior capsule with or without
g. IOL opacification10,11 capsulotomy.
Surgical techniques are same as secondary implant, 2. Release of posterior synechia or synechiotomy.
except a superonasal or superotemporal section is 3. Release of peripheral anterior synechia (PAS).
made generally without a conjunctival flap and the 4. Sphincterotomy.
use of viscoelastic substance is almost mandatory.12,13 5. Anterior vitrectomy.
Although IOL exchange is a form of secondary In a series of 79 cases of IOL exchange18 the analysis
IOLI both the conditions are not synonymous because of the indications are shown in the table below. Most
a great deal of distinction exists with significant tissue of the cases had useful post exchange vision but few
damaging complications. Therefore, the long-term developed complications like glaucoma and retinal
results of exchange implant cannot be compared to detachment.
Types of IOLI Percentage effect with associated motion related problems such
Posterior chamber IOL 61% as recurrent iritis, pigment dispersion, UGH,
Anterior chamber IOL 39% intermittent corneal endothelial touch, etc.
Replaced by PCIOL 76% In cases of PC IOLI an additional iridectomy is
Replaced by ACIOL 24% done, after insertion of the IOL generally away from
the previous site, if and any, proximal to the foot of
Indications for explantation
IOL displacement 41.7% the haptic.
Endothelial decompensation 27.75
Incorrect power 12.6% Management of Vitreous in Anterior Chamber
UGH syndrome 10%
Presence of vitreous in the AC can be treated by
pushing air into the anterior chamber; this will press
the vitreous either behind the iris or toward the wound
Secondary IOLI Following ICCE where it can be treated by a wick sponge. Vitreous
The ideal case would be the eye with an intact vitreous strands attached to the cataract wound should be
face posterior to the iris plane with a round pupil. excised.
Incision Secondary IOL Implantation in Children

It is better to avoid the original site of incision and a Unilateral aphakia due to congenital or traumatic
new temporal or nasal incision is made. cataract extraction in young children poses a special
therapeutic problem. Though controversial, the use
Peripheral Anterior Synechiolysis of secondary IOLI is the best alternative for rapid
visual rehabilitation. The major considerations for
After opening the anterior chamber with a stab IOLI in children are:
incision, peripheral anterior synechia, if any, are i. to preserve vision
released by a cyclodialysis spatula or iris repositor all ii. to prevent amblyopia
around the angle preferably after forming the chamber iii. preservation or development of fusion.
with viscoelastic substance. The section is enlarged The type of IOLI to be one, whether anterior
with scissors a little more than the diameter of the IOL chamber or posterior chamber, depends on previous
(7-7.5 mm). surgery, that is whether a discission, needling or a pars
plana lensectomy was done. Older children, more than
Viscoelastic Substance
7 years of age in whom the visual system has already
Viscoelastic substance is used to form the anterior been developed prior to cataract formation, and
chamber. It prevents vitreous bulging and patients with bilateral cataract have a better prognosis
pseudophacoendothelial touch. The iris plane should than younger children with unilateral cataract whose
be horizontal; an excessively deep anterior chamber vision does not resolve even after aggressive
with a concave iris plane is avoided to prevent iris amblyopic therapy.17
tuck13 during IOL insertion.
Indication for Secondary IOLI in Children
Measurement of IOL Length i. Monocular aphakia.
The common method of measuring the diameter of ii. Child unable to tolerate spectacle or contact lens.
an anterior chamber IOL is to measure white to white iii. Cases with anterior chamber or iris clip IOLs done
in the horizontal diameter of the cornea and addition earlier and better exchange is suggested.
one millimeter to it. The measurement should be done iv. Limitations of doing epikeratophakia or other
under a microscope. refractive surgery.
An over-sized IOL produces pupillary distortion, v. Scleral fixated posterior chamber IOL where
tenderness to touch, uveal or angle tissue chafing, posterior capsule is absent (after lensectomy).18
corneal endothelial touch and decompensation. An vi. A recently traumatized eye with existing inflam-
undersized IOL will move in the eye with a propeller mation will show severe reaction to surgical
Chapter 59: Secondary Intraocular Lens Implantation 437
trauma. So some ophthalmologists suggest a REFERENCES
primary aspiration, and later do IOLI as a 1. Azar RF. Secondary implantation of IOL. Ann Ophthalmol
secondary procedure after the eye is quiet.19 1978;658.
Results of secondary IOL implantation in children 2. Hirdenberg FE. Secondary IOL implantation-I. Ophthalmic
are variable. Some reports show encouraging results Surg 1977;8:70.
with a satisfactory visual acuity without much sub- 3. Choyce D. The choyce mark VIII anterior chamber implant.
Ophthalmic Surg 1977;8:46.
sequent complications. 17 Patients with congenital
4. Hirdenberg FE. Secondary IOL implantation-II. Ophthalmic
cataract showed a poor result with secondary implants Surg 1977;8:76.
than primary ones, whereas no significant difference 5. Miles PV, Lewes EM. Contact lens wear in unilateral aphakia.
in visual acuity was noted in cases of traumatic Br J Ophthalmol 1971;53:46.
cataract.20,21 6. Parelman AG. Monocular aphakia and contralateral pseudo-
phakia. Ophthalmic Surg 1976;7:83.
7. Kwetko ML. Secondary IOL implantation—A treatment for
Complications of Secondary IOLI simple macular degeneration in phakic patient. Contact
Intraocular Lens Med J 1978;4:56.
Secondary implantation is one of the controversial and 8. Aquavella JV, Shavo EL, Rao JN. Intraocular lens implantation
challenging aspects of pseudophakic surgery. All the combined with PKP. Ophthalmic Surg 1977;8:113.
complications of primary IOLI operations (which are 9. Lendstorm RL. Secondary and exchange posterior chamber
IOL. Am Intraocular Implant Society J 1982;8:353.
described separately) are likely to occur in secondary 10. Werner L, Apple DJ, Kaskalogu M et al. Opacification of the
IOLI surgery. The additional points to be considered optical component of hydrophilic intraocular lens. A
are: clinicopathological analysis of 9 explanted lenses. J Cataract
a. The eye undergoing secondary implantation is Refract Surg 2001;27:1485.
already traumatized and compromised even with 11. Izak AM, Werner L, Pandey SK, Apple DJ. Opacification of
modern foldable hydrogel intraocular lens designs. Ete
a reasonably good visual acuity.
2003;17:393.
b. The risks and rate of postoperative complications 12 Kruff HJF. Secondary IOL implantation of anterior chamber
are augmented when the vitreous is disturbed and lens. Am Intraocular Implant Society J 1983;9:913.
the cornea is decompensated. 13. Brown DC. IOL implant exchange. Am Intraocular Implant
c. The severity of postoperative complications Society J/II, 1985;376.
14 Azar RF. Secondary implant for IOL. Annal Ophthalmol
depends upon the preoperative status of the eye,
1978;10:658.
surgical skill and manipulation as well as 15. Krumeich JH, Daniel J, Gost R. Closed system technique for
postoperative management. implantation of iris supported negative power intraocular
However, incidence of endophthalmitis may be lens. J Refract Cataract Surg 1996;12:334.
higher than in standard IOLI, viz in cases of vitreous 16. Johnson SJ. Improved technique for secondary anterior
loss during surgery and secondary IOLI in presence chamber lens insertion. Am Intraocular Implant Society J
1983;9:306.
of a filtration bleb the incidence may be higher. Since 17. Argon C, Aron JJ, Rosa D. IOL Implantation in unilateral
the operative manipulations are more in secondary congenital cataract. Am Intraocular Implant Society J
IOLI, one may expect higher incidence of post- 1983;9:306.
operative endophthalmitis in these cases. It may be 18. Johnson SJ. Improved technique for secondary implant
concluded that for many patients any form of insertion. Am Intraocular Implant Society J 1982;8:267.
19. Heles DA. Part II-Infantile cataracts: Cataract surgery in
secondary IOLI (anterior chamber, posterior chamber children. Cataract 1984;1:7.
or ciliary sulcus fixated one) may be a helpful for visual 20. Rozenman Y, Nelson RB, Folberg R. Painful bullous
rehabilitation, with good visual acuity and without keratopathy following paediatric cataract surgery with
any significant complications such as cystoid macular intraocular lens implantation. Ophthalmic Surg 1985;16:373.
edema, retinal detachment or corneal decom- 21. Biemfal MF. IOL Implantation in children with unilateral trau-
matic cataract (Netherland). International Ophthalmology
pensation.22 But mere aphakia is not an indication for
1990;14:271.
secondary implant. So proper cases should be selected 22. Hayward JM, Noble S, George N. Secondary intraocular lens
with due caution. implantation eight years experience. Eye 1990;4:548.
Chapter 60
Scleral-Fixated PCIOL
Dinesh Mittal, YR Sharma
Scleral-fixated posterior chamber intraocular lens (PC INDICATIONS

IOL) is gaining popularity since its original
A. Secondary procedure (In cases of ICCE Aphakia)
description by Malbarn and his associates 1 in
conditions in which capsule support for PCIOL is i. Young patients
lacking and anterior segment structure is disturbed ii. Loss/absence of iris tissue
so that ACIOL insertion is ruled out. The goal in iii. Surgical iridectomy/Aniridia
scleral-fixated PCIOL is placement of haptics in ciliary iv. Compromised angle
sulcus. Scleral-fixated PCIOL can be sutured by B. Primary procedure
passing the needles from outside of the eye inward i. Capsulozonular deficiency (PC rent intra-
(ab-externo) or inside out (ab-interno). Adequate operatively)
anterior vitrectomy2,3 is mandatory before placement ii. Subluxated/dislocated crystalline lens
of IOL to avoid vitreous base related complications. iii. IOL exchange
It has been shown that when needles passed iv. IOL exchange in PK
perpendicular to sclera at 1,2 and 3 mm posterior to
the limbus, it exited internally at the ciliary sulcus,
AB-INTERNO APPROACH
pars plicata, and pars plana, respectively.4 Anatomical
studies have shown that ciliary sulcus is 0.83 mm and Initially it was the ab-interno technique that was
0.46 mm posterior to the limbus in the vertical and described for scleral-fixated PCIOLs. In this
horizontal meridian, respectively.4 These anatomical technique, two partial thickness scleral flaps are made
studies clearly show that surgeon should be very 180° apart. In right handed persons, superior flap
precise in introducing the needle. Any needle that is
should be made toward 1 o’clock and inferior flap
too posterior will have high incidence of vitreous base
toward 7 o’clock because of ease of maneuverability.
and retina related complications. Any needle that is
Ethicon CIF-4 long tapered needle can be used to
too anterior will lead to iris movement as needle
pass polypropylene suture through inferior scleral
penetrates the peripheral iris stroma. Some surgeons
flap and Ethicon TG 160-65 small curved needle can
prefer to put haptic of the IOL horizontally and some
be used to pass polypropylene suture through
vertically but most agree that one should avoid the 3
and 9 o’clock positions because of long ciliary arteries superior scleral flap. The suture can be looped
and nerves. Following examinations are essential through the eyelets of haptic, tied to the haptic or a
before deciding upon scleral fixation PCIOL: girth hitch suture can be used. These can be a two
a. Specular microscopy and pachymetry point or four point fixation of the IOL. After passing
b. Gonioscopy to assess the chamber angle, and out the polypropylene sutures through scleral flap,
c. Thorough indirect ophthalmoscopy to scan the ends of the suture are tied in a 3-1-1 Knot. The ends
retinal periphery for retinal problem. of the knot are cut one mm long. Then scleral flaps
If any peripheral retinal pathology predisposing are tied with 6.0 Vicryl. Corneoscleral wound is closed
to retinal detachment is detected then one should do with 10.0 monofilament nylon and overlying
scleral-fixated PCIOL with extreme caution. conjunctival wound is closed with 6.0 Vicryl (Fig.
Chapter 60: Scleral-Fixated PCIOL 439
Fig. 60.1: Ab-interno approach
60.1). four point fixation of the IOL then the above steps
are repeated (Fig. 60.2). It should be noted that the
AB-EXTERNO APPROACH6 main advantage of the ab-externo approach is its
Some surgeons are not comfortable in passing suture greater precision in the location of scleral sutures.
below the iris through sclera blindly by ab-interno The polypropylene suture knot should not be kept
method. The ideal location of IOL placement is exposed because it causes irritation and may lead to
positioning of haptics in ciliary sulcus. To ensure this endophthalmitis. Scleral flaps are recommended to
placement, ab-externo approach was introduced. But cover it. If possible the knot should be buried in the
this outside to inside approach is more time consu- sclera. The posterior chamber IOLs used for scleral
ming as compared to inside to outside approach. For fixation should be of large diameter optics (7 mm)
Ab-externo approach one needs to have long straight and haptics should have eyelets. If IOLs with eyelets
needle, e.g. Ethicon STC-6 or Alcon SC-5. After are not available then some surgeon do cautery to
making partial thickness flap the straight needle is the ends of the haptics to make it beaded. Some of
passed approximately 0.75 mm posterior to limbus scleral sutured IOLs available in the market are the
through one side; on other side a hypodermic hollow Pharmacia U15287, Alcon C270BD8, and ORC optical
needle of 25, 27, or 28 gauge should be passed. The radiation corporation C540MC.
straight needle is then negotiated through the hollow
hypodermic needle. The hypodermic needle should
COMPLICATIONS
be withdrawn with the straight solid needle, inside
it. Anterior chamber is entered and suture is taken There is a tendency toward an increased risk of
out with a hook, the suture is cut and end is tied to serious complications with scleral-sutured PCIOLs.
eyelet of the IOL haptics. If surgeon wants to have a The serious complications include retinal detachment,
Fig. 60.2: Ab-externo approach
posterior dislocation of IOL and suprachoroidal of erosion of scleral sutures; to obviate it partial
hemorrhage.5,9 Cystoid macular edema is the most thickness flaps use was started. But with them, there
common complication associated with scleral sutured can be still erosion of sutures. To decrease the
PC IOLs.1 Glaucoma is the next common complication. incidence further, some surgeons recommend burying
It should be noted that this glaucoma may not be the sutures in the sclera. The exposed sutures can
related to scleral-fixated PC IOL.5 Other reported lead to endophthalmitis. With scleral-fixated PC IOL
complications include endophthalmitis, polypropy- there is increased risk of retinal detachment.1 Between
lene knot erosion, corneal edema, and risk of failure 2.5 and 5.5 percent risk of retinal detachment has
of polypropylene suture.10 There is essentially no been reported in scleral fixated PC IOLs.
inflammation and fibrosis around optics or poly- Histologically, in many eyes the haptics of the IOL
propylene suture. So if there is failure of poly- was found to be near pars plana11 instead of being in
propylene suture, or it is cut accidentally there will ciliary sulcus. This may be responsible for high risk
be displacement of IOL posteriorly. There is danger of retinal detachment. Therefore, it is emphasized
Chapter 60: Scleral-Fixated PCIOL 441
that haptics should be placed in the ciliary sulcus. 2. Smiddy WE, Sawusch MR, O’ Brien TP et al: Implantations of
Moreover, before putting IOL, one should do scleral-fixated posterior chamber intraocular lenses. J Cataract
Refract Surg 16: 691-96, 1990.
sufficient anterior vitrectomy. 3. Lindquist TD, Agapitos PJ, Lindstrom RL et al: Transscleral
fixation of posterior chamber intraocular lenses in the absence
RECENT ADVANCES of capsule support. Ophthalmic Surg 20: 769-75, 1989.
4. Duffey RJ, Holland EJ, Agapitos PJ, Lindstrom RL: Anatomic
Recently, transscleral fixation of a foldable, multifocal study of transsclerally sutured intraocular lens implantation.
intraocular lens (IOL) as an alternative form of optical Am J Ophthalmol 108: 300-09, 1989.
correction to monofocal IOL implantation in aphakic 5. Heidemann DG, Dunn SP: Transsclerally sutured intraocular
children and young adults intolerant to contact lenses lenses in penetrating keratoplasty. Am J Ophthalmol 113: 619-
in the absence of sufficient capsular support has been 25, 1992.
6. Lewis JS: Ab-externo sulus fixation. Ophthalmic Surg 22: 692-
found feasible.12
93, 1991.
To summarize, scleral fixation PCIOL is a useful 7. Stark WJ, Goodman G, Goodman D, Gottach J: Posterior
technique in cases in which there is no capsule chamber intraocular lens implantation in the absence of posterior
support, anterior chamber IOL cannot be put because capsule support. Ophthalmic Surg 19: 240-43, 1988.
of disturbed anterior segment anatomy and the 8. Kershner RM: Vertical transscleral sulcus fixation of intraocular
lenses in the absence of a posterior capsule. J Cataract Refract
patient is not tolerant to contact lens. But it is
Surg 18: 201-02, 1992.
associated with some serious complications and 9. Sundmacher R, Althans C, Wester R, Geter H: Two years
studies with long-term results are not available. It experience with transscleral fixation of posterior chamber lenses.
may be expected that with time there will be Dev Ophthalmol 22: 89-93, 1991.
refinement of materials and techniques, and there 10. Apple DJ, Price FW, Gwin T et al: Sutured retropupillary
will be better acceptance of this technique. posterior chamber intraocular lenses for exchange of secondary
implantation. Ophthalmology 96: 1241-47, 1989.
REFERENCES 11. Lubricosin AJ, Holland EJ, Van Meter WS et al: Histologic
study of eyes with transsclerally sutured posterior chamber
1. Malbran ES, Malbran EJ, Negri I. Lens guide sutures for intraocular lenses. Am J Ophthalmol 110: 237-43, 1990.
transport and fixation in secondary IOL implantation after 12. Jacobi PC, DietleinTS, Jacobi FK. Scleral fixation of secondary
intracapsular extraction. Int Ophthalmol Clin 1986;9:131. foldable multifocal intraocular lens implants in children and
young adults. Ophthalmology 109: 2315, 2002.
Chapter 61
Management of Postoperative
Endophthalmitis
S Natarajan, B Dutta
More than half of the cases of endophthalmitis are of Table 61.1: Showing the etiology of 20 cases of
postoperative etiology. Endophthalmitis remains a endophthalmitis (Gopal et al 20032)
catastrophic complication of intraocular surgery and Endogenous 6 cases
penetrating ocular trauma despite recent advances in Post-traumatic 3 cases
diagnosis and therapy. Some of the cases are Post-cataract operation 8 cases
postoperative, the incidence has decreased nowadays Bleb-related 1
due to an improved knowledge, better availability of Post-vitrectomy 1
diagnostic facilities and management options Post-pneumatic retinopexy 1
(Table 61.1).
Most of the cases of postoperative endophthalmitis infusion and by intramuscular route was the mainstay
occur following cataract surgery as it is the commonest of therapy for endophthalmitis. The blood retinal
intraocular surgical procedure being performed.1 barrier prevents adequate penetration of antibiotics,
Postoperative endophthalmitis following cataract particularly the hydrophilic ones like penicillin,
surgery usually occurs in the first postoperative week aminoglycosides, etc into the vitreous cavity. The
and 88% of the cases occur in the first six weeks after current modality of treatment is the use of intravitreal
surgery.3 Delayed endophthalmitis following cataract antibiotics and vitrectomy.
surgery is due to less virulent organisms like Staphylo-
coccus epidermidis or Propionibacterium acnes4 or fungi.
Gram- negative bacilli and fungi constitute a vast
majority of the cultured organisms. Bacterial endo-
phthalmitis can also occur in filtering blebs4, (Fig. 61.1)
and following penetrating keratoplasty 4 . But
endophthalmitis following vitreoretinal surgery is
relatively uncommon.
The risk factors proposed for postoperative endo-
phthalmitis by most of the authorities include diabe-
tes, history of prior ocular surgery, chronic alcoholism,
complicated surgery like capsule rupture, vitreous
loss, contamination of IOLs, and IOLs in general.
The bacterial toxins liberated within the vitreous
cavity are not washed away but remain and cause
damage to the retina and surrounding tissues. Fig. 61.1: Endophthalmitis with hypopyon in
Antibiotics administered topically, by intravenous filtration ulcer infection (Naturajun)
Chapter 61: Management of Postoperative Endophthalmitis 443
MEDICAL TREATMENT are recommended on initial presentation7 and the
following are used:
Success in medical therapy depends on the prompt
• Cefazolin—100 mg
diagnosis and institution of appropriate antibiotics.
• Gentamicin—20 mg
Intravitreal injection of antibiotics was first studied
• Amphotericin B—5 mg.
by Von Sallmann and associates4 who successfully
treated early experimental Staphylococcal endo- Systemic antibiotics Recent reports have shown good
phthalmitis in rabbits with intravitreal injection of intravitreal penetration of cephazolin, ciprofloxacin
nontoxic doses of penicillin. The procedure of intra- and ceftazidime from systemic administration.8-10
vitreal injection was further refined by Peyman and Care should be taken in monitoring the toxic effect
Foster.5 like nephrotoxicity of aminoglycosides and hepato-
toxicity of the antifungals like ketoconazole. The
Drug Pharmacokinetics following antibiotics are recommended systemically:
Cefazoline:
Drugs are eliminated from the vitreous cavity by an
adults = l g every 6 hourly IV
anterior and a posterior route.6 The posterior route is
child = 40 mg/kg/day in divided doses IV
constituted by the retinal pump which eliminates the
Gentamicin:
beta-lactam antibiotics and the steroids. The amino-
adults = 80 mg every 8 hourly IV
glycoside antibiotics are eliminated by the anterior
child = 5 mg/kg/day in divided doses IV
route by simple diffusion into the anterior chamber
Ciprofloxacin:
and aqueous outflow channels. In endophthalmitis,
adults = 750 mg every 12 hours orally
drug elimination through the anterior route is
Ketoconazole:
increased but elimination through posterior route is
adults = 200 mg every 8 hours orally.
decreased due to functional impairment of the retinal
pump. Intravitreal antibiotics This is the route of choice for
Even before Gram stain results are known, imme- the administration of antibiotics in infective endoph-
diate therapy is instituted because the first few hours thalmitis. Cefazoline, a first generation cephalosporin
are critical and interpretation of the smears can be and highly active against many of the Gram-positive
difficult. The most common organism causing post- organisms and gentamicin, an aminoglycoside and
operative endophthalmitis is coagulase-negative drug of choice against many Gram-negative micro-
Staphylococcus hence broad spectrum antimicrobial organisms have been the mainstay in the initial
therapy is preferred in order to cover the full range of treatment regimen for bacterial endophthalmitis. The
ocular penetration. changing patterns of bacterial sensitivity and the
recent reports of retinotoxicity by aminoglycosides11
ROUTES OF ADMINISTRATION have prompted the current use of vancomycin (active
against Gram-positive organisms) with amikacin
Topical antibiotics The concentration of the drugs
(effective against Gram-negative microorganisms)
instilled topically is very poor in the vitreous. But
intravitreally. Recently, amikacin has also been found
topical drugs are still used for the management of
to be not free of retinotoxicity and hence there is an
concomitant problems like suture abscess or corneal
increasing tendency of use of ceftazidime in place of
ulcer. Routine therapy consists of instillation of
amikacin. Ceftazidime is highly effective against
fortified antibiotics, cycloplegics and steroids at every
Gram-negative organisms and is free of retinal toxicity.
one or two hour intervals. The following antibiotics
In case of fungal endophthalmitis amphotericin-B
are recommended topically as initial therapy.
is used intravitreally. The dose of intravitreal
• Gatifloxacin
antibiotics is as follows:
• Sparfloxacin
Vancomycin : 1 mg in 0.1 ml
• Cefazolin—50 mg/ml
Ceftazidime : 2.25 mg in 0.1 ml
• Gentamicin—15 mg/ml
Amikacin : 400 microgram in 0.1 ml
• Natamycin
Cefazolin : 2.25 mg in 0.1 ml
Subconjunctival antibiotics Subconjunctival antibiotics Gentamicin : 200 microgram in 0.1 ml
have a better concentration in the aqueous but poor Amphotericin B : 5 microgram in 0.1 ml.
intravitreal concentrations. Subconjunctival antibiotics
SURGICAL TREATMENT SURGICAL TECHNIQUE

The precise timing for surgical intervention by General anesthesia is preferred to local anesthesia
vitrectomy in the management of endophthalmitis because of the hazards and difficulty in obtaining
remains controversial. The risks of vitrectomy must adequate anesthesia in an inflamed eye by retrobulbar
be weighed against the potential benefit in individual block. However, the surgery should not be delayed
patient. Generally, patients with mild infection (retina for the nonavailability of facility for general anesthesia
visible, even if hazily), specially if the infection is or if there is medical risk for general anesthesia. In
suspected to be due to less virulent organisms like such cases, peribulbar technique is preferable to
Staphylococcus epidermidis, can be managed well retrobulbar method.
without vitrectomy. Vitrectomy is generally recom- The general surgical technique is same as 3-port
mended in the following situations: pars plana vitrectomy for any other condition except
1. If there is no improvement or worsening of the that a few additional points are to be kept in mind.
condition within 48 hours of conservative trea- If a leaking cataract wound or ruptured filtering
tment. bleb is present, it must be tightly sutured before
2. Patients with moderate to advanced stage of beginning vitrectomy.
infection (absence of or very faint fundal glow, no The first problem that arises is in the placement of
retinal view). the infusion cannula. Haziness of the media prevents
3. If Gram staining of smear prepared from vitreous visualization of the internal opening of the infusion
aspirate sample shows presence of Gram-negative cannula which prevents its use in the initial part of
rods or other virulent organisms. the operation till the opening is clearly visualized.
4. Ultrasound examination shows presence of However, as the placement of the infusion port is
organized vitreous opacities. easier in a firm eye, it is better to fix it before proceeding
5. Strong suspicion of fungal endophthalmitis. with other sclerotomies. Till the time of visualization
6. Bleb-associated or trauma-related endophthalmitis of cannula, a 20 G 30 degrees bent needle can be used
as they are frequently caused by virulent organisms for infusion through the upper nasal sclerotomy
which responds poorly to conservative treatment. opening. As the choroid is thickened due to
7. Endophthalmitis associated with the presence of inflammation, a 6 mm infusion cannula is preferred
intraocular foreign body. to the 4 mm one.
8. In post-infectious cases for removal of vitreous The anterior chamber often contains hypopyon and
opacities to improve vision and for the manage- exudative membrane which interferes with adequate
ment of chronic sequele of parasitic infestation. visualization of the anterior vitreous. In aphakic
patients, the bent infusion needle and the ocutome can
RATIONALE FOR VITRECTOMY be brought anteriorly through the pupil to remove the
1. Vitrectomy is equivalent to incision and drainage debris. In pseudophakic and phakic patients, two
of abscess anywhere else in the body, removing separate incisions are made at limbus at approxi-
sequestered pockets of infection from the eye. mately 10 o’clock and 2 o’clock positions for the
2. It removes the bulk of infective organisms, inflam- introduction of bent infusion needle and either
matory debris, and toxins from the eye. ocutome or another 20 G 30 degree bent needle fixed
3. It provides more material from the infected site to a syringe without plunger for excavation of
increasing the likelihood of identifying the causa- hypopyon under hydraulic pressure.
tive organisms. In phakic eyes, poor dilatation of the pupil, opaque
4. Organisms are believed to be more effectively lens due to trauma or inflammation and poor
cleared from anterior chamber than from posterior visualization of the internal structures, lens removal
chamber and removal of vitreous in an aphakic eye is necessary through the pars plana either by ocutome
allows the anterior chamber and vitreous cavity to or by fragmatome depending on the hardness of the
become one. lens. In case of pseudophakic eyes, the lens is left in
5. It clears media opacities, thereby allowing early place in most of the cases because any attempt at its
restoration of vision. removal is likely to cause more damage like intra-
6. It reduces the risk of late complications related to ocular hemorrhage, iris injury, endothelial damage
cellular proliferation on the vitreous matrix. and retinal detachment as has been shown in clinical1
and experimental 12 studies. IOL explantation is 2.25 mg of Ceftazidime and 1 mg of vancomycin
needed in cases of gross infection caused by Gram- intravitreally has been found to be safer than
negative organisms and fungi. Explantation was also gentamicin and provide adequate coverage against
suggested in cases of Propionibacterium acnes both Gram-positive and Gram-negative organisms.
endophthalmitis, though the present trend is to After conjunctival closure, some antibiotics are
perform a generous capsulotomy, either to retain or injected subconjunctivally.
exchange the IOL and injection of antibiotics near the
remnants of the capsular bag.13 Use of Corticosteroids
After making the sclerotomies, the first step is to The use of intraocular steroids in the treatment of
collect adequate vitreous sample for culture and endophthalmitis is controversial. Recent studies, how-
staining. This is done by connecting a sterile 5 ml ever, support the beneficial role of steroids in
syringe to the suction tube of outcome and vitreous is endophthalmitis. Visual and anatomic outcomes in
withdrawn into the syringe using manual suction. It endophthalmitis is related to a combination of damage
is better to obtain an undiluted vitreous sample before by the causative organisms as well as host’s reaction
the fluid infusion is started to get a rich micro- to inflammatory responses on the tissues. 14 The
organismal isolation. The material is then immediately inflammatory reaction is usually mediated by the host
sent to the laboratory, preferably in a self-sealing polymorphs. Bacteria liberate exotoxins and when
vacuum tube and if this is not available, then in the killed by polymorphs they liberate endotoxin.7 These
same syringe which is used for aspiration. toxins in association with the bacterial enzymes like
Once adequate sample of vitreous is collected, ante- hyaluronidase, collagenase, hemolysins, etc cause
rior vitrectomy is performed using low suction under severe tissue damage and scarring. Intraocular
coaxial illumination of the operating microscope. After corticosteroid reduces the intraocular inflammation
the anterior vitreous is cleared and the infusion and lessens the destruction of the retinal tissue15 which
cannula is better visible internally, the bent infusion may facilitate a better visual outcome.
needle is replaced by the endoilluminator, while the Along with the antibiotics, 400 microgram of
intraocular volume is maintained by the regular dexamethasone is injected intravitreally at the end of
infusion cannula. surgery. This dose has been found to be nontoxic to
The vitrectomy is now progressively carried poste- the retina.16
riorly with the help of wide angle observation systems.
The aim is to perform a “core” central vitrectomy. No Postoperative Management
attempt should be made for a complete vitrectomy as If the treatment is adequate there is marked reduction
this often results in tears of inflamed or necrotic retina in ocular pain and improvement in fundal glow.
producing retinal detachment which is very difficult In the early postoperative period, systemic
to treat. For the same reason, no attempt should be antibiotics are given but they probably do not have
made for membrane peeling or vacuum cleaning. significant intraocular penetration. Systemic steroid
When a satisfactory fundal glow is visible, the proce- is given orally in tapering dose to reduce inflam-
dure is terminated and the sclerotomy sites are closed mation. However, their administration is withheld
watertight using 6/0 vicryl suture followed by until the culture reports are available and specific anti-
conjunctival closure. biotics are given for atleast 24 hours.7 The recom-
In severe cases, the cornea may be totally opaque. mended dose is 1-1.5 mg/kg/day prednisolone and
In such cases, vitrectomy can be combined with is given in three divided doses to maintain a uniform
therapeutic keratoplasty. The central corneal button concentration throughout the day. Steroids are,
is removed, an open sky vitrectomy is performed however, avoided in cases of fungal endophthalmitis.
followed by suturing of the donor button in position. Topically, one hourly instillation of a broad-spectrum
antibiotic like ciprofloxacin (0.3%) drops, atropine
Use of Antibiotics
(1%) drops three daily and steroid drops four times
Use of antibiotics in the infusion fluid is not preferred or more are advised.
because of the difficulty in assessing the total dose to If the condition deteriorates inspite of this
which the retina is exposed and the consequent toxic treatment and if the sensitivity report shows that the
effect. At the end of surgery, intravitreal injection of organism is sensitive to the antibiotics used, a second
intravitreal injection of the appropriate antibiotic is in this trial. Visual acuity was PL or better and the
to be repeated after 48 to 72 hours of the last injection. patients read fewer than 36 letters on the
Very rarely, a third injection has to be given but is Endophthalmitis Vitrectomy study visual acuity chart.
never repeated before 72 hours of the last injection. In It was required that the cornea and anterior chamber
such cases it is better to perform a vitreous lavage, of the involved eye be clear enough to allow visualiza-
followed by an intravitreal injection according to the tion of at least some portion of iris and the cornea clear
sensitivity report. enough to allow the possibility pars plana vitrectomy.
The patients had hypopyon in the involved eye or
COMPLICATIONS clouding of the anterior chamber or vitreous which
The two major complications during surgery are was severe enough to obscure visualization of second
hemorrhage and retinal tears. Hemorrhage can usually order retinal arterioles.
be controlled by increasing the infusion bottle height. All patients in this study underwent immediate
If this is not successful intraocular bipolar unimanual anterior chamber and vitreous cultures and received
diathermy may be needed. Retinal breaks usually go intravitreal antibiotics [amikacin sulfate (0.4 mg) and
undetected during surgery. If noticed, they should be vancomycin hydrochloride (1 mg)], subconjunctival
supported by a scleral buckle. antibiotics [vancomycin (25 mg) and ceftazidime (100
Postoperative complications may be corneal mg)] topical antibiotics (vancomycin and amikacin),
edema, glaucoma, opacities in the vitreous and and topical cycloplegics. Topical, periocular, and
cataract. However, retinal detachment is the most systemic steroids were also administered.
feared complication of vitrectomy as it is difficult to Patients were randomly assigned to 4 groups.
treat and is associated with proliferative vitreo- Group one underwent immediate pars plana vitrec-
retinopathy. In such cases, OPD fluid gas exchange tomy with intravenous antibiotics (ceftazidime and
can be tried initially. Injection of gas improves the view amikacin) and group two underwent pars plana
and helps in application of laser. If this fails, standard vitrectomy without intravenous antibiotics. Group
buckling procedures can be tried. three underwent initial tap of vitreous (vitrectomy was
deferred) with intravenous antibiotics, and group four
Preparation of Commonly underwent as initial tap without intravenous
Used Intravitreal Solutions antibiotics. Vitreous taps involved removal of no more
1. Vancomycin (500 mg vial) than 0.2 ml of vitreous fluid for culture. Additional
• Add 5 ml of sterile water for injection treatment, if required was given between 36 to 60
• Withdraw 1ml and dilute in 9 ml of water hours after the initial procedure. Eyes which originally
• Use 0.1 ml. underwent taps, underwent vitrectomy and
2. Ceftazidime (250 mg vial) reinjection of intravitreal antibiotics. Eyes that initially
• Add 1ml of sterile water for injection underwent vitrectomy had repeat culture of the
• Withdraw 0.1 ml and dilute on 0.9 ml of water vitreous done and intravitreal antibiotics were
• Use 0.1 ml. reinjected.
3. Dexamethasone (4 mg/ml) The primary outcome determinants in this trial
• Withdraw 0.2 ml of solution with tuberculin were visual acuity assessed by an early treatment of
syringe diabetic retinopathy study acuity chart and clarity of
• Withdraw 0.1 ml ocular media measured clinically and photo-
• Use 0.1 ml solution. graphically. The initial endpoints were assessed at 3
months, following which, procedures to clear residual
ENDOPHTHALMITIS VITRECTOMY STUDY17 vitreous opacification were performed. Final end point
assessment was done at 9 months.
A prospective randomized multicenter clinical trial
was designed to find out the roles of pars plana vitrec-
Results18
tomy and intravenous antibiotics in the management
of acute postoperative endophthalmitis. There was no difference in final visual acuity or media
Patients with the clinical signs and symptoms of clarity with or without the use of systemic antibiotics.
bacterial endophthalmitis within 6 weeks of cataract Whether or not an immediate pars plana vitrectomy
surgery or secondary lens implantation participated was performed in patients whose initial visual acuity
were hand motions or better, there was no difference 6. Gedde S, Scott IU, Tabandeh et al. Late endophthalmitis
in visual outcome. In the subgroup of patients who associated with glaucoma drainage implant. Ophthalmology
2001;108,1323.
had initial ‘light-perception only’ vision, there was a
7. Gupta A, Gupta V, Gupta A et al. Spectrum of clinical practice
statistically significant difference between vitrectomy of post-cataract surgery endophthalmitis in North India. Ind
and vitreous tap or biopsy over the entire range of J Ophthalmol 2002;51,139.
vision. This is because immediate pars plana 8. Kern G, Alhalel A, Bartov E et al. The intravitreal penetration
vitrectomy produced a three-fold increase in the of orally administered ciprofloxacin in humans. Inves
frequency of achieving 20/40 or better acuity, Ophthalmol Vis Sci 1991;32:2388-92.
9. Martin A, Ficker LA et al. Vitreous cefazolin levels after intra-
approximately a two-fold chance of achieving 20/100 venous injections: Effects of inflammation, repeated antibiotic
or better acuity and a 50 percent decrease in the doses, and surgery. Arch Ophthalmol 1990;108:411-14.
frequency of severe visual loss over vitreous tap or 10. Aguilar HE, Meredith TA et al. Vitreous cavity penetration
biopsy. of ceftazidime after intravenous administration. Retina
The length of hospital stay and cost is reduced by 1995;15:154-59.
11. Campochiaro PA, Conway BP. Aminoglycoside toxicity: A
the omission of systemic antibiotics. Moreover,
survey of retina specialists: Implication of ocular use. Arch
systemic antibiotic-induced toxicities are also avoided. Ophthalmol 1991;109:946-50.
Thus, routine immediate vitrectomy is not neces- 12. Hopen G, Mondino BJ et al. Intraocular lenses and
sary in patients whose vision is better than light experimental bacterial endophthalmitis. Am J Ophthalmol
perception at presentation but patients with only light 1982;94:402-07.
perception vision at presentation will improve 13. Benson WE. Current Management of Postsurgical Endo-
phthalmitis. In Laibson PR (Ed): The Year Book of Ophthal-
substantially with immediate vitrectomy. mology 1989;181-84.
14. Schulman JA, Peyman GA. Intravitreal corticosteroids as in
REFERENCES adjunct in the treatment of bacterial and fungal endoph-
1. Driebe W, Mandelbaum S, Forster RK. Pseudophakic endophthalmitis: A review. Retina 1992;12:336-40.
thalmitis: Diagnosis and management. Ophthalmology 15. Maxwell DP Jr, Brent BD et al. Effect of intravitreal dexa-
1986;93:442-47. methasone on ocular histopathology in a rabbit model of
2. Gopal L, Ramaswamy AA, Madhuban HN et al. Endophthal- endophthalmitis. Ophthalmology 1991;98:1370-75.
mitis caused by Acinetobacter calcoaceticus. A profile. Ind J 16. Graham RO, Peyman G. Intravitreal injection of dexame-
Ophthalmol 2003;51,335. thasone: Treatment of experimentally induced endo-
3. Hilton SF, Tornambe PE. Retinal surgery study group. pahtalmitis. Arch Ophthalmol 1974;92:149-54.
Pneumatic retinopexy. Retina 1991;11,285. 17. Doft BH. The endophthalmitis vitrectomy study (EVS)
4. Leveille AS, Mc Mullan FD, Cavanagh HD. Endophthalmitis (Editorial). Arch Ophthalmol 1991;109:487-89.
following penetrating keratoplasty. Ophthalmology 18. Results of the endophthalmitis vitrectomy study: A rando-
1983;90,38. mized trial of immediate vitrectomy and of intravenous
5. Kaflam HM, Flynn HW, Pftelgfelder SC. Nonocomial antibiotics for the treatment or postoperative bacterial
endophthalmitis survey. Current incidence of infection after endophthalmitis. Endophthalmitis Vitrectomy Study Group.
intraocular surgery. Current Ophthalmol 1991;98,227. Arch Ophthalmol 1995;113(12):1479-96.
Chapter 62
Ophthalmic Viscosurgical
Devices
Suresh K Pandey, Jaya Thakur, Liliana Werner, Nick Mamalis, Vidushi Sharma,
David J Apple, Aman Chandra, Girish Chandra
INTRODUCTION working space for the ophthalmic surgeon. These

agents are also designed to protect the delicate corneal
Viscoelastic substances are solutions with dual
endothelial cells during the surgery.
properties; they act as viscous liquids as well as elastic
The viscoelastic substances have been termed
solids or gels. The ideal viscoelastic substance in
“ophthalmic viscosurgical devices” (OVDs)2,5. A
ophthalmology should be viscous enough to prevent
detailed discussion regarding biocompatibilty,
collapse of the anterior chamber at rest, yet liquid
physical, and rheological properties of the OVDs are
enough to be injected precisely through a small
beyond the scope of this book. The viscoelastic
cannula. It should be elastic or shock-absorbing and
substances must be non-toxic, nonpyrogenic, non-
should enhance coating yet has minimal surface
inflammatory, nonimmunogenic, and sterile for use
activity. It should be cohesive enough to be removed
in the human eyes. The substance should not interfere
easily from the anterior chamber but not so cohesive
with the normal metabolism of the cells in contact with
that it is aspirated during irrigation and aspiration,
it. Substances that are immunogenic, may cause
which would provide no protection to endothelial cells
granulation or capsule formation, stimulate cell
during surgical manipulations. It should be eliminated
invasion, or interfere with epithelization or blood
from the eye in the postoperative period without an
coagulation cannot be used in the eyes. 4,6 Each
effect on intraocular pressure.1-4
viscoelastic substance has unique physicochemical
Viscosurgery was a term coined by Balazs3 to
properties which determines its clinical appili-
describe the use of these solutions that had viscous,
cations.4,7 Figure 62.1 is a gross photograph showing
elastic and pseudo-plastic properties during and after
physical characteristics of 3 different concentrations
surgical procedures. During viscosurgery, viscoelastic
of the sodium hyaluronate solution (Healon®, Healon-
substances are used as a fluid or a soft surgical
GV® and Healon-5®).
instrument. The viscoelastic sodium hyaluronate was
first used in ophthalmic surgery in 1972, when it was
CLASSIFICATION OF THE OVDS
introduced as a replacement for vitreous and aqueous
humor.3 These agents facilitate delicate and often Table 62.1 presents summary of the currently available
difficult intraocular manipulations during various OVDs. OVDs can be classified according to their zero
ophthalmic surgical procedures. They are used during shear viscosity and cohesion. The zero shear viscosity
cataract surgery and intraocular lens implantation is directly proportional to the molecular weight. This
(IOLI) to maintain the anterior chamber depth and classification describes the surgical behavior of the
capsular bag distention, thus creating and preserving viscoelastics and is as follows.8
Chapter 62: Ophthalmic Viscosurgical Devices 449
Figs 62.1A to C: Gross photograph showing physical characteristics (viscosity) of 3 different concentration
of the sodium hyaluronate solution. (A) Healon®, (B) Healon-GV®, (C) Healon-5®
1. High viscosity—cohesive OVDs Super viscous –cohesive agents are better in current
a. Super viscous—cohesive OVDs (> 1,000,000 day techniques where topical and intracameral
mPs) anesthesia are used and the surgeries are “entirely in-
b. Viscous—cohesive OVDs (Between 100,000 and the-bag” phacoemulsification. High cohesiveness of
1,000,000 mPs) superviscous and viscous materials result in easy
2. Lower viscosity –dispersive OVDs removal as a single mass at the end of the surgical
3. Viscoadaptive OVDs (e.g. Healon-5®) procedure, thus preventing the increased intraocular
pressure postoperatively. The potential disadvantage
HIGH VISCOUS—COHESIVE OVDS is loss of endothelial protection when easily washed
or aspirated out of anterior chamber during phacoe-
The super viscous-cohesive group includes Healon- mulsification.
GV® and I-visc plus® while the viscous–cohesive
group includes products like I-visc®, Provisc®, LOWER VISCOSITY-DISPERSIVE OVDs
Healon®, Amvisc®, Amvisc plus® and others. All
these products contain sodium hyaluronate. Dispersive agents have low molecular weight and
High viscous-cohesive OVDs are indicated in many shorter molecular chains. Medium viscosity, dispersive
routine procedures and are used to create space and OVDs possess zero shear viscosities between 10,000
also stabilize the surgical microenvironment. and 100,000 mPs. Very low viscosity, dispersive agents
Examples of the situations where they are used include include all of the unmodified hydroxyproply methy-
deepening the anterior chamber, to enlarge small cellulose (HPMC) agents.
pupils, to dissect adhesions, and during IOL implan- Most of the dispersive OVDs are HPMC—
tation to push back the iris and vitreous. hydroxypropyl methylcellulose, derived from wood
pulp. Cellugel® is a chemically modified HPMC.
Viscoat® is a combination of sodium hyaluronate and
SUPER VISCOUS—COHESIVE OVDS chondroitin sulphate. Vitrax® is a compound of low
Healon-GV® (greater viscosity) is a sterile, non- molecular weight molecular hyaluronate.
pyrogenic agent produced from rooster coombs. It has The dispersive OVDs provide superior endothelial
a concentration of 1.4 percent sodium hyaluronate and protection. The disadvantage of lower viscosity
a molecular weight of 5 million Daltons. dispersive OVDs is that they do not maintain or stabi-
It is used as a surgical aid in various anterior lize spaces as compared to higher viscosity cohesive
segment procedures such as cataract extraction, IOL agents. They tend to be aspirated in smaller fragments
implantation, corneal transplant surgery and glau- during irrigation/aspiration thus leading to irregular
coma surgery. In presence of high positive pressure, viscoelastic aqueous interface, thus partially obscuring
Healon-GV has 3 times more resistance to pressure the surgical view of the posterior capsule. They also
than Healon®. I-visc was introduced as a Healon- form microbubbles and can be trapped at the irregular
GV® clone. It has superior viscous and cohesive interface thus further obscuring visibility. Moreover
properties at low shear viscosity when compared to they are difficult to be removed at the end of the
Healon-GV® (Table 62.1). surgery because of low cohesion.
450
Table 62.1: Classification of ophthalmic viscosurgical devices (OVDs)
HIGHER VISCOSITY—COHESIVE OVDs

Viscosurgical Manufacturer Molecular Source Chemical Osmlality Viscosity Vo (MPs)
agents wt(D) compound (mOsm/liter)
Viscoadaptive Pharmacia Inc. 5.0 M Rooster combs Hyaluronic acid 322 2.3 NA HA 7.0 M
(fracturable) (23 mg/ml)
Healon-5®
Super Viscous
Healon-GV® Pharmacia Inc. 5.0 M Rooster combs Hyaluronic acid 310 1.4 Na Ha 2.0 M
(14 mg/ml)
I-Visc Plus® I-Med Pharma 7.9 M Rooster combs Hyaluronic acid — 1.4 Na Ha 4.8 M
(14 mg/ml)
Viscous
I-Visc® I-Med Pharma 6.1 M Roster combs Hyaluronic acid 336 1.0 Na Ha 1.0 M
(10 mg/ml)
Healon® Pharmacia Inc. 4.0 M Rooster combs Hyaluronic acid 302 1.0Na Ha 230 K
(10 mg/ml)
Provisc® Alcon 2.0 M Microbial Hyaluronic acid 307 1.0Na Ha

fermentation (10 mg/ml) 280 K
Section 4: Diseases of the Lens
Amvisc Plus® IO lab 1.0 M Rooster combs Hyaluronic acid 340 1.6Na Ha 100 K
(B & L surgical) (16 mg/ml)
Amvisc® IO Lab 1.0 M Rooster combs Hyaluronic acid 318 1.2 Na Ha 100 K
(B&L surgical) (12 mg/ml)
Biolon® Biotech 3.0 M Bacterial Hyaluronic acid 279 1.0 Na Ha 215 K

general corp fermentation (12 mg/ml)
Contd...
Contd...
LOW VISCOSITY DISPERSIVE OVDs
Viscosurgical Manufacturer Molecular Source Chemical Osmlality Viscosity Vo (MPs)
agents wt(D) compound (mOsm/liter)
MediumViscosity
Viscoat® Alcon 500 K Bacterial Hyaluronic acid 325 3.0 NaHa 41 K
fermentation Chondriotin 4.0 CDS
Shark Fin sulphate (40 mg/ml)
Vitrax® Allergan 500 K Rooster combs Hyaluronic acid 310 3.0 Na Ha 25K
(30 mg/ml)
Cellugel® Vision Biology 100K Synthetic Hydrooxypropyl 305 2.0 Chemically 38 K
(alcon) methyl cellulose modified HPMC
Ocucoat® Storz 86 K Wood Pulp Hydroxypropyl 285 2.0 HPMC 4K

(B & L surgical) methyl cellulose (20 mg/ml)
Visilon® Shah and Shah 86 K — — — 2.0 HPMC 4K

(20 mg/ml)
Viscon Dr. Agarwal’s 86 K — Hydroxypropyl — 2.0 HPMC 4K
Pharma methyl cellulose (20 mg/ml)
Visicrome® Croma — — — — 2.0 HPMC —

Chapter 62: Ophthalmic Viscosurgical Devices
Pharma (20 mg/ml)

Vo (mPs) = Zero shear viscosity (milli Pascal Second), (D) = Daltons, M = millions, K= thousand, Na Ha = sodium hyaluronate,
HPMC = Hydroxypropylmethylcellulose, CDS = Chondroitin sulphate
451
SOFT SHELL TECHNIQUE of the aqueous humor. It has a viscosity at rest about
4 7 million times higher than aqueous humor.
This technique was developed by Arshinoff , in order
Hyaluronate is a polysaccharide made up of
to take advantage of the best properties of both lower
disaccharide units linked by glycosides bonds. It
viscosity—dispersive agents and high viscosity-
occurs naturally on the corneal endothelium bound
cohesive agents and to minimize the drawbacks of
to specific receptors. The natural hyaluronate is
each by using them together. In this technique first
reduced during irrigation but can be restored by an
the lower viscosity dispersive is injected into the
exogenous one. Healon-5® has a high affinity to the
anterior chamber, followed by high viscosity-cohesive
receptors. It acts as a scavenger by neutralizing the
agent, which is injected into the center of the lower
free radicals formed during cataract surgery using
viscosity-dispersive viscoelastic thus pushing it
ultrasound.
outwards and compressing it into a smooth, even layer
against the corneal endothelium. This protects the
endothelium during lens removal. Characteristics and Advantages
Prior to the implantation of the IOL, the reverse is of the Viscoadaptive OVDs
done. High viscosity cohesive is injected first to
1. Viscoadaptive OVD (Healon-5®) specifically deve-
partially fill the anterior chamber and the capsular bag,
loped so that, at different flow rates it has different
followed by injection of lower viscosity dispersive into
functions. At lower flow rates it behaves as a very
the center of high viscosity cohesive agent. This allows
cohesive viscoelastic like a Healon-GV®. At higher
the free movement of the IOL through the dispersive
flow rates, e.g. in chopping techniques, it begins
agent, with better stabilization of the surrounding iris
to fracture and behaves similarly to a dispersive
and the capsular bag by the high viscosity agent.12
viscoelastic, such as Viscoat®. Hence Healon-5®
Removal of the OVDs is easily accomplished at the
has features that can change according to the needs
end of the surgery, since low viscosity dispersive OVA
of the surgeon during various stages of cataract
can be aspirated from the central anterior segment
surgery.
first, followed by higher cohesive agent. DuoVisc® is
2. It is crystal clear as pure water and has somewhat
a combination of high viscocity –cohesive Provisc®
higher refractive index than the aqueous humor.
and the lower viscosity dispersive Viscoat®.
Hence it increases the clarity within the surgical
field.
VISCOADAPTIVE OVD- HEALON-5Â
3. Has the ability to protect the delicate corneal
The existing viscoelastic products all have drawbacks. endothelial cells from debris and turbulence during
A cohesive viscous product used to create and phacoemulsification, particularly in eyes with very
maintain space may not stay in the eye during low endothelial cell count. In a recent study by
phacoemulsification. On the other hand, a less viscous Holzer et al13 reported that average loss of corneal
dispersive product stays during phacoemulsification endothelial cells was lowest in ocular surgeries
but often traps lens fragments or air bubbles and does using Healon-5® compared to other OVDs.
not maintain adequate space during the surgical 4. Viscoadaptive OVD (Healon-5®) is also helpful in
procedure. patients with suboptimal pupil size because the
Recently the new viscoadapative viscoelastic viscomydriasis allows for a larger capsulorhexis
Healon-5® has been developed to change its behavior and keeps the pupil larger during phacoemulsifica-
at different flow rates.10 It acts as a viscous cohesive tion by increasing the visibility.
viscoelastic agent at lower flow rates and as a 5. OVD neutralizes the positive vitreous pressure
pseudodispersive viscoelastic agent at higher flow allowing the surgeon to determine what is going
rates. It is all in one device that adapts its behavior to on inside the eye, analyze his or her options and
the surgeons needs during the entire course of surgery. effect the appropriate management.
Healon-5® is a steam sterilized, non-pyrogenic 6. The high viscosity of Healon-5® creates space and
solution. It is highly purified non-inflammatory, high stabilizes the anterior segment. The elasticity
molecular weight sodium hyaluronate at a concen- absorbs shock and protects ocular tissues during
tration of 23 mg/ml (2.3%) dissolved in a physiological IOL unfolding, which is slowed down and is more
buffer. It has an osmolarity and a pH similar to those controlled.
7. Healon-5® is also easy to remove. The widely used unchanged during BSS® injection and also avoids
method for Healon-5® removal is the two compart- increase in pressure, which can be produced with
ment technique (TCT).11 Full advantage of the excessive amount of BSS® known as capsular
agent’s viscoadaptive properties is taken in this blockade.
technique. The superior space maintaining capacity
of Healon-5® in the anterior chamber is utilized Nuclear Emulsification
while removing the substance from the capsular
During phacoemulsification, the viscoelastic is likely
bag. In the second step the anterior chamber is
to remain in the anterior chamber instead of leaking
cleaned. The “Rock and Roll” technique with suita-
out of the eye (Fig. 62.2C). OVDs help in preserving
ble settings for each type of phacoemulsifications,
the space and also because of their low cohesiveness,
was found to be a safe method for complete
they remain in the anterior chamber despite high
removal of it. In this technique there is sufficient
irrigation flow. Moreover OVDs adhere to the corneal
turbulence created and this fractures Healon-5®
endothelium, thus protecting the corneal endothelial
into small pieces.
cells (Fig. 62.2D).
SURGICAL APPLICATION OF THE OVDs
Irrigation and Aspiration
In recent years the field of viscosurgery has broadened
The role of viscoelastic during this procedure is the
rapidly. It has been used both intraocularly as well as
protection of the endothelium. This is possible due to
extraocularly, which includes cataract, cornea,
high adhesiveness. It remains where it is placed,
glaucoma, viteroretinal, strabismus and oculoplastic
without mixing with the cortex because of its low
surgeries.4, 8, 13, 14
cohesiveness thus helping in easy removal of cortex.
Use of OVDs in Cataract and Refractive Surgery
Capsular Bag Filling and IOL Implantation
OVDs are helpful in each step of modern cataract
During IOL implantation, it is necessary to expand
surgery using phacoemulsification with IOL implan-
the capsular bag with a viscoelastic. It allows the
tation.12, 15, 16 Some of these details are shown in the
surgeon to keep the bag well-opened and formed, thus
schematic photograph (Figs 62.2 and 62.3).
allowing easy IOL implantation. OVD is also helpful
in correct positioning, centering and allowing for
Capsulorhexis
possible IOL rotation maneuvers (Figs 62.2E and F).
In order to perform an intact and successful capsulo- Beside posterior chamber IOL implantation, OVD has
rhexis, the contents of the anterior chamber have an also been used for implantation of other IOL designs
important role. Till date balanced salt solution (BSS®), (e.g. anterior chamber, iris fixated, artisan lenses, etc.)
air and OVDs have been used. Out of these three the (Fig. 62.3).
best is viscoelastic as it is considered the easiest, safest,
and the most reproducible method in both routine and Cataract Surgery in Pediatric Cases
difficult cases (Figs 62.2A and B). To perform a good
Pediatric cataract surgery like the adult cataract
capsulorhexis, the viscoelastic to be used should have
surgery has undergone major changes in recent years
the four basic features:
with the evolution of techniques including small
1. High molecular weight and high viscosity at zero
incision and the development of modern IOLs. In
shear rate, which maintains the anterior chamber.
pediatric cataract surgery it is difficult to perform a
2. Excellent visibility provided by its high transpa-
good capsulorhexis due to high capsular elasticity.
rency.
Additionally, low scleral rigidity and greater intra-
3. High elasticity and pseudoplasticity.
vitreal pressure make the capsulorhexis even more
4. It should give a good capsular flap control, provi-
difficult. But with the use of viscoelastic, e.g. Healon-
ding the soft and permanent spatula effect.
GV® the effective push is in the opposite direction
and hence completion of capsulorhexis becomes
Cleavage of Lens Structure by OVD
easier.
It is best performed with the use of OVDs. The ideal In pediatric cases, in order to prevent radial exten-
viscoelastic material keeps the anterior chamber shape sion the capsulorhexis must be started in the central
A B
E F
Figs 62.2A to F: Schematic photograph showing use of the OVD (viscoadaptive OVD-Healon-5® in this figure) during the
various steps of the cataract surgery. (Courtesy: Pharmacia Inc. Peapack, NJ, USA): (A) Injection of the viscoadaptive OVD in
the anterior chamber through a 25 G cannula, (B) Capsulorhexis is in progress, (C) Phacoemulsification in progress, (D)
Viscoadaptive OVD is transparent and easy to see during removal (left). Note the presence of the air bubbles within the anterior
chamber after use of dispersive viscoelastic solution (right), (E) Implantation of a posterior chamber intraocular lens in the
capsular bag, (F) Removal of the viscoadaptive OVD using irrigation-aspiration tip
creates a bypass by which aqueous humor reaches
Schlemm’s canal, skipping the trabecular meshwork.
A chamber is produced inside the sclera, which is in
direct communication with the Schlemm’s canal.
The OVDs should have high pseudoplasticity to
allow injection into Schlemm’s canal through a small
needle and should have high viscosity at shear rate of
zero to maintain the spaces as long as possible. Healon-
GV® and Healon-5® are viscoelastics of choice for this
procedure.
OVDs for Intraocular Delivery

of Dyes or Anesthetic Agents
Researchers and vision scientists have been using
OVDs as a vehicle to deliver capsular dyes for use
Fig. 62.3: Beside posterior chamber IOL fixation in the capsular during cataract surgery.19 Mixing these substances
bag, OVDs can also be used for implantation of the various with the viscoelastic agent was attempted to prolong
phakic and aphakic IOL designs in the anterior chamber, ciliary
sulcus etc. Use of the OVD facilitated the implantation of the
their effect and to limit the adverse effect on ocular
Artisan® IOL as shown in this photograph. (Courtesy: Camil tissues. Ciba Vision Corp. (Duluth, GA, USA), has
Budo, MD) recently proposed mixing an OVD with lidocaine.
This was termed “viscoanesthesia” and was
portion and not towards the equator. The high density
intended to prolong the anesthetic effect of intra-
viscoelastic agents stabilize the posterior chamber and
cameral lidocaine, as a complement to topical anes-
push back the vitreous face during the posterior
thesia. Also, the steps of intracameral injection of
capsulorhexis. During IOL implantation, the capsular
OVDs and of intracameral injection of lidocaine, as a
bag is kept open and the anterior chamber is well
complement to topical anesthesia, would be combined
formed thus ensuring easy and safe implantation of
in only one step.
the IOL in the bag. These agents also help to dilate the
pupil and maintain a good intraoperative mydriasis.17
Viscostaining of the Anterior Lens Capsule
Use of the OVDs in Glaucoma Surgery Various non-toxic ophthalmic dyes have been
extensively used as diagnostic agents for the detection
Viscocanalostomy
and management of different ocular disorders. Dyes
Viscocanalostomy is a new surgical procedure for such as fluorescein sodium, indocyanine green (ICG),
glaucoma therapy.18 Viscoelastics play an important and trypan blue have been increasingly used for
role in this procedure. Figures 62.4A to F illustrate the enhancing visualization by staining intraocular tissues
surgical steps of viscocanalosotomy. Viscocanalos- during the adult and pediatric cataract surgery and
tomy literally means “opening of the canal by means vitreoretinal surgery. Staining of ocular tissues by
of viscoelastic substance”. This procedure is a non- using ophthalmic dyes makes visual differentiation
penetrating and independent of external filtration. The and manipulation of tissues easier. Enhanced viewing
advantages are decreased risk of infection, and of ocular tissues can assist a surgeon’s ability to
decreased incidence of cataract, hypotony and flat evaluate clinical structural relationships and may help
anterior chamber as the anterior chamber is not attain surgical objectives with fewer complications.
opened, and with the absence of external filtration the Use of various capsular dyes for staining the
question of bleb formation does not arise. It excludes anterior lens capsule in white, mature cataracts have
the risk of late infections and conjunctival and been reported.20-23,24 The techniques originally repor-
episcleral scarring. ted for staining the anterior capsule using fluorescein
Viscocanalostomy allows the aqueous to leave the sodium are: staining from above under an air bubble
eye, through Schlemm’s canal and episcleral veins thus and intracameral subcapsular injection of fluorescein
restoring the natural outflow pathway. This procedure sodium (staining from below) with blue-light
Figs 62.4A to F: Surgical steps of viscocanalosotomy. (Courtesy: Dr. med. Tobias Neuhann, MD, Munich, Germany): (A) Deep
block construction incision, (B) Cutting the deep block in a single plane with a spoon blade, (C) Proximal to Schlemm’s canal
there is a subtle change in the scleral fibers, from a crossing pattern to a tangential pattern, with an increased opacity, (D)
Descemet’s window. (E) Cannulating Schlemm’s canal with three puffs of viscoelastic directed at the osteum, (F) Tight closure
suture of the flap
enhancement. The first technique (staining under an Use of OVDs in Topical Ophthalmic
air bubble) is currently used by most surgeons. One Anesthesia (Viscoanesthesia)
benefit is the staining of the peripheral anterior
Anesthetic techniques for cataract surgery have also
capsular rim, which is otherwise difficult to visualize
advanced significantly. General anesthesia was
during the phacoemulsification procedure. However,
preferred in past years, followed by various techniques
air in the anterior chamber makes it unsteady. Any
of injectable anesthesia including retrobulbar,
instrument entering the eye will cause some air to
peribulbar, sub-tenon, and subconjunctival anesthesia.
escape, with a rise of the lens-iris plane. A small
Due to marked improvements in surgical techniques,
amount of high-density viscoelastic placed near the
it is no longer essential to ensure complete akinesia of
incision can prevent the air bubble from escaping the
the eye and as a consequence, the technique of topical
anterior chamber, thus minimizing the risk of sudden
anesthesia has been popularized as “phacoanes-
collapse. Also, with this technique, there is a
thesia”. This includes eye drops application, sponge
progressive dilution of the dye by the aqueous humor.
anesthesia, eye drops plus intracameral injection, and
This may be a possible explanation for the fainter
most recently gel application.15,26 Topical anesthesia
staining observed with this technique in recent clinical
is the preferred technique for the members of the
reports, without compromising its usefulness. Most
American Society of Cataract and Refractive Surgery
of the drawbacks of this technique can be avoided by
(ASCRS) in the United States (49%; range 37%-63%)
careful use of a viscoelastic solution to seal the incision
according to a survey conducted by David Leaming
site. Some surgeons practice the “soft shell stain
in 2000.35 It revealed that as high as 82 percent of the
technique” for performing a CCC in white cataract
respondents using topical anesthesia preferred eye
cases. A small amount of viscoelastic (Viscoat®) is
injected into the anterior chamber followed by high drops in association with intracameral injection of
molecular weight viscoelastic material (Provisc®) to lidocaine.
fill up the chamber completely. Then ICG solution is As mentioned before mixture of a viscoelastic
injected on the lens surface with a bent G27 visco solution with an anesthetic solution (known as
cannula. The anterior capsule was uniformly stained VisThesia™) has had the advantages of visco-surgery,
in green and easily visualized while the cornea viz maintenance of the anterior chamber depth,
remained unstained. The soft shell stain technique is capsular bag expansion, protection of corneal endothe-
extremely useful for CCC in white cataracts. lium, etc. It also provides prolonged anesthesia and
Alternatively, the dye solution can be mixed with no extra surgical steps for intracameral injection of
viscoelastic agents a technique known as “visco- lidocaine is needed. VisThesia™ is manufactured by
staining of the anterior lens capsule”. Kayikicioglu and Vitrolife (Edinburgh, Scotland) and will be exclusively
coworkers25 proposed a technique for limiting the distributed by Ciba Vision Corp. (Duluth, GA, USA)
contact of trypan blue to corneal endothelium by in the future. VisThesia™ contains topical component
mixing the dye with a viscoelastic solution. These of 0.3 percent hyaluronic acid with 2 percent lidocaine
researchers mixed 0.4 percent trypan blue with in a single dose unit; and intracameral component of
1 percent sodium hyaluronate in a 2 mL syringe. The 1.5 percent hyaluronic acid with 1 percent lidocaine
dye, mixed in a viscoelastic solution, is injected onto in a sterile syringe.
the anterior lens capsule, which covers the anterior We have recently completed some studies to
capsule without coming in contact with the corneal evaluate the use of viscoelastic agents mixed with
endothelium. Trypan blue mixed with sodium topical anesthetic solution (lidocaine). The aim of these
hyaluronate greatly increases the visibility of the studies was to evaluate the safety of this new solution
anterior lens capsule without significantly touching (termed as viscoanesthesia) to intraocular struc-
the adjacent tissues. There is always a potential risk tures.11,20,27 Our animal and experimental studies were
of corneal decompensation after intraocular use of self- divided into 3 parts. In Part I,27 we determined the
mixed solutions; however, these authors used this toxicity of the viscoanesthetic solution to the corneal
technique without significant surgical and post- endothelium using a rabbit model. In Part II,27 we
operative adverse effects. evaluated the toxicity of viscoanesthetic solutions to
uveal tissues and retina in a rabbit model after Removal of the OVDs
performing phacoemulsification. Finally, in Part III,20 Several techniques have been reported in the literature
using postmortem human eyes, we evaluated and for removal of the OVDs. These include: Rock and Roll
compared to currently available OVDs in regard to technique, two-compartment technique and bimanual
the surgical aspects such as injection and aspiration irrigation/aspiration technique.1 Figures 62.5A to H
of the viscoanesthetic solutions. are photographs from a human eye obtained
postmortem (Miyake-Apple posterior view) showing
the sequence of the experimental surgical technique
of the removal of fluorescein-colored viscoelastic
solutions (green color as viewed with oblique illumi-
nation) from the capsular bag using the rock and roll
technique.
An effective technique to remove Healon-5® is to
create maximum turbulence to make it fracture into
large pieces. This can be accomplished using rock and
roll technique with standard I/A tip, 0.3 mm, with
high settings; a flow rate of 25 to 30 ml/min., and
vacuum 350 to 500 mm Hg, depending on the type of
pump. If a peristaltic pump is used the vacuum should
be set towards the lower limit. A bottle height of 60 to
70 cm above the eye level. Figure 62.6 summarizes
the removal technique of viscoadaptive agent, Healon-
5®.
An alternative technique has been developed
allowing the use of less turbulence, using a standard
I/A, tip 0.3 mm, with effectual flow at 20 to 25 ml and
vacuum 250 to 3000 mm Hg. The bottle height should
be 60 to 70 cm above eye level. Figure 62.7 presents
the steps of removal technique of the viscoadaptive
agent, Healon-5®, using another technique.
It is necessary to emphasize that a careful and
thorough removal of the OVDs from the capsular bag
and the anterior chamber of the eye is must after the
end of the surgery. This is important to avoid
Fig. 62.5A to H: Gross photographs from a human eye obtained complications such as rise in intraocular pressure,
postmortem (Miyake-Apple posterior view) showing the crystallization of the IOL surface (vide infra).28 Studies
sequence of the experimental surgical technique of the removal
have shown that complete removal of viscoelastic
of fluorescein-colored viscoelastic solutions (green color as
viewed with oblique illumination) from the capsular bag was
material from the capsular bag can be more difficult
documented by videotaping (A) This figure shows the eye after when some hydrophobic acrylic lenses are used
capsulorhexis and removal of lens substance (cortex and because of the IOL’s tacky surfaces.
nucleus) by phacoemulsification. Note the edge of the anterior
capsulectomy (arrows), (B) and (C) Injection of fluorescein- COMPLICATIONS OF USE OF OVDS
colored viscoelastic solution (in this example, Ophthalin Plus®), OVDs have many positive attributes but their
with a 27-gauge Rycroft cannula through the orifice of the drawbacks and complications must be given careful
anterior capsulectomy, (D) Capsular bag completely filled with considerations. Some of the important complications
viscoelastic solution, (E) Same eye after insertion of a one-
are described below-
piece, modified C-loop posterior chamber IOL in the capsular
bag (arrows), (F) Viscoelastic solution removal with automated Raised Intraocular Pressure (IOP)
aspiration, set at 250 mm Hg (Alcon Legacy 20,000), (G) Final
removal of viscoelastic substance. The surgeon reached behind Raised IOP is the most important postoperative
the IOL optical edge to remove all the viscoelastic material, (H) complication of OVDs. It was first noted with
Aspect after complete removal of the viscoelastic solution Healon®. The raised pressure can be severe and
Figs 62.7A and B: Schematic photograph showing an

alternative removal technique of viscoadaptive agent (Healon-
5®), as recommended by the manufacturer. (Courtesy:
Pharmacia Inc. Peapack, NJ, USA): (A) Start the removal
directly after IOL implantation, while the anterior chamber is
still filled with Healon-5® and before the IOL has been centered.
Go behind the IOL optic without engaging the flow of the I/A tip
(port up) and then start flow. Remove Healon-5® from the
capsular bag first and ensure that lens has adequately centered.
During removal of Healon-5® from the capsular bag, the
Figs 62.6A to C: Schematic photograph showing the one of continuous flow of irrigation fluid keeps the bag inflated and
the removal technique of viscoadaptive agent (Healon-5®), as reduces the risk of aspirating the capsular bag. While
recommended by the manufacturer. (Courtesy: Pharmacia Inc. maintaining continuous flow remove the tip from behind the
Peapack, NJ, USA): (A) The surgeon circles the I/A hand piece optic and place it on top of optic, and (B) Continue the removal
in the anterior segment at iris plane, (B, and C) The surgeon by circling the I/A tip at the iris plane, or on the optic surface,
gently rests the I/A hand piece on the anterior surface of the then make an additional sweep in the anterior chamber paying
optic. Press gently on the IOL optic on one side and rotate the particular attention to angles
I/A hand piece directing the flow into the bag. Direct the hand
piece port towards the equator of the capsular bag and stay in prolonged, if the material is not thoroughly removed
this position for a few seconds, and then repeat on the other at the end of the surgery. The rise in IOP occurs in the
side of the IOL optic until Healon-5® is completely removed. first 6 to 24 hours and resolves spontaneously within
Finally sweep the anterior chamber including the angles and 72 hours postoperatively 29, 30. The rise in IOP is due
repeat the step if necessary to the mechanical resistance at the trabecular
meshwork to the large molecules of the viscoelastic of these lenses, it was not uncommon to find crystals
material, which decreases the outflow facility. Hence, on their surfaces, which exhibited some degree of
to reduce the incidence of this complication, many birefringence (Figs 62.8A and B). Sometimes they had
have advocated thorough removal of the viscoelastic the typical fern-like appearance found after precipita-
material from the eyes at the end of the surgery.31 tion of viscoelastic or salt solutions. We believe those
crystals correspond to precipitation of viscoelastic
Crystallization on the IOL Surfaces solutions used by the surgeons during the explantation
procedure. These may crystallize on the surfaces of
Olson et al.32 reported a physician survey, laboratory
the IOLs sent to our Center in a dry state.
studies, and clinical observations of intraoperative
Many lenses sent to our Center were explanted
crystallization of OVD on IOL surfaces. These authors
because of the presence of crystalline deposits on their
sent a survey to all ophthalmologists in the states of
optical surfaces. They caused significant decrease in
Wyoming, Idaho, Montana, Utah, and Colorado (USA)
visual function requiring lens explantation/exchange
asking whether crystallization on the IOL surface had
(Figs 62.8A and B). Our analyses demonstrated that
occurred in any of their patients and what viscoelas-
these deposits were also composed of multiple
tics, IOLs, and other solutions were used. All returned
confluent small crystals, which sometimes did not
surveys were tabulated and analyzed by standard
assume a fern-like appearance, but rather an
statistical methods. A sample of crystallization from
amorphous arrangement.35 Therefore, it could not be
an IOL submitted by a physician on a glass slide was
confirmed whether they were related to deposition/
analyzed to ascertain the relative elemental
crystallization of viscoelastic material. Further studies
composition. During in vitro laboratory studies, BSS
are necessary to evaluate whether they may corres-
Plus® (Alcon Surgical, Fort Worth, Texas, USA) and
pond to the crystallization of residual viscoelastics in
BSS® (Alcon Surgical) were analyzed for precipitation.
an aqueous environment, late postoperatively. Most
Healon-GV® (Pharmacia/Upjohn, Kalamazoo,
specifically, scanning electron microscopy coupled
Michigan, USA) and calcium chloride were combined
with a surface analysis technique such as energy-
in various solutions and examined for precipitate
dispersive x-ray analysis could determine the
formation. Silicone IOLs were placed in different BSS®
elemental composition of the deposits observed on the
and BSS Plus® solutions with different viscoelastics
surfaces of our explanted lenses. These observations
and varying calcium concentrations. In seven patients,
highlight the fact that any viscoelastic agent should
prominent crystallization on IOL surfaces was
be thoroughly removed from the capsular bag and
examined, photographed, and followed for up to 3
anterior chamber of the eye during cataract surgery.
years. Results of this interesting survey revealed that
in 22 eyes (0.07%) intraoperative crystallization was
Capsular Block Syndrome or
observed on the IOL surface during 1993. The survey
Capsular Bag Distension Syndrome
indicated that there was a correlation with BSS Plus®
(chi-square = 4.9, P = 0.0268) and silicone IOLs (chi- Miyake and associate19 proposed a new classification
square = 6.8, P = 0.0093). The analyzed sample of capsular block syndrome (CBS), a newly described
submitted by one of the surgeons showed the cation complication of cataract-IOL surgery, to improve
to be calcium. The authors concluded that crystalliza- understanding of the etiology and provide effective
tion on the IOL surface during cataract surgery is a treatment. Three groups of eyes with CBS were
rare occurrence that may be associated with calcium reviewed by these authors: eyes originally reported
as the cation. An osmotic gradient around the IOL is and diagnosed as having CBS; eyes experiencing CBS
observed with increased calcium concentration. If after hydrodissection and luxation of the lens nucleus;
encountered surgically, the lens should be exchanged and eyes with CBS accompanying liquefied after-
in the operating theater after irrigating the anterior cataract or capsulorhexis-related lacteocrumenasia.
chamber with BSS® and completely filling the capsu- These researchers noted that in all 3 groups, the CBS
lar bag with a low molecular weight viscoelastic.33, 34 occurred in eyes with a capsulorhexis. It was
Since 1993 we received in our Center more than characterized by accumulation of a liquefied substance
9,000 IOLs explanted because of different within a closed chamber inside the capsular bag,
complications. During gross and microscopic analyses formed because the lens nucleus or the posterior
A B
Figs 62.8A and B: Crystallization on the IOL surfaces secondary to precipitation of the OVDs on the surfaces: (A) Light
photomicrographs taken from the anterior surface of intraocular lenses, which were explanted because of different complications
(including error in power calculation) and sent to our Center for analyses. A typical fern-like appearance of the crystals found on
the surface of the lenses can be observed. Birefringence under polarized light is observed in the bottom picture, (B) Gross and
light microscopic photographs taken from the posterior surface of a 3-piece silicone lens explanted because of opacification of
the lens optic caused by a whitish deposit. The crystals found on the surface of the lens do not have a typical fern-like appearance,
but exhibit birefringence under polarized light (bottom picture).
chamber IOL optic occluded the anterior capsular described CBS), and late postoperative (CBS with
opening created by the capsulorhexis. Depending on liquefied after-cataract). The etiology of the
the time of onset, CBS was classified as intraoperative accumulated substance and the method of treatment
(CBS seen at the time nucleus luxation following are different in each type. These authors concluded
hydrodissection), early postoperative (originally that CBS is a complication of cataract/IOL surgery
that can occur during and after surgery. Correct REFERENCES

identification of the type of CBS is crucial to the 1. Arshinoff SA. Dispersive–cohesive viscoelastic soft shell
understanding of nature and effective treatment of this technique. J cataract Refract Surg 1999;25,167.
disorder. 2. Arshinoff SA. New terminology: Ophthalmic viscosurgical
Of late use of high-density viscoelastic agents, such devices. J Cataract Refract Surg 2000;26:627.
as Healon-GV®, has been found to be associated with 3. Balazs EA. The development of sodium hyaluronate (healon)
complication of late CBS. Analysis of the transparent as a viscosurgical material in ophthalmic surgery. In Eisner
G (Ed): Ophthalmic viscosurgery. Bern, Switzerland:
liquid between the posterior lens capsule and the
Medicopia 1986;1-19.
posterior chamber (PC) IOL in early postoperative 4. Liesegang TJ. Viscoelastics. Int Ophthalmol Clin 1993;33,127.
capsular block syndrome. These results indicate that 5. Pandey SK, Thakur J, Werner L, Sharma V, Izak AM, Apple
the main ingredient of the transparent liquid in DJ. Ophthalmic viscosurgical devices: An update. In Garg A,
capsular bags is sodium hyaluronate and that the Pandey SK, Sharma V, Apple DJ (Eds): Advances in
distention is caused by aqueous humor being drawn Ophthalmology. Jaypee Brothers: New Delhi, India 2003, (in
into the capsular bag by an osmotic gradient across press).
6. Hyndiuk RA, Schultz RO. Overview of the corneal toxicity
the capsule when the capsulorhexis diameter is smaller
of surgical solutions and drugs: and clinical concepts in
than that of the PC IOL and by viscoelastic material corneal edema. Lens Eye Toxic Res 1992;9,331.
retained and trapped in the bag intraoperatively. 7. Poyer JF, Chan KY, Arschin SA. Quantitative method to
determine the cohesion of viscoelastic agents by dynamic
Pseudo-anterior Uveitis aspiration. J Cataract Refract Surg 1998;24,1130.
8. Arshinoff SA. Dispersive and cohesive viscoelastics materials
The pseudo-anterior uveitis occurs because of the
in phacoemulsification, Revisited 1998. Ophthalmic Practice
OVD’s viscous nature and also the electrostatic charge 1998;16,24.
of the materials.36 The red blood corpuscles (RBCs) 9. Arshinoff SA, Opalinski YAV, Ma J. The pharmacology of
and inflammatory cells remain in the anterior lens surgery: ophthalmic viscoelastic agents. In: Yanoff M,
chamber, thus giving it the appearance of uveitis. It Ducker JS (Eds): Ophthalmology. St Louis, Mosby-Yearbook,
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no treatment. Sometimes an intraocular hemorrhage 10. Anna Densjo. Healon 5, The World’s first Viscoadaptive.
Ophthalmic Express 1998;6:4.
gets trapped between the vitreous space and the OVD
11. Tetz MR, Holzer MP. Healon® 5 clinical performance and
in the anterior chamber and mimics the appearance special removal technique (Two Compartment Technique).
of vitreous hemorrage.36 In: Buratto L, Giardini P, Belluci R (Eds): Viscoelastics in
ophthalmic surgery, Thorofare, NJ, USA, Slack 2000;401-04.
SUMMARY AND CONCLUSIONS 12. Strobel J. Comparison of space maintaining capabilities of
The choice of a viscoelastic substance depends largely Healon and Healon GV during Phacoemulsification. J
Cataract Refract Surg 1997;23,1081.
on the intended surgical use. At the present time, no 13. Ram J, Pandey SK. Infantile cataract surgery: Current
single viscoelastic agent is ideal under all circums- techniques, complications and their management. In Dutta
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should consider the multiple physicochemical Delhi, India, 2000;378-84.
characteristics of each viscoelastic material available 14. Pandey SK, Ram J, Werner L, Gupta A, Apple DJ. Persistent
as well as their desirable and undesirable clinical pupillary membrane. Br J Ophthalmol 2000;84,554.
effects, then choose the most appropriate substance. 15. Ram J, Pandey SK. Anesthesia for cataract surgery. In: Dutta
LC. Modern Ophthalmology. Jaypee Brothers, New Delhi,
As new materials are developed and as our knowledge
India, 2000;325-30.
of the physical properties, clinical effects, and surgical 16. Ram J, Pandey SK. Indications and contraindications of
indications are better defined, the selection process phacoemulsification. In: Dutta LC (Ed): Modern
for choosing the best product should improve. Ophthalmology. Jaypee Brothers, New Delhi, India, 2000;437-
Widespread success in clinical situations has been 40.
achieved with pure hyaluronate and combination 17. Mamalis N. Ophthalmic viscosurgical Devices: Viscoadap-
sodium hyaluronate chondroitin sulfate material. tives, Viscoelastics, What does it mean? J Cataract Refract
Surg 2002;28,1497.
Although expensive, viscoadaptive agent, Healon-5®,
18. Stegmann R,Pienaar A, Miller D.Viscocanalostomy for open
has some distinct advantages. Methyl cellulose angle glaucoma in black African patients. J Cataract Refract
possesses special advantages of lower cost, no Surg 1999;25,316.
requirement of refrigeration, a larger quantity of the 19. Miyake K, Ota I, Ichihashi S et al. New classification of capsu-
material per unit. lar block syndrome. J Cataract Refract Surg 1998;24,1230.
20. Pandey SK, Werner L, Apple DJ, Izak AM, Trivedi RH, Macky 28. Storr-Paulsen A. Analysis of the short-term effect of two
TA. Viscoanesthesia Part III: Evaluation of the removal time viscoelastic agents on the intraocular pressure after
of viscoelastic/viscoanesthetic solutions from capsular bag extracapsular cataract extraction. Sodium hyaluronate 1% vs
of human eyes obtained postmortem. J Cataract Refract Surg hydroxypropyl methylcellulose 2%. Acta Ophthalmol
2003;23,563. (Copenh) 1993;71,173.
21. Pandey SK, Werner L, Apple DJ. Staining the anterior capsule. 29. Akahoshi T. Soft shell stain technique for the white cataract,
J Cataract Refract Surg 2001;27,647. presented at the ASCRS Symposium on Cataract, IOL, and
22. Pandey SK, Werner L, Escobar-Gomez M, Roig-Melo EA, Refractive Surgery, Boston, MA, May 2000.
Apple DJ. Dye-enhanced cataract surgery. Part I. Anterior 30. Barron BA, Busin M, Page C, et al. Comparison of the effects
capsule staining for capsulorhexis in advanced/white of Viscoat and Healon on post operative intraocular pressure.
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23. Pandey SK, Werner L, Escobar-Gomez M, Werner LP, Apple 31. Holzer MP, Tetz MR, Auffarth GU, Welt R, Volker H. Effects
DJ. Dye-enhanced cataract surgery. Part III. Staining of the of Healon 5 and 4 other viscoelastic substances on intraocular
posterior capsule to learn and perform posterior continuous pressure and endothelium after cataract surgery. J Cataract
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32. Cobo M, Beaty N. VITRAX? (sodium hyaluronate) in anterior
2000;26,1066.
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24. Werner L, Pandey SK, Escobar-Gomez M, Hoddinott DSM,
Ther 1990;7,51.
Apple DJ. Dye-enhanced cataract surgery. Part II. An experi-
33. Jensen MK, Crandall AS, Mamalis N, Olson RJ. Crystallization
mental study to learn and perform critical steps of phaco-
on intraocular lens surfaces associated with the use of Healon
emulsification in human eyes obtained post-mortem. J
GV. Arch Ophthalmol 1994;112,1037.
Cataract Refract Surg 2000;26,1060.
34. Nirankari VS, Karesh J, Lakhanpal V. Pseudo vitreous
25. Kayikicioglu O, Erakgun T, Guler C. Trypan blue mixed with hemorrhage: A new introperative complication of sodium
sodium hyaluronate for capsulorhexis. J Cataract Refract Surg hyaluronate. Ophthalmic Surg 1981;12,503.
2001;27,970. 35. Leaming DV. Practice styles and preferences of ASCRS
26. Pandey SK, Werner L, Apple DJ, Agarwal A, Agarwal A, members—2000 survey. J Cataract Refract Surg 2001;27,948.
Agarwal S. No anesthesia clear corneal phacoemulsification 36. Nirankari VS, Karesh J, Lakhanpal V. Pseudo vitreous
versus topical and topical plus intracameral anesthesia: Rand- hemorrhage: A new introperative complication of sodium
omized clinical trial. J Cataract Refract Surg 2001;27,1643. hyaluronate. Ophthalmic Surg 1981;12,503.
27. Trivedi RH, Werner L, Apple DJ, Izak AM, Pandey SK, Macky 37. Macky TA, Werner L, Apple DJ, Izak AM, Pandey SK, Trivedi
TA. Viscoanesthesia Part I: Evaluation of the toxicity to RH. Viscoanesthesia Part II: Evaluation of the toxicity to
corneal endothelial cells in a rabbit model. J Cataract Refract ocular structures after phacoemulsification in a rabbit model.
Surg 2003;23,550. J Cataract Refract Surg 2003;29,556.
Chapter 63
Complications of Intraocular
Lens Implantation
In addition to the complications of any intraocular POSTOPERATIVE COMPLICATIONS

operation the following are some of the specific
Incidence of postoperative shallow anterior chamber,
complications of IOLI operation.
striate keratopathy, corneal edema, iridocyclitis, iris
INTRAOPERATIVE COMPLICATIONS prolapse, hyphema, are not more in IOLI than in any
intraocular surgery.
Preexisting corneal guttata or low endothelial cell
count may predispose to more problems unless special Endophthalmitis
precautions are taken. Leaving aside causes like
turbulence-endotheliopathy, excess instrumentation, The incidence of endophthalmitis in IOLI is compar-
prolonged manipulation in the anterior chamber and able to that in routine cataract operation.1 An intact
pseudophako-endothelial touch are the specific points posterior capsule creates a barrier effect to prevent
to be noted. A momentary touch of the IOL will strip the extension of bacteria.2,3
off a layer of endothelium. Use of irrigating fluid, drugs, viscoelastic material
This can be avoided by the following: and the IOL itself may be the source of exogenous
1. Deepening the anterior chamber with viscoelastic infection.
material. An early diagnosis (differential diagnosis from
2. Taking a correct plane of insertion of IOL. sterile endophthalmitis) and prompt treatment is very
3. Maintaining the corneal dome by reducing the size essential to save the eye.
of the section.
LATE COMPLICATIONS
4. Coating the IOL with viscoelastic substance.
Malposition of PC IOLs
Iris tuck It means entrapment of the peripheral iris
between the IOL haptic and peripheral structures. A Decentration, subluxation, and dislocation have been
pathognomonic sign is an oval pupil with vertical axis and continue to be a problem with almost every type
corresponding to vertical axis of the IOL. of IOL, though least in PC IOL. Decentration means
In an anterior chamber IOL it may be due to the minimal horizontal or vertical displacement of the
following: implant in relation to the pupil. Incidence of
1. Larger IOL (incorrect size) malposition of secondary, PC IOL is slightly higher
2. Wrong plane of insertion than primary ones due to the following:
3. Too much dilated a pupil. 1. More tissue handling in secondary surgery carries
In posterior chamber IOL it occurs during more risk of zonular rupture.
insertion of the upper haptic. It can be correct by 2. Less postoperative fibrotic tissue reaction, where
dialing the IOL. firm IOL fixation is generally not achieved.
Chapter 63: Complications of Intraocular Lens Implantation 465
PC IOL malposition can be divided into two cate- of aqueous humor causing low intraocular pressure.
gories: Moreover, there is high risk for ‘bleb’ infection
a. decentrations that are unrelated to zonular leading to endophthalmitis. Hence would leakage
disinsertion or capsular rupture. forming a filtration bleb must be repaired at the
b. subluxation or dislocations caused by intra- earliest. Systemic and/or topical steroid therapy
operative or postoperative damage to zonules during the early postoperative period of cataract
or lens capsule. operation may be a cause of filtering bleb formation.
Decentration Dislocations
Most satisfactory type of posterior chamber intra- Dislocation of anterior chamber IOL is much more
ocular lens (PCIOL) is in-the-bad fixation of both the frequent than posterior chamber ones.
haptics. For this type of fixation a continuous Causes of dislocation might be spontaneous or
curvilinear capsulorhexis (CCC) is essential. In can- traumatic. Intraoperative capsular or zonular trauma
opener type of capsultomy there is every likelihood is the most common causes of dislocation.
of tear in the capsular margin causing extrusion of
one of the haptics leading to decentration of the IOL. Lost Lens Syndrome
One haptic lying in the bag and the other not in the
It is defined as a complete dislocation of an IOL into
bag but in the sulcus can lead to gross astigmatic
the vitreous cavity. It is caused by severe zonular
refractive errors.
disinsertion or by posterior capsular rupture after
accidental trauma.
Pupil capture
An immobile IOL in the vitreous without any
It is a minor complication in which a part or whole of evidence of cystoid macular edema or retinal
the IOL is displaced anteriorly with synechiae detachment does not need removal immediately.
formation between the posterior surface of the optic Criteria for removal with vitrectomy would be retinal
and the underlying iris. injury (contusion or tear), cystoid macular edema,
persistent uveitis, a mobile IOL in the vitreous or
Iris Chaffing location of the IOL over the macular region.
In anteriorly angulated posterior chamber IOL loops
Intermittent Corneal Touch
can rub against the posterior surface of the iris and
can cause posterior iris damage. This causes iris This occurs in AC IOL either with a malpositioned
pigment epithelial transillumination with occasional or too small an IOL. Signs are ciliary flush, localized
minimal hyphema and visual obscuration. The corneal edema and CME. It should be recognized
pigment dispersed from the iris can be deposited on early before permanent irreversible corneal edema
the posterior surface of the cornea, anterior surface occurs. It is advisable to remove the IOL.
of the iris, trabecular meshwork and on the pseudo-
phakos. Pigment deposited on the trabecular mesh- Secondary Glaucoma
work may cause elevation of intraocular pressure.
In the early postoperative period it occurs due to the
Wound Dehiscence following:
i. Pseudophakic pupillary block.
In large incision cataract surgery wound dehiscence ii. Temporary hindrance of the outflow channel by
can potentially cause blindness. Incidence has almost plasmoid aqueous and cells due to iridocyclitis
completely declined appreciably due to growing shift or inadequate washing out of viscoelastic subs-
to small incision self closing incision. tances.
Pseudophakic pupillary block glaucoma can occur
Formation of Filtering Bleb
both in AC or PC IOL. The chances increase in sulcus
Filtering bleb can also occur in non-phaco large fixated IOLs small peripheral iridectomy, blockage
incision cataract surgery. Wound leak under com- of iridectomy hole by vitreous, and in PC lens without
pletely healed conjunctival incision can lead to leakage posterior angulation.
Management decompensation as well as cystoid macular edema

which is termed as CRIS (Corneal-Retinal Inflam-
1. Medically, by beta blockers, carbonic anhydrase
matory Syndrome). This is very resistant to con-
inhibitor, and hypertonic agents.
ventional therapy; in some cases exploration is
2. YAG laser iridectomy or surgical iridectomy may
needed.
be needed in the following cases:
a. If medical management fails. Persistent Corneal Edema and Decompensation
b. If iridectomy hole is blocked by exudate or
Protection of corneal endothelium during surgery
vitreous.
plays a major role to avoid and minimize this disaster.
3. If the anterior chamber is deeper and peripheral
Following points need to be mentioned:
anterior synechia is present then gonioplasty may
1. Deep and formed anterior chamber during instru-
be attempted with argon laser.
mentation in the anterior chamber and insertion
of IOL to avoid touch of endothelium by IOL and
UGH (Ellingson’s) Syndrome
instruments.
This syndrome is characterized by uveitis, glaucoma, 2. Judicious use of viscoelastic substances.
and hyphema. 3. Avoidance of excessive corneal manipulation.
Mechanism of UGH syndrome is the mechanical 4. Selection of ideal irrigating fluid with the stream
laceration or rubbing of the iris on a rough or sharp of flow directed away from the endothelium.
edge—due to the improper finishing quality of the 5. Avoidance or minimum use of therapeutic concen-
IOL (in AC and iris clip IOL), which was seen mostly tration of medicine (like gentamycin/adrenaline)
in the seventies. But cases have been reported with in irrigating solutions as they are toxic to endo-
PC IOL also. So the etiology is multifactorial and still thelium.
not fully elucidated.5 6. Proper wound closure to avoid postoperative
shallow anterior chamber related complications.
Management Despite all the precautions, some cases will
manifest some signs of corneal decompensation.
Following forms of therapy have been advocated:
The important causes are the following:
i. Tropicamide or pilocarpine to reduce the mecha-
i. Preexisting endothelial pathology
nical chaffing of iris due to constant rubbing.6
ii. Surgical trauma
ii. Steroids, ocular hypotensives and antiglaucoma
iii. Improperly managed postoperative compli-
therapy to reduce inflammation and associated
cations
glaucoma.
iv. IOL related problems.
iii. Argon laser vessel obliteration when the bleeding
Endothelial cell population density is reduced by
source is identified near the haptic.7
15 to 50 percent in anterior chamber IOL and 1 to 30
iv. As a last resort IOL exchange.4 One should not
percent in posterior chamber IOLI. Preexisting
allow an UGH syndrome to persist too long so
endothelial pathology plays a major role in the
as to cause corneal dystrophy or permanent
causation of corneal decompensation. Preoperative
macular degeneration due to prolonged cystoid
associated uveitis and glaucoma reduces the func-
macular edema.
tional reserve of the diseased endothelium. Cell
counts of 1500 to 2200 mm2 are at a slightly greater
Late Uveitis
risk than that of normal one, and eyes with count
Chronic low grade smouldering inflammation is one 1000 to 1500 mm2 are at special risk. An eye with a
of the dreaded complications. Constant IOL uveal cell count less than 1100 mm2 is to be considered with
contact and toxic material of the IOL leads to chronic serious risk.
breakdown of the blood-aqueous barrier with
resultant inflammation which leads to tissue des- Problems Related to IOL
truction with fibrosis, synechiae, and media opaci- Faulty lens design and size will lead to intermittent
fication. Release of different inflammatory mediators corneal touch and decompensation over a longer
and activation of complement factors lead to corneal period of time. Defective lens material may lead to
slow release of monomers inciting harmful chemical
Chapter 63: Complications of Intraocular Lens Implantation 467
reaction which may lead to corneal problems. permanent damage to the retina occurs. If there is
extensive thickening of the macula treatment within
Management 2 to 3 months should be started. Topical non –
steroidal anti-inflammatory agents like Ketorlac
If corneal edema fails to clear up within 8 months
trimethamine 0.5 percent or Flurbiprofen 0.03 percent
with adequate medical therapy by topical steroid and
topical solution. Peribulbar/oral steroid and
antiglaucoma drugs, the only way left is penetrating
acetazolamide are the drugs used for the treatment
keratoplasty. An important decision to be taken is
of CME.
whether IOL should be left behind or removed or
exchanged.
REFERENCES
In an opaque cornea, pseudophakia bullous
keratopathy (PBK) with a red inflamed eye, the IOL 1. Roussel TJ, Stirn WH. Postoperative mycobacterial endoph-
should be removed since its retention may lead to thalmitis. Am J Ophthalmol 1989;107:403.
2. Crose, K A, Pearce JL. Protective barrier effect of the posterior
graft failure. An exchange implant will also be a risky lens capsule in exogenous, bacterial endophthalmities: I A
one, unless judged very meticulously. In an opaque case report. J Cataract Refractive Surgery 1980;12:413.
cornea with a white eye the IOL may be left in situ. 3. Ruth M, Mannon, Christopher R Canneng. Posterior lens capsule
abscess due to P. acne and Staph epidermidis follow/during
Cystoid Macular Edema ECCE. Br J Ophthalmol 1991;75:710.
4. Shepard DD. Indications for IOL removal. Ophthalmic Surgery
Cystoid macular edema (CME) is a more frequent 1977;8:144.
complication following secondary IOL implantation. 5. Pazandak B. Recurrent intraocular hemorrhage associated with
Vitreous disturbance plays a major role in causation PC lens implantation. Am Intraocular Implant Society J
of CME. 1983;9:327.
6. Nuholson DH. Occult Iris Erosion: A treatable cause of recurrent
Management hyphema in iris supported with. Ophthalmology 1982;89:113.
7. Magarel LE: Recurrent hyphema in the pseudophakic eye.
The principle of treatment of CME is to treat it before Ophthalmology 1983;90:1231.
SECTION 5: GLAUCOMA
Chapter 64
Gross and Microanatomy of the

Angle of the Anterior Chamber
S Choudhary
The angle of the anterior chamber is a space, peripheral patient. The space is influenced however by the
to a line drawn between Schwalbe’s line anteriorly and following factors:
the last roll of the iris process posteriorly. 1. Development of the circular muscle of the ciliary
The importance of having the knowledge of the body.
minute anatomy of the angle of the anterior chamber 2. Length of the iris root, which affects the position
lies in the fact that it forms the major drainage pathway of the last roll of the iris.
of aqueous humor, and it tends to be impeded here in 3. Position of the anterior surface of the lens, which
the angle in primary glaucoma. For this reason, it is normally moves progressively forward throughout
frequently termed as the filtration angle or the life as a result of lens growth.
iridocorneal angle. 4. Accommodation and swelling of the lens or
The outer or corneoscleral wall of the angle extends vitreous body.
from Schwalbe’s line anteriorly to scleral spur 5. Adhesions following an operation or inflammatory
posteriorly and includes the trabeculae and the canal conditions.
of Schlemm. The apex of the angle is located in the The angle is generally wider in myopic eyes and
anterior face of the ciliary body and is 1 to 2 mm narrow in hypermetropes. In emmetropic eyes, the
behind the limbus (Fig. 64.1). Angle width is probably horizontal meridian of the chamber angle is 1 mm,
an anatomic characteristic inherent in the individual whereas the vertical meridian is 0.75 to 1 mm posterior
to the peripheral cornea.
The major pathway of aqueous humor from the
anterior chamber to the venous system includes the
trabecular meshwork, the endothelium of Schlemm’s
canal, and the collector channels. Each of these tissues
has been described in detail below:
It is only in higher primates and humans that
“trabecular meshwork” has developed in the true
sense of the word. The expression trabecular mesh-
work is derived from the Latin diminutive of trab,
meaning a beam. It has a trabeculated and reticular
appearance, and is composed of a number of
superimposed fibrocellular sheets. It encircles the eye
in an annular fashion, and forms a three sided
Fig. 64.1: Anatomy of the apex of the anterior chamber prismatic bend.
Chapter 64: Gross and Microanatomy of the Angle of the Anteior Chamber 469
The trabecular meshwork is divided into two to Hans Virchow (1910)3 it is made up of two parts
broader parts:(1) Nonfiltering part, (2) Filtering part differing in structure. An outer, stouter and larger part
(Fig. 64.2). comprising practically the whole of the trabeculae—
the corneoscleral meshwork, and a few delicate
Nonfiltering Part elements lying on the inner surface of this—the uveal
meshwork. To this may be added a third element
It has no contact with Schlemm’s canal, and is therefore
between the outermost trabecular sheet surface and
termed as the nonfiltering part of trabecular mesh-
the endothelial lining of Schelmm’s canal known by a
work. The most anterior portion lies adjacent to the
variety of names, endothelial meshwork (Speakman),4
Schwalbe’s line. This part consists of three to five
pore tissue (Flocks) 5 or juxtacanalicular or peri-
trabecular beams covered by small trabecular cells
canalicular connective tissue.
which lie closely together. They are in contact with
The width of the trabecular band varies from
the keratocytes of the posterior lamellae of the
fraction of a millimeter to over 1 millimeter; but in
cornea.1,2 Morphological and histological studies have
the majority of cases, it is 0.33 to 0.50 mm.
shown that the cell system of the corneal endothelium
and that of the trabecular cells are different, viz. the
Corneoscleral Meshwork
corneal endothelial cells contain a large amount of
carbonic anhydrase enzyme, whereas the trabecular It extends from scleral spur toward the cornea, filling
cells do not. the scleral sulcus. It comprises of the main bulk of the
In the nonfiltering region, Descemet’s membrane trabecular meshwork and consists of flat, interlacing
tapers off toward its posterior end, splitting into beams, each lamella contains a central core, consisting
several lamellae that are continuous with the basement of ground substances, collagenous and elastic like
membrane like sheets of trabecular beams. This fibers. Normally, they are completely covered by a
relationship between Descemet’s membrane, and the single layer of endothelial lining and is supported by
subendothelial membranes of the trabecular beams a basement membrane.
become evident with immunofluorescent studies
using antibodies against laminin, and collagen type Uveal Meshwork
IV.
Anteriorly, it is anchored to the inner layers of the
corneal stroma or corneoscleral meshwork, while it
Filtering Part
continues posteriorly with the ciliary body and root
The filtering portion of the trabecular meshwork of the iris. The uveal meshwork consists of irregularly
covers the inner wall of Schlemm’s canal. According arranged strands or sheets running radially. These
strands are connected with each other, forming a
broad network with oval or round pores. These
strands are covered by endothelial cells that rest on a
relatively thick basement membrane. The core of the
uveal strands consists mostly of collagenous fibers
with elastic fibers in between. The fiber system is
arranged less regularly than the lattice like pattern of
the corneoscleral portion.
Juxtacanalicular Tissue
It is a thin layer of tissue, 2 to 20 mm thick and
comprises of the outermost part of the trabecular
meshwork, adjacent to the inner wall of the endo-
thelium of Schlemm’s canal. It contains a network of
Fig 64.2: Schematic drawing of human iridocorneal angle: A.
fine fibrils, elastic like fibers and a number of
nonfiltering trabecular meshwork. B. filtering trabecular elongated fibroblast like cells arranged in layers. The
meshwork. C. uveoscleral route. D. aqueous humor flow from cells are embedded in a homogenous extracellular
ciliary processes. Arrows 1-5 aqueous humor flow matrix, and in electron microscope, it shows as empty
470 Section 5: Glaucoma
spaces. These spaces may represent preferential septa or tissue bridges. Anteriorly, the lumen is most
aqueous pathway toward the inner wall endothelium often collapsed, whereas posteriorly it is wider and
of Schlemm’s canal. occasionally shows extensions into the trabecular
meshwork; Theobald7 called them “internal collector
Trabecular Spaces channels of Sondermann”. Their functional signi-
ficance may be to increase the filtering area in a region,
The open spaces in the trabecular system result from
where the diameter of the meshwork is maximum.
spatial separation of superimposed trabecular sheets.
Schlemm’s canal is covered by a single layered
The spaces vary from 0 mm to 8 mm in size and
endothelial lining, the structure of which differs in the
communicate through perforations or stomas in
outer and inner walls. The endothelial cells of the inner
individual trabecular sheets, that is, intratrabecular
wall normally have an elongated spindle like shape
spaces, which vary from 25 mm to 75 mm in the uveal
with an average length of 160 mm, area 408 mm,2
sheets to 2 mm to 20 mm in the outer layers of
whereas the outer wall cells are shorter and have an
corneoscleral sheets. Perforations or stomas in the
area of 792 mm. 2 The inner wall cells are firmly
trabecular sheets are not directly superimposed on
connected with each other by maculae adherents and
succeeding layers, but rather communicate by
zonulae occludentes.8 Many of these cells contain giant
tortuous pathways. A collapse of the trabecular
vacuoles of various sizes9 that are not found in the
meshwork thus reduces the effective area of the
outer wall of the endothelium. The intracellular giant
opening and a fanned trabecular meshwork as occurs
vacuoles communicate both with the subendothelial
with the contraction of ciliary muscle; posterior pull
layer, and with the lumen of the canal by small pores.
of the scleral spur increases the porosity.
In humans, the diameter of the pores on the canal side
varies between 0.5 to 1.5 mm, and on the meshwork
Schlemm’s Canal (Fig. 64.3) side between 0.12 to 0.38 mm. The frequency and size
Schlemm’s canal represents a more or less circular of the giant vacuoles are proportional to the pressure
channel measuring about 36 mm in circumference and in the anterior chamber, increasing with a rise in
embedded within the scleral sulcus, comparable to a intraocular pressure and decreasing if the intraocular
lymphatic vessel than to a vein or capillary. In sagittal pressure is reduced.10,11 Thus, giant vacuoles are pre-
sections the diameter of the canal varies between 350 existing structures forming transcellular microchan-
to 500 mm.6 The canal is not uniform in shape and nels by which aqueous humor can pass into the
size, but frequently splits into branches separated by Schlemm’s canal.
Fig. 64.3: Schematic three dimensional picture of schlemm’s canal (SC) and adjacent
trabecular meshwork (TM) in a fully devoloped eye
Chapter 64: Gross and Microanatomy of the Angle of the Anteior Chamber 471
It has been suggested that the inner wall may found that contraction of the ciliary muscle leads to
function as an oneway valve, preventing reflux of pulling of the spur posteriorly, which increases the
blood cells of proteins from the canal into the intratrabecular space, and prevents the Schlemm’s
meshwork and anterior chamber. After a paracentesis canal from collapse.
or sudden decrease of intraocular pressure, the inner
wall endothelium can rupture, and plasma proteins
Schwalbe’s Line
can enter into the anterior chamber.12 A moderate
paracentesis leads only to reduction in the number of It is a line, which runs circumferentially around the
giant vacuoles.13 globe, and has an irregular elevation of 50 to 150 mm
The outer wall endothelium is supported by a in width. This line marks the termination of
complete basement membrane, in contrast to the inner Descemet’s membrane, and the insertion of the
wall endothelium, which has hardly any basement trabecular meshwork into the corneal stroma.
membrane. The canal is surrounded by collagenous
fiber bundles, and by a network of elastic like fibers Innervation
embedded in a substance rich in glycosaminoglycan.
Normal width of Schlemm’s canal is 276 ± 52 mm. Most of the nerves of the trabecular meshwork and
in eyes of POAG that have been successfully treated Schlemm’s canal area originate from the supraciliary
by filtration surgery becomes very much smaller plexus, and a few fibers are derived from the ciliary
(178 ± 71); but in eyes treated successfully with topical plexus in the region of the scleral spur. The nerve fibers
drugs , the width of the canal is almost normal. The are predominantly nonmyelinated. Holland, et al17
clinical relevance is that the decrease in width of believes that both somatic and autonomic nerves are
Schlemm’s canal after successful filtration surgery present.
could make glaucoma more difficult to control if the There appears to be a greater concentration of the
bleb ultimately fails.14 nerve endings in the region of the juxtacanalicular
tissue. This distribution may influence the functional
status of the trabecular wall of Schlemm’s canal,
Collector Channels directly or indirectly.
Schlemm’s canal is drained by 20 to 30 collector In a recent study Tamm, et al18 have identified
channels, which are connected to the vascular system structures, which have the morphological features of
of the limbal region, the course and relations of which mechanoreceptors within the scleral spur. The
have been intensively studied by a number of possibility, that there is some form of neurological
workers.15,16 They are more numerous in the nasal and control of the intraocular pressure, raises the possibility
lower temporal quadrants. It has been found that the for valuable future research.
following two different collector channels exist:
REFERENCES
Direct There are four number, in which connect
1. Lutjen-Drecoll E, Futa R, Rohen JW. Ultrahistochemical
directly with the episcleral venous plexus and
studies on tangenital sections of the trabecular meshwork
conjunctival veins, and they have a laminar flow of in normal and glaucomatous eyes. Invest Ophthalmol Vis Sci
aqueous humor and blood. 1981;21:563.
2. Lutjen-Drecoll E, Kaufman PL. I. Long-term timolol and
Indirect They are smaller and numerous in number epinephrine in monkeys. II. Morphological alterations in
and connect with the intrascleral capillary network. trabecular meshwork and ciliary muscle. Trans Ophthalmol
Soc UK 1986;105:196.
3. Hans Virchow. Cited from Duke Elder. Text book of Ophthal-
Scleral Spur mology 1969.
4. Speakman JS. Drainage channels in the trabecular wall of
It is a fibrous ring and on meridional section appears
Schlemm’s canal. Br J Ophthalmol 1960;44:513.
as a wedge projecting from the inner aspect of the 5. Flocks BS. Observation on the drainage angle in man and
sclera. The spur is attached anteriorly to the trabecular rhesus monkey. Invest Ophthalmol 1964;3:601.
meshwork, and posteriorly to the sclera, and the 6. Hogan MJ, Alvarado JA, Weddall JW. Histology of Human
longitudinal portion of the ciliary muscle. It has been Eye. Philadelphia, 1971.
7. Theobald GD. Schlemm’s canal, its anastomosis and anatomic 13. Okisaka S. Effects of paracentesis on the blood aqueous
relations. Trans Am Ophthalmol Soc 1934;32:574. barrier. Light and electron microscopic study on monkey.
8. Raviola G, Raviola E. Paracellular route of aqueous outflow Invest Ophthalmol Vis Sci 1976;15:824.
in the trabecular meshwork and canal of Schlemm. Invest 14. Johnson DH, Mitsumato Y. Schlemm’s canal becomes smaller
Ophthalmol Vis Sci 1981;21:52. after successful filtration surgery. Arch Ophthalmol
9. Holmberg A. The fine structure of the inner wall of Schlemm’s 2000;118:1251.
canal. Arch Ophthalmol 1959;62:935. 15. Archer KW. Aqueous veins: A preliminary note. Am J
10. Grierson I, Lee WR. Changes in the monkey’s outflow Ophthalmol 1942;25:31.
apparatus at graded levels of IOP. Exp Eye Res 1974;19:21. 16. Ashton N. Aqueous veins. Br J Ophthalmol 1952;30:265.
11. Okisaka S. The effect of prostaglandin E on the ciliary 17. Holland MG, von Sallman L and Collins EM. A study of the
epithelium and the drainage angle of monkeys: A light and innervation of the chamber angle. Am J Ophthalmol
electron microscopic study. Exp Eye Res 1976;22:141. 1957;44:206.
12. Raviola G. Effects of paracentesis on the blood aqueous 18. Tamm ER, Flugel C, Stefani FH, et al. Nerve endings with
barrier: An electron microscopic study. Invest Ophthalmol structural characteristics of mechanoreceptors in the human
Vis Sci 1974;13:828. scleral spur. Invest Ophthalmol Vis Sci 1994;35:1157.
Chapter 65
Gonioscopic Appearances
of Normal and
Pathological Conditions
S Choudhary
Proper evaluation of the anterior chamber angle plays also inspection of the pupillary area, lens, and the
a pivotal role in the diagnosis and management of entire surface of the iris. Synechia at the pupillary
glaucoma. The detailed study of the angle is not border or the white flaky dandruff like material in
possible by slit lamp biomicroscopy alone. The pseudoexfoliation is more easily seen at the pupillary
problem is with the critical angle of the air-cornea area through a gonioscopic lens than through the slit
interface. To eliminate this optical effect of the front lamp. The examiner’s gaze should pass over the plane
corneal surface, special contact lens (gonioscopic) is of the iris, noting its flatness when the anterior chamber
used so that the structures are thoroughly visualized. is deep or its convexity with shallow anterior chamber.
Gonioscopy is helpful diagnostically, prognostically, Iridodonesis is particularly easy to recognize with the
and therapeutically. Before viewing the angle through gonioscope. Small iris nodules, neovascularization,
the gonioscopic lens, slit lamp biomicroscopy is hypoplasia, atrophy of iris can also be noted (Fig. 65.2).
essential as the latter gives added information to the
examiner about the angles in respect of the following:
a. Cornea KP’s, guttatae, Krukenberg’s spindle,
vascularization, edema, etc.
b. Anterior chamber Depth, aqueous flare, etc.
c. Iris Nodules, atrophic, patches, holes, PAS, Irido-
dialysis, neovascularization, etc.
d. Pupil Reaction to light, sphincter atrophy,
sphincter tear, flaky dandruff like materials,
synechia, etc.
e. Lens Spherophakia, pigmentation over the
anterior capsule, pseudoexfoliation of the capsule,
subluxation, glaukomflecken, etc (Fig. 65.1).
Gonioscopic examination should consist not only Fig. 65.1: Post-traumatic angle picture with clear lens
the study of the angle of the anterior chamber, but dislocation in the anterior chamber (Arrow shows lens border)
beginning at Schwalbe’s line, or with the indirect

gonioscopic lens the corneal parallelepiped of the slit
lamp beam comes together at this point (Fig. 65.3).
Trabecular meshwork It consists of a meshwork of
fibers extending from the Schwalbe’s line anteriorly
to the scleral spur posteriorly. It has an irregularly
roughened surface, which in childhood is glistening
and translucent, and with increasing age its trans-
parency decreases. The roughness is caused by the
large openings of the uveal meshwork. It can be
divided into two parts: the anterior nonfiltering
portion and the posterior filtering portion, and these
two portions are usually quite different on gonioscopic
Fig. 65.2: Gonioscopic appearance of a thalassemia patient appearance (Reason for the difference is probably
after receiving blood transfusion. Hyphema at the inferior functional).
quadrant The anterior portion overlying the corneoscleral
tissue has no function as an exit channel for aqueous
GONIOSCOPIC ANATOMY OF humor, and as a result remains nonpigmented and
THE NORMAL CHAMBER ANGLE white. The posterior portion of the trabecula overlies
The use of gonioscopy permits visualization of the the canal of Schlemm, and through this portion the
angle of the anterior chamber, that is, concealed from aqueous humor escapes from the anterior chamber.
direct view because of its location behind the translu- As the aqueous filters through the porous meshwork
cent limbal tissue. The structures that may be made of the trabecular fibers, cells and pigments are
out are the anterior surface of the iris and its root, a collected. In course of time the collected cells may give
portion of the anterior surface of the ciliary body, iris a diffuse tan or brown pigmentation. The pigmen-
processes, scleral spur, trabecular meshwork, line of tation of the posterior portion of the meshwork is quite
Schwalbe, and posterior aspect of the cornea. different in appearance from that of Schwalbe’s line.
Pigmentation of Schwalbe’s line is coarse and
Schwalbe’s line It marks the most anterior extension superficial, whereas pigmentation of the meshwork
of the meshwork and the termination of the Desce- is diffuse and within the substance of the structure.
met’s membrane of the cornea, and it is the first The appearance of pigmentary changes is extremely
landmark which should be identified in examining the helpful in orientation of the angle, particularly when
angle of the anterior chamber. After identifying the Schwalbe’s line is difficult to be identified. Variations
Schwalbe’s line, the examiner is at once oriented to in pigmentation is seen from patient to patient.
the following:
Everything central to Schwalbe’s line is anterior
chamber proper and everything peripheral belongs
to the anatomy of the angle. Identification of Schwal-
be’s line, usually is easy. The landmark is represented
by a prominence on the inner aspect of the corneal
surface at the point where Descemet’s membrane ends.
Here the corneal radius of curvature changes to the
larger radius of the sclera. Schwalbe’s line as a rule, is
pigmented, particularly at the lower quadrants.
Pigmentation consists of a series of somewhat coarse,
discrete pigment dots appearing on its surface
(Sampaolesi’s line), when it is nonpigmented,
identification is somewhat difficult. But by shifting Fig. 65.3: Gonioscopic appearance of a case of pigmentary
the angle of light, the examiner usually can perceive a glaucoma with excessive degree of pigmentation of the
difference in curvature of the corneoscleral wall trabecular meshwork and Sampaolessi line
Chapter 65: Gonioscopic Appearances of Normal and Pathological Conditions 475
However, deep pigmentation is seen in pigment
dispersion syndrome, pigmentary glaucoma, iritis,
surgery or trauma. Pigmentation can be graded as +1
to +4 depending on the intensity of the color.
Schlemm’s canal is present in the depth of the
posterior filtering portion of the trabecular meshwork
as a slightly darker grayline, than the meshwork itself
and it is normally not seen gonioscopically. When the
canal is filled with blood, it forms a narrow but well
demarcated reddish line. This is visualized by
increasing the pressure on the ipsilateral jugular vein
or by exerting and releasing the pressure on the cornea
with the gonioscopic lens.
Fig. 65.5: Gonioscopic appearance of a wide open angle with
Scleral spur It receives the trabecular fibers anteriorly
pigmentation of the trabecular meshword +4
and serves as an insertion for the ciliary body
posteriorly. Gonioscopically, it appears as a gray-
insertion of the iris into the ciliary body. The width of
white line of varying width at the outer end of the
the band depends on the site of the iris insertion, and
angle recess. If blood is in Schlemm’s canal, it lies just
it tends to be wider in myopic eyes and narrower in
anterior to the spur. As it is the insertion point for
hypermetropes. The color may vary from dull brown
most of the longitudinal muscle fibers of the ciliary
to pale gray, and although it has the same color of the
body, it may regulate the facility of aqueous outflow.
iris, it is usually much darker.
Iris processes These bridge the angle and are usually
visible as semitransparent bands that run vertically PATHOLOGICAL CONDITIONS
from the root of the iris upward and join midway with Open angle glaucoma In open angle glaucoma, all the
the uveal meshwork. They have a wider span toward normal structures of angle can be seen, and the minute
the base. They are few in numbers and frequently gonioscopic examination does not reveal any specific
found at the nasal quadrant of the angle. They are seen morphological alteration, which may indicate an
in only 35 percent of normal individuals. They are increased resistance to outflow, and it is impossible
considered as normal variants and remnants of to diagnose a case of open angle glaucoma by simple
mesodermal tissue, and usually do not hinder the gonioscopy alone. Some relevant information may be
outflow facility (Fig. 65.5). found, e.g. inflammatory precipitates, network of
Ciliary body band It is that portion of the ciliary body minute blood vessels, excessive pigmentation, etc.
band, which is visible in the angle as a result of Narrow angle glaucoma In narrow angle, the following
points should be particularly noted and have to be
kept in mind. Is it narrow angle or closed angle? Is it
appositional closure or synechial closure? Is the entry
narrow? Is it plateau iris configuration? Treatment
with miotics narrows the angle further as a result of
increased pupillary block and forward lens shift.
There are two methods to estimate the extent to
which an angle is opened behind the concealing iris.
In the first method, with the slit lamp follow the
parallactic displacement of the focal lines (Figs 65.6A
and B). If there is contact between the iris and anterior
wall, whether synechial or appositional, the two lines
meet at one point which marks the location of the
Fig. 65.4: Gonioscopic appearance of a wide open angle contact. If there is parallactic displacement, it means
with moderate processes that there is a space behind the convex iris which leads
to the recess. With less displacement of the line of accompanying congestive reaction will lead to the
contact the angle is termed as functionally closed. The formation of definite, numerous permanent gonio-
second method is the manipulative gonioscopy. synechia (Fig. 65.7).
Forbes in 1966 used the Zeiss four mirror gonioscopic
Secondary glaucoma with PAS Peripheral anterior
lens to indent the cornea, and search for appositional
synechiae in secondary glaucoma are always due to
or synechial closure of the angle. In 1967 Gonin
iridocyclitis. In cyclitis and iritis of the ciliary part of
advocated the Goldmann lens to manipulate the angle
the iris PAS forms most frequently. Due to the
recess.
formation of posterior synechia and seclussio pupillae
Goniosynechia At the beginning of a closed angle there is retention of aqueous humor in the posterior
glaucoma or after mild and creeping attacks, the angle chamber, followed by forward bulging of the iris root
may remain completely free. If the congestive crisis which becomes adherent to the periphery of the cornea
lasts for 24 hours, partial goniosynechia form which in front of Schwalbe’s line.
may break again, at least partly under the action of In some cases of chronic iridocyclitis PAS
miotics. But if the crisis is prolonged beyond 2 to 3 (Figs 65.8A and B) forms gradually. It begins with an
days, or it is repeated or if it is very acute, the exudate in the angle recess, and the surface of the iris
(ciliary part) is pulled up in the process of organization
of the exudate. Some of the synechiae are ciliary, some
reach up to the mid-trabecular region, and others may
advance up to the line of Schwalbe. They are thin,
bridge like, conical or broad based. They usually do
not interfere with outflow of aqueous humor. Even
the broad based synechiae that bridges the angle may
allow aqueous to flow underneath them as if under a
tunnel.
PSEUDOEXFOLIATION SYNDROME
The materials are sticky, and are not easily cleared
through the drainage channels as easily as the
pigments. The particles are visible on the ciliary body,
trabecular meshwork and peripheral part of the
Fig. 65.6A: Gonioscopic appearance of a narrow angle with
narrow entry with the patient looking at a straight gaze cornea. Pigments are deposited in the deeper layers
(note the peripheral convexity of the iris) of the trabecular meshwork, close to the canal of
Fig. 65.6B: Gonioscopic appearance of a narrow angle with

narrow entry with the patient viewing towards the gonioscopic Fig. 65.7: Gonioscopic appearance of a angle closure.
mirror PAS visible after indentation
Chapter 65: Gonioscopic Appearances of Normal and Pathological Conditions 477
IRIDOCORNEAL ENDOTHELIAL SYNDROME
Progressive iris atrophy The iris is diseased and shows
defects in the stroma, and there is pulling of the
peripheral iris toward the angle (Fig 65.9). Glaucoma
is due to the progressive closure of the angle, first by
PAS, and then by formation of a hyaline membrane
secreted by the ectopic corneal endothelium,which
covers the angle (Fig. 65.10). In Chandler’s and Cogan-
Reese syndromethere are bridges like synechiae.
ANIRIDIA
Endothelial cells invade the angle structures and cover
the stump of the congenitally defective iris and may
Fig. 65.8A: Gonioscopic appearance of a gonio synechia form a glass like membrane. In association with this
misplaced tissue, there are sheets of tissue belonging
to the stump of the defective iris itself. The stump of
the iris root has a tendency to cover the trabeculae
which block the outflow.
Fig. 65.8B: Gonioscopic appearance of an angle of old

iridocyclitis with broad based multiple PAS
Schlemm. These particles are flaky dandruff like Fig. 65.9: Gonioscopic appearance of a case of
materials deposited throughout the angle structures progressive iris atrophy
as lattice like track, and present mostly in the inferior
quadrant. On the Schwalbe’s line deposition of
pigments is typical, and known as Sampaolesi’s line.
PIGMENT DISPERSION SYNDROME

Pigment may fill every available space between the
trabecular meshwork, sinuous spaces of the juxta-
canalicular tissue and the canal of Schlemm. Large
particles of pigment remain on the surface of the
trabecular tissue and form a dense dark line in front
of the canal of Schlemm. Elimination of pigment from
the eye may explain the cause of pigment dispersion
syndrome without glaucoma, and spontaneous
remission of high intraocular pressure in eyes with Fig.65.10: Gonioscopic appearance of an angle with multiple
glaucoma. PAS after ALT
AXENFELD SYNDROME SOME POSSIBLE MISINTERPRETATIONS

There is hypertrophy of the line of Schwalbe and Iris processes and synechia Iris processes appear as thin
extension of trabecular meshwork into the clear cornea strands of iris tissue crossing the angle recess and
along an irregular line. Other features are hypoplasia finally inserting in the trabecular meshwork. They
of the iris and columns of iris tissue bridging the angle, may be numerous but in no way they affect the
and inserting on the anterior wall of the angle. It may outflow of aqueous. They are considered as normal
be mistaken with PAS. The iris columns may vary in findings.
length, width, and site of insertion. PAS on the other hand are more broad based and
conical, and rather than representing normal anatomic
NEOVASCULARIZATION OF THE IRIS AND ANGLE
variants, represent either present or past coaptation
The new vessels grow initially from the pre-existing of the iris root and the trabecular meshwork. It may
iris capillary beds found near the root of the iris or lead to misdiagnosis of angle closure glaucoma.
near the sphincter pupillary area. They appear as
hidden tufts of vessels, which unlike normal iris vessel Ciliary body band and trabecular meshwork The
leak fluorescein. In the angle initially, they may appear excessive presence of iris pigment in aqueous humor
as filliform tufts of vessels and later as fibrovascular together with the filtering action of the trabecular
membrane causing closure of the angle. There is lifting meshwork may result in an apparent hyperpigmenta-
of peripheral iris toward the anterior wall blocking tion of the trabecular band, when seen gonioscopically.
the outflow of aqueous humor (Fig. 65.11). This appearance frequently causes the meshwork to
be confused with the highly pigmented ciliary zone.
TUMORS Should the pigmented trabeculae be considered as part
Angle remains closed as a result of extension of a of the ciliary body, an angle which is narrow, in reality
growing tumor of the iris leading to blockage of the may be diagnosed as one that is wide open.
outflow drainage channels. This may occur also in case Sampaolesi’s line When pigment particles liberated
of cyst of the iris or ciliary body. Angle closure may from the iris pigment epithelium settle on the shelf of
also be due to inflammatory reaction in the anterior Schwalbe’s line, a pigment line is created known as
segment resulting in either synechial closure of the Sampaolesi’s line. This line of pigment may mimic the
angle or there is posterior synechia, which leads to trabecular meshwork in an eye with a closed angle,
pupillary block with iris bombe and secondary closure leading to the erroneous impression that the angle is
of the angle. The trabecular meshwork may be open.
obstructed in an open angle by loose pigment, pigment
laden macrophages or by massive invasion by Abnormal new vessels and normal vessels The early
malignant cells. signs of impending neovascular glaucoma with a fine
network of blood vessels like a grape arbor growing
anteriorly over the trabecular meshwork is sometimes
mistaken with the normal radial vessels of the major
circle of iris.
BIBLIOGRAPHY
1. Gorin G and Posner A. Slit lamp gonioscopy. Baltimore:
Williams and Wilkins Co, 1957.
2. Lowe RF. Etiology of the anatomical for primary angle closure
glaucoma. Br J Ophthalmol 1970;54:161.
3. Scheie HG. Width and pigmentation of the angle of the
anterior chamber. Arch Ophthalmol 1957;58:510.
4. Shaffer RN. Stereoscopic manual of gonioscopy. St Louis: The
CV Mosby Co, 1962.
5. Spaeth GL. Gonioscopy uses old and new. The inheritance of
occludable angles. Ophthalmology 1978;85:222.
Fig. 65.11: Gonioscopic appearance of a case of neovascular 6. Tornquist R. Chamber depth in primary acute glaucoma. Br
glaucoma Massive neovascularization at the angle J Ophthalmol 1956;40:421
Chapter 66
Primary Open Angle Glaucoma

Devindra Sood, NN Sood
Traditionally Primary Open Angle Glaucoma (POAG) When both optic nerve head and automated visual
intraocular pressure was defined as a classical triad fields criteria were used, the prevalence fell to
of a raised (IOP), optic nerve head damage and 2.4 percent.
corresponding visual field defects in the presence of It is estimated that 67 million people worldwide
open angles on gonioscopy. Glaucoma is the second suffer from glaucoma.1 POAG is estimated to affect
leading cause of blindness worldwide. 1 Primary 33 million people worldwide, majority of whom
glaucomas have been classified into primary open (about 26 million) reside in developing countries. 90
angle glaucoma (POAG) and primary angle closure to 100 percent of those affected in developing countries
glaucoma (PACG). The American Academy of are unaware that they have the disease. Visual
Ophthalmology Preferred Practice Pattern (1996) impairment is also more severe.1,15 The estimated risk
defines POAG as “ a chronic, generally bilateral and of blindness (above 12-20 years) from POAG ranges
often asymmetrical disease, which is characterized (in from 14.5 to 27 percent (unilateral) and from 7 to 9
at least one eye) by all of the following: percent (bilateral).16-18 With an expected increase in
1. Evidence of glaucomatous optic nerve damage the population and longevity, POAG is likely to
from either or both of the following: become a major cause of ocular morbidity in the
• The appearance of the disk or retinal nerve fiber developing world.
layers: Thinning or notching of the disk rim,
and progressive, nerve fiber layers defects. Magnitude of the Problem in India
• The presence of characteristic abnormalities in
The Andhra Pradesh Eye Study 19 indicated a
the visual field, e.g. arcuate, scotoma, nasal step,
prevalence of 2.56 percent for POAG and 0.42 percent
paracentral scotoma, generalized depression in
for ocular hypertension among 934 people more than
the absence of other causes.
40 years of age. The Vellore study reported 0.4 percent
2. Adult onset
POAG and 3.08 percent ocular hypertension.20 Studies
3. Open normal appearing anterior chamber angles.
in rural India showed a prevalence of 5.6 percent in
4. Absence of known other (e.g. secondary) causes of
people more than 40 years of age 21 (As uniform
open angle glaucoma.2
methodology was not adapted in these two studies,
the prevalence rate quoted may not be accurate—Ed).
The Problem, Worldwide
The current definition of POAG does not include
Depending on the definition of POAG, the prevalence intraocular pressure (IOP). Population based studies
of the disease in population based studies ranged from which included IOP in their diagnosis of POAG3-14s
0.4 to 8.8 percent.3-14 Most of these studies used the have shown higher prevalence of POAG amongst
appearance of both the optic nerve head and visual whites and African Americans with higher levels of
field as a part of the diagnostic criteria. A prevalence screening IOP. In 1989, Sommer et al discussed the
of 5 to 6 percent was reported by the Blue Mountain’s importance of IOP only as a risk factor in POAG. In
Eye Study when optic nerve damage alone was the Baltimore Eye Survey , 47 of the 3571 eyes with an
deemed sufficient to satisfy the diagnosis of POAG.13 IOP of 16 to 18 mmHg, 0.01 percent, met the definition
of POAG.22 Though these statistical associations are supported by the observation that eyes with higher
all consistent with IOP as a risk factor for POAG, they screening IOP have a larger relative risk of for POAG.22
however, do not prove that IOP causes POAG in all Likewise patients with asymmetric glaucomatous
cases. There is however, evidence to suggest that IOP optic nerve cupping usually have a large cup in the
is a causal risk factor for POAG. eye with a higher IOP.25,26
Even the collaborative Normal-Tension Glaucoma
RISK FACTORS FOR POAG Study found that by reducing the IOP by at least 30
percent, a significant reduction in vision loss can be
Risk factors are factors, the presence of which increases
achieved as compared to controls.27
the possibility of having glaucoma (Table 66.1).
Age
Intraocular Pressure
Nearly every population based study has shown a
Several studies have demonstrated that with an
statistical association between increasing age and
elevated IOP, the prevalence of POAG increases.3-7
POAG.3-14 Most chronic diseases are more common
Several population based studies have shown a
in the elderly population. However, we do not know
consistent association between the level of IOP and
why POAG is more prevalent in the elderly. Genetic,
POAG.4,7,8,11,13 The Baltimore Eye Study22 reported an
biological or environmental factors are also considered
increase in the strength of the association between
to be responsible.
POAG with higher IOP’s. Compared to eyes with
screening IOP less than or equal to 15 mmHg the
Gender
relative risk for POAG was higher12-8 with IOP’s 30-
34 mmHg. There is a marked discordance amongst population
Vascular ischemia , decrease perfusion of the optic based studies on the association between gender and
nerve head, mechanical compression of the lamina POAG. The Frammingham28 and Barbados11 studies
cribrosa and decrease axoplasmic flow are all likely reported higher rates of POAG amongst males. The
causes of glaucomatous optic nerve damage which can Blue Mountains14 and St Lucia Study12 reported higher
be caused by a raised IOP. The temporal relationship rates in females. Others found no significant statistical
between IOP and POAG has been emphasized in the association.4,7,8
non-human primate model of glaucoma23 and also in
human eyes with acute angle closure glaucoma, where Race
a raised IOP causes glaucomatous optic nerve damage.
The importance of ethnicity in POAG has been
Kass and coworkers also demonstrated that
demonstrated by several studies7,5,29 showing that
lowering the IOP in ocular hypertensives reduces the
individuals of black African heritage were at an
risk of developing POAG.24 The Ocular Hypertension
increased risk of developing POAG. The exact cause
Treatment Study (OHTS) further bolstered this view.
of this higher prevalence of glaucoma in those of
Lowering IOP by 20 percent in eyes with an elevated
African origin is unknown. It is hypothesized that
IOP reduced the probability of developing POAG to
larger cup disk ratios,30 large disks and more nerve
4.4 percent after 5 years, as compared to the untreated
fibers may be contributory factors. The Baltimore Eye
group. The possibility that IOP causes POAG is
Survey found a greater prevalence of POAG in African
Table 66.1: Risk factors in POAG American at each specific level of IOP, as compared
to whites even though they had similar IOP distri-
• IOP
• Optic nerve head cupping
bution.
• Age
• Race Steroid Usage
• Family History
POAG has a strong association with steroids. The
• Steroid usage
• Thin Central Corneas strength of the association is reinforced by the strong
• Diabetes tendency to have a steroid induced rise in IOP
• Systemic Hypertension amongst POAG patients as also the connection
• Myopia between the glaucoma gene and its glucocorticoid
• Migranes induction in the trabecular meshwork.
Chapter 66: Primary Open Angle Glaucoma 481
Family History studies found that the odds of a diabetic having POAG
were two times greater than those of a non-diabetic.
Population based studies have supported an
Diabetes mellitus may or may not be a risk factor for
association between a positive family history for
POAG. However, diabetics tend to have higher IOP,
glaucoma and POAG. In the Barbados Eye Study31
than non-diabetics.
undiagnosed subjects were more likely to develop
glaucoma if they had a history of glaucoma in one or
Systemic Hypertension
more siblings (odds ratio = 4.5). In Rotterdam32 the
population based familial aggregation study showed The Barbados and Baltimore studies did not find a
a life time risk of glaucoma in siblings and offspring statistical correlation with systemic hypertension.
of glaucoma patients was 9.2 times higher than in However, individuals with diastolic perfusion
controls. The Baltimore Eye Survey revealed an age- pressures less than 30 mmHg were six times more
race adjusted odds ratio of 2.85 for an association likely to have POAG than those with a perfusion
between POAG and a history of glaucoma amongst pressure of 50 mmHg or more.
first-degree relatives.33
Myopia
Central Corneal Thickness (CCT)
Myopes have more problems with vision, need glasses
Goldmann applanation tonometry is affected by the and are more frequently subjected to ocular exami-
CCT. An increase in the CCT is associated with an nation, thus having greater opportunity to be
artificially raised IOP, while a decrease in the CCT diagnosed as POAG.
causes the IOP to be less than the actual IOP. Wilson et al in a case control study have57 reported
that patients with POAG were twice more likely to
Optic Nerve Cupping have myopia than controls. The Blue Mountain Study
showed a statistical association between POAG and
The size of the physiological cup also appears to be
myopia of 1.5 diopters and more.41
another possible risk factor for POAG.34 Wide deep
physiological cups have been observed to be at higher
Migraine
risk of developing glaucomatous visual field loss. The
strong association of race and family history with Migraine headaches or a vasospastic tendency are risk
POAG is suggestive of a significant genetic basis for factors for POAG.42 However, this association remains
many cases of POAG. controversial. 43,44 Vasospasm can theoretically
The OHTS confirmed the correlation of age, large encourage optic nerve head damage by decreasing
horizontal and vertical cup to disk ratio and higher blood flow to the optic nerve head.
IOP.35 It also identified the pattern standard deviation
on full threshold perimetric testing and thin corneal Disk Hemorrhages
measurements as risk factors for POAG. Disk hemorrhages are suggestive of microinfarction
and ongoing optic nerve head ischemia . In one study
Diabetes Mellitus 56 percent of eyes with disk hemorrhages had
A statistical association between diabetes and POAG progressive optic nerve head damage as compared to
has been reported in several case control studies.36-38 13 percent in eyes with no hemorrhages.45
This may be due to the fact that diabetics often
undergo a detailed eye examination to rule out retinal PATHOGENESIS
involvement. The Baltimore Eye Survey did not find
Raised IOP
any statistical correlation between diabetes mellitus
and POAG. However, individuals where POAG was A raised IOP usually results from resistance of the
diagnosed prior to the study, a positive correlation aqueous humor outflow. This obstruction in POAG
did exist.39 The Beaver Dam40 and Blue Mountain has been associated with alterations in the
conventional outflow pathway. In the trabecular corneal edema from a raised IOP may cause colored
meshwork there is a decrease in the endothelial cell halos. Patients with advanced damage often have
number46 though cellular activity may increase with altered vision.
thickening of the basement membrane.47-49 The normal
continuous loss of trabecular meshwork cells is Evaluation
exaggerated in POAG.46,50 Loss of the trabecular
Careful determination of history and physical findings
beams is associated with an increased resistance to
often helps in timely diagnosis. These are centered
aqueous outflow resulting in decreased outflow
around ocular and systemic risk factors. A review of
facility. Alteration in the endothelial cell function also
past records helps in detailing refractive error, ocular
contributes to decreased aqueous outflow.
and/or systemic disease, medication used (with a
Collagen abnormalities within the trabecular
special emphasis on steroid usage), intolerance to
meshwork beam in eyes with POAG include frag-
medication and previous ocular surgery. Involvement
mentation, orientation changes and abnormal
of glaucoma amongst family members and impact on
spacin. 52-54 Even the inter trabecular spaces are
quality of life, should also be inquired.
decreased. There is a progressive increase in plaque
like deposits, derived from elastic—like fibres55 and a
Examination
decrease in giant cell vacuoles.56,57
Stereo-biomicroscopic examination of the anterior
Mechanism of Optic Nerve Damage segment in POAG may not show any abnormalities.
In 1857, von Graefe, after examining the fundus, However, slit lamp examination helps exclude
described glaucoma as a special type of “glauco- secondary glaucoma with open angles. Measurement
matous optic neuropathy”. von Graefe did not find a of IOP, assessing structural damage to the optic nerve,
raised IOP—because the Tonometer was introduced documenting functional loss with automated peri-
only in 1905. Today also glaucoma is considered as a metry and evaluating the status of the angle outflow
progressive optic neuropathy characterized by structures on gonioscopy are essential pre-requisites
morphological changes (optic disc cupping) resulting to diagnosis of POAG.
from the death of retinal ganglion cells which may be
pressure dependant or pressure independent. Retinal Intraocular Pressure
ganglion cell death may partly be due to apoptosis, The diagnosis of POAG generally includes an IOP
which is a programmed cell death of cells of all the measurement > 21 mmHg.
other organs of the body. A wide variety of hypothesis
Current significance of 21 mmHg: The distribution of IOP
explain the pathogenesis of the optic neuropathy in
in the general population as studied by Leydecker
glaucoma, including ischemia of the papillary nerve
(normal IOP was statistically defined two standard
head, blockage of retrograde axonal transport,
deviations above and below mean, as 11-21 mmHg)
alteration of laminar glial or connective tissue, direct
is not Gaussian (Fig. 66.1), but is slightly skewed
mechanical effect on retinal ganglion cells, and now
towards higher IOP’s (Fig. 66.1). Nearly 10 percent of
neurotransmitter (glutamate) mediated excitotoxic
death of the retinal ganglion cell. Nitric acid can also the population over 40 years can have IOP’s higher
trigger cell death. Nitric acid is found in higher than 21 mmHg, in the presence of open angles and
concentration in the optic nerve of rats and humans normal optic disks. Such individuals, who were often
with glaucoma. Inhibitors of nitric oxide formation labeled ocular hypertension, may not develop
(aminoguanidine) retard ganglion cell death in glaucoma. Classical cases of open angle glaucoma
experimental glaucoma in rats. An injury can be have a raised IOP, characteristic optic nerve head
propagated beyond its original extent by secondary changes and visual field changes in the presence of
degeneration. open angles on gonioscopy. It is now realized that
nearly 40 to 50 percent of cases of open angle glaucoma
can have an IOP less than 21 mmHg but with charac-
DIAGNOSIS
teristic optic nerve head and visual field changes
Symptomatology (normal tension glaucoma). In such cases ischemia of
POAG patients have few symptoms in the early stages. the optic nerve plays an important role and IOP is of
Rarely a high IOP may cause brow ache. Transient secondary importance. It is thus, obvious that not all
60
millimeters of Hg Corneal thickness above or below
the normal standard 0.52 mm may also impact erro-
neous tension measurements, approximately
0.5 mmHg per 10 mm difference from the standard.59
Advantages of the Goldmann tonometry 60-65
include little inter examiner variability, suitable for
gas filled eyes, follow penetrating keratoplasty and
measurements are independent of scleral rigidity. It
is however, unreliable on scarred, irregular corneas
and with thick/thin corneas.
The TonoPen is a miniaturized modification of the
MacKay-Marg. 65 The Tono-pen is commercially
available, battery operated and portable electronic
tonometer. The tip of the Tono-Pen is protected by a
Fig. 66.1: Distribution of IOP in the general population disposable latex cover, containing a 1.02 mm diameter
(solid line) versus Gaussian distribution (dotted line) plunge attached to a strain gauge transducer that
similarly extends beyond the footplate. When the
plunger is perpendicularly flattened against the
cases with IOP greater than 21 mmHg can be labeled
corneal surface, a voltage change is amplified by the
as glaucoma, just as glaucoma can exist with IOP in
transducer that is digitized and stored by a single chip
the normal statistical range. microprocessor if the voltage waveform notch is
Measurement of IOP: In clinical tonometry, IOP adequately configured.
measurement is by correlating the deformation of the The measurement is rejected if the microprocessor
globe to the force responsible for the deformation. does not sense a proper shape to the voltage wave-
Typically the globe is deformed by corneal indentation form. Two to ten valid pressure measurements are
(indentation tonometry e.g. Schiotz tonometer) or by collected, as indicated by audible clicks and a beep
corneal applanation, resulting in surface flattening, indicates the endpoint. The mean digitized value in
either directly by tonometer contact (Goldmann ) or millimeter of mercury is displayed along the bar over
indirectly by non-contact with a puff of air . Measuring a range of the coefficient of variance , from 5 to 20
the IOP by applanating the sclera has shown variable percent in 5 percent increments on a liquid crystal
results owing to non uniformity of the conjunctiva and readout. When readings of more than 30 mmHg are
ciliary body. 58 These tonometers have been used detected, the transducer sensitivity changes to
primarily to quantitate the IOP at any particular point accommodate the higher pressure range. Advantages
of time. Some designs have been adapted, in an of the Tono-Pen include 63, 66-69 scarred, irregular
attempt to monitor the diurnal variation of IOP. An corneas, post keratoplasty, IOP through bandage
additional tonometric technique, manometry directly contact lens, IOP post PRK/LASIK, similar accuracy
measures the IOP by means of ocular cannulation has in gas filled eyes upto 30 mmHg and reduced risk of,
experimental application; for clinical application it is pathogen transfer. However, the Tono-Pen underesti-
of no use. mates IOP > 30 mmHg, over estimates IOP < 10
Goldmann applanation tonometry (GAT) is the mmHg, diurnal pressure reading is unreliable for
proven gold standard for variable force tonometry in glaucoma screening.
patients with normal corneas and normal or abnormal If the detected waveforms are inadequate or
variability is excessive within a 20 second interval, the
scleral rigidity. It is based on the Imbert- Fick Law
Tono-Pen will not provide a reading and re-tapping
P=F/A (P: pressure F= Force require to flatten the
the cornea is necessary. Clearing the tip of residual
surface of an ideal sphere, A = Area of flattening. With
cornstarch from the latex cover with an air jet and
the GAT, an adjustable force is applied to a standard
calibrating the instrument daily for proper functioning
central corneal area of 3.06 mm in diameter. With this
are essential pre-requisites.
diameter, the force from the surface tension, negates
the elastic force of the cornea, resulting in a more Measurement of diurnal variation of IOP: The range of
accurate grams force × 10 scale conversion to IOP varies over a 24-hour period. Though diurnal
means “during daytime” for this clinical test it means papillary region of the optic nerve head and retinal
24 hours day and night. The pressure peaks or troughs nerve fiber layer.
on different subjects do not occur at the same time A. Intra papillary changes
but may vary throughout the day and are more • Disk size
marked in glaucoma patients. The trend is to have low • Disk shape
IOP’s during the night and elevated IOP’s early in the • Rim size and cup size
morning with a decline as the day progresses. • Rim shape (Vessel signs)
B. Parapapillary characteristics
Office diurnal: A commonly used method where
• Retinal Nerve Fiber Layer (RNFL)
information on the diurnal IOP variations consists of
• Hemorrhages
performing repeated tonometry in the clinic during
• Vessel diameter
working hours. IOP measurements can also be done
• Parapapillary atrophy (alpha and beta)
over a number of days, at different times of the day
The optic disk area is not constant among
but it is not accurate. Though office diurnals are
individuals. Some normal eyes can have small optic
practical and inexpensive there is only a 40 to 50
disks, while others can have large optic disks.72 Optic
percent chance of detecting a pressure peak.69
disk area is independent of age beyond 3 to 10 years.
Nocturnal diurnal: It involves measuring the IOP at The difference in disk size in eyes with –5 to +5
various points of time at night. A combined office and diopters of refractive error is slight.73 Myopic disk 5
nocturnal diurnal increases the likelihood of detecting have larger optic disk size as compared to hyperopia
an IOP peak. where the disk size is smaller. The optic disk is usually
slightly oval. An abnormal shape, correlates with an
Home tonometry: Applanation and indentation
increased incidence of corneal astigmatism and
tonometry can be done at home, with proper patient
amblyopia. In normal eyes, the neuroretinal rim
instruction, to obtain diurnal curves. Wilensky and
shows (Fig. 66.2) a characteristic conformation, based
coworkers used the Self Tonometer70 to show that a
on the vertically oval shape of the disk and
large number of patients with apparently well
horizontally oval shape of the optic cup. The
controlled IOP, have peaks above the measured IOP.
neuroretinal rim is the widest in the inferior disk
The IOP peaks were associated with progressive visual
region, followed by the superior disk region, the nasal
field loss, independent of the mean IOP. In certain
disk area and finally the temporal disk region (ISNT
patients, IOP peaks which may have a direct effect on
rule).
vision loss, usually disappear before the patient can
reach his doctor and may actually prognosticate
glaucomatous progression.
In the same study, with a population having a 30
percent prevalence of progressive loss of visual fields
with office IOP’s less than 22 mmHg, 75 percent of
patients who had peaks in IOP with Self Tonometry
had progressive visual loss and 75 percent of those
without peaks did not have visual field progression.
The Self-Tonometer is no longer being manufactured.
However Proview, a non-corneal- dependent tono-
meter with a pressure phosphene endpoint may prove
beneficial in detecting abnormal pressure peaks not
recorded on an outpatient basis.71 The US Food and
Drug Administration have approved Proview.
With self tonometry the timing of medication can
also be individualized so that the peak effects coin-
cides with the diurnal IOP spikes to maximally retard
it.
Fig. 66.2: A large but normal optic disk with a large cup-disk
Examination of the Nerve Head ratio.Note the normal shape of the neuroretinal rim – broadest
Glaucomatous optic neuropathy is described by inferiorly, followed by the superior disk region. The rim is
morphological changes in the intra papillary and para smallest in the temporal disk region . “ ISNT rule ”
In glaucoma, the neuroretinal rim is lost in all
sections of the optic disk with regional preference
depending on the stage of the disease. 72,74 Early
glaucoma, neuroretinal rim loss is predominately in
the inferior temporal and superior temporal disk
regions. Moderate glaucoma, marked loss of rim in
the temporal horizontal disk region and in advanced
glaucoma rim remnants are located mainly in the nasal
disk sector with layer of rim in the upper nasal than
the lower nasal region.
This regional loss of the disk sector (inferio-
temporal, superotemporal, temporal horizontal,
inferionasal and superonasal), correlates with
progression of the visual field changes with early
perimetric defects in the nasal upper quadrant of the
visual field and lastly, the island of inferiotemporal
vision. For an early diagnosis, the inferiotemporal and
superotemporal disk sectors in particular should be Fig. 66.3A: Splinter or flame shaped hemorrhages, in early
checked for glaucomatous changes.74-76 glaucoma are usually located at the inferiotemporal or
Splinter/flame shaped hemorrhage at the border superotemporal margin of the disk. Though not pathognomonic
of the optic disk is a common sign of glaucomatous for glaucoma they are suggestive of a progressive disk damage
optic nerve damage. Disk hemorrhages, rarely found in glaucoma
in normal eyes, are present in 4 to 7 percent glauco-
matous eyes. In an early glaucoma, they are usually
located in the inferiotemporal or superotemporal
disk region. They are associated with localized
retinal nerve fiber layer defects, neuroretinal rim
notches and circumscribed perimetric loss.
Disk hemorrhages are indicative (Figs 66.3A and
B) of glaucomatous optic nerve damage, even if the
visual fields are unremarkable. In addition they are
suggestive of glaucoma progression. Disk hemorr-
hages are however, not pathognomonic for glaucoma.
They also occur in other diseases like blood dyscrasias,
hypertension, diabetes, etc.
Glaucomatous optic nerve damage early diagnosis: The
most important sign of early (POAC) is a symmetry
between the optic cups of the disks of the two eyes.
Other signs of glaucomatous optic nerve damage in
ocular hypertensive eyes before the development of
visual field loss are:
1. Shape of neuroretinal rim (Fig. 66.2)
2. Size of optic cup in relation to size of the optic disk Fig. 66.3B: Evident inferior notch
3. Decreased visibility of the retinal nerve fiber layer (complete loss of neural tissue)
4. Occurrence of localized retinal nerve fiber layer
defects and hemorrhages. In eyes with small disks, the neuroretinal rim
If the rim is not markedly broader in the inferior cannot be clearly delineated from the optic cup, so
and superior disk region compared to the temporal the shape of the rim cannot be well determined. In
disk region, a glaucomatous loss of rim tissue may be these eyes, the variable cup size and column in relation
suspected in the inferior and superior disk regions of to the disk size are the most important intra papillary
the optic disk.72 factors to detect glaucomatous optic nerve damage.72
Glaucomatous versus non-glaucomatous optic neuro- Table 66.3: Checklist to assess changes
pathy: Glaucomatous and non glaucomatous optic in the optic nerve head
neuropathy have the following in common. 1. Determine disc size (Elschnig canal)
1. A decreased diameter of the retinal arterioles inclu-
2. Check for unusual disk shape
ding the presence of focal arteriolar narrowing.
3. Determine cup/rim size in relation to disk size
2. Reduced visibility of the retinal nerve fiber layer.72
Localized defects in the retinal nerve fiber layer 4. Evaluate rim shape (smallest rim width)
can be found in many types of non glaucomatous optic 5. Check RNFL (red-free illumination)
nerve damage such as in optic disk drusen and long 6. Look for disk hemorrhages: Rule out glaucoma
standing papilledema. In comparison to non glauco- 7. High myopia: Rule out glaucoma
matous optic atrophy, the glaucomatous optic neuro-
pathy is characterized by an enlarging optic cup which
fiber layer which is essential and critical in glaucoma,
deepens, and in a complementary manner the neuro-
until recently have been subjective with a high inter
retinal rim decreases. Enlargement of the optic cup
observer and intra observer variability (Table 66.3).
and loss of neuroretinal rim may also be found in eyes
The parameters of IOP and automated perimetry can
with arteritic anterior ischemic optic neuropathy and
miss the diagnosis of glaucoma, especially in the early
in a few patients who have intrasellar tumors.
stages. In fact upto 40 percent of the ganglion cells
A magnified stereoscopic view and a dilated pupil
must be lost for a detectable field loss on automated
are preferred to visualize the changes. Stereopsis is
perimetry. As optic nerve damage is irreversible early
best obtained at the slit lamp with fundus lenses like
detection is crucial. The objective of imaging of the
the Goldmann/ Zeiss four-mirror contact lens, Hruby
optic nerve head and retinal nerve fiber layer is to
lens, El Bayadi lens, or the Volk 90D lens. The three
precisely quantify (with maximum reproducibility)
dimensional view allows estimation of the cup depth,
these and also help in the early detection of glaucoma.
thinning of the neuroretinal rim, nerve fiber layer
Stereoscopic photography allows the physician to
thickness, sloping of the cup walls and ONH tilting.
document the longitudinal change in the optic nerve
A diagram aids documentation and is useful to
head. Interpretation may be subjective. Nerve Fiber
document change over a period of time.
Analysis like the GDx, provide for a quantitative
The direct ophthalmoscope provides a highly
assessment of the nerve fiber layer by measuring the
magnified view, which is useful in evaluating the
rotation of polarized light reflected from the retina. It
nerve fiber layer thickness and also subtle changes like
is assumed that the rotation is proportionate to the
nerve fiber layer hemorrhages when used in conjunc-
thickness of the nerve fiber layer and the main
tion with the stereoscopic techniques (Table 66.2). The
birefringent tissue is the retina and its birefringence
direct ophthalmoscope helps provide information in
is homogeneous. Birefringence from the cornea and
difficult situations and is indispensable in evaluating
the lens are additional confounding factors and require
patients who are unable to withstand slit lamp
compensation. The newer model of the GDx comes
examination.
with the VCC (variable corneal compensator).
Optic nerve imaging techniques in glaucoma: The The Optical Coherence Tomograph (OCT) provi-
evaluation of the optic nerve head (ONH) and nerve des for high resolution cross sectional imaging of the
Table 66.2: Techniques of optic disk evaluation

Technique Advantage Disadvantage
Direct ophthalmoscopy High magnification No stereopsis
Portable
Easily available
Small pupil
Slit lamp techniques Upright direct image Coupling fluid
Goldmann, Zeiss Lenses No air cornea interface
60 D, 78 D and 90 D lenses Convenient, good stereopsis Virtual and inverted image
and illumination Air corneal interface
human retina and nerve fiber layer. The nerve fiber • Reflection image of the optic nerve is divided into
layer measurements are automated and displayed by 6 sectors. The rim (green and blue) and the disk
quadrants, clock hour and an overall mean. Imaging area (red, green and blue) for each sector are
techniques of the optic nerve head and nerve fiber compared to a normal database and classified by
layer will help in the early detection of glaucoma and Moorfields Regression Analysis as within normal
its management (see Chapter 68). limits (signified by a green ! mark), borderline
(yellow ! point), or outside normal limits (red x).
Confocal scanning laser ophthalmoscopy: The Heidelberg • A graph with red and green vertical bars represents
Retinal Tomograph (HRT), (Heidelberg Engineering the results of Moorfields regression analysis. Each
GmbH, Heidelberg, Germany) is a scanning laser whole column represents the total optic nerve head
ophthalmoscope utilizing confocal scanning diode area for a specific sector and is divided into the
technology to provide topographic measurements of percentage of rim area (green) and cup area (red).
the optic disk and peripapillary retina.77 In a confocal Four black lines across the red/green graph reflect
system a laser beam is scanned across the retina and the percentage of (ONH) in the normal database
reflected back to a detector through a system of two that have a rim area larger than the limit delineated
conjugate pinholes, one in front of the laser source and by the line. The “predicted” line indicates that 50
the other in front of the detector. Through the use of percent of the ONH in the normal database have a
algorithms that account for eyes movements, each larger rim area than this limit. From upper to lower,
scanned image in the series can be aligned.69 respectively, the lower lines indicate that 95.0/
The original HRT has been used extensively in
99.0/99.9 percent of the ONH in the database have
research. The newer HRT II uses a fixed 15° field of
a larger rim area than these limits. If the percentage
view with 384 × 384 pixels per image plane and is
of the patient’s rim area is > the 95 percent limit,
friendlier clinically with automated fine focus and
the respective sector will be classified with a green
quality control checks to ensure image quality.78
ü (within normal limits), between 95 percent and
Moorfields regression analysis is based on samples
99 percent limits with a yellow! (borderline), and
with a refractive error of < 6D and a disk size between
with red x (outside normal limits) if lower than
1.2 and 2.8 mm2.
the 99 percent limit.78,81
HRT II is most helpful in evaluating the optic nerve
head for evaluating glaucomatous progression. • A table with the stereometric analysis of the ONH.
Measurements of optic disk stereometric parameters This table provides absolute quantification of the
by HRT are highly reproducible. Research suggests patient’s optic nerve head parameters and is not a
that there may be a subset of patients with ocular comparison to a database. The most important
hypertension in whom sequential follow-up with HRT parameters here are the rim area, rim volume, cup
may reveal optic nerve head changes which predate shape measurement, height variation contour, and
development of glaucomatous field changes. 79 mean RNFL thickness, of which cup shape measure
Advantages of the HRT II include rapid image appears to be the more predictive characteristic82—
acquisition time, lack of need for pupillary dilation the more negative the better. The cup shape
and images can be obtained through contact lenses or summarizes the distribution of depth within the
refractive errors can be compensated for prior to cup78 and is independent of the reference plane.
scanning. The topography standard deviation number serves
Once the scan is obtained, a contour line must be as an image, quality control. It should be as low as
drawn around the disk, which is most easily possible and ideally below 30.
accomplished utilizing the black and white image or • Mean height contour graph, where the height
three-dimensional image of the nerve on the monitor. difference between the red reference line and the
The recommended location to draw the contour line green height profile line corresponds to the
is on the inner edge of Elschnig’s scleral ring.80 thickness of the RNFL along the contour line drawn
The followings are displayed on the initial HRT II in the reflectance image. The profile line always
printed report81 (Fig. 66.4). starts temporal at 0° and is drawn clockwise for
• A topography image, where the cup is displayed the right eye and counterclockwise for the left. The
in red and the rim in blue and green, representing subadjacent red reference line indicates the location
sloping and stable neuroretinal rim, respectively. of the reference plane (separation between cup and
Fig. 66.4: HRT initial report for a glaucoma suspect

neuroretinal rim); it is approximately at the base Newer strategies: Threshold determination at each point
of the nerve fiber layer. of the visual field is tedious and time consuming.
• Horizontal and vertical height profiles— provides Because, by definition threshold is tested by the
information about the shape, slope, and the depth staircase algorithm, where every patient can see only
of the cup and its walls. Walls that tend to be steep 50 percent of the stimuli presented, newer techniques
or deep are suspicious. aim to make the procedure as short as possible, to
A follow-up report (Fig. 66.5) can be generated ensure that the patient maintains concentration and
beginning with the second follow-up examination thus, provides better reliability.
(third actual scan; the first and second scans are used
Swedish Interactive Thresholding Algorithm (SITA) is
to determine a baseline). The viewer will display a
similarly based on the fact that a response at one
row of topographic and reflectance images of the first
location has implications at the point tested and also
and subsequent examinations. The quality of all the
its neighboring points. Just as one tested point is
examinations being compared should be of similar
normal, other points on the visual field are likely to
quality (assessed via the standard deviation value).
be normal too.
For objective comparability. All follow-up
examinations are matched to the initial one, correcting Tendency Oriented Perimetry (TOP) is available on the
for possible shift, tilt, rotation, or magnification Octopus perimeter and takes advantage of each
differences. These displacements can be cause black response of the patient five fold. It tests and adjusts
edges to appear around the images of the follow-up the location where the stimulus is presented and
examination. 83 With the HRT II, the contour line assesses the threshold of the four neighboring
drawn in the first examination will automatically be locations by interpolation.
placed in the same location on subsequent tests to Several threshold tests are available on the two
allow for proper serial analysis. On the printed follow- commonly available Octopus and Humphrey
up report, the image is always in black and white, with perimeters. In each test a certain number of points can
significant changes in the ONH displayed in red be tested. The number of points tested in a given test
(decreased height) or green (increased height) is actually a compromise between the time applied
overlays. A stereometric analysis table will show any and precision, which depends on the type of damage
changes in the values.81 looked for as well as the diagnostic and therapeutic
implications resulting therein. The response at each
Visual field Examination threshold point is compared with a group of normal
patients. The likelihood of such a response in this
Visual field examination84 is a clinical component of
population of normal patients is expressed as a
glaucoma management. In the early stages perimetry
probability symbol for each tested point. These
is important as a diagnostic tool. Accepted definition
probability symbols increase in significance from a set
of POAG today includes the presence of visual fields
of 4 dots to a black box, p < 5 percent, < 2 percent, < 1
as a cardinal sign.1 When performed as a diagnostic
percent and 0.5 percent. A blackened box indicating
tool in glaucoma the question is “Is the field normal
that few normal subjects will have that score, does not
or abnormal”. And in case it is abnormal “ Are the
necessarily correspond to an absolute defect. Many
defects glaucomatous? ”
points with p < 0.5 percent are relative defects, their
The sensitivity of the visual field is by determining
actual threshold is available from the raw data.
the threshold value at each point by the bracketing
technique. After presenting a light stimulus the Test programs: The standard programs on the
machine waits for a yes / no response. If the stimulus Humphrey are the 30-2, 24-2, 10-2 and the macular
is not seen, the intensity of the light seen should be grid program. In the 30-2 the central 30 degrees of the
increased in steps of 4dB, till the response comes visual field are tested. It consists of 76 points 6 degrees
(machine records this as supra threshold level). apart on either side of the vertical and horizontal axes,
Subsequently, light stimuli are decreased in steps of such that the innermost points are three degrees from
2dB till the stimulus becomes invisible. (Infra- fixation. In the 24-2 program 54 points are examined.
threshold). The actual threshold is between the supra- It is near similar to the 30-2 except that the two
threshold and infra threshold. peripheral nasal points at 30 degrees on either side of
Fig. 66.5: HRT follow-up report . Areas with increased cupping are represented in red in the black and white image.
Change in parameters are listed in the stereometric parameters
the horizontal axis are included while testing the
central 24 degrees. The 10-2 program tests 68 points 2
degrees apart in the central 10 degrees. This program
helps to assess and follow up fixation characteristics
in patients with an advanced disease along with the
macular test which examines sixteen points in the
central five degrees, each being 2 degrees apart. The
efficiency and results of an examination are reflected
by the location of the points tested.
The two commonly used programs on the Octopus
are the G1X and the G2 which test 59 locations in the
central 30 degrees. Here the test points are
concentrated in the central field, arcuate region and
nasal midperiphery to maximize detection of
significant changes Fixation characteristics are
assessed with the macular program M2X which tests
45 locations, in the central 4 degrees, which are 0.7
degrees apart.
In the Humphery (Fig. 66.6) single field printout
there are eight parts:
i.. Reproducibility
ii. Reliability
iii. Gray scale
iv.. Total deviation
v.. Pattern deviation plot Fig. 66.6: Humphrey single field printout from a patient
with a moderately advanced glaucoma
vi. Numeric data
vii. Global indices and
glaucoma, assessing fixation characteristics is
viii. The glaucoma hemifield test).
important to plan ahead.
Each has to be examined serially before drawing a
How often should the fields be done? This is a
conclusion.
question often asked in glaucoma management.
Octopus single field printout (Fig. 66.7): The commonly Though there is no consensus guidelines do exist:
used seven-in-one printout is nearly identical to the 1. If the results of the field test are sufficient to confirm
Humphrey single field printout having a systematic the diagnostic conclusion, fields must be repeated
and sequential approach (reproducibility, reliability, at least once more.30 A change in therapy on the
grayscale, comparison, corrected comparison, numeric basis of a single abnormal visual field test is only
data, visual field indices and Bebie’s Curve) help in rarely appropriate.
interpretation. As before there are eight parts to the 2. Ocular hypertension: Establish a baseline and
single field printout. Each has to be examined serially perform follow up fields on the basis of degree of
before drawing a conclusion. risk for developing glaucoma. Patients with low
After determining the presence of the disease IOP, negative family history, or optic nerves that
visual field examination is used to stage the disease.2 appear healthy, test every one or two years.
Shallow or isolated field defects are characteristic of Patients with unstable high IOP or other risk
early glaucoma, whereas extensive deep deficits, factors, fields should be done every 3-6 months.
encroaching fixation are characteristic of late or end 3. Stable glaucoma: Initially every 6-12 months.
stage glaucoma. Patient compliance needs to be kept in mind. Visual
In patients with mild to moderate glaucoma visual fields by measuring the cumulative damage are
field examination is necessary to determine if disease sensitive to detect progression especially when IOP
progression has been halted. This would also hold true appears to be well controlled (assessment of
for patients with advanced glaucoma. In advanced compliance).
Fig. 66.7: Octopus single field printout from a patient with a moderately advanced glaucoma
4. Unstable glaucoma: One can ask for several fields is called “learning curve”. Thus, first tests in an
within a span of few months. This would hold good inexperienced patient should be taken with
for people who have a relative contraindication to caution.
surgery.
• To be clinically significant the visual field should
While assessing single field printouts, the following should
be kept in mind be reproducible.
• After the first field test the patient becomes more • Miotic pupils and media opacities cause a genera-
proficient. The resulting improvement in the fields lized depression of the visual fields.
Table 66.4: Differential diagnosis of POAG
Diagnosis Differentiating features
Normal-tension glaucoma IOP < 21 mmHg on diurnal testing
Creeping angle closure glaucoma Closed angle on gonioscopy
Ocular hypertension Lack of optic nerve damage
Pseudoexfoliative glaucoma Exfoliative material seen on lens capsule with dilation, irregular trabecular pigment
Steroid-induced glaucoma History of steroid use
Pigment dispersion glaucoma Iris transillumination defects, concave iris contour, marked trabecular pigment
Undiagnosed traumatic glaucoma Subtle angle recession, pigment deposition in angle, history of trauma
Juvenile onset glaucoma Anterior iris insertion
Mild inflammatory glaucoma Subtle anterior chamber cells and flare
Elevated episcleral venous pressure Dilated episcleral veins
• Changes in the visual field must correlate with modalities used. That is to prevent further
changes in the optic nerve head. damage of the retinal ganglion cells.
• Unexplained visual field defects must be To date, the only proven method to prevent
substantiated by a clinical evaluation of the retina, damage to the optic nerve head is by reducing
optic nerve or visual pathways. the IOP.
2. All treatments have side effects, hence no treatment
MANAGEMENT can be justified without assessing the risk to
benefits of treatment.
Principles
1. One of the important principles in the management Ocular Hypertension (OHT)
of glaucoma, which must be clearly defined and Traditionally OHT is defined by an IOP > 21 mmHg
understood by both the physician and the patient in the absence of glaucomatous optic nerve damage
deals with and visual field loss with open angles on gonioscopy.
• What is glaucoma? Since there is a strong association between high IOP
• What is the therapeutic goal ? and glaucoma, these patients are at risk of developing
such changes with time and warrant regular
What is glaucoma?
measurement of IOP and examination to rule out any
In glaucoma damage to different eye tissues is
damage to the optic nerve. The rate of conversion of
common. However, the primary concern is the
ocular hypertensives to POAG is approximately 1
damage to retinal ganglion cells and the optic
percent per year.85,86,87 Ocular Hypertension Study
nerve head. Damage to the optic nerve head
(OHTS) suggested a conversion rate of 2 percent. In
leads to the glaucomatous cupping. It is
the same study, patients with IOP more that 26 mmHg
partially related to high IOP.
and corneal thickness less than 555 micrometer, the
What is the therapeutic goal in glaucoma? rate was over 7 percent per year (36% after 5 years of
The objective of treatment in any disease is to follow up).
maintain or enhance a person’s health. In the In an ocular hypertensive study at the National Eye
context of glaucoma this would involve Institute of US 1637 patients with IOP > 21 mmHg
maintaining or enhancing the health of the followed up for 60 months gives some clue whether
person, restoring or at least preventing visual OHT cases need any therapy. In this study the patients
loss and enhancing the person’s emotional, were divided into two groups: One group topical
spiritual, psychological and physical health medication used to lower 20 percent IOP. The other
without causing any damage by the therapeutic group was observed without any therapy. After 60
months the cumulative probability of developing Treatment is usually begun with a topical drug.
POAG was 44 percent in the medicated group and 9.5 When drugs fail to control the intraocular pressure,
percent in the observation group. The result of the laser energy applied to the trabecular meshwork (laser
study indicates that topical hypotensive medication trabeculoplasty) may help increase aqueous outflow.
is effective in delaying the onset of POAG in the OHT When drugs and laser trabeculoplasty fail to control
group.88,89 the intraocular pressure, a new route for aqueous
The aim of treatment today is to lower the IOP to a egress can be created surgically.
level where the rate of loss of ganglion cells does not
exceed the loss of ganglion cells from the normal age Medical Treatment
related decay by apoptosis. This level of IOP is called Medical treatment is both, an art and a science. It is
target pressure. The target pressure varies amongst necessary to tailor the treatment to the needs of the
patients and may need to be modified during the patient,91 when doing so, the following need to be kept
course of the disease, if damage to the ONH progresses in mind:
despite IOP’s within the desired target range. A. The target tissues of topically applied ocular
hypotensive medication are within the eye. Ocular
Choosing a Target Pressure conditions which can limit bioavailability such as
tear film deficiency, corneal scarring, chronic non-
Although it is difficult to specify exact guidelines for
specific blepharoconjunctivitis and intraocular
target IOP levels, the following levels may be used as
inflammation may co-exist.
a reasonable guide.90
B. Patient’s compliance with instructions for instilling
1. Any IOP greater than 32 mmHg should be reduced
eye drops can be improved by
to at least the low 20s.
i. Educating patient about nature of the disease
2. Eyes with cup-to-disk ratios greater than 0.5, slight
ii. Emphasizing need for life long treatment.
asymmetry of the cup-to-disk ratio or IOP, high
iii. Assessing patient’s ability to instill eye drops
myopia, a strong family history of glaucoma, or correctly and in accordance to dosage schedule.
African ancestry should have IOPs below iv. Educating patient about possible side effects
18mmHg. v. Avoiding eye drops with specific side effects,
3. Patients with early glaucomatous optic disk on individual patients.
damage and visual field loss above or below central vi. Use drops which affect patients daily routine
fixation should have IOPs below 18 mmHg. minimally.
4. Patients with moderate to advanced glaucomatous vii. Can the treatment regimen maintain the desired
optic disk damage (cup-to-disk ratios greater than target IOP for 24 hours in a day
0.8) and superior and inferior arcuate scotomatous viii. Is the patient amenable to follow up to assess
visual field loss should have IOPs consistently the response to treatment.
below 15 mmHg (many would choose a target of ix. Simpler the treatment regimen, better the
12 mmHg) compliance.
5. Patients with advanced glaucomatous optic disk x. Fewer side effects mean better patient
damage (cup-to-disk ratios greater than 0.9) and compliance
extensive visual field loss within the central 10 xi. Multiple drops are less likely to be instilled
degrees of fixation require an IOP below 12 mmHg. correctly as compared to single preparations.
xii. Combination drops are more likely to be
TREATMENT instilled correctly than drops from multiple
To Decrease IOP bottles.
xiii. Fixed drug combinations offer the advantage
Intraocular pressure can be lowered either by of less toxicity by preservatives and lower costs,
decreasing the amount of aqueous humor produced than fixed preparations
by the ciliary body or by increasing its outflow xiv. Combination therapy with identical mechanism
through the trabecular meshwork, through the of action should be avoided.
uveoscleral pathway, or through a surgically created Most drugs for glaucoma are applied topically.
pathway. Because of the brief contact time and the strong
protective barrier of the eye, the drug solutions need trabeculoplasty (ALT) / selective laser trabeculoplasty
to be concentrated. Excess drug drains through the (SLT ) provides a clinically significant reduction of IOP
nasolacrimal duct into the nose, where it may be in approximately 75 percent of initial treatments.98 The
absorbed into the systemic circulation. For example, advantages of trabeculoplasty over medical treatment
Timolol administered to one eye enters the blood- include lack of systemic adverse effects, minimal
stream in a concentration sufficient to cause a measu- patient compliance, and decreased incidence of ocular
rable decrease in intraocular pressure in the opposite problems that could possibly compromise subsequent
eye.92,93 Patients who use topical drugs should be surgical therapy.99
taught to occlude the nasolacrimal duct with either Because it lacks the complications of filtering surgery,
digital pressure or simple eyelid closure for about five trabeculoplasty should also be considered for patients
minutes, this maneuver increases intraocular drug inadequately controlled on maximum medical
concentrations and decreases systemic concen- therapy. However, it seldom reduces the number of
trations.94 required glaucoma medications. Patients uncontrolled
The drug given initially to patients with most types by medical therapy, initial treatment with ALT
of glaucoma is a non selective, topical beta adrenergic- provides better preservation of visual function than
antagonist drug, such as Timolol maleate , because of trabeculectomy.63 Indications for ALT are:
the excellent pressure lowering efficacy, long duration 1. Patients who are poor candidates for conventional
of action, and few ocular side effects of this class of medical management.
drugs. A second drug, if needed, might be a prosta- 2. Patients in whom a target IOP level is unlikely to
glandin analogue (such as Latanoprost), an alpha 2 be achieved with topical medications.
adrenergic agonist (Brimonidine). Topical carbonic 3. Visual field loss such that any further progression
anhydrase inhibitors (such as Dorzolamide) constitute would affect the patient’s quality of life.
the third choice. Cholinergics like Pilocarpine have 4. Patients who have a known rate of progression,
often been relegated to the last to the choice because such that quality of life would suffer unless rapid
of their ocular and visual side effects. However in the IOP stabilization occurs at a target pressure level.
Indian context they provide effective IOP lowering Results on outcome of ALT in Indian eyes are
which is cost effective. It is important to select the right limited.
candidates – aphakes and pseudophakes who are not
high myopes. Surgical Treatment
When therapy with a topical drug is instituted, it Glaucoma surgery is strongly indicated in patients
is to be applied to one eye, with the opposite, untreated who have a progressive visual field loss or optic nerve
eye used as a control. This method makes it possible damage on MTMT. Indications for primary filtering
to determine whether any change in intraocular surgery include.100
pressure is due to the drug or to the normal variation 1. Patients who are poor candidates for conventional
of intraocular pressure. However, this is usually not medical treatment.
possible in the Indian scenario. 2. Patients in whom the target IOP is unlikely to be
If there is no response, the drug should be disconti- achieved with topical medications alone.
nued in order to avoid unnecessary cost and side 3. Visual field loss is such that further progression is
effects. If there is a substantial decrease in intraocular likely to affect the patients quality of life
pressure but the pressure remains high, another drug 4. Patients with rapidly progressive glaucomatous
should be added. Different classes of drug have optic neuropathy where quality of life would suffer
additive effects on intraocular pressure.95,96 Exceptions unless rapid IOP lowering occurs to the desired
are nonselective beta adrenergic-antagonist drugs and target level.
nonselective adrenergic agonist drugs, which have Filtering surgery reduces the IOP and often
little additive effect when given together. 96,97 eliminates the need for medical treatment. Although
Cholinergic drugs and Prostaglandins with adequate effective in 85 to 95 percent of previously unoperated
spacing can be used together. eyes, the potential success of the operation must be
measured against the potential effect of complications
Laser Treatment on the patient’s quality of life.
Most patients with POAG can be controlled by Although long-term control is often achieved with
antiglaucoma medications. Alternatively, argon laser filtering surgery, many patients will require repeat
Table 66.5: Side effects of glaucoma medications 496
Medication Mechanism of Efficacy Ocular side effects Systemic side effects Relative
Class Action contraindications
Parasymoathomimetics
Pilocarpine HCl 1-4% Increased outflow through ++(+) Miosis, dim vision Headaches brow ache Uveitis, neovascular glaucoma,
Pilocarpine nitrate 1,2, 4% the trabecular meshwork accommodative spasm, retinal breaks, succinylcholine
induced myopia, induced general anesthesia
posterior synechiae,
cataracts*, iris cysts*
pseudopemphigoid*,
retinal detachments
Non-selective adrenergic
agonists
Dipivefrin HCl 0.1% Increased outflow +(+) Hyperemia, Headache, anxiety, Aphakia, pseudophakia,
blepharoconjuctivitis, palpitations, elevated narrow angles, patients using
adrenochrome deposi- blood pressure resperine, MAO inhibitors or
tion, mydriasis, pseudo- incidence (fewer side trycylic, antidepressant, labile
pemphigoil, cystoid effects with Dipivefrin) hypertension. Cardiac
macular edema, stains, arrhythmias thyrotoxicosis
soft contacts lenses
α-Adrenergic agonists Decreased aqeous production ++(+) Toxic dermatitis, Dry mouth, lethargy Babies and young children
Aproclonodine 0.5 , 1% Increased unveoscleral outflow blepharoconjunctivitis, patients using MAO inhibitors
Brimonidine 0.15 , 0.2% ++ lid retraction+, or sedatives, significant cardiac,
conjunctival blanching+, renal hepatic, or cerebro-
hypotension and apnea vascular disease,
in babies and children Raynaud’s disease,
Section 5: Glaucoma
thromboangiitis obliterans
β Adrenergic Decreased aqueous production +++ Corneal anesthesia, Bronchoconstruction, Asthma, chronic obstructive
antagonists selective ++ blepharoconjunctivitis, bradycardia, exacerbates pulmonary disease,
Betaxolol HCL 0.25, 0.5% betaxalol delayed choroidal heart block and con- bradycardia second or third
detachments gestive heart failure, degree heart block, congestive
fatigue, malaise, heart failure brittle diabetes,
Non selective depression, dizziness, thyrotoxicosis, myasthemia
Timolol Maleate 0.25, 0.5% impotency, memory gravis. Use with caution in
Levobunolol 0.5% loss (fewer side patients taking resperine ,
Carteolol 1% effects with betaxolol) guarnethidine quinidine
Metipranolol 0.3% (Contraindications of greater
concern with non-selective β-
blockers)
Contd...
Contd...
Medication Mechanism of Efficacy Ocular side effects Systemic side effects Relative
Class Action contraindications
Prostaglandins
Latanoprost 0.005 Increases Unveoscleral outflow ++++ Iris color change Myalgias
Bimatoprost 0.03% hazel and mixed green/
Travoprost 0.004% (brown irides),
Unoprostone conjunctival hyperemia,
uveitis, cystoid, macular
edema, hypertrichosis
CAIs Decreases aqueous production
+++ Transient myopia, Metallic taste to food, Sulfa allergy, Kidney stones,
Oral delayed choroidal malaise, depression, diabetic ketoacidosis, chronic
Acetazolamide detachments weight loss, anorexia, respiratory acidosis, hypo-
125, 250 mg chronic diarrhea, kidney kalemia, patients using
stones, Stevens-Johnson thiazide diuretics or phenytoin
syndrome, aplastic sodium, sickle cell anemia,
anemia, metabolic hepatic disease
acidosis, hypokalemia,
acidosis with
chronic aspirin use
Topical ++(+) Burning on instillation Metallic taste, Significant sulfa allergy

Dorzolamide 2% (dorzolamide) theoretical potential
Brinzolamide 1% for same side effects
as oral CAIs but no
definitive evidence
to date
Chapter 66: Primary Open Angle Glaucoma
497
surgery or supplemental medical management, or To Protect Irreversible Damage of Glaucoma

both. Glaucoma surgery combined with cataract The end result in glaucoma is irreversible damage to
extraction, may be indicated in patients who require the optic nerve head. Since the end result is damage
visual rehabilitation with cataract extraction, in to the retinal ganglion cells and because factors other
addition to IOP lowering. than IOP can be responsible extensive research in vitro
Aqueous drainage devices are generally reserved and in vivo is ongoing to detect pharmacological
as a last resort for patients with glaucoma that is interventions aimed at preventing retinal ganglion cell
refractory to standard filtering surgery. This includes death (neuroprotection). Some of these include:
patients with extensive conjunctival scarring, chronic a. Prevention of initiation of apoptosis program by
inflammation, and ocular trauma. IOP lowering with brain derived neurotrophin delivery to retinal
glaucoma drainage devices is generally not as effective ganglion cell (RGC).
as with filtering surgery. Cyclophotocoagulation is b. Protection of undamaged but at risk axons and
another alternative for patients with glaucoma that is ganglion cells from noxious stimuli released by
refractory to other interventions and where the visual proximate damage to issue or retrograde axonal
potential is poor. degeneration-NMDA glutamate receptor
Table 66.6: Landmark studies in Glaucoma (abridged 101)

Name Study design No. of Follow up Results
patients duration
Ocular IOP > 21 mmHg, no disk 1,637 5+ 20% lowering of IOP reduced risk of
Hypertension or VF damage effect of (25%) black) developing glaucomatous VF loss from
Treatment 20% medical lowering 9.5% to 4.4%. Age, disk damage IOP, and
study 3a, 4,59 of IOP vs observation corneal thickness associated with damage
on visual field loss/nerve conversion to POAG
Early manifest Newly diagnosed POAG; 255 4+ years Ongoing study

Galucoma Trial treatment with ALT plus
(EMGT) (62) beta blocker vs no treatment
Collaborative Newly diagnosed POAG, 607 5+ years No difference in VF change between

Initial Glaucoma immediate filtering surgery (38% black) treatment modalities. Higher rate of
Treatment Study vs initial treatment with cataracts with filtering surgery
(CIGTS) (63,63a) medication
Glaucoma Laser Newly diagnosed POAG 203 6-9 years Initial laser trabeculoplasty found as
Trial (GLT) (64) effective as initial topical Timolol to lower
IOP and preserve vision
Advanced Black and white patiens 581 7 years Greater IOP reduction with trabeculec-
Galucoma with advanced POAG, (57% black) tomy first. For black patients, better visual
Intervention Study laser trabeculoplasty first preservation with laser first; for white
(AGIS) (65,66) vs traveculectomy first, patients, better visual preservation with
followed by opposite trabeculectomy first (65). Low IOP
intervention if first associated with reduced visual field defect
intervention fails progression (66)
Normal Tension Combination of Medical, 140 5 years Reduction of normal pressures by 30%
Glaucoma Study laser and surgical treatment slowed the rate of glaucomatous pro-
(67,68) to produce a 30% reduction gression in a significant number of
in IOP vs no treatment in patients
patients with progression
normal tension glaucoma
antagonists (block excitotoxicity), Calcium 5. Wallace J, Lovell HG. Glaucoma and intraocular pressure in
Jamaica. Am J Ophthalmol 1969;67:93.
channel blockers (block program by which
6. Lindblom B, Thorborn W. Prevalence of visual field defects
apoptosis is signaled) and active or passive due to capsular and simple glaucoma in Halsingland,
immunization against myelin basic protein (MBP) Sweden. Acta Ophthalmol 1982;60:353.
c. Rescue of marginally damaged axons and RGC – 7. Tielsch JM, Sommer A, Katz J.et al. Racial variation in the
prevalence of primary open-angle glaucoma. The Baltimore
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Nitric Oxide synthase inhibitors and Lazaroids 8. Klein BE, Klein R, Sponsel WE, et al. Prevalence of glaucoma.
(which block lipid peroxidation) The Beaver Dam Eye Study. Ophthalmology 1992;99:1499.
Various strategies for regeneration of RGC axons 9. Coffey M, Reidy A, Wormald R, et al. Prevalence of glaucoma
in the west of Ireland. Br J Ophthalmol 1993;77:17.
include: 10. Dielemans I, Vingerling JR, Wolfs RC, et al. The prevalence
a. Utilizing the ability of axons to extend into of primary open-angle glaucoma in a population-based study
peripheral nerve grafts—autologous sciatic nerve or in the Netherlands. The Rotterdam Study. Ophthalmology
1994;10:1851.
other nerve grafts, donor grafts with HLA match- 11. Leske MC, Connell AMS, Schachat AP, et al. The Barbados
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peripheral nerve to induce extension and geneti- Ophthalmol 1994;112:821.
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the prevalence and risk factors of glaucoma in St. Lucia, West
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b. Regulating the immune response within the optic 13. Mitchell P, Smith W, Attebo K, Healey PR. Prevalence of open-
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14. Wensor MD, McCarty CA, Stanislavsky YL, Livingston PM,
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15. Sood NN, Agarwal HC. Glaucoma statistics. Presented at the
CONCLUSION National Symposium on Glaucoma, New Delhi, 1987
16. Hattenhaer MG, Johnson DH, Ing HH, et al. The probability
Primary open angle glaucoma is characterized by a of blindness from open-angle glaucoma. Ophthalmology
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22. Sommer A, Tielsch JM, Katz J, et al. Relationship between
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41. Mitchell P, Hourihan F, Sandbach J, Wang JJ. The relationship Tonometry in normal and in post-keratoplasty eyes. Br J
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42. Phelps CD, Corbett JJ. Migraine and low-tension glaucoma: of the Oculab Tono-Pen. Am J Opthalmol 1987;104:168.
a case-control study. Invest Ophthalmol Vis Sci 1985;26:1105. 66. Levy Y, Zadok D, Glovinsky Y, et al. Tono-Pen versus
43. Klein BEK, Klein R, Meuer SM, Goetz LA. Migraine headache Goldmann tonometry after Excimer laser photorefractive
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44. Wang JJ, Mitchell P, Smith W. Is there an association between precision of the Tono-Pen in measuring intraocular pressure
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Graefes Arch Klin Exp Ophthalmol 1979;209:269. Hyertension Treatment Study. A randomized trial determines
71. Fresco BD: Anew tonometer-the pressure phosphene that topical ocular hypotensive medication delays or prevents
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72. Jonas JB, Budde WM, Panda-Jonas S. Ophthalmoscopic 89. Alvarado J, Murphy C, Juster R. Trabecular meshwork
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73. Ramrattan RS, Wolfs RCW, Hofmann A, Jonas JB, de Jong 90. American Academy of Ophthalmology. Preferred Practice
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74. Hitchings RA, Spaeth GL. The Optic disk in glaucoma. II: Haefliger IO, Flammer J. (eds.) Nitric Oxide and Endothelin
Correlation of the appearance of the optic disk with the visual in the Pathogenesis of Glaucoma. Lippincott Raven/
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75. Hitchings RA, Wheeler CA. The optic disk in glaucoma. IV: 92. Zimmerman TJ, Kaugman HE Timolol: a beta-adrenergic
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76. Schwartz B. Optic Disk changes in ocular hypertension. Surv 93. Shin DH. Bilateral effects of monocular Timolol treatment.
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77. Zangwill LM, Bowd C, Berry CC, et al. Discriminating 94. Zimmerman TJ, Kooner KS, Kandarakis AS, Ziegler LP.
between normal and glaucomatous eyes using Heidelberg Improving the therapeutic index of topically applied ocular
Retina Tomograph, GDx Nerve Fiber Analyzer and Optical drugs. Arch Ophthalmol 1984;102:551.
Coherence Tomograph. Arch Ophthalmol 2001;119:985. 95. Villumsen J, Alm A. The effect of adding prostaglandin F2
78. Clinical applications of scanning laser ophthalmoscopy- alphaisopropylester to Timolol in patients with open angle
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79. Kamal DS, Garway-Heath DF, Hitchings RA, Fitzke FW. Use 96. Kass MA. Efficacy of combining Timolol with ocular
of sequential Heidelberg Retina Tomograph images to antiglaucoma medications. Surv Ophthalmol 1983;
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2000;84:993. Combined Timolol and epinephrine therapy for open angle
80. Roff EJ, Hosking SL, Barnes DA. The influence of contour glaucoma. Surv Ophthalmol 1983;28:Suppl:280.
line size and location on the reproducibility of topographic 98. Dielemans I, Vingerling JR, Wolfs RCW, et al. The prevalence
measurement with the Heidelberg Retinal Tomograph. of primary open-angle glaucoma in a population-based study
Opthal physiol Optics 2001;21:173. in The Netherlands. The Rotter-dam Study. Ophthalmology
81. HRT II. How to read the printout brochure provided by 1994;101:1851.
Heidelberg Engineering. 99. Jampel HD. Laser Trabeculoplasty is the treatment of choice
82. Lester M, Mikelberg FS, Swindale NV, Drance SM. ROC for chronic open-angle glaucoma. Arch Ophthalmol
analysis of Heidelberg Retina Tomograph optic disk shape 1998;116:240.
measures in glaucoma. Canad J Ophthalmol 1997;32:382. 100. Hitchings R, Surgery is the treatment of choice for open-angle
83. HRT II Operating Instructions, Software version 1.6 (revision glaucoma. Arch Ophthalmol 1998;116:241.
1.6-aD, April 2001). 101. Allen MY and Higginbotham: Primary Open Angle Glaucoma
84. Johnson Chris. Perimetry in , Morrison JC and Pollack IP in Morrison JC and Pollack IP Glaucoma Science and practice:
Glaucoma Science and practice :Theime 2003;125. Theime 2003;153.
Chapter 67
Normal Tension Glaucoma

S Choudhury
Normal tension glaucoma (NTG) or low tension According to Drance 7 the term low tension
glaucoma (LTG) refers to a clinical entity which com- glaucoma is a misnomer, since the intraocular pressure
prises of glaucomatous optic nerve head change and is rarely low in this disease, but rather in the normal
corresponding glaucomatous visual field defects, open range. He proposed that the condition can be called
angles without elevated intraocular pressure and “glaucoma with normal pressure”. Another possibility
absence of any contributing ocular or systemic could be that the low IOP in NTG could be due to
disorders. decreased central corneal thickness (CCT) showing
Low tension glaucoma was first described by Von lower IOP during tonometry.
Graefe in 1857 without instrumental tonometry but
after ophthalmoscopic examination. There was CLINICAL PICTURE
vigorous opposition to the concept of glaucoma
The clinical picture of normal tension is similar to that
without high pressure but Von Graefe stuck to his own
of to primary high tension glaucoma except for the
belief in the existence of the condition. The intro-
absence of elevated intraocular pressure. Patients
duction of the Schiötz tonometer in 1905 and its
affected by this condition often have borderline or low
acceptance by the clinicians were followed by
facilities of outflow and wide diurnal and postural
additional reports of NTG.1 By the middle of the
fluctuations of intraocular pressure. Clinical presen-
twentieth century, the existence of normal tension
tation may be of two modes. They either complain of
glaucoma was firmly established, although it was
loss of vision or visual difficulties resulting from gross
thought to be uncommon.
visual field loss detected all on a sudden, or the
abnormal optic nerve head appearance noted during
DEFINITION
routine eye examination. The disease is frequently
A number of definitions of normal tension glaucoma missed unless a careful optic nerve head evaluation is
have been proposed from time to time. Von Graefe’s performed by Hruby or 78 diopter lens, and slit lamp
original definition of low tension glaucoma is purely is used to examine with stereopsis under high magni-
descriptive, viz. “presence of cupping of the optic disc fication. Controversy remains over the appearance of
without palpably elevated intraocular pressure”. the optic nerve head in normal and high tension
Duke-Elder and Jay2 included the abnormality of glaucoma. Duke-Elder and Jay2 could not find any
aqueous humor dynamics in addition to cupping and difference in the appearance of the optic nerve head
visual field loss while Chandler and Grant and in primary open angle glaucoma (POAG) and normal
Hoskins3,4 included progressive visual field loss and tension glaucoma (NTG). Epstein8 in his study found
progressive optic nerve cupping in their definitions no contributing difference. Levene9 did not find any
of low tension glaucoma. Spaeth, 5 Kolker, and difference but he felt that there was disproportion
Hetherington6 stressed that NTG should include optic between the amount of cupping and visual field loss
nerve damage induced by intraocular pressure even in the two conditions and optic disk hemorrhage was
though the intraocular pressure is mostly found to be more frequent with NTG. Anderson10a suggested that
within normal range in population studies. peripapillary halos are more common in NTG.
Chapter 67: Normal Tension Glaucoma 503
Disk hemorrhage is due to leakage of blood from
the capillaries of the optic disk or adjacent para-
papillary area of the upper and/or lower pole of the
optic disk. Disk hemorrhage is one of the risk factors
of POAG and it is more common in normal tension
glaucoma than in POAG. The hemorrhage, usually
splinter-shaped and disappears in 2 to 3 days. It is
mostly found in the temporal side of the poles of the
disk, more commonly in the infero-temporal quadrant
of the disk. When blood is more than a splinter, blood
may travel along the underlying nerve fiber bundles
near the disk margin resembling a flame-shaped
hemorrhage. The ocular causes of disk hemorrhage
are incipient central retinal vein occlusion, ischemic
optic neuropathy, papillitis, diabetic retinopathy and Fig. 67.1: Disc appearance of a case of normotensive
posterior vitreous detachment. 10b However, disk glaucoma (Note: shallow cupping)
hemorrhage over the optic disk may sometimes be
seen in some nonocular causes like blood dyscracias, type of visual fields in both conditions are comparable.
hypertension, diabetes mellitus and anemia. Some observed the following differences: (a) defects
In NTG disk hemorrhage is present in 30 percent in high tension glaucomas are more diffuse, while
and in POAG 10 percent of cases of open angle those in low tension glaucomas are more localized
glaucoma having evidence of optic nerve damage.11a within 10 0central visual field (b) defects in high
Most significant feature of disk hemorrhage in NTG tension glaucoma are evenly distributed over the
is that in course of time field defect is likely to upper and lower half of the visual fields than in low
deteriorate in most of the cases.10a tension glaucoma; (c) defects in low tension glaucoma
Greve and Geijssen11b found that patients with high have steeper slopes and are closure to fixation (Figs
intraocular pressure tended to have larger and steeper 67.2A and B).
excavations of the optic nerve head whereas patients The progression of visual field damage in normal
with LTG had more pale, sloping and “moth eaten” tension glaucoma is most likely multifactorial.
optic nerve heads. The effect of age may play a major Diabetes mellitus, choroidal sclerosis, peripapillary
role. Caprioli and Spaeth12 found that the neural rims atrophy or venous filling time, had significant
were significantly thinner in the temporal and influence on the progression of visual field damage
inferotemporal portions of the disc and the cups had in NTG, whereas Araie et al19 observed that cup: disk
sloping margins in LTG (Fig. 67.1). However, with the ratio, intraocular pressure, and relative size of
advent of computerized optic disk topography King parapapillary chorioretinal atrophy had a significant
et al 13 reported no detectable difference in the influence on progression of visual field defect in NTG.
appearance of the optic nerve head of NTG compared In the early stages visual field study reveals field
and primary open angle glaucoma. defects within 100 of the fixation spot.
Splinter hemorrhages of optic disk were noted with As a rule, NTG is seen in older individuals
greater frequency in patients with normal tension especially those over the age of 60 years. There is an
glaucoma. Drance et al14-16 pointed out that their increased prevalence of cerebral infarcts in patients
presence is a risk factor for future progressive optic with NTG. Indirect evidence of neuronal loss is also
nerve damage. Retrospective studies by Drance,15 evident by the greater extent of corpus callosum
Chumbley,17 Levene9 and Kitazawa18 revealed the atrophy in patients with NTG; and it is also postulated
presence of optic disk splinter hemorrhages in 24.4 that NTG is an accelerated form of ageing of the
percent, 10.4 percent, 11.3 percent and 20.5 percent, nervous system20 (Figs 67.3A and B).
respectively; but prospective study by Kitazawa The disease appears to occur more often in women
showed a much higher incidence (43.1%). The opinions than in men which also reflects the fact that there are
of researchers on the existence of a difference between generally more women than men in the elderly popu-
visual fields in high tension and normal tension lation of Western societies. No clear association exists
glaucoma are divided.9-12 One group believes that the between normal tension glaucoma and race or
Fig. 67.3A: MRI findings of corpus callosum of a normal

patient (Courtesy: Ophthalmology 102, 11, 1995)
Figs 67.2A and B: (A) Visual field defect of a 72 years male

patient of normo tensive glaucoma. (B) Visual field defect of
the patient after one year with medication (progressive type)
refractive error, but there is some evidences that black

patients are at a greater risk and greater prevalence
of axial myopia in low tension glaucoma patients
compared with patients of high tension glaucoma.21
In NTG there is an association between systemic
blood pressure and optic nerve damage. Hypotension
of one form or another, including postural
Fig. 67.3B: MRI findings in low tension glaucoma thin corpus
hypotension, may be more prevalent in patients with callosum in low tension glaucoma (Courtesy: Ophthalmology
NTG.22 Patients with NTG have significantly greater 102, 11, 1995)
nocturnal blood pressure drops than control.23 Drance
pointed out that NTG patients often have a history of NTG patients.7 A large number of patients with NTG
a previous acute hypotensive episode, or “hemodyna- and concomitant systemic vascular disease is quite
mic crisis”. Other studies also have found a high striking. Goldberg et al24 found a higher prevalence
prevalence of a history of a hemodynamic crisis in of cardiovascular disease and a sedentary lifestyle
among NTG patients than among ocular hypertensive Others
controls. Migraine is strikingly more common among
A. Ocular disorders:
patients with NTG than in patients of high tension
1. Myopia (progressive)
glaucoma, ocular hypertension or normal patients.25
2. Retinal degenerations
DIFFERENTIAL DIAGNOSIS 3. Myelinated nerve fibers
4. Branch vascular occlusions
Many conditions can produce visual field loss and an
5. Choroidal nevus, melanomas, rupture
abnormal appearance of the optic disk without an
6. Chorioretinal atrophic patches.
elevated intraocular pressure or it can be said that the
B. Systemic vascular conditions:
elevated intraocular pressure has been present but is
1. Severe anemia
undetected or an “ersatz glaucoma” (congenital or
2. Acute blood loss and hypotensive episodes
acquired optic nerve diseases that are sometimes
3. Carotid artery obstruction.
associated with changes in the optic nerve and visual
C. Hysteria and malingering.
field loss that bears a superficial resemblance to
The concept of “burned out glaucoma” is trouble-
glaucoma).
some. It is a condition seen in an older patient with
A modified classification (from Diagnosis and
extensive cupping and visual field loss, normal intra-
Therapy of the glaucoma by Becker and Schaffer’s)
ocular pressure and a very low outflow facility. These
may be found useful to understand the differential
patients are thought to have had high intraocular
diagnosis.
pressure in the past, but because of the ciliary body
Glaucoma atrophy and concomitant hyposecretion, they now
have normal intraocular pressure.
A. Elevated intraocular pressure not detected:
1. Undetected wide diurnal variation EPIDEMIOLOGY
2. Low scleral rigidity
3. Systemic medications The prevalence of a disease is largely dependent on
4. Elevation of IOP in supine position only. the definition of the disease. A very restrictive defi-
B. Glaucoma in remission: nition that excludes certain classes of patients will
1. Postcorticosteroid administration result in a much lower prevalence than a broad, widely
2. Pigmentary glaucoma inclusive definition. The higher the pressure used as
3. Associated with postuveities or trauma the cut off between normal and high tension glaucoma,
4. Glaucomatocyclitic crisis the higher the prevalence. More frequent measure-
5. Burnt out glaucoma. ment of intraocular pressure may reveal high tension
glaucoma. Evidence from several independent studies
Ersatz Glaucoma suggests that incidence of normal tension glaucoma
A. Congenital optic nerve conditions: is fairly high. Hollows and Graham26 in Wales showed
1. Pits 35 percent and Leibowitz et al27 at the Framingham
2. Colobomas eye study found 52.5 percent to be as much as 65.6
3. Tilted disks. percent.
B. Compressive lesions of optic nerve and chiasm:
1. Tumors Work-up
2. Aneurysms To develop a rational approach to the diagnostic
3. Cysts evaluation of a patient presenting with cupping of the
4. Chiasmatic arachnoiditis. optic nerve, visual field loss and normal intraocular
C. Ischemic optic neuropathy: pressure, a thorough and meticulous work-up
1. Arteritic including a careful history is essential. This includes
2. Nonarteritic. information about previous elevation of intraocular
D. Drusens of the optic nerve head pressure, inflammation, ocular trauma, present and
E. Demyelinating conditions past medication, exposure to toxin, etc. Special
F. Inflammatory diseases attention should be paid to history of systemic
G. Hereditary optic atrophy. corticosteroid therapy for eye or skin conditions.
Patients should be asked for hemodynamic crisis, diseases in patients with normal tension glaucoma is
including blood loss, anemia, arrhythmias, transfu- also high.
sions, and hypotensive episodes. General examination Electron microscopic study of trabecular mesh-
includes complete physical examination, including work reveals that in all cases, the trabecular beams
blood pressure and electrocardiography. Auscultation appear thickened. There are clusters of lattice (curly)
and palpation of the carotid arteries may reveal collagen deposited predominantly within the elastic
obstructive diseases. Neurological examination is also like fiber sheaths. The most surprising finding is the
necessary. Blood tests include an erythrocyte large amount of SD-plaque material, deposited
sedimentation rate, measurement of hematocrit and beneath the endothelial lining of Schlemm’s canal and
hemoglobin levels, and antinuclear antibodies and within cribriform layer. The inner wall appeared
serologic tests for syphilis. Carotid angiography to rule thickened and somewhat distorted by these unevenly
out obstructive diseases. Routine computed tomogra- distributed clusters of plaque.Between the trabecular
phy scans of skull and orbit or magnetic resonance lamellae, elongated and often enlarged trabecular cells
imaging is still a controversy, but may be required are found to contain a well developed endoplasmic
when there is progressive visual field loss or when reticulum with many cisternae, golgi complexes,and
excessive pallor of the optic disk is seen relative to the mitochondria.Lipid inclusions are also occasionally
amount of cupping. seen (Fig.67.4).
It is very important to assess the diurnal variation These observations indicate that in NTG, the trabe-
of the intraocular pressure. The patient should be cular cells are stimulated by some unknown factors
available for tonometry every 2 hours during the to produce extracellular materials, which appears to
course of the day in the sitting and supine position. accumulate within the cribriform layer.
Tonography may be performed to assess outflow
facility, but is rarely helpful in the diagnostic
TREATMENT
evaluation of NTG.
The objective of treatment of NTG is not to lower
pressure but to arrest visual field defect progression
PATHOGENESIS
and to prevent blindness.
Controversy surrounds the pathogenesis of NTG. The natural history of NTG is ill-understood.
Some authorities believe NTG is a variant of open Chumbley and Brubaker17 reviewed 34 eyes of 17
angle glaucoma in which the optic disc demonstrates patients with more than one visual field examination
great vulnerability to the effects of intraocular and who were followed for 4 to 12 years. They found
pressure. Other authorities believe NTG and POAG that 41 percent of these patients showed progression
have different etiologies. Another possibility is that
the central corneal thickness is less than normal
therefore on tonometry lower tension is recorded—
otherwise it is a high tension open angle glaucoma.
There are ischemic and mechanical theories about
the pathogenesis of normal tension glaucoma and
damage to the optic nerve fibers. The ischemic theory
suggests that poor blood perfusion of the optic nerve
head causes ischemia and resultant loss of optic nerve
fibers.28,29 The mechanical theory suggests that the
weakness of the supporting tissues of the optic nerve
head makes it susceptible to mechanical deformation
by intraocular pressure with resultant nerve fiber
damage.30 There may be systemic vascular abnor-
malities in normal tension glaucoma. Incidence of Fig. 67.4: Low tension glaucoma. Electron microphotograph
myocardial ischemia in patients with normal tension of trabecular meshwork (Magnification x 26000), arrows show
glaucoma is more than that of patients with high enlarged cisternae, arrowheads ** Golgi complexes, elastic-
tension glaucoma. Incidence of cerebrovascular like fibers
9
of visual field defect. Levene also noted progression 7. Drance SM. Low tension glaucoma: Enigma and opportunity.
in 40 percent of his series of 34 eyes in 23 cases. Arch Ophthalmol 1985;103:1131.
Hitchings et al31 showed 40 percent progression of 56 8. Epstein DL. Chandler and Grant’s Glaucoma. 3rd ed.,
Philadelphia: Lea and Febiger, 1986.
patients followed for a period of 3.5 to 10 years.
9. Levene RZ. Low tension glaucoma: A critical review and new
As such, for the purpose of treatment low tension material. Surv Ophthalmol 1980;24:621.
glaucoma may be classified in two types: (a) Non- 10a. Anderson DR. Correlation of peripapillary anatomy with the
progressive or static type, and (b) Progressive type. disc damage and field abnormalities in glaucoma. DOC
The nonprogressive type developed due to some past Ophthalmol Proc Ser 1983;35:1.
ischemic status and the progressive type is due to some 10b. Shields MB. Hemorrhage in the optic disk in normal tension
ongoing ischemic process. As such for the treatment glaucoma. Am J Ophthalmol 2000;129,796.
11a. Ishida K, Yamamoto T, Suguyama K et al. Disk hemorrhage
purpose it is essential to identify the two groups
is a significant negative prognostic factor in normal tension
accurately. Once done so, one can leave alone the glaucoma. Am J Ophthalmol 2000;129,707.
nonprogressive or static type of NTG without any 11b. Greve EL, Geijssen HC. The relationship between excavation
medication or any other therapeutic modality. Use of and visual field in patients with high and low intraocular
ocular hypotensive drugs, laser procedures, and pressures. DOC Ophthalmol Proc Ser 1983;35:35.
filtering surgery are of no avail. Calcium blocker drugs 12. Caprioli J, Spaeth GL. Comparison of the optic nerve head in
like nifedipine are being tried to increase the nutrition high and low tension glaucoma. Arch Ophthalmol
1985;103:1145.
of the optic nerve at capillary level.
13. King D, Douglas GR, Drance SM, et al. Optic nerve analysis
In the midst of controversies and confusion about in low tension glaucoma versus high pressure glaucoma.
management of NTG SM Drance, DR Anderson and Invest Ophthalmol Vis Sci Suppl 1986;27:41.
M Schulzer published two reports of their Collabora- 14. Begg IS, Drance SM, Sweeney VP. Ischaemic optic neuropathy
tive Study for Management of Low Tension Glaucoma in chronic simple glaucoma. Br J Ophthalmol 1971;55:73.
in the October 1998 issue of American Journal of 15. Drance SM, Kottler MS. Studies of haemorrhage on the optic
Ophthalmology.32, 33 140 eyes of 140 patients were disc. Can J Ophthalmol 1986;11:102.
16. Drance SM, Fairclough M, Butler DM et al. The importance
involved in the study. By randomized selection the
of disc haemorrhage in the prognosis of chronic open angle
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progression of visual field damage in eyes with NTG.
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Louis: The CV Mosby Co, 1981. 1981;65:56.
5. Spaeth GL. Low tension glaucoma: Its diagnosis and manage- 25. Phelps CD, Corbett JJ. Migraine and low tension glaucoma.
ment. DOC Ophthalmol Proc Ser 1980;22:263. Invest Ophthalmol Vis Sci 1985;26:1105.
6. Kolker AE, Hetherington J Jr. Becker Shaffer’s Diagnosis and 26. Hollows FC, Graham PA. Intraocular pressure, glaucoma,
Therapy of the Glaucoma (5th edn), St. Louis: The CV Mosby and glaucoma suspects in a defined population. Br J
Co, 1983. Ophthalmol 1966;50:570.
27. Leibowitz HM et al. The Framingham eye study monograph. 31. Hitchings RA. Low tension glaucoma: Is treatment
Surv Ophthalmol 1980;24:(Suppl):335. Worthwhile? Eye 1988;2:6,636-40.
28. Hayreh S, Revie IHS, Edwards J. Vasogenic origin of visual 32. Collaborative Normal Tension Glaucoma Study Group.
field defects and optic nerve change in glaucoma. Br J Comparision of glaucomatous progression between untreated
Ophthalmol 1970;54:461-72. patients with normal tension glaucoma and patients with
29. Sossi N, Anderson DR. Blockage of axonal transport in optic therapeutically reduced intraocular pressure. Am J
nerve induced by elevation of intraocular pressure: Effect of Ophthalmol 1998;126,487.
arterial hypertension induced by angiotensin I. Arch 33. Collaborative Normal Tension Glaucoma Study Group. The
Ophthalmol 1983;101:94-97. effectiveness of intraocular pressure reduction in the
30. Minckler DS, Spaeth GL. Optic nerve damage in glaucoma. treatment of normal tension glaucoma. Am J Ophthalmol
Surv Ophthalmol 1981;26:128-48. 1998;126,498.
Chapter 68
Optic Nerve Head and Retinal

Nerve Fiber Layer Imaging
B Shantha, K Krishnakumar
Advances in computerized optical imaging continues RODENSTOCK OPTIC NERVE HEAD ANALYZER
to generate more and more sophisticated methods The Rodenstock optic nerve head analyzer (Roden-
to evaluate the structures of the optic disk and stock Instruments Gm BH, Munich, Germany) has
peripapillary region (RNFL). undergone extensive evaluation within the stereo-
The concept of computerized image analysis of photogrammetry group of instruments.3-6 It uses a
the optic nerve head was pioneered by Dr.Bernard stereoscopic video camera to produce digitized
Schwartz, who developed prototypes for analysis of images while projecting two sets of seven evenly
both contour and pallor of the disk. 1 Since then spaced lines on the optic nerve head. Disparity
several techniques have been developed, which utilize between corresponding points along the light stripes
a variety of principles, including stereogrammetry, of stereo pairs is used to generate vertical contour
confocal laser scanning, raster stereography and lines and three-dimensional contour maps. The disk
optical coherence tomography (all these techniques margin is determined manually over the computer
focus on early diagnosis of glaucoma). screen, by marking four cardinal points, and the
computer uses this information to fit on the ellipse
STEREOPHOTOGRAMMETRY that outlines the disk. The cup margin is determined
Principle by first constructing a reference plane over the disk
that corresponds to the level of peripapillary retina.
Stereophotogrammetry utilizes the basic principle of A method has also been developed to make height
Stereopsis, in which disparity between corresponding measurements of the peripapillary surface relative
points of stereo pair images are used to generate to a retinal reference plane, which is established in
contour lines and three-dimensional contour maps. the peripheral portions of the videographic image.7,4
Instruments Advantage
These are the Rodenstock optic nerve head analyzer, It is less labor intensive than manual stereo-
(ONHA), Topcon IMAGE NET and Humphrey photogrammetry.
retinal analyzer which come under the same
category. All these instruments require a highly Disadvantages
trained personnel and a fundus camera capable of • It is technically complex to perform.
simultaneous stereophotography. 2 Computerized • It requires relatively wide pupillary dilation and
image analysis with digitized simultaneous clear media.
stereoscopic videographic images has been used to • It requires a reference plane to estimate both the
quantify structural variations of the optic nerve head optic disk cup as well as the relative nerve fiber
and peripapillary retina. layer height.7
Parameters Measured diagnostic technologies ToPSS, Rodenstock 101

confocal scanning laser ophthalmoscope (CSLO) and
Cup to disk ratio, neural rim area, disk area, cup
Nerve fiber analyzer (NFA) are the few instruments
volume, disk evaluation, disk diameter, and relative
based on confocal laser scanning principle.
nerve fiber layer height.
HEIDELBERG RETINA TOMOGRAPH
Accuracy and Sources of Error
The Heidelberg retina tomograph (Fig. 68.1—HRT
Magnification determination to estimate disk size was
II; Heidelberg Engineering, Heidelberg, Germany)
not precise in this instrument, and this affected the
uses a diode laser beam (670 nm) that is projected
accuracy of neural rim area measurement. Although
onto the retina via a confocal system. Due to its high
new software has been developed to correct this
spatial resolution, the confocal principle ensures that
factor, there was no assurance that the computed
only light reflected from a defined focal plane is
dimensions and contours accurately reflect the true
detected by the integrated photomultiplier. The depth
measurements of the optic nerve head.8 In addition,
of the scanning range is 0.5 to 4.0 mm with a 0.5 mm
estimation of cup margin underestimates large cups
increment. Within this scanning depth range the
and overestimates small cups.8
instrument performs 32 consecutive scans. The first
O’Connor and associates 9 showed diagnostic
section image has to be localized above the reflection
precision (DP) of qualitative disk evaluation (DP 82%,
of the first retinal vessel and the last section image
sensitivity 72%, specificity 87%) was greater than that
has to be localized beyond the bottom of the optic
of quantitative disk parameters and nerve fiber layer
cup. From this series, the integrated computer
(DP range 59 to 68%, sensitivity 52 to 74%, specificity
calculates the height position for each of the pixels of
57 to 63%).
the whole image, which covers a rectangle 10 × 10
degrees of the retinal area surrounding the area of
CONFOCAL LASER SCANNING
interest. The three dimensional information is
Principle displayed in two images, the so-called topographic
Confocal laser scanning is a technique for obtaining
high resolution images by using a focused laser beam
to scan over the area of the fundus to be imaged.
Only a small point on the fundus is illuminated at
any instant, and the light reflected determines the
brightness of the corresponding pixel on a TV
monitor. To improve contrast, a pinhole, or confocal
aperture, is placed in front of the photodetector to
eliminate scattered light. The aperture is conjugate
to the laser focus, and the image so obtained is said
to be confocal. The instanteneous volume of tissue
from which reflected light is accepted by the confocal
aperture is called a voxel, and the smaller the
aperture, the smaller the voxel and the higher the
confocality of the image. By scanning the fundus with
the laser, a two dimensional image can be built up as
an array of pixels (confocal scanning laser
ophthalmoscopy). If a series of such images are
obtained at successive planes of depth in the tissue,
these can be used to construct a 3-dimensional image
(confocal scanning laser tomography).
Instruments
Heidelberg retinal tomography (HRT), Laser Fig. 68.1: HRT II—instrument
Chapter 68: Optic Nerve Head and Retinal Nerve Fiber Layer Imaging 511
image and the reflectivity image.
Advantages
• Images can be obtained through an undilated pupil
and cataracts
• It uses low light intensity
• A real-time image can be obtained for immediate
evaluation
• It has better axial resolution than the Rodenstock
Optic Nerve Head Analyzer.
Disadvantages
It requires a reference plane.
Parameters Measured
Disk area, cup to disk ratio, cup shape, height
variation, contour, rim area, rim volume, maximum
cup depth, cup area, cup volume, retinal nerve fibre
layer cross-section area, and mean retinal nerve fiber
layer thickness. Figure 68.2 shows normal optic nerve
2-dimensional images with Moorfields’ regression
model for glaucoma analysis.
Accuracy and Sources of Error

Cross-sectional images are limited by ocular aberra-
tions and pupillary size to 300 μm axial resolution.
Fig. 68.2: HRT II—Normal eye with Moorfields
Compared with photographic measurement of the
regression analysis
neuroretinal rim, the HRT discloses larger values for
the relative width and relative area of the neuroretinal
rim. This may be explained by the inclusion of the
retinal vessels as part of the rim. Also, the optic disk
margin is better detected on the disk photographs
than on the HRT videographs.
SCANNING LASER POLARIMETRY

Scanning laser polarimetry, e.g. nerve fiber analyzer
with integrated GDx software, (Fig. 68.3—GDx; Laser
Diagnostic Technologies, San Diego, CA) is a scanning
laser ophthalmoscope that utilizes the birefringent
properties of the nerve fiber layer. It is a method of
measuring retinal nerve fiber layer thickness (RNFLT)
using a scanning laser ophthalmoscope with polariza-
Fig. 68.3: GDx—Nerve fiber analysis being performed
tion modulation, a cornea polarization compensation,
and a polarization detection unit. The birefringence
property of the nerve fiber layer causes a change in properties of the retinal nerve fiber layer. In vitro
the stage of polarization of a laser beam, which is studies demonstrated a positive correlation between
known as retardation. The retardation is quantified polarization retardation and retinal nerve fibre layer
by and is linearly related to the thickness and optical thickness.
The light source consists of near—infrared diode

laser (780 nm) in which the state of polarization is
modulated. The polarized light penetrates the retinal
nerve fiber layer and is also partially reflected back
from the deep layers of the retina; in effect, it double
passes through the retinal nerve fiber layer before
the light emerges from the eye. The light emerging
from the eye is collected by the instrument and is
separated from the illuminating light beam by a
nonpolarized beam splitter. The polarization detector
unit analyzes the polarized state of light, which in
turn is digitized. The complete scan consists of 256 ×
256 pixels covering 15 degrees. The value of each pixel
represents the amount of retardation at a particular
location. All measurements are obtained from a band
1.5 to 2.3 disk diameters concentric to the disk. Figures
68.4 and
Fig. 68.4: GDx—Normal eye
68.5 shows normal and glaucomatous eye images
respectively.
Advantages
• It acquires polarimetric readings more quickly and
objectively than visual fields do.
• It has a higher sensitivity than the Glaucoma
Hemifield Test (96% compared with 94%).
• It does not require pupillary dilation.10
• Measurements are obtained directly without
reference plane and independent of magnification.
• It is independent of the optical resolution of the
human eye.
Disadvantages
• Other polarizing structures of the eye, such as the
cornea and the lens, may theoretically change
retardation.
• Peripapillary atrophy and chorioretinal scarring
may increase retardation values.
Fig. 68.5: GDx—Eye with glaucoma showing thinning
of nerve fiber layer
Accuracy/Resolution
Weinreb and coworkers 11 showed excellent
correlation (v = 0.83) between retardation and the top-to-bottom. It involves series of horizontal dark/
histopathologic measurement of the retinal nerve light line pairs projected on to the disk and peripapil-
fibre layer thickness. The resolution of measurements lary retina at a fixed angle, and the computer scans a
in vitro was estimated to be 13 μm. video image of the lines in a raster fashion. Since the
lines are deflected proportional to the height of the
RASTER STEREOGRAPHY disk and retinal surfaces, a computer algorithm can
translate the deflections into height numbers and
Principle create a topographic map.
“Raster” means scanning pattern, side-to-side or from
Chapter 68: Optic Nerve Head and Retinal Nerve Fiber Layer Imaging 513
Instrument (about 10 μm), cross sectional imaging of the eye. In
OCT, a beam of low coherence light is split to the
Glaucomascope (Ophthalmic Imaging Systems, Inc.,
tissue of interest and to a reference mirror at a
Sacramento, CA).
variable position. Multiple echoes are reflected or
backscattered from the eye, but for the two beams
GLAUCOMA SCOPE
to recombine and produce positive interference on a
The glaucoma scope system consists of an optical photodetector their pulses must arrive simulta-
head, used for image acquisition, a monitor that shows neously, or within the short coherence length of the
a video image of the optic nerve head, and a
computerized image analysis component. A halogen
lamp using near infrared light (750 nm) produces a
series of approximately 25 parallel horizontal, and
equally spaced lines, which are projected onto the
optic nerve head at an angle of 9 degree. The projected
lines are deflected proportional to the depth of optic
cup.
The reference point and the disk margin are
selected by the operator. The refractive error of the
eye is recorded for correction of magnification in the
disk measurements.
The optic nerve head and projected lines are
viewed in real time on the video monitor and the
operator may optimize focus and illumination.
Multiple images are captured and stored in digital
form on optical disks. The quality of the captured
image is assessed on a logarithmic scale and depends
on the ratio of horizontal line data to non-horizontal
line data (blood vessels), and on the degree of over Fig. 68.6: OCT—Picture of the instrument
exposure. The analysis system automatically analyzes
the image with the highest quality scale. Horizontal
line data will be converted into numerical depth
values. The depths or elevations of over 8,750 real
data points are calculated in an area of approximately
350 × 280 pixels (20°).
Disadvantages
• Need for a pupil size of atleast 4.5 to 5 mm, clear
media and experienced operator.
• Only surface topography can be analyzed.
Parameters
Vertical and horizontal cup to disk ratio, minimum
rim width within the 60° and 90° sectors and rim
and cup area.
OPTICAL COHERENCE TOMOGRAPHY

Optical coherence tomography (OCT—Fig. 68.6) is a
new diagnostic imaging technology that utilizes
interferometry and low coherence light in the near Fig. 68.7: OCT—Picture showing the normal ONH image
infrared range (840 nm) to achieve high resolution
light source. Thus, it is the low coherence light source REFERENCES

that primarily determines the longitudinal resolution. 1. Nagin P, Schwartz, B. Detection of increased pallor over time.
Transverse resolution is determined by the probe Computerized image analysis in untreated ocular
beam diameter (20 μm) and transverse pixel spacing. hypertensions. Ophthalmology 1984;91:252.
Figure 68.7 shows the normal optic nerve image. 2. Takamoto T, Schwartz B. Reproducibility of photogrammetric
optic disk cup measurements. Invest ophthalmol Vis Sci
1985;26:814.
Advantages
3. Caprioli J, Klingbeil U, Sears M. Pope B. Reproducibility of
No reference plane is required to determine retinal optic disk measurements with computerized analysis of
stereoscopic video images. Arch Ophthalmol 1986;104:1035.
nerve fiber layer thickness.
4. Shields MB, Martone JF, Shelton AR et al. Reproducibility of
topographic measurements with the Optic Nerve Head
Sensitivity and Specificity Analyzer. AMJ Ophthalmol 1987;104:581.
5. Bishop KI, Werner EB, Krupin T et al. Variability and
Sensitivity was 79 percent and specificity was 79 reproducibility of optic disk topographic measurements with
percent for OCT.12 the Rodenstock Optic Nerve Head Analyzer. AMJ Ophthalmol
1988;106:696.
6. Caprioli J, Miller JM, Sears M. Quantitative evaluation of the
CONCLUSIONS optic nerve head in patients with unilateral visual field loss
from primary open – angle glaucoma. Ophthalmology
The technologies mentioned above represent the 1987;94:1484.
efforts of many investigators to differentiate between 7. Caprioli J, Miller JM. Measurement of relative nerve Fiber layer
surface height in glaucoma. Opthalmology 1989;96:633.
normal and glaucomatous eyes as soon as possible in
8. Shields MB, Tiedman JS, Miller KN et al. Accuracy of
the disease process, and to detect the progression of topographic measurements with the Optic Nerve Head
the condition. As these techniques become more Analyzer. AM J Ophthalmol 1989;107:273.
refined, its importance in clinical practice will be a 9. Weinreb RN, Dreher AW, Coleman A, et al. Histopathologic
great boon. validation of Fourier-Ellipsometry measurements of retinal
nerve Fiber layer thickness. Arch Ophthalmol 1990;108:557.
10. Tjon-Fo-Sang MJ, Lemij HG. The sensitivity and specificity of
ACKNOWLEDGEMENT nerve Fiber layer measurements in glaucoma as determined
with scanning laser polarimetry. Am J Ophthalmol 1997;123:62.
We acknowledge with thanks Dr S Natarajan, Aditya 11. Weinreb RN, Shakibha S, Zangwill L. Scanning laser polarimetry
Jyot Eye Hospital, Mumbai for their valuable contri- to measure the nerve fiber layer of normal and glaucomatous
bution in sending the OCT images for this chapter. eyes. Am J Ophthalmol 1995;119:627.
12. Hoh ST, Greenfield DS, Liebmann JM et al. Factors affecting
image acquisition during scanning laser polarimetry.
Ophthalmic Surg Lasers 1998;29:545.
Chapter 69
Automated Perimetry
B Shantha
Manual perimetry with either the Bjerrum’s tangent Fixation Control

screen or the Goldmann type bowl perimeter has
The most popular method used for this purpose is
been the popular method for evaluating the visual
the Heijl-Krakau method. After plotting the location
field in patients with glaucoma. However, it is time
and size of the blind spot, a very bright
consuming, nonstandardized and is limited by the
suprathreshold stimulus is projected in this area after
subjectivity of the patient as well as the perimetrist.
every 8 to 12 stimuli. If the patient responds to this
Automated perimetry allows standardization of test
stimulus, a fixation loss is recorded.
conditions. Therefore high quality, reproducible
A closed circuit TV monitor can be used to monitor
visual field testing capable of both screening and full
fixation. The computer is programmed to disregard
thresholding examination is now available. Statistical
the points tested when a fixation loss has occurred
interpretation of the data obtained is another
and to retest the same location.
significant advantage with regard to the diagnosis
as well as the follow-up of glaucoma patients. Data Storage
INSTRUMENTATION Most automated perimeters are run by micro-

computers with the capacity to store patient test data.
The three basic features1 of any automated perimeter This also permits statistical interpretation of the data
are the following: obtained.
1. Stimulus source
2. Fixation control TESTING STRATEGIES
3. Data storage.
The basic strategies1 used to evaluate the visual fields
Stimulus Source include the following:
1. Suprathreshold screening
1. Projection systems provide a light source using 2. Threshold related screening
filters and mirrors such as in Goldmann 3. Full threshold strategies.
perimetry. This allows flexibility in selecting test
point locations and spacing. However, this system Suprathreshold Screening
is potentially vulnerable to mechanical failure and
needs periodic maintenance. A stimulus, which is intense enough to be seen in all
2. The LED source system utilizes Light Emitting the test locations by nearly all normal patients, is used
Diodes that are embedded in the surface of the across the entire visual field. This method is restricted
perimeter bowl. This system is inexpensive to to screening examinations to rule out gross pathology
manufacture and requires minimum maintenance. only.
3. Video monitor systems present dark and light
Threshold Related Screening
combinations of stimuli against a diffused back-
ground. However, the extent of the visual field All stimuli presented are suprathreshold, but those
that can be tested is limited to the central 30o. presented centrally are dimmer than those in the
periphery. Therefore the contour of the hill of vision

is suspected.
Once a scotoma is detected, various strategies can
be used to get additional information. The extent of
the defect can be quantified by surrounding the
missed points with additional points. The missed
points can be retested with brighter stimuli to
differentiate relative from absolute scotomas; this is
called ‘Zone’ tests. The missed points can undergo a
full threshold determination to yield a numerical
value to the depth of the defect. This is the ‘quantify
defect’ screening strategy.
Threshold Determination
The threshold is determined at each location in the
area to be tested. A bracketing strategy is utilized
for this purpose. The initial stimulus is presented at
an intensity that the patient is expected to see. In
subsequent presentations, the stimulus intensity is
decreased in 4 dB increments until the patient does
not see the stimulus. The intensity is then increased
by 2 dB until the threshold is crossed again. The
midpoint between the suprathreshold and infrathres-
hold values is taken to represent the actual threshold
value at the location tested.
Test Patterns Fig. 69.1: A macula threshold test showing split fixation
Since numerous strategies are available in most
automated perimeters, a standardized approach to as the actual test result obtained. The first parameter
select the test pattern is essential. to be checked is the reliability of the test result. This
1. First determine if a full threshold or screening in turn is dependent on the following:
test pattern is required. Consistency on Testing
2. Choose the test pattern best suited to reflect field
changes in the area of interest. The pattern a. Maintenance of pupil size, preferably more than
selected will vary according to the pathology in 3.5 mm for all examinations.
question. b. The best refractive correction possible.
The more commonly used test patterns are limited c. Consistent test parameters should be used for all
to the central 24o to 30° with a 6o separation between tests performed by the same patient, namely
test locations. In advanced glaucoma, tighter grids stimulus size, blind spot check size, etc.
can be used especially for the central 10o (e.g. the
Reliability Factors
macula threshold test—Fig. 69.1). Programs are also
available to study the peripheral field beyond 30o Fixation loss rate This should be less than 20 percent.
either in the nasal quadrant alone or over 360o. These The false-positive rate This refers to the number of times
can be performed in conjunction with a central field that the patient responds to the audible click of the
program to provide additional information. perimeter shutter or to the spaced rhythm of the test
when no target is presented.
INTERPRETATION OF RESULTS The false-negative rate This refers to the number of
Interpretation of the test result includes an evaluation times that the patient fails to respond to a
of the patient’s performance and reliability as well suprathreshold target placed in a seeing area. The
false-positive and false- negative rates should not
Chapter 69: Automated Perimetry 517
exceed 33 percent. 2. Pattern standard deviation (PSD) It is the standard
deviation of the difference between the threshold
Fluctuations value at each test location and the expected value.
It is a measure of localized nonuniformity of the
Short-term fluctuation This is a measure of fluctuation
contour of the hill of vision. It is sensitive to
of threshold responses during a single visual field
localized field loss.
examination. It is calculated at the variance of multiple
3. Short-term fluctuation It has already been
readings obtained at preselected locations in the
discussed.
visual field. The normal limit of short-term fluctuation
4. Corrected pattern standard deviation (CPSD) It is simi-
is said to be less than 2 dB.2
lar to pattern standard deviation but is adjusted
Long-term fluctuation This is reversible variation of downward for short term fluctuation.
visual field threshold over 2 or more examinations. By looking at the mean deviation and pattern
It has a homogenous and a heterogeneous component. deviation, it is possible to anticipate the nature of
The homogenous component affects the threshold the field defect. If both the MD and the PD are within
equally in all locations, whereas heterogeneous the normal range, the visual field is most probably
component affects only some areas of the field and is normal. If the MD is abnormal, but the PD is normal,
balanced by opposite changes in other areas. In there is probably a generalized depression. If the MD
glaucoma patients, a long-term fluctuation of upto is normal but the PD is abnormal, there is a localized
7 dB can occur without signifying deterioration.3
Statistical Interpretation of Results

There are following two steps in diagnosing glauco-
matous visual field loss by automated perimetry:
1. To differentiate normal from abnormal.
2. If abnormal, to differentiate glaucomatous from
nonglaucomatous.
Use of Probability Statistics to

Define the Normal Visual Field
The term normal when applied to perimetry describes
the range of test results found in the nondiseased
population. This range has been determined and the
results stored in the computer of the most automated
perimeters. By utilizing statistical analysis, it is
possible to determine the probability of finding, a
particular visual field in a normal individual.
Humphrey Field Analyzer

The Humphrey visual field analyzer is the most
commonly used automated perimeter. Therefore, the
statistical software available with this perimeter will
now be discussed.2,3
The STATPAC printout of the Humphrey visual
field analyzer contains the following 4 basic indices:
1. Mean deviation (MD) It refers to the average Fig. 69.2: Visual field effect showing a large defect with a
significant localized component. The glaucoma-hemifield test
departure of each test location from the age-
is outside normal limits. The total deviation and pattern deviation
related normal value. It is mainly an index of the plots show many probability symbols. The symbols are
size of a visual field defect. It is very sensitive to distributed equally in both hemifields in the total deviation plots,
generalized loss of sensitivity but purely localized but are confined mostly to the superior hemifield in the pattern
defects that are large enough can also affect it. deviation plot
defect or an artifact. If both are abnormal, there is a

large defect present with a significant localized
component (Fig. 69.2).
The graphic probability plots indicate how
frequently a total or pattern deviation at the
particular test location will be found in the normal
population. There are 4 symbols, ranging from p < 5
percent to p < 0.5 percent. The grouping of symbols
in a portion of the visual field signifies a high
probability of abnormality.
The Glaucoma-Hemifield test attempts to provide
information about the differences between the
superior and inferior halves of the visual field.4 The
differences in threshold of mirror image groups of
points on either side of the horizontal meridian are
evaluated.
There are five interpretative messages that may
appear depending on the relationship of the
thresholds in the superior and inferior halves of the
field.
Evaluation of the Gray Scale

In constructing the gray scale, the machine notes the
Fig. 69.3: Visual field showing a peripheral constriction typical
sensitivity of the actual points thresholded and then of patients inexperienced with automated perimetry; the learning
interpolates the predicted slope between these points. artifact
Symbols which correspond to the sensitivity of
these points are filled in at 1° intervals. Therefore, mid-periphery. Such depression disappear with
the gray scale can be used to get a general impression experience (Fig. 69.3).5
of the test result. However, it merely highlights the
Effect of ptosis Significant ptosis can produce midperi-
areas of interest to be noted in the total deviation
pheral depression.
and pattern deviation plots.
Conclusively, the evaluation of STATPAC’S single Low patient reliability Trigger happy patients may
view analyzer follows a logical sequence. produce high false positive rates that make interpreta-
a. Printed data (at the top of the page) tion difficult.
b. Parameters, e.g size of stimulus, blind spot check
A high false-negative rate This results in an under
size, etc.
estimation of the sensitivity of the visual field.
c. Visual acuity, refraction, pupil size
d. Reliability parameters Fixation losses The most striking finding associated
e. Examination of the gray scale with fixation losses is the disappearance of the blind
f. Examination of the total and pattern deviation spot. Conversely, it is unlikely that a field defect with
plots a well defined blind spot was obtained with a poorly
g. Global indices and their probability values fixating patient regardless of the result of catch trials
h. Evaluation the glaucoma-hemifield test. (Fig. 69.4).
Fatigue effect Prolonged testing results in a
Artifacts Simulating Visual Field Defects
pronounced depression of the midperipheral field.
False depression can occur due to the following Trial lens artifacts A misaligned trial lens can result in
physiological phenomena: a depression in the peripherally located circle of
Field of the patient inexperienced in performing threshold points. Such a depression 360 o is unlikely to be
tests These are characterized by depressions in the pathological in the absence of high refractive errors.
Fig. 69.5: Change analysis printout showing a stable visual

field. The box plot frequency distributions demonstrate
significant long-term fluctuation but do not show progression.
The mean deviation slope is not significant
Fig. 69.4: Visual field showing a significant number of fixation

along the Y-axis represents the difference between
losses. The well-defined blind spot signifies a fairly reliable result the measured thresholds and the age-related normal
despite the result of the catch trials values. Positive values represent test locations with
thresholds above normal and negative values
Detection of Progressive represent locations with threshold below normal. The
Glaucomatous Visual Field Loss highest value in the box plot is the top of the ‘T’ and
is the best value in the visual field. The top of the
The visual field of glaucomatous eyes are especially box represents the 85th percentile, and the bottom
prone to a large degree of long term fluctuation. represents the 15th percentile. The bar in the middle
Therefore, it is difficult to decide if the difference is the median value. The bottom of the ‘T’ is the worst
between two fields is due to true progression or value in the visual field.
merely the result of long-term fluctuation. When large number of the tests are available, a
To assist the clinician in making a decision, the quick glimpse of the box plots can often detect a trend
STATPAC-2 software of the Humphery’s perimeter toward progression.
provides three ways to display serial visual field data The glaucoma change probability analysis print
to assist in determining the presence of progression, out compares the rate of change in the patients visual
i.e. the overview printout, the change analysis print- field with that of stable glaucoma patients (Fig. 69.6).
out, and the glaucoma change probability analysis.6 Clear triangles represent locations showing
The overview printout displays the gray scales, improvement, whereas solid ones show points of
the measured thresholds, and the total and pattern deterioration. Progression is represented by a cluster
deviations, on a single sheet of paper. Statistical of black triangles in the same area increasing in size
analysis is not provided, however. with time (Figs 69.7 and 69.8).
The change analysis printout displays serial visual A minimum of 6 to 8 fields would be necessary in
field data in the form of box plots (Fig. 69.5). The order to differentiate progression from long-term
normal distribution of thresholds is shown as a fluctuation. The first two visual fields may be
sample box to the left of the display. The number disregarded if they depict a significant learning curve.
Fig. 69.6: Glaucoma change probability analysis printout. The

glaucoma probability column (far right) shows no consistent
pattern of black triangles, indicating no significant change
Fig. 69.8: A nasal step with paracentral

defects in the superior hemifield
RECENT ADVANCES IN AUTOMATED PERIMETRY

Swedish Interactive
Thresholding Algorithm (SITA)7
This is a new family of threshold algorithms for
computer assisted static threshold perimetry that
provides considerably faster testing without loss of
test accuracy.
Two SITA versions SITA standard and SITA fast, are
intended to replace the full threshold and fastpac
algorithms, respectively and provide results of the
same quality with approximately 50 percent test time
reduction.8
Short Wave Automated Perimetry (SWAP) A new visual
field test is now included in commercially available
perimeters. It is identical to standard perimetry
except that it tests only an isolated part of the vision
system, which processes information collected by the
short wave length (blue cones) channeled through a
subset of ganglion cells—the blue yellow cells. It does
Fig. 69.7: Visual field with significant general reduction in
this by presenting a violet target on a bright yellow
sensitivity as depicted in the total deviation plot and the background.
glaucoma-hemifield test The advantages of this method is that it identifies
abnormal fields 2 to 5 years earlier than standard REFERENCES
white on white perimetry in 83 percent of eyes.
1. Liebermann MF. Computerized Perimetry: A Simplified Guide
Progression of visual field loss is seen 1 to 3 years (2nd edn), Slack Incorporated 1992.
before standard perimetric changes. However, it is 2. Werner EB, Piltz Seymou J. What constitutes a glaucomatous
more susceptible to changes in lens density. Statistical visual field defect. Seminars in Ophthalmology 1992;7(2):110.
software, using this technique is also not available. 3. Zulauf M, Caprioli J. What constitutes progression of glauco-
matous visual field defects. Seminars in Ophthalmology
1992;7(2):130.
CONCLUSION 4. Susanna R Jr, Nicolela MT, Soriano DS et al. Automated
Perimetry: A study of the glaucoma-hemifield for detection of
Automated perimetry is very useful as a reliable, early glaucomatous visual field loss. Journal of Glaucoma
reproducible test reflecting the status of a patient’s 1994;3:12.
visual field. However, it should not be viewed in 5. Heijl A, Asman P. Pitfalls of automated perimetry in glaucoma
diagnosis. Current Opinion in Ophthalmology 1995;6(11):46.
isolation but should be interpreted in conjunction with 6. Werner EB. New Developments in Glaucoma. Ophthalmol
clinical parameters, especially with regard to disc and Clinics N Am 1995;229-57.
nerve fiber layer changes. 7. Bengtsson B, Olsson J, Heijsl A et al. A new generation of
algorithms for computerized threshold perimetry. SITA Acta
Ophthalmologica Scandinavia 1997;75:368.
8. Johnson CA. Diagnostic value of short-wavelength automated
perimetry. Current Opinion in Ophthalmology 1996;7(2):54.
Chapter 70
Primary Angle
Closure Glaucoma
A Neelakanthan, S Rao
HISTORICAL BACKGROUND segment in angle closure glaucomas, thereby laying

the foundations of ocular biometry. Chandler further
Lawrence in 1829 gave an accurate clinical description
advanced the understanding of the anatomic relation-
of a condition which he vaguely termed “acute glau-
ships underlying the physiologic changes involved in
coma”, which can now be recognized as acute angle
pupillary block.
closure glaucoma. He however, made no reference to
hardness of the eye to touch which was emphasized
by Mckenzie (1830) in his classic textbook. Von ANATOMICAL FEATURES
Grafe (1856) revolutionized the management of
Biometry
these inflamed hard eyes by his mysteriously acting
iridectomy. Anatomical features of the anterior segment of the eye
However, the awareness of angle closure glaucoma are amenable to measurement or biometry.
as a distinct entity was slow to develop, and even in Eyes with primary angle closure glaucoma show
1922, Elliot wrote that acute and chronic glaucoma significant biometric variation from normal eyes.
were merely particular phases of the same disease. Compared to the mean normal eye, the “mean angle
Raeder (1923) classified it into two groups—one with closure glaucoma eye” has the following charac-
shallow anterior chambers (AC) and the other with a teristics (Table 70.1).1-4
deep or normal AC. Curran (1931) and Banziger (1922) 1. Smaller corneal diameter
introduced the concept of physiological obstruction 2. Smaller radius of anterior corneal curvature
of flow of aqueous through the pupil. After 1900, the (steeper corneal curvature)
development of gonioscopy led to the recognition of 3. Smaller radius of posterior corneal curvature
synechial angle closure and provided the basis for 4. Shallower anterior chamber
differentiation into open angle and angle closure 5. Thicker lens
glaucomas. 6. Smaller radius of anterior lens curvature (Steeper
Curran (1931) reported peripheral iridectomy to lens surface)
be successful in eyes with shallow chambers, but not 7. Anterior lens position
in eyes with normal depth chambers. Following their 8. Shorter axial length.
introduction in 1876 (Weber) miotics were shown to However, in the general population, there exist a
be beneficial in these eyes. Until Becker introduced number of eyes with smaller physical characteristics
acetazolamide in 1954, these acutely inflamed eyes which do not develop angle closure glaucoma. These
were prepared for surgery by intensive miotic therapy, eyes have a normal function with a normal distribution
purges, and the application of leeches. of refractive errors with an inclination toward
In 1890, Priestly Smith showed by dissection the hyperopia. Hyperopia is not a prerequisite for angle
importance of a large lens and crowded anterior closure glaucoma. Very rarely there occurs a unilateral
Chapter 70: Primary Angle Closure Glaucoma 523
Table 70.1: Mean values with SD for various ocular dimensions of eyes with primary angle
closure glaucoma (ACG) compared to normal controls
Parameters Normal ACG Authors
Corneal diameter (mm) 11.76 (0.42) 10.85 (0.37) Delmarcelle2
11.05 10.72 Tomlinson and
Leighton3
Anterior corneal radius (mm) 7.67 (0.24) 7.61 (0.29) Lowe1
7.92 (0.29) 7.64 (0.25) Delmarcelle2
True AC depth (mm) 2.80(0.36) 1.80 (0.25) Lowe1
2.91 (0.40) 1.72 (0.22) Delmarcelle2
Lens thickness (mm) 4.50 (0.34) 5.09 (0.34) Lowe1
4.46 (0.42) 5.43 (0.46) Delmarcelle2
Anterior lens radius (mm) 10.29 (1.78) 7.96 (0.99) Lowe1
Axial length 23.10 (0.82) 22.01 (1.06) Lowe1
22.58 22.06 Tomlinson and Leighton3
Lens thickness/Axial length ratio 2.27 (0.17) Panek5
failure of the compensatory procedures with one eye are situated more forward. Continued growth of the
showing typical features of angle closure glaucoma lens in adult life resutls in about 0.75 to 1.1 mm
and the other having normal features. increased thickness at the age of about 50 years of
The most important biometric features predis- which about 0.4 mm is contributed by forward
posing to primary angle closure glaucoma are the lens movement of the anterior lens surface.1,2,4
thickness-ocular axial length ratio4,5 and the relatively As thickness of lens increases, the anterior lens
forward position of the anterior lens surface in relation curvature decreases. The radius of curvature of the
to the root of the iris (shallow AC). anterior lens surface (7.50 to 25.38 mm, mean
10.29 mm) is very large compared to the radius of
Anterior Chamber Depth curvature of the anterior corneal surface and it
The mean AC depth of primary angle closure correlates well with the AC depth. In a series of eyes
glaucoma eyes is one millimeter shallower than the with angle closure glaucoma, the radii of the anterior
mean AC depth of normal eyes (Table 70.1). Of this lens curvatures were found to be very steep, the mean
0.35 mm is contributed by lens thickness and 0.65 mm being 7.96 mm.
by the more forward lens positioning. The AC of
primary angle closure glaucoma patients is distributed Lens Thickness: Ocular-Axial Length Ratio
around a mean of 1.8 mm with an AC depth greater Normal mean value for the lens thickness-ocular axial
than 2.5 mm. length ratio has been estimated to be 1.91 (SD ± 0.44).4
Slight asymmetry of the AC depths between the Strong correlation exists between the need for a peri-
two eyes is common. Considerable inequality alerts pheral iridectomy and an increasing lens thickness-
the possibility of a change in the lens position. The ocular axial length ratio.5 Eyes with angle closure
greater the difference, the lesser is the risk of angle glaucoma and occludable angles have similarly
closure glaucoma in the fellow eye. shorter axial lengths, shallower anterior chambers and
greater lens thickness compared to normal eyes.6
Lens Position, Thickness, and
Anterior Lens Curvature
The position of the anterior lens surface is determined Width and Depth of Angle
by the position of the lens along with optic axis and The width of the angle depends upon the convexity
lens thickness. Lens thickness too is largely genetically of the iris, the thickness, length, and position of
determined and lenses which are genetically thicker insertion of the iris root. The depth of the angle recess
depends upon the distance between the scleral spur

and the junction of the anterior surface of the iris root
with the ciliary body. Eyes with typical features which
predispose to primary angle closure glaucoma charac-
teristically have narrow and shallow angles, whereas
in large myopic eyes the angles are wide and deep.
The angle is normally narrow and shallower in the
superior aspects than in the inferior aspects of the
angle. It is also narrower nasally than temporally.
With the advent of ultrasound biomicroscopy it is
now possible to study the anterior chamber angle
structures in greater detail. 50 to 100 MHz probes are
used to visualize the angle structure with microscopic
resolution. Pavlin et al have measured the iris
thickness at its root, the angle opening distances and
the trabecular meshwork—ciliary process distance.7 Fig. 70.1: Pupillary block leading to an
appositional angle closure
Physiology
role in the development of pupillary block angle
Impedance to the bulk flow of aqueous humor from closure.
the posterior to the anterior chambers is an important
determinant of primary angle closure glaucoma. The Lens Factors
position of the iris lens diaphragm at equilibrium is
Shallow ACs have an anteriorly situated steep anterior
determined by the production of aqueous humor, the
lens surface. The more anterior the lens, the greater is
facility of outflow and the degree of pupillary block.
the resistance to aqueous flow. On removal of the lens,
When the anterior chamber depth is less than
the iris normally assumes a more posterior position.
2.5 mm, and especially with depth below 2 mm due
In very shallow ACs the anterior lens surface is
to forward positioning of the anterior lens surface, the
extremely steep and the shallowness extends to the
pressure differential across the pupil reaches at a
periphery of the anterior chamber. As the pupil dilates
critical value. There is sufficient impedance to the flow
in such an eye the lens appears to protrude into or
of aqueous causing the pressure in the posterior
even beyond the pupillary margin. An increased
chamber to be higher than that in the anterior chamber.
apposition between the iris and the lens can be readily
The peripheral iris is bowed forward, but as long as
observed with the slit lamp. In an eye with a deeper
there is a sufficient flow of aqueous through the pupil,
AC, the iris normally clears the lens surface and
the angle stays open and this condition is known as a
abolishes the pupillary block. But in an eye with a
“relative pupillary block”. This condition normally
shallow AC, this is unlikely and the “doughnut” of
causes no symptom or disturbance of function;
tissues around the sphincter area is more closely
however if it is sufficient to cause an appositional
applied to lens.
closure of a part of the angle, peripheral anterior syne-
The lens normally maintains a stable position
chia may gradually form leading to a chronic angle
within the eye. Due to dislocation or swelling of the
closure.
lens, there occurs an anterior movement of the lens
If the pupillary block becomes absolute, posterior
and the pupillary block is increased. Some anterior
chamber pressure pushes the iris in the periphery
movement may occur in the prone position, which is
further forward, causing it to lose the angle and cover
of possible importance in provocative testing.
the trabecular meshwork resulting in rise in intra-
ocular pressure (acute angle closure glaucoma) (Fig.
Iris Factors
70.1). Clark in a recent review stresses the importance
of autonomic nerve function on the position of the iris Iris texture and thickness play important role in the
lens diaphragm.8 development of angle closure glaucoma. A flaccid iris
Several mechanical factors such as the lens, zonules usually becomes more convex than a rigid one. This
and iris stroma, and musculature play an important may account for the fact that Asians and Blacks are
more prone to gradual angle closure, as their irides of angle morphology is required in susceptible
are normally thick and rigid. patients for proper diagnosis and treatment.
Pupillary constriction causes an increased tautness,
causing an unfolding and drawing away of the peri- Clinical Pathology
pheral iris, relieving the angle closure.
The pathology of primary angle closure glaucoma is
basically due to (a) an increase in the relative pupillary
Muscle Factors
block, and (b) the effects of raised intraocular pressure.
As dilator pupillae muscle extends centrally beneath Due to certain yet unknown mechanisms, the
the sphincter, in active pupillary dilation, the dilator relative pupillary block gets augmented and a higher
muscle pulls the sphincter backward toward the lens. pressure builds up in the posterior chamber. This
In a shallow AC with the lens situated forward, this increases the forward iris convexity, such that the
posteriorly directed force of the dilator muscle is peripheral iris stroma now comes into contact with
greater and it enlarges the pupillary block. the lateral wall of the angle recess and the angle is
The constrictor pupillae is a sphincter with its usual closed.9 Brief attacks of subacute angle closure usually
direction of action in plane anterior to the lens surface. resolve spontaneously and the angle may reopen
With an increasing forward lens movement, more of completely or the deposition of products of inflam-
this force is directed posteriorly against the anterior mation at the 6 o’clock position may leave behind
lens surface. However, this force is very small in a peripheral anterior synechiae. The clinical pathology
constricted pupil. Secondly, a constricted pupil draws in intermittent angle closure glaucoma varies in the
the peripheral iris away from the angle by tightening different ethnic groups. In Caucasians the attacks are
the iris and this opens up closed angles. Thus miotics mostly monocular and they never last overnight, thus
have contradictory actions in angle closure glaucoma. the angle remains open and synechiae do not form.
This posteriorly directed force of the sphincter pupillae However, amongst the Chinese and the Blacks, though
increases as the pupil dilates and the lens protrudes the attacks are of a short duration peripheral anterior
into the anterior chamber. After dilation, as the pupil synechiae do form above, where the angle is the
is constricting the sphincter pulls the entire pupillary narrowest or at the sides. These synechiae progress
area over the anterior lens surface increasing the with repeated attacks, causing a rise in the baseline
appositional pressure of the iris against the lens. The intraocular pressure.
more forcible the sphincter activity the greater is the The effects of this raised intraocular pressure on
pupillary block. the globe depends upon its magnitude and rapidity
Pupillary block force has been shown to be maxi- of the rise. The first and the mildest symptoms are
mal when the pupil is fixed in the mid-dilated position usually caused by stretching of the globe, disturbing
(pupillary diameter 3.8 to 4.2 mm) as a result of relative the corneal lamellae and thus blurring of vision.
parasympathetic and sympathetic activity. This This begins with acute rise of pressure to around
provides a physiological explanation of the semidi- 40 mm Hg. With higher pressures the endothelial
lated pupil typically seen during acute angle closure pump fails leading to corneal edema with epithelial
glaucoma attacks and also has been used as a base for bullae. This edema is the major cause of haloes and
some provocative tests by instilling phenylephrine blurred vision. The pupil reacts sluggishly to light and
after pilocarpine drops. The sphincter pupillae when tends to assume a vertically oval partly dilated shape,
maximally contracted is seen to develop twice the but it may be oblique or even horizontal with a rise in
force of the dilator muscle on maximal stimulation. pressure to around 60 to 70 mm Hg. All these previous
Therefore, impairment in the parasympathetic tone changes get intensified, the inflammation becomes
has been proposed as a major determinant in severe and iris and lens changes begin to manifest with
causing a pupillary block. Systemic parasympathetic pressure rises to over 90 mm Hg. The inflammation
dysfunction has been found in 58 percent of angle becomes very severe and eyelids become swollen,
closure patients as compared to 6.8 percent in a control accompanied by intense circumcorneal congestion and
group. conjunctival chemosis.
Anterior chamber depth and development of a Dilated vessels manifest in the edematous iris
pupillary block are dependent on many factors. Since which may be irregular due to ischemia and can lead
these factors are dynamic, a continued reevaluation to an erroneous diagnosis of neovascular glaucoma.
Severe damage to the intraocular structures occur if

the pressure remains very high for 24 hours or less,
but if the initial high pressure falls to around
50 mm Hg, the damage may take a few days to appear.
Thus in an acute attack, the eye is severely compromi-
sed and an urgent reduction of intraocular pressure
becomes necessary.
Angle
In an acute angle closure, the angle is at first totally
occluded appositionally, followed by a sticky adhesion
and later on by peripheral anterior synechiae over
wide areas. Prompt relief of this angle closure usually
leaves behind a wide open angle. Closure is usually
inferiorly from 5 to 7 o’clock position despite the angle
being the widest inferiorly. This is caused by the Fig. 70.2: Ischaemic iris sphincter atrophy following
an acute angle closure attack
settling of pigment and inflammatory products on to
the inferior angle, which then causes the formation of
are anterior capsular cataracts. With severe attacks
anterior synechiae.
there can occur fibrosis of the anterior lens capsule.
In creeping angle closure glaucoma seen in Cauca-
Anterior cortical opacities commonly follow severe
sians, usually there is no overt inflammation, but
attacks of angle closure glaucoma. They usually show
peripheral anterior synechiae gradually form and
up initially as faint irregular streaks within the anterior
occlude the angle. The root of the iris closes the angle
lens cortex. However these opacities progress, leading
leading to shallowing or shortening of the angle.
to a rapid severe loss of vision.
Iris
Zonules
Ischemic iris atrophy occurs following high rise of
An acute attack of angle closure glaucoma usually
intraocular pressure which is typically segmental and
causes zonular damage. Very commonly following
it affects mostly the sphincter area (Fig. 70.2). With a
surgery in these eyes the lens moves forward leading
rise in intraocular pressure to 60 mm Hg and above
to the development of malignant or ciliary block glau-
the pupil becomes resistant to miotics, probably due
coma. In badly damaged eyes the opaque lens occasio-
to the direct pressure on the sphincter muscle cells. If
nally slowly dislocates over the years and sinks below
the intraocular pressure is lowered, the pupil usually
the pupil.
responds to miotics.
Optic Nerve and Retina
Lens
The retinal function is depressed with a rise in
In primary angle closure glaucoma the following types
intraocular pressure and in severe attacks the vision
of lens damage can occur: (1) Glaukomflecken, (2)
may drop to hand movements or light perception. Due
anterior capsular cataract, (3) pigment deposition,
to corneal edema it is not possible to examine the
posterior synechiae, and fibrosis, (4) cortical cataract,
fundus during or immediately following an acute
and (5) nuclear sclerosis. Glaukomflecken is thought
attack of PACG. Optic disk cupping, retinal hemorr-
to be due to the pressure necrosis of the tips of the
hage, may be seen during examination of the fundus
anterior lens fibers and do not occur at the posterior
when the cornea clear4 after treatment.
pole. Glaukomflecken usually appears entirely within
the pupillary area according to its size at the time of
Epidemiology
the attack.
Small white plaques resembling glaukomflecken Primary angle closure glaucoma accounts for approxi-
may show up in the anterior surface of the lens, which mately 6 percent of all patients with glaucoma. It
persists with no signs of sinking into the lens. These occurs in 0.6 percent or less of the general population.
Sex along the optic axis of the patient’s eye. The right eye
is viewed through the right ocular and left eye through
Among Europeans with angle closure glaucoma,
the left ocular. The slit beam is turned horizontally
women are affected about 3 to 4 times as often as men.
and the lamp housing is set at 60 degrees temporally
Amongst the American blacks, the sex incidence is
and the pillars are locked into position. The nasal end
reported to be equivocal.
of the slit beam is focused on the midpoint of the
Age corneal endothelium and behind it there will be
another out of focus slit beam on the lens. The length
The AC decreases in depth and volume with age.11 of the slit is adjusted until its nasal end on the cornea
The prevalence of primary angle closure glaucoma at endothelial level is in line with its temporal end on
also increases with age, and peaking between the ages the lens. The length of the slit in mm is read from the
of 55 to 70 years. PACG is common in younger indi- scale, multiplied by 1.1 and added to 0.5. The standard
viduals. Therefore finding of angle closure glaucoma deviation of error is 0.12 which is sufficiently accurate
in a young individual should be investigated specially for clinical measurements.
with ultrasound biomicroscopy to exclude the Pachymetry with the Haag-Streit pachymeter is
possibility of other causes of angle closure such as iris also a quick and accurate method of measurement.
pigment epithelial cysts.12 The anterior surface of the cornea is aligned with the
Race anterior lens surface and the scale shows the distance,
the corneal thickness measured must be subtracted.
The prevalence of primary angle closure glaucoma Direct measurement from the posterior cornea to the
varies with different ethnic groups. Eskimos living in anterior lens surface is inaccurate. Linear A-scan
Denmark have deeper ACs and a lower incidence of ultrasonographic measurements of AC depth are now
angle closure glaucoma, suggestive of environmental readily available, however this is not a strictly accurate
influences. Acute angle closure is rare amongst the method but it is adequate for clinical purposes.15
blacks in America or Central Africa; they develop a
chronic angle closure glaucoma.13 Peripheral AC Depth
In Asians, the incidence of acute angle closure
appears to be intermediate in whites and blacks. The depth of the AC in the periphery is dependent
Primary angle closure glaucoma occurs a decade both on the anterior lens surface and the degree of iris
earlier in the Indians. convexity caused by the pupillary block. The
Shallow ACs are commonly seen amongst close peripheral AC depth can be assessed clinically. A
relatives of those with angle closure glaucoma. In one narrow slit lamp beam is aligned vertically to the
study 20 percent of 95 such relatives were found to peripheral cornea either temporally or nasally. The
have potentially occludable angles. However, only 10 distance between the corneal endothelium and the
percent of such angles actually developed closure.14 surface of the iris is compared to the thickness of the
corneal optical section. When the peripheral AC depth
SPECIAL METHODS OF EXAMINATION exceeds one-half of the corneal thickness, the
peripheral AC is deep and the angle is wide and
1. Estimation and measurement of AC depth
unlikely to close. Peripheral AC depth of one-fourth
2. Gonioscopy
the corneal thickness usually points to a narrow
3. Intraocular pressure
occludable angle, while peripheral AC depth less than
4. Visual fields.
one-fourth of corneal thickness indicates a very narrow
Central AC depth is related primarily to the
slit-like angle. This is a very useful method for
position of the anterior lens surface.
population screening.
It can easily be estimated by use of a penlight torch,
shown from the temporal side close to the eye at the
Primary Angle Closure (Glaucoma)
level of the iris. If the central AC is shallow the
Suspect (PACS)
temporal iris will be illuminated, whereas the rest of
the iris will be in shadow. Syn: Occludable angle: Eyes with PACS may have
Central AC depth can also be easily measured on synechiae and for raised IOP. It is a risk factor of
a Haag-Streit slit lamp using the method of Redmond PACG. Prophylactic measure is Laser peripheral
Smith.14 The oculars of the slit lamp are set for viewing iridectomy.17
Gonioscopy
The precise assessment of primary angle closure
glaucoma demands gonioscopy. It is essential to dis-
tinguish between creeping angle closure glaucoma
and chronic simple glaucoma with shallow ACs and
narrow angles (Fig. 70.3). On examining the angle it
should be assessed for the following 4 factors:
a. The degree of iris convexity may be graded as none
(flat iris), moderate or marked. In general the
shallower the AC, the greater the iris convexity.
b. Width of the angle is determined both by iris
convexity and the extent to which the iris is pushed
forward by the lens and the iris root insertion. The
slit lamp beam on the back surface of the cornea
meets the beam running across the iris without a
Fig. 70.3: Gonioscopy showing angle closure
break when the angle is closed. If the beams on the
iris and cornea do not meet directly, but are dis-
placed along side each other, the entrance to the tests have been designed to reproduce the clinical
angle will be open. settings in which acute angle closure attacks might
c. The depth of the angle depends on the site of occur with the rationale that it is better for this to occur
insertion of the iris root onto the ciliary body or in the clinic than where it may go unrecognized.
the scleral spur. In wide angles a band of ciliary However, the present provocative tests are too
body can be seen between the scleral spur. In a very inaccurate with high false-positive and false-negative
shallow angle, the iris inserts close to the trabe- rates. Because of this and the advent of laser, intensive
culae. In creeping angle closure the iris root creeps provocative is rarely used.
up the lateral wall to shorten the angle. The dark room test done with the patient in a
d. Peripheral anterior synechiae may be deep in the supine position is considered the most physiologic
angle and hidden from view. They form parti- test.34 The patient is placed in a dark room for 1
cularly when the angle is narrow and shallow, and to 2 hours, with his eyes open. While measuring
may occupy large areas of the circumference. These the intraocular pressure, there should be minimal
synechiae are difficult to see when the angle is very exposure to light. A rise of 8 mm Hg is considered
narrow and the iris is very convex. In acute attacks, diagnostic with confirmation foe angle closure on
the initial pressure recorded gives an idea of the gonioscopy. Mydriasis is the important part of this
amount of risk to the eye involved and the degree test.
of urgency for its control. A slow and incomplete In the prone provocative test, the patient lies face
fall of pressure is an indicator of persisting angle down with his forehead on the back of his hands or
closure. Tonometry should be repeated after 6 to 8 on a firm pillow for about an hour in a darkened room
hours of initiating therapy. without going to sleep. A rise of 8 mm Hg is
considered positive. 7.5 percent of patients still show
Visual fields The visual field recording is useful in the
positive prone provocative test after peripheral
different stages of angle closure glaucoma. Visual field
iridectomy.35 The mechanism here is unrelated to
testing is not appropriate for the involved eye at the
mydriasis and is said to be due to the slight anterior
acute stage. On the other hand, if the disc is cupped
movement of the lens.
or the pressure raised in the fellow eye, visual field
In the mydriatic test, the pupil is semidilated with
testing of the fellow eye can be of help in decision for
a weak cycloplegic agent and the pressures are
surgery of the involved eye.
measured at one or two hours interval. A rise in
pressure of 8 to 10 mm Hg is suggestive of glaucoma.
Provocative Tests
Dilation of the pupil in these eyes with shallow
A variety of tests have been developed to determine chamber is a risk and the eye should be observed until
whether a narrow angle is actually occludable. These the pupil has constricted, because the angle may be
open while the pupil is dilated; however it may close activity. These attacks, usually relieved by analgesics
when constricting. or rest, are usually self-limiting. They last for about
Amongst the various pharmacological tests, the half an hour after cessation of the inciting activity and
Phenylephrine-Pilocarpine test is the most widely are always relieved by sleep. Relief of an attack during
used. After a base line record of IOP, 2 percent pilo- sleep is usually attributed to sleep induced miosis and
carpine and 10 percent phenylephrine are instilled. possibly due to decreased intraocular pressure
The phenylephrine is then repeated half hourly till resulting from decreased aqueous humor secretion. If
there is a rise in intraocular pressure by 8 mm Hg. If these symptoms persist, they usually indicate that
by two and half-hours there is no rise then the test is acute angle closure has supervened. Haloes which are
terminated with instillation of 0.5 percent thymo- seen every night are usually due to cataracts, corneal
xamine. Positive tests of 8 mm Hg or more are termi- disease or persistently high intraocular pressure.
nated with thymoxamine and intravenous aceta- These intermittent attacks usually occur at intervals
zolamide 500 mg. Wishart has studied the prognostic of weeks or months, but the intervals may become
value of this test and has concluded that the test shorter till they recur almost every night. They may
significantly lacks both sensitivity and specificity and continue for months or years. Usually unilateral, but
therefore is of limited value in the diagnosis and bilateral attacks also can occur.
management of angle closure glaucoma. The most important diagnostic feature of
intermittent angle closure is classical history. The eyes
CLINICAL TYPES AND FEATURES are normally quiet between attacks such that there is
a tendency to miss the diagnosis. The common
Following are the classical types of primary angle
misdiagnoses are migraine, anxiety or systemic
closure glaucoma:
hypertension.
1. Intermittent and subacute angle closure
Examination of these eyes usually reveals shallow
2. Acute angle closure
ACs, convex irides, and narrow angles sometimes with
3. Chronic angle closure and its variant
an enlarged or oval pupil. Provocative testing can
4. Creeping angle closure.
result in angle closure and a reproduction of the
Acute and subacute angle closures and creeping
patient’s symptoms.
angle closure with time usually develop into chronic
Approximately 30 percent of patients with acute
or absolute glaucoma (Fig. 70.4).
angle closure have a history of previous intermittent
attacks. 17 Very occasionally the attacks may be
Intermittent Angle Closure Glaucoma
accompanied by a creeping angle closure glaucoma.
Intermittent angle closure glaucoma is defined as
repeated episodes of raised intraocular pressure
caused by pupillary block and angle closure which
clears spontaneously, affecting eyes with shallow ACs
and narrow angles, with normal ocular function in
between the attacks.
The angle closure is more often partial than
complete, affecting particularly the more narrow
superior part of the angle. These attacks usually follow
events such as fatigue, emotion or close work invol-
ving concentration.
The cardinal symptoms are a dull ache in or around
one eye, blurred vision, and colored haloes around
lights and transient uniocular visual loss,16 haloes are
due to stretching of the corneal lamellae, causing the
cornea to act as a diffraction grating producing a blue-
green central and yellow-red peripheral halo.
The attacks tend to recur under similar circumstan-
ces at the same time of the day such that the individual
may recognize the cause and avoid or reduce the Fig. 70.4: Clinical types of angle closure glaucoma
Intermittent angle closure glaucoma is a surgical diagnosis may be confused due to the systemic
condition and a typical history supported by the symptomatology.19,20
characteristic anatomy justifies an iridectomy to break Corneal edema may limit a gonioscopic and
the pupillary block. In most eyes this is enough to cure posterior segment examination. Examination of the
the glaucoma. Although pilocarpine will ease off the fellow eye is important to rule out neovascular uveitic
attacks, it is unsafe because it misleads the patient into or phacolytic glaucoma. Early in the attack the optic
thinking it to be a cure. In symptom-free period the disc is usually edematous and hyperemic.21 With
patient may discontinue pilocarpine use and an attack prolonged attacks optic disk pallor and cupping along
of angle closure may set in. Despite the use of miotics, with visual field damage sets in. Central retinal venous
an attack of acute angle closure may occur causing occlusion may occur as a result of an acute attack or
severe damage to the globe. may precipitate one.22
An attack may terminate spontaneously either due
Subacute Angle Closure Glaucoma to the tissue necrosis which may allow aqueous to
percolate through the iris stroma, but more frequently
In this stage the attacks occur more frequently and
it occurs secondary to suppression of aqueous forma-
are more prolonged than in intermittent attacks. The
tion as a result of the high intraocular pressures.
symptomatology is more marked and the attacks may
occur over months or years, finally leading to an acute
Creeping Angle Closure Glaucoma
attack. Subacute attacks can cause severe damage
without much inflammation. They may produce a An insidious and asymptomatic angle closure that
chronically dilated pupil, mild iris atrophy, peripheral occurs from within the depth of the angle is known as
anterior synechiae and pigmentation of the iris close creeping angle closure. The closure occurs
to the inferior angle. The intraocular pressure levels circumferentially and begins in the deepest portion
and the visual field changes vary depending upon the of the angle. The iris usually creeps up the ciliary face
severity and duration of the attacks. to the scleral spur and then to the trabecular mesh-
work. The appearance over time is that of a
Acute Angle Closure Glaucoma progressively more anterior iris insertion.
The symptoms of creeping angle closure are
Various stimuli may trigger the onset of acute angle
usually absent until the intraocular pressure rises high
closure glaucoma. Although pupillary block is the
enough to blur vision or to cause haloes. The field loss
common mechanism, the course of the disease
progression is much faster than in POAG. Congestion
depends upon the degree and suddenness of the block,
in these eyes is usually not present and there are no
the flaccidity and physiological responses of the iris,
pupillary abnormalities or signs of inflammation as
and width and depth of the AC angle.
seen following an acute attack. Diagnosis is confirmed
The common precipitating events are illnesses,
by gonioscopy.
emotional stress, trauma, intense concentration and
pharmacological pupillary dilatation. A recent report
Chronic Angle Closure Glaucoma
described acute angle closure glaucoma occurring
during childbirth.18 These attacks rarely begin simulta- Chronic angle closure is defined as patchy or total
neously in both eyes; the eye with the shallower closure of the angle by peirpheral anterior synechia.
chamber is usually involved first. Most of the attacks It results from multiple intermittent or subacute and
begin around sunset as a mild one which rapidly prolonged acute attacks. The angle usually becomes
increase in severity. Patients who have had previous chronically occluded as a result of the attacks with
intermittent attacks usually go to sleep expecting mild inflammation. The peripheral anterior synechiae
relief, but the symptoms get aggravated and the form in the superior angle as pinpoint synechiae
patient usually awakens with a full-blown attack. The reaching to the midtrabecular meshwork and then
symptoms are intense pain allover the head and face gradually expand in width.
accompanied by blurred vision with lacrimation and Chronic angle closure glaucoma is a useful clinical
lid edema. Nausea and vomiting may be profuse along term to describe the duration of the pathology. If
with anxiety and fatigue. Vasovagal responses may chronic angle closure has been caused by previous
cause bradycardia and diaphoresis, and the acute angle closure then a peripheral iridectomy will
usually make the fellow eye permanently safe, but if of chilled fruit juice with ice chips is usually adminis-
creeping angle closure is present, the peripheral tered. If there is severe nausea and vomiting 20 percent
iridectomy may not always prevent angle closure in mannitol in a dose of 1.5 to 2 G/kg body weight is
the fellow eye. given intravenously over 45 minutes. These agents
usually decrease the intraocular pressure within 30 to
MANAGEMENT 60 minutes after administration and the effect lasts
for about 5 to 6 hours. Hyperosmolar coma can be a
Treatment in primary angle closure glaucoma has
serious complication of these agents, due to CNS
three goals:
dehydration. Patients with renal or cardiovascular
1. To eliminate pupillary block
disease or those in dehydration from severe vomiting
2. To reopen the filtration angle
are at high risk. Acetazolamide is very effective in
3. To prevent further optic nerve damage by lowering
treating an acute attack of angle closure glaucoma. It
the intraocular pressure.
causes rapid reduction in the IOP and can open up
Iridectomy is used to break the pupillary block.
some closed angles, even in the presence of a pupillary
Medical therapy is useful to control the intraocular
paralysis and ischemic iris atrophy. Large doses of
pressure both before and after the iridectomy. Filtra-
acetazolamide such as 500 mg orally and 500 mg
tion surgery may be required if the above measures
intravenously are started (if intravenous injections are
fail to control the intraocular pressure. The type of
not available 1000 mg can be administered orally). The
treatment instituted depends upon the stage at which
advantage of the intravenous injection is its rapidity
the patient presents and the level of the IOP.
of action and when severe vomiting is present.
Following oral therapy, maximal effect occurs at 2
Intermittent and Subacute
hours and this effect lasts for around 5 to 6 hours.
Angle Closure Glaucoma
Carbonic anhydrase inhibitors markedly decrease
In a patient with a typical history of intermittent or the aqueous formation and the hyperosmotics suck
subacute attacks, an iridectomy or iridotomy usually up the remaining aqueous in the posterior chamber
relieves the symptoms by relieving the pupillary through the uveoscleral outflow. This results in a
block. Long-term usage of miotics may reduce further marked lowering of the pressure in the posterior
acute attacks but it does not prevent the development chamber and a transient increase in the anterior cham-
of either acute or chronic angle closure. In eyes where ber pressure. Due to this the iris is forced back and in
there is a high risk of developing chronic angle closure, the absence of synechiae, a closed angle will open.23
the base pressure will modify the treatment. When it The beta adrenergic blockers, topical carbonic
is normal only an iridotomy may suffice. However, if anhydrase inhibitors and prostaglandin preparations
it is not controlled with medicine then surgery is are usually additive with acetazolamide in decreasing
indicated. the IOP. They are more useful once the acute phase
has been tided over, in maintenance of the reduced
Acute Angle Closure Glaucoma pressure before iridectomy.
Acute angle closure glaucoma is a medical emergency.
Therapy is directed toward (a) rapid lowering of IOP, Miotics
(b) opening the filtration angle, (c) supportive therapy,
In the past intensive miotic therapy was the classical
and (d) preventing future acute attacks.
treatment for acute attack of PAG. After starting oral
and systemic hyperosomotic drug along with carbonic
Medical Therapy
anhydrase, few instillation of pilocarpine drop may
Hyperosmotic agents are the commonly used first line be enough to constrict the pupil.
of drugs to help reduce the IOP rapidly. These agents When IOP is around 60 mm Hg, the pupil is
raise serum osmotic pressure and withdraw fluid from unresponsive to miotics due to inactivity of the sphinc-
the eye, especially the vitreous humor. Vitreous dehy- ter. Pilocarpine may paradoxically worsen the
dration further assists in opening up the angle, by condition in an acute angle closure attack. However,
allowing the lens to move posteriorly and deepening there may be ciliary spasm causing anterior movement
the anterior chamber. Oral glycerol in a full dose of of the iris lens diaphragm with further shallowing the
1 ml/kg body weight diluted with an equal volume AC thus decreasing the uveoscleral outflow which
may be an important channel for drainage in these 3. Administer either oral glycerol or intravenous
eyes. Most eyes with an acute attack have a large mannitol if the pressure is over 30 mm Hg.
degree of pupillary block contributory to the angle Intravenous acetazolamide, if available may be
closure. In these eyes, pilocarpine is usually effective given simultaneously.
in breaking the block. However, if the angle closure is 4. Oral 500 mg acetazolamide is then administered
caused by anterior lens movement or an intumescent and a drop of topical beta-blocker may be instilled
lens, then miotics worsen the situation. Thus miotics in the affected eye.
should be used cautiously in the treatment of an acute 5. Have the patient lie supine to permit the lens to
attack. fall backward with vitreous dehydration.
Thymoxamine is a miotic agent that causes para- 6. Reassess the ocular findings at the end of one hour
lysis of the dilator muscle. It is an alpha adrenergic and if possible a gonioscopy is performed. The IOP
antagonist and depends upon an active sphincter may have decreased but angle usually remains
muscle to produce the miosis. However, it produces appositionally closed. A drop of 2 percent or 4
the miosis without affecting the lens position and percent pilocarpine is instilled.
thickness. With markedly raised pressures and an 7. The patient is again examined 30 minutes later and
ischemic sphincter neither pilocarpine nor thymoxa- a gonioscopy performed.
mine will act. a. If the pressure has fallen adequately and the
angle has opened up then the pressure fall is
Physical Methods maintained by use of oral acetazolamide 250 mg
6 hourly, topical beta-blockers and 2 percent
Despite intensive medical therapy, the angle fails to
pilocarpine three times a day. Topical anti-
open and the pressure remains high, certain physical
inflammatory drugs are also begun to quieten
methods have been described to break an acute attack.
the eye. Laser iridotomy is usually performed,
Indentation of the central cornea with a cotton-tipped
once the eye quietens down.
applicator, a Zeiss four-mirror gonioscopy lens or a
b. If the pressure remains elevated, and the angle
muscle hook forces the aqueous into the angle
remains closed then the lens related angle
periphery and opens it temporarily. Repeated cycles/
closure should be suspected and further
of 30 seconds indentation followed by 30 seconds
pilocarpine is stopped. In these eyes argon laser
release of pressure may allow enough aqueous to flow
iridoplasty is indicated.26,27
out of the angle to decrease the intraocular pressure,
so that miotics may be effective.24
Iridectomy
Supportive Therapy Iridectomy is the definitive management as it relieves
the pupillary block (Fig. 70.5). Unless extensive
In case of severe pain adequate narcotic analgesics synechial closure has occurred, the angle also widens.
such as pentazocine or pethidine may be administered Laser iridotomy has become the procedure of choice
in a dose based upon the body weight. Severe in these cases due to its ease, patient acceptability, and
vomiting can be countered by injectable antiemetics. low rate of complications. In the dark brown Indian
Adequate hydration should be maintained; in case of eyes, the Nd: Yag laser alone or in combination with
severe dehydration hyperosmotics are contraindi- the argon has been found to be useful in obtaining
cated. Topical nonsteroidal anti-inflammatory drugs adequate iridectomies in a single treatment session
should be started to decrease the inflammatory res- (Fig. 70.6).28 Long-term follow-up data indicate that
ponse prior to laser or surgery. 30 percent of the eyes with primary angle closure
glaucoma successfully treated with immediate laser
Summary of the Approach25 peripheral iridoplasty followed by laser peripheral
1. Compile a detailed history specifically relating to iridotomy develop peripheral anterior synechiae
previous intermittent attacks in the fellow eye and resulting in high IOP.29
precipitating factors.
2. Examine both the affected and unaffected eye Iridoplasty
under a slit lamp with respect to the shape of the Peripheral argon laser iridoplasty may open up the
iris and depth of the central and peripheral AC. angle partially, but it does not eliminate the pupillary
IOP measured and gonioscopy performed to
differentiate the mechanisms of the postdilation
pressure rise.
b. In presence of appositional closure after an
iridectomy (if iridoplasty has not been already
performed) the mechanism may be a plateau iris,
a large lens, forward lens movement or malignant
glaucoma. If the closure encompasses more than
half of the angle, then usually a peripheral irido-
plasty is indicated. A few days later a drop of cyclo-
plegic is applied. If there is a deepening of the AC
and opening of the angle then the patient can be
maintained on long-term cycloplegia unless it does
not affect the intraocular pressure. If, however, the
angle closes, then further cycloplegic is avoided.
Fig. 70.5: Microspherophakia If the closure is partial then pilocarpine is dis-
continued after measuring AC depth. The patient
is re-examined after 2 days, if the angle is open
and the anterior chamber deepens, it indicates that
the appositional closure was caused by the miotic
agent. If the intraocular pressure is normal, the
patient is maintained off miotics, however if the
patient requires miotics for control of IOP, then a
peripheral irido-plasty may be performed.
Long-term Management
Repeated gonioscopy at requisite intervals is essential
for proper management. If the IOP remains elevated,
after an iridectomy and the angle is more or less open,
medical therapy is usually necessary similar to open
angle glaucoma. Argon laser trabeculoplasty is also
Fig. 70.6: Peripheral iridectomy releiving the pupillary block
successful in these eyes with residual open angle
glaucoma after reopeniong the angle, if the synechiae
are present for less than 180o or if circumferential
block and is not a substitute for iridectomy which is
peripheral anterior synechiae do not extend above the
performed as soon as the eye is quiet. However it helps
scleral spur.31 Cumulative probability success rate of
in lowering the intraocular pressure sufficiently for a
66 percent at 36 months following argon laser
few days till the eye quietens down, even in eyes with
trabeculoplasty in 19 patients who has 50 percent or
extensive synechial closure. It is a safer alternative to
less of their angles closed postiridectomy, is claimed.32
surgical iridectomy in these tense inflamed eyes.
Goniosynechiolysis33 may be a surgical option for
patients with medically uncontrolled angle closure
Management After Iridectomy
glaucoma. Campbell and Vela first reported this
Once the pupillary block component has been procedure designed to strip the peripheral synechiae
eliminated by iridectomy, the status of the iridocorneal from the trabecular meshwork.9 However, this proce-
angle should be reassessed by indentation tonometry. dure is apparently successful only if the synechiae
The angle may be open, partially open, or closed. have been present for less than a year.
a. When the angle is open with or without synechiae If the intraocular pressure remains uncontrolled
but no appositional closure, the eye is maintained despite maximum tolerable medical therapy, filtration
on antiglaucoma medications and topical steroids surgery may be indicated with or without the use of
till inflammation subsides. Once the eye quietens, adjunctive antimetabolites, depending upon the status
the pupil is dilated with phenylephrine and the of the optic disk.
Chronic and Creeping Angle 3. Tomlinson A, Leighton DA. Ocular dimensions in the heredity
Closure Glaucoma of angle closure glaucoma. Br J Ophthalmol 1973;57:475.
4. Panek WC, Christensen RE, Lee DA et al. Biometric values in
Laser iridectomy is indicated for all stages of chronic patients with occludable anterior chamber angles. Am J
angle closure glaucoma. This usually opens up those Ophthalmol 1990;110:185.
5. Markowitz SM, Morin JD. Ratio of lens thickness to axial
areas of the angle not involved by synechiae and length for biometric standardisation in angle closure
prevents further synechial closure. Postiridectomy glaucoma. Am J Ophthalmol 1985;99:400.
treatment is similar to that of open angle glaucoma. 6. George R, Paul PG, Baskaran M et al. Ocular biometry in
The need for medical treatment is determined by the occludable angle and angle closure glaucoma: A population
level of intraocular pressure and the status of the optic based Study. Br J Ophthalmol 2003;87,398.
7. Pavlin CJ, Ritch R, Foster FS. Ultrasound biomicroscopy of
disk. If medical treatment alone is insufficient to the anterior segment structure in normal and glaucomatous
control the pressure, surgical filtration is performed. eyes. Am J Ophthalmol 1992;113:381.
In chronic angle closure glaucoma diode laser transs- 8. Clark CV. The prevalance of autonomic neuropathy in the
cleral cyclophotocoagulation is effective in lowering primary glaucomas. Doc Ophthalmol 1990;74:277.
the intraocular pressure. 9. Bigar F, Witmer R. Corneal endothelial changes in primary
acute angle closure glaucoma. Ophthalmolgy 1982;59:596.
10. Campbell DG, Vela A. Modern goniosynechiolysis for the
Plateau Iris treatment of synechial angle closure. Ophthalmology
1984;91:1052.
If after a laser iridectomy the angle still remains
11. Fontana SC, Brubaker RF. Volume and depth of anterior
appositionally closed or occludable then usually the chamber in the normal ageing human eye. Arch Ophthalmol
patient is put on low dose miotics. Miotics usually 1980;98:1803.
control the intraocular pressure well, if the angle still 12. Alsbrik PH. Anterior chamber depth, genes, and environment:
remains appositionally closed then a peripheral A population study among long-term Greenland Eskimo
iridoplasty is indicated. In cases of complete plateau imigrants in Copenhagen. Acta Ophthalmol 1987;64:593.
13. Wilensky J. Racial influences in glaucoma. Ann Ophthalmol
iris syndrome, where the pressure rises postdilation, 1977;9:1545.
treatment is indicated. But if is an incomplete 14. Spaeth GL. Goniosocpy uses old and new: The inheritance of
syndrome and the pressure remains normal then occludable angles. Ophthalmology 1979;85:222.
observation is preferred. 15. Smith RJH. A new method of estimating the depth of the
In cases of plateau iris configurations with open anterior chamber. Br J Ophthalmol 1979;63:215.
16. Ravitz J, Seybold ME. Transient monocular visual loss from
angles diagnosed incidentally, care must be exercised narrow angle glaucoma. Arch Neurol 1984;41:991.
on dilation of the pupil. The patient should be 17. Thomas R, George R, Parikh et al. Five year risk of progressive
followed-up with regular gonioscopy for signs of primary angle closure suspect to primary angle closure. A
spontaneous angle closure. population based study. Br J Ophthalmol 2003;87:450.
18. Kearns P and Dhillon B. Angle closure glaucoma precipitated
by labor. Acta Ophthalmol 1990;68:225.
MANAGEMENT OF THE FELLOW EYE AND
19. Watson N, Kirkby GR. Acute glaucoma presenting with
ASYMPTOMATIC NARROW ANGLES abdominal symptoms. Br Med Jr (Clin Res) 1989;229:254.
20. Wohl J, Zalta H, Gingold M. Atypical chest presumed
Acute angle closure attacks are usually unilateral,
secondary to angle closure glaucoma. Glaucoma 1989;11:77.
however, there is a high risk of the fellow eye deve- 21. Sonty S, Schwartz B. Vascular accidents in acute angle closure
loping an acute attack within one year of the attack in glaucoma. Ophthalmology 1981;88:225.
the first eye. Hence, a prophylactic iridectomy is 22. Mendelsohn AD, Jampol LM, Schoch D. Secondary angle
indicated for the fellow eye following an attack of closure glaucoma after central retinal vein occlusion. Am J
primary angle closure glaucoma. Drug therapy with
23. Lowe RF, Ritch R. Angle closure glaucoma: Clinical types. In
pilocarpine or betablocker is not reliable; it may rather Ritch R, Shields M and Krupin T (Eds): The Glaucomas. St
lead to an acute attack. Louis: CV Mosby Co, 1989.
24. Anderson Dr. Corneal indentation to relieve acute angle
REFERENCES closure glaucoma. Am J Ophthalmol 1984;88:1091.
25. Kramer P, Ritch R. The treatment of angle closure glaucoma—
1. Lowe RF. Primary angle closure glaucoma: A review of ocular revisited (editorial). Am J Ophthalmol 1984;16:1101.
biometry. Aust J Ophthalmol 1977;5:9. 26. Ritch R. Argon laser treatment of medically unresponsive
2. Delmarcelle Y. Biometric ocular clinique 9 oculometric. Bull attacks of angle closure glaucoma. Am J Ophthalmol
Soc Belge Ophthalmol 1976;172 (fascule 1). 1982;94:197.
27. Ritch R, Liebman J. Laser iridectomy and iridoplasty. In Ritch 32. Hovding G, Aasved H. Angle closure glaucoma. Cur Opin
R, Shields MB and Krupin T (Eds): The Glaucomas St Louis: Ophthalmol 1992;3:149.
CV Mosby Co, 1989. 33. Friedman Z, Neumann E. Comparison of prone position,
28. Jacobi PC, Dietkin TS, Luke C et al. Primary phacoemulsifi- darkroom, and mydriatic tests for angle closure glaucoma
cation and intraocular lens implantation for acute angle before and after peripheral iridectomy. Am J Ophthalmol
closure glaucoma. Ophthalmology 2002;109:1597. 1976;74:24.
29. Ritch R, Lowe RF, Reyes A. Therapeutic overview of angle 34. Mapstone R. Provocative tests in closed angle glaucoma. Br J
closure glaucoma. In Ritch R, Shields MB and Krupin T (Eds): Ophthalmol 1976;60:115.
The Glaucomas. St Louis: CV Mosby Co, 1989. 35. Wishart PK. Does pilocarpine-phenylephrine provocative test
30. Shirakasi M, Iwata K, Makayama T. Argon laser trabeculo- helps in management of acute and subacute angle closure
plasty for chronic angle closure glaucoma uncontrolled by glaucoma. Br J Ophthalmol 1991;75:284.
iridotomy. Acta Ophthalmol 1989;67:265. 36. Ang LPK, Aung T, Shew PTK. Acute primary glaucoma in
31. Shingelton B, Chang M, Bellows A et al. Surgical gonio- an Asian population: Long term outcome of the fellow eye
synechiolysis for angle closure glaucomas. Ophthalmology after prophylactic laser peripheral iridotomy. Ophthalmology
1990;97:551. 2000;107:2092.
Chapter 71
Secondary Glaucoma
NK Dutta, LC Dutta
INTRODUCTION ii. Outflow block This is due to pathology in the

trabecular meshwork, Schlemm’s canal,
1. Secondary glaucoma (Table 71.1) may be due to
collector channels and venous system.
some systemic diseases or ocular and orbital
3. Secondary glaucoma may be open angle type or
diseases.
close angle type. In some cases close angle develops
2. Basic mechanism may be due to the following:
in open angle glaucoma. Without going into the
a. Hypersecretion of aqueous humor without any
open angle or close angle classification, a random
pathology in the outflow pathways. Classical
description will be made depending upon the
example being epidemic dropsy glaucoma.
anatomical or histopathological anomalies causing
b. Blockage in the aqueous drainage pathways:
the raised intraocular pressure (IOP).
i. Internal flow block Pupillary or ciliovitreo-
retinal block mostly causes angle closure SECONDARY GLAUCOMA DUE TO
glaucoma. SYSTEMIC DISEASE
Table 71.1: Secondary glaucoma
Epidemic Dropsy Glaucoma
• Secondary open angle glaucoma
• Pseudoexfoliation
Epidemic dropsy is an acute systemic disease caused
by the toxic effect of the oil of the seeds of Mexican
• Pigmentary – Pigment dispersion
poppy (Argemon mexicana). This seed simulates the
• Steroid induced glaucoma
mustard seeds; thus mustard oil (a common cooking
• Post-traumatic ? angle recession medium amongst the people in Eastern India) can be
• Postuveitis adulterated with this toxic agent. The toxic substance
• Postsurgical in the oil is sanguinarine which causes dilation and
— Cataract operation engorgement of the capillars of the deeper layers of
— Retinal detachment operation the skin, cardiac and skeletal muscles, and vital organs
— Penetrating Keratoplasty
of the body including the eye.1
• Secondary angle closure glaucoma Ocular complication of epidemic dropsy is open
• With pupillary block angle glaucoma with about 70 to 80 mmHg intraocu-
— Total posterior synechiae – iris bombe lar pressure in a painless white eye. It is hypersecretive
— Microspherophakia glaucoma. First described in Calcutta about a century
— Traumatic anteriorly dislocated lens
back;2 periodic epidemics still break out, the last being
• Intraocular tumor
the one near Delhi in 1983-84. 3 Systemic manifesta-
— by pushing the iris forwards
tions of epidemic dropsy are edema of feet, ascites and
• Iris neovascular membrane/adherent leucoma pericardial effusion. The glaucoma is bilaterally
— by pulling the iris root forwards
symmetrical and younger individuals are more
• Iridocorneal –endothelial syndrome susceptible. If treatment is delayed, optic disk cupping
• Posterior polymorphous corneal dystrophy with gross visual field defect is possible.
Chapter 71: Secondary Glaucoma 537
Treatment consists of immediate discontinuation CHILDHOOD SECONDARY GLAUCOMA
of use of mustard oil and institution of antiglaucoma Retinoblastoma
therapy along with oral indomethacin. Drugs used for
POAG may be necessary if IOP remains high after Glaucoma in retinoblastoma may be due to the
discontinuance of use of mustard oil. Surgical treat- following:
ment, trabeculectomy,3 may be necessary in cases a. Invasion of iris and trabecular meshwork by tumor
resistant to medical therapy. cells
b. Rubeosis iridis
Systemic Amyloidosis c. Forward displacement of the iris-lens diaphragm,
thereby blocking the filtration angle (pushing
Amyloidosis is a hereditary systemic disease in which mechanism).6
amyloid material is deposited in the tissues of almost
all the organs of the body including the eye and ocular Retinopathy of Prematurity (ROP)
adnexa. Amyloid is an albuminous substance similar
in chemical reaction to starch. The cause of glaucoma Development of retrolental fibrotic membrane may
in systemic amyloidosis is deposition of amyloid in cause forward displacement of the iris-lens diaphragm
the trabecular meshwork leading to decreased leading to angle closure glaucoma. Secondary glau-
aqueous outflow. In about twenty five percent of coma due to the same mechanism may also develop
patients with hereditary systemic amyloidosis in adults, if the patient had ROP in childhood.7, 8
secondary open angle glaucoma develops during the
third to fifth decade of life. Glaucoma may be Aniridia
associated with pigment dusting of the corneal Aniridia is congenital absence of the iris. Though the
endothelial surface, and trabecular meshwork along complete iris is not developed, the most peripheral
with iris transillumination defect as occurs in pigment part of the iris in the form of a fibrous sheet is adhered
dispersion syndrome. It may also resemble pseudoex– to the anterior margin of the ciliary body, which can
folilation syndrome; white fluffy flakes are seen on be seen in gonioscopic examination.9 Most of the cases
the iris surface near the pupillary margin and on the of aniridia have strong family history, and often it is
equatorial lens capsule. Ultramicroscopic histopa- of dominant hereditary character. Incidence of aniridia
thological examination of the trabeculectomy speci- is I in 100,000 births. Usually bilateral, it also occurs
men reveals heavy accumulation of amyloid fibrils as an association of some systemic diseases like mental
and pigment granules in the trabecular meshwork.4 retardation, Wilm’s tumor, genito-urinary defect and
Medical management of secondary glaucoma in craniofacial dysostoses.
amyloidosis is similar to that of POAG. Trabeculec- In most cases of aniridia, glaucoma develops in late
tomy is indicated if IOP is not controlled with medical childhood or early adulthood or may not develop even
treatment. in ripe adulthood. Aniridic glaucoma may also be
associated with trabecular dysgenesis, and this may
Pseudoexfoliative Syndrome be a cause for development of secondary glaucoma.10
Exfoliative or pseudoexfoliative syndrome, which is The hypoplastic fibrous tissue stump attached to the
basically a systemic disorder which affects the eye and ciliary body, representing the iris but hidden by the
produce open angle glaucoma.5 The deposits of some sclera underneath the limbus, sweeps anteriorly with
abnormal substances may be in the trabecular aqueous outflow and covers the trabecular meshwork
meshwork, as well as in other parts of the eye, viz. and causes angle closure secondary glaucoma. Before
over the lens capsule, surface of iris, zonules and even the development of glaucoma, gonioscopic exami-
over the anterior vitreous face. Thirty one percent of nation reveals the appearance of the chamber wall.
cataract cases are reported to have exfoliation Aniridia may be associated with a large number
syndrome.5 True exfoliation seen in persons working of ocular lesions including peripheral corneal opacity,
in steel and glass factories may also cause glaucoma. lens opacity, ectopia lentis, foveal hypoplasia,
True exfoliation of the lens capsule is best seen by dila- choroidal coloboma, nystagmus, and strabismus. The
ting the pupil, because it occurs in the area normally peripheral corneal opacity involves the epithelium or
covered by the iris (also see chapter 74). superficial layers of substantia propria extending upto
the central part of the cornea, causing loss of visual the sclera and layer of choriocapillars resulting in
acuity necessitating keratoplasty.11 spontaneous choroidal detachment in early adult life.
Glaucoma with aniridia responds poorly to Slowly, the fluid continues to accumulate in this space
medical therapy. Drugs which decrease formation of and spreads peripherally towards the ciliary body.
aqueous humor like betablocker, topical carbonic This annular choroidal detachment thus formed may
anhydrase inhibitor formulations are effective in lowe- be associated with forward rotation of the ciliary body
ring IOP by decreasing aqueous flow. Surgical opera- resulting in relaxation of the zonules leading to
tion like goniotomy can help if done under view. forward bulging of the crystalline lens, iridocorneal
Trabeculectomy is an effective surgical procedure. In apposition and relative pupillary block ultimately
refractory cases of aniridic glaucoma, cycloablation resulting in angle closure glaucoma. 15 However,
by cryo or laser may be of help in lowering IOP; unless secondary open angle glaucoma may also be asso-
it is done with accurate titration, it may lead to phthisis ciated with nanophthalmos. The treatment of angle
bulbi. closure glaucoma is in the same line of PACG.
Betablockers, carbonic anhydrase inhibitors and
Nanophthalmos (nanos Gr. = dwarf) hyperopsmotics should be tried. Laser iridotomy and
Nanophthalmos is a bilateral condition resulting from laser peripheral iridoplasty (gonioplasty) are indicated
arrest of development of the globe with a corneal if the corneal transparency is good.
diameter of 9.5 to 11 mm, axial length of the eye ball
14.5 to 20 mm and combined thickness of the sclera LENS INDUCED GLAUCOMA (Table 71.2)
and cornea 1 to 2 mm. The size of the nanophthalmic Glaucoma due to Lens Swelling (Phacomorphic)
eye is about two-thirds of the normal eye. The condi-
This is also called phacomorphic glaucoma. Swelling
tion is hereditary and commonly autosomal recessive
of the lens can occur in the following conditions:
but may also be dominant. Majority of the cases of
Early cataract Early stage of cataract formation due to
nanophthalmos are highly hypermetropic to the extent
lens intumescence.
of +10.0 D to +20.0 D. Very rarely the eye may be
emmetropic or may be low myopic (Fig. 71.1).
Angle closure glaucoma in elderly person is the Table 71.2: Causes of lens induced glaucoma
main complication of nanophthalmos. Glaucoma is 1. Dislocation or subluxation of lens
considered to be related to the thickness of the 2. Phacomorphic—due to lens intumescence
sclera.12,13 The anatomic characteristics of the nano- 3. Phacolytic glaucoma
phthalmic eye are shallow anterior chamber with 4. Lens particle glaucoma
prominent iris convexity, reduced axial length and 5. Phacoanaphylactic glaucoma
disproportionately large crystalline lens contributing
to the development of angle closure glaucoma.
The mechanism of development of angle closure
glaucoma in nanophthalmos is also related to effusion
of fluid in the suprachoroidal space: Increased scleral
thickness plays the key role in development of sponta-
neous choroidal effusion. In physiological conditions
some proteinous molecules pass from the intra-
vascular choriocapillars to the suprachoroidal space
and maintain the osmotic molarity. Some fluid may
be present in the space between the sclera and
choroids; but the fluid can percolate and go out
through the sclera of normal thickness. In nano-
phthalmos the sclera is abnormally thick due to the
presence of large collagen bundles and increased
glycosaminoglycans.14 Moreover, the vortex veins are
strictured by the abnormally thick sclera. This leads Fig. 71.1: Digital biometry of a highly hypermetropic eye
to collection of fluid in the potential space between approaching nanophthalmos. Intraocular pressure was normal
Hypermature cataract In hypermature intumescent i. Lens is engaged in the pupillary area causing
cataract the lens becomes swollen due to imbibation pupillary block.
of more fluid by the lens protein to maintain osmotic ii. Lens may be eccentrically lodged in the anterior
balance.16 chamber; in this situation glaucoma may develop
partly due to increased secretion of aqueous
Drug idiosyncrasy Lens intumescence in drug idiosyn-
humor and partly due to mechanical obstruction
crasy and systemic disease is associated with
of the angle by the lens. Treatment is by removal
transitory myopia.
of the dislocated lens after lowering the IOP with
Hypermature Cataract and Phacolytic Glaucoma topical beta blocker, carbonic anhydrase inhibi-
tors and hyperosmotic drugs; use of miotics may
Hyperosmotic glaucoma aggravate the condition.
In both these two conditions open angle secondary iii. Subluxated lens may directly move forward but
glaucoma develops accompanied by variable grades does not enter the anterior chamber, this may
of iritis. In hypermature cataract the liquefied lens push the iris forward causing secondary angle
matter leaks out through the degenerated lens capsule closure glaucoma. Peripheral argon laser
and causes glaucoma by retaining more intracameral iridotomy is effective to lower the IOP and the
fluid due to raised osmotic pressure of the aqueous.16 lens may settle back on the patellar fossa. The
Soluble lens protein and also the cellular and residual glaucoma is to be controlled by drug
exudative inflammatory deposits may block the therapy.
trabecular meshwork to cause decreased facility of iv. In case of dislocation of the lens into the vitreous
outflow of aqueous and cause glaucoma.17 cavity, secondary glaucoma develops several
years after the lens dislocation. Classically, this
Phacolytic Glaucoma type of glaucoma develops after couching
Literally phacolytic glaucoma means glaucoma “Operation”.
associated with rupture of the lens capsule in
hypermature cataract. However, the capsule may not Lens—particle Glaucoma
rupture in all the cases. The lens capsule becomes In penetrating injury of the eye or after extracapsular
hyperpermeable to macromolecular proteins after cataract operation, lens material can obstruct the
dissolution of the lens matter, leading to retention of trabecular meshwork. However the severity of glau-
an enormous volume of intracameral fluid. These coma depends on the amount of the lens material
macromolecular proteins engulfed by the macro- liberated, the inflammatory process of the eye and the
phages, may clog the aqueous outflow apparatus ability of the trabecular meshwork to clear the lens
leading to stagnation of aqueous resulting in high matter. Characteristic features of this type of glaucoma
intraocular pressure. is a pseudohypopyon and fluffy cortical matter in the
Clinically, it is an ocular emergency characterized lower part of the anterior chamber. In mild cases heavy
by pain and redness of the eye. Intraocular pressure flare and cells and white particles of lens matter can
may be as high as 80 mmHg or more. Corneal epithe- be seen in aqueous humor.
lial edema and pseudohypopyon due to deposition The principle of treatment of this type of secondary
of proteinous material along with macrophages in the glaucoma, is to remove the residual lens particles by
lower part of the anterior chamber may be present. aspiration-irrigation procedure as soon as possible to
Treatment consists of removal of the lens after prevent anterior uveitis or peripheral anterior
lowering the intraocular pressure with carbonic synechiae.
anhydrase inhibitors and osmotic agents like oral
glycerol and intravenous mannitol. Phacoanaphylactic Glaucoma
In phacoanaphylaxis, the patient becomes sensitized
Displacement of Lens to its own lens protein. This may develop with
In concussion injury of the eye due to rupture of the penetrating injury of the lens, extracapsular cataract
suspensory ligaments, the lens becomes spherical and extraction, and also in hypermature cataract.
its diameter is reduced. Glaucoma may develop due Phacoanaphylactic glaucoma cannot be diagnosed
to the following causes: accurately, clinically. It is a pathological entity.18 Two
essential findings for labeling phacoanaphylactic Table 71.3: Major causes of neovascular glaucoma
glaucoma are polymorphonuclear leukocytes in the
Central retinal vein occlusion 36%
aqueous and vitreous specimen, and an insufficient
amount of lens protein in aqueous to cause glaucoma Diabetic retinopathy 32%
by itself. Carotid artery occlusive disorder 13%
Miscellaneous causes 19%
NEOVASCULAR GLAUCOMA (NVG)
(SYN: THROMBOTIC GLAUCOMA, Clinically NVG may be described in two stages:
HEMORRHAGIC GLAUCOMA, RUBEOTIC a. Early stage without raised IOP
GLAUCOMA, 100 DAYS GLAUCOMA, AND b. Stage of raised IOP with clouding of the cornea
CONGESTIVE GLAUCOMA) and circumciliary vascular congestion.
In the early stage, neovascularization of the iris and
Neovascular glaucoma (NVG) is a potentially the chamber angle can be seen by the slit lamp bio-
devastating secondary glaucoma caused by formation microscope and goniscopic examination. In all the
of a fibrovascular membrane, covering the surface of cases of iris neovascularization (NVI) gonioscopy is
the iris, trabecular meshwork and the angle of the absolutely necessary. It should be kept in mind that
anterior chamber. Neovascular glaucoma was first the iris neovascularization frond may rupture even
described by Coats in 1906 by histological finding of with the simplest trauma causing hyphema (Amsler’s
new vessels on the iris in a case of central retinal vein sign). The mild trauma caused during gonioscopic
occlusion (Fig. 71.2). Table 71.3 shows a rough esti- examination may lead to hyphema. In the early stage
mate of the causes of neovascular glaucoma. 19-21 of NVI with angle neovascularization the IOP may be
Retinal vein occlusion (36%) and diabetic retinopathy normal. And it is of utmost importance to find out the
(32%) are the most common causes of NVG. The cause of NVI and institute necessary treatment.
important point to note is that the changes in the The earliest sign of vascular proliferation appears
anterior segment of the eye causing NVG are not at the pupillary margin and later spreads all over the
primary, rather, there is always a predisposing patho- iris surface.21 New vessels may proliferate even from
logic condition elsewhere—and most commonly a the major arterial circle at the root of the iris. It is
disturbance in normal retinal circulation. thought that the VEGF liberated from the hypoxic or
ischemic retina passes anteriorly and along with the
Pathogenesis aqueous humor passes through the pupil to the
Hypoxia of the retina is the main factor in pathogenesis anterior chamber and this is the cause why neovascu-
of neovascular glaucoma. From clinical and experi- larization first starts at the pupillary margin.21 Fine
mental studies, it has been accepted that ischemic tortuous and randomly oriented tufts of vessels on
condition of the retina leads to liberation of an the surface of the iris are formed near the pupillary
angiogenic factor that stimulates new vessel forma-
tion. This factor is identified as vascular endothelial
growth factor (VEGF) .20
Pathologic Process of Neovascularization

The initial pathological process of new vessel
formation is budding from the venous side of the
capillary of the parent vessel. The caliber of the
capillary is increased with associated increased
metabolic activity of the endothelial cells, which
subsequently break down through the surrounding
basement membrane. The budding endothelial cells
first form solid columns but later get partially
separated to form a lumen. In the next step the newly
formed capillaries fuse at their tips to establish Fig. 71.2: Fundus photograph of central
circulation. retinal vein occlusion
margin. In dark irides these tufts may not be visible.
Table 71.4: D/D of iris neovascularization
Early stage of iris neovascularization should be
differentiated from the conditions listed in Table 71.4 1. Postsurgical dilation of iris vessels
Neovascular membrane covers the angle. Chamber 2. Essential iris atrophy
3. Fuchss heterochromic iridocyclits
angle neovascularization may be present without NVI.
4. Retinopathy of prematurity
Gonioscopy reveals new vessels that grow from the 5. Congenital iris tufts of vessels.
circumferential artery of the ciliary body, coming up 6. Secondary to uveitis
to the iris surface and from there extend over the ciliary 7. Pseudoexfoliative syndrome
body band, and scleral spur and the trabecular 8. Acute angle closure glaucoma
meshwork. The IOP may not be elevated in the early
stage of neovascularization. The fibrovascular
membrane also contains some proliferating myo- from diabetic patients 95 percent showed retinal
epithelial cells which are, in fact, fibroblasts with neovascularization.8 Thus it may be concluded that
muscle differentiation. When a fibrovascular memb- the time factors of development of diabetes and
rane is first formed over the chamber angle and cause diabetic retinopathy is predictable but the time
open angle secondary glaucoma.32 Contraction of this sequence between onset of diabetic retinopathy and
membrane pulls the iris forward causing angle closure. NVI is variable.24 The interval between development
This is the “pulling” type of angle closure glaucoma. of NVI and NVG in untreated cases varies from 1 to 3
Further progress of the pathological process leads to years.
ectropion of uveal pigment from the posterior pigment
layers of the iris. Not uncommonly, fibrotic iris leads NVG in CRVO
to a dilated pupil.
On rough estimate about one-third of the patients with
The most common causes of NVG are diabetic
CRVO develop neovascular glaucoma. Based on
retinopathy (43%) and CRVO (37%) . The main causes
fundus fluorescein angiography, CRVO is classified
are detailed in the Table 71.5 Brown et al22 in 1984, on
into two types:
the basis of etiological consideration of a large number
a. Ischemic type with capillary non-perfusion
of cases reported CRVO 36%, Diabetic retinopathy
b. Non-ischemic type with satisfactory capillary
32% and carotid artery occlusive disease (CAOD) 13%
perfusion.
and the rest due to miscellaneous conditions like
In the former type NVG develops at any time
intraocular malignant tumor, Giant cell arteritis, Eales’
between two weeks to two years.25 This NVG was also
disease, Coats’ disease, etc.
named 100 days glaucoma because it usually develops
Diabetic retinopathy is a common cause of NVI.
mostly around 100 days after CRVO. In more than
Proliferative diabetic retinopathy almost always leads
80% of patients with NVI (Rubeosis iridis) and NVG
to NVI.22 In non-proliferative diabetic retinopathy also
appears within first six months after CRVO 19 .
NVI can develop in cases, which show extensive areas
Sometimes in early post thrombotic period it may not
of non-perfusion in FFA. Diabetes mellitus is classified
be possible to ascertain the degree and extent of
into Type I or insulin dependent diabetes also known
capillary non-perfusion following the CRVO because
a juvenile onset diabetes (15%) and Type II, non-
of the overlying retinal hemorrhage which blocks the
insulin dependent, also known as maturity onset
fluorescence in 30% of the FFA studies. In addition to
diabetes (80%); the rest 5% is secondary diabetes
this, some non-ischemic type may convert to ischemic
mellitus. In Type I cases retinopathy develops in 10%
type within 8 months. Not infrequently CRVO and
after 10 years, 50% of cases after 15years and 90% of
pre-existing POAG may be present so much so that
cases after 25 years.
about 75% of cases of CRVO is associated with age
related primary open angle glaucoma. A casual
NVI and NVG in Diabetes
fundoscopy might suggest that the deep wide cup
NVI and NVG are two ocular involvement of facilitated the occlusion of the CRVO at the disk
proliferative diabetic retinopathy (PDR). Incidence of margin. Secondary angle closure glaucoma also can
NVI in unselected cases of diabetes is 1 to 17%.6 But develop due to anterior pulling of the iris by the
in eyes with PDR the incidence of NVI may be as high fibrovascular membrane. However, as indicated in the
as 65%.23 In histopathologic study of eyes removed pathologic process, neovascular process may involve
Table 71.5: Causes of neovascular glaucoma

A. Ocular Vascular Diseases
a. Retinal vascular occlusive diseases
(in order of frequency):
i. Central retinal vein occlusion
ii. Hemiretinal vein occlusion (Figs 71.3A and B)
iii. Branch vein occlusion
iv. Branch arterial occlusion
b. Diabetic retinopathy25
c. Eales’ disease
d. Sickle cell retinopathy
B. Ocular tumors
a. Retinoblastoma
b. Uveal melanoma
c. Metastatic tumor
C. Other ocular diseases
a. Long-standing uveitis
b. Long-standing rhegmatogenous retinal detachment
(Fig. 71.4).
D. Extraocular vascular diseases (rare)
a. Carotid occlusive disease including carotid ligation
b. Pulseless disease
c. Giant cell arteritis.
d. Neurofibromatosis
e. Caroticocavernous fistula
Rhegmatogenous Retinal Detachment

Glaucoma in rhegmatogenous retinal detachment may
Figs 71.3A and B: Fluorescein fundus angiography branch occur due to neovascularization of the iris and angle
vein occlusion. (A) Early arterial phase; (B) Arteriovenous
of the anterior chamber, and also due to deposition of
phase
pigment in the trabecular tissue.27 The first description
the trabecular tissue causing decreased aqueous of chronic OAG secondary to rhegmatogenous detach-
outflow. ment was reported by Schwartz. This is also known
Diabetic retinopathy is the second most common as Schwartz syndrome.
cause of NVG. 31 Important points about NVG in
diabetic retinopathy are:
1. Commonly occurs in cases of proliferative diabetic
retinopathy; but if capillary nonperfusion areas are
large, it occurs in nonproliferative stage also.
2. Incidence is directly proportionate to the duration
of the diabetes.23
3. Incidence is more if associated with hypertension.
4. More common after intracapsular than extra-
capsular lens extraction.
5. After vitrectomy operation, incidence is more
because normally the lens and the vitreous act as a
barrier to passage of the angiogenic factor pro-
duced in the retina.
6. Angle neovascularization precedes iris neovascu- Fig. 71.4: Tobacco-dust deposits in a late case of rhegmato-
larization.26 genus retinal detachment with raised intraocular pressure
Carotid Artery Insufficiency operation reduces the neovascularization process by
28 relieving the stagnation of the angiogenic factor inside
Carotid artery disease may cause NVG. This NVG
the anterior segment of the eye. Trabeculectomy with
has been reported after carotid ligation.29 NVG may
intraoperative use of antimetabolite and artificial
also occur after various therapeutic procedures, viz.
drainage devices are useful surgical procedures
after radiation therapy for ocular malignancy30 and
utilized in NVG.
retinal detachment surgery. Neovascular glaucoma is
also reported in carotico-cavernous fistule.29
Cyclo-ablative Procedure
Management of Neovascular Glaucoma In the past extremes of temperatures (cyclodiathermy
As indicated earlier the two most common causes of or cyclocryotherapy) were used to decrease the
NVG are CRVO and proliferative diabetic retinopathy; production of aqueous humor by cycloablative
retinal vein occlusion constitutes about 40% of NVG.24 procedure.
In a study of a large number (100) of eyes Magaengal Cyclocryotherapy is applied at –60° to –80° C with
et al reported that none of the eyes with CRVO treated large tip cryo applicator transsclerally 2.5 mm
by panretinal photocoagulation (PRP) developed posterior to the limbus over one half of the circum-
NVG.24 Therefore, it is essential to have an FFA study ference of the ciliary body.35 If satisfactory ocular
in all cases of CRVO. However, in case of CRVO with hypotensive effect is not attainable then another 1/
extensive retinal hemorrhage, the presence of capillary 4th of the circumference of the ciliary body keeping
dropout cannot be detected by FFA. Therefore, it is the remaining 1/4th untreated to prevent the eye from
necessary to have another FFA in such cases after becoming phthisical.
resolution of the retinal hemorrhage. When capillary
non-perfusion is present then retinal cryoablation is Laser Cycloablation
the treatment of choice for prevention of NVG.
However, in 1997 Central Retinal Vein Study Group Both Nd-YAG and semiconductor, Diode laser are
recommended that even in presence of capillary non- utilized for cyclophotocoagulation by non-contact
perfusion retina, PRP may not be necessary as an transscleral method or by endoscopic delivery system.
immediate line of action; rather the patients should Diode endocyclophotocoagulation is done using
be reviewed at monthly intervals to detect any early endoscopic delivery system in eyes with good corneal
signs of NVG and NVI with gonioscopic examination clarity. Nd-YAG delivered in continuous mode via a
to rule out development of NVG. When such exami- fiber optic system applied on the conjunctiva about
nation reveals the beginning of the neovascular 0.5 to 1mm posterior to the surgical limbus. Laser
process then only PRP is to be done.33 Of course, the setting is 4 -9 w power, 0.5-0.7 second duration and
success of this modality of management depends 20-30 applications.36
entirely upon the compliance of the patient in main- Goniophotocoagulation36 This also has been tried but
taining the regularity of visiting the doctor. PRP is also unless the angiogenic stimulus is eliminated, this will
the only treatment to prevent NVG in patients with not be effective.
proliferative diabetic retinopathy.35
Seton operations These operations can be performed
Treatment of Acute Episode using Molteno implant, 37 Ahmed’s glaucoma
Not infrequently patients with NVG reports with implant39 or Krupin-Denver valve.38
painful blind eye with corneal edema or extensive
epitheliopathy. These patients need some IOP GLAUCOMA DUE TO UVEAL CAUSES
lowering topical agents along with systemic carbonic Uveal Inflammation
anhydrase inhibitors. Atropine 1% eye drops and
Anterior Uveitis
topical steroid NSAID preparations render some relief.
If refractive media permits, PRP should be done to Intraocular pressure in acute iritis or iridocyclitis may
lessen the progress of the neovascularization process. be low, normal or high depending upon the resistance
of outflow and the severity of the inflammation; the
Surgical Treatment latter decreases efficiency of formation of aqueous.
Drainage operations are indicated for providing a Usually due to associated trabeculitis the resistance
comfortable cosmetic eye. Not infrequently such of aqueous outflow is increased.40 However, without
affecting the outflow resistance, high osmotic pressure Schwartz Syndrome

of aqueous due to increased proteinous content may
This is a condition of anterior segment inflammation
increase the volume of intracameral fluid, causing high
with glaucoma associated with rhegmatogenous
IOP. In subacute and chronic uveitis the following
retinal detachment. This was first reported by Shaffer
causes are attributed to secondary glaucoma.
in 1963 and confirmed by Schwartz in 1973. After
i. Blockage of trabecular spaces by inflammatory
surgical reattachment, glaucoma and anterior inflam-
cells and debris. Accumulation of inflammatory
mation subside.45 Shaffer made the first mention of
cells resembling KP bodies may be seen gonio-
this association of anterior inflammation and
scopically on the surface of the trabecular
glaucoma with rhegmatogenous retinal detachment
meshwork.
in 1963. 46 Other findings in this condition are
ii. Swelling of the trabecular fibrils.
diminished outflow facility having open angle with
iii. Formation of hyaline or cuticular membrane
cells and flare in aqueous humor. Causes may be
covering the angle.
deposition of pigment granules released by the
iv. Neovascularization.
retinal pigment epithelium, and glycosaminoglycans
v. Formation of peripheral anterior synechiae.
synthesized by the photoreceptors in the trabecular
vi. Forward displacement of the iris-lens diaphragm.
meshwork.
After topical steroid therapy, the IOP may rise but
it may not be an indication of steroid glaucoma; the
Glaucoma Caused by Other
inflammation of the ciliary processes is reduced by
Diseases of the Iris
steroids, and hence more aqueous is formed but as
the outflow facility is still in a compromised state, the Pigment Dispersion Glaucoma
IOP is raised.
Pigment dispersion syndrome is characterized by loss of
In Fuchs’ heterochromic cyclitis, scarring of the
pigment from the pigment epithelium of the iris.
trabecular meshwork decreases the facility of aqueous
Pigment dispersion syndrome appears to be an
outflow and causes glaucoma. Treatment of this
autosomal dominant disorder. It occurs primarily in
condition is in the line of POAG.40
the Whites and is rare in Blacks and Asians. The actual
cause of release of pigments from the iris is not known;
Posner-Schlossman Syndrome:
but as only the mid-peripheral part of the iris is
Glaucomatocyclitic Crisis41
affected, it may be due to the rubbing of the iris by
It is an unilateral recurrent type of mild anterior uveitis the zonules.47 Pigment is deposited in various intrao-
characterized by the following: cular structures, like back of the cornea, trabecular
i. High IOP in the range of 40 and 70 mm of Hg meshwork, and anterior surface of the lens. Intraocular
ii. Few fine KP pressure is raised due to blockage of the trabecular
iii. Faint flare spaces by pigment deposits. Usually the intraocular
iv. Open angle pressure is in the range of 35 to 40 mm of Hg, but the
v. Decreased outflow facility. patient may not have any pain or discomfort in the
It is common in the age group of 20 to 50 years and eye. Diagnosis of pigment dispersion may be
starts with acute onset of symptoms like ocular suspected by the presence of pigment, on the posterior
discomfort, blurred vision and seeing of haloes. surface of the cornea during tonometry. Treatment of
Though unilateral, the other eye may be affected after glaucoma in pigment dispersion cornea is the same
the first affected eye is cured. The cause of this as in POAG. Pigment dispersion syndrome occurring
condition is unknown. with the implantation of posterior chamber intraocular
Glaucomatocyclitic crisis is treated with beta- lenses are also observed.48
blocker, and or topical carbonic anhydrase inhibitors.
Essential Atrophy of the Iris
Secondary Glaucoma Resulting from
The stroma of the iris undergoes atrophic change
Miscellaneous Inflammation
leaving the epithelium intact; but in the late stages
Secondary glaucomas have been reported in uveitis through and through openings appear in the iris
in herpes simplex, 42 herpes-zoster, 43 juvenile leading to polycoria or the pupil is pulled eccentrically
rheumatoid arthritis, and syphilis.44 (correctopia). The cause of the glaucoma is not due to
blockage of the trabecular spaces by cellular debris, glaucoma.49 Jona et al reported that 50 percent of
but by an endothelial lining that develops along most patients with progressive atage of AMD or diffuse
of the circumference of the chamber angle interfering diabetic macular edema treated with intravitreal
with the drainage of aqueous humor. injection of 25 mg of triamcinolone actonide developed
IOP elevation after 2 months.50
Secondary Glaucoma due to The possible cause of steroid glaucoma is decrease
Tumification of the Uveal Tract of the facility of aqueous outflow by the following
mechanisms:
Angle closure glaucoma (ACG) due to multiple cysts of
i. Accumulation of glycosaminoglycans in the
ciliary body and iris Intraepithelial cysts of iris and
trabecular meshwork by stabilizing lysosomal
ciliary body may push the base of the iris forward
membranes, and inhibiting release of catabolic
causing shallowing of the anterior chamber producing
enzymes.51
goniosynechia. Diagnosis of this etiology may be
ii. Accumulation of acid mucopolysaccharides
suspected during gonioscopy, when the width of the
(AMPs) in the outflow channels, suggests the role
chamber angle is found to be different in various parts
of this substance in reducing the facility of
of its circumference.
outflow.52
Glaucoma due to intraocular tumor Common intraocu- iii. Inhibition of the phagocytosis of foreign matter
lar primary tumors to produce glaucoma are by trabecular endothelial cells.
malignant melanoma of the uveal tract in adults and iv. Decreased synthesis of prostaglandins that
retinoblastoma in children. The probable mechanisms regulate aqueous humor outflow.
are the following: Glaucoma secondary to posterior sub-Tenon depo
1. Extension of the tumor into the trabecular triamcinolone acetonide in the treatment of pars
meshwork. planitis (intermediate uveitis) is not rare. If the injec-
2. Pigment dispersion. tion is nearer to the ciliary body, glaucoma occurs even
3. Inflammation caused due to necrosis of the growth. if the patient tested negative in provocative test with
4. Neovascularization of trabecular meshwork. steroid drop instillation prior to sub-Tenon depo
5. Angle closure due to pushing forward of the iris- steroid injection. Antiglaucoma medication is not
lens diaphragm by the tumor mass. effective in lowering the IOP. Removal of the
6. Melanolytic glaucoma due to trabecular block unabsorbed portion from the injection site by local
caused by the macrophages containing melanin excision of the disk shaped area of conjunctiva-Tenon
pigment released from the tumor necrosis. is essential.53
Different corticosteroids have different intraocular
IATROGENIC CAUSES OF pressure raising potentials: For example, dexame-
SECONDARY GLAUCOMA thasone and betamethasone has a higher potential than
fluoromethalone.
Steroid Glaucoma
Corticosteroid glaucoma is a secondary open angle POSTOPERATIVE GLAUCOMA
glaucoma. After prolonged use of steroid drop or
Secondary glaucoma may develop after the following
ointment in conditions like vernal conjunctivitis,
surgical procedures:
uveitis, and chronic blepharitis open angle glaucoma
1. Cataract operation
develops more often in persons having strong family
2. Retinal detachment operation
history of glaucoma. IOP comes down after the steroid
3. Vitrectomy operation
is discontinued; but the damage caused by the raised
4. Nd: Yag laser posterior capsulotomy
IOP to the optic nerve head is irreversible. Long-term
5. Laser trabeculoplasty
systemic administration of steroid, as in cases of renal
6. Penetrating keratoplasty.
transplant, does not produce glaucoma whereas
cataract formation is a constant feature in such
Glaucoma after Cataract—IOLI operation
conditions. Systemic steroid does not have an additive
intraocular pressure raising effect. Hence, it is believed Mild rise of intraocular pressure (IOP) after otherwise
that local application of steroid can augment the onset successful cataract operation is a common pheno-
of POAG in people having strong family history of menon. The causes of raised IOP are:
a. Postoperative inflammation causing trabeculitis UGH and PUGH syndrome (Table 71.6) Uveitis-
leading to swelling of the trabecular matrix, glaucoma-hyphema (UGH)54 and pigment-uveitis-
endothelial cell dysfunction and/or accumulation glaucoma-hyphema (PUGH) syndromes are common
of inflammatory cells and debris in the trabecular in anterior chamber angle supported56 or posterior
space leading to diminished aqueous outflow chamber iris supported lenses.55 However, now these
leading to secondary angle closure glaucoma. procedures are not frequently practiced. Anterior
b. Postoperative aseptic iritis can cause peripheral chamber hemorrhage months or years after cataract
anterior synechiae thus causing secondary open surgery may develop from neovascularization of the
angle glaucoma. incisional site or vascular iris tufts in contact with the
c. Due to aberrant placement of the IOL, uveitis, PCIOL or haptic in the ciliary sulcus. Thus, patients
glaucoma and hyphema was a common may present with painless transient blurring of vision
complication both in anterior chamber 54 and due to haziness of aqueous following leakage of blood
posterior chamber IOLI. 55 However after from these sources.58
technological improvements, presently it is a non-
Vitreous in anterior chamber59 This is also a cause of
existent clinical entity.
postoperative glaucoma specially after intracapsular
d. Retained lens fragments and lens particles may also
lens extraction; an intact anterior hyaloid face seen in
cause glaucoma. In cases of rupture of the posterior
the early postoperative period may rupture when IOP
capsule, nuclear fragments may drop into the
is suddenly raised during coughing, sneezing, etc.
vitreous causing uveitis, glaucoma and retinal
Intraoperative prolapse of formed vitreous in young
detachment.57 Vitrectomy is the only treatment in
persons frequently results in secondary glaucoma
such cases.
because this type of vitreous cannot be meticulously
e. Viscoelastic substances used during intraocular
removed from the iris surface and the angle of the
lens implantation is another cause of post operative
anterior chamber. As the vitreous is in contact with
glaucoma.55 Methyl cellulose is the most commonly
the trabecular meshwork, normal rate of aqueous
used viscoelastic in developing countries. It is an
outflow is deranged. Sometimes, in course of time
absolute necessity to meticulously remove all
vitreous may retract and tension is controlled but
remnants of the viscoelastic used during the
usually intractable glaucoma results.
operative procedure. The macromolecules of the
visco substances cannot pass through the Secondary Glaucoma after
trabecular spaces, rather these particles block the Scleral Buckling Operation
trabecular spaces causing glaucoma. Viscoelastic
agents used during cataract surgery cause a Secondary glaucoma may develop in about 4 percent
significant rise in IOP. The IOP rise peaks between of cases after scleral buckling operation. It is a narrow
4 to 7 hours postoperatively and may return to angle glaucoma with shallow anterior chamber
normal after 24 to 48 hours.57 associated with collection of either blood or serous
f. Anterior chamber hemorrhage months or years fluid in suprachoroidal space.60 Prolonged operative
after successful cataract surgery may be a cause of procedure and application of a broad encircling band
secondary glaucoma. This type of hemorrhage are also thought to be the causative factors of this
occurs from neovascularization of the incisional glaucoma. The mechanisms of shallowing of the
site or from vascular iris tufts in contact with the anterior chamber are the following:
PC IOL or its haptic in the ciliary sulcus. Initial a. Forward displacement of vitreous and lens by
symptom in this complication is painless transient scleral indentation and suprachoroidal fluid.
blurring of vision due to haziness of aqueous b. Rotation of the ciliary processes forward by the
following leakage from the sites as mentioned fluid that separates the ciliary body from the sclera.
above. Treatment Energetic treatment with beta-blockers,
carbonic anhydrase inhibitors, hyperosmotic fluid and
Malignant glaucoma This may develop soon after or miotics should be started after establishing the
within a period of 24 to 48 hours after cataract diagnosis. Surgical interference may be necessary
operation (described in detail in Chapter 72). which consists of drainage of the suprachoroidal fluid.
Table 71.6: Glaucoma in aphakic and pseudophakic eyes Treatment will depend on the actual cause. In most
(Modified from Becker Shaffers’ Diagnosis and Therapy cases, the IOP comes down after drug therapy. For
of the Glaucomas, (6th edn) silicone oil glaucoma, inferior peripheral iridectomy
A. Open angle glaucoma is indicated.
a. Early onset
i. Malignant glaucoma Glaucoma after Nd: YAG Laser
ii. Pre-existing POAG Posterior Capsulotomy
iii. Early raised IOP
Secondary glaucoma after Nd:Yag laser capsulotomy
iv. Viscoelastic substances
v. Inflammation
is a common complication. The cause of glaucoma is
vi. Hyphema impairment of outflow facility by the following mecha-
vii. Pigment dispersion. nisms:
b. Late onset i. Forward displacement of vitreous causing angle
i. Inflammation closure glaucoma.62
ii. Corticosteroid induced ii. In cases without a pseudophakos the anterior
iii. Ghost cell glaucoma hyaloid face is ruptured due to inaccurate targe-
iv. Uveitis-glaucoma-hyphema (UGH) syndrome
v. Pigment-uveitis-glaucoma-hyphema (PUGH)
ting or the capsulotomy is unnecessarily wide
syndrome causing vitreous to flow and fill the anterior
vi. Lens particle chamber completely causing disastrous
vii. After Nd-YAG laser posterior capsulotomy complications.
viii. Glaucoma caused by vitreous in AC. iii. Normally there is a gap between the posterior
B. Angle closure glaucoma capsule of the lens and the anterior hyaloid
a. Early onset membrane. If due care is not taken to target the
i. Pre-existing PACG laser beam over the posterior capsule then the
ii. Pupillary block hyaloid membrane may rupture.
iii. Air block Treatment of glaucoma following Nd:YAG laser
iv. Malignant glaucoma application without rupture of the anterior hyaloid
v. Peripheral anterior synechia.
membrane is by beta blocker eye drops.
b. Late onset
i. Pupillary block
Glaucoma after Penetrating Keratoplasty
ii. Neovascular glaucoma
iii. Peripheral anterior synechia The most common mechanism of glaucoma following
penetrating keratoplasty is formation of peripheral
anterior synechia. Even after peripheral iridectomy,
After Vitrectomy Operation
postkeratoplasty, secondary chronic angle closure
Open angle glaucoma may develop after vitrectomy glaucoma may develop. This may have some relation
operation. The causes differ depending upon the indi- with prolonged postoperative hypotony which may
cations of vitrectomy and other procedures under- cause peripheral anterior synechia. Other possibilities
taken alongwith vitrectomy. Some of the causes are of glaucoma may be the viscoelastic substance used
the following: during the procedure, which has been inadvertently
a. Ghost cell glaucoma, if vitrectomy was for vitreous left behind in the anterior chamber and use of topical
hemorrhage. steroid for prolonged periods.
b. Neovascular glaucoma, if proliferative vitreore-
tinopathy was an indication of vitrectomy. SECONDARY GLAUCOMA FOLLOWING INJURY
c. Blockage by intraocular gases or liquids, used for Injury to the eye causes secondary glaucoma by the
tamponade of the retina after vitrectomy, viz. following mechanisms:
i. Air
ii. Perfluorocarbons Perforating Injury
iii. Viscoelastic substances a. After repair of perforating injury of the anterior
iv. Silicone oil.61 segment of the eye incidence of anterior synechia
d. Deposition of cellular debris and hemosiderin pig- is more; this leads to secondary angle closure
ments in the trabecular meshwork. glaucoma.
b. Injury to the lens leads to secondary glaucoma by Ghost cells may be formed inside the vitreous in
different mechanisms. cases of absorbed or incompletely absorbed vitreous
hemorrhage. They may be detected under slit lamp
Concussion Injury biomicroscopy or direct ophthalmoscopy as spherical
dark colored bodies. Unless the anterior hyaloid face
The causes of secondary glaucoma after concussion
is disrupted, these cells cannot migrate to the anterior
injury of the eye may be the following:
chamber. Glaucoma develops after about a month
Displacement of the lens Discussed above. after injury. IOP ranges between 30-50 mmHg.
Hemolytic glaucoma in another almost similar
Hyphema It is commonly due to rupture of the vessels condition which may develop even with intact anterior
of the circulosus arteriosus major near the base of the hyaloid face in cases of anterior chamber hemorrhage
iris. The blood usually is absorbed after overnight due to trauma or spontaneously in patients with
bandaging of the eye with complete bed rest. One bleeding diatheses. In this condition the macrophages
important point to remember is that aspirin is to be engulf the products of the lysis of the RBC. The cause
avoided as it delays the clotting process. of glaucoma is decreased aqueous outflow due to
Secondary hemorrhage into the anterior chamber blockage of the trabecular flow by the macrophages.
is a disastrous situation and glaucoma is inevitable. Treatment of ghost cell glaucoma and neovascular
In this condition, the color of the blood in the anterior is the same and it consists of usual ocular hypotensive
chamber becomes bluish red or even sometimes black. topical drugs. Irrigation of the anterior chamber
If hemorrhage is not controlled then irreversible visual through paracentesis incision is indicated if the IOP
damage may occur due to secondary glaucoma and cannot be lowered with medication. As the flow of
blood staining of the cornea. Treatment of this the ghost cells from the vitreous to the anterior
condition consists of lowering of the IOP by beta chamber may continue IOP may rise again. However
blockers, CAI and hyperosmotic drugs followed by as indicated before ghost cell production is a transient
removal of the clotted blood through a small limbal process, the condition may die down by itself.
incision. Epsilon aminocaproic acid, an antifibrinolytic
drug, is often used to prevent occurrence of rebleeding Glaucoma Due to Disruption of Angle Structure
after traumatic hyphema. But use of this drug requires
i. In early glaucoma occurring within a week or two
close monitoring for IOP spikes after cessation of
after the contusion, the mechanism may be
therapy.
obstruction to the outflow channels by cellular
Hemolytic glaucoma: Ghost cell glaucoma element, debris or pigments. The tear in the
Ghost cell glaucoma is a transitory secondary open trabecular meshwork may heal within several
angle glaucoma.63 It is associated with intravitreal weeks or months leaving an area of scarring,
hemorrhage in eyes with dehiscence of the anterior which may combine with peripheral anterior
hyaloid membrane following trauma, intraocular synechia thus leading to glaucoma.64
operations like vitrectomy or cataract surgery with or ii. Glaucoma developing a month or so after the
without intraocular lens implantation. The main injury may be explained by the fact that both the
pathology in degeneration of the red blood corpuscles outflow facility and aqueous production are
following bleeding into the vitreous. The denatured reduced immediately after the trauma; when
RBCs migrate forwards to the anterior chamber aqueous production recovers outflow facility
through the disrupted anterior hyaloid membrane.63 continues to be reduced.
While degenerating within 1 or 2 weeks in the vitreous, iii. Glaucoma may develop decades after the injury
the shape of the RBC becomes spherical and degra- in an otherwise quiet eye with open angle; gonio-
dation of hemoglobin leads to a khaki coloured cell scopically the attachment of the iris appears to
with the denatured hemoglobin called Heinz bodies. be further posterior than normal throughout the
As opposed to the RBC, the ghost cells are less pliable whole 360° of the angle. Though it is called angle
through the trabecular spaces and hence block the recession glaucoma, the anatomical angle cannot
spaces causing obstruction to normal aqueous outflow be recessed by trauma. It may be due to formation
leading to secondary glaucoma. Occasionally ghost of a cuticular membrane covering the recessed
cells form a layer in the AC as pseudohypopyon. angle, which blocks the aqueous outflow.65
Miscellaneous Causes of 5. Streeton BW, Park AJ, Wallace RN et al. Pseudoexfoliation
fibrillopathy in the skin of patients with ocular
Secondary Glaucoma
pseudoexfoliation. Am J Ophthalmol 1990;110:490.
Glaucoma due to raised extraocular venous pressure 6. Yoshizumi MO, Thomas JV, Smith TR. Glaucoma inducing
mechanisms in eyes with retinoblastoma. Arch Ophthalmol
as in carotidocavernous fistula,66 cavernous sinus
1978;96:105.
thrombosis, endocrine exophthalmos, cardiopulmo- 7. Smith J, Shivitz J. Angle closure glaucoma in adults with
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Sturge-Weber syndrome and superior venacava 1984;77:261.
obstruction.68 8. Polland ZF. Secondary angle closure glaucoma in cicatrical
fibroplasias. AM J Ophthalmol 1980;89,651.
9. Elsas F, Maumenne I, Kenyon K et al. Familial aniridia with
Angle Closure Glaucoma in preserved ocular function. Am J Ophthalmol 1977;83,718.
Non-rubeotic CRVO 10. Grant WM, Walton DS. Progressive changes in the angle in
congenital aniridia with development of glaucoma. Am J
Secondary non-rubeotic ACG after central retinal vein Ophthalmol 1979;78,842.
occlusion has been described.69 Possible mechanisms 11. Machemer G, Brishtwell F, Qpitz J. Corneal changes in
involved in pathogenesis of this condition are the aniridia. Am J Ophthalmol 1979;84,497.
12. Yue BY, Kurosawa H, Duvall J et al. Nanophthalmic sclera
following:
fibronectin study. Ophthalmology 1988;95,56.
1. Marked swelling and vascular congestion of the 13. Neelakanthan A, Venkataramakrishnan P, Rao BS et al.
ciliary body causing its anterolateral displacement Familial nanophthalmos. Management and complications.
resulting in relaxation of the zonules allowing the Ind J ophthalmol 1994;42,139.
lens to move anteriorly and become more convex; 14. Grass JDM, Jallows S. Idiopathic serous detachment of the
choroids, ciliary body and retina (Uveal Effusion Syndrome)
this results in shallowing of the anterior chamber. Ophthalmology 1982;89,1018.
2. Transudation of fluid into the retina, vitreous, and 15. Kimbrough RI, Trempe CL, Brockhurt RJ et al. Angle closure
retrovitreal space exerts pressure to displace the glaucoma in nanophthalmos 1979;88,572.
iris and lens anteriorly to precipitate ACG. 16. Epstein DL. Diagnosis and management of lens induced
glaucoma. Ophthalmology 1978;89:227.
17. Epstein DL, Jedisiniak JA, Grant WM. Obstruction of aqueous
Secondary Glaucoma due to Scleritis outflow by lens particles and heavy molecular weight
In about 12 to 46 percent of cases of posterior scleritis, proteins. Invest Ophthalmol Vis Sci 1978;17:272.
18. Perlman EM, Albert DM. Clinically unsuspected phako-
intraocular pressure is increased.70 The mechanisms anaphylaxis after ocular trauma. Arch Ophthalmol
for raised IOP may be the following: 1977;95:244.
a. Increased viscosity of the aqueous 19. Laatikainen I, Back RK. Behaviour of the iris vasculature in
b. Inflammation of the outflow channels central retinal vein occlusion: A fluorescein angiographic
study of the vascular response of the retina and iris. Br J
c. Obstruction of trabecular meshwork by inflam-
matory cells and debris 20. Peev J, Folbery R, Itrin A. Vascular endothelial growth factor
d. Peripheral anterior synechia uprequisition in human central retinal vein occlusion.
e. Neovascularization of the outflow passage Ophthalmology 1998;105:412.
f. Raised episcleral venous pressure. 21. Hayreh SS, Rajas P, Podhajsky P et al. Ocular neovascula-
risation with retinal vascular occlusion III. Incidence of ocular
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with choroidal effusion which pushes the iris lens logy 90: 488, 1983.
diaphragm leading to ACG.71 22. Brown GC, Migargal LE, Schachat A et al. Neovascular
glaucoma. Etilogic classification. Ophthalmology 1984;91:315.
23. Ohrtv. The frequency of rubeosis iridis in diabetic patients.
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53. Helm CJ, Hollan GN. The effects of posterior sub-Tenon
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44. Tsukahara S. Secondary glaucoma due to inactive intersitial 66. Pheles CD, Thompson HS, Ossoinig KC. The diagnosis and
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47. Campbell DG. Pigmentary dispersion and glaucoma: A new 69. Mendelsohn AB, Jampol LM, Shoch D. Secondary angle
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48. Samplex JR, Buskirk MV. Pigmentary glaucoma associated Ophthalmol 1985;100:581.
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49. Mitchell P, Cumming RG, Mackey DA. Inhaled corticosteroid, 71. Dodds LM, Lowder CY, Barnhorst DA et al. Posterior scleritis
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1999;106,2301. 1995;120:677.
Chapter 72
Malignant Glaucoma
SK Narang
DEFINITION OF MALIGNANT GLAUCOMA operation for angle closure glaucoma especially with
peripheral anterior synechiae. The level of intraocular
It is a clinical condition with continuing flattening of
the anterior chamber in an eye postoperatively with pressure (IOP) and type of operation performed have
normal or high intraocular pressure (IOP) despite the little relationship to its occurrence.5 It has occurred
presence of one or more peripheral iridectomies. The after filtration operations, whether free or controlled,
condition has been observed both in phakic and and cyclodialysis. To the best of our knowledge it
aphakic eyes. In the aphakic eyes the absence of the has rarely occurred after surgery in an open angle
lens and the zonules (in intracapsular cataract extra- glaucoma and laser iridotomy. One case has been
ction), the vitreous moves forwards into apposition reported by Robinson and associates6 after prophylac-
with the ciliary body and posterior iris surface thus tic laser iridotomy. Another case of malignant
causing aqueous humor to flow directly into the glaucoma reported 7 was following NdYag Laser
vitreous cavity (aqueous misdirection). Aqueous cyclophotocoagulation used in the treatment of
humor may pass to the anterior chamber only through refractory glaucoma. The author suggests that
a relatively small area of the anterior hyaloid inflammatory process following the laser procedure
membrane, which may become relatively permeable. caused congestion of the ciliary body leading to
This may be confused with a vitreopupillary block,
anterior movement of the ciliary processes to cause
an iridectomy would relieve the condition causing
peripheral anterior synechiae, and under such
the aqueous humor to pass from the posterior
chamber to the anterior chamber through the circumstances the aqueous humor is diverted into the
iridectomy opening. In malignant glaucoma there is vitreous.
no posterior chamber, the iris is in direct contact with Malignant glaucoma occurs in a variety of other
the vitreous. clinical forms of glaucoma:
Malignant glaucoma was first described by von 1. Spontaneously
Graefe1 in 1869. It is an uncommon but serious condi- 2. Use of miotics in an unoperated eye8
tion, which has been responsible for blindness of one
3. Cataract extraction (both intracapsular and extra-
or both eyes of many patients. He named this
capsular)9
condition as malignant glaucoma because it responds
poorly to conventional therapy. As the name is often 4. Trauma or intraocular inflammations
confused with the idea of cellular malignancy, it is 5. Following retinal detachment surgery10
proposed that it may be called interchamber block. 6. Retinopathy of prematurity.11
Other names suggested are ciliary block glaucoma, It is not clear whether all of these forms of glau-
aqueous misdirection syndrome and ciliovitreolenti- coma occur through the same mechanism although
cular block by different authors.2-4 they share the same clinical features.
After intraocular surgery, this type of glaucoma
CONDITIONS OF DEVELOPMENT occurs in 0.6 to 4 percent of eyes with angle closure
Malignant glaucoma develops characteristically after glaucoma. Malignant glaucoma occurs more often in
small eyes with anatomically narrow anterior

chamber angles.
Pathogenesis
The most commonly accepted theory on the patho-
genesis of malignant glaucoma, is that the anterior
hyaloid is thickened and less permeable with some
abnormality of the vitreous body. After surgery or
some insult to the eye, the hyaloid moves forward
and comes in contact with the iris, lens, ciliary body
and a pseudophakos if present (Fig. 72.1). The newly
formed aqueous humor leaves the ciliary body and
passes into the vitreous through some leaks at the
region of contact of ciliary body in vitreous pockets,
and the space posterior to the detached vitreous. Fig. 72.1: Schematic drawing of mechanism of ciliary block
Following factors also may play a role in the glaucoma. Vitreous face touching lens, ciliary body and iris.
pathogenesis of malignant glaucoma. These structures are displaced forward blocking the angle
a. Swelling of the ciliary processes pressing against
lens or anterior hyaloid as seen in inflammations mydriatic and cycloplegic agents and adverse
of eyes. response to miotics. In longstanding cases corneal
b. Slack zonules or ciliary muscle spasm leading to decompensation takes place and the lens becomes
anterior displacement of lens as seen after use of opaque.
strong miotics. To summarize, the following criteria should be
c. Patients with small anterior segments as seen in taken into consideration in diagnosis of malignant
angle closure glaucoma patients. glaucoma:
It is likely that more than one factor is responsible 1. Flattening or shallowing of the central part of the
for its pathogenesis leading to iridovitreolenticular anterior chamber along with the peripheral flatte-
block in phakic or pseudophakic eyes, and iridocilio- ning.
vitreal block in aphakic eyes. Aggregation of these 2. Intraocular pressure is greater than the anticipated
factors in a particular patient leads to this entity. pressure after filtration surgery, when malignant
glaucoma follows after filtration surgery.
CLINICAL PICTURE 3. Absence of pupillary block which is confirmed by
patent peripheral iridectomy.
In a classical case of malignant glaucoma following 4. Absence of suprachoroidal effusion or
surgery, it may appear at the time of surgery, or the hemorrhage confirmed by B-mode
next day; the onset may be delayed by some days, ultrasonography.
weeks or months. The later onset in some cases
appears to coincide with the discontinuation of DIFFERENTIAL DIAGNOSIS
mydriatic-cycloplegic drugs or with the initiation of
miotic drops some weeks or months after surgery. If Following conditions come in the differential diag-
one eye develops malignant glaucoma after surgery, nosis of malignant glaucoma.
the other eye is likely to follow a similar course. a. Suprachoroidal hemorrhage: This condition follows
The patient with malignant glaucoma complains soon after opening of the anterior chamber during
of pain, congestion of eyes, watering, and diminution intraocular operations on the operating table or
of vision. On examination the anterior chamber is after the surgery at any time within a week. IOP
very shallow even though a patent iridectomy is may be normal or elevated. However this
present. Intraocular pressure is usually quite high in condition is not common in small incision cataract
the range of 40 to 60 mmHg. However, normal surgery including phacoemulsification.
intraocular pressure in the early stages due to b. Choroidal effusion: Choroidal effusion is associated
associated ciliary shock postoperatively is not with shallow anterior chamber after filtration
unusual. Usually, there is a therapeutic response to surgery. IOP is usually low. Peripheral choroidal
Chapter 72: Malignant Glaucoma 553
detachment is found on ophthalmoscopic examina- as 5 days. In case the anterior chamber forms and
tion. B-mode ultrasonography may show periphe- the tension comes to normal, mydriatic-cycloplegic
ral choroidal separation.12 regimen should be continued for indefinite period.
c. Pupillary block glaucoma: In this condition the IOP Fifty percent of the phakic eyes can be relieved by
is elevated with shallow anterior chamber but this medical line of treatment. In case there is no
the central part of the AC is deeper uniformly. response in 5 days, laser or surgery is employed.
Even in cases in which peripheral iridectomy,
either incisional or laser was done before; the Laser Therapy
opening may be closed by inflammatory exudates
The argon laser has been used to treat ciliary
, retained lens matter after cataract operation or
processes hugging the lens or anterior vitreous. The
by pseudophakos. The patency of the iridectomy
rationale of this treatment is that laser energy shrinks
opening can be detected by intravenous injection
the ciliary processes and reduces ciliolenticular or
of 10 ml of 5 percent fluorescein dye. Normally
ciliovitreal block. The argon laser is directed to the
after intravenous injection the dye appears in the
ciliary processes through a previously created
anterior chamber after 30 seconds. But if the
surgical iris coloboma.16, 17
iridectomy hole is closed the dye will be seen to
pool in the posterior chamber and cannot be seen
Nd: YAG Laser
in the anterior chamber.13
d. Wound leakage: Overfiltration of glaucoma filtration It is used to treat the anterior hyaloid in aphakic and
surgery and wound leakage also come in the pseudophakic eyes. Laser treatments are given to the
differential diagnosis of malignant glaucoma. The anterior hyaloid using energy levels of 0.5 to 2 mJ.
significant point of difference is the IOP. In wound This can be done either through the iridectomy site
leakage the eye is very soft and in malignant or through the pupil. In eyes that have undergone
glaucoma the IOP is elevated, the eye feels hard extracapsular, cataract extraction, it is often necessary
on palpation. However, there may be possibility to do a small capsulotomy prior to anterior-
of anterior movement of the hyaloid membrane hyaloidotomy.18 Some workers have used this laser
and its apposition with the ciliary body leading in phakic patients also through a large iridectomy
to raised intraocular pressure. Wound leak is which is peripheral to lens edge.
confirmed by Seidel Test.
Surgery
MANAGEMENT
If medical therapy and laser therapy fails to resolve
Medical malignant glaucoma surgical intervention is required.
Surgical therapy required removal of aqueous pockets
Before the modern medical treatment for malignant
from the vitreous and restoration of the anterior
glaucoma was developed, miotics were used for
chamber. Surgical therapies in phakic and aphakic
nearly 80 years with uniform lack of success.14,15 On
eyes are as follows:
the Contrary, as we know today, it may worsen the
condition.
Phakic Eyes
In 1962, the use of mydriatic-cycloplegic drops
represented a major turning point in the medical Classical procedure for aspiration of aqueous from
therapy of malignant glaucoma.15 At present we use the vitreous pockets and restoration of anterior
1 percent atropine and 10 percent phenylephrine chamber is done as follows:
drops 4 times a day. These mydriatic and cycloplegic A corneal paracentesis is made by sharp
drops tighten the zonules and thus push the lens back, instrument taking care that lens and iris are not
helping in the formation of anterior chamber. This injured. A stab incision of 3 mm posterior to the
helps only in phakic eyes; it has no therapeutic effect limbus is made through the sclera, pars plicata of the
whatsoever in aphakic eyes. ciliary body, and anterior hyaloid to enter the
The hyperosmotic agents like 50 percent glycerine vitreous body. The opening must be large enough to
orally or 20 percent mannitol intravenously in full accommodate a vitrectomy probe. The vitrector is
dosage may dehydrate the vitreous and reduce the introduced into the center of the vitreous cavity and
posterior pressure displacing the lens iris diaphragm. approximately 0.5 to 1.0 ml of liquid and formed
The therapeutic response may be delayed for as long vitreous is removed from the eye. If vitreous surgery
instruments are not available, a 20 gauge disposable and without losing vitreous humor, the malignant
needle may be used to aspirate liquid vitreous glaucoma usually persists. In rare cases malignant
similarly (Fig. 72.2). The anterior chamber is filled glaucoma can occur after uncomplicated intracapsular
via the paracentesis with saline. Care should be taken cataract extraction.
not to inject too much of fluid. The eye should remain In these cases, we make a small limbal incision in
soft at the end of the procedure. Entry into the globe the region of a coloboma of the iris, pass a 20 gauge
more than 3.5 mm posterior to the limbus will cause needle toward optic nerve and 1 to 1.5 ml of vitreous
the probe to pass through the vitreous base without is aspirated. 20 Instead of this procedure anterior
rupturing the anterior hyaloid. vitrectomy can be contemplated with formation of
If the possibility of suprachoroidal fluid or blood anterior chamber with saline or air.
causing the shallow chamber exists, it should be
investigated using ultrasonography. Ultrasound REFERENCES
biomicroscopy gives a better picture of suprachoroidal 1. von Graefe A. Bietrage zur pathologie and therapie des
fluid when the fluid is present in front of the glaucoms. Arch Fur Ophthalmol 1869;15:108.
equator.19 If fluid is present, posterior sclerotomy 8 2. Shaffer RN, Hoskins HD. Ciliary block (malignant) glaucoma.
to 10 mm posterior to the limbus may be made and Ophthalmology 1978;85:215.
fluid drained. If the globe becomes hypotonus, the 3. Weiss DI, Shaffer RN. Ciliary Block (malignant) glaucoma.
Trans Am Acad Ophthalmo Otolaryngol 1972;76:450.
diagnosis of malignant glaucoma is doubtful, and 4. Levene R. A new concept of malignant glaucoma. Arch
surgery for this is deferred, and anterior chamber Ophthalmol 1972;87:497.
filled as above. In case ultrasonography is not 5. Simons RJ. Malignant glaucoma. Br J Ophthalmol 1972;56:263.
available, routinely suprachoroidal drainage can be 6. Robinson A, Prialnic M, Deustch D et al. The onset of malignant
tried, before surgery for malignant glaucoma is glaucoma after prophylactic laser iridotomy. Am J Ophthalmol
1990;110:95.
undertaken.
7. Hardlin DR, Brown JD. Malignant glaucoma after NdYag
cyclophotocoagulation . Am J Ophthalmol 1991;112,245.
Aphakic Eyes 8. Riesler JC, Schwartz B. Miotics-induced malignant glaucoma.
Arch Ophthalmol 1972;87:706.
If the lens is extracted from an eye with classical 9. Hanish SJ, Lamberg RL, Gordon JJ. Malignant glaucoma
malignant glaucoma without rupturing the hyaloid following cataract extraction and intraocular lens implant. Surv
10. Weiss ID, Deiter PD. Malignant glaucoma syndrome following
retinal detachment surgery. Ann Ophthalmol 1974;6:1099.
11. Kushner BJ. Ciliary block glaucoma in retinopathy of prematu-
rity. Arch Ophthalmol 1982;100:1078.
12. Dugal PR, Heave DK, Thash Ab et al. Anterior peripheral
choroidal detachment simulating aqueous misdirection after
glaucoma surgery. Ophthalmology 1997;104,439.
13. Ray RR, Binkhorst RD. The diagnosis of pupillary block
glaucoma vy intravenous injection of Fluorescein. Am J.
Ophthalmol 1966;61,981.
14. Chandler PA, Grant WM; Mydriatic-cycloplegic treatment in
malignant glaucoma. Arch Ophthalmol 1962;68,353.
15. Chandler PA. Malignant glaucoma. Trans Am Ophthalmol
Soc 1950;48,128
16. Herschler J. Laser shrinkage of the ciliary processe. A treatment
for malignant (ciliary block) glaucoma. Ophthalmology
1980;87,1155.
17. Weber PA, Henry MA, Kapefanesky FM et al. Argon L:Aser
treatment of the ciliary processes in aphakic glaucoma with
flat anterior chamber. Am J Ophthalmol 1984;97,82.
18. Little BC. Treatment of aphakic malignant glaucoma using
Nd.Yagposterior capsulotomy. Br J Ophthalmol 1994;78,499.
19. Teflo C, Chi T, Shepps G et al. Ultrasound biomicroscopy for
pseudophakic malignant glaucoma. Ophthalmology 1993;100,
Fig. 72.2: Vitreous pocket containing aqueous
410.
humor being drained with needle 20. Byrnes GA, Legh MM. Wong et al. Vitrectomy for ciliary block
(malignant) glaucoma. Ophthalmology 1995;102,1308.
Chapter 73
Primary Pigmentary
Dispersion Syndrome and
Pigmentary Glaucoma
Primary pigmentary dispersion syndrome (PDS) is a strong association between PDS and myopia. It was
clinical entity characterized by a triad of iris transil- initially believed to affect young myopic persons in
lumination defect, heavily pigmented trabecular the age group of 45-50 years; but according to later
meshwork and Krukenberg’s spindle in the corneal reports7-9 it also occurs in women and elderly men.
endothelium. All the cases of PDS may not present with raised
Pigmentary glaucoma is a form of secondary open intraocular pressure (IOP). Glaucoma develops in
angle glaucoma. The term pigmentary glaucoma was about 10 percent of cases after 5 years and 15 percent
first introduced by Sugar in 1949.1 Even before this, of cases after 15 years of PDS; therefore it is
Sugar reported the presence of melanin pigment mandatory to keep track of IOP in all cases of PDS.
granules in gonioscopic examination of eyes of patients
with primary open angle glaucoma.2 CLINICAL FEATURES
The source of melanin pigment granules seen in Primary pigmentary dispersion syndrome is a bilateral
this condition is recognized to be the pigment neuro- condition; butt one eye may be affected much earlier
epithelium lining mainly at the posterior surface of than the other. Therefore in the initial stage it may
the iris and occasionally of the ciliary body. After be clinically described as unilateral till the other eye
liberation from the pigment epithelial cells, the shows typical manifestations. The signpost of the
pigment granules are dispersed in the aqueous humor disease is presence of transillumination defect in the
and gets deposited on the structures of the anterior iris due to loss of pigment granules from the pigment
segment of the eye which come in contact with the epithelial cells. These iris defects varying from a few
aqueous humor. The structures, where the pigment to about 60 to 70 in number, are radially arranged in
is deposited occurs include corneal endothelium, iris, the mid peripheral part of the iris. However the
anterior lens capsule, zonular fibers, trabecular transillumination defects may not be always present.
meshwork, endothelial layer of canal of Schlemm and Further they are difficult to be detected in early
not infrequently the pars plana area of retina and stages of the disease. Iris transillumination defect can
posterior capsule of the lens adjacent to the capsulo- be detected by slit lamp biomicroscopic examination
zonular area. by narrowing a slit beam of light to fit into the
Primarily PDS is a disease of the white and rare undilated pupil positioning the light beam co-axial
in Africans and Asians.3-5 It may have autosomal to the microscope and observing the transillumination
hereditary character;6 of course familial cases are rare under low magnification. For accurate assessment of
while sporadic cases are common.6 There exists a transillumination defect, fiber optic light source is
used for scleral transillumination and look for a defect to be elevated. Recent studies by quantitative
in the iris. It is difficult to transilluminate the iris estimation of pigment particles with “laser flare-cell
with dense stroma even though there may be areas meter” reveals that higher number of aqueous
of pigment loss. Under such conditions melanin granules is associated with more extensive
transillumination defect seems to be a supportive sign field defect in PDS.29-31
and may not be required to be present for diagnosis When pigment particles remain in the trabecular
of PDS. spaces for a long-time an irreversible structural patho-
Deposition of melanin pigment granules in almost logy develops in the trabecular meshwork. In this
all or some of the structures of the anterior segment stage, the endothelial cells of the trabecular fibers
of the eye is a characteristic and diagnostic sign of degenerate, cell debris and trabecular beams appear
PDS. In the cornea, deposits of pigmentary granules sclerotic.32 This terminal pathological state is called
may be seen scattered al over the corneal endothelial trabecular sclerosis. Once sclerosis develops, there is
layer. But the most characteristic form of corneal no chance of restoration of function of trabecular
endothelial deposition of pigment is a vertically meshwork. Topical therapeutic measures fail to lower
oriented brown band of pigments in the central part the IOP.
of the cornea known as Krukenberg’s spindle. The
size of the spindle varies from 3 to 6 mm in length Gonioscopic Findings
and 1 to 2 mm in width. Pigment deposition does
Homogenous pigment deposition in the trabecular
not alter the features of the endothelial cells as
meshwork is the most conclusive sign of PDS with
determined by specular microscopy. The number and
pigmentary glaucoma. Therefore, gonioscopic
size of the individual endothelial cells and corneal
examination is essential in all cases of PDS with or
thickness remain unchanged. 10-12 Though the
without elevated IOP. Compared with the normal
Krukenberg spindle is a prominent sign of PDS, it is
eye, the anterior chamber of eyes with PDS is
not pathognomic of the disease; neither it is invariably
characteristically deeper and the iris assumes concave
present. On the other hand it may be grossly missed
configuration specially in the mid peripheral area.
unless the corneal endothelium is specifically
However in patients having miotic drops or after
examined with slit lamp biomicroscope employing
peripheral iridectomy, “iris concavity” may not be
high magnification. Though the spindle consists of
present. Typically pigment collection initially starts
extracellular aggregation of pigments over the
in the trabecular meshwork in the lower part of the
endothelium, some intracellular pigment granules
angle. As the pigment dispersion progresses, pigment
may also be detected under histopathological
deposition extends upto the anterior part of
examination. Further, pigments have also been
Schwalbe’s line. In course of time pigment may cover
reported to be present on the endothelial cells of the
the initial width of the trabeculum giving it the
canal of Schlemm.
appearance of a brown circular band. A linear
pigmented line in front of Schwalbe’s line called
PIGMENT DISPERSION GLAUCOMA Sampaulesi’s line becomes prominent.
About 355 to 50 percent of patients with PDS develop
pigmentary glaucoma.13-23 Experimental,24 clinical25 Other Associated Findings
and histopathological13 evidence are available to Anisocoria may be an additional feature of PDS.10
believe that elevated IOP in PDS is due to decreased The eye with dilated pupil shows a greater area of
outflow facility through the trabecular spaces iris transillumination defect with higher intraocular
resulting from deposition of melanin pigment pressure than the fellow eye. The cause of dilated
granules and subsequent pathological changes in the pupil is not clearly defined. But histopathological
trabecular meshwork. Clinical evidence for this view study reveals hyperplasia of the dilator pupillae
is obtained from history of patients with PDS who muscle and degeneration of the nerve fiber in the
experience occasional showers of pigment in the eye with dilated pupil.11,12
aqueous humor either spontaneously or after
vigorous exercise27 or after dilation of the pupil with
Retinal Disorder
phenylephrine;28 in such situations the IOP is found
Chapter 73: Primary Pigmentary Dispersion Syndrome and Pigmentary Glaucoma 557
Patients with pigmentary dispersion syndrome have precedes the degenerative process in the pigment
an increased risk of retinal detachment.4,5,13 Lattice epithelial cells.
degeneration of retina, which is a precursor of Heredity plays a significant role in pigment disper-
rhegmatogenous retinal detachment, is reported in sion syndrome and pigmentary glaucoma. Autosomal
20 percent of cases of PDS with or without dominant inheritance is common. About 25 percent
glaucoma.14 Scheie and Cameron5 after the study of of the immediate relatives of patients having pigment
799 eyes of 407 patients with pigment dispersion dispersion syndrome develop the disease.20 Heredi-
syndrome collected from a glaucoma population of tary character may be reflected in structural pattern
9200 cases found that 65 percent eyes were myopic and the morphologic configuration of the structure
and out of these myopic eyes 64 percent developed of the anterior segment of the eye viz. cornea, lens,
retinal detachment. 4,5 In addition to lattice anterior chamber, etc. Patients with pigment
degeneration, patchy degeneration of pigment dispersion syndrome and pigmentary glaucoma have
epithelium of the central retina has also been deep anterior chamber compared to age, sex and
reported.26 refraction matched controls.22 Deep anterior chamber
results in concavity of the peripheral iris which causes
Pathogenesis of Pigmentary Dispersion its possible rubbing by the abnormally attached
Syndrome packets of zonules. Aqueous melanin granules may
be accurately quantified with the laser flare cell meter.
The cause of pigment dispersion from the neuro—
In PDS the pigment granule count in aqueous helps
epithelial cells of iris has been speculative for quite a
to assess the result of treatment (laser iridotomy) in
long time until Campbell in 1979 proposed a patho-
patients with pigmentary glaucoma.22
genic mechanism which accounts for many of the
features of pigment release. According to Campbell,
Course of the Disease
melanin pigment granules are dislodged mechanically
from the pigment epithelial cells of the iris by a back Pigment dispersion syndrome usually starts at the
and forth rubbing process of the posterior surface of age of 25 to 30 years. Active pigment dispersion
the mid peripheral portion of the iris against the accelerates during the following decade until it is
zonular packets that are inserted to the equatorial burnt out by the age of 55 to 60 years when pigment
part of the anterior lens capsule. The back and forth dispersion ceases in most patients. Increase in lens
movement of the iris corresponds to the dilatation diameter and decrease in pupil size with age may
and constriction of the pupil almost throughout the create a situation of relative pupillary block causing
whole day. Campbell’s view is supported by peripheral iris to move anteriorly and away from the
ultrasound biomicroscopy of the anterior segment zonules; this stage negates the rubbing effect of the
of the eye which showed iridozonular contact iris by the zonules causing cessation of pigment
corresponding to the areas of transillumination defect release. Abnormal deposition of pigment in the
of the iris resulting from pigment liberation from the structures of the anterior segment of the eye including
iris epithelial cells.28,29 Brandt et al reported a case of the trabecular meshwork, corneal endothelial surface
pigment dispersion with pigmentary glaucoma and over the iris surface may clear subsequently and
following implantation of posterior chamber phakic disappear completely.33 Intraocular pressure may
refractive lens (PCRL) which is a form of refractive return to normal.34 The iris transillumination defect
surgery indicated in very high myopia in patients may fill in by restoration of the lost pigment and iris
intolerant to contact lenses.30 Deep anterior chamber stroma. 16 In some cases of pigment dispersion
in high myopia enables the iris to rub against the glaucoma with the passage of time intraocular
PCRL. An inherent tendency for some pressure returns back to normal and there may not
pathophysiology of the iris tissue and its vasculature be any sign of pigment dispersion whatsoever. But
is indicated by fluorescein angiographic study of the as the legacy of raised IOP in the active stage of the
anterior segment of one eye of a patient with pigment disease there might be significant disk damage and
dispersion syndrome as compared with the field defect. Hence, there may be indication to believe
unaffected other eye. Fluorescein study reveals that some cases of normal tension glaucoma may in
hypoperfusion of iris tissue and decreased number fact be due to self-controlled pigment dispersion
of radial vessels.35 This suggests that vascular changes glaucoma.35,37
During the course of the disease there may be
remarkable fluctuation of IOP. Some patients have pigment deposition include iris and ciliary body cyst,
periods of ‘crisis’ of elevated IOP and then return to glaucoma due to systemic amyloidosis, diabetes,
normal. During such crises there may be acute symp- post-traumatic, siderosis and anterior segment
toms of visual loss with corneal edema and halos. postoperative conditions. Cases of pigmentary
The crisis of pressure elevation seems to be related glaucoma have been reported after posterior chamber
to excessive liberation of pigment into the anterior intraocular lens implantation41,42 and in combined
chamber. procedures of penetrating keratoplasty with
intraocular lens implantation.43,44 After lens implant
DIFFERENTIAL DIAGNOSIS pigment dispersion occurs at the site of iris touch by
the haptic of the implant.45
Pseudoexfoliation syndrome is the most similar condi-
tion to be differentiated from primary pigmentary
MANAGEMENT OF PIGMENTARY GLAUCOMA
dispersion syndrome with or without glaucoma. The
most prominent sign of pseudoexfoliative syndrome Pigment dispersion syndrome and pigmentary
is deposition of snowflake type of material at the glaucoma are two successive processes of the same
pupillary margin, over the anterior surface of the lens, disease process, where pigment granules are deposi-
in the angle of the anterior chamber and over the ted in structures of the anterior segment of the eye.
trabecular meshwork. In both of these two conditions Initially the process is benign but later pigment
pigment band is more prominent in the lower half of deposition in the trabecular meshwork hampers
the chamber angle; of course in most of the normal drainage of aqueous humor causing glaucoma.46 The
eyes the lower half of the anterior chamber angle is single essential aim in management of pigment
more prominent.36,37 Melanin pigment granules are dispersion (or pigmentary) glaucoma is to lower the
commonly interspersed with pseudoexfoliative IOP. Usually the intraocular pressure rise is insidious
material. Pigments may also be seen scattered over and may go up to 50 or 60 mm Hg. On the other
the endothelial surface of the cornea even in the form hand there may be a wider fluctuation of IOP. Very
of Krukenberg’s spindle. In pseudoexfoliative syn- rarely a sudden crisis of high IOP may develop. All
drome, iridolenticular friction may disrupt the the pressure lowering topical medications are
pigments of the iris neuroepithelium at the sphincter employed for primary open angle glaucoma may be
region and therefore transillumination defect may effective in the initial stage of pigmentary glaucoma;
be seen near the papillary area of the iris but not in but in long standing cases, where the pigments cause
its midperipheral region. 38 Pseudoexfoliation irreversible pathological changes (trabecular sclerosis)
syndrome is common in Scandinavian people at in the trabecular meshwork, IOP cannot be lowered
around the age of 60 years or so and in 50 percent of by medical therapy.47 In the early stage of PDS miotic
the patients it is unilateral; but pigmentary glaucoma (pilocarpine) may help in decreasing the process of
is commonly bilateral and develops usually in the pigment liberation by straightening the iris contour
third or fourth decade of life and undergoes and diminishing the iris concavity which in turn
regression in the fifth and sixth decade of life.39 The prevents rubbing of the iris by the zonules. But
incidence of pseudoexfoliative glaucoma increases pilocarpine is poorly tolerated by patients of younger
steadily from middle age onwards. As both the age group in which pigment dispersion syndrome is
diseases are equally common one would expect some common. Moreover the association of lattice
individuals of pigmentary dispersion syndrome and degeneration of the retina with PDS and its possibility
pseudoexfoliative syndrome in the same eye with to lead to rhegmatogenous retinal detachment should
glaucoma or ocular hypertension.40 In fact Mudumbai be kept in mind in case of continuing pilocarpine
et al described a case of Paradigm of overlap treatment for long duration.48
syndrome where distinct features of PEX and PDS Argon laser trabeculoplasty (ALT) has been
with raised IOP were present.41 reported by several authors. 49-51 Though initial
Presence of pigment in the structures of the response to ALT was favorable, failure to lower IOP
anterior segment of the eye commonly denotes either in long-term follow-up was common during the post-
aging, degenerative process or postinflammatory ALT period even though there was no evidence of
status of the anterior uveal tract. Other causes of pigment dispersion. Histopathological examination
Chapter 73: Primary Pigmentary Dispersion Syndrome and Pigmentary Glaucoma 559
of the eyes in which ALT could not control IOP immediately. 54,56 The effect of ND-Yag laser
revealed sclerosis and collapse of the trabecular iridotomy can be verified by counting of pigment
spaces. 12,47 It may be possible that increased granules post operatively by Laser flare cell meter.22
trabecular sclerosis prevents the ‘tightening’ effect Shuttleworth56 of Bristol Eye Hospital described a
of ALT to open up the trabecular spaces. Duration of rare but interesting case to impress upon the
pressure lowering effect of ALT is inversely importance of prophylactic iridotomy in PDS to
proportional to the degree of sclerosis. ALT on the prevent pigmentary glaucoma. A 39-yrs-old man had
other hand may worsen the condition. Therefore, a traumatic “iridotomy” in his left eye during
patients who received ALT should be followed up childhood. The patient had IOP R-35 and L-20 mmHg.
carefully to detect any sign of deterioration.52,53 Krukenberg spindle and mid peripheral radial iris
transillumination defect on temporal side with
Surgical Treatment cupping of the disk. Left eye cornea was clear, a two
clock hour iris dialysis. Both eyes anterior chamber
The two modalities of surgical treatment are:
were equally deep. Gonioscopy showed heavy
a. Trabecular aspiration
trabecular pigmentation in the right eye but none in
b. Peripheral iridotomy
the left eye.
Trabecular Aspiration Trabeculectomy
The ideal approach to treatment of pigmentary When the above modalities fail to lower the
glaucoma is to eliminate the cause of elevation of IOP: intraocular pressure then trabeculectomy is indicated.
And the main cause is obstruction of the trabecular Success rate of trabeculectomy is good.
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Ophthalmol 1984;101,81. R, Sheilds MB, Krupin T (Eds). The Glaucomas. St Louis CV
34. Gillies WE. Pigmentary glaucoma. A clinical review of anterior Mosby 1986.
segment pigment dispersion syndrome. Aust. NZ J Ophthalmol 56. Shuttleworth GN. A peripheral iridotomy protects against
1988;13,325. pigment dispersion and pigmentary glaucoma. Br J
35. Richter CV, Richardson TM, Grant WM. Pigmentary dispersion Ophthalmol 1999;83,376.
Chapter 74
Pseudoexfoliation Syndrome
Mayuri Khamar
Pseudoexfoliation syndrome(XFS) is an age related When PEX syndrome is associated with glaucoma
disorder of the extracellular matrix characterized by it is called PEX glaucoma. It often starts as unilateral.
production and progressive accumulation of small The IOP is usually high and rising, giving aggressive
white deposition of a fibrillar extracellular material course with increasing cupping of the disk and visual
in many ocular tissues. The deposits are most field defects.
commonly seen on the pupillary border, lens capsule
and zonules: Characteristic signs of pigment liberation
HISTORY
and deposition throughout the anterior segment help
in the diagnosis. Intraocular deposition of the material The first observations of changes compatible with PEX
may also be seen on the retina near pars plana. In syndrome seem to have been made by Axenfeld cited
addition to ocular structures, deposition of the mate- by Lindberg (1917), but it was the latter who gave the
rial may also be seen in the conjunctiva and orbital first detailed description.
structures.1-4 Vogt (1925), Busacca (1927), Hoeven (1937), etc.
made important contributions in understanding of
DEFINITION PEX glaucoma.
Dvorak-Theobald (1954) suggested pseudo-
SYN: Senile exfoliation, capsular exfoliation, fibrillo-
exfoliation of the lens capsule to differentiate it from
pathia epitheliocapsularis, etc.
true exfoliation in glass blowers.
It is a complex degenerative disturbance of anterior
Tarkkanen5 (1962) concluded from information
ocular segment engaging both anterior and posterior
available that the prevalence of the PEX syndrome
chambers. In a typical case, biomicroscopy demons-
varied enormously in different parts of the world.
trates advancing atrophy of the pupillary and
peripupillary (neuroectodermal) iris with a liberation
of pigment granules. These are launched into the EPIDEMIOLOGY
aqueous and may be stranded on iris, corneal endo-
Incidence without Glaucoma
thelium, and trabecular meshwork. The pigments may
disseminate from ciliary body.1 There is strong relation between glaucoma and PXS.
In addition to pigment, dandruff, flakes, and Subjects with PXS have an increased risk for glaucoma
membranes of a dull grayish hue (PEX material) and eyes with PXS has higher risk for glaucoma.
gradually appear on the pupillary margin on the Glaucoma develops in about 50 percent of cases of
anterior lens surface and in the anterior chamber angle. exfoliative syndrome.
It may be seen on ciliary body and between zonules. Reported prevalence rates of exfoliation vary
The development from first pigmentary changes to widely in different geographic locations. Although
the full scale grossly exfoliative picture may take 5-10 originally associated with Scandinavian countries, it
years. The accumulation of pigments and flakes may is now well established that exfoliation occurs
or may not lead to glaucoma. worldwide, virtually no area being spared.3
The prevalence of exfoliation ranges from zero and nonspecific form of pigmentation of the
percent among the Eskimos to as high as 38 percent endothelium. In patients of pseudoexfoliation with
in Navajo Indians (Faulkner 1971). 7 Age is an glaucoma there is significant decrease in endothelial
important determinant in the incidence of exfoliation cell density, polymegathism, pleomorphism, white
in patients both with and without glaucoma. deposits, and guttata.
Prevalence rates increasing markedly from age 50 to
the late 80s. Iris and Pupil
Small flakes on the pupillary margin of the iris are
Incidence with Glaucoma
hallmark of exfoliation syndrome. There may be fine
The reported incidence of exfoliation in patients with pigments on the surface of iris, especially in the folds
glaucoma varies according to authors and population and crypts. Prince and Ritch11 noted particulate pig-
studied, ranging from practically zero to as high as 93 ment deposition on the sphincter to be a characteristic
percent. Luntz found exfoliation in 1.4 percent of sign of exfoliation syndrome.
Whites and 20 percent of Blacks with open angle glau- Transillumination defects occur at the pupillary
coma in South Africa. Exfoliation was reported in 8.1 ruff and margin, in contrast to the midstromal slit-
percent of Australian aborigines with glaucoma and like defects found in pigmentary glaucoma.
46 percent to 57 percent of glaucoma patients in Phakodonesis and iridodonesis may be seen.12
Iceland. Angiographic abnormalities of the iris vessels
Monocular involvement seems to be more common include diminution in number, lack of normal radial
in PEX syndrome. Hansen and Sellevold8 found, how- pattern, neovascular clumps, and leakage of dye.13
ever, that exfoliation developed in the second eye in
40 percent of men and in 31 percent of woman over 5 Anterior Chamber and Angle
years.
Rarely, small pigments are seen floating in aqueous
in eyes with undilated pupil. Pigmentation of the
Systemic Associations
trabecular meshwork is a prominent feature of the
No clear cut association of exfoliation with any syste- disease and may be an early diagnostic sign. Pigmen-
mic disease has been shown. Association with cataract tation in superior angle should suggest the presence
formation is not clear. Since both entities occur in the of exfoliation. Pigmentation in unilateral cases is
aging population, it is difficult to ascribe a common always more marked in the eye with exfoliation.14
etiologic association. In unilateral cases pigmentation is more marked
in that eye.15 However, pigmentation is much less than
Heredity that seen in pigmentary glaucoma. It is spotty and not
as well defined. Less commonly small flecks of exfo-
No clear pattern of inheritance has been discerned.
liation material can be observed in angle. Angle
However, patients with exfoliation but without
closure glaucoma may be associated with exfoliation,
glaucoma respond to topical steroid testing similarly
but the majority of patients have open angles.
to the normal population.9,10
Lens, Zonules, and Ciliary Body
CLINICAL PICTURE
Exfoliation material on the lens surface is the
Conjunctiva and Cornea
syndrome’s most consistent and important diagnostic
Clinically, the conjunctiva is normal in exfoliation feature. Clinically three distinct zones of the anterior
syndrome. Fluorescein angiography reveals loss of the cusps may be present, i.e. a translucent central disk; a
regular limbal vascular pattern and neovascula- granular girdle around periphery; and a clear zone
rization in advanced cases. separating these two areas. The posterior capsule does
Small flakes or clumps of exfoliation may be found not appear to be involved in the exfoliative syndrome.
on corneal endothelium. There is usually a small The exfoliative material appears to be brought by
amount of pigment inferiorly on the endothelium. aqueous circulation and gets deposited on the surface
Rarely, there may be sufficient pigmentation to form of the lens because the underlying lens capsule
a Krukenberg’s spindle, but most often it is a diffuse remains intact and does not show evidence of
Chapter 74: Pseudoexfoliation Syndrome 563
production of the material. Surprisingly this substance Anterior Segment
has been reported to be deposited on the surface of
Exfoliation material appears to be intimately involved
implant after cataract extraction.16
with the adventitia of the iris vessels. Obliteration of
The central disk is present in approximately 20
the lumen resulting in neovascularization and leakage
percent of cases, accounting for the occasional lack of
of dye, correlates well with these findings. Deposits
pupillary flecks. The intermediate clear zone is appa-
occur on the trabecular meshwork and intertrabecular
rently caused by pupillary rubbing in eyes not in
spaces.
miotic therapy. A curled-up edge of the central zone
may be seen after dilatation. The peripheral zone is
Lens and Zonules
always present; it may be granular in the periphery
and frosty white centrally, and radial striations are Minute vacuoles in the deep and superficial layers of
often seen. the lens capsule with exfoliation material appearing
Deposits on zonules may explain the tendency to to flake off the capsular surface are seen. The debate
spontaneous subluxation or dislocation of lens in is whether it is primary involvement of the capsule
advanced cases. Deposits occur on the anterior hyaloid and epithelial cells of the lens, or secondary deposits.
face after intracapsular cataract extraction suggesting Flakes on the zonules were described but weakness
that the lens is not the only source of exfoliation of the zonules is not confirmed. Nonpigmentary
material.17 epithelium of ciliary body is found to be involved.
Intraocular Pressure Etiopathogenesis

Mean IOP in normotensive eyes with exfoliation is Exact nature and chemical composition of the PEX
usually higher than in those without exfoliation. In material is unknown. Overproduction and abnormal
cases with raised IOP, mean pressure is higher at metabolism of glycosaminoglycans have been sugges-
detection than it is in primary open angle glaucoma ted as one of the key changes in PEX. The protein
(POAG). Glaucomatous optic disk changes and visual content of the PEX material include both noncollage-
field defects also tend to be more in exfoliation nous basement membrane components and contribu-
glaucoma than in POAG. Surgical treatment for glau- tion from elastic fiber system such as fibrillum.
coma is more often necessary in eyes with exfoliation Regardless of the etiology, typical exfoliation fibers
than in POAG. have been demonstrated by electron microscopy in
close association with the pre-equatorial lens
Blood-Aqueous Barrier in epithelium, the non pigmented ciliary epithelium, the
Pseudoexfoliation Syndrome iris pigment epithelium, the corneal epithelium,
Impairment of blood-aqueous barrier with increase trabecular endothelium and almost all cell types of
in aqueous protein concentration is a feature of PEX the iris stroma1. The presence of PEX material should
(pseudoexfoliation) and may be quantified both by be taken seriously for the increased risk of intraocular
flare measurement and biochemical protein surgery with special reference to zonular dehiscence,
determination. This impairment may be at the level capsule rupture and vitreous loss during cataract
of the iris and less frequently and to a lesser extent, at surgery.
the level of the ciliary body. The extensive blood- There are increasing evidence for an etiological
aqueous barrier breakdown in eyes with PEX association of PEX with cataract formation and
following intraocular surgery is important risk factor possibly with retinal venous occlusion. PX is suspected
for early or late postoperative complications.17 The to be a systemic disorder which may be associated
alternations of the blood-aqueous barrier should be with transient ischemic stroke, systemic hypertension
considered in the medical and surgical treatment of and myocardial infarction.
eye with PEX.
Nature of the Exfoliative Material
PATHOPHYSIOLOGY
Biochemical nature of the exfoliation material remains
Origin of Exfoliation Material unknown. It has been suggested that it could be
It is formed from lens capsule and epithelium, ciliary amyloid like or an amyloid. In some pseudoexfoliation
body epithelium, and iris pigment epithelium. syndrome eyes miosis is connected with degenerative
changes both in stromal tissue and in the muscular

layer of the iris.
Netland et al 18 (1995) had demonstrated site-
specific elastosis in the lamina cribrosa of patients
with pseudoexfoliation syndrome with glaucoma,
suggesting an abnormal regulation of elastin synthesis
and/or degradation in optic nerve of patients with
this disease.
MECHANISM OF GLAUCOMA
The debate as to whether exfoliation is an incidental
finding in POAG or is actually the cause of the glau- Fig. 74.1: White flakes are seen on pupillary border
coma continues. Glaucoma may be due to blockage
of the trabecular meshwork by exfoliation material or
pigment liberated from iris, dysfunction of trabecular
endothelial cells or it may be concomitant primary
open angle glaucoma.
Extensive deposits of exfoliation material have
been found in the angle of normotensive eyes. The
most recent explanation of the association between the
two conditions is the presence of material in an already
glaucomatous eye as indicated by work where the
noninvolved eye may be classified as having glaucoma
in up to 24 percent of the cases. Another possible
explanation is that secondarily induced glaucoma may
be present with a great deal of exfoliation material or
a high association of adhesions of the pupillary area
with the lens.
The production of PEX material by trabecular cells Fig. 74.2: Gonioscopy of exofoliation syndrome: Arrow is
may be principally responsible for glaucoma develop- showing white dandruff like material and pigmenta
ment. Accumulation of locally produced PEX material
in the juxtacanalicular tissue (JCT), followed by
dysfunction of endothelial cells and disorganization Differential Diagnosis
of JCT and Schlemm’s canal, appear to be causative
1. Pigmentary glaucoma—pigmented band in angle,
factors in the development of a special type of
Krukenberg’s spindle, young myopes, and transil-
secondary open angle glaucoma in pseudoexfoliation
lumination defects in peripheral iris.
syndrome.
2. True exfoliation of lens capsule—seen in glass-
blowers, associated with cataract and no glaucoma,
DIAGNOSIS deposits from heat induced cataract is rolled up in
a characteristic thin sheet in contrast to the frosty
Techniques
appearance of exfoliation.
1. Slit lamp biomicroscopy (Fig. 74.1) 3. Iritis with pigment dispersion in meshwork—
i. pupillary border examination. peripheral anterior synechiae with posterior syne-
ii. after dilatation put slit beam at 45 degrees, this chiae, no exfoliation material on lens capsule.
will highlight the deposits on the endothelium. 4. Toxic exfoliation from iridocyclitis and foreign
iii. transillumination of pupillary edge. body—like copper or brass.
2. Gonioscopy (Fig. 74.2) 5. Other conditions—like Fuchs’ heterochromic irido-
3. Cycloscopy. cyclitis, pigmentation of angle due to aging or post-
Chapter 74: Pseudoexfoliation Syndrome 565
operative or intraocular tumors are to be differen- ECCE
tiated from exfoliation syndrome.
More complications like capsule rupture, lens disloca-
6. Systemic amyloidosis with deposition of white
tion, zonular dialysis and in sufficient mydriasis are
flaky material in the anterior segment.
seen compared to normal eye.
MANAGEMENT
Prognosis
Medical Therapy
• Poorer compared to POAG
Initial approach is same as in primary open angle • Glaucoma damage starts early
glaucoma. Treatment is given as a single drug remedy • Many patients of exfoliation never develop glau-
or in combination or several drugs. coma.
1. Beta-blockers like timolol
2. Epinepherine compounds
REFERENCES
3. Miotics.
• Usually this type of glaucoma is resistant to 1. Ritch R, Schloetzon-Schrehardt U. Exfoliation Syndrome. Surv
medical treatment Ophthalmol 2001;45, 265.
2. Ritch R. Exfoliative syndrome. Curr options in Ophthalmol
• Miotics may lead to synechia formation 2061;12,124
between the pupillary margin and anterior lens 3. Ruth M, Epstein DL. Exfoliative syndrome. Am J Ophthalmol
capsule 1980;89,477.
• Dilatation may result in acute rise in IOP 4. Swartz MF, Green WR, Mitchell RG et al. An unusual case of
accompanied by diffuse pigment dispersion in ocular involvement of primary non-fmilial amyloidosis.
Ophthalmology 1982;89,394.
anterior chamber. 5. Pohjola S, Horsmanheimo A: Corticosteroids in glaucoma
capsulare. Arch Ophth 1971;85:150.
Laser Therapy 6. Forsius H. Exfoliation syndrome in various ethnic population:
Arch Ophthalmol 1988;66(Suppl)71.
Argon laser trabeculoplasty: It gives good results in the 7. Faulkner HW Pseudoexfoliation of the lens among the Navajo
beginning but after passage of some time it has a Indians. Am J Ophthalmol 1971;72,206.
tendency for rise in IOP, which requires repetition of 8. Roth M and Epstein DL: Exfoliation Syndrome. Am J Ophth
the procedure.14 1980;89:477.
9. Brooks AMV, Gillies WE: The development of
Laser iridotomy: If angle is narrow or closed this may
microneovascular changes in the iris in pseudoexfoliation of
be helpful. the lens capsule. Ophthalmology 1987;94:1090.
10. Wishart PK Spaeth GL, Poryzees EM: Anterior chamber angle
Trabeculectomy in the exfoliation syndrome. Br J Ophth 1985;69:103.
11. Rouhiainen H, Teravista M: Pigmentation of anterior chamber
Results of the trabeculectomy are comparable to those angle in normal and pseudoexfoliation eyes. Acta
seen in POAG. Many a times this appears to be the Ophthalmologica 1990;68:700.
only solution. 12. Kuchle M, Nguyen NJ, Hannappel E. The blood-aqueous
barrier in eyes with pseudoexfoliation syndrome. Ophthalmic
Res 1995;27(Supp 1):136.
Trabecular Aspiration
13. Netland PA, Ye H, Streeten BW et al. The lamina cribrosa in
This new surgical modality, removing intertrabecular pseudoexfoliation syndrome with glaucoma. Ophthalmology
102(6):878.
and pretrabecular debris of trabecular meshwork, can
14. Tuulonen A, Airaksinen PJ. Laser trabeculoplasty in simple
be effective in the management of pseudoexfoliation and capsular glaucomas. Acta Ophthalmologica 1983;61:1009.
glaucoma. Aspiration is done in lower half using a 15. Gillies WE. Trabeculotomy in pseudoexfoliation of the lens
specially designed irrigation-aspiration device to fit capsule. Br J Ophth 1973;54:46.
anterior chamber angle. The suction force used is 100 16. Jacobi PC, Krieglstein GK: Trabecular aspiration: A new mode
to treat PEX glaucoma. Invest Ophth Vis Sci 1995;36(11):2270.
to 200 mm of Hg.
17. Gillies WE: Effect of lens extraction in pseudoexfoliation of
Lens extraction was suggested initially. But the lens capsule. Br J Ophth 1973;54:46.
deposits continue after the surgery, so lens extraction 18. Watson NJ, Winder S, Green FD: Pupil dilatation in pseudo-
is done to improve the vision. exfoliation syndrome Eye 1995;9(3):341.
Chapter 75
Pharmacognosy and
Pharmacokinetics of
Ocular Hypotensive Agents
R Ramakrishnan, S Puthalath
Glaucoma is a condition in which the intraocular 2. Selective alpha-adrenergic agonists

pressure (IOP) is high to cause optic nerve damage a. Clonidine
and potential visual field loss. The goal of therapy is b. Apraclonidine
to reduce the pressure so that optic nerve damage and c. Brimonidine.
progress of field defects are prevented or arrested. B. Adrenergic blocking agent (Antagonists)
Because of the chronicity of the disease and availability 1. Nonselective (beta-1 and beta-2 blocker),
of wide variety of drugs, the pressure reduction should non-ISA
be achieved using the least amount and fewest a. Timolol
numbers of drugs that are efficacious to minimize the b. Levobunolol
risk of local and systemic adverse side effects. Even c. Metipranolol.
though the pathogenesis of glaucoma has changed, 2. Selective beta-1 blocker (Cardio)
i.e. the IOP is only a risk factor; most of the drugs used a. Betaxolol
in the management of glaucoma are cornered around 3. Nonselective with ISA (beta-1 and beta-
the reduction in IOP. Apart from cholinergic and 2 blocker)
adrener-gic agents, and carbonic anhydrase inhibitors, a. Carteolol
many new groups of drugs have appeared to play the III. Carbonic anhydrase inhibitors
role in the management of glaucoma. 1. Oral
Antiglaucoma drugs can be classified as below: a. Acetazolamide
I. Cholinergic drugs b. Methazolamide
A. Parasympathomimetics c. Ethoxzolamide
• Pilocarpine d. Dichlorphenamide.
• Carbachol. 2. Topical
B. Anticholinesterases a. Dorzolamide or MK-507
• Echothiophate lodide b. MK-927
• Isofluorophate c. MK-417 (Sezolamide)
• Demecarium bromide IV. Hyperosmotic agents
• Physostigmine. 1. Oral
II. Adrenergic agents a. Oral glycerine
A. Agonists (sympathomimetics) b. Isosorbide.
1. Nonselective alpha-adrenergic agonists 2. Intravenous
a. Epinephrine a. Mannitol
b. Dipivefrin b. Urea.
Chapter 75: Pharmacognosy and Pharmacokinetics of Ocular Hypotensive Agents 567
V. Prostaglandins the darker eyes. Peak IOP lowering effect is seen at 2-
1. PGF-2 Alpha 3 hours of application and lasts for 6-8 hours.
2. PHXA-41.
VI. Neuroprotective agents Preparations
1. NMDA-receptor antagonists Pilocarpine is available as nitrate and hydrochloride
2. Calcium channel blocker salt, but there is no significant difference in their thera-
3. Nitric oxide synthase inhibitors peutic action. The drug may be used as:
4. Antioxidants a. Drops—in concentration of 1%, 2% or 4% solution
5. Vasodilators. four times a day.
b. Diffuse membrane delivery system (ocusert):
CHOLINERGIC DRUGS — 20-40 microgram/hour
— ocusert P20
Parasympathomimetics — ocusert P40
Pilocarpine Dose 1 insert for 7 days.
Pilocarpine is a natural alkaloid, obtained from the Advantages of ocusert are:
leaves of pilocarpus microphyllus. It has prominent i. Once a week application
muscarinic action and it also stimulates ganglia. Pilo- ii. No question of drug noncompliance
carpine acts as the parasympathomimetic at the iii. Uninterrupted pressure reduction
muscarinic receptor site, as does the physiologic Disadvantages of ocusert are:
mediator, acetylcholine. i. Foreign body sensation
ii. Unpredictable pressure reduction
Mechanism of action
iii. Expensive
a. Angle closure glaucoma Stimulation of parasympa-
c. Pilocarpine gel—4% (Acrylic gel).
thetic nerve ending causes constriction of the
Dose
pupillary sphincter muscle leading to miosis.
— once daily at night
Peripheral iris is pulled away from trabecular
— causes blurring and haziness of vision.
meshwork, thereby preventing the crowding of iris
d. Pilocarpine polymer—piloplex is an aqueous emul-
at the angle and also it prevents relative pupillary sion consisting of polymeric material to which
block. pilocarpine base is bound.
b. Open angle glaucoma Pilocarpine reduces IOP by e. Soft contact lens—lens used as a reservoir for the
increasing aqueous outflow facility. Pilocar- medicine. Lens is soaked for 2 minutes in 0.5
pine causes contraction of longitudinal fibers percent pilocarpine and then placed over the
of the ciliary muscles inserted into the scleral cornea.
spur. This causes opening up of the trabecular
pores and leads to increased drainage of aqueous Clinical indications
humor. a. Primary open angle glaucoma
Miosis not associated with lowering of IOP may b. Acute and chronic angle closure glaucoma
be considered as adverse side effect of the drug. c. Certain noninflammatory secondary glaucoma
Intraocular penetration of pilocarpine is excellent d. For opening the angle wider for laser trabeculo-
because of the biphasic solubility of the pilocarpine plasty1
molecules. Molecules of nonionized drug are lipid e. Tightening the iris longitudinal fibers to minimize
soluble and easily cross epithelium. Ionized molecules laser applications during iridotomy.
are water-soluble, thus readily cross the stromal
Contraindications of uses of pilocarpine
barrier before reconverting to the nonionized form and
a. Neovascular glaucoma
cross the endothelium. Although high levels of b. Glaucoma secondary to uveitis.
pilocarpine are detectable in the aqueous 5 minutes
after topical instillation, the binding of the drug by Drawbacks of cholinomimetics
serum proteins and ocular melanin alters drug a. Miosis It causes reduction of visual acuity in adult
availability at receptor sites. A dark brown iris will with lens opacity.
bind more drug than a blue iris, resulting in less b. Cyclotonia It causes unwanted accommodation in
lowering of pressure, but longer duration of action in young patient.
Suitable cholinomimetic agent is yet to be found: this results in contraction of the longitudinal fibers of
i. that will not produce miosis but only increases the ciliary muscle thus, like pilocarpine, widening the
outflow facility. trabecular meshwork spaces and increasing facility of
ii. without any effect on accommodation. outflow. There is also an intense miotic effect, that is
iii. agents which will exert its cholinomimetic unrelated to the IOP reduction. It has weak anticholi-
effect directly on trabecular meshwork. nesterase action, it causes less fluctuating myopia.
Adverse side effects Preparations
Ocular side-effects These are as follows: • Topical agent 0.75-3.0 percent solution commonly
• Reduced vision in low illuminations secondary to used 3 to 4 times daily.
pupillary miosis • Intracameral—for reduction of IOP in postopera-
• Myopia due to ciliary muscle contraction tive period.
• Supraorbital and temporal headache • Miochol (Intraoperatively) before implanting an
• Allergic blepharoconjunctivitis anterior chamber intraocular lens.
• Ocular pemphigoid Indications
• Lacrimation a. In patients who develop resistance or intolerance
• Corneal epithelial staining and vascularization to pilocarpine, carbachol can be used as substitute
• Atypical band keratopathy for pilocarpine.
• Iris hyperemia, cyst formation b. Postoperative IOP control.
• Nuclear sclerosis of lens
• Retinal hole formation Anticholinesterases
• Retinal detachment
• Vitreous hemorrhage. Long-acting
• Echothiophate (Phospholine)
Systemic effects These are as follows:
• Isoflurophate
• Absorption of drug across the nasolacrimal and
• Demacarium bromide.
conjunctival mucous membranes occasionally may
result in increased systemic muscarinic activity Short-acting
• Hiccough, nausea, vomiting, diarrhea • Physostigmine (Eserine)
• Lacrimation, salivation • Neostigmine.
• Bronchospasm, pulmonary edema.
Echothiophate (Phospholine Iodide)
Additive effect These act well with epinephrine, beta-
blockers and carbonic anhydrase inhibitors. Echothiophate is an organophosphorous drug. It acts
through irreversible binding of both anionic and
Carbachol esteratic sites of cholinesterase to produce an extrem-
ely stable phosphorylated enzyme. This allows
Carbachol is the other cholinergic agent widely used
accumulation of acetylcholine at the neural effector
in glaucoma management. It is a synthetic derivative
junction. It is very potent in action. Clinically the effect
of choline. It differs structurally from acetylcholine,
is similar to that of pilocarpine. Intraocular penetration
and possesses a carbamyl group rather than an acetyl
is excellent because of biphasic nature of the molecule.
group. It is resistant to hydrolysis by cholinesterases.
Miosis begins in 5-10 minutes and lasts up to 1 week.
It contains quarternary nitrogen which gives the
molecule a polar charge and low bipolarity causes low Preparations
corneal penetration. It has greater effect on diurnal • Concentration of 0.03-0.25 percent for topical use
fluctuation of IOP. It has more prolonged effect than • Marketed as powder
pilocarpine. • Unstable at room temperature.
• Storage at 4°C.
Mechanism of action
Carbachol works both as a direct acetylcholine-like Indications
parasympathetic drug and indirectly by displacing • In pilocarpine resistant cases.
acetylcholine from the parasympathetic terminals and • In young people to avoid fluctuating myopia
also by inhibiting cholinesterase. Pharmacologically, because of long duration of action.
Adverse side effect Physostigmine (Eserine)
Ocular side- effects These are as follows: • Short-acting anticholinesterase
• Allergic conjunctivitis • Natural alkaloid
• Contact dermatitis • Action and intraocular penetration are similar to
• Chronic conjunctival hyperemia those of demecarium (vide supra)
• Pemphigoid • IOP lowering effect begins within 30 minutes
• Posterior-synechiae, pupillary cyst • Duration of action is 24 hours
• Lens—anterior subcapsular and nuclear opacity • Available as ointment or drops of 0.25-
• Retinal detachment, vitreous hemorrhage, vitreous 0.5 percent
floaters. Indication, adverse side effect, and contraindi-
Systemic effects Same as pilocarpine but more toxic. cation are similar to those of echothiophate.
Contraindications ADRENERGIC AGONISTS
a. Presence of shallow anterior chamber that may
precipitate acute angle closure glaucoma by for- Nonselective Alpha-Adrenergic Agonists
ward movement of the iris-lens diaphragm. Epinephrine
b. Glaucoma secondary to uveitis may be aggravated
by drug-induced breakdown of the blood-aqueous It is a naturally occurring catecholamine that acts on
barrier with subsequent enhanced inflammation. both the alpha and beta-receptor sites in the eye.
c. Angle closure glaucoma secondary to neovascular Mechanism of action
membrane and peripheral anterior synechiae. Stimulation of beta-receptors in eye results in
increased cyclic AMP production with enhanced
Isoflurophate
aqueous outflow facility. The mechanism of action of
• An irreversible inhibitor of cholinesterase epinephrine is complex. The intraocular pressure
• Onset, duration of action, and pharmacologic effect lowering effect is the net result of the balance between
on eye are similar to those of echothiophate alpha and beta-adrenergic receptor stimulation.
• Intraocular penetration is good because of high Alpha-adrenergic stimulation by epinephrine causes
lipid solubility of the drug, which enhances constriction of blood vessels in the ciliary processes,
passage across epithelium and endothelium. reducing the pressure for ultrafiltration and indirectly
Preparations reducing aqueous formation. Beta-adrenergic stimu-
• Available in an anhydrous vegetable oil or oint- lation of the adrenoceptors in the ciliary epithelium
ment base in concentration of 0.01-0.1 percent causes an increase in aqueous production. Beta-
• Maximum lowering of IOP is achieved with 1 drop adrenergic stimulation of the ciliary muscle may
once or twice daily increase uveoscleral outflow and trabecular outflow.
• Clinical indications and adverse effects are similar These events balance, resulting in an overall reduction
to those of echothiophate. in intraocular pressure. Epinephrine increases both
conventional and uveoscleral outflow facility.
Demecarium Bromide The pharmacologic effects of the drug on the eye
causes 10-30 percent reduction in IOP, which is
• Short-acting anticholinesterase
maximum with 2 percent concentration. Onset of
• Synthesized by the linking of two neostigmine
decreased IOP is within 1 hour of instillation and the
molecules
maximum effect 2-4 hours later. Intraocular pene-
• Increase outflow facility
tration is good. Mydriasis is due to activation of iris
• Miosis is tight, not related to lowering of IOP
dilator pupillary muscle.
• Onset and duration of clinical effect are similar to
those of echothiophate Preparations and dosage
• Used as 0.12-0.25 percent drops • Marketed as borate, hydrochloride or bitartrate salt
• IOP lowering effect lasts upto 4 days after 1 drop • No significant difference in clinical efficacy of these
• Indication, adverse side effect, and contraindica- preparations lowering effect on IOP
tion are similar to those of echothiophate. • Concentration available 0.25-2 percent
• Combination with pilocarpine is also available results is increased bioavailability and longer duration
• Dosage—usually twice daily. of action of the drug compared to ephinephrine.
Intraocular penetration of dipivefrin across the
Clinical indications
cornea is almost 17 times more than that of epine-
• Primary open angle glaucoma
phrine. The presence of the pivalic acid group renders
• Secondary open angle glaucoma
the prodrug more lipophilic. 0.1 percent solution of
• Though it is contraindicated in eye at risk of angle
DPE induced IOP lowering is comparable to that of 2
closure glaucoma, it may be used with miotics in
percent topical epinephrine.3
chronic angle closure glaucoma.
Preparations
Contraindications
• Aqueous solution of 0.1 percent dipivefrin hydro-
• Patient with cardiovascular diseases
chloride available
• Hyperthyroidism
• Dosage once every 12 hours
• Diabetes
• Additive effect in reduction is IOP with cholinergic
• Cerebrovascular diseases
and carbonic anhydrase.
• Aphakia and pseudophakia.
Indications
Adverse side effects • Primary open angle glaucoma
Ocular effects These are as follows: • Secondary open angle glaucoma
• Rebound conjunctival hyperemia, irritation, and • Certain chronic angle closure glaucoma
stinging • Inflammatory glaucoma.
• Allergic conjunctivitis and periocular dermatitis
• Adenochrome deposition over cornea and conjunc- Adverse side effects
tiva Ocular effects These are as follows:
• Ocular pemphigoid • Burning, stinging, rebound conjunctival hyperemia
• Cystoid macular edema. • Superficial punctate keratitis (SPK).
• Follicular conjunctivitis (bulbar conjunctiva)
Systemic effects are: • No adrochrome deposition
• Hypertension, angina, tachycardia. • Cystoid macular edema (CME).
Systemic effects Adverse effect is less as compared to
Dipivefrin Hydrochloride
epinephine.
[Dipivalyl Epinephrine (DPE)]
Dipivefrin is a synthetic prodrug created by the addi- Selective Alpha-Adrenergic Agonists
tion of two pivalic acid groups to the epinephrine Alpha-adrenoreceptor agonists have been used exten-
molecule. The clinical usefulness of epinephrine is sively in some European countries for prolonged
limited by its bioavailability and side effects. The therapy of glaucoma and in US, primarily for prophy-
prodrug form of epinephrine, dipivefrin, was synthe- laxis for pressure spikes occurring after laser proce-
sized to enhance corneal penetration and to minimize dure in the anterior segment.
toxicity using a lower concentration. Increase in
bioavailability of epinephrine minimizes the toxicity Clonidine
through lower concentration and long duration of the
Clonidine was the first drug of this group. This was
drug.2 first used as a nasal decongestant and later, as a syste-
mic hypotensive agent. Harrison and Kaufman in 1977
Mechanism of action demonstrated that clonidine is an effective ocular
It is similar to that of epinephrine in that this drug is hypotensive agent. On the other hand, they found that
both an alpha and beta-receptor stimulant. The topical clonidine could produce marked adverse
pharmacologic effect on the eye is both inhibition of cardiovascular effects. It produces no change in pulse
aqueous formation by the ciliary body and increased rate, but significantly lowers the systolic and diastolic
facility of outflow via the trabecular meshwork. blood pressure. In addition, it might also decrease
Dipivefrin is metabolized in eye by esterases for remo- vascular perfusion to the optic nerve. Theortically, this
val of pivalyl acid group. This results in release of decreased ocular perfusion might cause progressive
epinephine slower than that of epinephine alone. This optic nerve damage inspite of adequate IOP lowering.
Later clonidine was tried as a “minidrop” of b. Effective ocular hypotensive in acute glaucoma like
15 microliter (0.25%). This produced sufficient lowe- primary acute congestive glaucoma and lens
ring of IOP without serious systemic adverse effects. induced glaucoma.8
However, a minidrop of 15 microliter cannot reliably
Adverse side effects
be delivered commercially.
Ocular effects These are as follows:
Mechanism of actions • Upper lid retraction
a. It has central neural effect. • Conjunctival blanching
b. It decreased production of aqueous humor. • Pupillary mydriasis
c. It reduces blood flow to limbal blood vessels which • Subconjunctival hemorrhage.
could alter the episcleral venous pressure. Systemic effects These are as follows:
d. Dose—0.125-0.25 percent twice daily. • Bradycardia, vasovagal attack, palpitation,
postural hypotension, insomnia
Apraclonidine • Abdominal pain, nausea, vomiting, diarrhea.
Apraclonidine hydrochloride is a clonidine derivative Brimonidine

which is a relatively selective alpha-agonist. The only Brimonidine is similar to clonidine in its relative alpha-
chemical difference between clonidine and apraclo- 2 adrenoreceptor agonism, lipophilicity, and relative
nidine is a molecular alteration on the C4 position of lack of alpha-1 adrenoreceptor agonism. It has higher
the benzene ring; apraclonidine has an amide group selectivity of alpha-2 receptor than clonidine and
attached at this site while clonidine does not. This apraclonidine.9 The selectivity and chemical structure
change in molecular structure prevents the central of the drug may provide an advantage for brimonidine
effect which is responsible for the systemic side effect. over apraclonidine. It is more potent in penetrating
Apraclonidine is an extremely potent ocular hypo- the cornea than apraclonidine. It lowers IOP in
tensive agent.4 One percent apraclonidine solution normotensive, glaucomatous and ocular hypertensive
decreases IOP by almost 40 percent at approximately patients by dual mechanism of decreasing inflow and
3 hours and 25 percent at 12 hours. IOP lowering effect increasing uveoscleral outflow. It may also be used to
is similar in both volunteers and in patients with reduce the incidence of IOP spikes after laser trabe-
elevated IOP.5 culoplasty. It produces sustained long-term ocular
Mechanism of actions hypotensive effect. It has no contraindication in
a. It causes reduction in secretion of aqueous humor. patients with pulmonary diseases.
b. It has no effect on outflow facility. Preparations
• Brimonidine tartrate 0.5-2 percent
Clinical indications and dosage • Dose—three times daily.
a. One percent apraclonidine is effective in blunting
the IOP rise following Nd: Yag laser iridotomy, Adverse effects
capsulotomy and argon laser trabeculoplasty • Oral dryness, headache, and ocular hyperemia
(ALT). One drop to be instilled 1 hour prior to laser • Burning and stinging, blurring or vision
procedure and 1 drop immediately after the laser • Foreign body sensation
procedure. • Conjunctival follicle formation
b. Half percent apraclonidine was marketed in 1993 • Ocular allergic reactions
and used as an adjuvant to maximum medical • Corneal staining and erosion
therapy. But its prolonged use has been limited due • Photophobia
to its tachyphylactic reaction. • Abnormal taste
c. Usual dose is twice daily. • Depression, hypotension, sedation, anxiety, insom-
nia
Other Indications • Palpitation, nasal dryness and syncope.
a. It causes vasonstriction and mydriasis, in addition
to its IOP lowering effect. So it can be used in cata- ADRENERGIC BLOCKING AGENTS
ract surgery6,7 to reduce bleeding and to prevent Now beta-blockers are the most commonly used class
IOP elevation. of drug for treating glaucoma world over. Because of
their almost universal efficacy and minimal ocular side production without altering facility of aqueous
effects, these drugs usually are the first-line agents for outflow whether given topically or systemically.10 The
medical therapy of all types of glaucoma. Adrenergic relationship between duration of therapeutic effect
antagonists have an affinity for adrenoreceptors and drug-binding affinity at the receptor is not
because they share a structural similarity. They block understood. It appears that timolol releases from the
the adrenoreceptors, interfering with the stimulation receptor site as early as 3 hours after topical adminis-
of an adrenergic response. Most antagonists have tration, yet the clinical effect may last up to 2 weeks.11,12
limited or no capacity to stimulate the receptors. Those This may be the result of a “depot effect,” where there
that can stimulate are said to have intrinsic sympatho- is significant accumulation of the drug bound to the
mimetic activity (ISA). Adrenergic antagonists blocks iris pigment epithelial melanin. Gradual release of
the receptors by competitive inhibition. timolol from this depot in the eye would result in
In the eye, adrenergic receptors appear to be beta- prolonged duration of the drug effect. It also may
2 and these are primarily present in the ciliary pro- explain the reduced pressure effect on heavily
cesses. There are scattered sparse beta-1 receptors in pigmented eyes. It lowers the IOP in both glauco-
the eye, but their role in drug action is still speculative. matous and normotensive eyes. Intraocular pene-
Beta-blocker (propranolol) possesses the membrane tration of timolol is good because of its lipophilicity.
stabilizing effect. This makes them unsuitable for Clinical effect may last up to 2 weeks after topical use.
topical use in glaucoma because of the induction of Peak level of drugs appears within 1-2 hours.
corneal anesthesia. Unlike miotic, beta-blockers have Preparations
no effect on pupillary dilation or accommodation. • Available as 0.25 percent and 0.5 percent drops
Unlike epinephrine compounds, the beta-blockers do • Timolol maleate also available as an ophthalmic
not cause mydriasis or reactive hyperemia. gel forming solution. Dose is once daily at bedtime
• IOP reduction occurs within 30-60 minutes
Available Beta-Blockers • Use of 0.25 percent drop every 12 hours may be
1. Nonselective, non-ISA more effective than 0.5 percent once daily.
• Timolol Combination of timolol with pilocarpine or CAI
• Levobunolol reduces aqueous output by more than 50 percent.
• Metipranolol Many studies have been conducted to conclude that
2. Selective, non-ISA timolol 0.5 percent and pilocarpine 2 percent can be
• Betaxolol made available in the same container. The stability of
3. Nonselective with ISA the combination is questionable. It is available as
• Carteolol “timpilo” in European countries in a double layered
container. The dose is twice daily. The IOP reducing
ISA (Intrinsic Sympathomimetic Activity) effect is almost equal to timolol 0.5 percent b.i.d. and
pilocarpine 2 percent q.i.d.
• Heart rate—no effect on heart rate
— Bronchopulmonary—lower propensity to cause Indications
bronchoconstriction • Primary open angle glaucoma
— Blood lipids—less effect on plasma lipid profile. • Secondary open angle glaucoma
• Secondary angle closure glaucoma after penetra-
Timolol ting keratoplasty,
Timolol was the first beta-blockers to become commer- • Aphakic and pseudophakic glaucoma
cially available for ophthalmic use and introduced in • Acute and chronic primary angle closure glaucoma
• Developmental glaucoma
September 1978. Timolol inhibits both beta-1 and beta-
• Secondary glaucoma in children.
2 activities. It exists in both l and d-isomer forms. The
d-isomer produces less pressure reduction than l- Contraindications
timolol. Timolol is approximately five times as potent Bronchial asthma, heart block, recent myocardial
as propranolol. infarction.
Mechanism of actions Tolerance

Timolol maleate is a nonspecific beta-1 and beta-2 • Tolerance to timolol—in some patients it is mani-
blocker that induces decreased aqueous humor fested by gradual decrease in IOP control
• Short-term escape develops within days of initia- Metipranolol
ting therapy. This form of tachyphylaxis is very
• Nonselective beta-1 and beta-2 blockers
rare.
• Its action, administration, and efficacy are similar
• More common is long-term drift. This gradual rise
to timolol; available as 0.3 percent and 0.6 percent;
in pressure despite continued therapy may develop
after many months or years of treatment and this dose schedule twice daily.
may occur as a result of drug modulation of ocular Adverse effect
receptors. Aqueous suppression is nearly 50 • Burning and stinging (most common)
percent at the end of first week of timolol therapy; • Granulomatous uveitis.
may be near 25 percent suppression after 1 year.
Betaxolol
Adverse side effects
Timolol is relatively well tolerated. Ocular side effects Many of the systemic side effects of beta-blockers are
are nonspecific. results of nonselective inhibition of both beta-1 and
beta-2 receptors. 14 Betaxolol hydrochloride was
Ocular adverse effects These are as follows:
• Allergic conjunctivitis, orbital pain introduced in the early 1980s as the first topical, cardio-
• Blurred vision selective, beta-1 adrenergic antagonist for ophthalmo-
• Ocular myasthenia gravis logic use. By minimizing beta-inhibition, it offers a
• Diplopia reduced potential for side effects, particularly pulmo-
• Keratoconjunctivitis sicca, SPK, corneal erosion, nary problems.
corneal anesthesia. Its mechanism of action is similar to that of timolol.
Although there is no definite proof, betaxolol is
Systemic effects These are as follows:
thought to reduce aqueous formation through
• Bronchospasm, aggravating asthma, emphysema,
blockade of the beta-receptors of the nonpigmented
bronchitis
ciliary epithelium. However, ciliary body adreno-
• Heart failure in pulmonary edema have occurred
ceptors are predominantly of beta-2 subtype. Some of
in patients with cardiomyopathy
betaxolol block the beta-2 receptors in ciliary body.
• AV disassociation and cardiac arrest in patients
Betaxolol does not affect conventional or uveoscleral
with pre-existing partial heart block.
outflow facility and decreases both normal and
Levobunolol elevated IOP. It is less effective in both lowering IOP
and reducing aqueous flow as compared with timolol.
Levobunolol hydrochloride is a propranolol analog
with potent nonselective beta-adrenergic antagonism. Preparation
Levobunolol lowers intraocular pressure in normal • Available as 0.25 percent, 0.5 percent
subjects and in patients with ocular hypertension and • Onset of action within 30 minutes
glaucoma. Like timolol, levobunolol exists in both l • Maximum effect occurs in 2 hours.
and d-stereoisomeric forms. Bunolol is over 60 times
Concomitant therapy
potent than levobunolol. It exhibits neither intrinsic
sympathomimetic activity nor significant local anes- Ten to fifteen percent of additive effect on IOP when
thetic activity. used in combination with epinephrine or dipivefrin.
Levobunolol is similar to timolol, so far as side Adverse effects
effects and reduction of intraocular pressure are • It causes more burning and stinging than timolol
concerned. It has a longer half-life than timolol. It is Cardiac side effects are more with betaxolol
first metabolized to dihydrolevobunolol, which is • It is well-tolerated in patients with pulmonary
equipotent to the parent compound. The half-life of diseases.
dihydrolevobunolol is 7 hours. Onset of action is Indications
within 1 hour and peaks at 2-6 hours and duration up • Same as timolol
to 24 hours.13 • Glaucoma in patient with bronchoconstriction.
• Dose 0.5 percent once daily
• Additive effect with pilocarpine, CAI, epinephrine Carteolol
• Clinical indications and adverse effect same as
timolol Carteolol is a nonselective beta-blocker structurally
• No drug tolerance with levobunolol. related to timolol, levobunolol, and betaxolol.15
Cartelol has intrinsic sympathomimetic activity, c. Intravenous preparations

causing an early transient agonist response not found • 500 mg vials
in the other beta-blockers. It has more selective action • For intravenous use
on eye than cardiopulmonary system and induces less • Onset of action is immediate
bradycardia than timolol. Its action, administration, • Peak action at 30 minutes and remains up to
and efficacy are similar to timolol. 4 hours.
The half-life of its metabolite, 8-hydroxycarteolol,
is two to three times more than that of the parent Methazolamide
molecule. This may allow better bioavailability and
Preparation—tablet
increased duration of action compared with other
• Usual dose is 50 to 100 mg bid or qid
beta- adrenergic antagonists. It is available in 1 percent
• Greater lipid solubility and lower plasma binding,
and 2 percent concentration.
allowing better diffusion into ocular tissue
Adverse effects • Produces fewer renal side effect
Exacerbation of bronchial asthma, bradycardia, and • Plasma half-life is 15 hours
cardiac insufficiency. • Onset of action is within 3 hours with peak at 6
hours
CARBONIC ANHYDRASE INHIBITOR (CAI) • Duration of action up to 10-18 hours
• Useful alternative to acetazolamide.
Mechanism of action
In the eye carbonic anhydrase is present in the Dichlorphenamide (Daranide)
pigmented and non-pigmented epithelium of the cili-
Preparation—tablet
ary body. Its exact role is unclear, but it may provide
• Dose 50 mg to 100 mg two to three times daily
bicarbonate anions necessary to balance sodium
• Duration of action up to 6-12 hours
cations involved in aqueous humor formation. CAI
• Maximum effective dose is 200 mg/24 hours.
inhibits the enzyme carbonic anhydrase thereby
prevents the bicarbonate anions and sodium influx
Ethozolamide
and decreases aqueous formation.
CAI is useful as short-term treatment of acute • No longer available
glaucoma. Long-term therapy is usually for patients • Dose—62.5 mg to 250 mg t.i.d. or q.i.d.
with high risk of visual loss. They are rapidly absorbed
Adverse effects of CAI
from the gastrointestinal tract. Its onset of ocular
Up to 50 percent of the patients are unable to tolerate
hypotension is within one hour which has maximum
carbonic anhydrase inhibitors because of their adverse
effect at 4 hours. CAI decreases day time and night
effects. They occur more commonly in elderly people.
time aqueous flow. Effect of CAI on aqueous flow
Taking medication with food, lowering the dosage,
would be secondary to effect on acid-base balance;
supplementing with sodium bicarbonate or switching
acidosis decreases the aqueous formation.
to other medications will reduce the side effects of CAI.
Oral CAI
Symptoms
Acetazolamide a. Neurological/psychiatric
Preparations • Paresthesia
a. Tablet • Fatigue
• Given orally—125 mg and 250 mg • Malaise
• Onset of action within 1 hour • Depression
• Peak at 4 hours • Headache
• Half-life of acetazolamide 5 hours • Decreased libido.
• Duration of action up to 6-12 hours b. Gastrointestinal
• Dose—q.i.d. • Abdominal cramps and discomfort
b. Slow release capsule (diamox SR) 500 mg • Nausea
• Given orally, once or twice daily • Diarrhea
• Duration up to 24 hours. • Metallic taste.
c. Renal/metabolic Clinical indication of CAI
• Increased micturation frequency • Acute angle closure glaucoma
• Renal stones (5%)—This may be due to the • Adjunctive therapy to primary and secondary open
reduced excretion of citrate, which normally angle and angle closure glaucoma
helps to solubilize urinary calcium. Renal stone • Inflammatory and postoperative glaucoma.
formation is less frequent with methazolamide
• Hypokalemia—metabolic acidosis is due to PROSTAGLANDINS (PG)
increased excretion of bicarbonate. The acidosis The prostaglandins are the family of biologically active
may pose a risk in patients with other causes of classes of 20 carbon fatty acids derived mainly from
acidosis such as severe diabetes or hepatic, renal arachidonic acid. Early studies showed that prosta-
or adrenal insufficiency. Patients receiving high glandins mediated an acute ocular inflammatory
dose of opium or other salicylate compound response characterized by conjunctival and iridial
may risk salicylate intoxication hyperemia, miosis, breakdown of blood-aqueous
• Uric acid excretion is decreased and may cause barrier, and increase in IOP. However, it has been well-
exacerbation of gout. established that lower doses of certain prostaglandins,
d. Hematological—like other sulphonamide CAI may especially PGF-2 alpha, have a dramatic IOP lowering
cause bone marrow depression effect of longer duration in normotensive and glauco-
• Aplastic anemia—rare matous patients. Even though there was no effect on
• Thrombocytopenia, agranulocytosis, neutro- pupillary diameter and visual acuity; many patients
penia—all these will have an acute onset. They experienced conjunctival hyperemia, ocular irritation
are not dose related. They are reversible with and foreign body sensation. A new compound PHXA-
cessation of the drugs. 41,19,20 a phenyl substituted analog of PGA-2 alpha
e. Teratogenic effect—very rare
was developed. This is well-tolerated with minimal
• Various deformities have been reported in labo-
side effects.
ratory animals
• CAI are contraindicated in the first trimester of Mechanism of action
pregnancy. • PG induced reduction of IOP due to decrease
inflow resistance
Topical CAI • Increased uveoscleral flow by relaxation of ciliary
Dorzolamide or MK 507: (Trusopt) muscle
• IOP reduction at 3 hours after administration of
The main advantage of the topical carbonic anhydrase
drug
inhibitors is its much lower dose, which is applied
• IOP reduction significantly better than timolol
directly to the eye and fewer potential systemic side
• It has greater efficacy during day and night aqueous
effects.16 The efficacy of topical CAI depends on many
flow.
factors like its lipid and water solubility, its potency,
and its contact time with the cornea.17 • Approximately 100-fold greater potency than
Many related compounds like ethoxozolamide timolol
were tried topically. These compounds are potent and • Ability to increase outflow of aqueous rather than
water soluble. In a number of clinical trials, MK 927 suppress aqueous humor formation
has shown to be an effective ocular hypotensive agent • No effect on the following:
with minimal side effects.18 MK 417 (sezolamide) is i. Blood flow
much more potent than MK 927. MK 507 is the most ii. Blood-aqueous barrier
recent and most potent compound. It is specific for iii. Retinal vasculature.
carbonic anhydrase isoenzyme II, which is present in • Dose—0.05 percent latanoprost (xalatan) one drop
ciliary processes. It appears that MK 507 is more active once daily.20
in lowering IOP and somewhat better tolerated than Adverse effects
MK 417. • Burning, blurred vision, itching
Adverse side effects • Foreign body sensation
• Stinging, metallic taste, conjunctival hyperemia, • Conjunctival hyperemia
hypersensitivity reaction • Increased coronary blood flow
• Systemic side effects are rare. • Bronchoconstriction.
Iris sun-tan Syndrome Mannitol

Iris color change. Latanoprost produces a definite • Twenty percent concentration
increase in pigmentation on iris due to stimulation of • Less irritating on blood vessels; it is the choice for
melanin synthesis (melanogenesis). intravenous therapy
• Not metabolized, and excreted unchanged
HYPEROSMOTIC INTRAVENOUS AGENTS • Ocular penetration is very poor
• Can be used in diabetic patient
Mode of action • Not contraindicated in renal failure patients.
• Increase the osmolarity of plasma
• Leads to absorption of water from ocular tissue Disadvantage of mannitol
(mainly vitreous) • Large volume
• This process is transient till the osmotic equilibrium • Dehydration
is re-established • Diuresis.
• Hyperosmotic agent is of low molecular weight Dosage of mannitol
substance and remains in extracellular fluid space. • 1-2 gm/kg body weight or 5-10 ml/kg body weight
• Not more than 60 drops per minute over 20-
Adverse effect 30 minutes
• Headache, nausea, vomiting and confusion • Peak action within 30 minutes
• Coma, subdural hematoma • Duration of action up to 6 hours.
• Systemic hypertension
• Congestive heart failure and pulmonary edema Urea
• Urinary retention and hyperglycemia in diabetic • Less effective than mannitol
patients. • It penetrates eye readily
• Distributed in total body water
Indications • Rapid action, nonmetabolized, no caloric value
• Any type of acute glaucoma • Less cellular dehydration.
• Secondary glaucoma—hyperosmotic agents used
to prepare the patient for surgery Disadvantages
• Ciliary glaucoma (malignant). • Unstable solution
• Penetrate the eye
Oral Glycerol • Thrombophlebitis and sloughing of skin at infusion
• Most widely used drug therapy site.
• Fifty percent solution in dose of 1.5 to 3 ml/kg body
weight NEUROPROTECTIVE AGENTS21
• Poorly penetrates into the eye
In most of the patients with pressure independent
• Diabetic patients may have problems due to its
glaucomatous optic neuropathy, pressure reduction
caloric value, osmotic diuresis, and dehydration.
will not be beneficial to prevent visual loss. Many
studies are under trial to find out the means to protect
Isosorbide
the optic nerve from this damage. Strategies to develop
• Effective oral hyperosmotic agent therapies to protect the optic nerve are the following:
• Fewer side effects than glycerol 1. Block the endogenous substances which may have
• Administered in dosage of 1 to 1.5 gm/kg body damaging effect on ganglion cells/optic nerve.
weight 2. Prevent neuronal degeneration/promote regenera-
• Ninety-five percent drug is excreted unchanged in tion by altering pathological changes.
the urine 3. Block the endogenous substances that are believed
• Not metabolized, no caloric value to be released during glaucoma which may
• Safe in diabetic patient damage ganglion cells/optic nerve. The substances
• Less likely to produce nausea and vomiting. are the following:
• Excitotoxins—are the excitatory amino acid cataract extraction and trabeculectomy. Ophthalmology
transmitters which include glutamate and 1993;100:628.
7. Robin AL. Role of apraclonidine hydrochloride in laser
aspartate
therapy for glaucoma. Trans Am Ophthalmol Soc 1989;87:729.
• Elevated intracellular Ca++ 8. Serle JB, et al. The effect of brimonidine tartarate in glaucoma
• Nitric oxide patients on maximal medical therapy. Invest Ophthalmol Vis
• Free radicals Sci 1993;34(suppl):1137.
• O2/CO2 alterations. 9. Jampel Hd, et al. Beta-adrenergic receptors in human
Pharmological agents that prevent neuronal trabecular meshwork. Invest Ophthalmol Vis Sci 1987;28:772.
10. Zimmerman TJ, Kaufman HE. Timolol: A beta-adrenergic
degeneration and promote regeneration are the blocking agent for the treatment of glaucoma. Arch
following: Ophthalmol 1977;95:601.
• Calcium channel blockers22 11. Zimmerman TJ, Kaufman HE. Timolol: Dose response and
• Nitric oxide synthase inhibitors duration of action. Arch Ophthalmol 1977;95:605.
• Antioxidants 12. Wandel T, et al. Glaucoma treatment with once daily
levobunolol. Am J Ophthalmol 1986;101:298.
• Vasodilators.
13. Reiss GR, Brubaker RF. The mechanism of betaxolol: A new
Among the above mentioned group, calcium ocular hypotensive agent. Ophthalmology 1983;90:1369.
channel blockers are proved to be more useful 14. Stewart WC. Carteolol: An ophthalmic beta-adrenergic
especially in low tension glaucoma by improving the blocker with intrisic sympathomimetic activity. J Glaucoma
blood flow to the optic nerve head. Common calcium 1994;3:339.
channel blockers tried were nifedipine, verapamil, and 15. Bar-Ilan A, Pessah NI, Maren TH. Ocular penetration and
hypotensive activity of the topically applied carbonic
diletiazem.23-25 anhydrase inhibitors L-645, 151. J Ocul Pharmacol 1986;2:109.
The primary goal of glaucoma management is to 16. Brechue WF, Maren TH. A comparison between the effect of
preserve patients’ vision and to maintain the quality topical carbonic anhydrous inhibition (CAI) is affected by
of life. The traditional medical treatment of glaucoma drug ionization. Invest Ophthalmol Vis Sci 1992;33(Suppl):
is based on several classes of drugs, their efficacy and 1117.
17. Bron A, et al. Multiple-dose efficacy comparision of two
safety. Constant research is under way to find new
carbonic anhydrous inhibitors sezolamide and MK-927. Arch
classes of drugs which will prevent degeneration and Ophthalmol 1991;109:50.
promote regeneration of retinal nerve fibers with 18. Alun A, Villummen J. PHXA-34—a new potent ocular hypo-
minimum dose. tensive drug: A study on healthy volounteers. Arch
REFERENCES 19. Alun A, et al. Once daily application of latanoprost causes a
maintained reduction of intraocular pressure in glaucoma
1. Robin AL, Pollack IP, House B, et al. Effects of ALO 2145 on patients treated with timolol. Invest Ophthalmol Vis Sci
intraocular pressure following argon laser trabeculoplasty. 1993;34(suppl):932.
Arch Ophthalmol 1987;105:646. 20. Neuofield AH. Under pressure glaucoma 1994—American
2. Kohn AN, et al. Clinical comparison of dipivalyl epinephrine Academy of Ophthalmology and American Glaucoma Society
and epinephrine in the treatment of glaucoma. Am J on Oct 29, 1994. San Fransisco.
Ophthalmol 1979;87:196. 21. Abelson MB, Gilbert CM, Smith LM. Sustained reduction of
3. Kreigelstein GK, Leydhecker W. The dose response relation- intraocular pressure in humans with the calcium channel
ships of dipivalyl epinephrine in open angle glaucoma. blocker verapramil. Am J Ophthalmol 1988;105:155.
Grafe’s Arch Clin Exp Ophthalmol 1978;205:141. 22. Beatty JF, et al. Elevation of intraocular pressure by calcium
4. Abrams DA, Robin AL, Crandall AS, et al. A limited channel blockers. Arch Ophthalmol 1984;102:1072.
comparison of apraclonidine’s dose response in subjects with 23. Gasser P, Flammer J. Short- and long-term effect of nifedepine
normal or increased intraocular pressure. Am J Ophthalmol on the visual field in patients with presumed vasospasm. J
1989;108:230. Int Med Res 1990;18:334.
5. Wides SB, Muckenzic DCH. Control of IOP with apraclo- 24. Netland PA, Chaturvedi N, Dreyer EB. Calcium channel
nidine hydrochloride after cataract extraction. Am J blockers in the management of low-tension and open angle
Ophthalmol 1991;111:184. glaucoma. Am J Ophthalmol 1993;115:608.
6. Robin AL. Effect of topical apraclonidine on the frequency of 25. Payne LJ, et al. Effect of calcium channel blockers on
intraocular pressure elevations after combined extracapsular intraocular pressure. Ophthalmic Res 1990;22:337.
Chapter 76
Current Trends in
Drug Therapy of POAG
LC Dutta, NK Dutta
Glaucoma is the second most frequent cause of after medical therapy or after laser trabeculoplasty
blindness. 7.6 million people worldwide are blind due fails. In actual practice it is not uncommon to come
to open angle glaucom and angle closure glaucoma across many patients with POAG who prefer to have
combined. Primary Open Angle Glaucoma (POAG) medical therapy and avoid surgical treatment. The rate
affects the eye over an extended period of time and of successful IOP control after laser trabeculoplasty
therefore, long term clinical observation and therapy may be significantly reduced when more than 12
are essential.1 Incidence of POAG is much higher than months of topical antiglaucoma treatment has been
the other types of glaucoma. Lowering of intraocular given.3 Though other complications of surgery like
pressure (IOP) and maintaining it at a target level is post-trabeculectomy cataract, infection, and non-
the main goal of management of POAG. However, filtration may occur, comparison of visual acuity in
there is no universally accepted definition of the target the medically and surgically treated eyes does not
IOP. Physicians set a target IOP which they believe indicate any significant difference between them.2-7
will prevent further progression of optic nerve Argon laser trabeculoplasty (ALT), when intro-
damage. This target may vary from patient to patient duced first7 was viewed as an alternative to surgery
and in different hours of the day in the same patient. after failure of medication to control the progression
The principle of assessment is to lower the IOP by 25% of POAG; but subsequently it was considered as an
to 30% of the basic IOP of a particular patient. The adjunct or alternative to medication.8 Even now most
result of a long-term study by Midgal et al2 suggests of the surgeons worldwide do not practice laser
that the chances of visual field progression are therapy in most of their patients; rather they go for
lessened if the target IOP for high tension glaucoma drug therapy.
is kept in the range of mid or low teens. The main objectives of drug therapy for POAG are
The standard modalities to maintain the IOP at safe the following:
level in treatment of POAG are the following: 1. To reduce formation of aqueous humor— reduce
1. Drug therapy aqueous flow.
2. Laser Trabeculopasty 2. To increase outflow facility of aqueous humor
3. Fistulizing surgery. through (a) trabecular structure, (b) uveoscleral
There have been several studies to ascertain outflow.
whether laser trabeculoplasty or surgical fistulization During the last few decades agents and procedures
should be done as primary procedure or as secondary that radically changed glaucoma management, were
measure when drug therapy fails to maintain the IOP introduced. Beta blockers, topical carbonic anhydrase
at target level.2-4 Primary surgery is not without risk. inhibitors (CAI), and topical prostaglandin pre-
The risk of failure increases if the surgery is performed parations are introduced as effective medications for
Chapter 76: Current Trends in Drug Therapy of POAG 579
medical therapy. Antimetabolite adjunct therapy has and safety to be used for intraocular pressure lowering
been popularized for glaucoma filtering surgery in effect. But only four compounds, namely timolol,
high-risk glaucoma. betaxolol and levobunolol and carteolol 1% and 2%
The pattern of drug therapy practiced can be are being used as topical therapy for glaucoma. The
divided into the following stages: chemical structure of these drugs are shown in Figure
a. Before 1970 (and even till 1980), miotics specially 76.1. Beta 2 blocking agents have got no appreciable
pilocarpine was the drug most commonly used. If effect on pupillary size and accommodation as shown
miotics were not found to be satisfactory then by pupillographic study.10
epinephrine was added. If these two also failed to Beta blockers are broadly divided into two
control the IOP, then oral CAI was tried. classes—selective and non-selective. Presently the only
b. During the following two decades, beta adrenergic selective betablocker available for therapy is Betaxolol.
receptor blocking agents and newer alpha 2 Selective in the sense that it has got no undesirable
adrenergic agonist drugs have been applied in the effect on cardiovascular and respiratory system. Non
medical management of glaucoma. selective betablockers available for therapeutic use are
c. During the last part of the last century, introduction Timolol, Levobunolol, metipranolol, carteolol and
of topical CAI and prostaglandin analogues have pindolol. Till now the preparations of Timolol,
revolutionized glaucoma drug therapy. Betaxolol and Levobunolol (Betagan) are available as
topical ophthalmic preparations.
DRUG ACTION ON SYMPATHETIC ADRENERGIC
RECEPTORS Timolol
The sympathetic adrenergic receptors are the Timolol maleate, the first beta blocker drug used to
following: lower the IOP, was marketed initially in Sweden in
1. Alpha receptor—Alpha 1 and Alpha 2. 1978. It is available in 0.25 percent and 0.5 percent
2. Beta receptors strength and used twice daily. It is a nonselective beta
• Beta 1 receptors cause cardiac acceleration and blocker. Its pressure lowering effect starts after 30
help fatty acid metabolism. minutes of topical application with a peak effect at
• Beta 2 receptors increase aqueous production
and bronchial dilatation.
In treatment of glaucoma, beta receptor antagonist
and alpha receptor agonists drugs are commonly used.
Beta Blockers
Beta receptor antagonists are the most common drugs
that are used to lower the IOP. The principle of
lowering IOP by the beta blockers is reduction of
aqueous inflow, i.e. reduction of aqueous formation.
That beta adrenergic receptor blocking agents have
got ocular hypotensive effect was first established by
Phillips et al in 1967. They found that IOP was in lower
normal range in patients undergoing treatment with
50-100 mg of propranolol three times a day for cardio-
vascular diseases. Intravenous injection and topical
application of propranolol also reduced the intraocular
pressure.9 This IOP lowering effect is due to antagonist
action of the drug on the beta 2 adrenergic receptor
stimulation which causes increased formation of
aqueous humor.9 Since 1967 a large number of beta
adrenergic antagonist drugs used in the treatment of
cardiovascular diseases have been tested on efficacy Fig. 76.1: Structures of beta-adrenergic antagonists
two hours and the effect lasts for 12-24 hours. almost equivalent to timolol.15 It is used in 0.5 percent
However, not much difference in pressure lowering solution twice daily, sometimes in combination with
effect has been found in 0.25 percent and 0.5 percent other non-beta blocker drugs.16 According to some
strength. It means that if 0.25 percent timolol fails to workers it has more role in preserving visual field.17
show satisfactory pressure lowering effect, 0.5 percent Betaxolol is useful for treating many glaucoma
solution also will not give better results.11 patients with compromised pulmonary function; but
Timolol maleate is available in gel solution not all glaucoma patients with pulmonary diseases
(Timolol XE) or in gel forming solution both in 0.25% can tolerate betaxolol.18 It is contraindicated in patients
and 0.5% strength. The more viscous preparations with sinus bradycardia greater than a first degree
increase corneal contact time and theoretically will atrioventricular block, cardiogenic shock, and in
allow increased ocular bioavailability. Timolol gel patients with overt cardiac failure. It is prudent not to
forming solution (GFS) in Gellum gum forms a gel use betablockers whether selective or nonselective; in
when the formulation comes into contact with the any patient who requires respiratory medications,
ocular surface. This causes increased ocular bio- who has heart rate of less than 50 beats/min, who had
availability of timolol. This also reduces systemic or has had heart failure. Selective betablockers are
absorption when it is administered topically over the much safer in some cases but not entirely safe.
ocular surface in 0.25% and 0.5% solution. Xanthan Complications like diminished pulmonary function
gum is utilized as a gel forming polymer.12 or decreased exertion induced tachycardia may occur
Timolol causes a dramatic lowering of IOP in with its use – but they occur less frequently and may
normal and glaucomatous eyes. In some cases the be less severe Untoward ocular side effects like dry
effect wanes off during the subsequent days (short- eye syndrome, corneal anesthesia or punctate staining
term drug escape). In most cases the drug continues of the cornea also occur. But other symptoms like
to be effective for a long time. However, a small stinging, burning, and discomfort of the eye in
percentage of cases show a tendency for progressive instillation of the drop are common.19
rise of IOP; this is known as long-term drift. However,
this may not be entirely due to failure of drug action Levobunolol (Betagan)
but due to galloping progress of the disease process.
Levobunolol is a nonspecific beta 1 and beta 2 blocking
Maximum oral dose of timolol is 30 mg. One drop
agent. 0.25 percent or 0.5 percent solution of
of 0.5 percent timolol contains 1/150th of this dose,
levobunolol is recommended in once or twice daily
which comes to about 0.2 mg. Nevertheless, after
dose. Its action starts after 30 minutes with peak effect
prolonged use its beta 1 blocking side effect on the
at 2 hours and duration of action is about 24 hours.
heart like bradycardia with hypotension and beta 2
Pressure lowering effect of levobunolol is similar to
blocking side effect like exacerbation of bronchial
that of timolol 0.25 percent. Levobunolol once daily
asthma can occur. Therefore, topical use of timolol is
has the same pressure lowering effect in mild to
contraindicated in patients with bronchial asthma,
moderately increased IOP as compared to timolol 0.5
severe chronic pulmonary obstructive disease, sinus
percent once daily or 0.25 percent twice daily.20,21
bradycardia, second or third degree of a-v block and
Levobunolol produces blepharoconjunctivitis
cardiac failure.13 With the widespread use of the drug
more frequently than timolol does. 22 After com-
other side effects are now being reported. Fraund-
parative study of efficiency of different beta blockers
felder14 compiled 28 complaints of sexual dysfunction
in lowering the IOP after cataract surgery, it has been
after the use of timolol. Impotence was reported in 18
shown that out of timolol, betaxolol, and levobunolol,
patients and decreased libido in nine patients. In most
levobunolol has got the maximum pressure lowering
cases the symptoms promptly reversed after the drug
effect.23
was discontinued.
Alpha Receptor Agonist Drugs
Betaxolol 0.5% (Glucoptic, Iobet)
Epinephrine
Betaxolol hydrochloride is a cardioselective beta 1
adrenoreceptor blocking agent having pressure Though 1 or 2 percent epinephrine 1 to 3 times a day
lowering effect in ocular hypertension and glaucoma had been in use for POAG since 1930, its actual mode
of action is not clearly known. Higgins and Brubaker24 drugs. However, stinging and burning was more with
indicated that mechanism of lowering of IOP by betaxolol than with dipivefrin. Dipivefrin also
epinephrine is decrease of aqueous production. There produces slight pharmacological effect of mydriasis.
is reason to believe that epinephrine chiefly increases
the facility of outflow. Three different salts of Apraclonidine
epinephrine are used—hydrochloride, bitartrate, and Apraclonidine is a para-amino derivative of clonidine
borate. Commercially available epinephrine pre- (Fig. 76.2). It was a commonly used alpha 2 agonist
parations are described as the concentration of drug and had been found to be effective in lowering
epinephrine salt but not the concentration of the IOP in eyes having anterior segment laser application
available epinephrine. A two percent solution of like YAG laser posterior capsulotomy and laser
epinephrine bitartrate contains approximately 1.1 trabeculoplasty. Apraclonidine 0.5 percent before and
percent active epinephrine. Epinephrine causes some after anterior segment laser procedure is safe and
allergic reactions of lid margins and adrenochromic effective. But its topical allergy limits its long-term
staining of the conjunctiva. Soft contact lens worn by potential in the treatment of POAG. Long-term use of
the patient may also be stained after prolonged use of apraclonidine causes allergic type of follicular
epinephrine drops. conjunctivitis similar to the allergy produced in
epinephrine therapy. Average time of onset of allergic
Dipivefrin (Dipivalyl epinephrine, Propine) conjunctivitis is 1.5 months. However, this drug is not
approved by FDA for chronic use.
Dipivefrin is a synthetic analogue of epinephrine
(Fig. 76.2). This is a prodrug. During its passage Brimonidine Tartrate 0.2% (Alphagan)
through the cornea, the side chains are delinked and
It is a relatively selective alpha adrenergic agonist,
epinephrine is released which reaches the primary
which has got definite advantages over apraclonidine.
target tissue. 25 The intermediate metabolites of
It lowers the IOP by dual action, viz. reducing the
dipivefrin may also have some pressure lowering
inflow and increasing the uveoscleral outflow of
effect. Albright and associates26 in a multicentered
aqueous humor.27 In the US it is the only alpha 2
study, comparing the efficacy and safety of 0.1 percent
agonist to have received FDA approval for long-term
dipivefrin with 0.5 percent betaxolol, reported that
therapy. It is marketed by Allergan in its brand name
these two are equally effective equivalent hypotensive
Alphagan.
The efficacy and safety of Brimonidine (0.2%) twice
daily in lowering the IOP is almost similar to timolol
(0.5%) twice daily 28,29 and Dorzolamide 2%. 30
Latanoprost 0.005% once a day is a bit superior drug
as compared with brimonidine in terms of maintaining
low level of diurnal variation of IOP.31,32 Washout
period of brimonidine is 5 weeks and that of
latanoprost is 8 weeks.
Derrick33 recommended that 0.2 percent drop of
brimonidine is equally effective as its 0.5 percent
strength and there is less possibility in development
of allergic follicular conjunctivitis. Moreover,
brimonidine appears to have minimal effect on heart
rate and systemic blood pressure. 34 Schuman 35
reported that Alphagan lowers the IOP by 26.3 percent
and timolol 0.5 percent lowers IOP by 24.4 percent.
TOPICAL CARBONIC ANHYDRASE INHIBITOR—

DORZOLAMIDE 2% (TRUSOPT, MERCK)
That carbonic anhydrase inhibitor, CAI, (most
Fig. 76.2: Chemical structures of alpha adrenergic receptor popularly acetazolamide (Diamox) lowers the IOP was
agonist drugs used for glaucoma reported by Bernard Becker in 195736 and since then
this drug had been extensively used for this purpose. probably by slowing the formation of bicarbonate ions
However, CAI has got propensity for undesirable with subsequent reduction in sodium and fluid
systemic side effects. Systemic CAI is contraindicated transport.
in persons having systemic ailments along with The most frequent adverse effect reported with
involvement of liver, kidney, and suprarenal gland. topical dorzolamide therapy has been ocular burning,
Plasma ionic imbalance and metabolic acidosis along stinging, and discomfort immediately after ocular
with loss of body fluid resulting from diuresis, may administration. Superficial punctate keratitis has been
cause nausea, epigastric discomfort, vomiting, malaise reported in 10 to 15 percent of patients and symptoms
fatigue, weakness, depression, anorexia, loss of libido, of ocular allergic reactions have been reported in 10
and pins and needles sensation over the limbs.37 After percent.
prolonged use patients may develop aplastic anemia Rare severe effects include Stevens-Johnson
secondary to bone marrow suppression38 (Fraunfel- syndrome and toxic epidermal necrolysis. Rare toxic
der’s syndrome). effects reported with systemic administration of CAI
During the later part of the last century, there had like fulminant hepatic necrosis, agranulocytosis,
been numerous experimental studies to develop a aplastic anemia, and other blood dyscrasias are not
topical formulation of CAI that might be effective, safe, likely to occur after topical use of dorzolamide.
and convenient to be used as ocular hypotensive agent. Dorzolamide is available in 2 percent aqueous
Initially most of the researchers were working around solution. The recommended dose is one drop in the
the currently available CAI formulations like affected eye three times a day. The drug may be used
acetazolamide and methazolamide; but a clinically with another topical medication like pilocarpine and
useful long acting topical hypotensive agent could not timolol.41 Two percent dorzolamide three times a day
be prepared. Subsequently instead of using the is effective and well tolerated in patients with ocular
existing formulations of CAI, successful attempts had hypertension associated with pseudoexfoliation. 0.5
been made towards the synthesis of new compounds percent timolol twice daily has a greater level of IOP
specifically meant for topical ophthalmic use. These lowering action than dorzolamide. Two percent
agents enhanced corneal penetration and less dorzolamide twice daily produces additional lowering
propensity to produce local allergic manifestations. of IOP when given with 0.5 percent timolol twice
Merck Pharmaceutical Company synthesized three daily.42,43 Topical dorzolamide and oral acetazolamide
formulations. These include MK 927 (a racemate), combination has got no additive action.44 Either drug
Sezolamide (MK417), the more active S-enantiomer alone results in maximal reduction of IOP and aqueous
of MK 927, and Dorzolamide (MK 507). All these three humor formation. As such concomitant use of systemic
agents have ocular hypotensive efficiency. Sezolamide and topical CAI is not warranted.
and dorzolamide can augment the ocular hypotensive
effect of timolol. Dorzolamide demonstrated clinically BRINZOLAMIDE 1% (AZOPT, ALCON)
significant efficiency as monotherapy or as additional Brinzolamide, a highly specific topical carbonic
therapy in patients with glaucoma or ocular hyper- anhydrase inhibitor has been available for clinical use
tension. since 1998. It is the latest topical carbonic anhydrase
Dorzolamide 2% is marketed by Merck and Co of inhibitor (CAI). It selectively inhibits the carbonic
USA in the brand name of Trusopt in the middle of anhydrase type I isoenzyme which is present in the
1995. 39 The active principle of dorzolamide is iris, ciliary body and ciliary processes. It is easily
thienothiopyran-2-sulfonamide. It has got more absorbed into the eye from the conjunctival sac and
selective action on human carbonic anhydrase has relatively low half life in terms of days in the ciliary
isoenzyme-II, the predominant isoenzyme found in body, iris, cornea and retina. It is administered twice
the ciliary processes. In monotherapy it is used three or thrice daily. Used in the management of POAG or
times a day. 40 Dorzolamide eye drop by CIPLA OH as either monotherapy or adjunctive therapy with
(Dorzox) is available in India. topical betablocker, topical brinzolamide lowers the
As a topical preparation dorzolamide has the IOP significantly. 45 Brinzolamide is usually well
advantage of reducing the systemic side effects that tolerated and does not produce the adverse systemic
may occur with oral CAIs. The principle of reducing side effects associated with oral carbonic anyhydrae
secretion of aqueous humor by dorzolamide is inhibitors. Topically administered 1% brinzolamide
twice or thrice daily is as effective as Dorzolamide the safest and most efficacious compound for lowering
used three times a day. IOP in very low dose.49, 50 Study of pressure lowering
The incidence of the most common adverse effects effect of prostaglandin was initiated in 197748 and
like blurred vision and abnormal taste with brinzola- reports on its clinical trial started to appear in literature
mide are similar to those with 2% Dorzolamide. since mid 80’s.49 Latanoprost 0.005 percent topical
But ocular discomfort like burning and stinging solution is used once daily. Latanoprost is activated
sensation are less with brinzolamide than with during its passage through the cornea, and rapidly
dorzolamide.46 Topical 1% brinzolamide does not and completely metabolized in the liver.
produce the acid-base or electrolyte disturbances and The main known mechanism of lowering of IOP
severe systemic effects because its plasma level after by latanoprost is augmentation of the uveoscleral
topical administration is very low. Characteristic of facility of outflow.49 Of course, it may have some other
oral carbonic anhydrase inhibitors, brinzolamide unique mechanism of its own not shared by any one
can be used in patients who are unresponsive to of the currently used therapeutic agents for lowering
beta blockers or in whom betablockers are contra- of IOP. Pilocarpine is contraindicated along with
indicated.47 latanoprost because the former tends to block the
uveoscleral outflow of aqueous humor. Precipitation
PROSTAGLANDINS of the drug occurs if any other topical medication
Prostaglandin was discovered in the eye during the having thiomersol as preservative is used with
course of a search for mediators of ocular infla- latanoprost; such drugs can be used about five minutes
mmation (uveitis). They belong to a group of after latanoprost drops, but not simultaneously.
hormones that are produced, released and effective Reports of “Latanoprost Study Group” in US, UK,
locally in the tissues. They are formed basically from Japan, and Scandinavian countries51-55 suggest that
arachidonic acid. These hormones are present almost latanoprost is a wonder drug of the 90’s. It has got
in all kinds of tissue and fluid in the body. The higher pressure lowering effect in comparison to the
presence of prostaglandin in ocular tissue was other existing IOP lowering topical drugs, long term
detected in early 1950s and study of its IOP lowering effect is satisfactory (no long-term drift), no systemic
effect initiated in about the 1970s and reports of clinical side effects except minimal untoward ocular side
trials started to appear in literature since mid 1980s.42,43 effect. More importantly, IOP lowering effect is more
After extensive experimental work and clinical trials, than that of the currently used drug i.e. timolol. One
a new prostaglandin analog, latanoprost (13, 14 hydro of the studies51 reported that one drop of 0.005 percent
17 phenol 18, 19, 20 trinor prostaglandin F2 isopropyl latanoprost once daily lowered the IOP by 5.7 to 6.2
ester called PhX441) was identified to be the safest mm Hg (24.7 to 26.8%) before putting the next daily
and most efficacious compound for lowering IOP in dose, whereas 0.5 percent timolol lowered the IOP by
very low dose.48,49 Subsequently, till now three other 4.1 to 4.6 mm Hg (17.7 to 19%) before putting the next
prostaglandin analogus have been identified and twelve hourly dose. The results of three other studies
utilized as IOP lowering agents with acceptable safety are almost the same. Ultraviolet radiation causes rapid
and efficacy. degradation of latanoprost. Latanoprost exhibits
There are four prostaglandin derivatives (analogs) thermal and solar instability and ideally should be
that are used as topical IOP lowering agents in open stored below room temperature and in the dark. The
angle glaucoma and ocular hypertension. They are importance of these storage conditions should be
a. Latanoprost 0.005% (Xalatan, Pharmacia) clearly conveyed to the patient. Stored in room
b. Unoprostone 0.15% (Rescula, Novartis) temperature more than 25o C, latanoprost loses its
c. Bimatoprost 0.03% (Lumigan, Allergan) potency.
d. Travoprost 0.004% (Travotan, Alcon)
Untoward Side Effects of Latanoprost Therapy
Latanoprost
Following ocular side effects of latanoprost are
After extensive experimental work and clinical trials,
reported:
a prostaglandin analog named latanoprost (13, 14
hydro 17 phenol 18, 19, 20 trinor prostaglandin F2 Increased brownish coloration of the iris giving a suntan
isopropyl ester called PhX441) was identified to be appearance This is common but benign side effect of
latanoprost. Four of the 128 patients of the US study51 Unoprostone 0.15% (Rescula, Novartis)
and 51 of 277 patients of the UK study developed
Unoprostone isopropyl ophthalmic solution is a
brownish coloration of the iris after 24 months use of
prodrug like latanprost. After topical application to
latanoprost. 53 In both of these two studies the
the eye unoprostone isopropyl is absorbed through
brownish coloration developed in irides which were
the corneal and conjunctival epithelium and hydroly-
of blue, green or hazel color. The low incidence of iris
zed by esterase to unoprostone free acid. The actual
pigmentation in the US study was probably due to
mode of action is not known but could be direct
the fact that the number of the patients with deep
interaction of the drug with trabecular meshwork and
brown irides (African origin) were more, as such the
ciliary muscles, thereby increasing aqueous outflow
color change was insignificant. The iris color change
through a common pathway. Unoprostone is used
is due to increased melanin content of the stromal
twice a day.
melanocytes and not due to increased number of
Latanoprost 0.005% once daily is significantly more
melanocytes. This fact was confirmed by light
effective in reducing IOP compared to Unoprostone
microscopic and electron microscopic study of iris
0.15% twice daily in patients with POAG or ocular
tissue.
hypertension.58 Compared to Brimonidine 0.2% twice
Conjunctival hyperemia due to dilation of the conjunctival daily, unoprostone can decrease IOP over a 12-hour
blood vessels This is common but does not cause any period and is a better choice to maintain satisfactory
symptom except a cosmetic complain. However, mild diurnal variation of IOP. Unoprostone has some
stinging and discomfort on application of the drop neuroprotective effect as evidenced by arresting visual
occurs; this is a common occurrence in any kind of field depression due to increased uveoscleral blood
eye drop. flow to the optic nerve head. Common ocular adverse
effects are burning and stinging on instillation, itching,
Cystoid macular edema and anterior uveitis In a recent
increased length of the eye lashes (1 mm after 12
retrospective study of 163 eyes of 94 patients, Warwar
months) in about 10–25% of the patients.59,60
et al54 reported that 6.4 percent of 94 patients (4.9% of
163 eyes) had anterior uveitis and 2 patients, 2.1
percent of 94 patients (1.2% of 163 eyes) had cystoid Bimatoprost 0.03% (Lumigan, Allergan)
macular edema during a study period of 12 months. Bimatoprost, a synthetic analog (ethyl amide deriva-
Incidentally one of these two patients underwent tive of prostaglandin, is a new ocular hypotensive
ECCE with PCIOLI and had CME in the same eye 30 agent. It is used in 0.03% topical solution twice daily.
months before starting of latanoprost therapy and the Its IOP lowering effect starts after about 4 hours of
other eye had iritis and underwent ECCE with PCIOLI topical application and IOP comes down by 8 to
four years before. The authors concluded that the use 10 mm Hg by 12 hours. The mode of action is mainly
of latanoprost in a patient with history of, or currently by opening up of the uveoscleral drainage of aqueous.1
active iritis or CME should be approached with Bimatoprost 0.03% topical solution twice daily is as
extreme caution or avoided altogether particularly by effective as latanoprost 0.005% once daily in lowering
giving the other available ocular hypotensive agents. the IOP. But bimatoprost maintains the diurnal
variation better than latanoprost does.62 As compared
Iritis In experimental animals and also in human
to timolol 0.5% twice daily, the IOP lowering efficacy
clinical trials some disturbance of blood-aqueous
of bimatoprost is statistically superior; bimatoprost
barrier has been detected by intravenous fluorescein
lowers IOP by 2-3 mm more than timolol 0.5% twice
studies after using latanoprost. About 1.2 percent of
daily. In a recent study of 15 patients who were non-
cases show some aqueous flare and a few cells.
responsive to latanoprost were successfully treated
Therefore, it seems that there is a possibility of
with 0.03% bimatoprost.63-65 This tends to suggest that,
recurrence of iritis after latanoprost use.
in addition to creating uveoscleral drainage, bimato-
Corneal Lesions Punctate epithelial staining develops prost probably has another mechanism of IOP
in clinical studies comparing the efficacy of latano- lowering action and this could be by enhancing the
prost and timolol using placebo drops with benzal- conventional mode of increase in the facility of outflow
konium chloride as preservative.51 In clinical practice through the trabecular system.66,67 Another study by
corneal complication has not been reported. Whiter et al reported that individuals with glaucoma
uncontrolled on timolol alone, bimatoprost lowers the suprachroid→episcleral vessels by alpha adrener-
IOP more consistently than timolol combined with gic drugs and prostaglandin derivatives—
dorzolamide.67 latanoprost.
Side effects from the use of bimatoprost and Best scientific combination would be one of the
latanoprost as well as travoprost are almost similar.65 drugs from group (a) and one drug from group (b)
The side effects are conjunctival hyperemia, mild above, viz betablocker with a prostaglandin analog.
foreign body sensation and irritation. Pigmentation Ideal combinations would be the following:
of the eyelid skin, iridial pigments and increase in the 1. Latanoprost with timolol (Xalacom).
size and length of the eye lashes are more common 2. Latanoprost with dorzolamide.
with the bimatoprost than with latanoprost. Likeli- 3. Dorzolamide with timolol (Cosopt 2% with
hood of development of macular edema is more with 0.5% timolol).
bimatoprost than unoprostone, travoprost and Rulo et al reported additive IOP lowering effect of
latanoprost.66 latanoprost and timolol in patients with glaucoma.54
In yet another study by the same group of workers, it
Travoprost 0.004% (TRAVOTAN, ALCON) was found that combination of topical latanoprost
Travoprost is a highly selective and potent synthetic with suboptimal dose of systemic acetazolamide is
ester of prostaglandin PGF2α.Commercially available effective in long-term management of glaucoma. As
as travotan, it is a topical ocular hypotensive agent according to this finding they suggested that
used in 0.004% solution once daily at night.67 Travotan latanoprost once a day and dorzolamide twice a day
once daily as monotherapy causes greater IOP is a better combination than either drug alone.
reduction statistically superior to timolol 0.5% twice More recent studies by Heijl et al43 reported the
daily and equal to or greater reduction than latano- result of a multicentered study in 184 cases of
prost 0.005% once a day. 66 It can be used as an pseudoexfoliation and either glaucoma or ocular
adjunctive agent in patients with POAG uncontrolled hypertension in the Scandinavian countries (Sweden,
with 0.5% timolol BD. The specific advantage of Norway, Finland, Iceland, and Denmark) found that
travotan is its effect on maintenance of diurnal IOP lowering effect of 2 percent dorzolamide is lower
variation of IOP.68 Travotan is a very stable com- than that of 0.5 percent timolol.
pound, safe and well tolerated. It can maintain its
efficacy even after exposure to extremely low and high CONCLUSION
fluctuations of temperature, repeated freezing and Even after development of advanced technology of
thawing and exposure to light. treatment of glaucoma, drug therapy still remains as
a popular modality for IOP lowering in glaucoma.
Drug-Combination in Treatment of POAG Since the first publication of pressure lowering effect
In general the principles of lowering IOP are the of eserine in glaucoma in 188256 many formulations
following: have been discovered and clinically applied for IOP
lowering effect. Sympathetic adrenergic betareceptor
(a) Reducing Aqueous Formation blocking agents like timolol, betaxolol, and levo-
bunolol as well as alpha receptor agonist agents like
Common medications used for this purpose are beta-
epinephrine, dipivefrine, and apraclonidine have been
blockers. Systemic carbonic anhydrase inhibitors
cannot be used for long periods due to its notoriety in extensively used during the last couple of decades.
causing systemic harmful side-effects. Dorzolamide and latanoprost may be considered to
be the two wonder drugs of the 90’s. However, latest
(b) Increasing Aqueous Outflow report57 indicates that topical dorzolamide may cause
some corneal complications. These drugs are yet to
i. By conventional outflow through trabecular be popular in India. We have still got to use timolol,
structure with parasympathomimetic drug pilo- betaxolol, levobunolol, and dipivefrin as solo or
carpine (it causes undesirable miosis). combination drugs. Systemic acetazolamide definitely
ii. By unconventional uveoscleral outflow from cannot be used for long time. If these medications in
anterior chamber → ciliary muscle → choroid properly selected schedule fail to control the progress
of the diseases, by maintaining IOP at the target level, 19. Berrospi AR, Leibowitz HW. Betaxolol: A new beta-
then filtration surgery is imperative. adrenergic blocking agent for the treatment of glaucoma. Arch
20. Levobunolol Study Group: Levobunolol: A beta adrenergic
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1998;105:263. Ophthalmol 2001;860-68.
Chapter 77
Laser Applications in Glaucoma

S Ramalingam
INTRODUCTION for trabeculoplasty.

Laser trabeculoplasty is the appropriate treatment
to lower the IOP in eyes with open angle glaucoma Indications of Trabeculoplasty
which is not controlled with maximally tolerated 1. Primary open angle glaucoma with uncontrolled
medical treatment. It is also used as the initial intraocular pressure with maximum tolerated
treatment for open angle glaucoma.1 medical therapy.
The first attempts to use laser energy in treatment 2. Noncompliance of medical treatment.
of open angle glaucoma was made by Krasnov who 3. Enhancement of previous glaucoma surgery result.
used Q-switched Ruby laser to produce multiple
perforations of the trabecular meshwork in quad- Types of Glaucoma that
rants. 2 Initially IOP was lowered and facility of Respond to Trabeculoplasty
outflow improved; but after several weeks or months
IOP came back to original levels because the openings 1. Primary open angle glaucoma (POAG).
made by the laser application got obliterated. 2. Secondary open angle glaucoma
The use of laser in glaucoma has progressed in various — Pseudoexfoliation glaucoma
areas of glaucoma besides its use in iridectomy and — Pigmentary glaucoma
trabeculoplasty. Lasers are now being frequently used
for cyclophotocoagulation, gonioplasty, and laser Contraindication
suturelysis to titrate the intraocular pressure after The absolute contraindications are– Total angle
trabeculectomy; for treatment of failing blebs to incise closure and hazy media precluding visualization of
areas of subconjunctival fibrosis, and in cases of the angle structures. If ALT caused markedly elevated
hypotony to induce scarring. Besides, lasers can also IOPP in one eye, the fellow eye should not be treated
be used in goniophotocoagulation and with ALT. Inflammatory glaucoma is another
goniopuncture. contraindication.
ARGON LASER TRABECULOPLASTY (ALT) Technique

3
Wise and Witter reintroduced the laser treatment It is performed under topical anesthesia. Usually 180°
to the trabecular meshwork as a modality of of the angle is treated in the first sitting. It is
treatment of glaucoma. ALT involved application of recommended that one treats either the inferior angle
nonpenetrating circumferential argon laser burns to first (widest angle) or the temporal angle first so that
the trabecular tissue, which produces a superficial the nasal angle remains free for future use if filtration
scar in the trabecular meshwork; they hypothesized surgery is required. Whichever quadrant is chosen,
that this corrects the mechanical “sag” of the tissue. one should always follow the same protocol for all
In addition to Argon Laser, Diode laser is also used the patients, so that if retreatment required one does
Chapter 77: Laser Applications in Glaucoma 589
not repeat in the same angle. 2. Peripheral anterior synechiae (PAS) formation.
A Goldmann or a Ritch laser lens is used to PAS may develop in 45 to 50% of eyes after
perform trabeculoplasty. Approximately 50 burns trabeculoplasty.
should be applied over 180°, i.e. 8 to 9 spots per clock 3. Uveitis—Iritis is mild and responds to topical
hour. The laser settings are 50 μm spot size and 0.1 steroids rapidly
second duration. For Diode laser the spot size and 4. Corneal burns rarely occur but heal rapidly
duration is 106 μm and 0.2 sec respectively. The 5. Hyphema may occur
starting power is 60 mw and the power is increased
till a blanch or a bubble is seen. If the bubble bursts Results of ALT
the power is too high- the power is decreased; if there The effect of ALT persists in most patients for a few
is no blanch the power is too low. Burns are placed years. Occasionally Intraocular pressure may slowly
at the junction of the anterior third and posterior increase after 6 months especially in pseudo exfolia-
two thirds of trabecular meshwork, in order to tion glaucoma. ALT maintains intraocular pressure
prevent injury to the filtering trabecular meshwork. control in 80 percent of the eyes for one year, 50
Posterior burns are more likely to cause inflammation percent for five years, and 30 percent for 10 years.5
and hence, increase the incidence of peripheral Roughly, 30 percent respond to retreatement.6 Spaeth
anterior synechiae formation. and Baez5 found that ALT deferred filtration surgery
Post laser, the patient may experience minor by at least 5 years in 35 percent of patients with
photophobia and irritation. Topical steroids are pres- progressive uncontrolled glaucoma. To verify the
cribed and intraocular pressure is monitored. efficacy and safety of selective laser trabeculoplasty
Occasionally IOP lowering medication may have to Weiss et al7 after a study of primary treatment of 45
be prescribed if the intraocular pressure is high. The eyes of 31 patients with open angle glaucoma or
patient is reassessed the next day and subsequently ocular hypertension reported that laser
4 to 12 weeks later. trabeculoplasty is effective and safe. However in 11
% the IOP was not controlled and in 7% IOP was
Mechanism of Action increased by 2 to 5 mm Hg. The failure of laser
The exact mechanism of action is not known. trabeculoplasty is due to formation of a membrane
Following theories have been put forth: in the chamber angle.9, 10
Mechanical and thermal theory Laser treatment LASER PERIPHERAL IRIDOTOMY/IRIDECTOMY
causes shrinkage of the inner “trabecular ring” with
resultant separation of trabecular sheets which in turn In 1956, Meyer-Schwickerrath demonstrated the
causes opening up of the aqueous drainage channels, feasibility of creating iridectomy using xenon light
which in turn increases the out flow. energy. Laser is an improvement over xenon and is
safer to perform iridectomy. Lasers that can be used
Biological theory Rodrigues et al4 demonstrated are argon, diode or Nd: YAG.
areas of fibrosis and migration of corneal endothelial
cells, and possibly trabecular meshwork cells. ALT Indications
is supposed to induce a six-fold increase in division
1. Pupillary block with angle closure glaucoma
of these trabecular cells following ALT. The pressure
2. Chronic angle closure glaucoma
lowering effect may be due to the altered production
3. Combined mechanism glaucoma
of glycosaminoglycans by the new trabecular cells
4. Suspected malignant glaucoma to rule out
linings the aqueous channels.
pupillary block
Complications 5. Fellow eye in patients of acute angle closure
glaucoma
Complication of laser trabeculoplasty are not un- 6. Pupillary block after cataract surgery
common 7. Nanophthalmos
1. Long-term worsening of glaucoma—3 percent of 8. Plateau iris configuration
POAG patients may actually worsen following 9. Incomplete iridotomy.
ALT. 5 10. Pigment dispersion glaucoma
Contraindications usually travel toward the surgeon from the point of

Inability of the patient to sit at the slit lamp or a dense focus, it is helpful to have the focal point within the
corneal opacity. iris stroma.
An antireflective-coated lens such as Abraham
Pretreatment Regimen lens, that has a +66 diopter peripheral button, is
a. Topical miotics, e.g. pilocarpine 1 to 4 percent, helpful in performing the laser procedure. The firm
three applications every five minutes, to tighten control of the lens reduces saccades and extraneous
eye movements. It also helps in keeping the lids
the iris and pull it away from the periphery.
separated and the gonioscopy solution absorbs excess
b. Topical beta blockers, if not contraindicated, and
heat delivered to the cornea, while convex button
oral hyperosmotic agents, or carbonic anhydrase
provides good magnification. The usual site to
inhibitors in the presence of advance field loss.
perform iridotomy is between the 11 to 1 o’clock
Argon Laser Iridotomy position avoiding the 12 o’clock position.
Various types of argon laser burns have been Contraindications of Laser Iridotomy
described while performing iridotomy.
1. Patients who are unable to sit or co-operate at the
Contracture burns These are low power, large spot slit lamp.
size and longer duration burns. They are used for 2. Eyes with cloudy cornea
the following: 3. Widely dilated pupil
a. To increase the density of iris stroma and hence 4. Flat anterior chamber with iridocorneal touch
to facilitate laser energy absorption
b. To create a ‘hump’ on which penetrating burns Choice of Laser for Iridotomy
are placed. Among argon, diode and Nd: YAG, Nd: YAG is the
Stretch burns They are similar to contracture burns best; it can be used in all type of irides. In unusual
but are less effective than those. instances such as a very thick brown iris or a vascular
iris argon or diode laser needs to be used. Iridotomy
Penetrating burns High power, small spot size burns should be minimum 60 μm size, the lens capsules
are used to vaporize iris tissue and to create an should be easily seen on retroillumination, and good
opening. fundal glow should be seen through the iridotomy
Clean-up burns These burns are used after reaching opening.
pigment epithelium to minimize energy delivery to Post laser The patient is put on topical steroids and
anterior lens capsule. carbonic anhydrase inhibitors. Patients are reviewed
Laser settings are described in Table 77.1. after 1 hour, 1 day, 1 week and 4 weeks and
intraocular pressure be checked.
Nd:YAG Irodotomy
Either Q-switched or mode-locked Nd:YAG laser Complications
may be used for single burst; 4 to 8 mJ is usually — Hemorrhage especially with Nd:YAG—this can
adequate; in multiple bursts with an initial trial of 2 be managed by increasing the pressure over the
to 4 using 2 to 6 mJ per burst. eye using the lens
Precise focusing is important as shock waves — Corneal burns
— Lens opacities
— Uveitis
Table 77.1: Laser settings (argon laser) — Retinal burn
— Diplopia—if iridotomy performed in the
Types Spot size Duration Power
(μm) (sec) (mW)
horizontal meridian
— Late closure of iridotomy
Contracture 500 0.5 200-400 — Malignant Glaucoma.
Stretch 200 0.2 200
Penetration 50 0.1-0.2 600-1200 CYCLODESTRUCTIVE PROCEDURES
Clean up 50 0.1-0.2 300
Cyclophotocoagulation (CPC) contraindicated owing to active inflammation.
History
Contraindications
• Selective destruction of ciliary processes using
nonpenetrating diathermy was first described in 1. Phakic eyes with good vision
1933 by Weve 2. Thin sclera or limbal deformation.
• Vogt described penetrating diathermy for cyclo-
destruction in 1936 Techniques
• Bietti introduced cyclocryotherapy in 1950, and a. Trans-scleral
this remained the popular mode of b. Transpupillary.
cyclodestruction for nearly 2 decades
• Cyclophotocoagulation was introduced as a safer Trans-scleral CPC (TSCPC)
and less morbid alternative to cyclocryotherapy Non contact (transscleral) diode photocoagulation
by Weeker and later by Beckman causes optimum cyclodestruction but does not lead
• CPC involves destruction of the ciliary body using to phthisical eye. It can be used by contact methods
laser energy in order to reduce aqueous also.
production and hence, lowers intraocular pressure.
Lasers used
It is regarded as the last option when maximal
• 1064 nm Nd: YAG
medical therapy and repeated surgery have failed
• 81 nm semiconductor diode
to control intraocular pressure.
Their longer wavelengths allow good scleral pene-
tration with less back scatter.
Mechanism of Action
Laser mode
Theories CPC is based on the following principles:
1. Destruction of ciliary epithelium which leads to a. Pulsed—short predetermined intervals of energy
decreased aqueous production delivered, focus of intense laser energy over a
2. Absorption of laser energy by ciliary body small area causes mechanical disruption of tissues.
vasculature leads to thrombosis and ischemia of b. Free running, longer, sustained energy delivered
the ciliary body at intervals which can be adjusted by surgeon.
3. Associated inflammation which results in a Contact TSCPC Its procedures are as follows:
temporary decrease in aqueous production. • Energy from the delivery system is transmitted
directly to the ocular surface via a hand held fiber
Tissue Effects optic probe
• Usually done with the patient in the supine
Immediate Blanching and shrinkage of ciliary
position
processes, separation of ciliary epithelium from
• Laser energy in a continuous mode produces
stroma with coagulative necrosis and inflammatory
coagulation necrosis.
cell infiltration. Eventually, atrophy of ciliary
processes ensues. Procedure
• All antiglaucoma medications are continued till
Indications the day of the procedure
1. When intraocular pressure is uncontrolled despite • Retrobulbar anesthesia is use
maximum tolerated medical treatment and • Wire speculum is used to separate the eyelids
attempts at filtration/shunt surgery have failed • Probe is placed on the conjunctiva with its anterior
or run a high risk of failure, e.g. aphakic glaucoma, edge 0.5-1.0 mm from the limbus, the probe being
glaucoma postpenetrating keratoplasty held perpendicular to the surface to maximize the
2. Neovascular glaucoma with poor visual prognosis. effect
3. Intractable pediatric glaucoma • The probe should indent the globe a little and
4. Rarely in patients with uveitic glaucoma with constant contact should be maintained throughout
increase intraocular pressure which is causing energy delivery.
progressive optic nerve damage where surgery is Laser settings (Table 77.2)
Table 77.2: Laser settings for different indications
Sl. Indication Laser Power Time Spot size Number of units

No (Sec) (μm)
1 Gonioplasty Argon 150–300 mW 0.2 150-200 1-12 per clock hour
2 Suturolysis Argon 300-800 mW 0.1 50 One suture
3 Revision of bleb Nd:YAG 2-10 mJ — — 10–20
4 Hypotony Argon, Diode 200-300 mW 0.5 200 30–50
5 Cyclophotocoagulation Nd:YAG 4–9 mJ 2 — 15-20
Diode 1.5–2.5 W 1.5–2 5 —
6 Goniopuncture Nd:YAG 5–7 mJ — — 1–2 per clock hour
7 Goniophotocoagulation Argon 1000 mW 0.1 50
8 Iridotomy Argon 200-600 mW 0.2–0.6 200–500
Nd:YAG 2W
9 Cyclophotocoagulation Diode 2W 0.7 — 25 applications
Nd:YAG 4-6 mJ
10 Trabeculoplasty Argon 300–1200 mW 0.2–0.5 50 30–60
• Nd: YAG—5-6 mJ energy; 30-40 applications (8/ • Wire speculum/special contact lens (Sheilds) is
quadrant) sparing 3, 9 o’clock are placed 360° inserted with the patient comfortably seated at
around the limbus. the slit lamp
• Semiconductor diode; 1750-2000 MW power; 1.0- • The patient looks straight with the eyes in the
2.0 sec duration; 16-18 applications—270° treated primary position
at first sitting avoiding 3 and 9 O’clock positions • The laser beam is set parallel to visual axis.
Postoperative medications Nd: YAG The laser beam is offset 3 to 6 mm from
• Subconjunctival steroid is injected at the end of the aiming helium-neon beam. The aiming beam is
the procedure focused on the conjunctival surface 1.5 mm from the
• Eye is patched for 6 to 8 hours limbus. 13 to 50 applications are placed evenly 360°
• Analgesics prescribed around the limbus, avoiding 3 and 9 o’clock position.
• Topical steroids 6 times/day to control post- Diode laser 1200-1500 MW power; 1 sec duration;
operative inflammation 100-400 mm spot size.
• Atropine 2 times/day Applications are aimed 0.5-1.0 mm behind surgical
• All antiglaucoma medications (except miotics) are limbus, 18-20 applications are made over 270°.
continued until the effect of the procedure can be Postoperative regime is similar to that for contact
assessed. TSCPC.
Patient is reviewed after 1 hour and subsequently If at the end of one month the drop in intraocular
after 1 day, 1 week, and 1 month. pressure is found to be inadequate, repeat treatment
Noncontact TSCPS It uses a slit lamp delivery can be considered. The same area and an additional
system. The laser energy is transmitted through air. area is retreated, but one quadrant should be spared
Pulsed mode laser energy produces mechanical tissue to avoid phthisis. Thirty to fifty percent patients may
disruption. require retreatment.
Procedure Results
• Antiglaucoma medication continued • Cyclophotocoagulation results in an average drop
• Preoperative steroid drops used topically, if the in intraocular pressure of 44 to 60 percent which
eye is inflamed, to control the inflammation lasts for 6 months. It also lowers the requirement
• Procedure is explained to the patient of antiglaucoma medication
• Retrobulbar anesthesia is given • The effect is independent of the preoperative
intraocular pressure Desired reaction is a dark pit with a surrounding
• Response is better in whites and patients with white area. All visible portions of the ciliary processes
aphakic glaucoma as compared with neovascular should be treated.
glaucoma which has poorer results Postoperative Topical steroids are prescribed.
• Contact technique has the advantage of being less Antiglaucoma medication is continued till response
painful, requiring lesser energy and producing can be assessed.
lesser postoperative inflammation when compared Drawback The effect is short lasting and unpredic-
to the noncontact technique. table.
Common complications
• Pain and inflammation Other Modalities of CPC
• Reduction in visual acuity Intraocular cyclophotocoagulation
• Hypotony 1. Transpupillary visualization
• Cystoid macular edema. 2. Endoscopic visualization
Uncommon complications
• Hypopyon MISCELLANEOUS USES OF LASER
• Corneal epithelial defect Laser Gonioplasty
• Scleral thinning It is also called peripheral iridoplasty. Here low
• Graft failure energy, large size laser burns are applied to the
• Malignant glaucoma peripheral iris, and contracture of the surface iris
• Suprachoroidal hemorrhage collagen produces flattening of peripheral iris and
• Vitreous hemorrhage pulls the iris away from the angle.
• Hyphema
• Sympathetic ophthalmia Indications
• Phthisis bulbi.
1. Plateau iris
Advantages of TSCPC over cyclocryotherapy 2. Nanophthalmos
• Fewer complication 3. Media opacities preventing iridotomy
• Less postoperative inflammation 4. Laser settings (Table 77.2).
• Smaller postoperative intraocular pressure spike
• Lower incidence of visual loss. Complications
Mild iritis, corneal endothelial burns and transient
Transpupillary CPC
intraocular pressure rise may occur.
It allows treatment of ciliary processes under direct
visualization. Argon-Laser Suturelysis
Limitation By selectively cutting, the subconjunctival sutures
• It can be done only in the presence of a large sector during the postoperative period following trabe-
iridectomy or broad peripheral anterior synechiae culectomy one can titrate the intraocular pressure.
which displace the iris anteriorly, and allow visuali- By this way, one can avoid hypotony or bleb failure.
zation of the ciliary processes The laser suturelysis can be performed during the
• At least 25 percent of the ciliary processes need immediate postoperative period, but with the
to be treated for the effective treatment. concurrent use of antiproliferative agents suturelysis
Procedure can be delayed as much as two months.8,9 One can
It is done with argon laser at the slit lamp using an use a Hoskins lens or even the rounded corner trian-
indirect (Goldmann) gonioscope. gular lens of the 4-mirror gonioscope. In a congested
eye topical phenylephrine will constrict the overlying
Laser settings vessels. In the presence of subconjunctival
• 50-100 mm—spot size hemorrhage or pigmentation laser suturelysis should
• 700-1500 μW power be done. Argon or diode laser can be used. Laser
• 0.1-2.0 sec duration. setting as in Table 77.2. Only one suture is cut at a
time and if required gentle digital massage is applied. in Table 77.2. Laser is fired through trabecular
Topical steroid are prescribed postlaser. meshwork until bright white color of the outer wall
of Schlemn’s canal is visible. Usually done inferiorly,
Complications 1-2 clock hours.
Shallowing of the anterior chamber due to increase
outflow or conjunctival button holes. Laser Goniophotocoagulation
Rarely performed, it is helpful in ablating new blood
Laser Revision of Failing Blebs vessels growing across the trabecular meshwork
while waiting for panretinal photocoagulation to act.
Nd: YAG laser can revive a failing filtering bleb by
Laser settings as in Table 77.2. It is important to treat
cutting through the episcleral and Tenon capsular
the branch point of the vessels at its trunks to ensure
tissues, transconjunctivally. Additionally it can also
that the vessel is photocoagulated and not still
cut goniscopically any membranes or pigments
perfused.
occluding the ostium. Laser settings as in Table 77.2.
Following the laser digital massage is applied and if LASER TREATMENT FOR
required 5-FU injections are given. MALIGNANT GLAUCOMA
Laser Treatment of Bleb for Hypotony Nd: YAG laser is used to disrupt the anterior hyaloid
face.
Here the laser is used to incite inflammation and In an aphakic eye the laser is focused slightly
scarring. Lasers used are argon or diode. The bleb is posterior to the hyaloid face and the laser with one
painted with 2 percent fluorescein or methylene blue or two-pulse per burst mode is fired. In
if argon laser is being used, and indocyanine green pseudophakic eye either through the iridectomy or
in case of diode laser. Laser setting as in Table through the dialing hole the capsule-hyaloid face can
77.2. Conjunctiva is covered with laser burns as much be disrupted. Care must be taken, as the chamber is
as possible. usually shallow in these eyes. This mode of treatment
is very successful.13,14 Complications are same as in
Argon Laser Closure of user capsulotomy.
Cyclodialysis Cleft
Cyclodialysis cleft may be treated with argon laser Newer Laser Procedures for Glaucoma
under topical anesthesia. For very shallow anterior Glaucoma filtration surgery done by conventional
chamber, one may need to inject viscoelastic into the methods is very successful, however, there is a
anterior chamber to deepen it. Laser setting as in constant search for less invasive techniques which
Table 77.2. Laser is applied over both edges, and could minimize intraoperative and postoperative
depth of the cleft. After treatment, topical steroids complications. Subconjunctival scarring due to
and cycloplegics are applied for a week. If no fibroblast proliferation is the most common cause for
significant improvement is noted laser is repeated filtration surgery failure. In view of this, attention
after 1-2 weeks. Excellent results are obtained by this has been diverted toward the laser energy for creation
technique.10-12 of filtering fistula which involves minimum
conjunctival manipulation, thereby reducing the
Complications stimulus for fibroblast proliferation. Various appro-
Transient pressure rise after the treatment occurs aches and various lasers are used to achieve
which is treated with topical beta-blockers. sclerostomy.
In glaucoma filtering surgery target tissue is limbal
Laser Goniopuncture sclera which is composed basically of water and
protein. Laser sclerostomy requires the organic
This is useful in certain types of inflammatory polymers of the sclera be fragmented and ejected in
glaucomas, such as glaucoma associated with juvenile gaseous state. This can be brought about by the
rheumatoid arthritis; also occasionally used in angle following: (1) Photovaporization, i.e. thermal
recession glaucoma. Nd: YAG laser is useful though molecular fragmentation, e.g. Holmium YAG, (2)
the success is for a limited period. Laser settings as Photodisruption, i.e. plasma expansion and predomi-
nantly mechanical and molecular fragmentation, e.g. chamber to the proposed sclerostomy site. Nd: YAG
Q switched Nd: YAG and Nd: YLF, (3) Photo- laser in the continuous wave mode was used for ab-
dissoliation, i.e. direct nonthermal molecular decom- interno sclerostomies in the mid eighties, but resulted
position, e.g. Excimer and Er: YAG. in significant thermal damage. 308 nm excimer laser
Disadvantage of thermal lasers is the creation of by fiber optic delivery is used to successfully create
relatively large zones of thermal damage surrounding sclerostomy. Advantage here is that it produces
the sclerostomy. Advantage is their cautery effect. minimal thermal damage.
Amount of energy needed to create a sclerostomy
causes trauma to adjacent tissues with photodisrup- Invasive Ab-externo Procedures
tive lasers. Photoablative lasers have two major In 1993 ab-externo HO:YAG laser sclerostomy was
advantages, i.e. precise submicron excision and performed. Most commonly reported complication
minimal thermal effect to surrounding tissue. was iris plugging the sclerostomy. Erbium: YAG ab-
Surgical techniques explored using the lasers are externo sclerostomy is currently under investigation.
noninvasive ab-interno, invasive ab-interno and It is more precise than HO:YAG because its wave-
invasive ab-externo. length is much more highly absorbed by scleral tissue
than HO:YAG.
Non-Invasive Ab-interno Procedures
Photocoagulation to the angle without entering the Laser Sclerostomy Ab-externo vs Ab-interno
eye with instruments were attempted way back in Sclerostomies formed ab-interno may have the
1961 with xenon arc photocoagulation and with argon following advantages over ab-externo sclerostomies:
laser. Because of high energy and high exposure times 1. An internal approach can minimize trauma to the
these attempts were given up. conjunctiva because it requires no conjunctival
March et al used Q-switched Nd: YAG laser for incision avoiding conjunctival trauma, thereby
sclerostomy but energy required to perforate sclera minimizing fibroblast proliferation.
was very high and resulted in adjacent ocular damage 2. Lack of conjunctival manipulation can reduce
including corneal endothelium and the lens. Latina postoperative complications such as wound leak,
et al introduced the concept of matching the hypotony, and flat anterior chamber.
wavelength of a flash lamp, i.e. excited dye laser with Laser sclerostomy will undoubtedly become
microsecond pulses to the absorption spectrum of the viable alternative to conventional glaucoma filtering
dyed sclera. Iontophoresis of methylene blue into the surgery. At this time no laser procedure has proven
sclera at the limbus was performed to enhance laser universally effective or ideal. Technical modifications
light absorption. Nd: YLF lasers with wavelength of continue to develop in an effort to minimize the risks
1053 mm are currently being investigated for of intraocular surgery to improve the long-term
gonioscopic ab-interno filtration procedures. success of filtration. Once perfected, these new laser
Advantage of this picosecond pulse laser over the techniques may possibly become primary treatments
nanosecond Nd: YAG laser is that the optical of open angle glaucoma.
breakdown zone is markedly smaller with cavitation
bubble as small as 100 micron diameter. Smaller REFERENCES
cavitation bubble allows greater precision and results 1. Wise JB, Witter SL. Arogn-laser therapy for open angle
in less thermal and mechanical energy dispersion glaucoma: A Pilot Study. Arch Opthalmol 1979;97:319-22.
within target tissue. 2. Rodrigues MM, Spaeth GL, Donohoo P. Electron microscopy
of argon-laser therapy in phakic open angle glaucoma. Ophthal-
mology 1982;89:198.
Invasive Ab-interno Procedures 3. Shingleton BJ, Richter CU, Bellows AR et al. Long-term efficacy
Other approach to ab-interno sclerostomy is via intra- of argon-laser trabeculoplasty. Ophthalmology 1987;94:1513-
18.
cameral technique with a fiber optic delivery system 4. Richter CU, Shingleton BJ, Bellows R et al. Retreatment with
coupled to a laser source. Contact endoscope will be argon-laser trabeculoplasty. Ophthalmology 1987;94:1085-89.
passed through a corneal incision across the anterior 5. Spaeth L, Baez K: Argon-Laser trabeculoplasty controls one
third of cases of progressive, uncontrolled, open angle glaucoma
for 5 years. Arch Ophthalmol 1992;110:491. coagulation. Ophthalmic Surgery 1980;11:186.
6. Thomas JV, Simmons RJ, Belcher CD. Argon-laser trabeculo- 12. Ormerod LD et al. Management of hypotonous cyclodialysis
plasty in the presurgical glaucoma patients. Ophthalmology cleft. Ophthalmology 1991;98:1384.
1982;89:187-97. 13. Melamed S, Ashkanazi I, Blumenthal M. Nd:YAG laser
7. Weiss HS, Shingleton BJ, Goode SM et al. Argon-laser hyaloidotomy for malignant glaucoma following one piece 7
gonioplasty in the treatment of angle closure glaucoma. Am J mm intraocular lens implantation. Br J Ophthalmol
Ophthalmol 1992;114:14-18. 1991;75:501.
8. Elisa N, Monnelli et al. Laser suturelysis after mitomycin-C 14. Brown RH et al. Neodymium YAG: Vitreous surgery for phakic
trabeculectomy. Ophthalmology 1996;3(2):306-14. and pseudophakic malignant glaucoma. Arch Ophthalmol
9. Papa KS et al. Late argon suturelysis after mitomycin-C 1986;104:1464.
trabeculectomy. Ophthalmology 1993;100:1268. 15. Noureddin BN et al. Advanced uncontrolled glaucoma.
10. Harbin TS Jr. Treatment of cyclodialysis cleft with Argon-laser Nd:YAG cyclophotocoagulation or tube surgery. Ophthal-
photocoagulation. Ophthalmology 1982;89:1082. mology 1992;99:43.
11. Joondeph HC. Management of postoperative and post- 16. Wright MM, Grajewski AL, Feuer WJ. Nd:YAG cyclophoto-
traumatic cyclodialysis cleft with Argon-laser photocoagulation: Outcome of treatment for uncontrolled glaucoma.
Ophthalmic Surgery 199;22:279.
Chapter 78
Phacotrabeculectomy
R Raveendran, KM Ranganath
Recent advances in phacoemulsification techniques, trabeculectomy over the period of time.6a

pharmacologic modulation of wound-healing,
incision architecture, etc. have come together to ROLE OF ANTIMETABOLITES
revolutionize the surgical management of coexisting IN GLAUCOMA SURGERY
glaucoma and cataract.
In the past, each of the three usual management The introduction of anti scarring agents Mitomycin
strategies for such patients had major drawbacks. C (MMC) and 5-Fluoro Uracil (5-FU) markedly
Performing glaucoma surgery alone in the first sitting, improved the success of filtering procedure especially
further worsened the vision of the patients with in high risk glaucomas.7-10 Mitomycin C (MMC) is a
cataract. And subsequent to cataract surgery, 30 bifunctional alkylating agent that covalently links
percent of filtering blebs failed. 1 When cataract with guanine residues in DNA, permanently
surgery alone was performed as part of the two-stage preventing them from replication. A single application
procedure, the reactive postoperative IOP spike might of MMC on cellulose sponge to the scleral flap surface
further damage the already compromised optic nerve- and Tenon’s capsule undersurface has a permanent
head. 2 Also, subsequent filtration surgery might static effect on the exposed fibroblasts and other
poorly function in the scarred conjunctiva at the connective tissue elements. MMC exposed blebs
superior limbus. Both these strategies mean a therefore, tend to be ischemic and thin walled
prolonged visual rehabilitation course apart from delimited by a rim of hyperemic and thickened
subjecting the eye to the trauma of repeat intraocular conjunctiva. 5-FU on the contrary acts as a
procedure. The only other strategy of combining competitive inhibitor of DNA formation and also
cataract and glaucoma surgery is however, more by inhibiting thymidine synthetase, thus preventing
prone for increased filtration failure due to the incorporation of thymidine into new DNA 5-FU
aggravated postoperative uveitis following cataract therefore, needs to be applied repeatedly. With 5-
surgery with higher risk of posterior synechiae, FU use, the filtering blebs tend to be less delimited
pupillary capture, etc.3 and relatively more thick walled with fine superficial
With the advent of small-incision cataract surgery, vascularity. Corneal epithelial toxicity is its major
combined phacoemulsification and trabeculectomy drawback. Comparative studies of MMC and 5-FU
has been reported to be superior to combined ECCE- have confirmed the superiority of the former in
trabeculectomy in terms of earlier visual recovery, having a highly focal effect and prolonged IOP
less postoperative astigmatism, improved long-term control.11
IOP control and fewer postoperative complications.4,5
Lyle and Jin introduced the term TECHNIQUES
“Phacotrabeculectomy” to describe this technique that Conventional phacotrabeculectomy is performed
requires an incision about the same size as using the following procedures.
trabeculectomy alone. 6 However,
phacotrabculectomy may not be as effective as
Conjunctival Flap
A limbus or fornix based flap is fashioned

approximately 2 mm larger than anticipated scleral
incision. While the fornix based flap is technically
easier to perform, a tight cornea-conjunctiva interface
needs to be ensured postoperatively to prevent bleb
leak. Limbus based flap obscures the visibility and
may by troublesome during phacoemulsification.
Conjunctiva has to be handled with care to prevent
button holes. Adequate hemostasis has to be achieved
to prevent subconjunctival bleed that could impede
filtration and lead to scarring.
Mitomycin C
If MMC is to be used, a piece of Weckcell sponge
soaked in 0.3 mg/ml MMC is placed on the scleral
bed and conjunctiva pulled over it (Fig. 78.1). The
duration of exposure is varied (1 min to 5 mins) as
per basic to target pressure gradient and conjunctival
vascularity, e.g. for primary glaucomas with a smaller
IOP drop requirement, 1 minute exposure to MMC
would suffice. High risk cases with congested eyes
and a high IOP drop requirement need exposure for
as long as 5 minutes. After the exposure, the scleral
bed is copiously irrigated with balanced salt solution.
Scleral Tunnel Design Fig. 78.1: Sponge soaked with MMC is placed in the scleral
bed and covered with conjunctiva
A three-plane scleral tunnel is then fashioned through
a perpendicular initial scleral incision 2 mm posterior
to the limbus. The horizontal plane of the tunnel is
created in the corneal stroma by a crescent blade up
to the anterior aspect of vascular arcade (Fig. 78.2).
The anterior chamber is then entered with a 3.2 mm
keratome angled toward opposite pupillary margin
thus, creating another step.
Another option is to create a traditional
trabeculectomy flap and enter the anterior chamber
with keratome under the flap.
Pupil
Poor mydriasis in patients undergoing combined
cataract extraction and trabeculectomy continues to
Fig. 78.2: Using a cresent blade, a tunnel is fashioned in the
challenge the skill of phaco surgeon. Chronic miotic corneal stroma up to the anterior aspect of the vascular arcade
therapy, posterior synechia, pseudoexfoliation, etc.
commonly encountered in glaucoma patients Iris retractors anchored to the cornea is another
contribute to poor mydriasis. option. Alternatively, using two Kuglan iris hooks,
Several techniques have been described to improve one through the incision, another through
preoperative pupillary dilation. Multiple incisional paracentesis, iris can be pulled and pushed 180° apart.
sphincterotomies aggravate the postoperative inflam- Or else, linear iridotomy can be done which can be
matory response in addition to deshaping the pupil. later sutured with 10-0 nylon. Whatever technique,
Chapter 78: Phacotrabeculectomy 599
iris manipulation needs to be minimal while ensuring
increased visibility and enhanced safety.
Capsulorhexis
A 360° continued circular, centrally placed capsulor-
hexis of 5-6 mm diameter has then to be performed
using a bent 26 G needle or utrata forceps.
Phacoemulsification
An endocapsular phacoemulsification is performed
using the technique appropriate to the nucleus density
and surgeon’s comfort. Residual cortex is aspirated.
Trabeculectomy
Following placement of the IOL, the scleral tunnel is
converted into a trabeculectomy flap by vertical cut
at its either end with Vanna’s scissors. Using Kelly’s
Descemet’s punch clear cornea and trabecular Fig. 78.3: Using Kelly Descemet punch, deep posterior
meshwork are removed from the posterior lip of the sclerotomy is done to excise approximately 1.5 × 3 mm of
trabecular meshwork
scleral tunnel (Fig. 78.3). Another option is to excise
a 1 mm × 3 mm block of posterior lip in the region of
initially. If persistent, aqueous misdirection has to
trabecular meshwork. Subjacent peripheral
be ruled out.
iridectomy is then completed. The remaining
Topical steroid-antibiotics have to be
viscoelastic is washed out through the same port.
administered frequently to control the postoperative
inflammatory response. Cycloplegics are required to
Flap Closure
keep the pupil mobile and when the chamber is
The scleral flap may be closed with 10-0 nylon sutures, shallow.
the number and tightness of them determined by
anticipated target pressure. Postoperatively, Argon COMPLICATIONS
laser suturolysis using Hoskins lens may be used
Hypotony Maculopathy
preferably within 3rd week to titrate filtration.
Alternatively, single or double releasable sutures may With the use of MMC, the risk of hypotony maculo-
be used to regulate the filtration. The corneal ends pathy has been reported to be 3 to 24 percent in
of such sutures may sometimes cause “Wind shield primary filtering surgery and 2 to 5 percent in
keratopathy”. complex filtering surgery.12 It causes reduced vision
At the end of the procedure, adequate bleb filtra- by the presence of chorioretinal folds and by
tion is confirmed by injecting BSS through irregular astigmatism possibly due to scleral
paracentesis and consequent elevation of secured shrinkage. Hence, its occurrence is more common in
conjunctiva. previously stretched sclera such as in high myopia
and high IOP. It appears to be due to loss of scleral
Postoperative Care resistance to aqueous egress through the flap. It
Patient has to be watched closely for first few weeks promptly resolves upon resuturing the scleral flap.
However, prolonged hypotony may lead to
to look for bleb presence, under or excess filtration
permanent retinal folds.
and IOP. Gentle massage at the site of filtration in an
attempt to depress the posterior lip may encourage
Bleb Failure
bleb formation in early postoperative days. Shallow
anterior chamber could be due to overfiltration and It could be due to vascularization and scarring of
pressure patching. Simmon’s shield could be of help Tenon’s fascia and conjunctiva or episcleral fibrosis
around the flap or by obstruction of ostium by iris, detachment (3.8%) was the most frequent
vitreous or corneal endothelium. Evaluation of the complication.
failing bleb includes biomicroscopic examination to
detect Tenon’s cyst within the conjunctiva, inspection Nonstitch Phacotrabeculectomy
of the scleral flap using compression with a Ritch lens
To avoid the risks of releasable sutures, laser suturo-
and gonioscopy to visualize the internal ostium.
lysis, and antimetabolites, Paul N Arnold described
Tenon’s cyst can be ruptured in the outpatient by a
a technique that involves less surgical manipulation.
needle tip under aseptic condition. The scleral flap
The technique essentially consists of performing
can be elevated by compressing the overlying
phacoemulsification through a superior scleral incision
conjunctiva with Hoskins lens. The iris or vitreous
and punching out the trabecular tissue in the posterior
or membrane occluding the internal ostium can be
lip to the level of ciliary body. The conjunctiva is
slit open by Nd: YAG laser. dragged and sutured to episclera to envelope the
filtration site. In his series of 66 eyes, after a mean
Leaking Bleb follow-up of 13.2 months, he reported a mean IOP
A leaking bleb is not a rare occurrence with the use drop of 9.7 mm of Hg and detectable blebs in 92
of MMC. A therapeutic soft contact lens to percent of patients. Mean induced astigmatism was
tamponade the bleb is used to facilitate the conjunctiva 0.5 D against the rule by one month. Hyphema (64
to grow and seal the hole. percent), hypotony (24%), and choroidal effusion
(14%) were the major early complications.14
Endophthalmitis
Phacotrabeculectomy with Modified
Increased incidence of endophthalmitis with the use Scleral Tunnel and Single Stitch Closure
of antimetabolites in filtering surgery has been a
growing concern. Laser suturolysis or needling of To prevent the against the rule, astigmatic drift and
the filtering bleb appears to play significant causative delayed visual recovery, that could possibly happen
role. The risk of infection was less in with conventional phacotrabeculectomy using radial
preantimetabolite era possibly because these blebs sutures. Bradford J Singleton described a technique
were thick and vascular. But these blebs failed in half in which after performing phacoemulsification
the cases by five years. The choice between failure- through a conventional superior scleral incision, the
prone bleb and infection-prone bleb is a daunting anterior scleral roof was trexed with a central T-
dilemma to the glaucoma surgeon. relaxing incision over a preplaced horizontal suture.
Punch sclerectomy was then performed. Single
horizontal suture was then tied. In his series of 24
MODIFICATIONS OF PHACOTRABECULECTOMY
eyes after a mean follow-up of 7 months he reported
Over the last few years, conventional a mean IOP reduction of 5 mm of Hg.15
phacotrabeculectomy has been undergoing several
modifications in an attempt to retain all the benefits Twinsite Phacotrabeculectomy
of phacoemulsification while ensuring a safe and The presence of a leaking wound at the same site as
prolonged IOP control. phacoemulsification is contrary to the concept of
water tight incision of the latter. Also, it may not be
Combined Phacoemulsification with safe to expose the phaco incision to the action of
Trabeculotomy Ab-externo antimetabolites. Performing temporal corneal phaco-
Phacoemulsification incision is designed to be water emulsification and superior trabeculectomy
tight. Its architectural stability therefore, tends to be separately at two different sites, therefore, not only
jeopardized in presence of a filtration at the same eliminates these disadvantages, but also could
site. Howard V Gimbel et al have attempted to complement each other to check against the rule
address this aspect by creating a fistula between the astigmatic drift that could occur with a superior
anterior chamber and Schlemm’s canal combined with leaking incision. In a retrospective case control study
self-sealing incision phacoemulsification.13 In their of 40 eyes using 5-FU, Park et al reported that twin
series of 53 eyes, they reported a mean IOP drop of 6 site phacotrabeculectomy effectively lowers IOP and
mm of Hg after 2-year follow-up. Descemet’s reduces long-term antiglaucoma medications, but is
Chapter 78: Phacotrabeculectomy 601
not as efficacious as trabeculectomy alone in long- our prospective study of 34 eyes with assorted
term IOP reduction.16 glaucomas, after a mean follow-up 15 months, we
found mean IOP drop of 8.2 mm of Hg and 81 percent
Our Modification patients were off medication. The mean induced astig-
Current trabeculectomy techniques aim at external matic vector at 4 weeks was 1.12 thus permitting
aqueous drainage into the subconjunctival space. earlier and better unaided visual acuity. Fibrinous
Aqueous filters through and along the sides of flap reaction (28%) and hyphema (24%) were the most
randomly. Thus a critical amount of “bulk flow” frequent early postoperative complications. No
which is essential to maintain the patency of fistula hypotony maculopathy or aqueous misdirection were
does not always exist, thus often inviting fibroblastic observed during the course of this ongoing prelimi-
proliferation and filtration failure.17 Exposure of the nary study.
filtration site to antimetabolites aims to prevent this The development and integration of better
fibroblastic growth. But such a bleb tends to be techniques such as small pupil phacoemulsification,
ischemic, thin walled and likely to be ruptured by management of hard nuclei, titration of filtration,
trivial trauma inviting infection. Primary pharmacologic wound modulation and newer
trabeculectomy is now being increasingly advocated filtration techniques have contributed to quicker and
for better and prolonged efficacy of the filtering better visual rehabilitation. The judicious choice of
procedure rather than after years of topical the various options now available in the
medication.18 Safety and optimal control for long armamentarium of glaucoma surgeon has helped for
period is therefore, an important concern. In order a better management of patients with coexisting
to address these concerns, DeMelly et al described glaucoma and cataract.
the technique of nonpenetrating deep sclerectomy
combined with a collagen implant developing their REFERENCES
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with 10-0 nylon suture. In their retrospective study Surg 1990;21:339.
of 159 eyes of assorted glaucomas, they reported an 4. Wishart PK, Austin MW. Combined cataract extraction and
average drop in IOP of 9.1 mm of Hg with 76 percent trabeculectomy. Phacoemulsification compared with extracap-
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tomy was encountered.20
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Broadly based on these concepts, we modified 6. Lyle WA, Jin JC. Comparison of a 3 and 6 mm incision in
by combining temporal corneal phacoemulsification combined phacoemulsification and trabeculectomy. Am J
with a superior reservoir trabeculectomy. Here Ophthalmol 1991;111:189.
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block of deep sclera is excised with its base abutting intraocular pressure of phacotrabeculectomy compared to
trabeculectomy. Am J Ophthalmol 2003;87,850.
the trabeculectomy site. Thus a triangular lake of
7. Chen CW. Enhanced IOP controlling effectiveness of trabeculec-
aqueous reservoir is created protected by a more tomy by local application of mitomycin C. Trans Asia Pacific
resistant scleral roof. Since a critical amount of Acad Ophthalmol 1983;9:172.
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failure are minimized, fibrosis can be further reduced glaucoma filtering surgery; A Pilot Study. Ophthalmology
by antimetabolites which can be used safely. Since 1984;91:384.
9. Ramakrishnan R, Michon J, Robin AL et al. Safety and efficacy
the aqueous drainage into subconjunctival space is
of MMC trabeculectomy in Southern India: A short-term pilot
least, the bleb is flat or just detectable. The bleb related study. Ophthalmology 1993;100:1624.
problems are therefore, considerably minimized. In 10. The Flurouracil filtering surgery study group. Flurouracil
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1989;108:623. 16. Park HJ, Weitzman M, Caprioli J. Temporal Corneal phaco-
11. Skuta CL, Beeson CC, Higginbotham EJ et al. Intraoperative emulsification combined with superior trabeculectomy: A
MMC versus postoperative 5-FU in high risk glaucoma filtering retrospective case control study. Arch Ophthalmol
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12. Niryts RMMA, Greve EL, Geijseen HC et al. Treatment of 17. Petrus NJ, Gous, Paul Roux. Preliminary report of sutureless
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J Ophthalmol 1994;118:322. tunnel incision. J Cataract and Refract Surg 1995;21(2):160.
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response to combined phacoemulsification and trabeculectomy therapy on success of trabeculectomy. Arch Ophthalmol
ab externo versus phacoemulsification alone in primary open 1990;108:1543.
angle glaucoma. J Cataract and Refractive Surgery 1995;21:653. 19. Fyodorov SN, Kozlov VI, Timoshkina NT et al. Nonpenetrating
14. Arnold PN. Nonstitch phacotrabeculectomy. J Cataract and deep sclerectomy with collagen, IRTC Eye Microsurgery RSFSR.
Refractive Surgery 1996;22(2):253. Min of Public Health: Moscow 52:1989.
15. Shingleton BJ, Kalina PH. Phacotrabeculectomy with a modified 20. DeMelly P, Jeanteur et al. Nonpenetrating deep sclerectomy
scleral tunnel and single stitch closure. J Cataract and Refractive combined with a collagen implant in POAG: Retrospective
results. J Fr Ophthalmol 1996;19(11):659.
Chapter 79
Antimetabolites in Glaucoma
Filtration Surgery
R Ramakrishnan, Kavitha Ramakrishnan
Successful glaucoma filtration surgery (GFS) is into which inflammatory cells (circulating monocytes
characterized by formation of a cystic filtering bleb and macrophages) and fibroblasts migrate. Animal
with the drainage of the aqueous humor from the experiment studies show that proliferation and
anterior chamber to the subconjunctival space. migration of fibroblasts begin around the fifth
Inhibition of wound healing is desirable for success postoperative day.3,4 This is followed by degrada-
of the glaucoma filtering surgery to facilitate egress tion of fibrin-fibronectin network followed by laying
of aqueous humor in contrast to other ocular surgeries down of fibrovascular connective tissue which leads
in which water-tight wound closure is essential. A to formation of granulation tissue. Fibroblasts and
good functioning bleb must be avascular, polycystic, blood vessels disappear over time with remodeling
thin-walled, and slightly elevated above the conjunc- of the wound to form a dense collagenous
tival surface.1 subconjunctival scar.
GFS may fail due to the following reasons: Thus far, it is noted that fibroblast proliferation
a. Preoperative: Long-term miotics, GFS after and migration play prominent role in glaucoma
argon-laser trabeculoplasty, youth and trauma- filtering surgery wound healing. Precisely which
tic, neovascular, and inflammatory glaucoma. tissue factor is most important in the activation of
b. Intraoperative: Excessive tissue manipulation, fibroblasts after glaucoma filtering surgery is not
bleeding, excessive Tenon’s capsule mutilation. known. But many factors are considered to have
c. Postoperative: Hyphema, iritis, suprachoroidal chemotactic effect for fibroblasts amongst which
hemorrhage, aqueous misdirection, encapsu- platelet derived growth factor (PDGF) is a potent
lated blebs, etc. mitogen and chemoattractant for fibroblast.
Episcleral scarring is the most common cause for Success of filtering surgery in glaucoma depends
failure of GFS. It occurs most commonly after third on the preoperative condition of the patient’s eyes.5
postoperative week. This can be modulated by under- Good results have been obtained in patients with pri-
standing the sequence of events in wound healing. mary open angle glaucoma, chronic angle closure
glaucoma, pseudoexfoliation glaucoma, and
pigmentary glaucoma.
SEQUENCE OF EVENTS IN WOUND HEALING2
Increased risk of scarring and failure has been
Following surgical trauma to the conjunctiva, the epi- thought to be associated with neovascular glaucoma,
scleral and iris blood vessels constrict and cause previously failed filtration surgery, previous
leakage of plasma proteins, circulating fibrinogen, conjunctival surgery, previous cataract extraction,
fibronectin and plasminogen, and blood cells. When previous multiple intraocular surgery, uveitis, youth,
exposed to tissue factors, plasma or blood, or both, black race and topical medications for more than three
clot to form a gel-like fibrin called fibronectin matrix years (particularly pilocarpine or epinephrine).
In the recent years, modulation of wound healing Contraindications

by pharmacological agents have taken prime place in
1. Active corneal disease
the success of GFS. They are as follows:
2. Very recent penetrating keratoplasty
a. Corticosteroids
3. Known hypersensitivity to the drug
b. Antimetabolites
4. In patients with multiple filtering operations with
c. Inhibitors of collagen cross linkage.
severe scaring of conjunctiva.
Among these pharmacological agents, anti-
metabolites (like 5-Fluorouracil and Mitomycin-C)
Dosage and Modes of Application
play a dominant role in the glaucoma filtration
surgery. 5-FU was the first antimetabolite used in glaucoma
filtering surgery.
ANTIMETABOLITES IN GLAUCOMA
FILTRATION SURGERY Clinical Use
Proliferation of fibroblast is an important cause for There are two major methods of application5,10 of
the failure of the filtration surgery. Antiproliferative this antimetabolite:
agents have altered the outcome of glaucoma filtering
Subconjunctival injection Initial dosage 5 mg once
surgery. Blumenkranz and Kwong have tested a
daily subconjunctivally for the 1st week and to
variety of antimetabolites and have found that 5-
modulate the dosage according to the response and
Fluorouracil, bleomycin, doxorubicin, and cytarabine
the clinical condition for the 2nd week after surgery.
were successful in inhibiting fibroblast proliferation
This method was associated with significantly
in vitro. Subsequent clinical studies have confirmed
increased success rate but it was associated with
the advantages of 5-Fluorouracil6 and Mitomycin-C.
significant side effects, most of which were related
to the cornea.
5-Fluorouracil
Method 0.1 ml (5 mg) of 5-fluorouracil drawn from a
It is a fluorinated pyrimidine analogue that mimics
50 mg/ml vial or 0.5 ml from 10 mg/ml vial into a
uracil biochemically.
tuberculin syringe and injected into the anesthetized
cul-de-sac, subconjunctivally with a 30 gauge needle
Mechanisms of Action7
followed by copious irrigation of bulbar conjunctiva
The presence of a fluorine atom on the 5 carbon of and cul-de-sac followed by light tamponade at the
uracil prevents the methylation of deoxyuridylic acid needle track with a moist cotton tipped applicator.
to thymidylic acid. It irreversibly binds thymidylate The injection is usually given at a site, 180 degree
synthetase, the enzyme responsible for this reaction, away from the filtering bleb site. Care is taken to
thus interfering with DNA synthesis and to a much rule out conjunctival leak. Injections are withheld if a
lesser extent with RNA synthesis and its function. wound leak develops or corneal epithelial defect
The induced thymine deficiency and resulting occurs.
derangement in DNA and RNA metabolism result in
Intraoperative use In the recent years, 5-Fluorouracil
imbalanced growth and death of a cell. 5-Fluorouracil
is used during surgery as subconjunctival application.
has been considered to work primarily by disrupting
It is preferable to do a limbal based conjunctival flap.
the DNA synthesis phase (S-phase) of mitosis by
A cellulose sponge is fashioned to approximately 2 ×
decreasing the amount of thymidylate that is available
3 mm long and wide and about 0.5 mm thick piece
for DNA synthesis.
which is soaked in undiluted 5-FU (5 mg/ml) and
the sponge is kept on the sclera and left in position
Indications
for 2 to 5 minutes. Later the eye should be copiously
1. Primary GFS8,9 in blacks and young irrigated with 5 to 15 ml of balanced salt solution.
2. Eyes with previous failed GFS All gauze-pads and sponges soaked in 5-FU should
3. Aphakic and pseudophakic glaucoma be discarded.
4. Neovascular glaucoma Care is taken to obtain a partial thickness scleral
5. Uveitic glaucoma. flap at least 1/3 scleral thickness; thinner scleral flaps
Chapter 79: Antimetabolites in Glaucoma Filtration Surgery 605
will leak excessively. A watertight closure of glaucoma, and retinal detachments also have been
conjunctiva is made and checked by injecting balanced reported.
salt solution through the paracentesis track. 6. Experimentally 5-Fluorouracil related retinal
toxicity and dose dependent reversible reduction
Various newer methods The following newer methods
in b-wave amplitude has been documented.
have also been tried:
7. Higher incidence of cataract.
a. Permeable membrane release (polyvinyl alcohol)
b. Collagen sponge implant
Mitomycin-C (MMC)
c. Polymer vehicle placed at sclerostomy
d. Subconjunctival liposomal incorporation. It is an antibiotic antimetabolite first isolated from
the broth of Streptomyces caespitosus in 1958.
Mitomycin-C was first used in humans in the treat-
Complications7,11,12
ment of recurrent pterygium in 1962 and later was
1. Corneal complications: described as an adjuvant in GFS13,14 in which it was
a. Corneal epithelial defects which are dose found to have a longer duration of success, a cellular
dependent filtration sites and patent sclerotomies histologically
b. Corneal punctate keratopathy compared to controls. Mitomycin-C treated eyes had
c. Filamentary keratitis—treated by better and long-term postoperative success.
debridement, hyperosmotics, lubricants, and Mitomycin-C groups also required significantly fewer
antibiotics postoperative medications to achieve success. The
d. Dellen occurs because of tendency toward more ideal combination of drug concentration and contact
elevated bleb formation with 5-Fluorouracil time has not been determined as yet.
e. Corneal epithelial pigment line formation
f. Complications in pre-existing corneal diseases Mechanism of Action7
like keratoconjunctivitis sicca, bullous
It contains a mitosane ring, quinone and a urethane
keratopathy, exposure keratopathy, and
group and acts as an alkaline through irreversible
cicatricial pemphigoid include bacterial corneal
covalent binding with DNA.
ulcers, severe corneal thinning or perforation,
Mitomycin-C inhibits ocular fibroblasts prolife-
corneal keratinization with sterile anterior
ration in vitro by affecting the DNA synthesis. DNA
stromal infiltrates leading to scarring
synthesis is inhibited by cross linking between
g. Corneal endothelium is clinically not affected
adenine and guanine or by a single strand breakage,
by 5-Fluorouracil.
similar to ionizing radiations. This results in cell
2. Conjunctival wound leaks in the early post-
death.
operative periods:
a. Wound leaks should always be suspected in
Ocular Pharmacokinetics of Mitomycin-C
the presence of a low or flat bleb or hypotony.
b. Small microscopic wound leaks heal sponta- Half-life of Mitomycin-C at site of subconjunctival
neously. injection in rabbits is 0.18 to 0.30 hour in conjunctiva
c. Large wound leaks result in hypotony, shallow and 0.20 to 0.45 hour in sclera, as compared to 0.38
anterior chamber with increased incidence of hour in conjunctiva and 0.43 hour in sclera for 5-
choroidal detachment, cataract, and maculo- Fluorouracil.
pathy.
3. Higher rate of bleb related endophthalmitis even Dosage
after years due to formation of thin cystic avascular
Widely used dosage is 0.2-0.5 mg/ml for 2 to 5 mts
blebs have been reported. Late chronic bleb leak
(0.02-0.05%) depending on the type of glaucoma.
is more common and more difficult to treat.
4. Long-term hypotony and hypotony related
Surgical Technique
maculopathy is much less with 5-Fluorouracil than
Mitomycin-C. Mitomycin-C is used intraoperatively at sclerostomy
5. Suprachoroidal hemorrhages, malignant site. Inadvertent entry into the anterior chamber is
an absolute contraindication to the use of Mitomycin- 5. Hypotony20 and hypotonous maculopathy is more
C and is highly toxic to corneal endothelium and common with Mitomycin-C than with 5-
ciliary epithelium. Fluorouracil. Intraocular pressure less than 6 mm
Mitomycin-C soaked 1/2 thickness 3 × 4 mm of Hg is said to be hypotonic. Some patients with
cellulose sponge or a single 3 × 3 × 4 mm. Section of a ocular hypotony may go for hypotonous maculo-
mentor polypore nonlimiting sponge is used. Most pathy (1 to 9%). This is due to the direct toxic
widely used concentration of Mitomycin-C is 0.2 mg/ effect of Mitomycin-C on ciliary epithelium.
ml prepared by reconstituting commercially available 6. Hypotonous maculopathy:
2 mg vial (mitomycin). Sponge is placed over the • Intraocular pressure less than 4 mm or
sclera. The conjunctiva and Tenon’s tissue is draped unrecordable
over the sponge taking care that the cut edge does • Disk edema
not come into contact with the sponge. • Macular edema
After the desired time, sponge is removed and • Retinal folds
discarded and the surgical site is copiously irrigated • Marked drop in visual acuity
with 15 to 30 ml of balanced salt solution. Rest of the • Choroidal detachment
surgery is done in the usual manner. Finally, water • Cataract formation.
tight wound closure is ensured. In our long-term dose-response study of
mitomycin in GFS, the incidence of hypotonous
Indications of Mitomycin-C15-18 maculopathy was less (1.9%)15,16 when compared
to Caucasians (1-9%). This is because of its heavy
1. Limited to patients who are considered to be high
melanin content in our population.
risk for filtration failure (vide supra) or with failed
7. Choroidal effusion is much more common with
trabeculectomy with 5-Fluorouracil.
MMC than with 5-FU.
2. Primary trabeculectomy in young patients, and
8. Cataract formation is more (16%)15 with MMC.
Blacks.
The progression is faster in patients with pre-
3. Uveitic glaucoma and neovascular glaucoma.
existing cataract.
4. Mitomycin-C can be used in patients with pre-
9. Bleb related complications:
existing corneal disease, i.e. aphakic or pseudo-
a. Large overhanging cystic bleb will produce
phakic bullous keratopathy and keratoconjunc-
discomfort to the patient.
tivitis sicca in which 5-Fluorouracil is relatively
b. Dellen formation.
contraindicated.
c. Bleb rupture and bleb leak.
5. Mitomycin-C can also be used preferentially in
d. Bleb infection and endophthalmitis is more
eyes which had keratoplasty before.
common with MMC blebs than with 5-FU bleb,
6. Eyes having combined surgery.19
because the former are very thin, cystic, and
highly avascular.21-23
Complications of Mitomycin-C
1. Corneal surface toxicity is less common with INHIBITORS OF COLLAGEN
Mitomycin-C than 5-Fluorouracil: ORGANIZATION AND OTHERS
a. Folds in Descemet’s membrane. 1. Agents that interfere with collagen activity and
b. Mitomycin-C is highly toxic to corneal endo- synthesis:
thelium. Inadvertent entrance of Mitomycin- • B amino proprionitrile (BAPN) which inhibits
C into anterior chamber will lead to irreversible lysine oxidase an enzyme required for collagen
corneal decompensation. Care should be taken cross linkage
in patients with iridocorneal-endothelial • D Penicillamine (copper chelator) prevents
syndrome. cross linking by chelating lysyl derived
2. Conjunctival wound leak. aldehyde condensation bonds after they have
3. Retards healing of conjunctival flap if Mitomycin- formed
C comes in contact with the free margin of • C is 4 Hydroxyproline decreases collagen
conjunctiva. synthesis.
4. Heavy dose may produce scleral necrosis. 2. Oral colchicine which blocks the microtubules
Chapter 79: Antimetabolites in Glaucoma Filtration Surgery 607
assembly necessary for cell division and migration. 1994.
3. Daunorubicin, an anthracycline antibiotic which 8. Liebmann JM, Ritch R, Marmor. Initial 5-Fluouracil trabeculec-
tomy in uncomplicated glaucoma. Ophthalmology
inhibits human conjunctival fibroblasts in vitro. 1991;98:1036.
4. Postoperative subconjunctival implantation of 9. Whiteside-Mitched J, Liebmann JM, Ritch R. Initial 5-Fluouracil
bleomycin-impregnated collagen implants. trabeculectomy in young patients. Ophthalmology 1992;99:7.
5. Other antiproliferative agents include doxorubicin, 10. Henderson BC. 5-Fluouracil Ophthalmic use. Ophthalmology
prostaglandin inhibitors, vincristine, thiotepa, etc. Clinics of North America 1989;2(1).
11. The Fluouracil Filtering Study Group. Fluouracil filtering surgery
study: One year follow-up. Am J Ophthalmol 1989;108:625.
CONCLUSION 12. Egbert PR, Williams AS, Singh K et al. A prospective trial of
intraoperative fluouracil during trabeculectomy in a black
5-Fluorouracil and Mitomycin-C have revolutionized population. Am J Ophthalmol 1993;116:612.
glaucoma filtration surgery. Both 5-Fluorouracil and 13. Chen CW. Enhanced intraocular pressure controlling effective-
ness of trabeculectomy by local application of mitomycin-C in
Mitomycin-C are double edged weapon. So, adequate
refractory glaucoma. J Ocyl Pharmacol Ther 1990;6:175.
care should be taken in using these agents. Case 14. Palmer SS. Mitomycin as adjunct chemotherapy with trabe-
selection is very important. The dosage and exposure culectomy. Ophthalmology 1991;98:317.
time vary from individual to individual depending 15. Robin AL, Ramakrishnan R, Krishnadas R et al. A long-term
on the age of the patient, type of glaucoma, and other dose purpose study in mitomycin in glaucoma filtering surgery.
Arch Ophthalmol 1997;115:969.
local factors. The long-term effectiveness and safety
16. Ramakrishnan R, Michon T, Robin A. Safety and efficacy of
of these drugs need to be re-evaluated and reviewed mitomycin-C in trabeculectomy in southern India. Ophthal-
constantly. mology 1993;100:1619.
17. Krupin TH, Juzych MS, Shin DH et al. Adjunctive mitomycin-
C in primary trabeculectomy in phakic eyes. Am J Ophthalmol
REFERENCES 1995;119:30.
18. Zacharia PT, Deppermenn SR, Schuman JS. Ocular hypotony
1. Addicks EM, Quigley HA, Green WR et al. Histologic charac-
after trabeculectomy with mitomycin-C. Am J Ophthalmol
teristics of filtering blebs in glaucomatous eyes. Arch
1993;116:314.
19. Costa VP: Effects of topical mitomycin-C on primary
2. Skuta GL, Parrish II RK. Wound healing in glaucoma filtering
trabeculectomies and combined procedures. Br J Ophthalmol
surgery. Survey of Ophthalmology 1987;32(3):149-66.
1993;77:693.
3. Desjardins DC, Parrish RK II, Folberg R et al. Wound healing
20. Stamper RL, McMenetmy MG, Liebmann MF. Hypotony
after filtering surgery in owl monkeys. Arch Ophthalmol
maculopathy after trabeculectomy with subconjunctival 5-
1986;104:1853.
Fluouracil. Am J Ophthalmol 1992;114:544.
4. Seetner A, Morzin JD. Healing of trabculectomies in rabbits.
21. Skuta GL, Benson CC, Higgibotham EJ et al. Intraoperative
Can J Ophthalmol 1979;14:121.
mitomycin versus postoperative 5-Fluouracil in high risk
5. Robert Ritch, M Bruce Shields, Theodore Krupin (Eds). The
glaucoma filtering surgery. Ophthalmology 1992;99:438.
Glaucoma-glaucoma Therapy (2nd edn) 3.
22. Kitazawa Y, Kawase K, Matsushital H. Trabeculectomy with
6. Gressel MG, Parrish RK, Folbert R and 5-FU and GFS-1. An
mitomycin-C: A comparative study with fluouracil. Arch
animal model. Ophthalmology 1984;91:378.
7. Rappaport L, Leibmann J, Ritch R. Antimetabolites in glaucoma
23. Higginbotham EJ, Stevens RK, Musch DC et al. Bleb-related
filtration surgery. Advances in Clinical Ophthalmology. I:
endophthalmitis after trabeculectomy with mitomycin-C.
Chapter 80
Management of Bleb-
related Problems
Hemamalini Arvind, L Vijaya
The goal of glaucoma filtration surgery is to create a Type 1 bleb : Thin, multicystic bleb due to trans-
permanent fistula between the anterior chamber and conjunctival flow of aqueous. This is
the subconjunctival space. The earlier fistulizing associated with good filtration.
procedures i.e., sclerectoiridectomy, limbal trephi- Type 2 bleb : Flat, thin, diffuse and relatively avas-
nation, thermal sclerostomy and posterior lip cular bleb. Conjunctival epithelial
sclerectomy were full thickness procedures which microcysts are usually visible with
resulted in a high rate of complications. In 1968, Cairns high magnification. This is indicative
reported good success with trabeculectomy, 1 a of good filtration.
guarded filtration procedure, in which a partial Type 3 bleb : Nonfiltering bleb due to subconjun-
thickness scleral flap covers the sclerostomy and ctival fibrosis. It is flat, unassociated
drastically reduced the complication rate associated with microcysts and contains engor-
with full thickness procedures. Today, various ged blood vessels.
techniques like releasable sutures and use of antimeta- Type 4 bleb : Encapsulated bleb or Tenon’s cyst.
bolites have been developed to increase the success This is described later in detail.
of trabeculectomy. Successful filtering blebs continue to undergo
changes in morphology over several years.
FILTERING BLEBS
The bleb is the hallmark of glaucoma filtering surgery. BLEB HISTOLOGY
The purpose of performing the surgery is to create a In functioning blebs, the subepithelial connective
functioning filtering bleb over the sclerostomy site tissue is thin and loosely arranged, with clear spaces
which appears as a blister- like elevation of the con- corresponding to microcysts. The overlying epi-
junctiva over the sclerostomy site. The filtered thelium appears normal.4 The use of antimetabolites
aqueous in the subconjunctival space (i.e., the bleb) is associated with more hypocellularity and less
is absorbed by either the conjunctival veins or fibrous and vascular components in the stroma
lymphatics. In cases where the overlying conjunctiva produces blebs with thinner and more irregular
is thin, it can directly pass into the tear film.2 epithelium and fewer goblet cells.5
The appearance of the bleb is an indicator of how
effective it is. In the early postoperative period, the BLEB-RELATED PROBLEMS
conjunctiva and subconjunctival tissues are edema-
tous and hyperemic. Over time, these tissues undergo The purpose of glaucoma filtering surgery is to
modification and assume any one of the following produce an adequate filter that is just enough to bring
forms:3 the intraocular pressure into the target range–neither
Chapter 80: Management of Bleb-related Problems 609
greater nor lesser. However, this is easier said than
done and several complications related to the filtering
bleb can occur, ranging from excess filtration to failure
of filtration. In addition, early or late bleb leaks and
bleb infection can also occur, which can have
disastrous consequences for the eye.
OVERFILRATION
Overfiltration, or excess aqueous outflow through
the bleb, is more common after full thickness
procedures 6 than after trabeculectomy. In
trabeculectomy, it is more common when
antimetabolites are used, especially Mitomycin C.7 Fig. 80.2: Grades of shallow anterior chamber. From left to
right: Grade I,Peripheral irido-corneal touch; Grade II,Pupillary
Clinical Features border-corneal apposition; Grade III, Lenticulo-corneal touch
Overfiltration presents as a shallow anterior chamber,

well elevated bleb and ocular hypotony (Intraocular follows(5,8) (Fig. 80.2).
pressure < 6 mm Hg). Hypotony can induce ciliocho- Grade 1 Peripheral iris-corneal apposition; central
roidal detachment, decreased aqueous production anterior chamber formed.
and acceleration of cataractous changes. Chronic
hypotony, which persists for at least 3 months can be Grade 2 Pupillary border-corneal apposition but no
associated with decreased vision and hypotonic lenticulo-corneal touch.
maculopathy, which manifests as choroidal folds, Grade 3 Central lens-corneal touch
retinal striae and dilated and tortuous retinal vessels This grading is important for further decision
(Fig. 80.1). regarding management.
In all cases of ocular hypotony and shallow or flat
anterior chamber, the bleb should be carefully
MANAGEMENT OF OVERFILTERING BLEBS
assessed and a bleb leak should be ruled out. A
leaking bleb is usually flat and Seidel’s test CONSERVATIVE MANAGEMENT
demonstrates the leak. On the other hand, the
Hypotony and shallow anterior chamber caused by
overfiltering bleb is well elevated, with no leak
overfiltering blebs usually resolve with conservative
demonstrable on Seidel’s test.
management. When the degree of anterior chamber
The severity of the shallow anterior chamber
shallowing is grade 1 or 2, the management should
should be assessed at the slit lamp and graded as
be conservative:
• The patient should be advised to restrict physical
activity and Valsalva maneuver (coughing,
constipation etc). This is more important in aphakic
or vitrectomised eyes which are at higher risk of
suprachoroidal hemorrhage.
• Tamponade of the filtration site, either by pressure
patching, use of a symblepharon ring, large
diameter bandage contact lens (BCL) or a
Simmon’s shell.
Grade 1 shallow anterior chamber, almost always
resolves with conservative management. In grade 2
shallow anterior chamber, conservative treatment can
be tried, and if it is not successful, reformation of the
anterior chamber with viscoelastic, air or a non-
expansile mixture of SF6 or C3F8 in air can be done to
Fig. 80.1: Fundus photograph of hypotonic maculopathy
keep it formed till the ciliary body and choroid

reattach and aqueous production is re-established.
SURGICAL TREATMENT
A flat anterior chamber with lens-corneal touch
(Grade III) requires immediate surgical intervention,
because lenticulo-corneal contact can cause rapid
endothelial decompensation and rapid cataract
formation. Intervention involves reformation of the
anterior chamber with a viscoelastic, air or a
nonexpansile mixture of C3F8 or SF6 in air. If this does
not work, choroidal drainage may be required.
OTHER MODALITIES
Fig. 80.3: A leaking bleb–Seidel’s test positive
Other methods described to manage overfiltering
blebs and shallow anterior chamber aim at increasing confirmed with the Seidel’s test (Fig. 80.3).
inflammation and causing shrinkage of the bleb. They The tear film is stained with fluorescein by apply-
are: ing a fluorescein strip gently to the bleb. Without
a. Application of topical chemical irritants such as applying pressure, the eye is examined under cobalt
0.25–1% AgNO3 or 50% trichloroacetic acid9 blue illumination. If there is a leak, unstained aqueous
b. Cryotherapy10 will be seen flowing through the leak into the tear
c. Diathermy and cauterization11 film against the background of bright green
d. Argon laser12 fluorescein. If there is no spontaneous leakage,
e. Nd: Yag thermal laser,13 and pressure may be applied to the globe when the
f. Autologous blood injection14 into the bleb. suspicious area is examined.
BLEB LEAKAGE Management
Bleb leaks can occur either in the early postoperative Precautions During Surgery
period or can occur several months to years after
Whenever possible, it is best to prevent a bleb leak.
filtration surgery. Early postoperative bleb leaks can
Good, meticulous surgical technique can go a long
occur either through inadvertent button holes during
way in preventing early postoperative bleb leaks.
the surgery or through an inadequately sutured
Careful conjunctival dissection and manipulation,
conjunctival incision. They occur more commonly in
avoidance of toothed forceps and meticulous wound
trabeculectomy supplemented with antimetabolites
closure using continuous locking sutures (in limbal
(especially Mitomycin C) than in non-supplemented
based flaps) should be practiced. At the end of
surgeries.15
surgery, buttonholes should be looked for, and if
Late bleb leaks occur more commonly in thin,
present, should be sutured with 10-0 nylon using
avascular blebs that occur after full thickness
mattress or purse string sutures. When
procedures and after trabeculectomy supplemented
antimetabolites, especially Mitomycin C are used
with antimetabolites, especially Mitomycin C.
intraoperatively, contact between the sponge soaked
The leaking bleb can be associated with hypotony,
in Mitomycin C and the conjunctival wound edge
shallow or flat anterior chamber and choroidal
should be avoided and at the end of the exposure
detachment. It increases the risk of blebitis and
period, the tissues should be irrigated vigorously to
endophthalmitis. Early leak can flatten the bleb and
remove all traces of the drug.8
lead to subconjunctival fibrosis and subsequent
failure of bleb function. Treatment of Early Bleb Leaks
Clinical Findings Conservative Management
The leaking bleb, most often, is flat. The bleb leak is Conservative management should be tried initially.
This includes: development of corneal abrasions at the site of tissue
1. Medical therapy with aqueous suppressants i.e., adhesive applications.
either oral carbonic anhydrase inhibitors or topical In late bleb leaks occurring in thin, avascular blebs,
aqueous suppressants can decrease aqueous the procedure is much less effective and more
production enough to reduce aqueous flow dangerous because the glue does not adhere easily
through the leak, thereby allowing the surface to the conjunctiva and dislocation of the glue can
epithelium to proliferate and close the leak. increase the size of the opening. Autologous blood
2. Firm pressure patch: As an alternative to pressure injection to create inflammation within the bleb has
patching, large diameter (14–24 mm) BCLs16 that been successfully applied to leaking blebs.26
cover the site of leak can be tried. The BCL must
be left in place for atleast 1 week. Alternatively, Late Bleb Leaks
collagen shields, symblepharon rings 17 or
Simmon’s shell18 can be used. Topical antibiotics These are more difficult to manage than those that
and close observation are necessary during occur in the early postoperative period, probably
conservative management. because the leak edge has usually got epithelised and
3. Instillation of aminoglycoside drops (gentamycin) the conjunctiva is often very thin and friable.
that irritate the conjunctiva and can stimulate Conservative measures are almost never successful.
wound healing. Neither is simple suturing of the leak as the thin,
friable surrounding conjunctiva often cheesewires.
Free or rotational conjunctival grafts or conjunctival
Surgical Revision
flap advancement as described before are necessary
If the leak still persists and there is no improvement most of the time.
after 1 to 2 days of conservative management,
suturing the leak with 10-0 nylon (mattress or purse THE FAILING BLEB
string sutures) with anterior chamber reformation
can restore the architecture of the anterior chamber Failing or failed blebs are those associated with
and the filtering bleb.8 If suturing is not effective, impending or established obstruction to the flow of
surgical revision of the bleb may be necessary. Sliding aqueous and inadequate intraocular pressure control.
and rotational conjunctival and Tenon’s flap grafts,19- Early failing or failed blebs are those that occur within
21
free conjunctival grafts,22 and scleral grafts23 have the first postoperative month.
been described. One technique involves excising the Early undetected spikes in intraocular pressure
entire cystic leaking bleb and undermining and can occur quite frequently after glaucoma filtering
advancing the surrounding conjunctiva to cover the surgery. They could be due to viscoelastics, tight
defect. A circumferential relaxing incision may be scleral flap sutures or blockade of the internal ostium
made in the posterior conjunctiva close the fornix to with a blood clot, iris root, incompletely excised
relieve tension and the advanced conjunctiva sutured descemet’s membrane, ciliary processes, lens or
in place to the sclera.8 However, these measures are vitreous.
required more often for late bleb leaks than for early Gonioscopy is mandatory to assess the cause of
postoperative bleb leaks. raised intraocular pressure in the early postoperative
period. If the internal ostium is free of obstruction,
digital massage is often sufficient to form the bleb
Other Modalities
and cause a drop in intraocular pressure. Releasing
Successful closure of early postoperative bleb leaks sutures or argon laser suture lysis should be avoided
have been reported with tissue adhesives, both during the first 2 to 3 postoperative days as it may
cyanoacrylate and fibrin tissue glue.24,25 A small lead to excessive flow, especially when blood or
amount of tissue adhesive is applied on the site of viscoelastics later get absorbed. However, if the
leak under topical anesthesia after drying the internal ostium is blocked, laser or incisional surgery
conjunctival surface. The use of BCL or collagen may be necessary to prevent filtration failure.
shields can prevent the adhesive from getting Argon laser retraction or penetration of
dislodged. The most frequent complication is pigmented tissues or Nd: Yag photodisruption of
non-pigmented membranes may occasionally restore 1. Topical corticosteroids They are routinely adminis-
filtration without the need for further surgery 8. tered after glaucoma filtering surgery and help in
Sometimes, use of topical pilocarpine or intraocular decreasing inflammation and enhance chances of
acetylcholine may pull an incarcerated iris root out successful filtration.27
of the internal ostium and restore filtration. 2. Antimetabolites In early postoperative filtration
failure, 5-FU subconjunctival injections can help
Early Bleb Failure enhance filtration. 5-FU is given as 5 mg injections
Early failing or failed blebs are those that occur within subconjunctivally, either 180° or 90° away from
the first postoperative month. Early recognition of the bleb site, every day for a maximum period of
the signs and symptoms of filtration failure allows 2 to 3 weeks28 (Figs 80.5A and B). Complications
for timely intervention to prevent late failure. associated with postoperative 5-FU injection
Injection and vascularity of the bleb, in the include corneal and conjunctival epithelial toxicity,
presence of a flattening bleb herald failure (Fig. 80.4). conjunctival wound leaks, subconjunctival hemor-
These typically occur before elevation of intraocular rhage and inadvertent intraocular spread of 5-FU.
pressure. Causes of early failure include The complications are dose-related.
a. Obstruction at the site of the internal ostium, as
described.
b. Obstruction at the level of the sclera i.e., tight
scleral suture.
c. Subconjunctival or episcleral fibrosis.
Prevention and Management of Early Failing

Blebs
Intraoperative Measures
In patients at high risk of failure i.e., young patients,
previous intraocular surgery, uveitis, young patients
and previously failed surgery, precautions to prevent
failure include the use of antimetabolites. We
routinely use intraoperative 5-FU at a concentration
of 50 mg/ml for 1 min. in all patients and MMC
0.4/0.2 mg/ml for 1 to 3 min as appropriate in patients
at high risk of failure.
Postoperative Measures
Figs 80.5A and B: Subconjunctival injection of 5-FU. A. A

swabstick soaked in anesthetic solution is applied to the site of
injection. B. Injection of 5-FU subconjunctivally 180° away from
Fig. 80.4: A failed, vascularized bleb the bleb
3. Digital ocular compression Digital compression can the bleb is flat, anterior chamber deep and
be applied to the inferior sclera 29 or cornea intraocular pressure is high. Gonioscopy must be
through the inferior eyelid; 30 or to the sclera performed prior to argon laser suture lysis or
posterior to the scleral flap through the superior suture release to confirm an open internal ostium.
eyelid. Focal compression is applied with a Only one suture should be released or cut at a
moistened cotton tip at the edge of the scleral flap. time to prevent over-filtration.
Both may be used in the immediate postoperative 6. Intracameral injection of tissue plasminogen
period to elevate the bleb. However, no elevation activator (tPA) to lyse blood or fibrin clots has
of the bleb occurs when the internal ostium is been described, but is commonly complicated by
blocked. hyphema (36%).
If the bleb forms on digital compression, the 7. Laser internal revision Nd: YAG laser is useful in
patient can be instructed to perform compression cases where incarceration of the iris or vitreous
through the inferior eyelid 4 to 5 times a day at are responsible for filtration failure in the early
home. Because of the potential complications of postoperative period.8
corneal abrasion, hypotony, flat anterior chamber,
hyphema, or iris incarceration into the Late Failure of Filtration
sclerostomy, ocular massage is suitable only for Late failing or failed blebs are those with a history
those patients who have had a beneficial response of good bleb function and adequate control of
to the initial massage. intraocular pressure for at least 1 month
4. Releasable sutures The use of externalized releas- postoperative. The most common cause of late failure
able sutures allows tight closure of the scleral flap is subconjunctival or episcleral fibrosis.33 The normal
intraoperatively, which can be adjusted post- ocular healing response is responsible for late bleb
operatively depending on the need for increase failure and this is accelerated by young age, black
in filtration. race, postoperative subconjunctival hemorrhage and
The disadvantages of releasable sutures inflammation.
include the need for additional intraoperative Late failed blebs usually require medical treatment
manipulations and corneal epithelial defects, but to be restarted to control intraocular pressure. When
the benefits of improved intraocular pressure a failing bleb no longer responds to maximal tolerated
control far outweigh these disadvantages. medical treatment, either bleb revision or filtration
5. Argon laser suture lysis (ALS) In the early postope- surgery in an area with virgin conjunctiva is consi-
rative period, the use of argon laser suture dered.
lysis31,32 can help increase filtration across the In non-inflamed eyes with thin, obstructing
trabeculectomy. However, with the increasing use adhesion at the internal ostium, internal revision
of releasable sutures, the need for laser suture surgically or using Nd:Yag laser can be tried.
lysis has decreased. Laser suture lysis is associated However, in most eyes with late failure, the obstruc-
with an increased incidence of creating tion is due to subconjunctival fibrosis. Late external
conjunctival button holes. If there is any suspicion revision with excision of the fibrovascular tissue have
of leak after argon laser suture lysis, a Siedel’s been disappointing.33 The most effective approach is
test must be performed. filtration in an area that has not undergone previous
The timing of suture release or Argon laser surgery.
suture lysis is critical to its success. It should be
performed within 2 weeks after surgery if no THE ENCAPSULATED BLEB
antimetabolites have been used, else fibrosis of
the scleral flap will prevent any drop in intraocular Encapsulated blebs develop in 8.3 to 28 percent of
pressure. However, when antimetabolites are eyes after filtering surgery.8 The incidence is much
used, this period is prolonged. Suture release or lower in surgeries with Mitomycin-C. Risk factors
for encapsulation are younger age, prior argon laser
argon laser suture lysis can be effective several
trabeculoplasty, prior treatment with β-blockers,
weeks to months after Mitomycin C use. Suture
sympathetic and para-sympathomimetic drugs and
release or argon laser suture lysis is done when
prior surgery involving the conjunctiva. 5,8 Infla-
mmatory mediators have been implicated in their

development. Collagen–producing fibroblasts are
thought to play a major role in the formation of
Tenon’s cysts.34
The process of encapsulation consists of
fibroblastic proliferation that results in a dense,
opalescent bleb with a thick wall, in direct
communication with the anterior chamber. This
commonly occurs within 2 to 4 weeks after glaucoma
filtering surgery. Encapsulation is associated with an
increase in intraocular pressure after an initial period
of intraocular pressure control. Other complications
of bleb encapsulation include corneal dellen and
occasional discomfort.
Fig. 80.6: An exuberant bleb, which may be symptomatic
MANAGEMENT
Medical concert and mild foreign body sensation to symptoms
Initial management consists of topical aqueous related to defective blinking and tear film
suppressants, steroids and digital massage. The abnormalities like superficial punctate keratopathy,
decision regarding medical versus surgical manage- ocular surface irregularities and secondary dellen.
ment depends on the level of intraocular pressure, Astigmatism may also be induced by large filtering
severity of glaucomatous damage and the responses blebs and even mono-ocular diplopia has been
to conservative management. Many encapsulated reported.
blebs, especially those that were only partially
encapsulated, may respond to the above treatment. Management
If resolution does not occur, or if the intraocular Symptoms related to ocular surface abnormalities can
pressure is too high, surgery might be necessary. be managed by artificial tears. If the symptoms
persist, large blebs can be partially excised. Large
Surgical Management blebs that overhang the cornea usually lie on the
1. Needling: Needling involves cutting the fibrotic cornea rather than dissect into its tissue planes. They
wall of the cyst with a 27G needle to establish can be easily freed by blunt dissection excision of the
aqueous flow to the subconjunctival space. The overhanging portion with a cut parallel to the limbus.
use of 5-FU injection after needling increases the
chances of success of this procedure.35 Common
complications include subconjunctival hemorrhage
and transient wound leak.
2. If needling is not successful, excision of the fibrous
tissue may be required. The conjunctival incision
is opened, the conjunctiva is detached from the
underlying fibrotic wall by blunt dissection and
the capsule in excised. Again, the use of 5-FU
increases the chances of success.
THE SYMPTOMATIC BLEB

Filtering blebs, more often than not, are
asymptomatic. However, some large blebs, or those
that extend into the cornea may produce symptoms
Fig. 80.7: Treatment of an exuberant bleb with
(Fig. 80.6). The symptoms may range from cosmetic compression sutures
There is surprisingly little or no leak after this
procedure. Compression sutures 36 may also be
applied to compress large blebs. (Fig. 80.7).
Other methods to shrink blebs include cryo-
therapy, 37 Nd:Yag laser theremotherapy,38 argon
laser, 39 diathermy and cauterization. 40 All these
methods carry a risk of bleb failure.
Symptomatic nasal blebs can be managed by
performing a medial tarsorrhaphy. This can alleviate
symptoms and over time, the bleb may shift superior-
ly, when the tarsorrhaphy can be reversed.
BLEB-RELATED INFECTION (Fig. 80.8)

Infection of the bleb may occur months to years after
filtration surgery . ‘Blebitis’ refers to infection of the Fig. 80.8: A thin-walled cystic bleb after trabeculectomy with
bleb, which may spread easily into the anterior MMC. Such a bleb is prone to leak and infection
chamber, with which it is contiguous. The infection
may also spread further posteriorly into the posterior
segment, resulting in full-blown endophthalmitis.
There is no clear cut distinction between blebitis and
endophthalmitis and blebitis is only a limited anterior
form of endophthalmitis.
The reported incidence of late bleb related
endophthalmitis ranges from 0.2 percent to 9.4
percent.41,42 The incidence is higher in thin cystic blebs
resulting from the use of antimetabolites or full
thickness procedures and inferior blebs that are more
prone to drying and accidental minor trauma.
Infectious conjunctivitis and blepharitis can lead to
blebitis, especially in the presence of thin, cystic or
leaking blebs. Systemic diseases like diabetes mellitus
or other immunocompromised states can predispose Fig. 80.9: Blebitis; Milky white bleb with surrounding ciliary
the individual to bleb infection. and conjunctival congestion
The most commonly isolated organisms from bleb
related endophthalmitis are Streptococcus species, Management
H.influenzae and Staphylococcus species.5
On diagnosing blebitis or bleb-related endophthal-
mitis, it is important to first identify the organism
Clinical Features
responsible. The conjunctival exudates should be
Symptoms of blebitis or bleb-related endophthalmitis collected, stained and cultured. An anterior chamber
include pain, congestion, foreign body sensation and tap should be done in case of severe anterior chamber
blurred vision. On examination, conjunctival and involvement and endophthalmitis. A vitreous tap
ciliary congestion, purulent discharge and a milky may be done in case of endophthalmitis. Specimens
white bleb with a loss of clarity are seen (Fig. 80.9). should be stained with Gram and Giemsa and
Sometimes, a pseudohypopyon can be seen in the cultures should be inoculated in blood agar, chocolate
bleb. Seidel’s test may be positive in case of a leaking agar, enriched broth and Saboraud’s dextrose agar.
bleb. Anterior chamber reaction may be variable and However, there is controversy regarding the value
a hypopyon may be present. Vitreous exudates are of conjunctival culture in the etiological diagnosis
present in case of endophthalmitis. of blebitis. Mandelbaum et al found that only 5 to 18
eyes showed the same organism in the conjunctiva
and the vitreous.43 the chances of developing bleb-related endophthal-

In case of blebitis without anterior chamber or mitis.
vitreous involvement, a topical broad spectrum
antibiotic, e.g. fluoroquinolone can be given every CONCLUSION
half or one hourly. Ofloxacin may have better
The presence of the bleb predisposes the eye to its
penetration into the anterior chamber than other
attendant complications. They may range from
fluoroquinolones.
transient problems which require only observation
When the anterior segment is also involved but
to refractory problems requiring repeated surgeries,
the vitreous is clear, treatment with topical fortified
which are frustrating to the patient and the surgeon.
antibiotics around the clock must be used. Topical
The best way to eliminate these problems would be
fortified cefazoline (50 mg/ml) or vancomycin (25
to do away with the bleb. Non-penetrating filtering
mg/ml) for Gram-positive coverage and amino-
surgery may achieve just that in the near future. But
glycosides for Gram-negative coverage (amikacin 50
till such time that we have to depend on trabeculec-
mg/ml or tobramycin 4 mg/ml) may be used.
tomy as a means of intraocular pressure control after
Systemic antibiotics like fluoroquinolones which have
failure of maximal tolerated medical therapy, it can
high penetration into the vitreous can be used. Topical
be said that the ideal bleb is one that is “diffuse, with
steroids can be started after the antibiotics have been
microcystic conjunctival changes, mildly elevated,
used for 24 to 48 hours and the infection appears to
with moderate thickness of the wall and a relative
be controlled. Antibiotics should be later modified
paucity of blood vessels.”
depending on the results of culture and sensitivity.
In bleb-related endophthalmitis, intravitreal
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7. Costa VP, Wilson RP, Moster MR et al. Hypotony maculo-
No evidence exists to show that antibiotics pathy following the use of topical Mitomycin C in glaucoma
prophylaxis may decrease the incidence of bleb- filtration surgery. Ophthalmic Surg 1993;24:349.
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reasonable to use such prophylaxis in cases of high surgery; In Robert Ritch, M Bruce Shields, Theodore Krupin
(Eds): The glaucomas (2nd Ed): Mosby: 1996;3:1703.
risk of bleb infection like inferior blebs and blebs
9. Gehring JR, Ciccarelli EC. Trichloroacetic acid treatment of
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be periodically alternated with agents having 1972;74:622.
different spectrums of coverage to minimize the 10. Cleasby GW, Fung WE, Webster RG. Cryosurgical closure of
development of drug-resistant organisms. filtering blebs. Arch Ophthalmol 1972;87:319.
11. Krik HQ. Cauterization of filtering blebs following cataract
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promptly and the use of contact lenses should be 1973;77:573.
avoided. Patient education about early symptoms of 12. Fink AJ, Boys-Smith JW, Brear R. Management of large filtering
infection in the most important approach to minimize blebs with the argon laser. Am J Ophthalmol 1986;101:695.
13. Lynch MG, Roesch M, Brown RH. Remodeling filtering blebs filtering surgery to minimize the side effects. Ophthalmology
with the neodymium: YAG laser. Ophthalmology 1996; 1987;94:564.
103:1700. 29. Weinland M, Spaeth GL. Use of digital compression following
14. Leen MM, Moster MR, Katz LJ et al. Management of overfiltering glaucoma surgery. Ophthalmic Surg 1988;19:350.
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Ophthalmol 1995;113:1050. pressure: a new method to encourage filtration after
15. The Fluorouracil Filtering Surgery Study Group. Fluorouracil trabeculectomy. Ophthalmic Surg 1984;15:62.
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Ophthalmic Surg 1991;22:164. 103:1700.
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leak in filtering operations. Glaucoma 1989;11:86. blebs with the argon laser. Am J Ophthalmol 1986;101:695.
25. Zalta AH, Wieder RH. Closure of leaking filtering blebs with 40. Sugar HS. Complications,repair and reoperation of anti-
cyanoacrylate tissue adhesive. Br J Ophthalmol 1991;75:170. glaucoma filtering blebs. Am J Ophthalmol 1967;825.
26. Smith MF, Magauran RG III, Betchkal J, Doyle JW. Treatment 41. Freedman J, Gupta M, Bunke A. Endophthalmitis after
of post filtration bleb leaks with autologous blood. Ophthal- trabeculectomy. Arch Ophthalmol 1978;96:1017.
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27. Starita RJ, Fellman RL, Spaeth GL et al. Short–and long term Endophthalmitis after filtering surgery with Mitomycin C. Arch
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Ophthalmology 1985;92:938. 43. Mandelbaum S, Forster RK. Endophthalmitis associated with
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Chapter 81
Artificial Drainage Devices in

Glaucoma Surgery
R Thomas, SC Gieser
INTRODUCTION mented with a wide variety of materials implanted

The goal of glaucoma filtration surgery is to produce into the anterior chamber to try to form a permanent
a communication between the anterior chamber and drainage tract for aqueous for patients in whom
the subconjunctival space permitting filtration of conventional surgical filtration failed. These early
aqueous. While numerous studies have demonstrated devices were designed as paracentesis drains,
good results with modern techniques of trabe- cyclodialysis implants, or sclerostomy implants.
culectomy,1 certain groups of patients continue to have One of these descriptions of these setons was in
a poor prognosis for successful filtration. These 1906 by Rolle.2 He performed a double paracentesis
include patients with juvenile glaucoma, neovascular and threaded horse hair through the corneal punctures
glaucoma, secondary glaucoma, glaucoma in aphakia to assist drainage in eyes of patients with painful
and pseudophakia postkeratoplasty glaucoma, and in absolute glaucoma. Several years later Mayour and
those with previously failed filtration surgery. Zorab modified this technique by placing silk threads
In an effort to facilitate filtration in these high-risk to drain aqueous from the chamber angle to the
patients, surgeons have implanted a wide3,4 variety subconjunctival space. Zorab termed the procedure
of foreign materials to prevent closure of the fistula “aqueoplasty”.4
and provide a shunt for aqueous humor. These In the years that followed, investigators have
mechanical devices include setons, shunts, and valves. implanted setons that were made of gold, tantalum,
While many ophthalmologists group all drainage platinum, glass,5 autologous lacrimal canaliculus,
devices under the term “seton” this is technically polyethylene, teflon, gelatin film, and cartilage. The
incorrect. A seton, from Latin for “bristle”, refers to a first person to use an acrylic plate implant was
solid shaft that prevents wound apposition. Drainage Qadeer.6 These early implants were associated with
occurs either by bulk flow through a gap or by means high complication rates, poor results, and extensive
of surface tension alongside the material. A shunt intraocular inflammation.7
refers to a tubular structure, which allows fluid to It was not until the late 1960s when Molteno8,9 des-
passively flow through it. It is incapable of influencing cribed his acrylic drainage device;8,9 that implanted,
either anterograde or retrograde flow. A valve is a began to show promise for successful filtration in
tubular structure designed to promote unidirectional select glaucoma patients. His observations and
flow. We prefer the term “artificial drainage devices” innovations laid the groundwork for the current
(ADDs) when referring to the modern shunt and valve generation of ADDs (Table 81.1).
procedures.
POSTERIOR TUBE SHUNT IMPLANTS
HISTORICAL PERSPECTIVE
Shortly after the introduction of filtration surgery for The currently used ADDs are made of a nonreactive
glaucoma in the early 1900s, ophthalmologists experi- synthetic material, to which fibroblasts adhere poorly.
Chapter 81: Artificial Drainage Devices in Glaucoma Surgery 619
Table 81.1: Indications of ADD
1. Abnormalities of iridocorneal angle
2. Neovascular glaucoma
3. Excessive conjunctival scarring
4. Glaucoma after PK uncontrolled with medical therapy
5. After failure of repeated filtration operations
6. Aphakic glaucoma
7. Pediatric glaucoma due to Sturge-Weber syndrome
All these devices have an anterior chamber tube,

which is attached to a episcleral exoplant. The exoplant
establishes a potential space in which drained aqueous
can be sequestered for incremental absorption. In
addition, the Krupin and Joseph-Hitchings devices
have pressure sensitive valves to restrict the flow of Fig. 81.1: Photograph of the double-plate (left), single-plate
(centre) and paediatric (right) Molteno implant
aqueous humor.
Molteno Implant
Molteno developed a device that drained aqueous
from the anterior chamber through a fine tube onto
the surface of the acrylic plate. The tube is 7 mm long
with an external diameter of 0.6 mm and luminal
diameter of 0.3 mm. The conjunctival bleb that formed
over the implant could not contract to a size smaller
than the acrylic plate.
The Molteno implant consists, of a narrow silicone
tube (outer diameter 0.6 mm and inner diameter 0.3
mm) that opens onto the upper surface of a thin,
circular, acrylic plate 13 mm in diameter10 (Fig. 81.1).
The surface is concave to allow easy fitting to the
contour of the sclera. The edge of the plate has a Fig. 81.2A: A functioning Molteno implant. Note the position of
thickened rim 0.7 mm high which is perforated to the episcleral implant chamber. (Courtesy: Prof. Frank Billson)
permit attachment to the sclera with sutures. This
suturing prevents plate migration.
Implantation is performed via a fornix-based
conjunctival flap with two relaxing incisions directed
posteriorly. A large rectangular, 6 mm × 8 mm half-
thickness limbus-based scleral flap is then prepared
in order to cover as much of the tube length as possible.
The episcleral plate is placed into Tenon’s space and
the anterior portion is sutured to the sclera approxi-
mately 7 mm posterior to the limbus in the selected
quadrant (Fig. 81.2A). The silicone tube is placed
radially across the scleral flap and excess tube is
trimmed to allow it to overlap the limbus by 2 mm.
The anterior chamber is entered parallel to the iris
plane, and the tube is inserted into the anterior
chamber (Fig. 81.2B). The scleral flap is sutured over
the tube. Tenon’s tissue and conjunctiva are drawn Fig. 81.2B: A functioning Molteno implant. Note the tube in the
forward and sutured to the limbus. anterior chamber. (Courtesy: Prof. Frank Billson)
Many surgeons have modified Molteno’s technique

by covering the tube at the limbus with a scleral patch
graft instead of making a partial thickness scleral flap.
In this modification, the anterior chamber is entered
with a 21-gauge needle parallel to the iris plane. The
scleral graft prevents the silicone tube from touching
the corneal endothelium. The graft also strengthens
the sclera and prevents extrusion of the tube.11
A major complication of the Molteno implant is a
persistent flat anterior chamber resulting from
overfiltration. Surgeons have attempted to reduce this
complication with either suture ligatures around the Fig. 81.3A: Diagram of the two-stage procedure. In the first
external portion of the tube or suture occlusion of the stage, the implant is secured to the episclera and the tube is
internal lumen. 12,13 The latter method involves a hitched to the adjacent rectus muscle with a marker suture
chromic suture that is temporarily threaded inside the
lumen of the tube to occlude it. The other end is
brought out of the conjunctiva. The suture is then
removed in a ripcord fashion approximately one week
after surgery. This technique has been associated with
sterile hypopyon following the removal of the suture
due to autolysis of the suture material. In order to
prevent this complication, a nonabsorbable suture can
be used instead.
In an attempt to allow bleb formation without the
inflammatory stimulus of aqueous, Molteno used a
two-stage procedure.14 In the first stage, the plate is Fig. 81.3B: The tube is connected intracamerally
secured to the episcleral surface, but the tube is not
inserted into the anterior chamber (Figs 81.3A and B).
Six to eight weeks later, the tube is connected
intracamerally and aqueous is allowed to drain into
the preformed bleb, thereby preventing the free flow
of aqueous that would lead to hypotony and a flat
anterior chamber (Fig. 81.4).
Molteno describes a complicated regimen of anti-
inflammatory drugs to be used after the second stage,
but this is omitted by most other surgeons. A major
disadvantage of two-stage implantation is that the
intraocular pressure remains uncontrolled until the
second stage is performed. While this can be avoided
by performing a “temporary” trabeculectomy during
the first stage, most surgeons prefer to use a one-stage
operation.
Molteno designed several variations on his original Fig. 81.4: A diagram of the second stage, in which the tube is
model. The double plate Molteno implant consists of placed into the anterior chamber under a scleral flap or graft
two 13 mm plates (Fig. 81.1). They are connected to
each other by a 10 mm silicone tube entering 90 double plate involves more dissection and therefore
degrees away from the primary intracameral tube. The is more demanding than the single plate implant.
plates are sutured to adjacent quadrants with the The two plates in effect double the amount of
connecting tube placed either above or below the potential surface area through which aqueous can be
appropriate rectus muscle. The implantation of a absorbed (from 135 mm2 in one plate to 270 mm2 in
two plates). Molteno found that two plates provided observed that a space existed between the sclera and
better drainage than one, but four plates were not the silicone encircling bands used in retinal detach-
better than two.15 Billson and Thomas observed that ment surgery. Reasoning that this space might form a
children initially controlled with double plate suitable reservoir for the absorption of aqueous, he
implants may, over a period of years, require another and his colleagues18-20 developed a procedure where
double plate implantation for adequate control of an anterior chamber shunt tube is attached to a silicone
intraocular pressure.16 Molteno noted that the single encircling band.
plates have higher success rates in pseudophakic/ An appealing feature of the Schocket’s procedure
aphakic glaucoma, while double-plate implants had is that the materials necessary to fashion the shunt are
better success rate in neovascular glaucoma.17 readily available from existing materials. A 3 cm strip
Other variations of the Molteno implant include a of standard silastic tubing (outer diameter 0.6 mm,
pediatric size plate for use in eyes with short axial inner diameter 0.3 mm) is sutured into the grooved
lengths (Fig. 81.1), and the V-chamber plate. The V- portion of a No. 220 silicone band with the tube
chamber modification is designed to decrease extending 15 mm from the wall of the band. Alter-
postoperative hypotony from overfiltration. The V- natively, a 180 degree of a 360 degree encircling band
chamber implant contains a thin V-shaped rim of can be used. A 360 degree band provides a larger
polypropyline on the plate surface below the tube’s absorption area.
entry, occupying one-eighth of the plate’s area. Since As in a standard retinal procedure, a 360 degree
this V-shaped ridge is of the same height as the peritomy is performed and the four rectii muscles are
circumferential rim of the plate, the weight of the isolated. The encircling band is secured equatorially.
overlying, hydrated Tenon’s tissue is supposed to The silastic tube, having been sutured to the gutter of
collapse and forms a temporary roof for the smaller the encircling band, is then inserted into the anterior
V-chamber, thus limiting the extent of the bleb and chamber under a scleral flap or covered with donor
filtration. The clinical effectivenss of this design has sclera.
not yet been established.
Molteno’s concept of a bleb-promoting device is Krupin-Denver Valve Implant
incorporated into three other currently used ADDs i.e.
Schocket, Krupin, and Joseph-Hitchings. The Krupin-Denver implant utilizes a unidirectional
slit valve. The original Krupin-Denver valve was a
relatively short implant placed beneath a trabe-
Ahmed Glaucoma Valve (Mateen Ahmed PhD) culectomy scleral flap, meant to drain aqueous to a
It is made of polypropelene and measures 13 × 16 mm bleb 4 to 6 mm away from the limbus.21 It consisted of
with 1.9 mm height providing a surface area of a silastic tube, with one end placed into the anterior
184 mm 2. This is an unidirectional and pressure chamber. The other end had wings for scleral suturing
sensitive valve: When intraocular pressure is 8 mm of and was cemented to a silastic tube containing a
Hg the valve opens. The main advantage of this device unidirectional slit valve.
is that there is no chance of hypotension which may Since its introduction in the late 1970s, the original
result in hypotensive maculopathy. Krupin-Denver ADD never had wide-spread usage
because of a high incidence of fibrosis at the silastic
Baerveldt Implant end, which prevented flow. Additionally, the rigid
design and the anterior location of the device caused
It is a non-valved long tube shunt device made of frequent erosion through the conjunctiva.
silicone rubber. The implant is available in various Recently, it has been redesigned similar to the
sizes from 200 to 500 sq.mm with a slender tube of Schocket device, using an encircling band at the
7 mm. The pressure lowering efficiency is equal to that equator to provide a potential space for aqueous
of Molteno’s implant. secretion.22
SCHOCKET PROCEDURE Joseph-Hitchings Valve Implant

Schocket developed the anterior chamber tube shunt Joseph and Hitchings23,24 described the use of a valved
to encircling band (ACTSEB) procedure. Schocket tube attached to a silicone exoplant (Fig. 81.5). The
and congenital glaucomas, and in secondary glauco-

mas including uveitic glaucoma, neovascular glauco-
ma, glaucoma in aphakia and pseudophakia, and
glaucoma following penetrating keratoplasty.
Additionally, patients with glaucoma associated with
the iridocorneal endothelial (ICE) syndrome may
benefit from an ADD.
In rare cases, where there is an extremely poor
prognosis for filtering surgery, an ADD can be used
as a primary procedure. Such cases include active
neovascular glaucoma despite full panretinal photo-
coagulation, aphakic or pseudophakic glaucoma with
severe uveitis, and glaucoma with scarred conjunctiva
Fig. 81.5: Photograph of a Joseph-Hitchings implant 360 degrees around the limbus.
In most other eyes, trabeculectomy with an anti-
mitotic, such as 5-Fluorouracil or mitomycin, should
silicone anterior chamber tube has outer diameter of probably be attempted before an ADD is used.
0.6 mm and inner diameter of 0.3 mm. A slit in the
side of the tube functions as the valve, with an opening RESULTS
pressure between 4 and 20 mm Hg. The tube is Reports from the four major types of devices indicate
attached with silicone rubber adhesive to a rubber that approximately two-thirds to three-fourths of
strap which is 9 mm wide, 1 mm thick, and 85 mm many advanced glaucomas can eventually be con-
long. The valved implant reduces the frequency and trolled by ADDs. The success rate for intraocular
magnitude of postoperative hypotony and choroidal pressure control with the four devices are similar.
detachment, when compared with the open tubes of Because of the different subgroups of advanced
Molteno and Schocket. The width of the silicone band glaucoma patients and differing definitions of success,
can be varied, thereby controlling the area available exact comparison of the various devices is not possible.
for absorption. Molteno claims an enhanced success rate when using
double plate implant with his regime of fibrosis
INDICATIONS FOR USE
suppression therapy.12 Others report that an intra-
The implantation of ADD is associated with serious ocular pressure less than 21 mm Hg is achieved in 60
intraoperative and postoperative complications. to 80 percent of eyes.28 However, two-thirds of the
Because of these complications, ADDs should be successful cases require additional antiglaucoma
reserved only for high-risk glaucoma patients where medications to control the intraocular pressure.
the prognosis for traditional filtration surgery is poor, The success rate depends on the type of glaucoma.
or where previous surgical attempts have failed to The highest success rates occur in eyes with open or
control the intraocular pressure. These devices should closed angle glaucoma that have a history of prior
be reserved for eyes which still maintain some failure after filtration surgery. Success rates are poorer
potential vision. in eyes with neovascular and other types of secondary
Typically, patients requiring an ADD have few glaucoma, and in the pediatric patients. 16,29 The
other options. Refractory glaucomas can be treated patients with glaucoma following congenital cataract
with cyclodestruction, either with diathermy, surgery seem to have a better result than other
cryotherapy, or laser cyclophotocoagulation. Recently pediatric patients.16
published results with antimitotics, such as 5- Nearly every author cautions about the need for
Fluorouracil and mitomycin, are encouraging, and will intensive postsurgical management. This is a major
further decrease the need for seton surgery.25,26 reason why, in remote areas, ADDs should not be
ADDs are indicated in patients with elevated intra- considered as a primary procedure.
ocular pressure or progressive disk damage or field
loss despite maximally tolerated medical therapy and COMPLICATIONS
prior failure with conventional filtration surgery. Drainage device surgery is associated with a high rate
ADDs are used in primary open angle, close angle, of complications. This is in part due to the severity of
glaucoma and poor prognosis that these patients have tube to the episclera. Late erosion of either the tube or
to begin with. the episcleral exoplant can occur. Melting of the scleral
Intraoperative complications include perforation flap or the scleral patch graft results in the tube being
and exposure of uveal tissue during fixation of the covered only with the conjunctiva. The episcleral
implant to the sclera or during dissection of the scleral exoplant can erode either externally through the
flap, especially in eyes that have been operated on conjunctiva or internally through the sclera (Fig. 81.6).
several times previously. Complications can arise Epithelial ingrowth may result from the insertion
during the insertion of the tube. If the entry is too of the anterior chamber tube through a corneal wound.
posterior, ciliary body bleeding and vitreous loss can Similar to standard filtration surgery, other late
occur. If the entry incision is too large, there can be complications that can occur include choroidal
leakage around the tube with creation of a limbal bleb. effusion, choroidal hemorrhage, pupillary block
If the needle track is not parallel to the plane of the glaucoma, malignant glaucoma, infection, endo-
iris, kinking of the tube may result, with subsequent phthalmitis,31 retinal detachment, and phthisis bulbi
tube-cornea or tube-iris contact. (Fig. 81.7).
As in standard filtering surgery, other potential
intraoperative complications include hyphema, supra-
choroidal hemorrhage or expulsive, and vitreous
hemorrhage.
The most common postoperative complication is
excess flow through the drainage device. This occurs
early postoperatively, before encapsulation around the
exoplant occurs. The excess flow results in a flat
anterior chamber, prolonged hypotony, and choroidal
detachment. Drainage of the choroidal detachment
and reformation of the anterior chamber are parti-
cularly indicated if there is lenticulocorneal touch. This
complication is seen less frequently with valved
devices or where temporary occlusion of the tube
lumen has been affected.
The tube can touch the corneal endothelium and Fig. 81.6: An extruded Molteno implant following trauma. Note
can cause localized corneal edema or corneal how the episcleral implant has shifted forward and is eroding
decompensation. If it is away from the optical axis, it through the conjunctiva
usually does not affect the visual acuity. However,
diffuse corneal edema and bullous keratopathy may
develop. Incidence of tube-corneal touch may be
lowered by using a scleral patch graft instead of a
scleral flap,11 and also by having a longer corneal
intralamellar tract through which the tube is placed.
Tube-lens touch may be associated with cataract and
tube-IOL touch associated with dislocation of IOL.
Postoperative intraocular inflammation is fre-
quently intense in these patients. Patients should be
placed on frequent topical steroids. Occasionally,
systemic steroids are required.
The open-end of the anterior chamber tube can be
blocked with fibrin, blood, vitreous, or iris tissue. The
Argon or Nd: YAG laser can be used to free the
opening of debris or tissue or retract the iris from the
tube opening.30
Posterior migration of the tube out of the anterior Fig. 81.7: Retroillumination of a Molteno implant in a patient
chamber can result from inadequate anchoring of the with aniridia (Courtesy: Prof. Frank Billson)
SUMMARY 16. Billson F, Thomas R, Alward W. The use of two-stage Molteno

implants in developmental glaucoma. J Pediatr Ophthalmol
Modern artificial drainage devices (ADDs) have been Strabismus 1989;26:3.
effectively used in difficult glaucomas since early 17. Heuer DK, Abrams DA, Baerveldt D et al. Randomised
1970s, and are a valuable addition to the arma- clinical trial of single and double plate Molteno implants in
patients with poor clinical prognosis. Invest Ophthal Vis Sci
mentarium of the glaucoma surgeon. However,
1989;30:282.
although the results with ADDs are encouraging, they 18. Schocket SS. Investigations of the reasons for success and
should be reserved for eyes with extremely poor failure in the anterior shunt-to-the-encircling band procedure
surgical prognosis. in the treatment of refractory glaucoma. Trans Am Ophthal-
mol Soc 1986;84:743.
19. Schocket SS, Lakhanpal V, Richards RD. Anterior chamber
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glaucoma. Am J Ophthalmol 1975;79:831. 20. Schocket SS, Nirankari, VS Lakhanpal V et al. Anterior
2. Rollet M. Traitment de 1’hypopyon par le drainage capillarie chamber tube shunt to an encircling band in the treatment of
de la chambre antericeure. Rev Gen Ophthal 1906;25:481. neovascular glaucoma and other refractory glaucomas: A
3. Mayou MS. An operation for glaucoma: A preliminary report. long-term study. Ophthalmol 1985;92:553.
Ophthalmoscope 1912;10:254. 21. Krupin T, Podos SM, Newkrik JB. Valve implants in filtering
4. Zorab A. The reduction of tension in chronic glaucoma. surgery: A preliminary report. Am J Ophthalmol 1976;81:232.
Ophthalmoscope 1912;10:258. 22. Krupin T, Ritch R, Camrus CB et al. A long Krupin-Denver
5. Bock RH. Subconjunctival drainage of aqueous with a glass implant attached to a 180-degree scleral exoplant for
seton. Am J Ophthalmol 1950;33:929. glaucoma surgery. Ophthalmol 1988;95:1174.
23. Joseph NH, Sherwood MB, Trantus G. A one-piece drainage
6. Qadeer SA. Acrylic gonio-subconjunctival plates in glaucoma
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1986;105:657.
7. Krupin T, Feitl ME. Posterior tube shunt implants for
24. Hitchings RA, Joseph NH, Shepard MB et al. Use of a one-
glaucoma surgery. Semin Ophthalmology 1991;6:87.
piece valved tube and variable surface area exoplant for
8. Molteno ACB. New implant for drainage in glaucoma:
glaucoma drainage surgery. Ophthalmol 1987;94:1079.
Animal trial. Br J Ophthalmol 1969;53:161.
25. Heuer DK, Parrish RK, Gressel MG et al. 5-Fluorouracil and
9. Molten ACB. New implant for drainage in glaucoma: Clinical glaucoma filtering surgery, intermediate follow-up a pilot
trial. Br J Ophthalmol 1969;53:606. study. Ophthalmol 1986;93:1537.
10. Molteno ACB. New implant for glaucoma clinical trial. Br J 26. Ozdamar A, Aras C, Karakorlu M. Suprachroidal seton
Ophthalmol 1971;53:606. implantationin refractory glaucoma. A novel surgical
11. Freedman J. Scleral patch grafts with Molteno setons. Ophthal technique. J of Glaucoma 2003;12:354.
Surg 1987;18:532. 27. Melamed S, Fiore PM. Molteno implant surgery in refractory
12. Molteno ACB, Bevin TH, Herterson P et al. Glaucoma surgery glaucomas. Surv Ophthalmol 1990;34:441.
outcome Study: Long term followup cases of primary 28. Krupin T, Kaufman P, Mandell A et al. Filtering valve implant
glaucoma with additional risk factors drained by Molteno for eyes with neovascular glaucoma. Am J Ophthalmol
implants. Ophthalmology. 2001;108:2193. 1980;89:338.
13. Traverso CE, Tomey FK, Al-Kaff A. The Molteno draining 29. Munoz M, Tomey KF, Traverso C et al. Clinical experience
implant for the management of complicated glaucoma cases. with the Molteno implant in advanced infantile glaucoma. J
Ophthalmol (Suppl) 1987;94:80. Pediatr Ophthalmol Strabismus 1991;28:68.
14. Molteno ACB, Van Biljon G, Ancker E. Two-stage insertion 30. Fiore PM, Melamed S. Use of Neodymium: YAG laser to open
of glaucoma drainage implants. Trans Ophthalmol Soc NZ an occluded Molteno tube. Ophthal Surg 1989;20:201.
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Index
A laboratory tests 1328 treatment of dry AMD 1525
systemic findings 1326 AREDS findings 1526
A and V syndrome 901
treatment 1328 laser photocoagulation 1526
clinical features and diagnosis 903
medical therapy 1328 nutritional supplements 1525
etiology 902
Acute zonal occult outer retinopathy 1300 treatment of exudative AMD 1528
anomalies of muscle insertion 903
Adamantiades-Behcet’s disease 1320 alternative treatments 1529
combined patterns 903
Adenocarcinoma of lacrimal gland 656 feeder vessel photocoagulation 1530
horizontal school of urist 902
Adenoma 963 low vision aids 1531
vertical school 902
Adenoma sebaceum 661 pharmacologic intervention 1530
treatment 903
Adie’s syndrome 954 photodynamic therapy 1528
A mass in the orbit 675
Adnexal and anterior segment lesions in radiation therapy 1529
Abducens palsy of childhood 984
AIDS 1136 retinal translocation 1530
Aberrant regeneration 981
Adrenergic agonists 569 surgical removal of CNV 1530
Abnormal/anomalous retinal
nonselective alpha-adrenergic thermal laser treatment 1528
correspondence 880
agonists 569 transpupillary thermotherapy 1529
detection 881
dipivefrin hydrochloride 570 Albinism 819
harmonious 880
epinephrine 569 causes 819
treatment 882
selective alpha-adrenergic agonists 570 clinical classification 819
unharmonious 881
apraclonidine 571 heredity 820
AC/A ratio 876, 886
brimoniline 571 management 820
Acanthameba keratitis 165, 168, 169, 176,
clonidine 570 Alkaptonuria 821
1246
Adrenergic blocking agents 571 Allergic conjunctivitis 90
Accessioning system 181
beta-blockers 572 seasonal allergic 91
Accessory lacrimal glands 62
intrinsic sympathomimetic activity 572 clinical features 91
Accommodation 959
betaxolol 573 management 91
Accommodative esotropia 889
carteolol 573 Allergic granulomatous angitis 1224
acquired nonaccommodative 895
levobunolol 573 Alloplastic refractive keratoplasty 277
essential infantile 893
timolol 572 Alport’s syndrome 778
hypoaccommodative 891
Affinity membrane test 86 Alzheimer’s syndrome 978
nonrefractive accommodative 890
After image test 876 Amacrine cells 1439
partial accommodative 892
Age-related macular degeneration 1151, Amblyopia 744
refractive accommodative 889
1477, 1491, 1517, 1521, 1761 fixation pattern 745
Accommodative intraocular lenses 342
aging changes in RPE and Bruch’s pathogenesis 746
Acidophil adenoma 963
membrane 1522 straight eye 744
Acquired immunodeficiency syndrome
(ICG) and (FFA) 1524 treatment 747
1127, 1337
classic CNV 1524 CAM 749
Acquired retinoschisis 1562
classification 1523 occlusion 747
Acral lentigo maligna 53
clinical features 1523 visual acuity 746
Actinic keratosis 49
occult CNV 1524 with squint 745
Acute chemical burns 1175
animal models 1534 Amblyopia 803, 882
Acute disseminated encephalomyelitis
future directions 1532 CAM treatment 885
977
gene therapy 1532 fixation pattern 884
Acute epidemic hemorrhagic
photoreceptor cell transplantation squint 883
conjunctivitis 74
1532 straight-eye amblyopia 883
Acute posterior multifocal placoid
RPE transplantation 1532 Amblyoscope 875
pigment epitheliopathy 1298
genetic basis 1534 Amebiasis 1216
Acute retinal necrosis syndrome
microelectronic visual implants 1533 Amniotic membrane 1169
1130, 1292, 1325
cortical implants 1533 embryology, anatomy, physiology
clinical features 1325
epiretinal implants 1533 and histopathology 1169
complication 1326
subretinal implants 1522 functions 1170
differential diagnosis 1327
molecular basis 1534 tissue harvesting and use 1170
etiology 1327
prevalence 1521 transplantation 1171
histopathology 1328
risk factors 1522 clinical uses 1171
investigations for diagnosis 1327
1806 Modern Ophthalmology
glue application 1173 Argyll robertson pupil 955, 960 Benign 730
identification of epithelial surface Arteriosclerosis 1599 Benign mixed tumor 730
1172 Artificial drainage devices 618 Berger’s space 316
indications and surgical procedures classification 618 Bezold-Burcke effect 1144
1172 Ahmed glaucoma valve 621 Bifocals 920
limbal autograft transplantation Baerveldt implant 621 Bimatoprost 584
1173 Joseph-Hitchings valve implant 621 Biometry 522
persistent epithelial defect 1173, Krupin-Denver valve implant 621 Biostatistics 1092
1175 Molteno implant 619 analysis of variance 1099
preparation and preservation 1171 posterior tube shunt implants 618 arithmetic mean or average 1093
repair of leaking filtering bleb 1174 Schocket procedure 621 central tendency 1093
surgical technique 1172 complications 622 clinical significance 1097
Amniotic membrane transplantation indications for use 622 coefficient of variation 1094
1213, 1182 Ascorbic acid 1230 computer programs 1099
surgical procedure 1183 Asepsis or antisepsis 1121 correlation 1094
Amyloidosis 1225 Ash leaf spots 661 correlation coefficient 1095
Anesthesia for cataract surgery 361 Associated with ocular anomalies 761 dispersion 1094
regional 361 Associated with systemic anomalies 761 estimation 1096
Aneurysms 697, 698, 1004 differential diagnosis 761 hypothesis 1096
circle of willis 1005 treatment 762 inferential statistics 1096
internal carotid artery 1005 Astigmatic keratotomy 159 large sample tests 1098
ophthalmic artery 1005 clinical features 166 median 1093
Angiomatosis retinae 664 Astrocytes 1440 mode 1094
clinical picture 664 Astrocytic hamartomas 662 multiple regression analysis 1096
pathology 665 Asymptomatic narrow angles 534 non-parametric tests 1099
systemic features 665 Ataxia-telangiectasia 670 null hypothesis 1097
treatment 666 Atypical dry eye syndromes 106 paired ‘t’ test 1098
Angiosarcoma 55 Augmented surgical formula 892 regression analysis 1095
Angle of deviation and face turn 869 Automated perimetry 515 sampling distribution 1096
Angle of the anterior chamber 468 instrumentation 515 scale of measurement 1093
Aniridia 325, 477, 537, 765, 811 interpretation of results 516 scatter diagram 1095
clinical findings 766 recent advances 519 small sample tests 1098
management 766 testing strategies 515 standard deviation 1094
Anisocoria 961 Axenfeld syndrome 478 statistical methods 1099
Ankyloblepharon 6 Axenfeld-Rieger syndrome 766 statistical significance 1097
Ankylosing spondylitis 1223, 1269, 1372 extraocular features 767 student’s ‘t’-test 1098
Anomaloscope 1147 histopathological features 767 tests of significance 1097
Anophthalmos/microphthalmos 1033 management 768 variables 1092
Anterior chamber 333 ocular features 767 X2-test 1098
Anterior chamber paracentesis 1386 Birdshot retinochoroidopathy 1296
Anterior optic neuritis 973 B Bitot’s spot 753
Anterior segment ischemia 1735 Bacillary dysentery 1215 Bleb failure 599
Anterior staphyloma 134 Bacterial keratitis 165 Bleb-related problems 608
Anterior stromal infiltrates 209 Bacterial keratitis 166 encapsulated 613
Anterior uveitis 543, 584, 1138, 1222, 1268, Bacterial keratitis 173 management 614
1313, 1321, 1372 Bag sulcus fixation 358 failing bleb 611
management 1374 Bagolini lens 873 early 612
Antiglaucoma drugs 566 Balanced salt solution/saline 1756 late 613
Antimetabolites 597 Balloon catheter dilatation 714 prevention and management 612
Antimicrobial susceptibility testing 188 Balloon catheter dilatation 723 infection 615
Antiretroviral therapy 1140 Band shaped keratopathy 1175 clinical features 615
Antithyroid antibodies 703 Bandage contact lens 1211 management 615
Aqueous TAP 1422 Bangerter pleoptophore 746 prevention 616
Arcuate scotoma 969 Barraquer tonometer 296 leakage 610
Arcus senills 220 Basal cell clinical findings 610
Argemon mexicana 536 carcinoma 49 management 610
Argon laser closure of cyclodialysis cleft nevus syndrome 669 overfiltration 609
594 Basophil adenoma 963 clinical features 609
Argon laser trabeculoplasty 565, 588 Behcet’s disease 1377 management 609
Argon-laser suturelysis 593 Behcet’s syndrome 1223 symptomatic 614
Index 1807
management 614 Burkitt’s lymphoma 648 small incision 336
Blepharitis 17 ultra-small incision 338
classification 17 C Cavernous hemangiomas 55
anterior 18 Calcification in a phthisical eye 638 Cavernous sinus 985
clinical features 19 CAM visual stimultor 923 Cavernous sinus syndrome 967
differential diagnosis 20 Canalicular laceration 715, 716, 718 Cecocentral scotoma 969
management 20 Canalicular obstruction 718 Central corneal thickness 481
pathogenesis 18 Canaliculitis 184 Central retinal artery occlusion 1579
Blepharitis 32, 183 Canaliculodacryocystorhinostomy associated diseases 1581
Blepharochalasis 57 717, 722 management 1581
Blepharoconjunctivitis 106 Candidriasis 1296 ocular investigations 1580
Blepharophimosis 5 Capillary hemangioma 54 pathophysiologic mechanisms 1581
Blood supply of the visual pathways 946 Capillary hemangioma 830 signs 1579
Blood-retinal barrier 1440 Capsid 1324 Central retinal vein occlusion 1584
Blue cone monochromatism 1115 Capsular bag distension syndrome clinical characteristics 1585
Bony orbit 625 359, 460 electroretinography (ERG) 1586
apex 627 Capsular bag opacification 799 fundus fluorescein angiography
base 627 Capsular bag syndrome 410 (FFA) 1586
size, shape, and relations 625 Capsular block syndrome 460 newer techniques 1587
walls 626 Capsular contracture syndrome 359 ocular neovascularization 1587
inferior orbital 626 Capsular tension ring 398, 814 ophthalmoscopy 1586
lateral wall 626 Capsulopalpebral fascia 928 perimetry 1586
medial 626 Capsulorhexis 599 relative afferent pupillary defect
roof 627 Capsulotomy 380 1586
Bony orbits 629, 1024 Carbonic anhydrase inhibitor 574 visual acuity 1585
apertures at the base 630 oral 574 demographic characteristics 1584
fat and reticular tissue 630 topical 575 management 1589
globe 1025 Carotenoids and tocopherol 1229 laser photocoagulation 1590
retrobulbar space 1025 Caroticocavernous fistula 1007 medical therapies 1589
surgical spaces 629 Carotid artery imaging 1785 natural course and complications 1588
central 629 Carotid artery insufficiency 543 pathogenesis 1584
peripheral orbital 629 Carotid cavernous fistula 1050 systemic diseases 1589
sub tenon’s 629 Caruncle 64 Central retinal vein occlusion 1760
subperiosteal 629 Catalytic RNA 1106 Central scotoma 969
Botulinum toxin 922 Cataract 327 Central serous chorioretinitis 1358
Bourneville disease 660 biochemical changes 330 Central serous chorioretinopathy 1493
Boutonneuse (marseilles) fever 1341 classification 327 Central serous chorioretinopathy 1772
Bowen’s disease 111 cuneiform opacities 327 associated fundus finding 1775
Bowen’s disease 124 cupuliform 328 differential diagnosis 1776
Bowen’s disease perinuclear variety 328 general types 1772
(intraepithelial epithelioma) 49 definition 327 pathogenesis 1776
Bowman’s membrane 132 etiopathogenesis 329 treatment 1777
Brain stem 985 environmental factors 329 Central serous retinopathy 1761
Branch retinal artery occlusion 1582 other factors 330 Cephaloceles 825, 1036
Branch retinal vein occlusion 1591, 1761 personal factors 329 Chalazion (meibomian cyst) 30
associations 1594 formation 327 Chediak Higashi syndrome 820
clinical features 1591 medical therapy 330 Chemical trauma 231
complications 1593 aldose reductase inhibitors 331 evolution of tissue injury 234
management 1595 antioxidants 330 pathomechanism 233
laser photocoagulation 1595 Cataract 776, 861 treatment 236
medical 1595 anterior polar 77 surgical 238
ophthalmoscopic features and blue dot 776 Chemosis 68
fluoriscein angiography 1592 congenital 776 Chicken eyes 752
Brown syndrome 914 coronary 777 Chickenpox 1333
clinical features posterior polar 777 Chlamydia trachomatis 76
differential diagnosis 915 virus induced 778 Cholera 1216
management 915 zonular 777 Cholinergic drugs 567
Bruch’s membrane 1251 Cataract in post-trabeculectomy eyes 399 anticholinesterases 568
Bullous central serous chorioretinopathy Cataract surgery 336 demecarium bromide 569
1773 large incision 336
echothiophate effect of scarring 78 Collagen 1220
(phospholine iodide) 568 McCallans 77 Collagen shield 1211
isoflurophate 569 treatment 79 Collection of samples 182
physostigmine (eserine) 569 Clinical features 24 Collector channels 471
parasympathomimetics 567 Clinical pathology 525 Coloboma 1032, 775
carbachol 568 clinical types and features 529 Coloboma of lid 5
pilocarpine 567 acute 530 Color vision 1144
Chorioretinal biopsy 1427 chronic 530 anatomy 1146
external approach 1427 creeping 530 factors affecting 1144
internal/endoretinal approach 1428 intermittent 529 retinal distribution 1144
Chorioretinal inflammation 1559 subacute 530 testing 1146
Choroid 1251 epidemiology 526 theories 1145
Choroidal coloboma 1564 management 531 Communications with the orbit 1011
Choroidal detachment 1352, 1735 long-term 533 Compensatory head posture 864
anatomy 1352 medical 531 Compressive optic neuropathy 1003
clinical features 1353 physical 532 Computerized tomography 1020, 1028
etiology 1353 supportive 532 Computerized tomography scanning 639
investigations 1354 special methods of examination 527 Concussion injury 548
treatment 1355 gonioscopy 528 Condensing lenses 1445, 1554
Choroidal effusion 552 peripheral ac depth 527 Confocal laser scanning 510
Choroidal hemangioma 667, 1034, 1414, primary angle closure laser ophthalmoscopy 487
1763 (glaucoma) suspect 527 Congenital aphakia 775
circumscribed 1414 provocative tests 528 Congenital stationary 1113
clinical features 1414 clinical use of 1089 Conjugation 203
diagnosis 1415 cataract surgery 1089 Conjunctiva 61, 1013
differential diagnosis 1416 ECCE 1089 anatomy 61
management 1416 extraocular surgery 1090 arteries 63
photocoagulation 1416 glaucoma 1089 epithelium 63
diffuse 1416 ICCE 1089 lymphatics 64
clinical features 1417 keratoplasty nerve supply 64
diagnosis 1417 membrane surgery 1090 veins 64
management 1417 postoperative period 1090 wound healing and inflammation 63
pathology 1417 retinal surgery 1090 Conjunctiva-tenonplasty 239
Choroidal hemorrhage 1410, 1751 trauma 1090 Conjunctival diseases 66
Choroidal melanoma 1764 vitreous loss 1090 acquired pigmentation 70
Choroidal neovascular membrane 1777 Clivus ridge syndrome 1007 angular conjunctivitis 68
Choroidal neovascularization 1153 CMV retinitis 1294, 1668 chronic 75
classic 1153 clinical features 1668 concretions 68
combined 1154 management 1669 discharge 66
occult 1153 treatment 1669 edema 68
polypoidal 1154 anti CMV therapy 1671 follicles 67
recurrent 1156 immune reconstitution therapy follicular 71
classic 1157 1672 acute 71
occult 1157 prophylaxis 1672 chronic 74
Choroidal nevi 1410 toxic effects of anti CMV therapy hyperemia 67
Choroideremia 1114 1672 lymphadenopathy 69
Chromophobe adenoma 963 Coats’ disease 835, 853, 1031, 1653, 1763, membrane formations 67
Chronic chiasmal arachnoiditis 962 1681 nodule at limbus 68
Cicatrization 842 clinical presentation 1682 papilla 67
Cilia 2 demographics 1681 phlyctenular keratoconjunctitivis 68
Ciliary body 1250 diagnosis and ancillary testing 1684 pigmentations 69
Ciliary body band 475, 478 differential diagnosis 1684 subconjunctival hemorrhage 69
Ciliary muscles 1251 etiology 1681 ulcers 68
Cilioretinal artery occlusion 1582, 1588 histopathology 1683 Conjunctival flap 1212
Cinematography 728 management 1684 Conjunctival flap 597
City university color vision test 1147 pathophysiology 1681 Conjunctival glands 62
Classification 76 prognosis 1686 Conjunctival graft 1212
clinical picture 77 systemic association 1684 Conjunctival hyperemia 584
diagnosis 78 Cogan’s syndrome 1224, 987 Conjunctival impression cytology 103
Index 1809
Conjunctival impression cytology 1083 undesirable effects 1245 clinical patterns 1210
Conjunctival limbal autograft 1183 Contents of orbit 1011 management of acute epithelial defect
Conjunctival scraping 103 Continuous curvilinear capsulorhexis 370 1210
Conjunctival squamous cell carcinoma Contrast orbitography 643 contact lens/capping 1211
1137 Contrast sensitivity 426 medical 1210
Conjunctivitis 71, 80, 183 Contrast sensitivity and glare 333 surgical 1211
acute catarrhal 80 Conventional extracapsular microanatomy 1208
acute purulent 80 cataract surgery 407 Corneal esthesiometry 144
chronic catarrhal 80 Core biposy 644 Corneal grafting 128
membranous and pseudomembranous Cornea 1222, 333 congenital abnormalities 133
81 Cornea and ocular surface disorders 1063 cornea 131
phlyctenular kerato 81 Cornea farinata 219 development 132
clinical manifestations 81 Cornea plana 134 methods of examination 137
differential diagnosis 82 Corneal clouding 1735 role of vital dyes 141
signs 81 Corneal degenerations microanatomy 132
symptoms 81 endothelial dystrophies 217 Bowman’s membrane 132
Conjunctivodacryocystorhinostomy 722 corneal guttata 217 endothelium 132, 133
Connective tissue 1220 Fuchs’ dystrophy 217 posterior elastic membrane 132
Connective tissue disorders 1221 keratoglobus 218 substantia propria 132
acquired generalized disorders 1225 posterior polymorphous dystrophy pigmentation 134
acquired systemic metabolic disorder 218 copper 135
1225 epithelial and Bowman’s 213 gold 135
hereditary generalized disorder 1226 locational 219 iron 134
ocular manifestations 1222 central 219 melanin 135
Conradi syndrome 811 peripheral 220 silver 135
Constriction of pupil 406 membrane dystrophies 213 Corneal mucous plaques 209
Contact hypersensitivity 97 anterior crocodile shagreen or Corneal opacity 861
Contact lens 287 anterior mosaic dystrophy of vogt 215 Corneal opacity leucoma 134
Contact lens fitting 156, 157 band-shaped corneal opacity 214 Corneal scrapings 169
Contact lenses 1234 dystrophic recurrent erosion 215 Corneal sensitivity 144, 956
contraindications 1238 epithelial and Bowman’s 213 Corneal stem cell diseases 299
fitting of lens 1239 membrane dystrophies 213 possible stem cells diseases 300
evaluation of fit 1243 reis-buckler’s dystrophy 215 probable stem cell diseases 300
external examination 1239 stromal dystrophies 215 treatment 301
fitting procedures 1240 central crystalline dystrophy autogenous stem cell
insertion and removal of lens 1242 (schnelder’s crystalline transplantation 301
wearing schedule 1242 dystrophy) 216 bulbar conjunctival transplantation
indications 1236 fleck dystrophy speckeled 301
cosmetic 1238 dystrophy of francois corneal stem cell
diagnostic 1238 and neetens) 217 autotransplantation 301
occupational 1238 gelatinous drop like dystrophy 216 corneal stem cell
optical 1236 granular dystrophy-groenouw’s homotransplantation 301
therapeutic 1237 type I: (Bread-crumb dystrophy) transplantation of cultured corneal
materials used 1235 215 Limbal stem cells 302
glyceryl methacrylate lattice dystrophy unequivocal corneal stem cell loss 299
(GMA) polymers 1235 (biber-haab-dimmer) 216 Corneal suction ring 296
HEMA cross-linked with EGDMA macular dystrophy (groenouw II) Corneal topography 154, 288
1235 216 Corneal transplantation 1188
HEMA-PGMA copolymers 1236 Corneal diseases 156 complications 1189
polyelectrolyte complexes 1236 Corneal dystrophies 254 immunosuppression 1188
polymethyl methacrylate 1235 Corneal edema 798, 1751, 1789 Corneal ulcer 161
soft hydrophilic materials 1235 Corneal endothelium 150 diagnosis 169
optical principles 1234 Corneal epithelial dysplasia 1203 interpretation of cultures 171
types 1242 Corneal epithelial stem cells 1180 interpretation of smears 170
bifocal 1242 Corneal epithelium 1179, 1208 techniques 172
disposible 1247 examination 1208 etiologic factors 163
extended wear 1247 planimetry 1209 fungi 164
oxygen permeability 1243 slit lamp examination 1209 infective 163
rigid gas permeable scleral 1243 functions 1208 protozoa 164
soft 1242 healing 1209 viruses 164
pathogenesis 161 Cytomegalovirus (CMV) retinitis 1129 nephropathy 1606
histopathology and stages 161 retinal detachment 1130 pregnancy 1606
mechanisms 162 systemic hypertension 1606
risk factors 165 D Diabetic retinopathy 1759
treatment 173 Dacryoadenitis 105 Diagnostic vitrectomy 1424
medical 173 Dacryoadenitis 731 Diffractive multifocal lenses 424
surgical 178 Dacryocystectomy 724 Diffuse congenital hemangiomatosis 669
types 162 Dacryocystitis 184, 718 Diffuse large B cell lymphomas 648
acanthameba 163 Dacryocystography 712, 726 Diffuse subretinal fibrosis 1297
bacterial 162 radiography in operated cases of Diplopia 633, 684, 685, 879, 940, 949, 1736
fungal 163 sac 728 Direct goniotomy 763
herpes simplex ocular 162 techniques 727 Disciform keratitis 209
Corneal ulceration/keratomalacia 753 types 726 Dislocated nucleus 1788
Corneal xerosis 753, 754 Dacryocystorhinostomy 719 incidence 1788
Cortical cleaving 371 Dacryops or ductal cyst 730 laser tissue interactions 1793
Corticosteroids 94, 282 Dacryoscintigraphy 728 light absorption 1794
Cotton-wool spots 1583 Dalen-Fuchs nodules 1316, 1380 problems of retained lens matter 1788
Cover test 952 Decentration of an iol 801 risk factors 1788
Craniopharyngioma 964 Decompensation 466 role of the primary surgeon 1789
criteria for selection of material 1086 Degenerative myopia 1656 thermal effects 1794
Crouzon’s syndrome 811 histopathology 1656 chorioretinal photocoagulation
Cryotherapy 7 ocular manifestations 1656 1795
Cryptococcosis 657 pathogenesis 1656 grading of photocoagulation burns
Cryptophthalmos 6 treatment 1662 1795
Crystalline lens 1703 Dehiscence of orbital bones 638 photodynamic therapy (PDT) 1796
Crystalline lens 774 Demyelinating diseases 974 vascular photocoagulation 1796
congenital abnormalities 775 Depth of focus 426 timing of pars plana vitrectomy 1790
structure 774 Dermal eruption 211 complications of pars 1791
Cultivated limbal 1187 Dermatitis 33 Dislocations 465
Cultivated limbal transplant rejection Dermatome 1334 Disorders of visual integration 991
1190 Dermatomyositis 1224 Displacement of lens 324
Culture methods 186 Dermoid cyst 731 Displacement of lens 539, 949
anaerobic 187 Dermoid/epidermoid 1035 Distichiasis 7
bacterial 186 Dermoid/epidermoid cyst 824 Diurnal variation of IOP 483
fungal 186 Dermoids 123 DNA testing 1101
mycobacterial 187 Descemet’s membrane 132 Dominant behr optic neuropathy 1002
viral 187 Descemet’s membrane detachment 357 Donor cornea 255
Cutaneous horn 49 Diabetes mellitus 481 Donor corneal rims 184
Cyclic oculomotor palsy 982 Diabetic retinopathy 1605 Double elevator palsy 906
Cyclocryotherapy 301 clinical features 1607 classification 906
Cyclophotocoagulation 590 nonproliferative 1607 clinical characteristics 906
Cycloplegic refraction 877 proliferative 1609 differential diagnosis 907
Cyclosporine 94 genetic factors 1607 Double eye pads and bandage 1211
Cystic swellings 640 management 1612 Driving ability 428
Cystic tumors 824 antiplatelet therapy 1613 Dry eye 102, 299
differential diagnosis 825 focal photocoagulation 1616 Dry eye syndromes 105
Cysticercosis 1218 laser photocoagulation 1613 Duane’s retraction syndrome 984
Cystinosis 820 laser treatment 1617 Duane’s retraction syndrome (Stilling-
Cystoid macular edema 467, 584, 803, lipid reduction 1613 Turk-Duane’s syndrome) 912
1735, 1789 medical treatment 1612 treatment 914
Cytology 113 panretinal photocoagulation 1614 Ductions and versions 867
Cytomegalovirus 1329 peripheral retinal cryoablation 1617 Dysplastic nevus syndrome 53
clinical features 1330 vitrectomy 1618 Dystrophies 265
differential diagnosis 1330 risk factors 1605
histopathology 1331 age 1605 E
laboratory investigations 1331 control of blood glucose levels 1605 Eales’ disease 1653, 1675, 1761
route of transmission 1329 duration of diabetes 1605 clinical features 1675
treatment 1331 promptness of referral 1606 etiopathogenesis 1677
ganciclovir 1332 systemic factors 1606 immunological studies 1677
Index 1811
pathology 1678 bleb-associated 1539 clinical features 1689
management 1678 chronic 1539 complications 1691
anterior retinal cryotherapy 1678 traumatic 1540 etiology 1689
corticosteroids 1678 clinical diagnosis 1540 management 1690
photocoagulation 1678 complications 446 pathology 1690
vitrectomy 1679 endogenous 1306 surgical technique 1690
signs 1675 fungal 1306 Epiretinal membrane 1476, 1559, 1594,
inflammation 1675 fungal 1309 1779
macular changes 1676 late 464 treatment 1780
neovascularization 1676 management 1543 types and causes 1779
nonperfusion 1675 antibiotics 1544 Episcleral osseous choristoma 123
Ectopia lentis 1226 corticosteroids 1545 Episcleritis 307, 1222
Ectopia lentis 808 intravitreal drug injection 1545 Epitarsus 65
Ectopia lentis et pupillae 775 vitrectomy 1546 Epithelial cysts 63
Ectopia lenus et pupillae 323 medical treatment 443 Epithelial tumors 123
Ectropion 12 antibiotics 445 Epitheliopathy 102
Ehler-Danlos syndrome 136, 324, 811, 823, corticosteroids 445 Epithelium transplantation 1187
1226 microbiological diagnosis 1540 cultivation of epithelia 1188
Elastin 1220 antimicrobial susceptibility testing current status 1188
Electro-nystagmography (ENG) 861 1543 immunosuppression 1188
Electrolysis 7 culture 1542 transplantation 1188
Electron microscopy 88, 186, 1199, 1206 microscopy 1540 Epstein-Barr virus 1336
Electrooculogram 1455 molecular diagnosis 1543 Erythema multiforme 300
clinical measurement 1456 vitreous biopsy 1542 Erythema multiforme major (Stevens-
clinical uses 1456 postoperative management 445 Johnson syndrome) 83
fast oscillations of EOG 1457 surgical treatment 444 Erythema nodosum 1225
limitations of EOG recording 1457 treatment 1549 Esodeviations 889
Electroretinogram 1457 vitrectomy study 446, 1548 Esophoria 887
clinical protocol 1459 Endoscopic biopsy 644 Esotropia 984
clinical uses 1461 Endoscopic nasal lacrimal surgery 723 Essential blepharospasm 57
ERG measurements and recording Endothelial cell density 151 Euryblepharon 5
1460 Endothelitis 202 Ewing’s tumor 829
flash stimulus characteristics 1458 Enophthalmos 674, 684, 685 Excision biopsy 1428
ground electrodes 1458 Entropion 8 anterior segment tumors 1428
origin of 5 basic ERG waveforms 1460 cicatricial 10 external approach 1428
pediatric ERG recording 1460 cicatricial 14 internal approach 1429
recording electrodes 1457 congenital 8, 12 posterior segment tumors 1429
reference electrodes 1458 mechanical 16 external approach 1429
Electroretinography 1147, 1785 paralytic 14 internal approach 1429
Embryology of eyeball 1019 senile (involutional/atonic) 8 Excisional biopsy 644
Embryotoxon 134 senile or involutional 12 Exfoliative cytology 1205
Emphysema 684 spastic 8 Exodeviation 898
Empty Sella syndrome 964 Entropion surgery 1174 classification 898
Encephalitis periaxialis diffusa 977 Enucleation 1432 definition 898
Encephalofacial angiomatosis 667 Enzymatic vitrectomy 1630 etiology 898
clinical features 667 Enzyme-linked immunoabsorbent assay Exophoria 887
cutaneous involvement 668 203, 1385 Exophthalmometers 636
ocular involvement 667 Eosinophilic granuloma 651 Exophthalmometry (proptometry) 635
visceral involvement 668 Epiblepharon 4 Exophthalmos 702
treatment 668 Epicanthal folds 4 Exposure keratitis 58
Endocapsular ring 398 Epicapsular star 775 Exposure keratopathy 209
Endogenous fungal endophthalmitis 1296 Epidemic dropsy 1219 External examination of the eye 950
Endolaser 1710 Epidemic dropsy glaucoma 536 Extracapsular cataract extraction 367
Endophthalmitis 183, 359, 412, 442, 464, Epidemic keratoconjunctivitis 72 cortex removal 372
600, 799, 833, 1291, 1305, 1539, 1703, Epidemic typhus 1341 nucleus removal 372
1751 Epikeratophakia 276 preoperative evaluation 367
acute bacterial 1308 Epikeratophakia 784 fundus evaluation 368
chronic bacterial 1309 Epikeratoplasty 272 IOL power calculation 368
classification 1539 Epilation 7 refraction and visual acuity 368
acute postoperative 1539 Epimacular proliferation 1689
slit-lamp biomicroscope clinical features 1651 Fluorescence microscopy 185
examination 368 stage 1 1651 Fluorescent treponemal antibody-
special tests 368 stage 2 1651 absorption 1386
tonometry 368 stage 3 1653 Fluorophotometry 143
surgical techniques 369 diagnosis 1653 Flying spot 291
anesthesia 369 etiology 1650 Focal macular ERG 1471
anterior capsulotomy 369 histopathology 1650 Foldable IOLs 352
corneoscleral incision 369 inheritance 1651 accommodating intraocular 355
hydroprocedure 371 management 1654 aniridia 356
incision 369 platelet abnormalities 1651 blue light-filtering 357
Extraocular lesions 1035 Familial exudative vitreoretinopathy 835 collamer 353
congenital and developmental Familial exudative vitreoretinopathy 852 laser adjustable 355
conditions 1035 Familial exudative vitreoretinopathy multifocal intraocular 354
inflammatory conditions 1037 (FEVR) 1565 diffractive 354
neoplasms 1041 Farnsworth 100-hue test 1147 refractive 354
Exudative retinal detachment 1564 Farnsworth D-15 1147 negative spherical 357
Eye and adnexa 332 Fascia lata 1730 phakic 352
Eye bank 242 Fassanella servat operation 40 piggyback intraocular 355
cornea preservation 248 Fassanella servat surgery 41 smart lens 352
tissue media preservation 249 Fellucid marginal degeneration 220 suture-free 353
equipment 243 Ferry’s line 135 thinoptx rollable 356
organization 242 Fibrinoid necrosis 1220 toric intraocular 355
regulatory laws 243 Fibrous histiocytom 1202 with endocapsular ring design 353
strategies to enhance eye collection 243 Field changes 963 Foldable lenses 336
grief counseling 243 Field utilization device 1167 Follicles 67
legal improvement 243 Filtering bleb 465 Folliculosis 71
operational efficiency 243 Filtering blebs 608 Forced duction test 877, 926
publicity 243 Fine needle aspiration biopsy 1424 Foreign bodies 1053
structure and function 242 clear corneal approach 1426 Formation of retinal breaks 1558
tissue retrieval 244 limbal approach 1426 Foster kennedy syndrome 967
collection of blood 245 pars plana approach 1425 Freckle (ephelis) 52
donor cornea viability 246 transscleral approach 1426 Free radicals 1227
enucleation 245 Fine needle aspiration biopsy 643 defence against 1228
evaluation methods 246 Fine needle aspiration biopsy 653 pathophysiology 1228
in situ corneoscleral excision 246 complications 657 Friend test 950
preliminary procedures 244 cytological interpretation 655 Frontal gaze palsy 987
Eye bank specular microscopy 150 indications 655 Frontalis sling surgery 44
Eye tracking 290 limitations 658 Frosted branch angiitis 1132
Eyelid tumor 48 technique 653 Fuch’s heterochromic iridocyclitis 1272
epithelial 48 guidelines 654 Fuchs’ heterochromic uveitis 1362
benign 48 Fine-needle aspiration 1080 clinical features 1362
malignant 49 Flap closure 599 differential diagnosis 1363
melanocytic 52 Fleischer ring 135 etiology 1362
benign 52 Floppy eyelid syndrome 1192 HLA association 1363
glandular 53 management 1193 immunopathology 1364
malignant 53 pathology 1192 investigative procedures 1363
neurogenic 55 Floppy eyelid syndrome 58 electron microscopy 1364
vascular 54 management 59 light microscopy 1363
Eyelids 1 pathology 59 management 1364
blood supply 3 Flow cytometry 1079 ocular features 1363
development 1 Fluence test 289 pathology 1362
lymphatics 3 Fluid (vitreous, aqueous or other fluids) role of genetics 1362
nerve supply 3 cytology 1082 Functional vision 1160
structure 1 Fluid-gas exchange 1710 Functional visual loss 950
Fluorescein angiography 1359 Fundoscopy 288
F Fluorescein conjugated lectin 86, 1197 Fundus drawing 1508
Facial nerve paralysis 106 Fluorescein dye disappearance test 712 Fundus evaluation 877
Familial exudative vitreoretinopathy 1650 Fluorescein fundus angiography 1773, Fundus fluorescein angiography
attempts at grading 1651 1785 1315, 1319, 1480
Index 1813
angiographic characteristics 1482 Glands of krause 62 cavernous 1419
characteristics and uses 1480 Glare 359 ocular features 1419
characteristics of optic disk 1484 Glare control devices 1165 racemose 1420
conclusion and applications 1488 Glaucoma 263, 493, 802, 1063, 1190, 1735, Hemangiomata 125
fluorescein angiographic sequence 1788 Hemicentral retinal vein occlusion 1596
1481 Glaucoma after cataract 545 Hemolytic glaucoma 548
fluorescein solution 1481 Glaucoma filtration surgery 603 Hemorrhagic retinopathy 803
injecting the fluorescein 1481 5-fluorouracil 604 Herbert’s follicles 77
interpretation of fluorescein events in wound healing 603 Herpes simplex 199
angiography 1484 antimetabolites in glaucoma 604 Herpes simplex infection 167
autofluorescence 1484 mitomycin-C 605 Herpes simplex keratitis 265
blocked fluorescence 1486 Glaucoma in children 759 Herpes simplex virus 1332
filling defects 1486 clinical types 760 investigations 1333
hyperfluorescence 1486 examination techniques 759 ocular manifestation 1332
hypofluorescence 1486 symptoms and signs 759 aquired 1333
leakage 1485 Glaucoma in phakomatosis 769 congenital 1332
pseudofluorescence 1484 Glaucoma scope 513 treatment 1333
retrofluorescence 1486 Glaucoma surgery 1176 Herpes virus hominis 73
staining 1485 Glaucomatocyclitis crisis 1275 Herpes zoster 1274
transmission or window defect Glaucomatous optic nerve damage 485 Herpes zoster 33
1484 Glioma of the optic nerve and chiasm 965 Herpes zoster keratitis 207
monochromatic fundus photography Glomus tumor 55 Herpes zoster ophthalmicus 208, 1137,
1481 Glutathione 1231 1334
normal fluorescein angiogram 1481 Gnathostomiasis 1217 Herpes zoster ophthalmous (HZO) 175
stereoscopic fundus photography 1481 Goblet cells 62 Herpes zoster virus 1333
technique 1480 Goldmann posterior fundus contact lens Herpetic iridocyclitis 1273
Fundus fluorescein angiography 1683 1449 Hess chart 874
Fundus fluorescein angiography (FFA) Goldmann three mirror examination 1510 Heterophoria 886
1367 Goldmann three-mirror lens 1448 classification 887
Fungal infection 1136 Gonioscopy 528 etiology 886
Fungal keratitis 165, 166, 175 Goniosynechia 476 examination of phoria 887
Fungus identification 1197 Gout 1225 management 888
Fungus identification 86 Gradenigo’s syndrome 696 symptoms 887
Graft failure 266 High plus reading glasses 1165
G Graft infection 264 Highly active antiretroviral therapy 1139
Gaint retinal tears 1705 Graft rejection 264 Hirschberg’s light reflex test 869
Galactosemia 818 Granulocytic sarcoma 649 Histiocytoses 650
treatment 819 Granuloma 833, 834 Histiocytosis X 655
Ganglion cells 1439 Granulomatous uveitis 1381 Histocompatibility antigens 1607
Gaze palsy 951 Graves’ disease 700, 1039 Histopathology 1071
Gaze paresis 988 Graves’ ophthalmopathy 641 exenterated specimen 1074
Gene therapy 1647 Grid photocoagulation 1760 grossing 1072
Genetic information 1103 Ground substance 1220 corneal button 1072
genetic counseling 1103 grossing an eye 1072
genetic testing 1104 H lid biopsy 1072
Genetics 1100 Hamartias 660 immunologic and molecular
Genetics and cell biology 1648 Hamartomas 660 techniques 1077
Genital ulcers 1321 Hand-Schuller-Christian disease 651 molecular diagnostic tools 1079
Giant cell arteritis 696 Heidelberg retina tomograph 510 staining 1075
Giant papillary conjunctivitis 1193 Hemangioma 1048 electron microscopy 1075
management 1194 capillary 1049 special stains 1075
pathology 1193 cavernous 1049 tissue embedding and cutting 1075
Giant papillary conjunctivitis 1246 Hemangioma of the retina 1418 tissue fixation 1071
Giant retinal tears 1564, 1702, 1708 capillary 1418 tissue processing 1074
clinical evaluation 1708 clinical findings 1418 Histopathology 114
fellow eyes of GRT 1713 diagnosis 1418 treatment 115
surgical management 1708 differential diagnosis 1418 chemotherapy 118
Giardiasis 1216 systemic features 1419 cryotherapy 118
Gillespie’s syndrome 765 treatment 1419 immunotherapy 118
radiotherapy 118 exudative phase 1602 decontamination of OR surfaces 1124
surgical excision 117 sclerotic phase 1601 gowning and gloving 1125
HLA-B27 associated diseases 1372 vasoconstrictive phase 1601 handwashing 1121
Hodgkin’s lymphoma 650 Hypervitaminosis A 757 personnel of the OR 1124
Holladay formula 349 Hyphema 548 record keeping 1126
sources of error in iol power Hypotonic maculopathy 609 surgical scrub and skin preparation
calculation 349 Hypotony 1430 1125
a-constant error 350 Hypotony maculopathy 599 the OR environment 112
error in determination of axial Hypovitaminosis A 106 universal body substance precautions
length of the eye 350 HZV retinitis 1335 1122
error in keratometry 350 Infectious epithelial keratitis 200
Home tonometry 484 I sequelae 200
Homocystinuria 1226 Iatrogenic retinal tears 1751 Infectious keratitis 1137
Homocystinuria 323, 776, 810, 821 Idiopathic anterior uveitis 1268 Inferior orbital fissure 1012
biochemical tests 822 Idiopathic central serous Infiltrative optic neuropathy 1002
Hordeolum internum (acute meibomitis) choroidoretinopathy 1477 Inflammatory bowel disease 1270
31 Idiopathic intracranial hypertension 997 Inflammatory bowel disease 1374
HSV keratouveitis 1273 circulation of CSF 997 Inflammatory pseudotumor 731
Hudson-St hli’s line 135 diagnosis 998 Infraorbital canal 1012
Human crystalline lens 315 etiology 997 Inhibitors of collagen organization 606
dislocation or luxation 322 pathology 998 Injurious chemicals 231
etiology 322 symptoms 998 acids 232
ocular diseases causing treatment 998 acetic 233
displacement 325 surgical 999 chromic 233
traumatic displacement 325 Idiopathic juxtafoveolar retinal hydrochloric 233
growth 316 telangiectasis 1763 hydrofluoric 232
epithelial cells 318 Idiopathic polypoidal choroidal inflammation 233
lens capsule 316 vasculopathy 1493 nitric 233
substance (cortex and nucleus) 319 Idiopathic uveal effusion syndrome 1565 ocular surface damage 233
management 325 Imaging evaluation of the intracranial sulphuric 232
cataractous lens 326 visual pathway 1056 alkalis 231
dislocated lens 326 Immune recovery uveitis 1139 ammonia and ammonium
subluxated crystalline lens 325 Immunofluorescence/fluorescent hydroxide 231
subluxation 322 antibody test 203 calcium hydroxide 232
Human immunodeficiency virus 1337 Immunofluorescent staining 1199 magnesium hydroxide 232
laboratory test 1339 Immunological rejection 1189 sodium hydroxide 232
precaution against transmission 1339 Immunosuppressive drugs 705 Interlenticular opacification 418
treatment 1339 Implantable miniaturized telescope 356 Intermediate uveitis 1280
Human immunodeficiency viruses 1127 Inborn error of metabolism 818 anatomy 1280
Human leukocyte antigens 1385 Incisional biopsy 643 cataract extraction 1287
Human T lymphotropic virus 1340 Incontinentia pigmenti 1654 clinical features 1281
Humphrey field analyzer 517 Indocyanine green angiography 1151 differential diagnosis 1283
Hutchinson’s freckle) 53 additional consideration 1156 ancillary tests 1283
Hutchinson’s pupil 955 ICG guided laser photocoagulation electrophysiological 1284
Hyaline degeneration 219 1157 laboratory investigations 1284
Hyaluronidase 361 imaging 1152 systemic association 1283
Hydatid disease 1218 properties of 1151 ultrasonography 1284
Hydrodelineation 371 when to use 1158 heredity 1285
Hydrodissection 371 Indocyanine green angiography 1367 immunology 1284
Hyperemia 67 Indocyanine green angiography 1489 natural course, complication 1282
Hyperlysinemia 810 clinical applications 1491 nomenclature 1280
Hypermature cataract 539 clinical interpretation 1490 pathogenesis 1285
Hyperosmotic glaucoma 539 dosage 1490 pathology 1284
Hyperosmotic intravenous agents 576 physical and pharmacologic properties treatment 1285
Hyperphoria 887 1489 step 1 1285
Hypertensive choroidopathy 1600 Indocyanine green angiography 1773 step 2 1286
pathophysiology 1600 Infection 1190 step 3 1286
Hypertensive optic neuropathy 1603 Infection control practices 1121 step 4 1286
Hypertensive retinopathy 1601 care of instruments/sterile supplies/ Intermittent corneal touch 465
complications of sclerotic phase 1602 drugs 1122 Intermuscular septum 927
Index 1815
Internal retinochoroidotomy 1430 optics 347 management 224
Internal tamponade 1714 second generation 344 Keratoepithelioplasty 239
clinical application 1715 third generation 344 Keratolimbal allograft 1185
fluid-air exchange and internal Iridectomy 532, 533, 1428 Keratomalacia 754
drainage 1715 Iridocorneal endothelial syndrome 477 Keratometry 143
gas mixtures 1716 Iridocycletomy 1428 automated 143
Internuclear ophthalmoplegia 988 Iridocyclitis 1268 manual 143
Interstitial keratitis 209 Iridoplasty 532 Keratomileusis 278
Intraepithelial neoplasia 1203 Iris 1249 Keratomycosis 191
Intraocular biopsy techniques 1422 Iris chaffing 465 aetiology 192
Intraocular gases 1753 Iris nodules 1411 clinical features 192
characteristics 1754 Iris processes 475 filamentous fungus 192
complications 1754 Iris processes and synechia 478 yeast infection 192
contraindications 1754 Iris prolapse 406 common fungi responsible 191
indications 1754 Iris sun-tan syndrome 576 filamentous 191
postoperative care 1754 Iritis 584 yeast 191
Intraocular inflammation 1788 ISNT rule 484 incidence 191
Intraocular lens implantation 367, 374, 375 Isolated ectopia lentis 811 laboratory diagnosis 194
configuration 376 Isoniazid skin test 1358 corneal biopsy 195
looped design 376 culture 194
implantation site 375 J methods 195
asymmetric fixation 376 Jones’ dye tests 711 scraping and debridement 194
ciliary sulcus fixation 375 Juvenile arthritis 1374 smear 194
in the bag fixation 376 Juvenile chronic polyarteritis technique of scraping 194
IOL material 377 (Still’s disease) 1222 management 195
foldable 377 Juvenile rheumatoid arthritis 1270, 1375 adjunct therapy 196
PMMA 377 characteristics 1375 drugs 195
Intraocular lens implantation 464, 784, 794 management 1376 medical 195
complications of 464 management of complications 1376 surgical 196
intraoperative 464 Juxtacanallcular tissue 469 pathogenesis 192
postoperative 464 Keratophakia 277
Intraocular lymphomas 1301 K Keratoplasty 252
Intraocular metastatic tumor 1403 Keratoprosthesis 108
Kaposi’s sarcoma 126
clinical features 1405 Keratoses 124
Karichkoff lens 1450
anterior uvea 1405 Keratouveitis/endothelitis 209
Karyotyping 1079
ciliary body 1406 Kestenbaum formula 1162
Keratinizing metaplasia 751
iris 1406 Kissing nevus 51, 52
Keratitis 183
optic nerve head 1407 Klippel-Trenaunay-Weber syndrome 669
Keratoacanthoma 48
retinal 1408 Klippel-Trenaunay-Weber syndrome 771
Keratoconjunctivitis sicca 1137
diagnosis 1408 Krukenberg’s spindle 135
Keratoconjunctivitis sicca 1222
ophthalmoscopic examination 1408 Kveim test 1385
Keratoconus 134, 155, 222
pathogenesis 1405
etiology 22 L
sites 1404
connective tissue abnormality
time of metastasis 1404 Laboratory data management 182
theory 222
Intraocular pressure 480, 482 Laboratory tests 85
enzyme theory 222
Intraoperative 296 culture and isolation test 85
eye rubbing 223
Intraretinal hemorrhages 1607 cytological 85
genetic theory 222
Intraretinal microvascular abnormalities direct detection 85
hormonal theory 222
1608 serological tests 86
associations 223
Intraretinal neovascularization 1608 Lacrimal fistula 714
clinical features 223
Intravitreal hemorrhage 1625 Lacrimal gland 708, 729
diagnosis 223
Invasive squamous cell carcinoma 1204 anatomy 729
keratometry 223
Inverted follicular keratosis 49 tumors 730
keratoscopy 224
IOL development 344 Lacrimal gland pathology 1054
ophthalmoscopy 223
fifth generation 347 lesions of the lacrimal sac and duct
pachymetry 224
first generation 344 1055
retinoscopy 223
fourth generation 347 Lacrimal passage 726
slit lamp examination findings 223
IOL design features 348 Lacrimal passages 712
differential diagnosis 224
materials 347 Lacrimal system 708
histopathology 224
haptics 347
anatomy 708 delivery systems 1799 Louis-Bar syndrome 670
lacrimal apparatus 710 laser media 1798 Low vision 1160
lacrimal gland 708 laser output modes 1798 causes 1161
nasolacrimal duct 709 principles 1797 devices 1162
nerve supply 708 Late uveitis 466 computer systems 1167
diseases 713 Lateral geniculate body 945 non-optical 1166
acquired disorders 715 Lattice degneration 1557 optical 1162
benign lymphoepithelial lesion 713 Learning curve 492 video magnifiers 1167
congenital anomalies 713 Leber’s hereditary 1115 enhancing impaired vision 1161
infection 713 Leber’s hereditary optic atrophy 977 impact of ocular disease 1161
non-infective chronic inflammations Leiomyoma of iris 1411 Low vision aids 1531
713 Leishmaniasis 1216 Lowe’s oculocerebral syndrome 778
investigation 711 Lens 1066 Lowe’s syndrome
tests of lacrimal excretion 711 Lens capsule 316 (oculocerebrorenal syndrome) 772
tests of lacrimal secretion 711 Lens dislocation 358 Lumbar puncture 999, 1319
physiology 710 Lens implantation 333 Lumbar-peritoneal shunt 1000
drainage of tears 710 Lens induced glaucoma 538 Lupus erythematous (LE) cell 1221
secretion of tears 710 Lens subluxation 808 Lyme disease 1313, 1387
symptoms of dysfunction 711 acquired 812 Lymphadenopathy 69
Lactoferrin radial immunodiffusion assay et pupillae 812 Lymphangioma 55, 125, 830, 1049
103 heritable 809 Lymphoid tumors 646
Lamellar grafting 11 management 813 classification 646
Lamellar keratoplasty 268 surgical 814 leukemic lesions 649
advantages 268 traumatic 812 lymphocytic lesions 647
indications 269 Lens swelling (phacomorphic) 538 Lymphomas 125, 731, 1138
methods of lamellar dissection 269 Lens-induced uveitis 1310 Lymphoproliferative disease 1041
problems 268 Lens-particle glaucoma 539
surgical steps 270 Lens: associated uveitis 1276 M
conventional 270 Lensectomy 845, 1709 Macrodacryocystography 728
donor tissue preparation and Lenticonus 775 Macrophthalmos/buphthalmos 1033
fixation 273 Leprosy 1215 Macular edema 1476, 1588, 1595, 1608,
inlay modified segmental L K 270 Lesions of the bony orbit 1055 1609
onlay lamellar keratoplasty 272 Letterer-SIWE disease 651 Macular heterotopia 1611
onlay limbal transplantation 272 Leukemia 649, 829, 836, 854 Macular hole 1474, 1691
Lamp delivery system 1759 Leukoplakia 111, 124 basic surgical technique 1693
Langerhans’ cell histiocytoses 650 Levator aponeurosis 2 classification 1691
Lantern tests 1146 Lid edema 633 clinical examination 1692
Laser assisted in-situ keratomileusis 286 Lid edema or fullness 702 complications 1694
clinical examination 287 Lid infections 1137 indications 1693
complications 296 Lid retraction 46, 704, 701 management 1692
contraindications 286 Lid swelling 675 pathogenesis and pathology 1691
preoperative evaluation 286 Ligament of lockwood 928 use of adjuvants 1693
Laser cycloablation 543 Light microscopy 184 Macular holes 1564
Laser delivery system 290 Limbal allograft stem cell transplantation Macular pucker 1736
Laser goniophotocoagulation 594 1212 Maddox Rod test 873, 887
Laser gonioplasty 593 Limbal stem cells deficiency 1181 Magnetic resonance imaging 642, 1022
Laser goniopuncture 594 classification and etiology 1181 basics 1022
Laser interferometry 333 clinical features 1181 MR protocols for orbits 1024
Laser iridectomy 534 diagnosis 1182 Magnifiers 1163
Laser iridotomy 565 management 1182 Mainster lens 1449
Laser lenses 1449 preparation of the bed 1182 Malaria 1216
Laser peripheral iridotomy/iridectomy surgical techniques 1182 Malignant 731
589 Limbus test 868 management 732
argon laser iridotomy 590 Limulus amebocyte lysate assay 1197 Malignant glaucoma 551
Nd:YAG irodotomy 590 Limulus amebocyte lysate assay 87 clinical features 555
Laser revision of failing blebs 594 Lipid degeneration 219 clinical picture 552
Laser treatment of bleb for hypotony 594 Live related direct conjunctival limbal conditions of development 551
Laser-tissue interaction 288 allograft 1185 course of the disease 557
Laser-tissue interactions 1757 Loiasis 1217 differential diagnosis 552, 558
Lasers in retinal diseases 1797 Lost lens syndrome 465 management 553
Index 1817
laser therapy 553 Measurement of vergence 868 basic concepts 1108
medical 553 Mechanism of phacoemulsification 387 techniques 1108
surgery 553 Medulloepithelioma 853, 1032 chromosome walking and jumping
management 558 Megalocornea (anterior megalophthalmos) 1112
surgical 559 134 linkage 1110
trabeculectomy 559 Meibomian gland 21 polymerase chain reaction 1112
pathogenesis 552 anatomy and physiology 22 preparation of probes 1110
pathogenesis 557 pathogenesis 23 probes 1109
Malignant histiocytosis 651 treatment 26 pulsed field gel electrophoresis
Malignant melanoma 1397 Meibomian gland dysfunction 25 1111
clinical presentation 1397 Meibomitis 21 southern blotting 1109
diagnosis 1398 Melanocytoma 1411 X chromosome and the eye 1112
clinical appearance 1398 Melanoses 124 Molluscum contagiosum 34, 1137
fundus fluorescein angiography Melanosis 1204 Monoclonal antibody 88, 1198
1398 Mendelian inheritance 1102 Monocular telescope 1166
invasive technique 1399 Metastasis 1207 Monocular vs binocular vision 867
new diagnostic tests 1399 Metastatic lesions 1042 Mooren’s ulcer 227, 303
transillumination 1399 Metastatic tumor 676 clinical features 304
ultrasonography 1398 behavior of different tumors 676 diagnosis 305
pathology 1399 factors facilitating metastasis 677 epidemiological features 303
growth pattern 1399 presentation 677 etiology 303
histologic characteristic 1400 diagnostic modalities 677 management 306
pigmentation 1399 biopsy 679 pathogenesis 305
systemic evaluation 1402 computerized tomography 678 pathology 303
treatment modalities 1401 laboratory examination 678 Moorfields regression analysis 487
chemotherapy and immunotherapy magnetic resonance imaging 679 Mosaicism 1106
1402 physical examination 677 Mucin secretors 62
enucleation 1401 ultrasonography 678 Mucoceles 672, 1048
exenteration 1402 primary sites 676 Mucoepidermoid carcinoma 124, 1204
local resection 1401 treatment 679 Mucous membrane grafting 108
photocoagulation 1401 chemotherapy 680 Mšller’s cells 1439
Malignant melanoma of the choroid 1431 hormonal therapy 680 Muller’s muscle 2
current management 1431 radiotherapy 680 Multifocal choroiditis with panuveitis
enucleation 1432 surgery 680 1297
internal resection 1432 Metastatic tumors 829 Multifocal iols 421
brachytherapy 1433 Microaneurysms 1607 biometric considerations 422
photochemotherapy 1433 Microcornea 772 multifocal iol styles 423
photocoagulation 1432 Microcornea patient selection 422
radiotherapy 1433 (anterior microphthalmos) 133 postoperative outcome analysis 423
local resection 1432 Microglia 1440 principle of multifocality 421
periodic observation 1432 Microkeratome 291 Multifocal VEP multifocal ERG 1471
Malignant melanoma/melanocytoma Microphthalmos 772 Multiple evanescent white dot syndrome
1410 Microphthalmos 825 1298
Malignant uveal melanoma 1033 Microspectrophotometry 1148 Multiple myeloma 650
Management of amblyopia 922 anomalies 1148 Multiple sclerosis 975
Mandibulofacial dysostosis 811 disorders 1148 Multipuncture capsulotomy 369
Marchesani syndrome 1226 drugs causing deficiency 1149 Munson’s sign 223
Marcus gunn pupillary sign 956 systemic disorders causing deficiency Murine typhus 1341
Marfan’s syndrome 323, 775, 809, 822, 1149 Muscle force generation test 877
1226 Microspherophakia 323 Myasthenia gravis 916
Marginal keratitis 227 Microtropia 896 diagnosis 917
Marginal myotomy 931 Miosis 1735 Mycobacterial infection 1135
Masquerade syndromes 836, 1277, 1300 Miotics 531 Mydriasis 598
malignant diseases 836 Miotics 921 Myopia 481, 1559, 1653, 1656
nonmalignant diseases 837 Mitochondrial inheritance 1103 Myopia
Mass lesions of anterior segment 1067 Mitomycin C 598 Myotonic dystrophy 779
Massive subretinal hemorrhage 1704 Mixed adenoma 963
Mast cell stabilizers 93 Mobius’ syndrome 984 N
Maxillary hypoplasia 767 Modes of inheritance 1103 Nanophthalmos 1565
Mean height contour graph 487 Molecular genetics 1108 Nanophthalmos 538
Narrow angle glaucoma 475 retinal and optic nerve lesions 663 phacosandwich and phacosection
Nasolacrimal duct 709 systemic manifestations 663 techniques 384
Nasolacrimal duct (NLD) block 713 uveal tract 663 phacosandwich technique 382
Nasopharyngeal tumors 695 pathology 664 sclerocorneal pocket tunnel incision
Natural history 899 treatment 664 379
Negative lens 1447 Neurofibromatosis 770 wound closure 386
Neodymium 796 Neuromyelitis optica (devic’s disease) 977 Noninfectious corneal ulceration 176
Neonatal conjunctivitis 733 Neuroophthalmic lesions 1138 Noninfectious inflammation 799
clinical features 734 Neuroprotective agents 576 Nonpigmented ciliary epithelium 1250
chemical conjunctivitis 735 Neurotrophic keratopathy 201, 209 Nonsteroidal anti-inflammatory agents
chlamydial neonatal conjunctivitis Nevoid basal cell carcinoma syndrome 51 284
735 Nevus cell tumors 52 Nonsteroidal anti-inflammatory drugs 94
gonococcal neonatal conjunctivitis Nevus flammeus 55 Normal chamber angle 474
735 Nevus of ota 670 Normal tension glaucoma 502
herpes simplex neonatal Nevus of ota clinical picture 502
conjunctivitis 736 (oculodermal melanocytosis) 52 definition 502
laboratory diagnosis 736 New accommodating lens 425 differential diagnosis 505
etiopathogenesis 733 visual outcomes 425 epidemiology 505
prevention 739 New plant breeding 758 pathogenesis 506
treatment 738 newer 1088 treatment 506
Neoplasms 1138 Newer laser procedures for glaucoma 594 Norrie’s disease 852, 1114, 1653
Neoplasms of conjunctiva and cornea Night blindness 752, 1113, 1641 Nucelic acid hybridization reactions
1201 Night vision devices 1168 88, 1198, 1002
age and sex distribution 1205 Nitrogen mustard 300 Nystagmus 860
classification of 1201 Nodular melanoma 53 atypical congenital idiopathic 862
benign 1202 Non-infectious retinopathy 1128 latent 862
invasive malignant melanoma 1205 Non-infectious uveitis 1388 management 863
invasive squamous cell carcinoma degree of inflammation 1389 manifest congenital 863
1204 duration of inflammation 1389 neurological 862
melanocytic tumors 1204 history of previous uveitis 1389 see-saw 862
mesenchymal tumors 1202 management 1390 sensory defect 861
mucoepidermoid carcinoma 1204 ancillary treatment 1394 typical congenital idiopathic 862
pagetoid sebaceous cell carcinoma cytotoxic and immunosuppressive Nystagmus 989
1205 chemotherapy 1394 acquired forms 990
premalignant and malignant 1203 intravitreal steroids 1391 congenital motor 989
etiology 1205 incidence 1205 newer topical steroid 1391 monocular forms 989
management 1205 nonsteroidal anti-inflammatory physiologic 989
investigations 1205 drugs 1393 Nystagmus surgery 864
treatment 1206 pars plana vitrectomy 1394
cryotherapy 1207 periocular drugs 1391 O
immunotherapy and chemotherapy peripheral retinal cryopexy 1393 O’Brien’s block 362
1207 steroids 1390 Oblique dysfunction 868
radiotherapy 1207 systemic steroids 1392 Obstruction of canaliculus 722
surgery 1206 response to initial treatment 1389 Occlusion 747, 748
Neoplasms of the optic nerve 1045 risk of structural damage 1389 Occlusion test 899
Neovascular glaucoma 540 uveitis active or inactive 1389 Occlusion-induced amblyopia 922
management 543 Non-phaco small incision cataract surgery Octopus single field printout 491
pathogenesis 540 378 Ocular appendages 1012
pathologic process 540 anesthesia 378 choroid 1016
Neovascularization 1594 capsulotomy 380 ciliary body 1016
Neovascularization of the iris and angle completing the tunnel 380 eyeball 1014
478 fish hook technique 384 size 1014
Nephritis and uveitis 1276 hydroprocedures 380 structure 1014
Neuroblastoma 829 IOL implantation 385 eyelids 1012
Neurocutaneous syndromes 1037 microvectis technique 382 gross structure 1013
Neurofibromatosis 55, 662 nuclear delivery 381 margins 1012
clinical features 663 nucleus prolapse 381 lacrimal apparatus 1014
eyelid and orbital lesions 663 phacofracture/phacosection technique multislice (multidetector) 1021
glaucoma 663 383 outer tunic 1015
ocular involvement 663
Index 1819
cornea 1015 trochlear (fourth cranial) nerve 982 Optic nerve 969
sclera 1015 fasciculus 982 Optic nerve cupping 481
uveal tract 1015 peripheral 982 Optic nerve drusen 1001
retina 1016 trochlear nerve 983 Optic nerve dysplasia 1001
structure 1017 Ocular motor paralysis 976 aplasia 1001
scanning protocols 1021 Ocular neovascularization 1588 coloboma 1002
spiral CT 1020 Ocular surface 1179 hypoplasia 1002
the lens 1018 Ocular surface disorders 1174 morning glory disk 1002
vitreous humor 1018 Ocular surface squamous neoplasia 110 pit 1002
Ocular cicatricial pemphigoid Ocular syphilis 1135 Optic nerve glioma 1003
82, 300, 1195 Ocular toxocariasis 853, 1031, 1135 Optic nerve head 973
differential diagnosis 83 Oculocardiac reflex 940 Optic nerve meningioma 1003
pathology 83 Oculodermal melanocytosis 670, 771 Optic nerve sheath decompression 999
Ocular cysticercosis 1292 Oculomotor apraxia 987 Optic nerve trauma 1002
Ocular detachment 1033 Olivopontocerebellar atrophy 988 Optic nerve tumors 826
Ocular disease 1321 Onchocerciasis 1217 differential diagnosis 826
Ocular electrophysiology tests 1455 One and a half syndrome 988 treatment 827
Ocular helminthiasis 1217 Open angle glaucoma 475 Optic neuritis 675, 1040, 1115
Ocular hypertension 493 Ophthalmia neonatorum 733 Optic neuropathy 486
Ocular infections 189 Ophthalmic artery obstruction 1581 Optic tract 971
Ocular infective organisms 1196 Ophthalmic Kaposi’s sarcoma 1138 Optical coherence tomography
Ocular ischemic syndrome 1577, 1783 Ophthalmic photography 1083 513, 1367, 1474
ancillary studies 1785 Ophthalmic viscosurgical devices 448 Ora pear’s 1557
clinical features 1783 characteristics and advantages 452 Oral acyclovir 207, 211
differential diagnosis 1578, 1786 viscoadaptive ovd-HEALON-5A Oral aphthous ulcers 1320
etiology 1783 452 Orbicularis bracing 10
investigations 1577 classification 448 Orbicularis ocult 2
carotid angiography 1578 high viscous-cohesive 449 Orbital and periorbital cellulitis 1047
electroretinography 1578 higher viscosity-cohesive 450 Orbital apex syndrome 968
fundus fluorescein angiography low viscosity dispersive 451 Orbital blow-out fractures 682
(FFA) 1577 lower viscosity-dispersive 449 classifications 683
management 1786 super viscous-cohesive 449 clinical features 684
pathogenesis 1783 soft shell technique 452 incidence 682
signs 1577 surgical application of 453 management 685
symptoms 1577, 1784 use 453 surgical 686
systemic associations 1578 capsular bag filling and IOL management 687
treatment 1578 implantation 453 mechanism 683
Ocular ischemic syndrome 1783 capsulorhexis 453 medial blow-out fractures 687
Ocular lesions 1028 cataract surgery 453 clinical features 687
adult 1033 cleavage of lens structure 453 imaging studies 687
children 1028 glaucoma surgery 455 medical therapy 688
Ocular motility 951 irrigation and aspiration 453 surgical therapy 688
Ocular motor dysmetria 987 nuclear emulsification 453 roentgen examination 685
Ocular motor palsies 980 Ophthalmomyasis 1218 Orbital cellulitis 184, 689
abducens (sixth cranial) nerve 983 Ophthalmoplegic 38 clinical features 691
cavernous sinus and orbit 984 Ophthalmoplegic migraine 697, 982 complications 691
fasciculus 983 Ophthalmoscopy 957 differential diagnosis 691
nerve (petrous) 984 Opportunistic infections 1128 etiopathogenesis 689
peripheral nerve (subarachnoid) Opsocionus 987 predisposing factors 689
983 Optic atrophy 975 routes of infection 689
isolated oculomotor palsy 982 classification 978 laboratory and imaging studies 692
oculomotor nerve 980 pathology 978 management 692
fasciculus 980 treatment 978 antibiotics 692
nucleus 980 Optic chiasm 970 surgical 693
peripheral nerve 981 Optic disk area 484 microbiology 690
intracavernous space 981 Optic disk drusen 1035 bacteria 690
orbital space 981 Optic disk vasculitis fungi 690
subarachnoid space 981 (papillophlebitis) 1002 parasites 691
special syndromes 981 Optic foraman 1012 pathophysiology 690
Orbital cellulitis and abscess 671 Pars plana cysts 1505, 1557 intermediate 264
Orbital cysticercosis 1048 Pars plana surgery 1737 late 265
Orbital decompression 704 accessory instrumentation 1740 donor corneal preservation 255
Orbital fascia 628 complications 1750 intermediate-term storage 257
bulbi 628 full function system 1739 long-term storage 258
expansions 628 indications 1737 short-term storage 257
intermuscular septa/membrane 629 instrumentation 1738 indications 252
sheaths 628 cutting 1739 surgical techniques 259
Orbital fractures 1052 illumination 1738 anesthesia 259
Orbital infections 1138 infusion 1738 chamber entry and corneal button
Orbital lesions 631 suction 1739 removal 260
adulthood 632 principles 1737 eye exposure, fixation, and scleral
childhood 631 types 1737 support 259
Orbital meningioma 632 Pars plana vitrectomy 1790 field preparation and draping 259
Orbital neuralgia 675 Pars planitis 835, 1280 graft placement and chamber
Orbital pseudotumor 830, 1037 Pars plicata 1249, 1250 maintenance 261
Orbital radiation 705 Patellar fossa 316 iol insertion 260
Orbital septum 9 Pattern electroretinogram 1467 management of the lens 260
Orbital trauma 1051 clinical uses 1468 management of vitreous 260
Orbital varix 830 recordings and measurements 1468 suturing the corneal button 261
Orbitocranial diseases 995 Pediatric cataracts 397 trephination of donor material 260
Orthoptics 922 subluxated or dislocated cataract 397 trephining of recipient button 259
Oscillopsia 949 Pediatric cataracts 780 Penetrating keratoplasty 253, 547
Osteogenesis imperfecta 1226 anterior capsule management 789 Perfluorocarbon 1709
Osteomyelitis 675 bipolar radiofrequency Perfluorocarbon liquids 1701
capsulotomy 792 applications 1701
P can-opener anterior capsulotomy complications 1704
Pachometry 288 790 Perfluorocarbon liquids 1755
Pachometry (pachymetry) 142 curvilinear capsulorhexis 789 complications 1755
Pagetoid 53 fugo plasma bladeTM anterior uses 1755
Panfundoscopic lens 1449 capsulotomy 793 Perfluorocarbon liquids 1790
Pannus 78 intraocular lens implantation 794 Periorbita 628
Panretinal photocoagulation 1614, 1615, lens substance removal 794 Periosteitis 675
1760 manual continuous 789 Peripheral corneal ulces 226
Panuveitis 1303 vitrector-cut anterior capsulectomy clinical features 226
fungal 1305 790 etiological factors 226
infectious causes 1303 diagnosis 780 Peripheral granuloma 1291
Papilledema 992 dye-enhanced pediatric cataract Peripheral iridotony 559
differential diagnosis 995 surgery 797 Peripheral retina 1496, 1497
fluorescein angiography 994 indications for treatment 780 applied anatomy 1497
ophthalmoscopic appearance 993 IOL implantation 785 degenerative lesions 1498
pathogenesis 992 power selection 785 degenerative peripheral cystoid
pathology 993 size 785 degneration 1499
symptomatology 993 optical rehabilitation 782 full thickness retina tear 1501
Papillitis 973 aphakic glasses 783 lattice 1498
Papilloma 123 contact lenses 783 partial thickness retina tear 1501
Paralysis of upgaze 988 epikeratophakia 784 pavingstone 1503
Paralytic squint 938 intraocular lens implantation 784 retinal hole 1502
Paralytic strabismus 935 perioperative and postoperative retinal tuft 1500
Paranasal sinus diseases 671 medications 797 snail track 1499
Parasellar syndrome 697 posterior capsule management 795 white with pressure and white
Paravasalsinuses 689 postoperative complications and without pressure 1500
Parinaud’s Dorsal midbrain syndrome management 797 developmental anatomy
960 surgical techniques 786 lesions 1497
Pars plana 1249, 1250, 1505 anesthesia 788 microanatomy 1497
applied anatomy 1505 wound construction 788 Peripheral retinal cryopexy 1393
developmental anatomy 1505 Penalization therapy 923 Peritomy 301
lesions 1505 Penetrating corneal transplantation 252 Persistent corneal edema 466
microanatomy 1505 complications 262 Persistent hyaloid system 775
surgical anatomy 1505 early 262
Index 1821
Persistent hyperplastic primary vitreous Phacoemulsification in uveitic eyes 401 Pinguecula 127
1030 Phacoemulsification with small pupil 400 Pituitary apoplexy 697
Persistent hyperplastic primary vitreous Phacolytic glaucoma 539 Pituitary tumor 962
772 Phacomachine 387 Plasma cell tumors 649
Peter’s anomaly 768 aspiration pump 388 Plasmacytoma 655
clinical features 768 diaphragmatic pump 389 Plasmapheresis 705
management 769 foot pedal 389 Plateau iris 534
mechanism of glaucoma 769 irrigation aspiration handpiece 388 Pleomorphic adenoma 656, 730
ocular abnormalities 768 peristaltic pumps 388 Pleoptics 748
pathogenesis 769 phaco tips/needles 388 Pleoptics 923
Peyman vitreophage 1739 ultrasonic handpiece 387 Plexiform neurofibroma 56
PFCL-silicone oil exchange 1711 venturi pump 389 Plica semilunaris 65
Phaco in colobomatous eyes 398 Phacotrabeculectomy 597, 600 Pneumatosinus dilatans 673
Phacoanaphylactic glaucoma 539 Phagocytic inflammatory cells 1381 Pneumocystis carinii choroidopathy 1136
Phacoanesthesia 335 Phakic intraocular lens 224 Polyarteritis nodosa 1224
Phacoemulsification 402 Phakomatosis 660 Polyarteritis nodosa 229
problems faced by a surgeon 402 Pharmacologic mydriasis 960 Polymerase chain reaction 204, 1079, 1107,
mental block 402 Pharyngoconjunctival 72 1112
phaco machine specification 403 Phlyctenular keratoconjunctitivis 68, 81 Polymorphisms 1101
problem of coordination 402 Phlyctenulosis 82 Polymyositis 1224
role of phaco skill transfer courses Photocoagulation 1432 Positive aspheric lenses 1447
403 Photorefractive keratectomy 159 Posner-schlossman syndrome 544
selection of eye 403 Photorefractive keratectomy 279 Post-PK astigmatism 157
selection of initial patients 403 medical treatment 282 Posterior capsular rupture 358, 406
surgeons ability 402 corticosteroids 282 Posterior capsular tear 411
understanding phaco setting for nonsteroidal anti-inflammatory Posterior capsule opacification 341, 412,
403 agents 284 414
use of operating microscope 403 wound healing modulators 285 barrier effect of iol optic 417
transition and their management 404 preoperative evaluation 279 evaluation techniques 416
continuous curvilinear prk for astigmatism 281 immunological inhibitors 418
capsulorhexis 404 cylindrical ablation 282 management 418
hydrodissection and elliptic ablation 282 pathogenesis 415
hydrodelineation 404 surgical technique 280 pharmacological techniques 418
phaco incisions 404 Photostress test 949 prevention 416
phacoemulsification techniques 405 Phthisis bulbi 754 biocompatibility of iol 417
Phacoemulsification 409 Physiology 524 capsulorhexis edge on the IOL
complications 409 Pierre-Robin syndrome 772, 811 surface 417
anterior capsulotomy 410 Piggy-back foldable intraocular lenses hydrodissection-enhanced cortical
chamber collapse 410 430, 803 clean-up 416
corneal 410 complications 432 in-the-bag fixation of iol 417
general 409 depth of focus using a piggy back maximum iol optic posterior
glaucoma due to viscoelastic 412 system 432 capsule contact 417
related to hydro procedures 410 image quality 432 why to eliminate 415
related to incision 410 power calculation 431 Posterior capsule scraping 374
retained lens matter 411 primary implantations 431 Posterior capsulorhexis 795
retinal 412 secondary implantation 432 Posterior capsulotomy 547
Phacoemulsification 599 primary 430 Posterior nucleus dislocation 406
Phacoemulsification in a vitrectomized high hyperopes 430 Posterior pole granuloma 1291
eye 398 minus power piggyback lenses 431 Posterior scleritis 1319
Phacoemulsification in different type of multifocal piggyback iol 431 Posterior segment lesions 1128
cataracts 395 toric piggyback iols 431 Posterior uveitis 833, 1289, 1313, 1492
hard nucleus 396 secondary 431 differential diagnosis 1289
intumescent cataract 396 Pigment dispersion glaucoma 556 infectious 1289
posterior polar cataract 395 Pigment dispersion syndrome 477 non-infectious 1289
white cataract 395 Pigment dispersion syndrome 544 Posterior vitreous detachment 1259
Phacoemulsification in patients with Pigmentary degeneration depositions 219 Posterior-uveitis in acquired
pseudoexfliation 400 Pigmented ciliary epithelium 1251 immunodeficiency syndrome 1294
Phacoemulsification in postsurgical eyes Pigments over the anterior lens capsule Posteriorly dislocated 1703
398 775 Postkeratoplasty astigmatism 266
Postoperative 297 pathogenesis 1633 evaluation 38
lasik procedure 291 risk factors 1635 Beli’s phenomenon 39
Postoperative glaucoma 545 Proliferative vitreoretinopathy (PVR) 1705 phenylephrine test 40
Postsurgical uveitis 1308 Proptosis 632 surgical treatment 40
Postvitrectomy glaucoma 1751 Proptosis 672 aponeurotic repan 45
Potential acuity meter 332 Prostaglandins 575 fassanella servat operation 40
Power calculation 349 Prostaglandins 583 frontalis sling surgery 44
calculating iol power by biometry 349 latanoprost 583 levator resection 41
empirical 349 Prostigmin 37 other surgical procedures 45
Precancerous lesions 49 Protein energy malnutrition 752 Pulsed field gel electrophoresis 1111
Preoperative 296 Provocative tests 528 Punctal atresia 715
preparations 1087 Pseudo-anterior uveitis 462 Punctal ectropion 715
cellugel 1088 Pseudo-Duane’s syndrome Punctal stenosis 715
chondroitin sulfate 1088 (acquired retraction syndrome) 913 Punctate inner choroidopathy 1298
collagen 1088 Pseudocarcinomatous hyperplasia 48 Punctiform opacity 776
hydroxy propyl methyl cellulose Pseudodendrites 208 Pupil in Horner’s syndrome 956
1088 Pseudoexfoliation syndrome 476 Pupil size 288
ocugel 1088 Pseudoexfoliation syndrome 561 Pupillary block glaucoma 552
sodium hyaluronate 1087 clinical picture 562 Pupillary capture 800
Presumed ocular tuberculosis 1356 anterior chamber and angle 562 Pupillary dilator pathway 953
diagnosis 1357 blood-aqueous barrier 563 Pupillary pathways 958
Pretectal afferent pupillary defects 960 conjunctiva and cornea 562 afferent 958
Prevalence 899 intraocular pressure 563 afferent 959
Primary 760 iris and pupil 562 parasympathetic 958
Primary angle closure glaucoma 522 lens, zonules, and ciliary body 562 parasympathetic 960
anatomical features 522 definition 561 sympathetic 958
Primary open angle glaucoma 479 diagnosis 564 sympathetic 960
diagnosis 482 epidemiology 561 Pupilloconstrictor pathway 954
management 493 heredity 562 Pupils and pupillary reactions 952
pathogenesis 481 incidence with glaucoma 562 Pyridostigmin (mestinon) 37
optic nerve damage 482 incidence without glaucoma 561
raised IOP 481 systemic associations 562 Q
risk factors 480 etiopathogenesis 563 Q fever 1341
the problem 479 history 561
treatment 494 management 565 R
laser 495 mechanism of glaucoma 564
Radial keratotomy 158, 277
medical 494 pathophysiology 563
Radiation dermatosis 49
surgical 495 Pseudoexfoliative syndrome 537
Radiation keratopathy 300
Primary pigmentary dispersion syndrome Pseudohypopyon 836
Radiopaque dyes 726
555 Pseudoisochromatic color plates 1147
Raeder’s paratrigeminal syndrome 696
Primary posterior capsulotomy 795 Pseudomelanoma 1398
Raised intraocular pressure 458
Primary posterior capsulotomy 796 Pseudophakic bullous keratopathy 1175
Rapid antigen detection 203
Prism bar cover test 870 Pseudopterygium 128
Raster stereography 512
Progressive hepatolenticular disease Pseudotumor
Rathke’s pouch cyst 964
(Wilson’s disease) 821 (inflammatory orbital disease) 656
Reactive lymphoid hyperplasia 647
Progressive iris atrophy 477 Pseudotumor cerebri 997
Recombinant DNA technology 1107
Progressive outer retinal necrosis 1131 Pseudoxanthoma elasticum 1226
Reflection image 487
Progressive outer retinal necrosis 1293 Psoriatic arthritis 1269
Refraction 287
Progressive outer retinal necrosis 1336 Psoriatic arthritis 1374
Refraction errors 886
Progressive supranuclear palsy 988 Pterygium 127
Refractive 423
Proliferative diabetic retinopathy 1702 Pterygium surgery 1175
Refractive correction 920
Proliferative diabetic retinopathy 1705 Ptosis (blepharoptosis) 35
Refsum’s syndrome 811
Proliferative vitreoretinopathy 1633 classification 35
Reiter’s disease 1223
classification 1633 aponeurotic 37
Reiter’s syndrome 1269, 1373
clinical features 1635 mechanical 38
Relapsing polychondritis 230, 312, 1225
investigations 1637 myogenic 35
Removal of subincisional cortex 391
management 1637 neurogenic 37
extension of the incision 391
adjuvant therapy 1638 pseudoptosis 38
mobilization cortex 392
prophylaxis 1637 synkinetic 38
mobilization of the cortex 392
surgical 1638 complication 45
Index 1823
system using two separate cannulas 392 orbital/episcleral (Lincoff) balloon field of view 1444
advantages of bimanual technique 1574 fundus examination documentation
394 pneumatic retinopexy 1574 1446
incisions for two cannulas 393 primary vitrectomy 1575 magnification 1444
principles for use of two cannulas suprachoroidal implantation 1575 non-contact system 1453
393 anesthesia for scleral buckling 1569 BIOM 1453
technical features of the two closure of retinal breaks 1571 optical principle of wide-angle lens
cannulas 392 buckling materials 1571 1453
technique 393 configuration of buckle 1571 SDI 1453
technique of using viscoelastic 392 episcleral exoplants 1572 optics of indirect ophthalmoscopy
technique with a curved coaxial intrascleral implants 1572 1443
cannula 392 intraoperative complications 1574 surgical lenses 1450
verticalization of the coaxial tip 391 drainage complications 1574 Retinectomy 1710, 1720
Reporting system 181 localization of retinal breaks 1570 Retinitis pigmentosa 1641
Residual refractive error 803 management of subretinal fluid 1572 evaluation and investigations 1642
Reticulin fiber 1220 drainage technique 1573 management 1646
Retina 1435 nondrainage technique 1572 molecular genetics 1646
anatomy 1436 preparation of the operative field 1569 current state of research 1647
central retina 1436 rationale and goals 1569 signs 1642
peripheral fundus 1437 surgical exposure 1569 symptoms 1641
blood supply 1440 treatment of retinal breaks 1571 variants 1645
embryology 1435 Retinal detachments 1704 Retinoblastoma 537, 831, 835, 836, 849,
structure 1438 Retinal dialysis 1559, 1564, 1750 1028, 1116, 1764
amacrine cells 1439 Retinal disease 1321 age at diagnosis 849
bipolar cells 1439 Retinal disorder 556 clinical features 850
ganglion cells 1439 Retinal dysplasia 852 developmental abnormalities 852
horizontal cells 1439 Retinal edema 1563 differential diagnosis 851
photoreceotors 1438 Retinal hemorrhages 1216 genetics 849
retinal pigment epithelium 1438 Retinal hole 1502 hereditary conditions 852
supporting structure of retina 1439 Retinal holes 1558 inflammatory conditions 853
Retina sparing internal resection 1430 Retinal incarceration 1703 management 854
Retinal angiomatous proliferation 1154 Retinal neovascularization 1596 chemotherapy 857
Retinal arterial macroaneurysms 1763 Retinal pigment epithelium 1438 cryotherapy 855
Retinal astrocytomas 853 Retinal tamponade 1712 enucleation 856
Retinal breaks 1764 Retinal tear and detachment 1789 external beam radiotherapy 856
Retinal capillary hemangioma 1763 Retinal tears 1558 laser photocoagulation 855
Retinal chip research 1647 Retinal telangiectasis 1511 orbital exenteration 857
Retinal detachment group 1 1511 plaque brachytherapy 855
characteristics of the types 1563 differential diagnosis 1512 thermotherapy 855
clinical features 1560 group 2 1512 pathogenesis 849
signs 1561 differential diagnosis 1516 pathology 851
symptoms 1560 natural course 1515 tumors 853
differential diagnosis 1562 pathogenesis 1517 Retinoblastoma 851
pathogenesis 1558 treatment 1518 Retinocytoma 850
precipitating factors 1559 group 3 1518 Retinopathy of prematurity 537, 773, 835,
predisposing factors 1560 Retinal tuft 1501 838, 1031, 1653, 1704
Retinal detachment 1594, 1703, 1706 Retinal venous macroaneurysms 1763 classification 839
Retinal detachment 802 Retinal viewing system 1442 location of the disease 840
Retinal detachment surgery 1552 binocular indirect ophthalmoscopy plus disease 840
examination of the patient 1552 1443 regressed ROP 840
indirect ophthalmoscopy 1553 biomicroscopy of the retina 1446 stages of the disease 840
instrumentation 1554 contact lenses 1447 threshold ROP 840
method 1554 noncontact lenses 1447 examination 842
principle 1553 compensation for refractive error 1444 prevention and treatment 843
normal retinal periphery and contact system 1450 recent advances 847
peripheral lesions 1555 conventional lenses 1450 risk factors 841
Retinal detachment surgery 1568 optical principle 1451 birthweight and gestational age 841
alternative techniques 1574 wide-angle system 1452 delicate balance 841
DACE technique 1575 direct ophthalmoscopy 1442 multiple gestation 842
examination technique 1445
prolonged intubation 842 Sample collection devices 182 indications 438
treatment 843 methods 183 recent advances 441
cryotherapy 843 sample collection devices 182 Scleritis 308, 1222
laser photocoagulation 844 bard parker blade numbers 15 182 associated systemic diseases 312
multicentric cryotherapy 844 calcium aigiate swab 182 etiology 311
vitreoretinal surgery 844 cotton swabs 182 infection of the sclera 313
vasculogenesis in 838 glass slides 183 infections 313
Retinoschisis 852, 1500, 1653, 1767 kimura platinum spatula 182 therapeutic regimes 313
basic types 1767 needle and syringe 182 episcleritis therapy 314
degenerative or senile 1767 Sarcoidosis 731, 1225, 1311, 1337 surgery 314
x-linked or juvenile 1767 causes of poor vision 1312 types 308
clinical features 1769 clinical features 1311 anterior 309
treatment 1769 diagnosis 1312 diffuse anterior 309
Retinotomy 1719 differential diagnosis 1313 necrotizing 310
Retrobulbar block 362 etiology 1311 nodular 310
comfortable regional 363 investigations 1313 posterior 310
general 365 ocular manifestations 1311 Sclerocornea 134
local 364 pathology 1312 Scleroderma progressiva systemica 1224
peribulbar (periocular) injection 363 posterior segment findings 1312 Sclerokeratitis 209
subtenon anesthesia 363 sarcoidosis in children 1312 Scleromalacia perforans 310
topical 363 SBK formula 349 Sclerotic scatter 139
Retrobulbar neuritis 974 Scanning laser polarimetry 511 Scrub typhus 1341
Retrogeniculate lesions 971 Schirmer test 711 Sealed capsule irrigation 341
Retroillumination 140 Schirmer’s test 102 Sebaceous gland tumors 53
Retrolental plate 845 Schistosomiasis 1217 Seborrheic keratosis 48
Rhabdomyosarcoma 827 Schlemm’s canal 470 Secondary corneal edema 209
diagnosis 828 Schwalbe’s line 471, 474 Secondary glaucoma 465, 536
differential diagnosis 828 Sclera 135 Secondary intraocular lens
pathology 827 blood supply 135 implantation 434
treatment 828 congenital anomalies 136 associated surgical procedures 435
Rhegmatogenous retinal detachment 1777 Scleral 1735 complications 437
Rhegmatogenous retinal detachment 542 Scleral bucking 846, 1708, 1713, 1730 contraindications 434
Rhegmatogenous retinal detachment 853 alternative techniques 1732 indication 434, 436
Rheumatoid arthritis 106, 228 alternatives 1734 IOL exchange 435
Rheumatoid arthritis 311 complications 1734 preoperative preparation 435
Rheumatoid factor 1385 intraoperative 1735 types 436
Rickettsial uveitis 1324 postoperative 1735 Secondary membrane formation 799
Rickettsial uveitis 1341 fate 1734 Secretomotor fibers 708
“Ridge” or “mesenchymal” shunt 842 length 1731 See-saw nystagmus 990
Rieger’s syndrome 324 life of the buckling effect 1731 Seidel test 141
Rift valley fever retinitis 1340 material of the buckle 1730 Sensory disturbances 949
Rigid lenses 336 currently used 1730 Sensory tests 871
Riley-day syndrome 106 newer materials 1731 Serologic test 204
Rodenstock optic nerve head analyzer 509 used in the past 1730 Serpiginous choroiditis 1299, 1366
Rollable lenses 338 orientation 1731 ancillary investigations 1367
Rose bengal 141 placement 1731 clinical features 1366
Rose Bengal stain 102 shape 1731 manifestation 1367
Round cell tumor (retinoblastoma) 657 techniques 1732 signs 1366
Rubella 1335 types and classifications symptoms 1366
Rubeosis iridis 1752 Scleral depression 1445, 1507, 1555 complications 1367
Rubinstein-taybi syndrome documentation 1508 differential diagnosis 1369
(broad thumb syndrome) 772 technique 1507 pathogenesis 1369
Rush disease 842 Scleral perforation 940 treatment 1371
Scleral spur 471, 475 Serpiginous ulceration 209
S Scleral tunnel design 598 Serum angiotensin converting enzyme
Saccharin test 711 Scleral-fixated PCIOL 438 1385
Salivary gland dysfunction 106 ab-externo approach 439 Seventh nerve block 362
Salzmann’s nodular degeneration 219 ab-interno approach 438 Short wave automated perimetry 520
Sampaolesi’s line 478 complications 439 Siderosis 134
Index 1825
Silicone oil 1704, 1716, 1754 Stereoscopic indirect ophthalmoscope 1506 surgical techniques 928
adherence 358 Sterilization 334, 348 anesthesia 928
applications of 1705 chemical 348 exposure of the muscle 929
complications 1706 gas 348 Stroma 1251
chemical properties 1754 radiation 349 Stromal diskiform keratitis 175
complications 1755 Steroid glaucoma 545 Stromal keratitis 201, 207, 211
indications 1755 Steroids 205 necrotizing 202
injection technique 1717 Stickler’s syndrome 822 stromal immune 202
mode of action 1754 Stiles-crawford effect 1145 Stromal ulceration 234
Sjögren’s syndrome 1377 Stoker’s lize Sturge-Weber syndrome 667, 764, 770, 811
Sjögren’s syndrome 229 Stoker-busaca line 135 Subarachnoid space 985
Skew deviation 989 Strabismus 867 Subconjunctival hemorrhage 69
Skin grafting 15 diplopia tests 872 Subdural hematoma 1007
Slit lamp biomicroscopy 102, 137, 1262 facultative inhibition 880 Subfoveal choroidal neovascularization
forms of illumination 138 haploscopic test 874 1721
diffuse 141 obligatory inhibition 880 management 1721
direct 138 stereoacuity estimation 871 adjuncts to surgery 1724
indirect 138 Strabismus surgery 924 case selection 1722
modern clinical 137 aims 924 complications 1724
Slit lamp examination 1510 amount of operation 936 feasibility of surgical excision 1725
Slit lamp indirect ophthalmoscopy 1510 closure of the wound 939 instrumentation 1722
Small B cell lymphomas 647 cyclovertical deviations 937 postoperative management 1724
Sodium fluorescein 141, 1480 horizontal deviations 937 retinotomy and foveal translocation
Sodium hyaluronate 1756 paralytic squint 938 1725
Soft tissue injuries 1053 postoperative care 939 surgical technique 1722
Solid tumors 640 special forms of strabismus 938 Submacular cysticercosis 1698
Southern blotting 1109 suturing the muscle to the sclera 939 Submacular hemorrhage 1694
Spasmus nutans 863 anatomical considerations 926 alternative techniques 1696
Spectacle devices 1162 capsulopalpebral fascia 928 indications for surgical intervention
Spectacle use and patient satisfaction 428 check ligaments 928 1695
Specular microscopy 147 extraocular muscles 926 Submacular hemorrhage 1726
clinical 148 fascial coverings 927 complications 1727
narrow slit of light 148 intermuscular septum 927 management 1726
wide slit of light 148 ligament of lockwood 928 surgical technique 1726
clinical applications 155 muscle capsule 928 Subretinal membrane 1703
evolution 154 orbital fat 928 Subretinal neovascularization 1697
factors affecting image quality 149 tenon’s capsule 927 indications 1697
indications 149 complications 939 surgical technique 1698
instrumentation 150 postoperative 940 Subretinal strands in proliferative
limitations 160 preoperative 939 vitreoretinopathy 1727
methods of evaluation 150 indications 924 Substantia propria 132
qualitative assessment 151 patient evaluation 925 Subvitreal hemorrhage 1625
quantitative assessment 151 surgical procedures 929 Sulfite oxidase deficiency 811
normal 155 adjustable sutures 934 Superior oblique muscle sheath syndrome
optical principles 147 anteroplacement of obliques 936 914
reading and interpretation 159 botulinum toxin to weaken the Superior oblique myokymia 983
techniques 149 action of a muscle 932 Superior orbital fissure 638, 1011
types 148 correction of A/V patterns 935 Superior orbital fissure syndrome 675,
Specular microscopy 255 marginal myotomy 931 966, 968
Sphenoidal ridge syndrome 966 muscle transposition operations 934 Suppression 879
Squamous cell carcinoma 51, 124 paralytic strabismus 935 Suprachoroid 1251
Squamous cell papilloma 48, 1202 posterior fixation suture 932 Suprachoroidal hemorrhage 552, 1704
Squash or imprint cytology 1081 recession 930 Supranuclear disorders 986
Stem cell 1179 resection operation 933 affecting the calibration of saccadic eye
characteristics 1180 strengthening operations 933 movements
Stem cell deficiency 1176 tenotomy or myectomy 931 affecting the conjugacy of gaze 988
Stem cell transplant 272 use of plastic materials 936 affecting the size and velocity of
Stem cells 298, 1647 weakening operations 929 saccades 988
Stereometric analysis 487 weakening-strengthening clinical disorders 987
Stereophotogrammetry 509 operations 934 affecting the initiation of eye
movements 987 investigations 102 Total limbal stem cell deficiency 1176
vertical eye movements 988 natural course of disease 105 Toxocara canis 833
Surface tension 1714 staining procedure 104 Toxocara infection (toxocariasis) 1218
Surgical lenses 1450 technique 104 Toxocariasis 833, 1291, 1653
Swedish interactive thresholding clinical features 111 atypical presentations 834
algorithm 489 diagnosis 113 clinical presentation 833
Sympathetic adrenergic receptors 579 differential diagnosis 105 differential diagnosis 835
alpha receptor agonist 580 etiology 110 laboratory tests 835
apraclonidine 581 fear film layer 99 cytology 835
brimonidine tartrate 581 aqueous 100 elisa test 835
dipivefrin 581 lipid 99 pathology 835
epinephrine 580 mucin 100 treatment 836
beta blockers 579 fluids of tear film 100 Toxoplasma gondii 1344
betaxolol 580 management 106 definitive hosts 1345
levobunolol (betagan) 580 anti-inflammatory therapy 107 intermediate hosts 1345
timolol 579 contact lenses 107 life cycle 1344
Sympathetic fibers 709 decreasing tear viscosity 108 Toxoplasmosis 1289, 1344, 1345, 1386
Sympathetic ophthalmia 1314 estrogen 108 additional therapeutic approaches
clinical features 1314 keratoprosthesis 108 1350
diagnosis mucous membrane grafting 108 cryotherapy 1350
differential diagnosis 1316 surgical measures 108 photocoagulation 1350
histopathology 1316 tear conservation 107 vitrectomy and lensectomy 1350
treatment 1316 tear stimulants 107 AIDS 1348
corticosteroids 1317 tear substitutes 106 clinical features 1345
enucleation 1316 topical vitamin A 108 complications 1348
immunomodulators 1317 physiology 99 diagnostic tests 1348
Sympathetic ophthalmia 1319 tear film abnormalities 101 treatment 1348
Sympathizing eye 1378 aqueous deficiency 101 Trabecular aspiration 559, 565
clinical features 1378 epitheliopathy 102 Trabecular meshwork 468
immunopathology 1380 lipid abnormality 101 filtering part 469
incidence 1378 mucin deficiency 101 nonfiltering part 469
laboratory investigations 1382 Telangiectasia 125 Trabecular meshwork 474
management 1382 Telecanthus 4 Trabecular spaces 470
ocular complications 1383 Telescopes 1164 Trabeculectomy 565, 599, 1174
pathogenesis 1380 Temporal arteritis 1224 Trabeculotomy ab externo 762
pathology 1380 Tendency oriented perimetry 489 Trachoma 599, 1218
time of onset 1378 Tenon’s capsule 628 “Train-track” sign 668
Syphilis 1274, 1303 Tenon’s capsule 927 Traction retinal detachment 1566, 1611
clinical features 1303 Teratoma 825 Transfixation 128
HIV 1304 Terrien’s degeneration 220 Transpupillary thermotherapy 1762
uveitis in syphilis 1303 Testing of visual function 949 Trauma 1702, 1705
Systemic amyloidosis 537 Theoretical formulae 349 Traumatic iridocyclitis 1276
Systemic lupus erythematosis 106, 229, Thermokeratoplasty 276 Traumatic mydriasis 960
1223 Third nerve palsy 960 Travoprost 585
Syte (hordeolum externum) 30 Thyroid function tests 637, 703 Treatment 899
Thyroid hormone 699 indications for surgery 900
T Thyroid myopathy 702 Treatment of viral retinitis 1132
T cell lymphomas 648 Thyroid myopathy 704 acyclovir 1133
Takayasu disease 1224 Tilted optic disk 1001 catheter-less therapy 1133
Tarsal wedge resection 10 Tissue adhesive 178, 1211 ganciclovir intraocular implant
Tarsitis 31 Tissue culture 1079 1134
Tarsorrhaphy 1213 Tissue retrieval 244 intravenous cidofovir 1133
Tear break-up time 711 Tolosa-Hunt syndrome 695 intravitreal medications 1134
Tear film break up time 102 Tonometry 635 oral ganciclovir 1133
Tear lysozyme assay 103, 711 Tonotomy or myectomy 931 foscarnet 1132
Tear osmolarity 103 Topical carbonic anhydrase inhibitor 581 ganciclovir 1132
Tears 99 brinzolamide 582 Trichiasis 7
associated conditions 106 dorzolamide 581 Trigeminal nerve paralysis 106
clinical features 102 Topical medications 1210 Trypanosomiasis (sleeping sickness) 1217
examination 102 Torticollis 865
Index 1827
Tuberculin skin test 1357 etiology 1260 Visual loss 633
Tuberculm (Mantoux test) 1385 examination 1257 Visual sensory system 943
Tuberculosis 1275, 1290, 1313, 1356 general 1259 blood supply of the visual pathways
Tuberous sclerosis 660, 771 local 1257 946
clinical features 661 history-taking 1256 lateral geniculate body 945
Tubular interstitial 1276 incidence 1260 occipital cortex 946
Tumors 478 sample uveitis questionnaire 1265 optic chiasm 944
Tumors of cerebellopontine angle 1008 family history 1265 optic disk 943
Tumors of illrd ventricle and internal medical history 1266 optic nerve 944
hydrocephalus 1008 signs 1255 optic radiations 946
Tumors of neural origin 1043 optic tracts 945
Tumors of pineal body and midbrain 1009 V retina 943
Turner’s syndrome 779 Variable penetrance and expressivity 1105 Visual symptoms 427
Types of lasers 1758 Varicella zoster virus 1333 Vitamin A deficiency 751
Types of variation in DNA 1100 disease 1130 assessment 755
Vascular lesions 1048 categories 751
U Vascular tumors 125 disorders cycle 752
UGH (Ellingson’s) syndrome 466 Vascular tumors of the retina 1418 treatment 755
UGH and PUGH syndrome 546 Vasculorhexis 1626 fortification of dietary items 757
Ulcer formation 1246 Vasoproliferative tumor of the retina 1420 periodic supplementation 757
Ultrasonography 639 Venous varix 1050 vitamin A prophylaxis 756
Ultrasound biomicroscopy 1062 Vergence system 990 Vitamin A prophylaxis 756
clinical applications 1063 Vernal conjunctivitis 1194 Vitelliform foveomacular dystrophy 1516
instrumentation 106 Vernal keratoconjunctivitis 91, 227 Vitrectomy 444, 1546, 1550, 1709, 1737,
principle 1062 atopic kerato 94 1742
technique 1062 management 95 indications 1742
Ultrasound biomicroscopy 145 giant papillary 95 management 1744
Unoprostone 584 differential diagnosis 96 anterior segment disorders 1749
Uvea 1066 management 96 diabetic retinopathy 1745
Uveal effusion syndrome 1319 pathomechanism of formation of Eales’ disease 1745
Uveal effusion syndrome 1354 papillae 96 endophthalmitis 1748
Uveal inflammation 543 vernal kerato 91 epiretinal membranes 1744
Uveal tract 1249 clinical features 91 giant retinal breaks 1747
congenital and developmental defects pathogenesis 92 intraocular foreign bodies 1748
1252 treatment 93 macular holes 1749
coloboma of choroid 1252 Vertical strabismus 908 ocular trauma 174
cysts of iris and ciliary body cysts dissociated vertical deviation 909 proliferative vitreoretinopathy 1747
1253 noncomitant vertical deviations 910 retinal detachment 1746
heterochromia iridis 1252 strabismus sursoadductorious 909 submacular surgery 1749
hypoplasia of iris 1252 Video indirect ophthalmoscopy 1510 vitreous hemorrhage 1744
persistent pupillary membrane Videokeratography 155,157,158 Vitrectorlexis 790
1252 Videokeratography 158 Vitreomacular traction syndrome 1477,
persistent tunica vasculosa lentis Viral keratitis 165, 167, 171, 173, 199 1691
1252 Viscocanalostomy 455 Vitreoretinal 1067
gross and microanatomy 1249 complications of use 458 Vitreous 1440
choroid 1251 topical ophthalmic anesthesia 457 embryology 1436
ciliary body 1250 Viscoelastic substances 448, 1086 optical anatomy 1440
iris 1249 Viscoelastic substances 789 Vitreous aspiration/biopsy 1386
Uveitis 211, 798, 1254, 1334 Visual acuity 425 Vitreous base 1506
basic mechanism 1255 Visual acuity estimation 867 Vitreous hemorrhage 1559, 1588, 1594,
classification 1254 Visual cycle and vitamin A 756 1611, 1624, 1789
according to type of inflammation Visual deficit 948 causes 1626
1255 Visual evoked potential 1468 complications 1630
anatomical 1254 clinical uses 1469 diagnosis and investigations 1627
etiological 1254 normal waveforms 1469 diagnostic ultrasound 1628
clinical approach to a patient 1261 recording and measurement 1468 MRI 1629
examination of patients 1262 Visual field defects 969 etiopathology 1626
history taking 1261 altitudinal 969 vitreous barriers 1626
laboratory evaluations 1264 Visual field examination 489 fate 1627
slit lamp biomicroscopy 1262 Visual field loss 1641 in vitrectomized eyes 1630
treatment 1629 Von Hippel-Lindau disease 664 Wildervanck syndrome 811
Vitreous substitutes 1741 Von Hippel-Lindau syndrome 771 Wilms’ tumor 829
Vitreous TAP 1423 Von Recklinghausen’s disease 55, 662 Wilson’s disease 220
Vitreous tap 1550 Wound dehiscence 265, 465
Vogt-koyanagi-harada (VKH) W Wyburn-Mason syndrome 669
syndrome 1317 Warts (verruca vulgaris) 34
ancillary investigations 1319 Wegener’s granulomatosis 229, 1224 X
clinical features 1317 Wegener’s granulomatosis and X-linked retinitis pigmentosa 1112
acute uveitic stage 1317 polyarteritis nodosa 312 Xanthelasma 57
chronic or convalescent phase 1318 Weil-Marchesani syndrome 324, 776, 810 Xanthogranulomas 651
chronic recurrent phase 1318 Weiss procedure 11 Xeroderma pigmentosum 49
prodromal stage 1317 Wernicke’s hemianopic pupil 956 Xerophthalmia 751, 752, 755
differential diagnosis 1319 Whipple’s disease 1377
etiology 1319 White limbal girdle of vogt 220 Y
extraocular signs 1318 Whitnall’s ligament 2 Yag laser posterior capsulotomy 796
treatment 1320
Yaws 1218

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First Edition: 1994

ISBN 81-8061-470-0 (Set)

Navneet Chauhan Nibaran Gangopadhyay MS SK Handique MD

Chitra Kannabiran PhD K Lakshmanamurthy N Medhi MD

S Narang Suresh K Pandey MD Jagat Ram MS

G Natchiar MS Avinash Pathengay FRCS Sreeram Ramalingum MS

M Srinivasan MS Sandeep Thakur MD Geeta G Vemuganti MD

24. Corneal Ulcer 161 42. Displacement of the Lens: Etiology

30. Peripheral Corneal Ulcers 226 47. Foldable IOLs 352

160. Anterior Uveitis: Diagnosis Section 11

Anatomy of the Eyelids

DEVELOPMENT OF THE EYELIDS Lid fold or crease is a fold of overhanging skin in

Skin Skin of the lid, about the thinnest in the body, is

Nerve Supply of the Eyelids

Congenital Eyelid Anomalies

Anomalies of the Eyelid

TRICHIASIS 4. Laser Lasers of different types are also used with

done. When more lashes are present, 2 mm wide hori-

Fig. 3.4: Senile entropion

Full Thickness Horizontal Shortening of the Lid

Lid Bracing Sutures (Snellen-Quickerdt)

Modified Wheeler’s Procedure

Fig. 3.7: Cicatricial entropion of the upper lid with

needles at the lid margin or just above the cilia.

Senile or Involutional Ectropion

Fig. 3.10: Senile ectropion

lateral canthus in cases of severe lid lengthening.

Mechanical Ectropion 5. Hornblass A, Hanig CJ. Oculoplastic, Orbital, and Reconstruc-

Blepharitis and Meibomian

INTRODUCTION Table 4.1: Classification schemes of blepharitis

Contd... respectively, which is simple and practical. Though

Table 4.2: Differentiating features of staphylococcal and seborrheic blepharitis4

Table 4.3: Signs of anterior blepharitis

There is usually conjunctival hyperemia along with Differential Diagnosis

MGD is cicatricial MGD seen in cicatrizing conjunc-

ANATOMY AND PHYSIOLOGY

Table 4.6: Lipid alteration in meibomian gland dysfunction35

Clinical Features Tear film

Fig. 4.10: Meibomian gland dysfunction with capping of the

Fig. 4.7: Severe Meibomian gland dysfunction with multiple

Fig. 4.11: Meibomian gland dysfunction with hyperkerati-

Fig. 4.8: Meibomian gland dysfunction with capping(arrow),

Fig. 4.12: Meibomian gland dysfunction with telengiectasia

orifices with pouting and decrease gland secretion.

gland dropout have been found to have a higher tear

STYE (HORDEOLUM EXTERNUM) Treatment

CHALAZION (MEIBOMIAN CYST)

HORDEOLUM INTERNUM (ACUTE MEIBOMITIS)

leprosy, and syphilis can be responsible for production

this lesion can produce follicular conjunctivitis due to

WARTS (VERRUCA VULGARIS)

Anomalies of the Eyelid Position

PTOSIS (BLEPHAROPTOSIS) Table 6.1: Showing the causes of ptosis

exercise. Difficulty in deglutition and respiration are

Figs 6.1A and B: Congenital unilateral ptosis.

Fig. 6.2: Bilateral congenital ptosis with head posture

Examination of the Eye