Clinical and Experimental Ophthalmology, Jun 1, 2004
ABSTRACT To analyse five cases of iridocorneal endothelial (ICE) syndrome and describe the micros... more ABSTRACT To analyse five cases of iridocorneal endothelial (ICE) syndrome and describe the microstructural characteristics observed by in vivo confocal microscopy. All five subjects presented with clinical characteristics suggestive of ICE syndrome and were examined clinically by Orbscan II pachymetry and by in vivo confocal microscopy. At least 600 sequential digital confocal images throughout the z-axis were analysed qualitatively and quantitatively for each cornea. Clinically, all subjects presented with: minimal to moderate corneal oedema, focal to diffuse 'beaten metal' appearance of the corneal endothelium, and varying degrees of iris atrophy. Three subjects had a history of elevated intraocular pressure. In vivo confocal microscopy highlighted two main patterns of endothelial change: small cells (mean maximal diameter of 13.6 +/- 1.5 micro m), with indistinct borders and very bright and prominent, uniform nuclei (two subjects) and larger, epithelioid-like cells (mean maximal diameter of 26.6 +/- 5.5 micro m), with irregular borders and non-homogenous, diversely shaped nuclei (three subjects). Different degrees of alteration of stromal structure, very prominent corneal nerves and unusual syncytia of keratocytes were also observed. Significant oedema of the basal epithelium with increased reflectivity of the intercellular spaces was prominent in all cases. Although ICE syndrome is considered to be primarily an endothelial disease, in vivo confocal microscopy demonstrated structural alterations throughout the entire cornea even in clinically mild cases. The ability of in vivo confocal microscopy to localize and accurately measure various elements in different corneal layers will assist differentiation of various presentations of ICE syndrome as this technique becomes increasingly available in clinical practice.
Journal of Cataract and Refractive Surgery, Aug 1, 2002
This case reports an association between 2 uncommon flap complications in 1 eye related to epithe... more This case reports an association between 2 uncommon flap complications in 1 eye related to epithelial toxicity and subsequent epithelial defect secondary to prolonged intraoperative exposure to topical anesthesia. A patient had hyperopic laser in situ keratomileusis (LASIK) for the correction of +2.75 +1.75 x 70 in the left eye. Because of the patient's anxiety and movement, additional topical local anesthesia was used and the flap remained reflected for 5 minutes. Immediately postsurgery, a toxic appearance was noted in the epithelium of the LASIK flap; 24 hours later, a large central epithelial defect was identified. Three days post- LASIK, the epithelial defect had healed but diffuse lamellar keratitis was noted in the interface, particularly underlying the location of the original epithelial defect. Over 6 weeks, a self-limiting epithelial ingrowth developed in the inferior interface. Fourteen months post-LASIK, the uncorrected visual acuity was 6/9 with a residual refraction of +0.50 +0.50 x 90.
Background Omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahex... more Background Omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory and neuroprotective properties. This study sought to determine the relationship between corneal parameters and systemic omega-3 fatty acid levels. Methods Forty-seven participants with no/mild peripheral neuropathy (26 with diabetes and 21 without) underwent comprehensive ocular surface and systemic PUFA assessments. Corneal anatomical parameters were assessed using in vivo confocal microscopy. Corneal sensitivity was measured using non-contact esthesiometry. Relationships between systemic PUFA levels and corneal parameters were evaluated with multiple linear regression, adjusted for age, sex, neuropathy symptom score, and presence of diabetes and dry eye disease. The relationship between corneal nerve fibre length (CNFL) and corneal sensitivity threshold was evaluated. Results The median Omega-3 Index, a measure of erythrocyte EPA and DHA, was 5...
Manually quantifying immune cells (ICs), commonly considered dendritic cells, in the corneal epit... more Manually quantifying immune cells (ICs), commonly considered dendritic cells, in the corneal epithelium from in vivo confocal microscopy (IVCM) images can be influenced by observer bias. This study sought to evaluate the repeatability of manual IC quantification. Cell counts were first performed for 184 non-overlapping IVCM images by a single observer. Quantifications were undertaken to establish the total cell numbers per image, and the numbers of three cell morphological subtypes: mature ICs (with elongated dendrites), immature ICs (with short- or non-discernible dendrites) and globular cells (with large bodies and no visible dendrites). Cell counts were then repeated by the same observer, and independently undertaken by a second observer. Prior to these counts, both observers undertook an agreement 'training' process to define IC appearance and delineate morphological subtypes. Total IC counts demonstrated excellent intra- and inter-observer reliability (intraclass correlation coefficients (ICC) > 0.90). Bland-Altman plots showed that interobserver measurement bias increased as a function of the total IC number in the image prior to consensus training. For total IC counts after the observer training process, there was no significant interobserver measurement bias. For IC morphological subtypes, there was a positive relationship between the mean inter-observer difference and average cell count for mature ICs and globular cells, but not immature ICs. In conclusion, higher variability in manual corneal IC counts exists when more cells are present in an IVCM image. Implementing an observer training process reduced inter-observer variability and minimised systematic measurement error.
PURPOSE Antimicrobial ultraviolet C (UVC) has proven efficacy in vitro against keratitis isolates... more PURPOSE Antimicrobial ultraviolet C (UVC) has proven efficacy in vitro against keratitis isolates and has potential to treat corneal infection if safety can be confirmed. METHOD Safety of 265 nm, intensity 1.93 mW/cm2 UVC (15-300 s exposures) was investigated in vitro via cyclobutane pyrimidine dimer (CPD) formation in DNA of human cultured corneal epithelial cells; ex vivo, by evaluating UVC transmissibility as a function of porcine corneal thickness; and in vivo, by evaluating CPD induction in the mouse cornea following UVC exposure. RESULTS A single exposure of 15 s UVC did not induce significant CPD formation (0.92 ± 1.45%) in vitro relative to untreated control (p = 0.93) whereas 300 s exposure caused extensive CPD formation (86.8 ± 13.73%; p < 0.0001). Cumulative exposure to 15 s UVC daily for 3 days induced more CPD (14.6 ± 8.2%) than a single equivalent 45 s exposure (8.3 ± 4.0%) (p < 0.001) but levels returned to baseline within 72 h (p = 0.29), indicating highly efficient DNA repair. Ex vivo, UVC transmission decreased sharply with increasing corneal thickness, confirming UVC effects are limited to the superficial corneal layers. In vivo evaluations demonstrated no detectable CPD after three consecutive daily 15 s UVC exposures, whereas a single 300 s exposure induced extensive CPD formation in superficial corneal epithelium. CONCLUSION Up to three daily doses of 15 s UVC, in vivo, appear safe with respect to CPD formation. Ongoing research exploring UVC as a possible treatment for microbial keratitis is warranted.
The goals of the TFOS DEWS II Definition and Classification Subcommittee were to create an eviden... more The goals of the TFOS DEWS II Definition and Classification Subcommittee were to create an evidence-based definition and a contemporary classification system for dry eye disease (DED). The new definition recognizes the multifactorial nature of dry eye as a disease where loss of homeostasis of the tear film is the central pathophysiological concept. Ocular symptoms, as a broader term that encompasses reports of discomfort or visual disturbance, feature in the definition and the key etiologies of tear film instability, hyperosmolarity, and ocular surface inflammation and damage were determined to be important for inclusion in the definition. In the light of new data, neurosensory abnormalities were also included in the definition for the first time. In the classification of DED, recent evidence supports a scheme based on the pathophysiology where aqueous deficient and evaporative dry eye exist as a continuum, such that elements of each are considered in diagnosis and management. Centr...
Dry eye disease is a large worldwide public health issue. It is common, chronic, and progressive ... more Dry eye disease is a large worldwide public health issue. It is common, chronic, and progressive and causes a significant reduction in quality of life and functional ability. Its prevalence increases with age, and no treatment is curative; therefore with an aging population, the prevalence will only increase. This will result in an ever expanding cost to society, both direct (need for medical care) and indirect (loss of productivity).
Journal of Cataract and Refractive Surgery, Apr 1, 2001
To evaluate the safety and predictability of laser in situ keratomileusis (LASIK) retreatment fol... more To evaluate the safety and predictability of laser in situ keratomileusis (LASIK) retreatment following primary procedures for high myopia and astigmatism. Corneal Diseases and Excimer Laser Research Unit, Department of Ophthalmology, University of Dundee, Dundee, United Kingdom. This prospective observational study of retreatment comprised a cohort of 109 eyes having primary LASIK for high myopia and astigmatism with a spherical equivalent (SE) of -9.70 diopters (D) +/- 4.06 (SD). Twenty-four eyes (22%) with an initial myopic SE of -9.83 +/- 3.50 D, a comparable subset of the entire group (P &lt; .05), had retreatment for residual myopia (-3.02 +/- 2.17 D) to improve uncorrected visual acuity (UCVA) by reelevating the corneal flap and ablating the stromal bed. The mean follow-up after retreatment was 12.8 +/- 5.1 months (range 1.5 to 24 months; 19 eyes &gt;/=6 months, 13 eyes &gt; or = 12 months). The mean myopic SE was reduced to +0.53 +/- 0.62 D at 1 week, +0.05 +/- 0.50 D at 1 month, +0.30 +/- 0.50 D at 6 months, and +0.18 +/- 0.42 D at the latest follow-up, 12.8 months. At the latest review, 62% of eyes were within +/-0.50 D of emmetropia and 100% were within +/-1.00 D. The mean refraction did not alter statistically between 1 week and subsequent times. The mean UCVA improved from 6/30 prior to retreatment to 6/9 at the latest follow-up. Uncorrected visual acuity of 6/6 or better, 6/9 or better, and 6/12 or better was achieved by 33.0%, 75.0%, and 95.8% of eyes, respectively. No significant complications that led to a loss of best corrected visual acuity were encountered, although retreatment procedures were more uncomfortable than primary procedures and self-limiting; epithelial ingrowth that did not threaten vision was common, and 2 patients complained of nighttime visual symptoms. Retreatment of residual myopia by reelevating the flap was relatively safe and predictable, with a low risk of sight-threatening complications. However, longer term studies may be required to detect late complications.
Page 1. 140 Journal of Refractive Surgery Volume 16 March/April 2000 ABSTRACT PURPOSE: To evaluat... more Page 1. 140 Journal of Refractive Surgery Volume 16 March/April 2000 ABSTRACT PURPOSE: To evaluate the efficacy of excimer laser in situ keratomileusis (LASIK) in the treat-ment of refractive errors after penetrating kerato-plasty. ...
Clinical and Experimental Ophthalmology, Jun 1, 2004
ABSTRACT To analyse five cases of iridocorneal endothelial (ICE) syndrome and describe the micros... more ABSTRACT To analyse five cases of iridocorneal endothelial (ICE) syndrome and describe the microstructural characteristics observed by in vivo confocal microscopy. All five subjects presented with clinical characteristics suggestive of ICE syndrome and were examined clinically by Orbscan II pachymetry and by in vivo confocal microscopy. At least 600 sequential digital confocal images throughout the z-axis were analysed qualitatively and quantitatively for each cornea. Clinically, all subjects presented with: minimal to moderate corneal oedema, focal to diffuse &#39;beaten metal&#39; appearance of the corneal endothelium, and varying degrees of iris atrophy. Three subjects had a history of elevated intraocular pressure. In vivo confocal microscopy highlighted two main patterns of endothelial change: small cells (mean maximal diameter of 13.6 +/- 1.5 micro m), with indistinct borders and very bright and prominent, uniform nuclei (two subjects) and larger, epithelioid-like cells (mean maximal diameter of 26.6 +/- 5.5 micro m), with irregular borders and non-homogenous, diversely shaped nuclei (three subjects). Different degrees of alteration of stromal structure, very prominent corneal nerves and unusual syncytia of keratocytes were also observed. Significant oedema of the basal epithelium with increased reflectivity of the intercellular spaces was prominent in all cases. Although ICE syndrome is considered to be primarily an endothelial disease, in vivo confocal microscopy demonstrated structural alterations throughout the entire cornea even in clinically mild cases. The ability of in vivo confocal microscopy to localize and accurately measure various elements in different corneal layers will assist differentiation of various presentations of ICE syndrome as this technique becomes increasingly available in clinical practice.
Journal of Cataract and Refractive Surgery, Aug 1, 2002
This case reports an association between 2 uncommon flap complications in 1 eye related to epithe... more This case reports an association between 2 uncommon flap complications in 1 eye related to epithelial toxicity and subsequent epithelial defect secondary to prolonged intraoperative exposure to topical anesthesia. A patient had hyperopic laser in situ keratomileusis (LASIK) for the correction of +2.75 +1.75 x 70 in the left eye. Because of the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s anxiety and movement, additional topical local anesthesia was used and the flap remained reflected for 5 minutes. Immediately postsurgery, a toxic appearance was noted in the epithelium of the LASIK flap; 24 hours later, a large central epithelial defect was identified. Three days post- LASIK, the epithelial defect had healed but diffuse lamellar keratitis was noted in the interface, particularly underlying the location of the original epithelial defect. Over 6 weeks, a self-limiting epithelial ingrowth developed in the inferior interface. Fourteen months post-LASIK, the uncorrected visual acuity was 6/9 with a residual refraction of +0.50 +0.50 x 90.
Background Omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahex... more Background Omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory and neuroprotective properties. This study sought to determine the relationship between corneal parameters and systemic omega-3 fatty acid levels. Methods Forty-seven participants with no/mild peripheral neuropathy (26 with diabetes and 21 without) underwent comprehensive ocular surface and systemic PUFA assessments. Corneal anatomical parameters were assessed using in vivo confocal microscopy. Corneal sensitivity was measured using non-contact esthesiometry. Relationships between systemic PUFA levels and corneal parameters were evaluated with multiple linear regression, adjusted for age, sex, neuropathy symptom score, and presence of diabetes and dry eye disease. The relationship between corneal nerve fibre length (CNFL) and corneal sensitivity threshold was evaluated. Results The median Omega-3 Index, a measure of erythrocyte EPA and DHA, was 5...
Manually quantifying immune cells (ICs), commonly considered dendritic cells, in the corneal epit... more Manually quantifying immune cells (ICs), commonly considered dendritic cells, in the corneal epithelium from in vivo confocal microscopy (IVCM) images can be influenced by observer bias. This study sought to evaluate the repeatability of manual IC quantification. Cell counts were first performed for 184 non-overlapping IVCM images by a single observer. Quantifications were undertaken to establish the total cell numbers per image, and the numbers of three cell morphological subtypes: mature ICs (with elongated dendrites), immature ICs (with short- or non-discernible dendrites) and globular cells (with large bodies and no visible dendrites). Cell counts were then repeated by the same observer, and independently undertaken by a second observer. Prior to these counts, both observers undertook an agreement 'training' process to define IC appearance and delineate morphological subtypes. Total IC counts demonstrated excellent intra- and inter-observer reliability (intraclass correlation coefficients (ICC) > 0.90). Bland-Altman plots showed that interobserver measurement bias increased as a function of the total IC number in the image prior to consensus training. For total IC counts after the observer training process, there was no significant interobserver measurement bias. For IC morphological subtypes, there was a positive relationship between the mean inter-observer difference and average cell count for mature ICs and globular cells, but not immature ICs. In conclusion, higher variability in manual corneal IC counts exists when more cells are present in an IVCM image. Implementing an observer training process reduced inter-observer variability and minimised systematic measurement error.
PURPOSE Antimicrobial ultraviolet C (UVC) has proven efficacy in vitro against keratitis isolates... more PURPOSE Antimicrobial ultraviolet C (UVC) has proven efficacy in vitro against keratitis isolates and has potential to treat corneal infection if safety can be confirmed. METHOD Safety of 265 nm, intensity 1.93 mW/cm2 UVC (15-300 s exposures) was investigated in vitro via cyclobutane pyrimidine dimer (CPD) formation in DNA of human cultured corneal epithelial cells; ex vivo, by evaluating UVC transmissibility as a function of porcine corneal thickness; and in vivo, by evaluating CPD induction in the mouse cornea following UVC exposure. RESULTS A single exposure of 15 s UVC did not induce significant CPD formation (0.92 ± 1.45%) in vitro relative to untreated control (p = 0.93) whereas 300 s exposure caused extensive CPD formation (86.8 ± 13.73%; p < 0.0001). Cumulative exposure to 15 s UVC daily for 3 days induced more CPD (14.6 ± 8.2%) than a single equivalent 45 s exposure (8.3 ± 4.0%) (p < 0.001) but levels returned to baseline within 72 h (p = 0.29), indicating highly efficient DNA repair. Ex vivo, UVC transmission decreased sharply with increasing corneal thickness, confirming UVC effects are limited to the superficial corneal layers. In vivo evaluations demonstrated no detectable CPD after three consecutive daily 15 s UVC exposures, whereas a single 300 s exposure induced extensive CPD formation in superficial corneal epithelium. CONCLUSION Up to three daily doses of 15 s UVC, in vivo, appear safe with respect to CPD formation. Ongoing research exploring UVC as a possible treatment for microbial keratitis is warranted.
The goals of the TFOS DEWS II Definition and Classification Subcommittee were to create an eviden... more The goals of the TFOS DEWS II Definition and Classification Subcommittee were to create an evidence-based definition and a contemporary classification system for dry eye disease (DED). The new definition recognizes the multifactorial nature of dry eye as a disease where loss of homeostasis of the tear film is the central pathophysiological concept. Ocular symptoms, as a broader term that encompasses reports of discomfort or visual disturbance, feature in the definition and the key etiologies of tear film instability, hyperosmolarity, and ocular surface inflammation and damage were determined to be important for inclusion in the definition. In the light of new data, neurosensory abnormalities were also included in the definition for the first time. In the classification of DED, recent evidence supports a scheme based on the pathophysiology where aqueous deficient and evaporative dry eye exist as a continuum, such that elements of each are considered in diagnosis and management. Centr...
Dry eye disease is a large worldwide public health issue. It is common, chronic, and progressive ... more Dry eye disease is a large worldwide public health issue. It is common, chronic, and progressive and causes a significant reduction in quality of life and functional ability. Its prevalence increases with age, and no treatment is curative; therefore with an aging population, the prevalence will only increase. This will result in an ever expanding cost to society, both direct (need for medical care) and indirect (loss of productivity).
Journal of Cataract and Refractive Surgery, Apr 1, 2001
To evaluate the safety and predictability of laser in situ keratomileusis (LASIK) retreatment fol... more To evaluate the safety and predictability of laser in situ keratomileusis (LASIK) retreatment following primary procedures for high myopia and astigmatism. Corneal Diseases and Excimer Laser Research Unit, Department of Ophthalmology, University of Dundee, Dundee, United Kingdom. This prospective observational study of retreatment comprised a cohort of 109 eyes having primary LASIK for high myopia and astigmatism with a spherical equivalent (SE) of -9.70 diopters (D) +/- 4.06 (SD). Twenty-four eyes (22%) with an initial myopic SE of -9.83 +/- 3.50 D, a comparable subset of the entire group (P &lt; .05), had retreatment for residual myopia (-3.02 +/- 2.17 D) to improve uncorrected visual acuity (UCVA) by reelevating the corneal flap and ablating the stromal bed. The mean follow-up after retreatment was 12.8 +/- 5.1 months (range 1.5 to 24 months; 19 eyes &gt;/=6 months, 13 eyes &gt; or = 12 months). The mean myopic SE was reduced to +0.53 +/- 0.62 D at 1 week, +0.05 +/- 0.50 D at 1 month, +0.30 +/- 0.50 D at 6 months, and +0.18 +/- 0.42 D at the latest follow-up, 12.8 months. At the latest review, 62% of eyes were within +/-0.50 D of emmetropia and 100% were within +/-1.00 D. The mean refraction did not alter statistically between 1 week and subsequent times. The mean UCVA improved from 6/30 prior to retreatment to 6/9 at the latest follow-up. Uncorrected visual acuity of 6/6 or better, 6/9 or better, and 6/12 or better was achieved by 33.0%, 75.0%, and 95.8% of eyes, respectively. No significant complications that led to a loss of best corrected visual acuity were encountered, although retreatment procedures were more uncomfortable than primary procedures and self-limiting; epithelial ingrowth that did not threaten vision was common, and 2 patients complained of nighttime visual symptoms. Retreatment of residual myopia by reelevating the flap was relatively safe and predictable, with a low risk of sight-threatening complications. However, longer term studies may be required to detect late complications.
Page 1. 140 Journal of Refractive Surgery Volume 16 March/April 2000 ABSTRACT PURPOSE: To evaluat... more Page 1. 140 Journal of Refractive Surgery Volume 16 March/April 2000 ABSTRACT PURPOSE: To evaluate the efficacy of excimer laser in situ keratomileusis (LASIK) in the treat-ment of refractive errors after penetrating kerato-plasty. ...
Uploads
Papers