RU2716756C1 - Method of treating acanthamoeba keratitis complicated by a secondary infection - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, specifically to ophthalmology. First, micro-diathermocoagulation of the infiltration zone within the involved corneal layer. That is followed by corneal collagen cross-linking. Riboflavin instillations are alternated with the antibiotic or antiseptic and mycostatic agent. If a dense surface of the infiltrate is present before the micro- diathermocoagulation, a superficial keratectomy is performed.

EFFECT: method enables increasing rate of resorption and cleansing of ulcer from purulent content, preventing spreading of inflammatory process in depth and in area of cornea.

1 cl, 1 ex

Description

The present invention relates to ophthalmology and is intended for the treatment of acanthamoebic keratitis complicated by a secondary infection.

Acanthamoebic keratitis [AK] is a relatively rare, but very dangerous disease of the cornea, its development is associated with the wearing of contact lenses, as well as with the presence of microtrauma of the cornea, followed by contact with soil or water particles [Kasparova EA, Kasparov A.A. , Marchenko N.R., Fedorov A.A., Egorova G.B., Kobzova M.V., Mitichkina T.S. "Clinical features, diagnosis, results of therapeutic and surgical treatment of acanthamoebic keratitis." Ophthalmology. 2017; 14 (4): 306-314.]. Often, acanthamoebic keratitis is complicated by the addition of a secondary infection. Thus, a concomitant bacterial infection in AK is often detected - according to N. Kaufman - in 58% of patients [Kaufman N.E., Barron B.A., McDonald M.V. Parasitic infections. The Cornea 2-nd Edition. Butterworth-Heinemann; 1998. p. 333]. Complicated purulent keratitis can be caused by a wide range of bacterial or fungal agents and is a sight-threatening disease characterized by clinical severity and transience, often leading the eye to death due to the development of endophthalmitis [Kasparova EA Purulent corneal ulcers - etiology, pathogenesis, classification. Bulletin of Ophthalmology. 2015; 131 (5): 87-97].

Various methods are known for the treatment of AK complicated by a secondary infection.

It is known to use frequent installations of solutions of antibiotics and antiseptics and antifungal agents in the conjunctival cavity. However, the increase in the number of resistant strains of microorganisms, as well as the development of pronounced toxic-allergic reactions with frequent installations of antibacterial or antifungal solutions, significantly complicates the treatment of mixed keratitis. Despite significant advances in drug treatment, subgroups of virulent bacteria, fungi and parasites that are resistant to anti-infection therapy remain [Garg P., Rao GN Therapeutic keratoplasty. Corneal Surgery theory technique and tissue. 4 ^th edition, 2009. Editor F. Brightbill. Mosby Elsevier: 439-449]. So far, no chemotherapeutic agent has been described as the only effective anti-AK agent. This is due to the existence of many factors, including a wide range of virulence, the formation of resistance of the pathogen to drugs, various duration and severity of the lesion. And although trophozoites are sensitive to conventional AK therapy, a specific drug capable of effectively destroying cysts with monotherapy does not yet exist [Marchenko NR, Kasparova EA Treatment of acanthamoebic keratitis. Bulletin of Ophthalmology. 2016; 132 (5): 110-116.].

Known surgical method for the treatment of AK, complicated by a secondary infection, in the form of corneal transplantation - therapeutic keratoplasty. However, after a therapeutic corneal transplant with active AK complicated by a secondary infection, there is a high percentage of complications, especially relapse of acanthamoebic keratitis on the graft and a relatively low percentage of transparent graft engraftment [Marchenko N.R. Dasparova E.A. Treatment of acanthamoebic keratitis. Herald of ophthalmology. 2016; 132 (5): 110-116.]. This method is taken as the closest analogue.

There is a method of treating an uncomplicated secondary infection with AK, including corneal crosslinking (CRL) [Garduo-Vieyra L, Gonzalez-Sanchez CR, Hernandez Da Mota SE. Ultrav / iolet A light and riboflavin therapy for acanthamoeba keratitis: a case report. Case Rep Ophthalmol. 2011; 2 (2): 291-295. https://doi.org/10.1159/000331707]. The known KRL method is carried out by installing a 0.1% riboflavin / dextran solution every 2 minutes for 30 minutes and irradiation with 365 nm ultraviolet A with a radiation intensity of 3 mV / cm ² for 30 minutes with a total radiation dose of 5.4 J / cm2. [Said D., Elalfy M., Gatzioufas Z., El-Zakzouk E., Hassan M., Saif M., MD, Zaki A., Dua H., Hafezi F. Collagen Cross-Linking with Photoactivated Riboflavin (PACK- CXL) for the Treatment of Advanced Infectious Keratitis with Corneal Melting. Ophthalmology. 2014 Jul; 121 (7): 1377-82].

The essence of the crosslinking method is the cross-stitching of stromal fibers of the cornea as a result of the combined effect of a photosensitizing substance - riboflavin (vitamin B2) and ultraviolet light. In case of KRL, fibrils “stick together” and thicken collagen fibers in the cornea under the influence of riboflavin and ultraviolet (UV), which leads to an increase in its biomechanical stability. Crosslinking is currently widely used in the treatment of keratoconus. In recent years, KRL began to be used to treat infectious keratitis. First, under the influence of UVA, bacterial DNA is damaged. Then UV-activated riboflavin causes a chemical modification of the functional groups of the bacterial DNA nucleic acids, making replication of pathogens impossible [Boldyreva EA, Galleev RS, Kuznetsov SL., Savelyev M.Yu. Crosslinking in the treatment of corneal ulcers (clinical case) Actual problems of ophthalmology 2011].

As a result of KRL, there is an increase in the biomechanical strength of the cornea [Hafezi F., Randelman B.J. "Corneal collagen crosslinking", 167 p., 2013, SLACK Incorporated]. The results of in vitro experiments indicate that in the course of CRL there is also a change in tissue properties, an increase in resistance to enzymes secreted by infectious agents responsible for the melting of corneal collagen. [Said DG1, Elalfy MSI, Gatzioufas Z2, El-Zakzouk ESI, Hassan MA3, Saif MY3, Zaki AA1, Dua HS4, Hafezi F5 //// Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the treatment of advanced infectious keratitis with corneal melting. Ophthalmology. 2014 Jul; 121 (7): 1377-82. doi: 10.1016 / j.ophtha.2014.01.01.01.]. However, the most important is the antimicrobial effect of RRL, which occurs due to the interaction of UVA with riboflavin [4]. The mechanism of action is represented by the direct effect of UVA on the genetic material of microbes, nonspecific damage due to oxidative stress and a more specific effect based on the intercalation of riboflavin, leading to the oxidation of guanine DNA / RNA microbes.

All of the listed effects of KRL with respect to corneal tissue — increasing biomechanical strength, increasing resistance to thermal effects and resistance to enzymes — provide the therapeutic effect of KRL in infectious diseases of the cornea.

A known method of treating purulent corneal ulcer (GJR) or purulent keratitis using microdermatocoagulation (MDC). However, this method is quite effective in the treatment of superficial purulent ulcers, capturing no more than 1/3 of the depth of the corneal stroma. [Kasparova E.A., Zaitsev A.V., Kasparova E.A., Kasparov A.A. Microdermatocoagulation in the treatment of infectious corneal ulcers. Ophthalmology. 2016; 13 (3): 157-162. DOI: 10.18008 / 1816-5095-2016-3-157-162].

The objective of the invention is to develop a combined method of treatment of acanthamoebic keratitis complicated by a secondary infection.

The technical result of the invention is to increase the rate of resorption and purification of the ulcer from the purulent contents, preventing the spread of the inflammatory process in the depth and area of the cornea, as well as eliminating the need for emergency keratoplasty and improving the conditions for possible subsequent keratoplasty.

The technical result is achieved by combining microdermatocoagulation of the inflammatory infiltration zone with corneal crosslinking.

Microdiatermocoagulation allows you to eliminate purulent infiltration, thereby providing access to UV radiation in the thickness of the cornea, in which the acanthambic infiltrate is localized. In addition, with the help of microdermatocoagulation, coagulation of the surface layers of the corneal stroma occurs, which are then removed in the form of a scab along with cysts. Thus, microdermatocoagulation allows the destruction of cysts, which, on the one hand, reduces the risk of recurrence, and on the other hand, “frees” the intercellular space of the corneal tissue from cysts, which probably reduces the obstacles to the photopolymerization of stromal fibers under the influence of the photo-mediator (Riboflavin solution) and low doses of ultraviolet radiation during XRD.

The method is as follows.

First, microdermatocoagulation of the infiltration zone is carried out within the affected layer of the cornea. Corneal collagen crosslinking (CRL) is then performed. At the same time, riboflavin installations alternate with antibiotic or antiseptic and mycostatic installations. In the presence of a dense surface of the infiltrate, superficial keratectomy is performed before microdermatocoagulation.

Example.

Patient A. 32 years old. In May 2019, against the background of wearing soft contact lenses on OU, acanthambic keratitis developed with the subsequent addition of a bacterial infection.

In June 2019, the patient turned to the FGBNI NIIIGB with complaints of a sharp decrease in vision (OD - 0.01 OS-0.02), severe pain in both eyes, severe corneal syndrome (lacrimation, blepharospasm, photophobia). At the time of the OD examination, an active purulent infiltrate was visualized in the center of the cornea, with a diameter of 7 mm, with blurry edges, a purulent infiltrate (grayish-colored keratitis) was visualized in the surface and middle layers of the corneal stroma, a grayish-colored infiltrate was seen. Active purulent infiltration with purulent melting surface _^(1/4) layers of the corneal stroma accompanied by the development hypopyon. OS is a dense surface purulent infiltrate without signs of fusion in the center of the cornea, 4.5 mm in diameter and a grayish ring-shaped infiltrate located below it (it captured more than half the thickness of the stroma). Light microscopy of the contents of the OU corneal scraping performed over and around the ulcer area, as well as intravital confocal microscopy, confirmed the presence of trophozoites and acantameba cysts, as well as bacteria.

The patient received the first stage of combined treatment according to the proposed method for OD - MDK, followed by crosslinking of corneal collagen. After installing the ophthalmic anesthetic solution three times into the conjunctival cavity under visual control, using the tip inserted into the handle of the microdermatocoagulator, the energy of the ulcer, its walls and the bottom was coagulated within apparently healthy tissues, then the working part of the same electrode of the diathermocoagulator was mechanically cleaned the resulting wound surface from coagulated tissues. Next, a riboflavin solution was alternately installed in the conjunctival cavity every 2 minutes, a chlorhexidine antiseptic solution of 0.02%, and fluconazole solution during the whole time of exposure to ultraviolet radiation with parameters generally accepted for SCRL (wavelength 365-375 nm, light exposure to UV rays, duration 30 minutes).

After 2 days on OS, the patient underwent crosslinking of corneal collagen with preliminary superficial keratectomy and microdermatocoagulation. A keratectomy on the OS was performed due to the fact that the surface of the infiltrate had the consistency of a dense crust. Microdermatocoagulation and crosslinking of corneal collagen was performed in the same way as on OD. In the postoperative period, the patient received active conservative treatment.

After 7 days, a distinct positive dynamics was observed in both eyes: purulent infiltration was absent, stromal lysis on OD was stopped, ring-shaped infiltrate persisted in the OS stromal layers, but the intensity of infiltration became less pronounced. After 12 days, complete epithelization occurred, the annular infiltrate was partially resorbed. 21 days after the procedure, almost complete resorption of the annular infiltrate was observed. Corneal syndrome was stopped, visual acuity increased from 0.01 to 0.1. The absence of pain and inflammation of the cornea. Thus, the proposed method allows to increase the rate of resorption, cleansing the ulcer from purulent contents, and accordingly, reduce the number of complications.

Claims (2)

1. A method of treating acanthamoebic keratitis complicated by a secondary infection, characterized in that the microdermatocoagulation of the infiltration zone is performed within the affected layer of the cornea, and then corneal collagen is crosslinked, with riboflavin installations alternating with antibiotic or antiseptic and mycostatic installations. 2. The method according to p. 1, characterized in that in the presence of a dense surface of the infiltrate before microdermatocoagulation, superficial keratectomy is performed.