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      Corneal Collagen Cross-linking for Treatment of Non-healing Corneal Ulcers

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          Abstract

          Purpose:

          To evaluate the efficacy of corneal collagen cross-linking (CXL) for treatment of corneal ulcers not responding to antimicrobial therapy.

          Methods:

          Eight patients with corneal ulcers associated with corneal melting, not responding to conventional antibiotic therapy, were treated with CXL. The procedure was performed according to the standardized protocol for keratoconus. Preoperative medications were continued after CXL in all cases. Microbiological exams revealed Pseudomonas aeruginosa in 3 cases. Follow up continued from 1 to 10 months.

          Results:

          In 6 of 8 eyes, progression of corneal melting was halted and complete epithelialization occurred. In one eye emergency keratoplasty was needed due to corneal perforation. A conjunctival flap was performed to treat severe localized corneal thinning in one of the patients a few days after CXL. Significant clinical improvement occurred in all cases of Pseudomonas aeruginosa keratitis.

          Conclusion:

          CXL can be considered as a promising new treatment in the management of refractory non-healing corneal ulcers, including Pseudomonas aeruginosa keratitis.

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          Most cited references34

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          Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking.

          Gregor Wollensak, Eberhard Spoerl, Theo Seiler (2003)
          To evaluate the biomechanical effect of combined riboflavin-ultraviolet A (UVA) treatment on porcine and human corneas. Department of Ophthalmology, Technical University of Dresden, Dresden, Germany. Corneal strips from 5 human enucleated eyes and 20 porcine cadaver corneas were treated with the photosensitizer riboflavin and irradiated with 2 double UVA diodes (370 nm, irradiance = 3 mW/cm2) for 30 minutes. After cross-linking, static stress-strain measurements of the treated and untreated corneas were performed using a microcomputer-controlled biomaterial tester with a prestress of 5 x 10(3) Pa. There was a significant increase in corneal rigidity after cross-linking, indicated by a rise in stress in treated porcine corneas (by 71.9%) and human corneas (by 328.9%) and in Young's modulus by the factor 1.8 in porcine corneas and 4.5 in human corneas. The mean central corneal thickness was 850 microm +/- 70 (SD) in porcine corneas and 550 +/- 40 microm in human corneas. Riboflavin-UVA-induced collagen cross-linking led to an increase in mechanical rigidity in porcine corneas and an even greater increase in human corneas. As collagen cross-linking is maximal in the anterior 300 microm of the cornea, the greater stiffening effect in human corneas can be explained by the relatively larger portion of the cornea being cross-linked in the overall thinner human cornea.
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            Induction of cross-links in corneal tissue.

            E Spoerl, M Huhle, T Seiler (1998)
            The aim of this study was to investigate the possibility of induction of cross-links in corneal tissue in order to increase the stiffness as a basis for a future conservative treatment of keratectasia. Collagenous biomaterials can be stabilized by chemical and physical agents. The epithelium of enucleated porcine eyes was removed. Eight test groups, 10 eyes each, were treated with UV-light (lambda=254 nm), 0.5% riboflavin, 0.5% riboflavin and UV-light (365 nm) blue light (436 nm) and sunlight, and the chemical agents-glutaraldehyde (1% and 0.1%, 10 min) and Karnovsky's solution (0.1%, 10 min). Strips of 5 mm in width and 9 mm in length were cut from each cornea and the stress-strain behaviour of the strips was measured to assess the cross-linking process. For comparison, ten untreated corneas were measured by the same method. Compared to untreated corneas treatment with riboflavin and UV-irradiation as well as weak glutaraldehyde or Karnovsky's solutions resulted in an increased stiffness of the cornea. The biomechanical behaviour of the cornea can be altered by glutaraldehyde, Karnovsky's solution, and with riboflavin and UV-irradiation which offers the potential of a conservative treatment of keratoconus. To optimize this effect further investigation is necessary regarding the dose-response and in-vivo application. Copyright 1998 Academic Press Limited.
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              Increased resistance of crosslinked cornea against enzymatic digestion.

              Eberhard Spoerl, Gregor Wollensak, Theo Seiler (2004)
              Collagen-crosslinking using combined riboflavin/ UVA treatment has been developed by us as a new treatment for keratoconus by stiffening the collagenous matrix. Recently, we have started to use the same method for the treatment of corneal ulcers. The aim of the present study was to evaluate the influence of the crosslinking treatment on the resistance of the cornea against enzymatic degradation. 60 enucleated porcine eyes were treated with the photosensitizer riboflavin and UVA-irradiation (370 nm; irradiance of 1, 2 or 3 mW/cm2) for 30 minutes and compared with 20 untreated control eyes. After crosslinking treatment, the corneal buttons were trephined and exposed to pepsin, trypsin and collagenase solutions. The extent of the corneal digestion was monitored daily. Selected cases were examined by light microscopy. The corneal buttons crosslinked with riboflavin/ UVA at 3 mW/cm2 were dissolved only by day 13 following pepsin digestion and by day 14 following collagenase treatment versus 6 days in the untreated control corneas. Digestion by trypsin was observed on day 5 in buttons crosslinked at 3 mW/cm2 compared to day 2 in the control corneas. Microscopically, a prolonged preservation especially of the anterior portion of the crosslinked corneas could be demonstrated. Photochemical crosslinking of the cornea using riboflavin and UVA results in a markedly increased resistance versus collagen digesting enzymes. The findings support the use of the new method in the treatment of corneal ulcers.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Ophthalmic Vis Res
                Journal ID (iso-abbrev): J Ophthalmic Vis Res
                Journal ID (publisher-id): JOVR
                Title: Journal of Ophthalmic & Vision Research
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 2008-2010
                ISSN (Electronic): 2008-322X
                Publication date (Print): Jan-Mar 2015
                Volume: 10
                Issue: 1
                Pages: 16-20
                Affiliations
                [1] Ophthalmic Infections Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                Author notes
                Correspondence to: Mitra Zamani, MD. Ophthalmic Infections Research Center, Ahvaz Jundishapur University of Medical Sciences, Azadegan Street, Ahvaz 61936, Iran. E-mail: zamanimitra1@ 123456gmail.com
                Article
                Publisher ID: JOVR-10-16
                DOI: 10.4103/2008-322X.156087
                PMC ID: 4424712
                PubMed ID: 26005547
                SO-VID: 53ddf930-213a-4856-b8b4-c051911391ba
                Copyright © Copyright: © Journal of Ophthalmic and Vision Research
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 23 September 2013
                Date accepted : 26 May 2014
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Ophthalmology & Optometry
                Keywords: corneal collagen cross-linking,corneal ulcer,riboflavin,ultraviolet-a
                Data availability:
                ScienceOpen disciplines: Ophthalmology & Optometry
                Keywords: corneal collagen cross-linking, corneal ulcer, riboflavin, ultraviolet-a

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