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      A comprehensive review on corneal crosslinking

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      Author(s): , *
      Publication date (Electronic):
      Journal: Taiwan Journal of Ophthalmology
      Publisher: Wolters Kluwer - Medknow
      Keywords: Cornea, cross-linking, ectasia, keratoconus, riboflavin

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          Abstract

          Corneal crosslinking (CXL) represents a paradigm shift in the management of corneal ectatic disorders. Before CXL was introduced, patients would need specialty contact lenses and possible corneal transplantation. CXL involves a biochemical reaction in which ultraviolet A light is used in conjunction with Riboflavin to form crosslinks in between corneal stromal collagen. This leads to strengthening and stabilizing of the collagen lamellae, resulting in mechanical stiffening of the cornea. Multiple protocols have been proposed including epithelium on versus off and varying light intensity and duration of treatment. All protocols appear to be safe and effective with few reported complications including infection, stromal haze, scarring, and endothelial toxicity. Overall, CXL has demonstrated to halt the progression of the disease clinically and in keratometry readings and improve the quality of life for patients. It is a minimally invasive, cost-effective procedure that can be performed in an outpatient setting with a fast recovery time and long-lasting results.

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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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            Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus.

            Gregor Wollensak, Eberhard Spoerl, Theo Seiler (2003)
            In animal eyes, a significant increase in corneal biomechanical stiffness has been found after collagen crosslinking by combined riboflavin/ultraviolet-A (UVA) treatment. The aim of the present study was to evaluate the clinical usefulness of riboflavin/UVA-induced collagen crosslinking for bringing the progression of keratoconus to a halt. Prospective, nonrandomized clinical pilot study. Twenty-three eyes of 22 patients with moderate or advanced progressive keratoconus (maximum K value, 48-72 diopters) were included. After central corneal abrasion, photosensitizing riboflavin drops were applied and the eyes exposed to UVA (370 nm, 3 mW/cm(2)) in a 1-cm distance for 30 minutes. Postoperative examinations were performed in 6-month intervals, including visual acuity testing, corneal topography, slit-lamp examination, measurement of endothelial cell density, and photographic documentation. The follow-up time was between 3 months and 4 years. In all treated eyes, the progression of keratoconus was at least stopped. In 16 eyes (70%) regression with a reduction of the maximal keratometry readings by 2.01 diopters and of the refractive error by 1.14 diopters was found. Corneal and lens transparency, endothelial cell density, and intraocular pressure remained unchanged. Visual acuity improved slightly in 15 eyes (65%). Collagen crosslinking may be a new way for stopping the progression of keratectasia in patients with keratoconus. The need for penetrating keratoplasty might then be significantly reduced in keratoconus. Given the simplicity and minimal costs of the treatment, it might also be well-suited for developing countries. Long-term results are necessary to evaluate the duration of the stiffening effect and to exclude long term side-effects.
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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): Taiwan J Ophthalmol
                Journal ID (iso-abbrev): Taiwan J Ophthalmol
                Journal ID (publisher-id): TJO
                Journal ID (publisher-id): Taiwan J Ophthalmol
                Title: Taiwan Journal of Ophthalmology
                Publisher: Wolters Kluwer - Medknow (India )
                ISSN (Print): 2211-5056
                ISSN (Electronic): 2211-5072
                Publication date Collection: Jan-Mar 2024
                Publication date (Electronic): 02 February 2024
                Volume: 14
                Issue: 1
                Pages: 44-49
                Affiliations
                [1] Department of Ophthalmology, The Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California, USA
                Author notes
                [* ] Address for correspondence: Dr. Edward E. Manche, The Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California, USA. E-mail: cornea@ 123456stanford.edu
                Article
                Publisher ID: TJO-14-44
                DOI: 10.4103/tjo.TJO-D-23-00055
                PMC ID: 11034691
                PubMed ID: 38654993
                SO-VID: 03b0fc1a-e1b8-4edf-9478-d5afdfe4caaf
                Copyright © Copyright: © 2024 Taiwan J Ophthalmol
                License:

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                Date received : 17 April 2023
                Date accepted : 01 September 2023
                Categories
                Subject: Review Article - Narrative Review

                Keywords: cornea,cross-linking,ectasia,keratoconus,riboflavin
                Data availability:
                Keywords: cornea, cross-linking, ectasia, keratoconus, riboflavin

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