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      Recent advances in corneal collagen cross-linking

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          Abstract

          Corneal collagen cross-linking has become the preferred modality of treatment for corneal ectasia since its inception in late 1990s. Numerous studies have demonstrated the safety and efficacy of the conventional protocol. Our understanding of the cross-linking process is ever evolving, with its wide implications in the form of accelerated and pulsed protocols. Newer advancements in technology include various riboflavin formulations and the ability to deliver higher fluence protocols with customised irradiation patterns. A greater degree of customisation is likely the path forward, which will aim at achieving refractive improvements along with disease stability. The use of cross-linking for myopic correction is another avenue under exploration. Combination of half fluence cross-linking with refractive correction for high errors to prevent post LASIK regression is gaining interest. This review aims to highlight the various advancements in the cross-linking technology and its clinical applications.

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          Most cited references81

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

          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.

            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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              Does ethnic origin influence the incidence or severity of keratoconus?

              Keratoconus affects all races, yet very little information exists as to the relative frequency in patients of different ethnic origin. We aimed to establish the incidence and severity of keratoconus in Asian and white patients. The hospital records of the ophthalmology department of a large Midlands hospital with a catchment population of approximately 900,000 (87% white, 11% Asian, 2% other) were examined retrospectively for the 10 year period from 1989 to 1998. For the age group 10-44 years the prevalence of keratoconus in Asians and whites was 229 and 57 per 100,000 respectively, a relative prevalence of 4 to 1. The incidence of keratoconus in the same age group was 19.6 and 4.5 per 100,000 per year respectively, a relative incidence of 4.4 to 1. Asians were significantly younger at presentation compared with whites (mean 22.3 +/- 6.5 vs 26.5 +/- 8.5 years, p < 0.0001). A first corneal graft was carried out on 14% of the Asian and 15% of the white patients. Of those having grafts, Asians were significantly younger than white patients at the time of diagnosis (mean 19.1 +/- 4.8 vs 25.7 +/- 7.3 years, p = 0.005) and at operation (mean 21.4 +/- 5.0 vs 28.7 +/- 7.7 years, p = 0.004). The interval from diagnosis to operation, though shorter for Asians, was not significantly different (mean 1.8 +/- 1.4 vs 2.5 +/- 1.7 years, p = 0.2). The results show previously unrecognised racial differences in the hospital presentation of keratoconus in the UK. Compared with white patients, Asians have a fourfold increase in incidence, are younger at presentation and require corneal grafting at an earlier age.
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                Author and article information

                Journal
                Indian J Ophthalmol
                Indian J Ophthalmol
                IJO
                Indian Journal of Ophthalmology
                Medknow Publications & Media Pvt Ltd (India )
                0301-4738
                1998-3689
                September 2017
                : 65
                : 9
                : 787-796
                Affiliations
                [1]Dr. Gitansha Shreyas Sachdev, The Eye Foundation, Coimbatore, India
                [1 ]Centre for Sight, New Delhi, India
                Author notes
                Correspondence to: Dr. Mahipal Sachdev, Centre for Sight, B-5/24, Safdarjung Enclave, New Delhi - 110 029, India. E-mail: drmahipal@ 123456gmail.com
                Article
                IJO-65-787
                10.4103/ijo.IJO_648_17
                5621259
                28905820
                bd3a1033-943c-45ea-90ec-2fc694ba4cb8
                Copyright: © 2017 Indian Journal of Ophthalmology

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 27 July 2017
                : 26 August 2017
                Categories
                Review Article

                Ophthalmology & Optometry
                accelerated cross-linking,corneal collagen cross-linking,customized cross-linking,photorefractive intrastromal cross-linking,pulsed cross-linking

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