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      Corneal Collagen Cross-Linking with and without Epithelial Removal: A Contralateral Study with 0.5% Hypotonic Riboflavin Solution

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          Purpose. Our main purpose was to compare safety and efficacy in the treatment of progressive keratoconus with “epithelium-on” and “epithelium-off” corneal collagen cross-linking (CXL). Our secondary purpose was to evaluate efficacy of CXL when hypotonic 0.5% riboflavin is used as photosensitizer. Methods. One eye of 20 patients with bilateral progressive keratoconus was randomly treated for “epithelium-on” CXL (group 1) while the fellow eye underwent “epithelium-off” CXL (group 2). Hypotonic 0.5% riboflavin was used in both groups. Visual acuity, refraction, corneal topography, and wavefront aberrometry were evaluated at baseline and after 1, 6, and 12 months. Specular microscopy was performed on 10 patients preoperatively and after 12 months. Postoperative pain was evaluated using a patient questionnaire. Results. Uncorrected and corrected distance visual acuity improved significantly in both groups. Refraction, topography, and aberrometry showed nonsignificant changes from the preoperative status throughout the 12-month follow-up in both groups. Moreover, the outcomes between the groups were comparable at all follow-up points. Endothelial cell-count was stable. Postoperative pain length was shorter in group 1 ( P < 0.001). Conclusion. “Epithelium-on” and “epithelium-off” CXL using hypotonic 0.5% riboflavin were equally safe and effective in stabilization of keratoconus. Topography and aberrometry outcomes in both groups failed to show any significant improvements. This study is registered at ClinicalTrials.gov: NCT01181219.

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

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            Safety of UVA-riboflavin cross-linking of the cornea.

            To study potential damage to ocular tissue during corneal collagen cross-linking (X-linking) by means of the riboflavin/UVA (370 nm) approach. Comparison of the currently used technique with officially accepted guidelines regarding direct UV damage and the damage created by the induced free radicals (photochemical damage). The currently used UVA radiant exposure of 5.4 mJ/cm and the corresponding irradiance of 3 mW/cm2 is below the known damage thresholds of UVA for the corneal endothelium, lens, and retina. Regarding the photochemical damage caused by the free radicals, the damage thresholds for keratocytes and endothelial cells are 0.45 and 0.35 mW/cm, respectively. In a 400-microm-thick cornea saturated with riboflavin, the irradiance at the endothelial level was 0.18 mW/cm, which is a factor of 2 smaller than the damage threshold. After corneal X-linking, the stroma is depopulated of keratocytes approximately 300 microm deep. Repopulation of this area takes up to 6 months. As long as the cornea treated has a minimum thickness of 400 microm (as recommended), the corneal endothelium will not experience damage, nor will deeper structures such as lens and retina. The light source should provide a homogenous irradiance, avoiding hot spots.
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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.

                Author and article information

                Biomed Res Int
                Biomed Res Int
                BioMed Research International
                Hindawi Publishing Corporation
                22 June 2014
                : 2014
                1SynsLaser Kirurgi AS, 9007 Tromsø, Troms, Norway
                2Eye Department, University Hospital North Norway, Sykehusveien 38, 9019 Tromsø, Troms, Norway
                3Department of Medical Biochemistry, Oslo University Hospital, 0450 Oslo, Norway
                Author notes
                *Aleksandar Stojanovic: aleks@ 123456online.no

                Academic Editor: George Asimellis

                Copyright © 2014 Aleksandar Stojanovic et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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