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      Current clinical practice in corneal crosslinking for treatment of progressive keratoconus in four Nordic countries

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          Abstract

          Purpose

          To evaluate clinical practice in the diagnosis and treatment of progressive keratoconus with corneal crosslinking (CXL) in four Nordic countries.

          Methods

          A questionnaire was sent to all centres at which keratoconus patients are evaluated and CXL is performed in Sweden, Denmark, Norway and Iceland. Nineteen of 20 centres participated.

          Results

          CXL is performed approximately 1300 times per year in these four Nordic countries with a population of around 21.7 million (2019). In most cases, progression is evaluated using the Pentacam HR, and the maximum keratometry reading ( K max) is considered the most important parameter. The most frequently used treatment protocol in Scandinavia is the 9 mW/cm 2 epi‐off protocol, using hydroxylpropyl methylcellulose riboflavin (HPMC‐riboflavin). The participants deemed the following areas to be in most need of improvement: adaptation of the CXL protocol to individual patients (5/19), the development of effective epi‐on treatment protocols (4/19), optimal performance of CXL in thin corneas (4/19), improvement of the definition of progression (2/19), and diagnosis of the need for re‐treatment (2/19).

          Conclusions

          We concluded that the diagnosis of progressive keratoconus and the diagnostic equipment used are similar. Treatment strategies are also similar but are suitably different to provide an interesting basis for the comparison of treatment outcomes. The high degree of participation in this survey indicates the possibility of future scientific collaboration on CXL focusing on the areas deemed to need improvement. It would also be of interest to evaluate the possibility of creating a Nordic CXL Registry. The high number of CXL treatments performed ensures sufficient statistical power to solve many questions. Such a registry could be an important contribution to evidence‐based care and would allow for longitudinal evaluation.

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          Most cited references48

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

            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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              Collagen fiber diameter in the rabbit cornea after collagen crosslinking by riboflavin/UVA.

              Collagen crosslinking of the cornea has been developed recently as a quasiconservative treatment of keratoconus. Biomechanical in vitro measurements have demonstrated a significant increase in biomechanical stiffness of the crosslinked cornea. The aim of the present study was to evaluate the effect of this new procedure on the collagen fiber diameter of the rabbit cornea. The corneas of the right eyes of 10 New Zealand White albino rabbits were crosslinked by application of the photosensitizer riboflavin and exposure to UVA light (370 nm, 3 mW/cm2) for 30 minutes. The left fellow control eyes were either left untreated (rabbits 1-4), deepithelialized (rabbits 5-7), or deepithelialized and treated with riboflavin/dextran solution (rabbits 8-10) to exclude an influence of epithelial debridement or hydration changes on the fiber diameter. On ultrathin sections of samples from the anterior and posterior cornea, the collagen fiber diameter was measured semiautomatically with the help of morphometric computer software. In the anterior stroma, the collagen fiber diameter in the treated corneas was significantly increased by 12.2% (3.96 nm), and in the posterior stroma by 4.6% (1.63 nm), compared with the control fellow eyes. In the crosslinked eyes, the collagen fiber diameter was also significantly increased by, on average, 9.3% (3.1 nm) in the anterior compared with the posterior stroma within the same eye. Collagen crosslinking using riboflavin and UVA leads to a significant increase in corneal collagen diameter. This alteration is the morphologic correlate of the crosslinking process leading to an increase in biomechanical stability. The crosslinking effect is strongest in the anterior half of the stroma because of the rapid decrease in UVA irradiance across the corneal stroma as a result of riboflavin-enhanced UVA absorption.
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                Author and article information

                Contributors
                ingemar.gustafsson@med.lu.se
                Journal
                Acta Ophthalmol
                Acta Ophthalmol
                10.1111/(ISSN)1755-3768
                AOS
                Acta Ophthalmologica
                John Wiley and Sons Inc. (Hoboken )
                1755-375X
                1755-3768
                10 July 2022
                February 2023
                : 101
                : 1 ( doiID: 10.1111/aos.v101.1 )
                : 109-116
                Affiliations
                [ 1 ] Department of Clinical Sciences, Department of Ophthalmology Lund University, Skåne University Hospital Lund Sweden
                [ 2 ] Department of Ophthalmology Sahgrenska University Hospital Mölndal Sweden
                [ 3 ] Department of Ophthalmology Aarhus University Hospital Aarhus Denmark
                Author notes
                [*] [* ] Correspondence

                Ingemar Gustafsson, Department of Ophthalmology, Skåne University Hospital, Kioskgatan 1, SE‐221 85 Lund, Sweden.

                Email: ingemar.gustafsson@ 123456med.lu.se

                Author information
                https://orcid.org/0000-0001-7001-0202
                Article
                AOS15213 ACTA-22-03-0290.R1
                10.1111/aos.15213
                10084360
                35811357
                8b93d50f-9dc9-458d-b92b-ea25204ab2d8
                © 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 May 2022
                : 09 March 2022
                : 26 June 2022
                Page count
                Figures: 1, Tables: 2, Pages: 8, Words: 5434
                Funding
                Funded by: Stiftelsen för Synskadade i f.d. Malmöhus län , doi 10.13039/100010816;
                Funded by: Synoptik Foundation, Denmark
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                February 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.7 mode:remove_FC converted:10.04.2023

                Ophthalmology & Optometry
                corneal crosslinking,keratoconus,questionnaire,survey
                Ophthalmology & Optometry
                corneal crosslinking, keratoconus, questionnaire, survey

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