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      Five‐year corneal cross‐linking outcomes: A Save Sight Keratoconus Registry Study

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          Abstract

          Background

          We aimed to determine the long‐term outcomes of epithelium‐off cross‐linking (CXL) in keratoconus patients.

          Methods

          An observational registry study from 41 centres across 5 countries was carried out. Primary outcomes included the mean change in visual acuity (VA), Kmax, K2, and thinnest corneal thickness (TCT) at 1–5 years. Secondary outcomes included the percentage of eyes with worsening, stable and improving outcomes.

          Results

          There were 976 eyes of 794 patients with 1‐year of complete follow‐up, 501 eyes with 2‐years, 355 with 3‐years, 235 with 4‐years and 162 with 5‐years. There was a significant improvement in mean VA from baseline by 3.7 logMAR letters ( p < 0.001) in year 1, and 6.9 ( p < 0.001) in year 5. Mean Kmax decreased by 1.2 dioptres (D; p < 0.01) in year 1. During subsequent years the Kmax flattening appeared sustained but this was not statistically significant. K2 flattened significantly from baseline in year 1 and then remained stable. At 1 year, 4.1% patients were poor responders to CXL in terms of VA, losing ≥15 letters. The proportion of the poor responders remained unchanged: 4.9% at 5‐years. The proportion of poor responders in terms of Kmax remained similar: 5.9% steepening by ≥2D at 1‐year and 7.5% at 5‐years. The proportion of K2 poor responders remained stable with 4.7% steepening by ≥2D at 1‐year and 5.8% at 5‐years.

          Conclusions

          Cross‐linking is effective at stabilising keratoconus up to 5 years in most patients. However, a small proportion of eyes failed to stabilise and had reduced vision.

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          Most cited references43

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          Global consensus on keratoconus and ectatic diseases.

          Despite extensive knowledge regarding the diagnosis and management of keratoconus and ectatic corneal diseases, many controversies still exist. For that reason, there is a need for current guidelines for the diagnosis and management of these conditions. This project aimed to reach consensus of ophthalmology experts from around the world regarding keratoconus and ectatic diseases, focusing on their definition, concepts, clinical management, and surgical treatments. The Delphi method was followed with 3 questionnaire rounds and was complemented with a face-to-face meeting. Thirty-six panelists were involved and allocated to 1 of 3 panels: definition/diagnosis, nonsurgical management, or surgical treatment. The level of agreement considered for consensus was two thirds. Numerous agreements were generated in definitions, methods of diagnosing, and management of keratoconus and other ectatic diseases. Nonsurgical and surgical treatments for these conditions, including the use of corneal cross-linking and corneal transplantations, were presented in a stepwise approach. A flowchart describing a logical management sequence for keratoconus was created. This project resulted in definitions, statements, and recommendations for the diagnosis and management of keratoconus and other ectatic diseases. It also provides an insight into the current worldwide treatment of these conditions.
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            Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study.

            To report the long-term results of 44 keratoconic eyes treated by combined riboflavin ultraviolet A collagen cross-linking in the first Italian open, nonrandomized phase II clinical trial, the Siena Eye Cross Study. Perspective, nonrandomized, open trial. After Siena University Institutional Review Board approval, from September 2004 through September 2008, 363 eyes with progressive keratoconus were treated with riboflavin ultraviolet A collagen cross-linking. Forty-four eyes with a minimum follow-up of 48 months (mean, 52.4 months; range, 48 to 60 months) were evaluated before and after surgery. Examinations comprised uncorrected visual acuity, best spectacle-corrected visual acuity, spherical spectacle-corrected visual acuity, endothelial cells count (I Konan, Non Con Robo; Konan Medical, Inc., Hyogo, Japan), optical (Visante OCT; Zeiss, Jena, Germany) and ultrasound (DGH; Pachette, Exton, Pennsylvania, USA) pachymetry, corneal topography and surface aberrometry (CSO EyeTop, Florence, Italy), tomography (Orbscan IIz; Bausch & Lomb Inc., Rochester, New York, USA), posterior segment optical coherence tomography (Stratus OCT; Zeiss, Jena, Germany), and in vivo confocal microscopy (HRT II; Heidelberg Engineering, Rostock, Germany). Keratoconus stability was detected in 44 eyes after 48 months of minimum follow-up; fellow eyes showed a mean progression of 1.5 diopters in more than 65% after 24 months, then were treated. The mean K value was reduced by a mean of 2 diopters, and coma aberration reduction with corneal symmetry improvement was observed in more than 85%. The mean best spectacle-corrected visual acuity improved by 1.9 Snellen lines, and the uncorrected visual acuity improved by 2.7 Snellen lines. The results of the Siena Eye Cross Study showed a long-term stability of keratoconus after cross-linking without relevant side effects. The uncorrected visual acuity and best spectacle-corrected visual acuity improvements were supported by clinical, topographic, and wavefront modifications induced by the treatment. Copyright 2010 Elsevier Inc. All rights reserved.
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              A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus: three-year results.

              To report the refractive, topographic, and clinical outcomes 3 years after corneal collagen cross-linking (CXL) in eyes with progressive keratoconus. Prospective, randomized controlled trial. One hundred eyes with progressive keratoconus were randomized into the CXL treatment or control groups. Cross-linking was performed by instilling riboflavin 0.1% solution containing 20% dextran for 15 minutes before and during the 30 minutes of ultraviolet A irradiation (3 mW/cm(2)). Follow-up examinations were arranged at 3, 6, 12, 24, and 36 months. The primary outcome measure was the maximum simulated keratometry value (Kmax). Other outcome measures were uncorrected visual acuity (UCVA; measured in logarithm of the minimum angle of resolution [logMAR] units), best spectacle-corrected visual acuity (BSCVA; measured in logMAR units), sphere and cylinder on subjective refraction, spherical equivalent, minimum simulated keratometry value, corneal thickness at the thinnest point, endothelial cell density, and intraocular pressure. The results from 48 control and 46 treated eyes are reported. In control eyes, Kmax increased by a mean of 1.20±0.28 diopters (D), 1.70±0.36 D, and 1.75±0.38 D at 12, 24, and 36 months, respectively (all P <0.001). In treated eyes, Kmax flattened by -0.72±0.15 D, -0.96±0.16 D, and -1.03±0.19 D at 12, 24, and 36 months, respectively (all P <0.001). The mean change in UCVA in the control group was +0.10±0.04 logMAR (P = 0.034) at 36 months. In the treatment group, both UCVA (-0.15±0.06 logMAR; P = 0.009) and BSCVA (-0.09±0.03 logMAR; P = 0.006) improved at 36 months. There was a significant reduction in corneal thickness measured using computerized videokeratography in both groups at 36 months (control group: -17.01±3.63 μm, P <0.001; treatment group: -19.52±5.06 μm, P <0.001) that was not observed in the treatment group using the manual pachymeter (treatment group: +5.86±4.30 μm, P = 0.181). The manifest cylinder increased by 1.17±0.49 D (P = 0.020) in the control group at 36 months. There were 2 eyes with minor complications that did not affect the final visual acuity. At 36 months, there was a sustained improvement in Kmax, UCVA, and BSCVA after CXL, whereas eyes in the control group demonstrated further progression. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                himal.kandel@sydney.edu.au
                Journal
                Clin Exp Ophthalmol
                Clin Exp Ophthalmol
                10.1111/(ISSN)1442-9071
                CEO
                Clinical & Experimental Ophthalmology
                John Wiley & Sons Australia, Ltd (Melbourne )
                1442-6404
                1442-9071
                24 October 2022
                Jan-Feb 2023
                : 51
                : 1 ( doiID: 10.1111/ceo.v51.1 )
                : 9-18
                Affiliations
                [ 1 ] Specialty of Clinical Ophthalmology and Eye Health, Sydney Medical School Save Sight Institute, The University of Sydney Sydney New South Wales Australia
                [ 2 ] Cornea & External Eye Diseases Hospital Universitario Ramón Cajal Madrid Spain
                [ 3 ] Abbondanza Eye Centers Rome and Milan Italy
                Author notes
                [*] [* ] Correspondence

                Dr Himal Kandel, Specialty of Clinical Ophthalmology and Eye Health, Sydney Medical School, Save Sight Institute, The University of Sydney, 8 Macquarie Street, Sydney, NSW 2000, Australia.

                Email: himal.kandel@ 123456sydney.edu.au

                Author information
                https://orcid.org/0000-0002-2895-3087
                https://orcid.org/0000-0002-6745-6411
                https://orcid.org/0000-0001-9070-9803
                https://orcid.org/0000-0002-3094-9132
                https://orcid.org/0000-0001-6699-1765
                Article
                CEO14177
                10.1111/ceo.14177
                10091974
                36240047
                bcf0cafa-f8e8-4cb3-82db-f5531e9ec98d
                © 2022 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.

                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
                : 18 September 2022
                : 24 March 2022
                : 07 October 2022
                Page count
                Figures: 2, Tables: 3, Pages: 10, Words: 6807
                Funding
                Funded by: Northcote Scholarship
                Funded by: Keratoconus Australia
                Funded by: Australian Vision Research
                Funded by: Kornhauser Research Fellowship
                Categories
                Original Article ‐ Clinical Science
                ORIGINAL ARTICLES
                Clinical Science
                Custom metadata
                2.0
                January/February 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.7 mode:remove_FC converted:12.04.2023

                adverse events,cross‐linking,keratoconus,outcomes
                adverse events, cross‐linking, keratoconus, outcomes

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