{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:06:24Z","timestamp":1779231984022,"version":"3.51.4"},"reference-count":26,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Klin Monbl Augenheilkd"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background To identify predictive factors for disease progression following corneal crosslinking (CXL) in keratoconus patients, focusing on tomographic, pachymetric, and patient-specific characteristics.<\/jats:p>\n                  <jats:p>Patients and Methods This retrospective study analyzed 147 eyes from 123 keratoconus patients who underwent conventional epithelium-off CXL (3\u2009mW\/cm2 for 30\u2009min) between 2011 and 2021, with a minimum follow-up of 12 months. Baseline parameters included preoperative maximum keratometry (pre-Kmax), dynamic preoperative annualised Kmax progression (pre-\u0394Kmax), corneal thickness at the thinnest point (pre-CTT), age, sex, and atopic dermatitis. A Linear Mixed Model (LMM) identified predictors of postoperative annualised \u0394Kmax progression (diopters\/year), while a Cox regression assessed risk factors for a single postoperative Kmax increase of &gt;\u20091 diopter (D), and both approaches accounted for inter-eye correlation.<\/jats:p>\n                  <jats:p>Results In the LMM, atopic dermatitis showed a trend toward a higher rate of postoperative Kmax progression (\u03b2\u2009=\u20090.00379, p\u2009=\u20090.093), corresponding to an estimated increase of +\u20091.38\u2009D per year. In contrast, a higher rate of preoperative progression (pre-\u0394Kmax; \u03b2 = \u2212\u20090.0684, p\u2009=\u20090.074) and higher baseline Kmax (pre-Kmax; \u03b2 = \u2212\u20090.000173, p\u2009=\u20090.070) demonstrated trend-level associations with reduced annual postoperative progression, reflecting greater corneal flattening over time. However, in Cox regression, higher pre-Kmax demonstrated a trend-level association with an increased risk of a single postoperative progression event (HR\u2009=\u20091.05; 95% CI: 0.99\u200a\u2013\u200a1.10; p\u2009=\u20090.095). Age, sex, and pre-CTT showed no significant associations in either model.<\/jats:p>\n                  <jats:p>Conclusion Atopic dermatitis was identified as a potential risk factor for keratoconus progression following CXL, and showed a trend-level association with a higher annual Kmax increase. Paradoxically, while higher pre-Kmax increased the risk of isolated progression events, it was simultaneously associated with a greater long-term flattening trend. Additionally, a rapid rate of preoperative progression was associated with a greater stabilising effect, suggesting that these corneas may be particularly responsive to treatment. These findings underscore the importance of integrating event-based and trend-based analytical approaches when interpreting post-CXL outcomes and their associated predictive factors.<\/jats:p>","DOI":"10.1055\/a-2815-9227","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T22:41:13Z","timestamp":1779230473000},"page":"595-602","source":"Crossref","is-referenced-by-count":0,"title":["Predictive Factors for Disease Progression Following Corneal Crosslinking in Keratoconus: a Novel Approach Using Dynamic Progression Metrics"],"prefix":"10.1055","volume":"243","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3608-1445","authenticated-orcid":false,"given":"Othmane","family":"Touirssa","sequence":"additional","affiliation":[{"name":"Ophthalmology, Medical Center \u2013 University of Freiburg Eye Center, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"B\u00f6hringer","sequence":"additional","affiliation":[{"name":"Ophthalmology, Medical Center \u2013 University of Freiburg Eye Center, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola Kammrath","family":"Betancor","sequence":"additional","affiliation":[{"name":"Ophthalmology, Medical Center \u2013 University of Freiburg Eye Center, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5324-7002","authenticated-orcid":false,"given":"Stefan J.","family":"Lang","sequence":"additional","affiliation":[{"name":"Ophthalmology, Medical Center \u2013 University of Freiburg Eye Center, Freiburg, Germany"},{"name":"Ophthalmology, University Hospital Brandenburg an der Havel GmbH, Brandenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Reinhard","sequence":"additional","affiliation":[{"name":"Ophthalmology, Medical Center \u2013 University of Freiburg Eye Center, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip Christian","family":"Maier","sequence":"additional","affiliation":[{"name":"Ophthalmology, Medical Center \u2013 University of Freiburg Eye Center, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/s0039-6257(97)00119-7","article-title":"Keratoconus","volume":"42","author":"Y S Rabinowitz","year":"1998","journal-title":"Surv Ophthalmol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1097\/APO.0000000000000332","article-title":"Biochemical Markers and Alterations in Keratoconus","volume":"9","author":"R Shetty","year":"2020","journal-title":"Asia Pac J Ophthalmol (Phila)"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"101559","DOI":"10.1016\/j.clae.2021.101559","article-title":"Keratoconus: An updated review","volume":"45","author":"J Santodomingo-Rubido","year":"2022","journal-title":"Cont Lens Anterior Eye"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1159\/000357979","article-title":"Corneal collagen crosslinking: a systematic review","volume":"232","author":"N Sorkin","year":"2014","journal-title":"Ophthalmologica"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1007\/s00417-024-06639-y","article-title":"Changing indications for keratoplasty: monocentric analysis of the past two decades","volume":"263","author":"J V Hoffmann","year":"2025","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12886-015-0070-7","article-title":"Prospective, randomized, double-blind trial to investigate the efficacy and safety of corneal cross-linking to halt the progression of keratoconus","volume":"15","author":"S J Lang","year":"2015","journal-title":"BMC Ophthalmol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.ophtha.2013.10.028","article-title":"A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus: three-year results","volume":"121","author":"C Wittig-Silva","year":"2014","journal-title":"Ophthalmology"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"191","DOI":"10.4103\/2211-5056.361974","article-title":"Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials","volume":"13","author":"P Sarma","year":"2023","journal-title":"Taiwan J Ophthalmol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1097\/ICO.0000000000003165","article-title":"Safety and Efficacy of Repeated Corneal Collagen Crosslinking in Progressive Keratoconus","volume":"42","author":"O Vorobichik Berar","year":"2023","journal-title":"Cornea"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e0263528","DOI":"10.1371\/journal.pone.0263528","article-title":"Predicting factors for the efficacy of cross-linking for keratoconus","volume":"17","author":"D Wajnsztajn","year":"2022","journal-title":"PLoS One"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"816","DOI":"10.3928\/1081597X-20210830-01","article-title":"Risk Factors for Progression of Keratoconus and Failure Rate After Corneal Cross-linking","volume":"37","author":"J Lenk","year":"2021","journal-title":"J Refract Surg"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.4103\/JOCO.JOCO_48_20","article-title":"Outcome of Corneal Collagen Cross-Linking in Keratoconus: Introducing the Predictive Factors","volume":"32","author":"A Peyman","year":"2020","journal-title":"J Curr Ophthalmol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"4109208","DOI":"10.1155\/2017\/4109208","article-title":"Predictive Factors of the Standard Cross-linking Outcomes in Adult Keratoconus: One-Year Follow-Up","volume":"2017","author":"A E Badawi","year":"2017","journal-title":"J Ophthalmol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.4103\/ijo.IJO_1191_19","article-title":"Relevance of IgE, allergy and eye rubbing in the pathogenesis and management of Keratoconus","volume":"68","author":"P Ahuja","year":"2020","journal-title":"Indian J Ophthalmol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1016\/j.jcrs.2009.03.035","article-title":"Complication and failure rates after corneal crosslinking","volume":"35","author":"T Koller","year":"2009","journal-title":"J Cataract Refract Surg"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"7487186","DOI":"10.1155\/2020\/7487186","article-title":"Safety, Efficacy, and Predictive Factors of Conventional Epithelium-Off Corneal Crosslinking in the Treatment of Progressive Keratoconus","volume":"2020","author":"R Farhat","year":"2020","journal-title":"J Ophthalmol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.jfo.2020.08.040","article-title":"Risk factors for keratoconus progression after treatment by accelerated cross-linking (A-CXL): A prospective 24-month study","volume":"44","author":"M Sot","year":"2021","journal-title":"J Fr Ophtalmol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1177\/1120672120964080","article-title":"Corneal flattening following collagen crosslinking for keratoconus: Findings at 5-year follow-up","volume":"31","author":"S Hoyek","year":"2021","journal-title":"Eur J Ophthalmol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1177\/1120672120947664","article-title":"Extreme corneal flattening following collagen crosslinking for progressive keratoconus","volume":"31","author":"P Padmanabhan","year":"2021","journal-title":"Eur J Ophthalmol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"250","DOI":"10.3928\/1081597X-20220114-02","article-title":"Repeatability and Comparison of Corneal Tomography in Mild to Severe Keratoconus Between the Anterior Segment OCT MS-39 and Pentacam HR","volume":"38","author":"T G Seiler","year":"2022","journal-title":"J Refract Surg"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1038\/s41433-020-01238-7","article-title":"Repeatability and reliability of measurements obtained by the combined Scheimpflug and Placido-disk tomography in different stages of keratoconus","volume":"35","author":"U Tun\u00e7","year":"2021","journal-title":"Eye (Lond)"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1007\/s10792-017-0699-8","article-title":"Pediatric keratoconus: a review of the literature","volume":"38","author":"S Mukhtar","year":"2018","journal-title":"Int Ophthalmol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"753","DOI":"10.3928\/1081597X-20121011-01","article-title":"Progression of keratoconus and efficacy of pediatric [corrected] corneal collagen cross-linking in children and adolescents","volume":"28","author":"N Chatzis","year":"2012","journal-title":"J Refract Surg"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1149641","DOI":"10.3389\/fmed.2023.1149641","article-title":"Outcome indicators for cross linking in pediatric keratoconus","volume":"10","author":"D Wajnsztajn","year":"2023","journal-title":"Front Med (Lausanne)"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/eye.2013.224","article-title":"Factors affecting outcomes of corneal collagen crosslinking treatment","volume":"28","author":"I Toprak","year":"2014","journal-title":"Eye (Lond)"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.ajo.2013.11.001","article-title":"A multivariate analysis and statistical model for predicting visual acuity and keratometry one year after cross-linking for keratoconus","volume":"157","author":"R PL Wisse","year":"2014","journal-title":"Am J Ophthalmol"}],"container-title":["Klinische Monatsbl\u00e4tter f\u00fcr Augenheilkunde"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2815-9227.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T22:41:35Z","timestamp":1779230495000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2815-9227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":26,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2026,5,19]]},"published-print":{"date-parts":[[2026,5]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2815-9227","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0023-2165","1439-3999"],"issn-type":[{"value":"0023-2165","type":"print"},{"value":"1439-3999","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]}}}