{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:17:40Z","timestamp":1791569860897,"version":"4.3.4"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> To investigate the demographic and corneal factors associated with the occurrence of delayed reepithelialization (DRE) after epithelium-off crosslinking (epi-off CXL).<\/jats:p><jats:p><jats:bold>Design:<\/jats:bold>Retrospective case series.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold>A chart review was performed to identify patients treated with epi-off CXL. DRE was defined as a corneal epithelial defect detected by fluorescein staining that persisted for more than 10 days. Slit-lamp examination, anterior segment optical coherence tomography, corneal topography, and corneal <jats:italic>in vivo<\/jats:italic> confocal microscopy (IVCM) were always performed preoperatively and at each follow-up visit (1, 3, 6, 12 months). A generalized estimating equation was used to assess the baseline factors associated with DRE.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>Data from 153 eyes were analyzed. The mean age of patients was 24.9 \u00b1 8.5 years, and 47 (30.7%) were women. The average reepithelization time was 4.7 \u00b1 1.8 days. Six eyes (3.9%) experienced DRE. In the multivariate model, both the age of the patient (OR = 1.30; <jats:italic>p<\/jats:italic> = 0.02) and the corneal steepest meridian (OR = 0.44, <jats:italic>p<\/jats:italic> = 0.047) were associated with DRE. Baseline nerve count was also associated with DRE (0.87, <jats:italic>p<\/jats:italic> = 0.03). Male gender was associated with a slower early nerve regrowth (1\u20136 months) (<jats:italic>p<\/jats:italic> = 0.048), but not with the occurrence of DRE (<jats:italic>p<\/jats:italic> = 0.27). Preoperative central corneal thickness was not related to DRE (<jats:italic>p<\/jats:italic> = 0.16). DRE was not associated with keratoconus progression after epi-off CXL (<jats:italic>p<\/jats:italic> = 0.520).<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold>The association between DRE and age may reflect the age-related decrease in the corneal healing response. Also, low baseline corneal nerve count is associated with DRE. Gender seems to affect reinnervation measured by IVCM but not the reepithelization time. DRE does not seem to affect the efficacy of epi-off CXL.<\/jats:p>","DOI":"10.3389\/fmed.2021.657993","type":"journal-article","created":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T02:31:44Z","timestamp":1634351504000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Delayed Re-epithelialization After Epithelium-Off Crosslinking: Predictors and Impact on Keratoconus Progression"],"prefix":"10.3389","volume":"8","author":[{"given":"Chiara","family":"Bonzano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo Alberto","family":"Cutolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Musetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Di Mola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Pizzorno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Scotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo Enrico","family":"Traverso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.preteyeres.2018.05.002","article-title":"Pathogenesis of keratoconus: the intriguing therapeutic potential of prolactin-inducible protein","volume":"67","author":"Sharif","year":"2018","journal-title":"Prog Retin Eye Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/S0039-6257(97)00119-7","article-title":"Keratoconus","volume":"42","author":"Rabinowitz","year":"1998","journal-title":"Surv Ophthalmol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/S0002-9394(02)02220-1","article-title":"Riboflavin\/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus","volume":"135","author":"Wollensak","year":"2003","journal-title":"Am J Ophthalmol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/j.jcrs.2017.05.030","article-title":"Accelerated 15 mW pulsed-light crosslinking to treat progressive keratoconus: two-year clinical results","volume":"43","author":"Mazzotta","year":"2017","journal-title":"J Cataract Refract Surg."},{"key":"B5","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.ophtha.2013.10.028","article-title":"Randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus","volume":"121","author":"Wittig-Silva","year":"2014","journal-title":"Ophthalmology."},{"key":"B6","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jcrs.2014.09.033","article-title":"Corneal collagen crosslinking with riboflavin and ultraviolet-A light in progressive keratoconus: ten-year results","volume":"41","author":"Raiskup","year":"2015","journal-title":"J Cataract Refract Surg."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1016\/j.ajo.2015.08.023","article-title":"Corneal cross-linking to halt the progression of keratoconus and corneal ectasia: seven-year follow-up","volume":"160","author":"O'Brart","year":"2015","journal-title":"Am J Ophthalmol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.jcrs.2007.12.039","article-title":"Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results","volume":"34","author":"Raiskup-Wolf","year":"2008","journal-title":"J Cataract Refract Surg."},{"key":"B9","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.ajo.2015.02.005","article-title":"Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial","volume":"159","author":"Soeters","year":"2015","journal-title":"Am J Ophthalmol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1097\/ICO.0000000000001878","article-title":"HafeziNL, Khandelwal SS, Torres-Netto EA, Hafezi F, Randleman JB. 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