{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:04:55Z","timestamp":1792008295920,"version":"4.4.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T00:00:00Z","timestamp":1632614400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T00:00:00Z","timestamp":1632614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eye and Vis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The purpose of the study was to determine the advantages and disadvantages of epi-on corneal cross-linking (CXL) techniques compared with standard epi-off CXL.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We searched MEDLINE and EMBASE for randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) and we evaluated the selected papers according to the Cochrane risk of bias tool. We considered, as primary outcomes, average Kmax flattening, changes in uncorrected and corrected distance visual acuity (UDVA and CDVA); as secondary outcomes, we considered changes in pachymetry values and endothelial cell density (ECD). We also investigated adverse events related to the treatments and treatment failure. Meta-analysis was conducted with a fixed or random-effects model using weighted mean difference (MD) with 95% confidence interval (CI) as the effect size.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 15 studies were included and among these 15 trials, 9 were RCTs and 6 were NRSIs, but only 4 studies showed no high risk of bias and were included in this meta-analysis. Our analysis revealed significant postoperative differences in CDVA (MD\u2009=\u20090.07; 95% CI\u20090.04 to 0.10; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), and no significative differences in UDVA, Kmax,\u00a0central corneal thickness (CCT) and ECD (<jats:italic>P<\/jats:italic>\u2009&gt;\u20090.05). Epi-on CXL protocol was found to be significantly less prompt to have risks of delay in epithelial healing (<jats:italic>P<\/jats:italic>\u2009=\u20090.035) and persistent stromal haze (<jats:italic>P<\/jats:italic>\u2009=\u20090.026).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Epi-on CXL is as effective as epi-off CXL. Except for a higher significant improvement in CDVA with current epi-on protocols, our meta-analysis demonstrates that epi-on and epi-off CXL have comparable effects on visual, topographic, pachymetric, and endothelial parameters. Epi-on CXL has clinical advantages in terms of comfort and avoidance of complications as it reduces the risk of developing delay in epithelial healing and persistent stromal haze.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40662-021-00256-0","type":"journal-article","created":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T04:02:40Z","timestamp":1632628960000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Corneal collagen cross-linking epithelium-on vs. epithelium-off: a systematic review and meta-analysis"],"prefix":"10.1186","volume":"8","author":[{"given":"Francesco","family":"D\u2019Oria","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Palaz\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8082-1751","authenticated-orcid":false,"given":"Jorge L.","family":"Alio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,26]]},"reference":[{"issue":"4","key":"256_CR1","doi-asserted-by":"publisher","first-page":"551","DOI":"10.4103\/ijo.IJO_1496_18","volume":"67","author":"R Arora","year":"2019","unstructured":"Arora R, Lohchab M. Pediatric keratoconus misdiagnosed as meridional amblyopia. Indian J Ophthalmol. 2019;67(4):551\u20132.","journal-title":"Indian J Ophthalmol"},{"key":"256_CR2","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.ajo.2020.09.041","volume":"222","author":"F D'Oria","year":"2021","unstructured":"D\u2019Oria F, Abdelghany A, Ledo N, Barraquer RI, Alio JL. Incidence and reason for intrastromal corneal ring segment explantation. Am J Ophthalmol. 2021;222:351\u20138.","journal-title":"Am J Ophthalmol"},{"key":"256_CR3","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1159\/000300309","volume":"111","author":"M Amsler","year":"1946","unstructured":"Amsler M. K\u00e9ratoc\u00f5ne classique et k\u00e9ratoc\u00f4ne fruste; arguments unitaires. Ophthalmologica. 1946;111:96\u2013101.","journal-title":"Ophthalmologica"},{"issue":"6","key":"256_CR4","doi-asserted-by":"publisher","first-page":"539","DOI":"10.3928\/1081-597X-20060601-05","volume":"22","author":"JL Ali\u00f3","year":"2006","unstructured":"Ali\u00f3 JL, Shabayek MH. Corneal higher order aberrations: a method to grade keratoconus. J refract surg. 2006;22(6):539\u201345.","journal-title":"J refract surg"},{"issue":"3","key":"256_CR5","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/j.jcrs.2010.10.046","volume":"37","author":"JL Ali\u00f3","year":"2011","unstructured":"Ali\u00f3 JL, Pi\u00f1ero DP, Ales\u00f3n A, Teus MA, Barraquer RI, Murta J, et al. Keratoconus-integrated characterization considering anterior corneal aberrations, internal astigmatism, and corneal biomechanics. J Cataract Refract Surg. 2011;37(3):552\u201368.","journal-title":"J Cataract Refract Surg"},{"issue":"1","key":"256_CR6","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s00347-002-0700-3","volume":"100","author":"G Wollensak","year":"2003","unstructured":"Wollensak G, Sporl E, Seiler T. Treatment of keratoconus by collagen cross linking. Ophthalmologe. 2003;100(1):44\u20139.","journal-title":"Ophthalmologe"},{"issue":"5","key":"256_CR7","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/S0002-9394(02)02220-1","volume":"135","author":"G Wollensak","year":"2003","unstructured":"Wollensak G, Spoerl E, Seiler T. Riboflavin\/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135(5):620\u20137.","journal-title":"Am J Ophthalmol"},{"issue":"1","key":"256_CR8","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1097\/ICO.0b013e31824d6fe3","volume":"32","author":"VC Ghanem","year":"2013","unstructured":"Ghanem VC, Ghanem RC, de Oliveira R. Postoperative pain after corneal collagen cross-linking. Cornea. 2013;32(1):20\u20134.","journal-title":"Cornea"},{"issue":"13","key":"256_CR9","doi-asserted-by":"publisher","first-page":"2841","DOI":"10.3390\/jcm10132841","volume":"10","author":"F D\u2019Oria","year":"2021","unstructured":"D\u2019Oria F, Puzo P, Incandela C, Sborgia A, Boscia F, Alessio G. Evaluation of demarcation line after epithelium off iontophoresis corneal collagen cross-linking for progressive keratoconus. J Clin Med. 2021;10(13):2841.","journal-title":"J Clin Med"},{"key":"256_CR10","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.ED000142","author":"M Cumpston","year":"2019","unstructured":"Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10:ED000142.\u00a0","journal-title":"Cochrane Database Syst Rev"},{"issue":"7","key":"256_CR11","doi-asserted-by":"publisher","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","volume":"6","author":"D Moher","year":"2009","unstructured":"Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.","journal-title":"PLoS Med"},{"issue":"10","key":"256_CR12","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1093\/aje\/kwm189","volume":"166","author":"I Shrier","year":"2007","unstructured":"Shrier I, Boivin JF, Steele RJ, Platt RW, Furlan A, Kakuma R, et al. Should meta-analyses of interventions include observational studies in addition to randomized controlled trials? A critical examination of underlying principles. Am J Epidemiol. 2007;166(10):1203\u20139.","journal-title":"Am J Epidemiol"},{"key":"256_CR13","volume-title":"General guidelines for methodologies on research and evaluation of traditional medicine","author":"World Health Organization","year":"2000","unstructured":"World Health Organization. General guidelines for methodologies on research and evaluation of traditional medicine. Geneva: World Health Organization; 2000."},{"key":"256_CR14","doi-asserted-by":"publisher","first-page":"i4919","DOI":"10.1136\/bmj.i4919","volume":"355","author":"JA Sterne","year":"2016","unstructured":"Sterne JA, Hernan MA, Reeves BC, Savovi\u0107 J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.","journal-title":"BMJ"},{"key":"256_CR15","doi-asserted-by":"publisher","first-page":"j4008","DOI":"10.1136\/bmj.j4008","volume":"358","author":"BJ Shea","year":"2017","unstructured":"Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008.","journal-title":"BMJ"},{"issue":"1","key":"256_CR16","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1258\/1355819021927674","volume":"7","author":"J Higgins","year":"2002","unstructured":"Higgins J, Thompson S, Deeks J, Altman D. Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice. J Health Serv Res Policy. 2002;7(1):51\u201361.","journal-title":"J Health Serv Res Policy"},{"key":"256_CR17","doi-asserted-by":"publisher","first-page":"d4002","DOI":"10.1136\/bmj.d4002","volume":"343","author":"JA Sterne","year":"2011","unstructured":"Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.","journal-title":"BMJ"},{"key":"256_CR18","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.ajo.2017.03.016","volume":"178","author":"Y Abdelmassih","year":"2017","unstructured":"Abdelmassih Y, El-Khoury S, Dirani A, Antonios R, Fadlallah A, Cherfan CG, et al. Safety and efficacy of sequential intracorneal ring segment implantation and cross-linking in pediatric keratoconus. Am J Ophthalmol. 2017;178:51\u20137.","journal-title":"Am J Ophthalmol"},{"issue":"5","key":"256_CR19","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1097\/ICO.0000000000001165","volume":"36","author":"M Choi","year":"2017","unstructured":"Choi M, Kim J, Kim EK, Seo KY, Kim TI. Comparison of the conventional Dresden protocol and accelerated protocol with higher ultraviolet intensity in corneal collagen cross-linking for keratoconus. Cornea. 2017;36(5):523\u20139.","journal-title":"Cornea"},{"issue":"6","key":"256_CR20","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1097\/ICO.0000000000000823","volume":"35","author":"AB Cummings","year":"2016","unstructured":"Cummings AB, McQuaid R, Naughton S, Brennan E, Mrochen M. Optimizing corneal cross-linking in the treatment of keratoconus: a comparison of outcomes after standard- and high-intensity protocols. Cornea. 2016;35(6):814\u201322.","journal-title":"Cornea"},{"issue":"5","key":"256_CR21","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1007\/s10792-018-0898-y","volume":"39","author":"SA Eissa","year":"2019","unstructured":"Eissa SA, Yassin A. Prospective, randomized contralateral eye study of accelerated and conventional corneal cross-linking in pediatric keratoconus. Int Ophthalmol. 2019;39(5):971\u20139.","journal-title":"Intern Ophthalmol"},{"issue":"1","key":"256_CR22","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1097\/ICO.0000000000002168","volume":"39","author":"DA Godefrooij","year":"2020","unstructured":"Godefrooij DA, Rooh\u00e9 SL, Soeters N, Wisse RPL. The independent effect of various cross-linking treatment modalities on treatment effectiveness in keratoconus. Cornea. 2020;39(1):63\u201370.","journal-title":"Cornea"},{"issue":"12","key":"256_CR23","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3928\/1081597X-20141117-02","volume":"30","author":"H Hashemian","year":"2014","unstructured":"Hashemian H, Jabbarvand M, Khodaparast M, Ameli K. Evaluation of corneal changes after conventional versus accelerated corneal cross-linking: a randomized controlled trial. J Refract surg. 2014;30(12):837\u201342.","journal-title":"J Refract surg"},{"issue":"6","key":"256_CR24","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/j.ajo.2015.08.027","volume":"160","author":"H Hashemi","year":"2015","unstructured":"Hashemi H, Miraftab M, Seyedian MA, Hafezi F, Bahrmandy H, Heidarian S, et al. Long-term results of an accelerated corneal cross-linking protocol (18 mW\/cm2) for the treatment of progressive keratoconus. Am J Ophthalmol. 2015;160(6):1164\u201370.","journal-title":"Am J Ophthalmol"},{"issue":"5","key":"256_CR25","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1007\/s10384-018-0610-9","volume":"62","author":"N Kato","year":"2018","unstructured":"Kato N, Konomi K, Shinzawa M, Kasai K, Ide T, Toda I, et al. Corneal crosslinking for keratoconus in Japanese populations: one year outcomes and a comparison between conventional and accelerated procedures. Jpn J Ophthalmol. 2018;62(5):560\u20137.","journal-title":"Jpn J Ophthalmol"},{"issue":"10","key":"256_CR26","doi-asserted-by":"publisher","first-page":"642","DOI":"10.3928\/1081597X-20190903-01","volume":"35","author":"B Knyazer","year":"2019","unstructured":"Knyazer B, Kormas RM, Chorny A, Lifshitz T, Achiron A, Mimouni M. Corneal cross-linking in thin corneas: 1-year results of accelerated contact lens-assisted treatment of keratoconus. J Refract surg. 2019;35(10):642\u20138.","journal-title":"J Refract surg"},{"issue":"1","key":"256_CR27","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/ceo.12571","volume":"44","author":"AL Ng","year":"2016","unstructured":"Ng AL, Chan TC, Cheng AC. Conventional versus accelerated corneal collagen cross-linking in the treatment of keratoconus. Clin Exp Ophthalmol. 2016;44(1):8\u201314.","journal-title":"Clin Exp Ophthalmol"},{"issue":"1","key":"256_CR28","first-page":"67","volume":"38","author":"MM Sadoughi","year":"2018","unstructured":"Sadoughi MM, Einollahi B, Baradaran-Rafii A, Roshandel D, Hasani H, Nazeri M. Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study. Int Ophthalmol. 2018;38(1):67\u201374.","journal-title":"Int ophthalmol"},{"key":"256_CR29","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.ajo.2016.02.029","volume":"166","author":"TG Seiler","year":"2016","unstructured":"Seiler TG, Fischinger I, Koller T, Zapp D, Frueh BE, Seiler T, et al. Customized corneal cross-linking: one-year results. Am J Ophthalmol. 2016;166:14\u201321.","journal-title":"Am J Ophthalmol"},{"issue":"60","key":"256_CR30","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/j.jcrs.2013.12.012","volume":"40","author":"M Tomita","year":"2014","unstructured":"Tomita M, Mita M, Huseynova T. Accelerated versus conventional corneal collagen crosslinking. J Cataract Refract Surg. 2014;40(60):1013\u201320.","journal-title":"J Cataract Refract Surg"},{"issue":"12","key":"256_CR31","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1097\/ICO.0000000000001383","volume":"36","author":"K Bilgihan","year":"2017","unstructured":"Bilgihan K, Yesilirmak N, Altay Y, Yuvarlak A, Ozdemir HB. Conventional corneal collagen cross-linking versus transepithelial diluted alcohol and iontophoresis-assisted corneal cross-linking in progressive keratoconus. Cornea. 2017;36(12):1492\u20137.","journal-title":"Cornea"},{"issue":"7","key":"256_CR32","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1097\/ICO.0000000000001965","volume":"38","author":"L Buzzonetti","year":"2019","unstructured":"Buzzonetti L, Petrocelli G, Valente P, Iarossi G, Ardia R, Petroni S, et al. Iontophoretic transepithelial collagen cross-linking versus epithelium-off collagen cross-linking in pediatric patients: 3-year follow-up. Cornea. 2019;38(7):859\u201363.","journal-title":"Cornea"},{"issue":"1","key":"256_CR33","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s40123-017-0076-8","volume":"6","author":"A Cantemir","year":"2017","unstructured":"Cantemir A, Alexa AI, Anton N, Ciuntu RE, Danielescu C, Chiselita D, et al. Evaluation of iontophoretic collagen cross-linking for early stage of progressive keratoconus compared to standard cross-linking: a non-inferiority study. Ophthalmol Ther. 2017;6(1):147\u201360.","journal-title":"Ophthalmol Ther"},{"issue":"7","key":"256_CR34","doi-asserted-by":"publisher","first-page":"e649","DOI":"10.1111\/aos.13538","volume":"95","author":"A Cantemir","year":"2017","unstructured":"Cantemir A, Alexa AI, Galan BG, Anton N, Ciuntu RE, Danielescu C, et al. Iontophoretic collagen cross-linking versus epithelium-off collagen cross-linking for early stage of progressive keratoconus - 3 years follow-up study. Acta Ophthalmol. 2017;95(7):e649\u201355.","journal-title":"Acta Ophthalmol"},{"issue":"7","key":"256_CR35","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1016\/j.jcrs.2014.10.041","volume":"41","author":"EE \u00c7erman","year":"2015","unstructured":"\u00c7erman EE, Toker E, Ozarslan OD. Transepithelial versus epithelium-off crosslinking in adults with progressive keratoconus. J Cataract Refract Surg. 2015;41(7):1416\u201325.","journal-title":"J Cataract Refract Surg"},{"key":"256_CR36","doi-asserted-by":"publisher","first-page":"445","DOI":"10.2147\/OPTH.S189183","volume":"13","author":"C Madeira","year":"2019","unstructured":"Madeira C, Vasques A, Beato J, Godinho G, Torr\u00e3o L, Falc\u00e3o M, et al. Transepithelial accelerated versus conventional corneal collagen crosslinking in patients with keratoconus: a comparative study. Clin Ophthalmol. 2019;13:445\u201352.","journal-title":"Clin Ophthalmol"},{"issue":"5","key":"256_CR37","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.clae.2018.06.001","volume":"41","author":"O Sarac","year":"2018","unstructured":"Sarac O, Caglayan M, Uysal BS, Uzel AGT, Tanriverdi B, Cagil N. Accelerated versus standard corneal collagen cross-linking in pediatric keratoconus patients: 24 months follow-up results. Cont Lens Anterior eye. 2018;41(5):442\u20137.","journal-title":"Cont Lens Anterior eye"},{"issue":"1","key":"256_CR38","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12886-018-0739-9","volume":"18","author":"M Tian","year":"2018","unstructured":"Tian M, Jian W, Sun L, Shen Y, Zhang X, Zhou X. One-year follow-up of accelerated transepithelial corneal collagen cross-linking for progressive pediatric keratoconus. BMC Ophthalmol. 2018;18(1):75.","journal-title":"BMC Ophthalmol"},{"key":"256_CR39","first-page":"3504","volume":"58","author":"SLG Serrao","year":"2017","unstructured":"Serrao S, Lombardo G, Giannini D, Lombardo M. Corneal topography and aberrometry changes one-year after transepithelial corneal cross-linking using iontophoresis versus standard corneal cross-linking. Invest Ophthalmol Vis Sci. 2017;58(8):3504.\u00a0","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"256_CR40","first-page":"3522","volume":"58","author":"RB Medina","year":"2017","unstructured":"Medina RB, Ramirez-Miranda AJ, Graue-Hernandez EO, Cabral J, Escudero-Rodriguez A. Efficacy, safety, clinical and topographic outcomes of two corneal crosslinking for the treatment keratoconus in a referral center. Invest Ophthalmol Vis Sci. 2017;58(8):3522.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"256_CR41","doi-asserted-by":"publisher","first-page":"4384","DOI":"10.1167\/iovs.18-24817","volume":"59","author":"ME Munoz Jas","year":"2018","unstructured":"Munoz JAS, Gonzalez Mendoza EA, Ramirez-Miranda AJ, Navas A, Graue-Hernandez EO. Comparison of corneal topographic characteristics between eyes with indication of transepithelial (epi-on) and epi-off cross linking for treatment of keratoconus in a reference center in Mexico City. Invest Ophthalmol Vis Sci. 2018;59(8):4384.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"supplement 262","key":"256_CR42","first-page":"4","volume":"97","author":"RS DA Godefrooij","year":"2019","unstructured":"Godefrooij DA, Rooh\u00e9 SL, Soeters N, Wisse RPL. The independent effect of various cross-linking treatment modalities on treatment effectiveness in keratoconus. Cornea. 2020;39(1):63-70.\u00a0","journal-title":"Acta Ophthalmol"},{"issue":"8","key":"256_CR43","doi-asserted-by":"publisher","first-page":"551","DOI":"10.3928\/1081597X-20180702-01","volume":"34","author":"R Atia","year":"2018","unstructured":"Atia R, Jouve L, Sandali O, Laroche L, Borderie V, Bouheraoua N. Early epithelial remodeling after standard and iontophoresis-assisted corneal cross-linking as evaluated by spectral-domain optical coherence tomography. J Refract surg. 2018;34(8):551\u20138.","journal-title":"J Refract surg"},{"issue":"2","key":"256_CR44","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1167\/iovs.13-12595","volume":"57","author":"M Cassagne","year":"2016","unstructured":"Cassagne M, Laurent C, Rodrigues M, Galinier A, Spoerl E, Galiacy SD, et al. Iontophoresis transcorneal delivery technique for transepithelial corneal collagen crosslinking with riboflavin in a rabbit model. Invest Ophthalmol Vis Sci. 2016;57(2):594\u2013603.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"6","key":"256_CR45","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1016\/j.ophtha.2017.01.040","volume":"124","author":"M Lombardo","year":"2017","unstructured":"Lombardo M, Giannini D, Lombardo G, Serrao S. Randomized controlled trial comparing transepithelial corneal cross-linking using iontophoresis with the dresden protocol in progressive keratoconus. Ophthalmology. 2017;124(6):804\u201312.","journal-title":"Ophthalmology"},{"issue":"5","key":"256_CR46","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1089\/jop.2014.0090","volume":"31","author":"E Yuksel","year":"2015","unstructured":"Yuksel E, Novruzlu S, Ozmen MC, Bilgihan K. A study comparing standard and transepithelial collagen cross-linking riboflavin solutions: epithelial findings and pain scores. J Ocul Pharmacol Ther. 2015;31(5):296\u2013302.","journal-title":"J Ocul Pharmacol Ther"},{"issue":"3","key":"256_CR47","doi-asserted-by":"publisher","first-page":"184","DOI":"10.3928\/1081597X-20190128-01","volume":"35","author":"P Vinciguerra","year":"2019","unstructured":"Vinciguerra P, Rosetta P, Legrottaglie EF, Morenghi E, Mazzotta C, Kaye SB, et al. Iontophoresis CXL with and without epithelial debridement versus standard CXL: 2-year clinical results of a prospective clinical study. J Refract Surg. 2019;35(3):184\u201390.","journal-title":"J Refract Surg"},{"issue":"7","key":"256_CR48","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.jcrs.2019.01.026","volume":"45","author":"M Lombardo","year":"2019","unstructured":"Lombardo M, Serrao S, Lombardo G, Schiano-Lomoriello D. Two-year outcomes of a randomized controlled trial of transepithelial corneal crosslinking with iontophoresis for keratoconus. J Cataract Refract Surg. 2019;45(7):992\u20131000.","journal-title":"J Cataract Refract Surg"},{"key":"256_CR49","doi-asserted-by":"publisher","first-page":"8","DOI":"10.2174\/1874364101913010008","volume":"13","author":"KAY Al Zubi","year":"2019","unstructured":"Al Zubi KAY, Nasser R. Transepithelial versus epithelium off crosslinking for treating keratoconus among Jordanians. Open Ophthalmol J. 2019;13:8\u201314.","journal-title":"Open Ophthalmol J"},{"issue":"3","key":"256_CR50","first-page":"e352","volume":"98","author":"M Iqbal","year":"2019","unstructured":"Iqbal M, Elmassry A, Saad H, Am Gad A, Ibrahim O, Hamed N, et al. Standard cross-linking protocol versus accelerated and transepithelial cross-linking protocols for treatment of paediatric keratoconus: a 2-year comparative study. Acta Ophthalmol. 2019;98(3):e352\u201362.","journal-title":"Acta Ophthalmol"},{"issue":"6","key":"256_CR51","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.1007\/s10792-017-0772-3","volume":"38","author":"S Rossi","year":"2018","unstructured":"Rossi S, Santamaria C, Boccia R, De Rosa L, D\u2019Alterio FM, Simonelli F, et al. Standard, transepithelial and iontophoresis corneal cross-linking: clinical analysis of three surgical techniques. Int Ophthalmol. 2018;38(6):2585\u201392.","journal-title":"Intl Ophthalmol"},{"issue":"2","key":"256_CR52","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1097\/ICO.0000000000001062","volume":"36","author":"L Jouve","year":"2017","unstructured":"Jouve L, Borderie V, Sandali O, Temstet C, Basli E, Laroche L, et al. Conventional and iontophoresis corneal cross-linking for keratoconus: efficacy and assessment by optical coherence tomography and confocal microscopy. Cornea. 2017;36(2):153\u201362.","journal-title":"Cornea"},{"issue":"12","key":"256_CR53","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1097\/ICO.0000000000001366","volume":"36","author":"MA Henriquez","year":"2017","unstructured":"Henriquez MA, Rodriguez AM, Izquierdo L Jr. Accelerated epi-on versus standard epi-off corneal collagen cross-linking for progressive keratoconus in pediatric patients. Cornea. 2017;36(12):1503\u20138.","journal-title":"Cornea"},{"key":"256_CR54","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.2147\/OPTH.S139358","volume":"11","author":"DA Godefrooij","year":"2017","unstructured":"Godefrooij DA, Kandoussi ME, Soeters N, Wisse RP. Higher order optical aberrations and visual acuity in a randomized controlled trial comparing transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus. Clin Ophthalmol. 2017;11:1931\u20136. https:\/\/doi.org\/10.2147\/OPTH.S139358.","journal-title":"Clin Ophthalmol."},{"issue":"4","key":"256_CR55","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1136\/bjophthalmol-2016-308914","volume":"101","author":"SW Rush","year":"2017","unstructured":"Rush SW, Rush RB. Epithelium-off versus transepithelial corneal collagen crosslinking for progressive corneal ectasia: a randomised and controlled trial. Br J Ophthalmol. 2017;101(4):503\u20138.","journal-title":"Br J Ophthalmol"},{"issue":"3","key":"256_CR56","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1097\/ICL.0000000000000255","volume":"43","author":"M Eraslan","year":"2017","unstructured":"Eraslan M, Toker E, Cerman E, Ozarslan D. Efficacy of epithelium-off and epithelium-on corneal collagen cross-linking in pediatric keratoconus. Eye Contact Lens. 2017;43(3):155\u201361.","journal-title":"Eye Contact Lens"},{"issue":"7","key":"256_CR57","doi-asserted-by":"publisher","first-page":"e600","DOI":"10.1111\/aos.13032","volume":"94","author":"G Bikbova","year":"2016","unstructured":"Bikbova G, Bikbov M. Standard corneal collagen crosslinking versus transepithelial iontophoresis-assisted corneal crosslinking, 24 months follow-up: randomized control trial. Acta Ophthalmol. 2016;94(7):e600\u20136.","journal-title":"Acta Ophthalmol"},{"issue":"10","key":"256_CR58","doi-asserted-by":"publisher","first-page":"672","DOI":"10.3928\/1081597X-20160629-02","volume":"32","author":"P Vinciguerra","year":"2016","unstructured":"Vinciguerra P, Romano V, Rosetta P, Legrottaglie EF, Piscopo R, Fabiani C, et al. Transepithelial iontophoresis versus standard corneal collagen cross-linking: 1-year results of a prospective clinical study. J Refractive Surg. 2016;32(10):672\u20138.","journal-title":"J Refractive Surg"},{"issue":"Suppl 10","key":"256_CR59","doi-asserted-by":"publisher","first-page":"S53","DOI":"10.1097\/ICO.0000000000000547","volume":"34","author":"MF Al Fayez","year":"2015","unstructured":"Al Fayez MF, Alfayez S, Alfayez Y. Transepithelial versus epithelium-off corneal collagen cross-linking for progressive keratoconus: a prospective randomized controlled trial. Cornea. 2015;34(Suppl 10):S53-6.","journal-title":"Cornea"},{"key":"256_CR60","doi-asserted-by":"publisher","first-page":"503","DOI":"10.2147\/OPTH.S73991","volume":"9","author":"S Rossi","year":"2015","unstructured":"Rossi S, Orrico A, Santamaria C, Romano V, De Rosa L, Simonelli F, et al. Standard versus trans-epithelial collagen cross-linking in keratoconus patients suitable for standard collagen cross-linking. Clin Ophthalmol. 2015;9:503\u20139.","journal-title":"Clinical Ophthalmol"},{"issue":"5","key":"256_CR61","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.ajo.2015.02.005","volume":"159","author":"N Soeters","year":"2015","unstructured":"Soeters N, Wisse RP, Godefrooij DA, Imhof SM, Tahzib NG. Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial. Am J Ophthalmol. 2015;159(5):821-8.e3.","journal-title":"Am J Ophthalmol"},{"issue":"4","key":"256_CR62","doi-asserted-by":"publisher","first-page":"e0195105","DOI":"10.1371\/journal.pone.0195105","volume":"13","author":"X Zhang","year":"2018","unstructured":"Zhang X, Zhao J, Li M, Tian M, Shen Y, Zhou X. Conventional and transepithelial corneal cross-linking for patients with keratoconus. PLoS One. 2018;13(4):e0195105.","journal-title":"PLoS ONE"},{"issue":"8","key":"256_CR63","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1097\/ICO.0000000000001632","volume":"37","author":"D Wen","year":"2018","unstructured":"Wen D, Song B, Li Q, Tu R, Huang Y, Wang Q, et al. Comparison of epithelium-off versus transepithelial corneal collagen cross-linking for keratoconus: a systematic review and meta-analysis. Cornea. 2018;37(8):1018\u201324.","journal-title":"Cornea"}],"container-title":["Eye and Vision"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40662-021-00256-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40662-021-00256-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40662-021-00256-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T15:26:05Z","timestamp":1634743565000},"score":1,"resource":{"primary":{"URL":"https:\/\/eandv.biomedcentral.com\/articles\/10.1186\/s40662-021-00256-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,26]]},"references-count":63,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["256"],"URL":"https:\/\/doi.org\/10.1186\/s40662-021-00256-0","relation":{},"ISSN":["2326-0254"],"issn-type":[{"value":"2326-0254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,26]]},"assertion":[{"value":"27 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Author Jorge L. Alio is a member of the Editorial Board for Eye and Vision. The other authors declare they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34"}}