{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:17:39Z","timestamp":1787314659234,"version":"build-2736575974"},"reference-count":28,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Customized cross-linking has been proposed as an alternative to conventional cross-linking in patients with progressive keratoconus, targeting greater flattening of the cone region and improved visual function. Epithelium-on cross-linking aims to reduce complications associated with epithelial removal, while the addition of oxygen aims to maintain treatment effect. Our study evaluates the combination of these novel treatment strategies to achieve a minimally invasive treatment targeting maximal functional outcomes. This prospective study included 42 eyes undergoing epithelium-on, accelerated, oxygen-supplemented, customized corneal cross-linking for progressive keratoconus. Outcome measures, including refraction, visual acuity, and corneal tomography were obtained at baseline and at 1, 3, and 6 months, and 1 year postoperatively. Logarithm of the minimum angle of resolution (logMAR) uncorrected visual acuity was significantly improved, from 0.87 \u00b1 0.53 preoperatively, to 0.78 \u00b1 0.56 1 year postoperatively (Wilcoxon rank sum test, p = 0.016). LogMAR best spectacle-corrected visual acuity was also significantly improved, from 0.19 \u00b1 0.36 preoperatively, to 0.11 \u00b1 0.33 postoperatively (p = 0.004). Manifest refractive cylinder was significantly decreased, from 4.50 \u00b1 2.96 D preoperatively, to 3.27 \u00b1 2.61 D postoperatively (p = 0.004). The baseline maximum keratometry (Kmax) was 53.04 \u00b1 7.91 D, significantly flattening to 52.25 \u00b1 7.31 D by 1 month, and remaining relatively stable at 1 year postoperatively (52.31 \u00b1 7.50 D) (p &lt; 0.001). No significant adverse events occurred in any eye. Epithelium-on, accelerated, oxygen-supplemented, customized corneal cross-linking is a promising new treatment approach, with reduced maximum keratometry, reduced astigmatism, and improved visual acuity at 1 year, with a favorable safety and patient comfort profile.<\/jats:p>","DOI":"10.3390\/jcm9103222","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T08:52:41Z","timestamp":1602147161000},"page":"3222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Visual and Topographic Improvement with Epithelium-On, Oxygen-Supplemented, Customized Corneal Cross-Linking for Progressive Keratoconus"],"prefix":"10.3390","volume":"9","author":[{"given":"Kazutaka","family":"Kamiya","sequence":"first","affiliation":[{"name":"Visual Physiology, School of Allied Health Sciences, Kitasato University, Kanagawa 252-0373, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Kanayama","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Kitasato University, Kanagawa 252-0374, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Kitasato University, Kanagawa 252-0374, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3719-0376","authenticated-orcid":false,"given":"Nobuyuki","family":"Shoji","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Kitasato University, Kanagawa 252-0374, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1097\/ICO.0000000000000408","article-title":"Global Consensus on Keratoconus and Ectatic Diseases","volume":"34","author":"Gomes","year":"2015","journal-title":"Cornea"},{"key":"ref_2","doi-asserted-by":"crossref","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":"ref_3","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.ophtha.2017.05.036","article-title":"U.S. Multicenter Clinical Trial of Corneal Collagen Crosslinking for Treatment of Corneal Ectasia after Refractive Surgery","volume":"124","author":"Hersh","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2174\/1874364101812010181","article-title":"A Review of Corneal Collagen Cross-linking \u2013 Current Trends in Practice Applications","volume":"12","author":"Lim","year":"2018","journal-title":"Open Ophthalmol. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000363371","article-title":"Toric topographically customized transepithelial, pulsed, very high-fluence, higher energy and higher riboflavin concentration collagen cross-linking in keratoconus","volume":"5","author":"Kanellopoulos","year":"2014","journal-title":"Case Rep. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3928\/1081597X-20170621-07","article-title":"Customized corneal crosslinking using different UVA beam profiles Customized corneal crosslinking using different UVA beam profiles","volume":"33","author":"Shetty","year":"2017","journal-title":"J. Refract. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2031031","DOI":"10.1155\/2016\/2031031","article-title":"Accelerated Corneal Collagen Cross-Linking Using Topography-Guided UV-A Energy Emission: Preliminary Clinical and Morphological Outcomes","volume":"2016","author":"Mazzotta","year":"2016","journal-title":"J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1097\/ICL.0000000000000084","article-title":"Advances in the Technology of Corneal Cross-Linking for Keratoconus","volume":"40","author":"Lytle","year":"2014","journal-title":"Eye Contact Lens"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nordstr\u00f6m, M., Schiller, M., Fredriksson, A., and Behndig, A. (2016). Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results. Br. J. Ophthalmol., 2016.","DOI":"10.1136\/bjophthalmol-2016-309210"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ajo.2016.02.029","article-title":"Customized Corneal Cross-linking: One-Year Results","volume":"166","author":"Seiler","year":"2016","journal-title":"Am. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3928\/1081597X-20170201-02","article-title":"Customized Topography-Guided Corneal Collagen Cross-linking for Keratoconus","volume":"33","author":"Cassagne","year":"2017","journal-title":"J. Refract. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.jcrs.2012.01.024","article-title":"Refractive and topographic results of benzalkonium chloride-assisted transepithelial crosslinking","volume":"38","author":"Koppen","year":"2012","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3928\/1081597X-20160428-02","article-title":"Transepithelial Corneal Cross-linking Using an Enhanced Riboflavin Solution","volume":"32","author":"Gatzioufas","year":"2016","journal-title":"J. Refract. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1167\/iovs.11-9385","article-title":"Photochemical Kinetics of Corneal Cross-Linking with Riboflavin","volume":"53","author":"Kamaev","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1080\/02713683.2019.1669663","article-title":"Optimization of Oxygen Dynamics, UV-A Delivery, and Drug Formulation for Accelerated Epi-On Corneal Crosslinking","volume":"45","author":"Hill","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Taneri, S., Oehler, S., Lytle, G., and Burkhard Dick, H. (2014). Evaluation of epithelial integrity with various transepithelial corneal cross-linking protocols for treatment of keratoconus. J. Ophthalmol., 2014.","DOI":"10.1155\/2014\/614380"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5006","DOI":"10.1167\/iovs.15-16903","article-title":"Transepithelial riboflavin absorption in an ex vivo rabbit corneal model","volume":"56","author":"Gore","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"438","DOI":"10.3928\/1081597X-20180515-02","article-title":"Enhanced-fluence pulsed-light iontophoresis corneal cross-linking: 1-Year morphological and clinical results","volume":"34","author":"Mazzotta","year":"2018","journal-title":"J. Refract. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1097\/ICO.0000000000001229","article-title":"Comparison of 2 Different Methods of Transepithelial Corneal Collagen Cross-Linking: Analysis of Corneal Histology and Hysteresis","volume":"36","author":"Park","year":"2017","journal-title":"Cornea"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1007\/s10792-017-0762-5","article-title":"Transepithelial accelerated corneal collagen cross-linking with higher oxygen availability for keratoconus: 1-year results","volume":"38","author":"Sun","year":"2017","journal-title":"Int. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/ijo.IJO_1227_17","article-title":"Photo Essay Clinical presentation following photorefractive intrastromal cross\u2014Linking for myopic correction","volume":"66","author":"Sachdev","year":"2018","journal-title":"Indian J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.jcrs.2018.11.008","article-title":"Transepithelial photorefractive intrastromal corneal crosslinking versus photorefractive keratectomy in low myopia","volume":"45","author":"Hout","year":"2018","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mazzotta, C., Sgheri, A., Bagaglia, S.A., Rechichi, M., and Di Maggio, A. (2020). Customized corneal crosslinking for treatment of progressive keratoconus: Clinical and OCT outcomes using a transepithelial approach with supplemental oxygen. J. Cataract Refract. Surg.","DOI":"10.1097\/j.jcrs.0000000000000347"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.jcrs.2018.08.021","article-title":"Transepithelial versus epithelium-off corneal crosslinking for corneal ectasia","volume":"44","author":"Kobashi","year":"2018","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.ophtha.2019.02.029","article-title":"Keratoconus Natural Progression: A Systematic Review and Meta-analysis of 11\u2009529 Eyes","volume":"126","author":"Ferdi","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1097\/ICO.0000000000001579","article-title":"Corneal Cross-Linking for Pediatric Keratcoconus Review","volume":"37","author":"Gaster","year":"2018","journal-title":"Cornea"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1007\/s10792-020-01446-w","article-title":"Comparison of the efficacy of accelerated corneal cross-linking therapy in different pediatric age groups having progressive keratoconus","volume":"40","author":"Ozer","year":"2020","journal-title":"Int. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jtos.2015.04.007","article-title":"In Vivo Confocal Microscopy after Corneal Collagen Crosslinking","volume":"13","author":"Mazzotta","year":"2015","journal-title":"Ocul. Surf."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/10\/3222\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:17:21Z","timestamp":1760177841000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/10\/3222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,8]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["jcm9103222"],"URL":"https:\/\/doi.org\/10.3390\/jcm9103222","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,8]]}}}