{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:55:49Z","timestamp":1784566549676,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"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>Purpose: To report long-term clinical results of transepithelial cross-linking with iontophoresis (I-CXL) for progressive keratoconus (KC). Methods: Nineteen eyes of 19 patients treated with I-CXL for progressive keratoconus were included in this prospective clinical study. Preoperatively and in all available follow ups (6, 12, 24, 36, 48, 60, 72 and 84 months), the following parameters were measured. Corrected distance visual acuity (CDVA), spherical equivalent and cylinder refraction, corneal topography and aberrometry (Costruzione Strumenti Oftalmici (C.S.O.), Florence, Italy), Scheimpflug tomography (OCULUS Optikger\u00e4te GmbH; Wetzlar, Germany). Definition of progression after I-CXL was 2\/3 of the following criteria: increase of \u201cA\u201d value, increase of \u201cB\u201d value, decrease of minimal thickness evaluated with the ABCD progression display above 95% confidence interval for post-CXL population when compared to the scan 12 months post-op. Results: The mean follow-up time of included patients was 63 months (range 12 to 84 months, 5 patients reached 84 months). The general linear model showed no significant change over time in CDVA, Maximum Keratometry, Thinnest point, and A, B, C values of the Belin Progression Display (p &gt; 0.05). Conversely, comatic and high order aberrations decreased significantly over time (both p =&lt; 0.001). Five cases (26.31%) showed significant progression after a mean of 55 months (range 36\u201372) of follow up. Conclusion: Our study shows the ability of I-CXL to slow down KC progression in the majority of included patients, improving high order and comatic aberrations. A 26% progression rate was reported.<\/jats:p>","DOI":"10.3390\/jcm11030678","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T05:26:17Z","timestamp":1643433977000},"page":"678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Transepithelial Iontophoresis-Assisted Cross Linking for Progressive Keratoconus: Up to 7 Years of Follow Up"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-9981","authenticated-orcid":false,"given":"Riccardo","family":"Vinciguerra","sequence":"first","affiliation":[{"name":"Humanitas San Pio X Hospital, 20100 Milan, Italy"},{"name":"The School of Engineering, University of Liverpool, Liverpool L69 3BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2694-2816","authenticated-orcid":false,"given":"Emanuela","family":"Legrottaglie","sequence":"additional","affiliation":[{"name":"Humanitas Clinical and Research Center\u2014IRCCS, Via Manzoni 56, 20089 Rozzano, MI, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costanza","family":"Tredici","sequence":"additional","affiliation":[{"name":"Humanitas Clinical and Research Center\u2014IRCCS, Via Manzoni 56, 20089 Rozzano, MI, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosimo","family":"Mazzotta","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, Post Graduate Ophthalmology School, University of Siena, 53100 Siena, Italy"},{"name":"Ophthalmology Operative Unit, Usl Toscana Sudest, Alta Val d\u2019Elsa Hospital, Campostaggia, 53100 Siena, Italy"},{"name":"Casentino Hospital, 52100 Bibbiena, AR, Italy"},{"name":"Siena Crosslinking Center, Monteriggioni, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Rosetta","sequence":"additional","affiliation":[{"name":"Humanitas San Pio X Hospital, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Vinciguerra","sequence":"additional","affiliation":[{"name":"Humanitas Clinical and Research Center\u2014IRCCS, Via Manzoni 56, 20089 Rozzano, MI, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, MI, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108328","DOI":"10.1016\/j.exer.2020.108328","article-title":"Genetics vs chronic corneal mechanical trauma in the etiology of keratoconus","volume":"202","author":"Rabinowitz","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/eye.2015.63","article-title":"Keratoconus: An inflammatory disorder?","volume":"29","author":"Galvis","year":"2015","journal-title":"Eye"},{"key":"ref_3","first-page":"6628923","article-title":"Tear Levels of Inflammatory Cytokines in Keratoconus: A Meta-Analysis of Case-Control and Cross-Sectional Studies","volume":"2021","author":"Zhang","year":"2021","journal-title":"BioMed Res. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1097\/ICU.0000000000000764","article-title":"The role of environment in the pathogenesis of keratoconus","volume":"32","author":"Goncalves","year":"2021","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3928\/1081597X-20180104-01","article-title":"Progression of Keratoconus in Patients While Awaiting Corneal Cross-linking: A Prospective Clinical Study","volume":"34","author":"Romano","year":"2018","journal-title":"J. Refract. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.jcrs.2008.11.036","article-title":"Biomechanical and histological changes after corneal crosslinking with and without epithelial debridement","volume":"35","author":"Wollensak","year":"2009","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1016\/S0886-3350(03)00407-3","article-title":"Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking","volume":"29","author":"Wollensak","year":"2003","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"869015","DOI":"10.1155\/2011\/869015","article-title":"Complications of corneal collagen cross-linking","volume":"2011","author":"Dhawan","year":"2011","journal-title":"J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1097\/ICO.0000000000001632","article-title":"Comparison of Epithelium-Off Versus Transepithelial Corneal Collagen Cross-Linking for Keratoconus: A Systematic Review and Meta-Analysis","volume":"37","author":"Wen","year":"2018","journal-title":"Cornea"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"256","DOI":"10.4103\/JOCO.JOCO_59_20","article-title":"Corneal Collagen Cross-Linking Using Epithelium Disruptor Instrument in Progressive Keratoconus","volume":"32","author":"Zaheryani","year":"2020","journal-title":"J. Curr. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3928\/1081597X-20150122-06","article-title":"Matched comparison study of total and partial epithelium removal in corneal cross-linking","volume":"31","author":"Hashemi","year":"2015","journal-title":"J. Refract. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4137\/OED.S38364","article-title":"Corneal Cross-Linking (with a Partial Deepithelization) in Keratoconus with Five Years of Follow-Up","volume":"8","author":"Galvis","year":"2016","journal-title":"Ophthalmol. Eye Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.jcrs.2013.03.026","article-title":"Transepithelial corneal collagen crosslinking for progressive keratoconus: 24-month clinical results","volume":"39","author":"Caporossi","year":"2013","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"404587","DOI":"10.1155\/2014\/404587","article-title":"Imaging mass spectrometry by matrix-assisted laser desorption\/ionization and stress-strain measurements in iontophoresis transepithelial corneal collagen cross-linking","volume":"2014","author":"Vinciguerra","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1097\/ICO.0000000000001965","article-title":"Iontophoretic Transepithelial Collagen Cross-Linking Versus Epithelium-Off Collagen Cross-Linking in Pediatric Patients: 3-Year Follow-Up","volume":"38","author":"Buzzonetti","year":"2019","journal-title":"Cornea"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3928\/1081597X-20190128-01","article-title":"Iontophoresis CXL with and without Epithelial Debridement Versus Standard CXL: 2-Year Clinical Results of a Prospective Clinical Study","volume":"35","author":"Vinciguerra","year":"2019","journal-title":"J. Refract. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e649","DOI":"10.1111\/aos.13538","article-title":"Iontophoretic collagen cross-linking versus epithelium-off collagen cross-linking for early stage of progressive keratoconus-3 years follow-up study","volume":"95","author":"Cantemir","year":"2017","journal-title":"Acta Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e600","DOI":"10.1111\/aos.13032","article-title":"Standard corneal collagen crosslinking versus transepithelial iontophoresis-assisted corneal crosslinking, 24 months follow-up: Randomized control trial","volume":"94","author":"Bikbova","year":"2016","journal-title":"Acta Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3928\/1081597X-20200406-02","article-title":"Iontophoresis Corneal Cross-linking With Enhanced Fluence and Pulsed UV-A Light: 3-Year Clinical Results","volume":"36","author":"Mazzotta","year":"2020","journal-title":"J. Refract. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00417-020-04861-y","article-title":"Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: Retrospective 5-year analysis","volume":"259","author":"Wu","year":"2021","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"657","DOI":"10.2147\/OPTH.S101386","article-title":"Patient selection for corneal collagen cross-linking: An updated review","volume":"11","author":"Galvis","year":"2017","journal-title":"Clin. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Vinciguerra, R., Belin, M.W., Borgia, A., Piscopo, R., Montericcio, A., Confalonieri, F., Legrottaglie, E.F., Rosetta, P., and Paolo, V. (J. Cataract Refract. Surg., 2020). Evaluating Keratoconus Progression prior to Crosslinking: Kmax versus the ABCD grading system, J. Cataract Refract. Surg., in press.","DOI":"10.1097\/j.jcrs.0000000000000475"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12345","DOI":"10.1038\/s41598-018-30173-7","article-title":"Improving precision for detecting change in the shape of the cornea in patients with keratoconus","volume":"8","author":"Brunner","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1055\/s-0042-100626","article-title":"Keratoconus: The ABCD Grading System","volume":"233","author":"Belin","year":"2016","journal-title":"Klin. Monbl. Augenheilkd."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1097\/APO.0000000000000333","article-title":"Determining Progression in Ectatic Corneal Disease","volume":"9","author":"Belin","year":"2020","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"838","DOI":"10.3928\/1081597X-20201021-01","article-title":"Corneal Cross-linking for Progressive Keratoconus: Up to 13 Years of Follow-up","volume":"36","author":"Vinciguerra","year":"2020","journal-title":"J. Refract. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"746","DOI":"10.3928\/1081597X-20141021-06","article-title":"Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: Initial clinical outcomes","volume":"30","author":"Vinciguerra","year":"2014","journal-title":"J. Refract. Surg."},{"key":"ref_29","first-page":"S227","article-title":"The role of amino acids in corneal stromal healing: A method for evaluating cellular density and extracellular matrix distribution","volume":"19","author":"Grizzi","year":"2003","journal-title":"J. Refract. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/eye.2013.266","article-title":"Objective evaluation of refractive data and astigmatism: Quantification and analysis","volume":"28","author":"Kaye","year":"2014","journal-title":"Eye"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1016\/S0886-3350(02)01639-5","article-title":"Analyzing refractive data","volume":"28","author":"Kaye","year":"2002","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/00006324-197601000-00005","article-title":"A matrix formalism for decentration problems","volume":"53","author":"Long","year":"1976","journal-title":"Am. J. Optom. Physiol. Opt."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ajo.2013.11.018","article-title":"Corneal Cross-linking: Intrastromal Riboflavin Concentration in Iontophoresis-Assisted Imbibition Versus Traditional and Transepithelial Techniques","volume":"157","author":"Mastropasqua","year":"2014","journal-title":"Am. J. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1167\/iovs.13-12595","article-title":"Iontophoresis Transcorneal Delivery Technique for Transepithelial Corneal Collagen Crosslinking With Riboflavin in a Rabbit Model","volume":"57","author":"Cassagne","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","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":"ref_36","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1097\/ICO.0000000000001505","article-title":"Corneal Collagen Cross-Linking with Riboflavin and Ultraviolet A Light for Pediatric Keratoconus: Ten-Year Results","volume":"37","author":"Mazzotta","year":"2018","journal-title":"Cornea"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8285649","DOI":"10.1155\/2019\/8285649","article-title":"10-Year Results of Standard Cross-Linking in Patients with Progressive Keratoconus in Romania","volume":"2019","author":"Nicula","year":"2019","journal-title":"J. Ophthalmol."},{"key":"ref_38","first-page":"CD013512","article-title":"Transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus","volume":"3","author":"Ng","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gustafsson, I., Bergstrom, A., Myers, A.C., Ivarsen, A., and Hjortdal, J. (2020). Association between keratoconus disease severity and repeatability in measurements of parameters for the assessment of progressive disease. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0228992"},{"key":"ref_40","doi-asserted-by":"crossref","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."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/3\/678\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:09:40Z","timestamp":1760134180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/3\/678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":40,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["jcm11030678"],"URL":"https:\/\/doi.org\/10.3390\/jcm11030678","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]}}}