{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:00:31Z","timestamp":1783720831871,"version":"3.55.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>This study performs comparative assessment of the results of different types of two-stage surgical treatment in patients with keratoconus, including combination of corneal collagen cross-linking with intrastromal corneal ring segments followed by topography-guided photorefractive keratectomy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>Prospective review of 101 patients (101 eyes) with keratoconus was performed. Patients underwent corneal collagen cross-linking (32 patients), intrastromal corneal ring segments (48 patients), and a combination of these two procedures (21 patients). Transepithelial topography-guided photorefractive keratectomy was performed as the second stage of treatment in all patients with obtained stable refractive results at 8 months after first stage. Main outcome measures were visual acuity (uncorrected distance and corrected distance) and corneal topographic indices.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Comparison of the studied parameters after first stage surgical treatment between non-combined CXL and combined groups demonstrated a statistically significant difference for uncorrected distance visual acuity, corrected distance visual acuity, and cylindrical refraction values (p&lt;0.05). We observed significant improvement of visual acuity and key corneal topographic indices after topography-guided photorefractive keratectomy in all study groups (p&lt;0.05). In 50 (49.5%) patients customized excimer laser ablation gave the possibility of full spherical and cylindrical corrections. Ten eyes (10%) had delayed epithelial healing, no corneal stromal opacities developed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>This study shows that combined two-stage surgical treatment of keratoconus, consisting of intrastromal corneal ring segment implantation with corneal collagen cross-linking followed by topography-guided photorefractive keratectomy, is clinically more effective to prevent keratectasia progression and increase visual acuity than the use of non-combined two-stage techniques.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0264030","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T18:32:26Z","timestamp":1646677946000},"page":"e0264030","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluation of the effectiveness of combined staged surgical treatment in patients with keratoconus"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-0343","authenticated-orcid":true,"given":"Polad M.","family":"Maharramov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fidan A.","family":"Aghayeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"issue":"2","key":"pone.0264030.ref001","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s40123-017-0099-1","article-title":"Keratoconus Treatment Algorithm","volume":"6","author":"KD Andreanos","year":"2017","journal-title":"Ophthalmol Ther"},{"issue":"12","key":"pone.0264030.ref002","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1038\/s41433-020-1065-z","article-title":"Current perspectives in the management of keratoconus with contact lenses","volume":"34","author":"L Lim","year":"2020","journal-title":"Eye (Lond)"},{"issue":"3","key":"pone.0264030.ref003","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s10792-018-0858-6","article-title":"Results of ethanol-assisted epithelium-on corneal cross-linking with and without intrastromal corneal ring implantation","volume":"39","author":"O Ayar","year":"2019","journal-title":"Int Ophthalmol"},{"issue":"2","key":"pone.0264030.ref004","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/ICO.0000000000001104","article-title":"Efficacy of intrastromal corneal ring segments combined with flash collagen cross-linking in keratoconus","volume":"36","author":"CH Gordillo","year":"2017","journal-title":"Cornea"},{"key":"pone.0264030.ref005","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2147\/OPTH.S151313","article-title":"Simultaneous intratunnel cross-linking with intrastromal corneal ring segment implantation versus simultaneous epithelium-off cross-linking with intrastromal corneal ring segment implantation for keratoconus management","volume":"12","author":"M Hosny","year":"2018","journal-title":"Clin Ophthalmol"},{"key":"pone.0264030.ref006","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.jcrs.2018.05.020","article-title":"Visual and keratometric outcomes of keratoconus patients after sequential corneal crosslinking and topography-guided surface ablation: early United States experience","volume":"44","author":"A Nattis","year":"2018","journal-title":"J Cataract Refract Surg"},{"issue":"1","key":"pone.0264030.ref007","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1177\/1120672119887874","article-title":"Corneal collagen cross-linking with and without simultaneous intrastromal corneal ring segment implantation: One-year pilot study","volume":"31","author":"IP Sharma","year":"2021","journal-title":"Eur J Ophthalmol"},{"issue":"9","key":"pone.0264030.ref008","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/j.ophtha.2017.03.052","article-title":"RajpalRK. 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Multicenter Clinical Trial of Corneal Colla-gen Crosslinking for Keratoconus Treatment","volume":"124","author":"PS Hersh","year":"2017","journal-title":"Ophthalmology"},{"issue":"10","key":"pone.0264030.ref009","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1097\/ICO.0000000000000248","article-title":"Long-term follow-up of corneal collagen cross-linking for keratoconus\u2014the Cretan study","volume":"33","author":"GD Kymionis","year":"2014","journal-title":"Cornea"},{"issue":"1","key":"pone.0264030.ref010","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":"F Raiskup","year":"2015","journal-title":"J Cataract Refract Surg"},{"key":"pone.0264030.ref011","doi-asserted-by":"crossref","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"},{"issue":"9","key":"pone.0264030.ref012","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1097\/ICO.0000000000001663","article-title":"Evaluation of the Effectiveness of Cross-Linking Combined with Photorefractive Keratectomy for Treatment of Keratoconus","volume":"37","author":"M Iqbal","year":"2018","journal-title":"Cornea"},{"issue":"12","key":"pone.0264030.ref013","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.18240\/ijo.2019.12.16","article-title":"Combined corneal CXL and photorefractive keratectomy for treatment of keratoconus: a review","volume":"12","author":"MM Al-Mohaimeed","year":"2019","journal-title":"Int J Ophthalmol"},{"issue":"Suppl 1","key":"pone.0264030.ref014","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s40123-019-00210-3","article-title":"Combined Protocols for Corneal Collagen Cross-Linking with Photorefractive Surgery for Refractive Management of Keratoconus: Update on Techniques and Review of Literature","volume":"8","author":"AY Zhu","year":"2019","journal-title":"Ophthalmol Ther"},{"issue":"5","key":"pone.0264030.ref015","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.jcjo.2017.12.003","article-title":"Outcomes of simultaneous photorefractive keratectomy and collagen crosslinking","volume":"53","author":"O Ohana","year":"2018","journal-title":"Can J Ophthalmol"},{"issue":"6","key":"pone.0264030.ref016","first-page":"1045","article-title":"Combined treatment for keratoconus","volume":"7","author":"E. Couskunseven","year":"2011","journal-title":"Ophthalmology Times Europe"},{"issue":"4","key":"pone.0264030.ref017","doi-asserted-by":"crossref","first-page":"e623","DOI":"10.1111\/aos.13986","article-title":"Standard cross-linking versus photorefractive keratectomy combined with accelerated cross-linking for keratoconus management: a comparative study","volume":"97","author":"M Iqbal","year":"2019","journal-title":"Acta Ophthalmol"},{"issue":"5","key":"pone.0264030.ref018","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.jcrs.2018.03.026","article-title":"Combined wavefront-guided transepithelial photorefractive keratectomy and corneal crosslinking for visual rehabilitation in moderate keratoconus","volume":"44","author":"DM Gore","year":"2018","journal-title":"J Cataract Refract Surg"},{"key":"pone.0264030.ref019","doi-asserted-by":"crossref","first-page":"581","DOI":"10.2147\/OPTH.S188517","article-title":"Management of progressive keratoconus with partial topography-guided PRK combined with refractive, customized CXL\u2014a novel technique: the enhanced Athens protocol","volume":"13","author":"AJ Kanellopoulos","year":"2019","journal-title":"Clin Ophthalmol"},{"issue":"2","key":"pone.0264030.ref020","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3928\/1081597X-20190114-01","article-title":"Haze and visual acuity loss after sequential photorefractive keratectomy and corneal cross-linking for keratoconus","volume":"35","author":"RLB Moraes","year":"2019","journal-title":"J Refract Surg"},{"key":"pone.0264030.ref021","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/j.jcrs.2017.06.047","article-title":"Combined transepithelial phototherapeutic keratectomy and conventional photorefractive keratectomy followed simultaneously by corneal crosslinking for keratoconus: Cretan protocol plus","volume":"43","author":"MA Grentzelos","year":"2017","journal-title":"J Cataract Refract Surg"},{"issue":"4","key":"pone.0264030.ref022","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/ICU.0000000000000675","article-title":"Refractive approaches to visual rehabilitation in patients with keratoconus","volume":"31","author":"KH Kim","year":"2020","journal-title":"Curr Opin Ophthalmol"},{"key":"pone.0264030.ref023","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1159\/000480242","article-title":"Corneal collagen crosslinking combined with phototherapeutic keratectomy and photorefractive keratectomy for corneal ectasia after laser in situ keratomileusis","volume":"59","author":"W Zhu","year":"2018","journal-title":"Ophthalmic Res"},{"issue":"9","key":"pone.0264030.ref024","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1097\/ICO.0000000000002739","article-title":"Keratoconus Management With Customized Photorefractive Keratectomy by Artificial Intelligence Ray-Tracing Optimization Combined With Higher Fluence Corneal Crosslinking: The Ray-Tracing Athens Protocol","volume":"40","author":"AJ Kanellopoulos","year":"2021","journal-title":"Cornea"},{"issue":"10","key":"pone.0264030.ref025","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1097\/ICO.0000000000002073","article-title":"Combined phototherapeutic keratectomy, intracorneal ring segment implantation, and corneal collagen cross-linking in keratoconus management","volume":"38","author":"G Rocha","year":"2019","journal-title":"Cornea"},{"key":"pone.0264030.ref026","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40662-016-0033-y","article-title":"Corneal surgery in keratoconus: which type, which technique, which outcomes?","volume":"3","author":"F Arnalich-Montiel","year":"2016","journal-title":"Eye Vis"},{"key":"pone.0264030.ref027","volume-title":"Medical-biological statistics [Mediko-biologicheskaia statistika]","author":"G. 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