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Ocular surface assessments, in vivo confocal microscopy for seven corneal nerve parameters, four corneal dendritic cell parameters, three corneal epithelial parameters, and tear neuromediator analysis were performed preoperatively and 1, 3, 6 and 12\u00a0months postoperatively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>There were no significant differences in all ocular surface assessments between CLEAR and SMILE throughout postoperative 1\u00a0year. CLEAR and SMILE led to significant and comparable reductions of corneal nerve fiber density (CNFD), nerve branch density, total branch density, nerve fiber length, area, and fiber fractal dimension, which did not restore even at 1\u00a0year. The reduction in CNFD was significantly correlated with the corrected spherical equivalent in both surgical types. Although post-SMILE eyes had significantly higher nerve growth factor concentrations at 1\u00a0month, there was no significant difference in substance P and calcitonin gene-related peptide (CGRP) concentrations between SMILE and CLEAR.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>CLEAR and SMILE had comparable effects on ocular surface, corneal denervation and postoperative neuroinflammation. Corneal nerve metrics did not restore even at 1\u00a0year for both procedures.<\/jats:p>\n            <jats:p>\n              <jats:bold>\n                <jats:italic>Trial registration number:<\/jats:italic>\n              <\/jats:bold> ClinicalTrials.gov NCT06774651, registration on 14 January 2025, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT06774651\" ext-link-type=\"uri\">https:\/\/clinicaltrials.gov\/study\/NCT06774651<\/jats:ext-link>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40662-025-00429-1","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:26:57Z","timestamp":1743467217000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Randomized controlled trial on corneal denervation, neuroinflammation and ocular surface in corneal lenticule extraction for advanced refractive correction (CLEAR) and small incision lenticule extraction (SMILE)"],"prefix":"10.1186","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct06774651","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Mingyi","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle Xin Yu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Wei-Tse","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina Kay Ting","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansa","family":"Anam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodhbir S.","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5408-0382","authenticated-orcid":false,"given":"Yu-Chi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"issue":"2","key":"429_CR1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.4103\/tjo.tjo_12_21","volume":"11","author":"M Fuest","year":"2021","unstructured":"Fuest M, Mehta JS. 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