{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T16:57:03Z","timestamp":1785603423202,"version":"3.56.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Graefes Arch Clin Exp Ophthalmol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To systematically evaluate the biomechanical, optical, and clinical outcomes of crosslinking (CXL) applied to corneal stromal lenticules derived from keratorefractive lenticular extraction, and to assess the rationale and efficacy of this approach for therapeutic re-implantation in corneal disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review with exploratory pooled analysis was conducted following PRISMA and MOOSE guidelines. Literature searches across five databases identified studies reporting outcomes following crosslinking of SMILE-derived lenticules. Risk of bias was assessed using appropriate tools for study design. Random-effects pooled analyses were performed for clinical outcomes where appropriate, with careful consideration of study heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nine studies met inclusion criteria (5 in vitro, 4 clinical). In vitro studies consistently demonstrated that both ultraviolet A (UVA)-riboflavin and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide\/N-hydroxysuccinimide (EDC\/NHS) chemical CXL enhanced lenticule stiffness, enzymatic resistance, and transparency, with chemical CXL showing superior mechanical performance. Because of the limited sample size and substantial between-study heterogeneity, pooled estimates should be interpreted as exploratory and hypothesis-generating rather than definitive evidence. Clinical data from 26 eyes across three heterogeneous studies showed variable outcomes. Maximum keratometry showed a non-significant trend toward improvement (random-effects weighted mean difference: -2.94 D; 95% CI: -6.24 to 0.35 D;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.08), though this finding was limited by substantial heterogeneity (I\u00b2 = 87.7%). No serious complications were reported in the limited follow-up periods available.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In vitro experimental studies consistently demonstrate that crosslinking enhances the structural resilience and therapeutic potential of SMILE-derived lenticules. Chemical CXL, particularly EDC\/NHS protocols, provides superior biomechanical reinforcement while preserving transparency in experimental settings. Preliminary clinical data suggest possible benefit in selected advanced keratoconus cases. However, current evidence remains insufficient to establish efficacy. Controlled trials are warranted to standardize protocols and validate long-term safety and efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00417-026-07418-7","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:08:08Z","timestamp":1785557288000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating the rationale and outcomes of crosslinking corneal stromal lenticules: a systematic review with exploratory pooled analysis"],"prefix":"10.1007","author":[{"given":"Raluca Bievel","family":"Radulescu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia-Elena","family":"Ranetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horia Tudor","family":"Stanca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Ponzin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"7418_CR1","unstructured":"Technology ZEISSM ZEISS extends its global refractive industry momentum with more than 10 million eyes treated with ZEISS SMILE and ZEISS SMILE pro. 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Search terms combined controlled vocabulary and keywords related to SMILE-derived lenticules (e.g., 'lenticule', 'stromal lens', 'SMILE') and crosslinking ('crosslinking', 'CXL', 'riboflavin', 'EDC'). Grey literature, including conference proceedings and dissertations, and the reference lists of included articles were also screened. Only English-language original studies were included.","order":4,"name":"Ethics","label":"Method of literature search","group":{"name":"EthicsHeading","label":"Declarations"}}]}}