{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:22:41Z","timestamp":1792092161487,"version":"4.4.0"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T00:00:00Z","timestamp":1588032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background\u2014It is recognized that inflammation is an underlying cause of dry eye disease (DED), with cytokine release involved. We systematically reviewed literature with meta-analyses to quantitatively summarize the levels of tear cytokines in DED. Methods\u2014The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus databases were reviewed until September 2019, and original articles investigating tear cytokines in DED patients were included. Differences of cytokines levels of DED patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying Newcastle-Ottawa-Scale and the GRADE quality score. Methods of analytical procedures were included as covariate. Results\u2014Thirteen articles investigating 342 DED patients and 205 healthy controls were included in the meta-analysis. The overall methodological quality of these studies was moderate. Systematic review of the selected articles revealed that DED patients had higher tear levels of interleukin (IL)-1\u03b2, IL-6, chemokine IL-8, IL-10, interferon-\u03b3, IFN-\u03b3, and tumor necrosis factor-\u03b1, TNF-\u03b1 as compared to controls. Evidence was less strong for IL-2 and IL-17A. Conclusions\u2014Data show that levels of tear cytokines in DED and control display a great variability, and further studies of higher quality enrolling a higher number of subjects are needed, to define a cut-off value.<\/jats:p>","DOI":"10.3390\/ijms21093111","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T10:30:58Z","timestamp":1588069858000},"page":"3111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":165,"title":["Dry Eye Disease and Tear Cytokine Levels\u2014A Meta-Analysis"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9064-4894","authenticated-orcid":false,"given":"Matilde","family":"Roda","sequence":"first","affiliation":[{"name":"Ophthalmology Unit, DIMES, Alma Mater Studiorum University of Bologna and S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2078-1978","authenticated-orcid":false,"given":"Ivan","family":"Corazza","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Letizia","family":"Bacchi Reggiani","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-6941","authenticated-orcid":false,"given":"Marco","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, DIMES, Alma Mater Studiorum University of Bologna and S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-8961","authenticated-orcid":false,"given":"Leonardo","family":"Taroni","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, DIMES, Alma Mater Studiorum University of Bologna and S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2617-0289","authenticated-orcid":false,"given":"Giuseppe","family":"Giannaccare","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2951-5337","authenticated-orcid":false,"given":"Piera","family":"Versura","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, DIMES, Alma Mater Studiorum University of Bologna and S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.jtos.2017.05.003","article-title":"TFOS DEWS II Epidemiology Report","volume":"15","author":"Stapleton","year":"2017","journal-title":"Ocul. 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