{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:23:42Z","timestamp":1775589822323,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"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>Dry eye disease (DED) is a prevalent and disabling condition. Artificial tears are commonly used but often inadequate for moderate-to-severe cases. Secretagogues such as pilocarpine, cevimeline, and diquafosol offer potential alternatives, though their comparative effectiveness remains unclear. To evaluate the safety and efficacy of these secretagogues versus artificial tears in adults with DED, we searched CENTRAL, PubMed, Scopus, LILACS, ClinicalTrials.gov, and WHO ICTRP without language restrictions. Randomized controlled trials (RCTs) comparing secretagogues to artificial tears were eligible. Data extraction and synthesis were conducted using Covidence and the Cochrane RoB 2 tool, and 19 RCTs (n = 2697) were included. Fifteen were analyzed quantitatively; however, only eight trials evaluating diquafosol were suitable for meta-analysis, as data for pilocarpine and cevimeline were insufficient for quantitative synthesis. GRADE was used to assess evidence certainty. PROSPERO registration: CRD42020218407. Diquafosol significantly improved rose bengal staining at 4 weeks and OSDI scores and TBUT in post-cataract patients at 4 and 12 weeks. However, it increased mild adverse events (RR, 1.81; 95% CI, 1.15\u20132.84). Evidence for pilocarpine and cevimeline was limited. Diquafosol 3% shows greater efficacy than artificial tears in post-cataract DED but with more side effects. Further research is needed for other secretagogues.<\/jats:p>","DOI":"10.3390\/ijms26178113","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T07:41:45Z","timestamp":1755848505000},"page":"8113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Safety and Efficacy of Diquafosol Compared to Artificial Tears for the Treatment of Dry Eye: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-219X","authenticated-orcid":false,"given":"Jos\u00e9 Gerardo","family":"Serrano-Robles","sequence":"first","affiliation":[{"name":"Instituto de Oftalmologia Fundacion Conde de Valenciana IAP, Mexico City 11520, Mexico"},{"name":"Centro de Investigaci\u00f3n en Ciencias de La Salud An\u00e1huac (CICSA), Facultad de Ciencias de La Salud, Universidad An\u00e1huac M\u00e9xico, Campus Norte, Mexico City 52786, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8138-678X","authenticated-orcid":false,"given":"Ana Karen","family":"P\u00e9rez-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ciencias de La Salud An\u00e1huac (CICSA), Facultad de Ciencias de La Salud, Universidad An\u00e1huac M\u00e9xico, Campus Norte, Mexico City 52786, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3417-256X","authenticated-orcid":false,"given":"Guillermo Raul","family":"Vera-Duarte","sequence":"additional","affiliation":[{"name":"Instituto de Oftalmologia Fundacion Conde de Valenciana IAP, Mexico City 11520, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9417-5711","authenticated-orcid":false,"given":"Alejandro","family":"Navas","sequence":"additional","affiliation":[{"name":"Instituto de Oftalmologia Fundacion Conde de Valenciana IAP, Mexico City 11520, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-5116","authenticated-orcid":false,"given":"Arturo","family":"Ramirez-Miranda","sequence":"additional","affiliation":[{"name":"Instituto de Oftalmologia Fundacion Conde de Valenciana IAP, Mexico City 11520, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3267-3915","authenticated-orcid":false,"given":"Enrique O.","family":"Graue-Hernandez","sequence":"additional","affiliation":[{"name":"Instituto de Oftalmologia Fundacion Conde de Valenciana IAP, Mexico City 11520, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3887-0629","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Kahuam-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Instituto de Oftalmologia Fundacion Conde de Valenciana IAP, Mexico City 11520, Mexico"},{"name":"Centro de Investigaci\u00f3n en Ciencias de La Salud An\u00e1huac (CICSA), Facultad de Ciencias de La Salud, Universidad An\u00e1huac M\u00e9xico, Campus Norte, Mexico City 52786, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/07853890.2022.2157477","article-title":"Dry eye disease: Identification and therapeutic strategies for primary care clinicians and clinical specialists","volume":"55","author":"Sheppard","year":"2022","journal-title":"Ann. 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