{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T20:24:42Z","timestamp":1783023882455,"version":"3.54.6"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Standard management of dry eye disease (DED) relies on artificial tears, anti\u2010inflammatory therapy, and punctal occlusion in selected cases. However, some patients continue to report persistent symptoms. The present article reviewed the efficacy of Botulinum Toxin A (BTX\u2010A) for DED that remained symptomatic after these interventions, excluding patients with blepharospasm or hemifacial spasm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a comprehensive search of seven databases (PubMed, Embase, Web of Science, Scopus, CENTRAL, Science Direct, and ProQuest), supplemented by grey literature searches (ProQuest, Scopus, OATD), hand\u2010searching key ophthalmology journals, and investigating clinical trial registries (ClinicalTrials. gov, ICTRP, ISRCTN). Inclusion criteria were clinical trials and cohort studies assessing BTX\u2010A in primary DED. Outcomes included tear break\u2010up time (TBUT), Schirmer's test, and Ocular Surface Disease Index (OSDI). Meta\u2010analyses utilized STATA 17, combining standardized mean differences (SMD) for TBUT and Schirmer's test, and mean difference (MD) for OSDI. Evidence certainty was evaluated using GRADE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Out of 5,064 records, five studies (144 eyes) were included. Meta\u2010analysis indicated no significant improvements in TBUT (Hedges's g\u2009=\u20090.43, 95% CI: \u22121.34 to 2.20) or Schirmer's test (Hedges's g\u2009=\u20090.23, 95% CI: \u22120.78 to 1.24). However, OSDI scores showed a significant reduction (MD \u201314.23; 95% CI: \u221215.86 to \u221212.59,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), with moderate\u2010certainty evidence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BTX\u2010A injections appear to offer symptom relief in persistent DED, though effects on objective measures remain inconclusive, limited by heterogeneity and low power. While initial safety data is favorable, the small number of methodologically weak studies highlights the need for larger, high\u2010quality trials to clarify BTX\u2010A's clinical role.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO Registration<\/jats:title>\n                    <jats:p>CRD420251031877.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.72338","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:34:10Z","timestamp":1776400450000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Is Current Evidence Sufficient to Establish the Efficacy of Botulinum Toxin A in Treating Persistent Dry Eye Disease? A Systematic Review and Meta\u2010Analysis of Interventional Studies With a Critical Review Using GRADE Tool"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2444-1172","authenticated-orcid":false,"given":"Mirsaeed","family":"Abdollahi","sequence":"first","affiliation":[{"name":"Nikookari Eye Center Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8964-419X","authenticated-orcid":false,"given":"Farbod","family":"Semnani","sequence":"additional","affiliation":[{"name":"National Center for Health Insurance Research Tehran Iran"},{"name":"Translational Ophthalmology Research Center, Farabi Eye Hospital Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4769-451X","authenticated-orcid":false,"given":"Hadi","family":"Vahedi","sequence":"additional","affiliation":[{"name":"Nikookari Eye Center Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0663-850X","authenticated-orcid":false,"given":"Navid","family":"Sobhi","sequence":"additional","affiliation":[{"name":"Translational Ophthalmology Research Center, Farabi Eye Hospital Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8817-8257","authenticated-orcid":false,"given":"Mahdi","family":"Mohammadkhani","sequence":"additional","affiliation":[{"name":"Nikookari Eye Center Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-4245","authenticated-orcid":false,"given":"Amin","family":"Nabavi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hamilton Eye Institute University of Tennessee Health Science Center Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4922-1923","authenticated-orcid":false,"given":"Ali","family":"Jafarizadeh","sequence":"additional","affiliation":[{"name":"Nikookari Eye Center Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.005"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(96)82013-3"},{"issue":"5","key":"e_1_2_15_4_1","first-page":"71","article-title":"The Pathophysiology, Diagnosis, and Treatment of Dry Eye Disease","volume":"112","author":"Messmer E. 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