Is Current Evidence Sufficient to Establish the Efficacy of Botulinum Toxin A in Treating Persistent Dry Eye Disease? A Systematic Review and Meta-Analysis of Interventional Studies With a Critical Review Using GRADE Tool.

[BACKGROUND AND AIMS] Standard management of dry eye disease (DED) relies on artificial tears, anti-inflammatory 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-A) for DED that remained symptomatic after these interventions, excluding patients with blepharospasm or hemifacial spasm.

[METHODS] 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-searching key ophthalmology journals, and investigating clinical trial registries (ClinicalTrials. gov, ICTRP, ISRCTN). Inclusion criteria were clinical trials and cohort studies assessing BTX-A in primary DED. Outcomes included tear break-up time (TBUT), Schirmer's test, and Ocular Surface Disease Index (OSDI). Meta-analyses 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.

[RESULTS] Out of 5,064 records, five studies (144 eyes) were included. Meta-analysis indicated no significant improvements in TBUT (Hedges's g = 0.43, 95% CI: -1.34 to 2.20) or Schirmer's test (Hedges's g = 0.23, 95% CI: -0.78 to 1.24). However, OSDI scores showed a significant reduction (MD -14.23; 95% CI: -15.86 to -12.59,  < 0.001), with moderate-certainty evidence.

[CONCLUSIONS] BTX-A 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-quality trials to clarify BTX-A's clinical role.

[PROSPERO REGISTRATION] CRD420251031877.