Comparative Effectiveness and Safety of Rebamipide Versus Diquafosol in the Treatment of Dry Eye Disease: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis aimed to compare the efficacy and tolerability of rebamipide (REB) and diquafosol (DQS), two widely used mucin secretagogues, in the treatment of dry eye disease.A comprehensive search of PubMed, Embase, Web of Science, Cochrane CENTRAL, and Scopus was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identifying six comparative studies enrolling 277 patients across South Korea and Japan.Pooled analyses were performed using random-effects models, standardized mean differences (SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes with 95% confidence intervals (CIs).Tear breakup time showed no significant difference between REB and DQS (SMD = -0.21seconds, 95% CI: -0.52 to 0.11, p=0.20).Subjective symptom scores were also comparable (SMD=0.11,95% CI: -0.16 to 0.38, p=0.40).Corneal staining scores were nearly identical (SMD=-0.002,95% CI: -0.324 to 0.321, p=0.993), while conjunctival staining showed a nonsignificant trend favoring REB (SMD=-0.403,95% CI: -1.508 to 0.702, p=0.475,I²=87.6%).These findings suggest comparable efficacy between both agents as first-line mucin secretagogues in the available studies, though formal equivalence cannot be established from this evidence base, and more large-scale trials are required to validate the findings.