Efficacy and Safety of Reproxalap 0.25% Ophthalmic Solution in Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Purpose: Dry eye disease (DED) is an ocular surface disorder characterized by tear-film instability, inflammation, and symptoms that can impair visual function and quality of life. Reproxalap is a topical reactive aldehyde species (RASP) inhibitor. This systematic review and meta-analysis assessed the efficacy and safety of reproxalap 0.25% ophthalmic solution vs vehicle in adults with DED. Methods: MEDLINE/PubMed, Embase, Cochrane CENTRAL/Cochrane Library, and ClinicalTrials.gov were searched through June 20, 2026. The PROSPERO-registered review (CRD420261425460) included randomized trials and public trial-registry results records with extractable 0.25% reproxalap-versus-vehicle data. Outcomes included Schirmer test change and response (at least 10 mm improvement), instillation-site irritation, treatment-emergent adverse events (TEAEs), and discontinuation. Risk of bias and certainty were assessed using RoB 2 and GRADE. Results: Six eligible sources involving 2230 randomized participants were included. Reproxalap improved Schirmer test score (mean difference [MD], 2.34 mm; 95% confidence interval [CI], 1.45 to 3.22; P < 0.0001; I Conclusions: Reproxalap 0.25% demonstrated rapid objective tear-production improvements vs vehicle, though routine clinical recommendation must be weighed against frequent, transient instillation-site irritation. No treatment-related serious ocular adverse events were reported. Certainty ranged from low to very low due to reliance on registry-only data, trial program endpoint restructuring, eye-level denominators, and small study numbers.