Reproxalap 0.25% in dry eye disease: A meta-analysis of randomized controlled trials

Background Dry eye disease (DED) is a common, chronic inflammatory disorder of the ocular surface that can impair vision and reduce quality of life. Reproxalap, a novel reactive aldehyde species (RASP) modulator, has shown potential as a targeted anti-inflammatory therapy. Objective To evaluate the efficacy and safety of reproxalap 0.25% in patients with DED, with allergic conjunctivitis included as a secondary exploratory analysis. Design Systematic review and meta-analysis. Data Sources and Methods PubMed, Embase, and ClinicalTrials.gov were systematically searched to identify randomized controlled trials (RCTs) evaluating reproxalap. Meta-analyses were performed using RevMan 5.4 with a random-effects model. Results Twelve RCTs were included, comprising 8 studies in DED (n = 2,283) and 4 studies in allergic conjunctivitis (n = 418). In DED, reproxalap significantly reduced ocular dryness scores (SMD: −0.23, 95% CI: −0.38 to −0.08; I 2 = 0%), increased Schirmer test mean change from baseline (MD: 2.32 mm, 95% CI: 1.55 to 3.10; I 2 = 0%), improved Schirmer test responder rates (RR: 2.05, 95% CI: 1.71 to 2.44; I 2 = 0%), and reduced conjunctival redness (MD: −0.13, 95% CI: −0.25 to −0.02; I 2 = 36%). Exploratory analyses of allergic conjunctivitis showed favorable effect estimates for ocular itching, tearing, and conjunctival redness. However, heterogeneity was substantial across outcomes (I 2 = 83–96%), the certainty of evidence was very low according to GRADE, and the findings were not robust in sensitivity analyses. Conclusion Reproxalap was associated with consistent improvements across key clinical outcomes in DED. Exploratory allergic conjunctivitis findings should be considered hypothesis-generating rather than clinically conclusive. Interpretation of the overall evidence is limited by exclusive industry sponsorship, evidence of publication bias, and the predominantly subjective nature of the primary endpoints. Further large-scale, independently funded RCTs in DED are warranted to further establish the efficacy and safety of reproxalap. Registration PROSPERO CRD420251070669.