Authors: Osama Almajhadi , Rana Alharthi , Ghadi Althobaiti , Elham Alharbi , Majed Al Qurashi

Abstract

Background: Reproxalap, a reactive aldehyde species inhibitor, has been proposed for dry eye disease (DED), but trial findings are inconsistent and no quantitative synthesis exists. We assessed the efficacy and safety of reproxalap 0.25% ophthalmic solution versus vehicle in adults with DED.

Methods: PubMed, Web of Science, ClinicalTrials.gov, gray literature, and manufacturer sources were searched to 30 July 2025 (PROSPERO CRD420251069765; PRISMA 2020). Two reviewers independently screened, extracted data, and assessed risk of bias (Cochrane RoB 2). Fixed-effects models pooled standardized mean differences (SMDs) for ocular dryness, mean differences (MDs) for conjunctival redness and tear production, and risk ratios (RRs) for adverse events, with 95% confidence intervals (CIs). Certainty was rated using GRADE.

Results: Eight randomized controlled trials (1,436 participants) were included. Reproxalap did not improve ocular dryness (SMD −0.07; 95% CI −0.24 to 0.10; I² = 47%; P = 0.43) or conjunctival redness (MD −0.03; 95% CI −0.08 to 0.02; I² = 74%; P = 0.28), but significantly increased tear production (MD 2.21 mm; 95% CI 1.49 to 2.94; I² = 0%; P < 0.00001). Adverse events were more frequent with reproxalap (RR 10.80; 95% CI 8.29 to 14.08; I² = 94%; P < 0.00001), predominantly mild, transient instillation-site discomfort. Certainty was high for adverse events, moderate for tear production, and very low for dryness and redness.

Conclusion: Reproxalap 0.25% increases tear production, largely under short controlled adverse environment exposure, without demonstrable benefit for ocular dryness or conjunctival redness. Larger, rigorous field trials with fully reported outcomes are required.

Keywords: Reproxalap, dry eye disease, reactive aldehyde species, ocular surface inflammation, meta-analysis, systematic review.