Pharmacologic Interventions for the Prevention and Treatment of Proliferative Vitreoretinopathy: A Systematic Review and Meta-Analysis.

TOPIC: To evaluate the efficacy and safety of pharmacologic interventions (including 5-fluorouracil, low-molecular-weight heparin, methotrexate, corticosteroids, anti-VEGF agents, and retinoids) compared with control treatments for preventing or treating proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment repair. CLINICAL RELEVANCE: PVR is the leading cause of anatomical failure after retinal detachment surgery. Despite advances in vitreoretinal techniques, no pharmacologic adjuvant has been established, and management remains primarily surgical. METHODS: We registered our protocol with PROSPERO (CRD420261435402). We systematically searched four databases from inception to June 2026 for studies evaluating pharmacologic therapies for PVR prevention or treatment. Risk of bias was assessed using validated tools, and random-effects meta-analyses were performed to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Sixty-nine studies were included, with 31 contributing to meta-analysis. No significant improvement in anatomical outcomes was observed with 5-fluorouracil plus low-molecular-weight heparin for prevention (RR, 0.94; 95% CI, 0.59-1.51), methotrexate for established PVR (RR, 0.96; 95% CI, 0.86-1.07), corticosteroids (RR, 1.11; 95% CI, 0.93-1.33), or anti-VEGF therapy (RR, 0.72; 95% CI, 0.32-1.64). Overall, pharmacologic therapy was associated with reduced redetachment risk (RR, 0.52; 95% CI, 0.28-0.94), mainly driven by methotrexate and anti-VEGF subgroups. Retinoids showed a potential benefit for reattachment. Certainty of evidence was low to very low. CONCLUSION: Current evidence does not support routine pharmacologic adjuvant therapy for PVR. Methotrexate, anti-VEGF agents, and retinoids show promising signals but require confirmation in adequately powered randomized controlled trials.