Effect of methotrexate in preventing retinal detachment after proliferative vitreoretinopathy surgery: A systematic review and meta-analysis.

Intravitreal methotrexate (MTX) is increasingly administered as an adjunctive therapy alongside surgical intervention in patients with proliferative vitreoretinopathy (PVR) or those at high risk of its development, with the aim of preventing recurrent PVR and subsequent retinal detachment; however, its efficacy remains uncertain. We searched PubMed, EMBASE, CINAHL, and the Cochrane Library from inception to December, 2024, for studies evaluating intravitreal MTX as an adjuvant therapy in PVR surgery. The primary analysis included randomized controlled trials (RCTs), while supplementary analyses incorporated non-randomized studies. All meta- analyses were conducted using random-effect models. Study quality was assessed using the Cochrane Risk of Bias (ROB2) tool, and the certainty of evidence was evaluated using the GRADE approach. Three RCTs with 145 eyes met the eligibility criteria. The meta-analysis showed a pooled RR estimate of 0.64 (95 % CI 0.30-1.38), indicating a 36 % reduction in the risk of recurrent RD in MTX-treated eyes, although this was not statistically significant. No significant differences were observed in visual acuity improvement (SMD = 0.04; 95 % CI -0.53-0.60). Additionally, our meta-analysis of 5 non-randomized studies involving 277 eyes found no evidence to suggest that MTX reduces the incidence of recurrent retinal detachment in eyes undergoing surgery for PVR (RR = 0.90; 95 % CI 0.49-1.64). The RCTs were rated as having moderate risk of bias, while most non-randomized studies were assessed as having high risk of bias. Funnel plots indicated potential publication bias, and the certainty of evidence was rated as moderate according to GRADE. Although MTX was associated with a clinically relevant 36 % reduction in recurrent RD risk, the effect was not statistically significant. Larger, high-quality RCTs with adequate power are needed to confirm these findings.