Prevention of postoperative proliferative vitreoretinopathy in complex retinal detachments with serial intravitreal methotrexate injections

Proliferative vitreoretinopathy (PVR) remains the leading cause of surgical failure after rhegmatogenous retinal detachment (RRD) repair. Intravitreal methotrexate (MTX) has emerged as a potential antiproliferative adjunct; however, the available evidence remains inconclusive. This study evaluated the safety and clinical outcomes associated with a standardized protocol of serial intravitreal MTX injections administered throughout the critical postoperative period in eyes with complex RRD. This retrospective observational analysis included 49 eyes of 49 patients selected from 50 consecutively screened patients undergoing pars plana vitrectomy (PPV) for complex RRD, defined as PVR grade C, recurrent retinal detachment due to PVR, or retinal detachment associated with penetrating ocular trauma. All included eyes were treated according to a standardized institutional protocol consisting of an intraoperative intravitreal MTX injection (400 µg/0.1 mL), followed by biweekly injections through postoperative week 12. The primary outcome was single-surgery anatomic success (SSAS), defined as retinal reattachment without fibrotic membrane formation at 12 weeks. Secondary outcomes included final retinal reattachment over total follow-up, changes in best-corrected visual acuity (BCVA), and safety outcomes. Forty-nine of 50 screened patients met the inclusion criteria and were included in the final analysis. SSAS at 12 weeks was achieved in 42 of 49 eyes (85.7%). Seven eyes required reoperation during follow-up, yielding a final retinal reattachment rate of 93.8% over the total follow-up period. Mean BCVA improved significantly from 2.52 ± 0.58 logMAR preoperatively to 1.23 ± 0.84 logMAR at 3 months (p < 0.001). Mean follow-up was 14.7 ± 10.8 months. The most frequent adverse event among analyzed eyes was conjunctival hyperemia, which resolved after completion of the MTX protocol. No severe ocular or systemic MTX-related adverse events were observed. Serial intravitreal MTX administered during the early postoperative period showed a favorable safety profile and was associated with encouraging anatomic and visual outcomes in this cohort of complex RRD. However, given the retrospective design, lack of a control group, cohort heterogeneity, potential selection bias, and the influence of adjunctive surgical procedures, these findings should be interpreted cautiously and as hypothesis-generating. Prospective controlled studies are required to better define the role of MTX in preventing postoperative PVR.