Mammalian Target Rapamycin Inhibition as a Therapeutic Target for Prevention of Proliferative Vitreoretinopathy

Importance The use of systemic mammalian target of rapamycin (mTOR) inhibitor (MTI) therapy may confer benefits against the development of proliferative vitreoretinopathy (PVR). Objective To examine the use of systemic MTI therapy for the prevention of PVR among patients who underwent initial retinal detachment (RD) repair. Design, Setting, and Participants This was a retrospective cohort study aggregating deidentified electronic health record data from January 2003 to January 2025, from 15 countries. The study included 681 patients who underwent primary RD repair while receiving systemic MTI therapy at least 3 months before and 1 year after initial RD repair. This cohort was compared with a control group of 47 626 patients never exposed to systemic mTOR inhibition. After propensity score matching, outcomes from 681 patients in each cohort were analyzed after 1 year following their initial RD surgery. Exposures Patients were stratified by use of systemic mTOR therapy or not using RxNorm code. Main Outcome and Measures Relative risk (RR) of developing a PVR-related RD and requiring a subsequent ocular intervention including pars plana vitrectomy (PPV), and complex RD repair within 6 months and 1 year of follow-up. Patients who underwent initial RD repair while receiving systemic MTI therapy were separately compared with a matched cohort of patients with concomitant use of systemic methotrexate (MTX) for the same measures at 6 months and 1 year. Results A total of 681 and 47 626 patients who underwent initial RD repair with concomitant use of an MTI or not, respectively, were identified prior to PSM. The mean (SD) age in the MTI cohort was 66.5 (15.4) years; 319 (46.8%) were female and 319 (46.8%) were male. In the control cohort, the mean (SD) age was 64.5 (17.6) years; 16 140 (33.9%) were female and 27 858 (58.5%) were male. At 1 year, concomitant use of systemic MTI therapy was associated with a decreased risk of developing a subsequent RD (RR, 0.58; 95% CI, 0.36-0.94; P = .03) compared with matched patients who underwent initial RD repair without exposure to systemic MTI therapy. Moreover, concomitant use of systemic MTI therapy was associated with a decreased risk of requiring subsequent PPV (RR, 0.57; 95% CI, 0.40-0.82; P < .001) and complex RD repair (RR, 0.60; 95% CI, 0.40-0.91; P = .01) when compared with matched patients who underwent initial RD repair without exposure to systemic MTI therapy at 1 year. There was no difference in the development of subsequent RD and need for PPV or complex RD repair when comparing patients who underwent initial RD repair with concomitant systemic MTI therapy to a matched cohort of patients with concomitant use of systemic MTX therapy at 6 months and 1 year. Conclusion and Relevance Patients who underwent initial RD repair and were concomitantly being treated with systemic MTI therapy were less likely to develop a subsequent PVR-related RD compared with matched patients not exposed to systemic MTI therapy. Future studies are needed to investigate MTI therapy safety and efficacy profile in this setting of potential PVR prevention.