Association between Systemic Methotrexate Therapy and Proliferative Vitreoretinopathy

Objective: Proliferative vitreoretinopathy (PVR) is a major cause for failure of retinal detachment (RD) repair. We sought to determine if patients taking systemic methotrexate (MTX) therapy had a lower incidence of PVR.

Design: Multicenter retrospective cohort study.

Participants: Patients aged ≥18 years who were documented in the Sight Outcomes Research Collaborative (SOURCE) repository to have received a diagnosis of RD and have undergone RD repair surgery between 2004 and 2024. We only included patients who had been in the SOURCE system for at least 6 months before the diagnosis date and had no prior record of RD repair surgery. We excluded patients with an unknown laterality of the primary RD repair, history of PVR, proliferative diabetic retinopathy, serous RD, retinal dialysis, or ocular trauma.

Methods: The exposure variable of interest was systemic MTX use, as documented from the medication list. The outcome of interest was the presence of new-onset PVR within 6 months of surgery. Incident PVR was modeled in log binomial regression models that included terms for systemic MTX use and method of primary RD repair. Regression models included inverse probability weights based on propensity scores for systemic MTX use. We conducted similar analyses for other antimetabolite agents (e.g., azathioprine and mycophenolate mofetil).

Main outcome measures: Cumulative incidence of PVR and adjusted risk ratio (RR) of developing PVR within 6 months of the initial RD.

Results: Of the 2674 eligible patients, 48 (1.8%) were taking systemic MTX at the time of RD repair. The 6-month cumulative incidence of PVR after the primary RD was 4.2% for patients taking systemic MTX compared with 9.2% for those not taking MTX (adjusted RR, 0.58; 95% confidence interval [CI], 0.47-0.71). Similar results were found for azathioprine (adjusted RR, 0.28; 95% CI, 0.22-0.37) but not mycophenolate mofetil (adjusted RR, 0.93; 95% CI, 0.77-1.11).

Conclusions: Patients taking systemic MTX or azathioprine were significantly less likely to develop PVR within 6 months of primary RD compared with those not taking MTX or azathioprine.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.