Tetracyclines and Risk of Proliferative Vitreoretinopathy after Rhegmatogenous Retinal Detachment

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OBJECTIVE: To evaluate the association between documented systemic tetracycline administration and the risk of proliferative vitreoretinopathy (PVR)-related outcomes after rhegmatogenous retinal detachment (RRD). DESIGN: Retrospective cohort study with 1-year follow-up. PARTICIPANTS: Adults aged 18 years or older with RRD were identified within a multicenter federated electronic health record network. After 1:1 propensity score matching, 2886 patients with documented systemic tetracycline administration were compared with 2886 matched controls. METHODS: Systemic tetracycline exposure was defined as a recorded prescription from 1 month before to 6 months after RRD-related cohort entry. Propensity score matching was performed on demographics, socioeconomic determinants, systemic and ophthalmic comorbidities, medications, laboratory values, and health care utilization. Time-to-event analyses were conducted using Kaplan-Meier estimation and Cox proportional hazards models. Prespecified sensitivity analyses and active comparator analyses were performed to assess robustness. MAIN OUTCOME MEASURES: Hazard ratios (HRs) for PVR-related outcomes, defined as complex retinal detachment repair, nondiabetic proliferative retinopathy, and tractional retinal detachment. Reoperation was evaluated as a secondary outcome. RESULTS: Baseline characteristics were well balanced after matching. During comparable follow-up, systemic tetracycline administration was associated with a lower risk of complex retinal detachment repair (HR, 0.33; 95% confidence interval [CI], 0.25-0.43), nondiabetic proliferative retinopathy (HR, 0.63; 95% CI, 0.45-0.89), and tractional retinal detachment (HR, 0.57; 95% CI, 0.43-0.75). Reoperation was also less frequent among tetracycline-exposed patients (HR, 0.34; 95% CI, 0.26-0.46). Findings remained consistent across prespecified sensitivity analyses, including alternative exposure definitions, follow-up durations, doxycycline-only exposure, and active comparator analyses. E-values suggested robustness to unmeasured confounding, and positive and negative control outcomes supported the internal validity of the observed associations. CONCLUSIONS: Documented systemic tetracycline administration was associated with a lower risk of PVR-related outcomes after RRD. These findings support further prospective evaluation of tetracyclines as a potential adjunctive strategy for PVR prevention. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

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