Systemic prostacyclin analogues in pulmonary hypertension are associated with reduced risk of age-related macular degeneration: a cohort study

Background/Objectives: To assess whether systemic prostacyclin analogue (PCA) therapy in patients with pulmonary arterial hypertension (PAH) is associated with a reduced long-term risk of developing age-related macular degeneration (AMD). Subjects/Methods: A retrospective cohort study was conducted using the TriNetX global health research network. Patients aged ≥50 with a diagnosis of PAH were included and stratified by PCA treatment. Propensity score matching (1:1) was applied to balance demographics and comorbidities. Incident diagnoses of non-neovascular AMD (non-nvAMD) and neovascular AMD (nvAMD) were compared across six follow-up intervals (3-15 years) using Kaplan-Meier analysis and Cox proportional hazards models. Results: Following matching, 9862 PCA-treated and 9862 untreated PAH patients were analysed. PCA-treated patients showed a consistently lower risk of non-nvAMD across all follow-up periods (hazard ratios [HRs] 0.30-0.37; all p < 0.001). A similar protective trend was observed for nvAMD, with significant associations emerging at longer follow-up (HR = 0.37-0.39 at 10-15 years; p < 0.05). The protective effect was robust and durable over time. Conclusions: Systemic administration of prostacyclin analogues is associated with a significant and sustained reduction in AMD risk among patients with PAH. These findings suggest a potential preventive role for PCAs in AMD pathogenesis and merit further investigation in broader populations.