Systemic immunosuppression and risk of age-related macular degeneration

A local immune response has been implicated in the pathogenesis of age-related macular degeneration (AMD), but it is unclear if systemic immunosuppressive/immunomodulatory therapy (IMT) protects against the onset and/or progression of AMD. We performed a retrospective cohort study using a Cox proportional hazards model of two cohorts. Cohort 1 included patients with stage V chronic kidney disease (CKD) status post kidney transplantation, on at least one IMT agent, and older than 50. Cohort 2 included patients with stage IV or V CKD who had not undergone kidney transplantation, were not on IMT, and were older than 50. The main outcomes were hazard ratios of a new diagnosis of dry AMD, wet AMD, or conversion from dry to wet. There were 10,813 patients in cohort 1, and 217,081 patients in cohort 2. After controlling for sex and age, there was no significant difference in the hazard of developing a new diagnosis of dry AMD (HR = 0.95, 95% CI 0.87-1.05, p = 0.32), developing a new diagnosis of wet AMD without any prior diagnosis of dry AMD (HR = 0.85, 95% CI 0.66-1.08, p = 0.18), or converting from dry to wet AMD (HR 1.24, 95% CI 0.94-1.62, p = 0.12). For patients over 70 on mycophenolate mofetil, there was a reduced hazard of converting from dry to wet AMD (HR = 0.92, 95% CI = 0.85-0.99, p = 0.02). In contrast, everolimus had an increased hazard of dry AMD (HR = 2.14, 95% CI 1.24-3.69, p < 0.01). Most systemic IMT does not affect the risk of onset or progression of AMD in patients with CKD. However, mycophenolate mofetil may confer some degree of protection against the conversion of dry AMD to wet AMD, suggesting that modulation of the immune response may prevent progression of the disease.