Uncovering statins with genetics in age-related macular degeneration

Abstract

Purpose : To assess the association between the risk for age-related macular degeneration (AMD) progression with the intake of statins and AMD genetic risk, and the interplay between statins and genetics capable of altering the risk for AMD progression.

Methods : In the Coimbra Eye Study, progressors progressed from grade 0 or 1 (no AMD at baseline) to grades 2,3 or 4 (Rotterdam Classification) between two visits (6.5 years follow-up). Non-progressors maintained grades 0 or 1. Only subjects who started taking statins within visits were considered. Participants were genotyped in the scope of EYERISK project. The Genetic Risk Score (GRS) was calculated individually. High GRS was considered equal or superior to the median GRS of participants. Low-strength statins were simvastatin, pravastatin, fluvastatin and pitavastatin and high-strength were atorvastatin and rosuvastatin. The association between statins and AMD progression was tested with an extended Cox model with statins intake as a time-dependent variable, adjusted for age, gender, body mass index, smoking status and diabetes assessed at the baseline (Model 1) and for GRS (Model 2). We used the individual eye as unit of analysis. Multiplicative and additive interactions were assessed.

Results : Out of 682 subjects, 560 were non-progressors and 122 were progressors. Statins (26.8%vs15.6%,p=0.009) and statins by strength (p=0.022) intakes were significantly associated with AMD progression. Median survival time was 7.50 years for not taking statins and 7.62 for taking statins,p<0.001. In Model 1, taking statins decreased AMD progression risk in 48% comparing to not taking statins (HR=0.52;95%CI 0.31-0.87,p=0.013). In Model 2, a high GRS increased the risk for progression almost by a two-fold (HR=1.88;95%CI 1.22-2.89,p=0.004), compared to a low GRS. Combined effects of no statin intake plus high GRS increased the risk for progression 4 times compared to taking statins plus low GRS (HR=4.25;95%CI 1.62-11.16,p=0.003). Stratified analysis by statins intake, for those not taking, an increased risk of progression was found for high GRS compared to low GRS (HR=1.80;95% CI 1.13-2.85,p=0.013). No multiplicative or additive interactions were found.

Conclusions : Concomitant medication indicated to treat other pathologies and which mechanism of action involves common pathways may be an option in the management of AMD, protecting patients against the disease.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.