Aspirin Use Found to Increase Risk of Early and Dry AMD

While some prior studies have suggested aspirin may have a protective effect against AMD, new genetic evidence argues that the opposite is true. Patients taking aspirin had decreased serum LDL-C and increased serum APOA1 levels, which conferred a greater risk of early and dry forms of the disease. Photo: Tanuj P. Banker, MD. Click image to enlarge. The impact of aspirin on age-related macular degeneration (AMD) risk has garnered attention in recent years, with several studies suggesting a potential protective effect, while others have indicated the drug may actually increase AMD risk. A recent study published in the journal Eye used Mendelian randomization to test whether aspirin use has a causal relationship with AMD and to identify possible biological pathways involved. Its findings revealed that regular use of the drug appears to increase the risk of early and dry forms of the disease through changes in lipid metabolism.The study used a bidirectional, two-sample, two-step Mendelian randomization design. Genetic instruments for aspirin use—serum LDL cholesterol (LDL-C) and apolipoprotein A1 (APOA1)—were drawn from the UK Biobank, while AMD outcome data came from the FinnGen study (n=500,000) and the Integrative Epidemiology Unit GWAS database. Aspirin use data included 45,012 users and 292,147 non-users. For AMD, the datasets included 11,023 overall AMD cases vs. 419,198 controls, 7,589 dry AMD cases vs. 298,486 controls and 14,034 early AMD cases vs. 91,214 controls. Using inverse variance weighted analysis, aspirin use was not significantly associated with overall AMD, but it was associated with increased risk of dry AMD and early AMD. Specifically, the odds ratio for dry AMD was 24.09 vs. 33.19 for early AMD.After examining possible mediators, the authors found that aspirin use was negatively associated with LDL-C and positively associated with APOA1. They reported that LDL-C accounted for 31.4% of the aspirin-dry AMD association and 33.3% of the aspirin-early AMD association, while APOA1 accounted for 18.4% and 6.0%, respectively.“By integrating univariable, two‑step, and multivariable MR, we not only confirmed the total causal effect of aspirin on AMD but also demonstrated that this effect is fully mediated by lipid metabolism, specifically through LDL‑C and APOA1, with no independent direct effect remaining,” the study authors explained in their paper.Since “many aspirin users also take lipid-lowering medications, such as statins and ezetimibe, to reduce serum LDL-C levels,” the authors argue that clinicians should consider monitoring AMD risk regularly in these patients via colour fundus photography and OCT, “particularly for those over the age of 55, as aspirin may contribute to AMD development in this cohort.” Click here for the journal source. Zhu J, Zeng C, Tang R, et al. Causal relationship between aspirin use and age-related macular degeneration. Eye. May 29, 2026. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.