Key Takeaways

  • A Mendelian randomization analysis found that genetically predicted aspirin use was associated with an increased risk of early and dry AMD
  • The association appeared to be mediated by changes in lipid biomarkers—specifically lower LDL cholesterol and higher apolipoprotein A1 levels—rather than a direct effect of aspirin itself
  • Researchers said the findings should not prompt patients to stop prescribed aspirin therapy but may provide new insights into the role of lipid metabolism in AMD development and progression

A new genetic epidemiology study led by researchers in China has found evidence that aspirin use may increase the risk of developing early and dry age-related macular degeneration (AMD), with the association appearing to be mediated through changes in lipid metabolism rather than a direct effect of the drug itself.1

The study, published in the journal Eye, used a bidirectional two-sample Mendelian randomization (MR) approach to investigate the long-debated relationship between aspirin use and AMD. While previous observational studies have produced conflicting results, the authors sought to determine whether a causal genetic association exists between aspirin use and AMD and to identify potential biological mediators.

Using genetic datasets related to aspirin use, AMD, and lipid biomarkers, the investigators found that genetically predicted aspirin use was associated with an increased risk of both early-stage AMD and dry AMD. Notably, they did not identify evidence supporting a direct causal pathway from aspirin use to disease. Instead, the relationship appeared to be fully mediated by reductions in low-density lipoprotein cholesterol (LDL-C) and increases in apolipoprotein A1 (APOA1) levels.

Multivariable MR analyses showed that once LDL-C and APOA1 were accounted for, the apparent effect of aspirin on AMD was no longer statistically significant, suggesting these lipid-related factors may be driving the association.

The findings add a new dimension to an ongoing debate in ophthalmology. Earlier epidemiologic studies have reported mixed results, with some suggesting an increased risk of AMD among long-term aspirin users and others finding no significant association. Randomized clinical trials, including analyses from the ASPREE and Women's Health Study cohorts, have likewise produced inconsistent conclusions.

The study highlights the growing role of genetic causal-inference methods in understanding AMD risk factors. However, the authors caution that the results should not be interpreted as evidence to discontinue aspirin therapy prescribed for cardiovascular indications. 

The research also reinforces emerging evidence that lipid metabolism plays a central role in AMD pathogenesis. Previous genetic studies have implicated several lipid biomarkers in AMD risk, and the new analysis suggests that aspirin-related changes in lipid profiles may intersect with these pathways.

According to the investigators, the study provides "robust genetic evidence" linking aspirin use with increased risk of early and dry AMD through lipid-mediated mechanisms. They suggest future research should further explore the biological interplay between lipid regulation and retinal degeneration, as well as the potential implications for AMD prevention and risk stratification.

Reference

1. Zhu J, Zeng C, Tang R, et al. Causal relationship between aspirin use and age-related macular degeneration. Eye. Published May 29, 2026.