Abstract Background Although caffeine is widely consumed and has demonstrated neuroprotective effects, its role in age-related macular degeneration (AMD) remains unclear, particularly across disease subtypes and dietary sources such as tea and coffee. Methods We analyzed 2005–2008 NHANES data using weighted logistic regression and restricted cubic splines to assess the dose–response relationship between caffeine intake and the prevalence of early and late AMD. Two-sample Mendelian randomization (MR) using GWAS summary statistics was employed to evaluate causal effects of tea and coffee consumption on AMD subtypes. Furthermore, a two-step MR approach was utilized to identify potential immune-mediated pathways. Results NHANES data showed that caffeine intake was inversely associated with late AMD (fully adjusted OR = 0.65, 95% CI: 0.44–0.96). Dose–response modeling revealed an L-shaped nonlinear relationship (P for nonlinear = 0.046), indicating that the protective effect of caffeine plateaued once daily intake exceeded approximately 110–150 mg. MR analysis further supported a causal protective association between tea consumption and dry AMD, including geographic atrophy (OR = 0.44, 95% CI: 0.20–0.97), which may be partially attributable to immunological mechanisms, specifically the downregulation of secretory regulatory T cells (% of CD4 + Tregs) and CD45RA- CD4 + T cell (% of CD4 + T cell). In contrast, coffee consumption showed no significant effect. Conclusions Tea, a specific source of caffeine typically corresponding to moderate intake levels, may confer protection against dry AMD, including geographic atrophy, potentially through modulation of immune cell profiles. These findings suggest a potential preventive strategy and warrant further clinical investigation. Graphical abstract
Yang et al. (Mon,) studied this question.