Frailty and the Risk of Age-Related Macular Degeneration: A Prospective Cohort and Mendelian Randomization Study

Background Both frailty and age-related macular degeneration (AMD) are related to aging and may share some common mechanisms. We aimed to examine the observational and causal association between frailty and the risk of AMD.Methods We included 320 810 participants free of AMD at baseline from the UK Biobank. Frailty phenotypes were defined according to 5 components: weight loss, exhaustion, slow gait speed, low grip strength, and low physical activity. Cox proportional hazard models were used to evaluate the association between frailty phenotype and the risk of AMD. A causal relationship between frailty phenotype and AMD was examined using 2-sample Mendelian randomization (MR) analysis.Results During a median follow-up of 12.81 years, 7 222 AMD cases were documented. After adjusting for confounding factors, compared with nonfrail participants, both pre-frail and frail participants were significantly associated with an increased risk of AMD (hazard ratio [HR] 1.17, [95% confidence interval {CI}: 1.11, 1.23] for pre-frailty and HR 1.55 [95% CI: 1.40, 1.73] for frailty). With each 1-point increase in frailty phenotype score, the risk of AMD increased by 14%. Results from the 2-sample MR analysis supported the potential causal effect of frailty phenotype on AMD.Conclusions Our findings suggested that frailty assessment may help identify at-risk populations and serve as a potential strategy for early prevention and management of AMD.