Association between diabetic retinopathy,age-related macular degeneration,and ischemic stroke:a combined cross-sectional and Mendelian randomization analysis
FAN Chao
CHEN Chengming
ZHANG Huan
LAN Yanyan
XIE Tingke
ZHANG Xiaohong
WANG Zhifu
HAN Jing
Abstract：Objective To investigate the association and potential causal relationship between diabetic retinopathy(DR),age-related macular degeneration(AMD),and ischemic stroke.Methods First,logistic regression models were adopted to analyze the association of DR and AMD with the incidence of ischemic stroke.Subsequently,based on the data from genome-wide association study,a bidirectional Mendelian randomization(MR)approach was applied to assess potential causal relationships between stroke subtypes,DR,and AMD.The inverse variance weighting(IVW)method served as the primary analytical approach,supplemented by the weighted median,weighted mode,and MR-Egger regression methods for validation and sensitivity analysis.Results Analysis based on NHANES data revealed significant associations of stroke with both DR[OR=1.70,95％CI(1.69,1.70),P＜0.001]and AMD[OR=1.84,95％CI(1.83,1.84),P＜0.001].Further bidirectional MR analysis indicated that DR significantly increased the risk of cardioembolic stroke[ORIVW=1.15,95％CI(1.06,1.25),P=0.000 7],which was consistent in both MR-Egger regression and weighted median methods.When AMD was set as the outcome,cardioembolic stroke also demonstrated a potential causal effect on AMD risk[ORIVW=1.15,95％CI(1.04,1.27),P=0.004],which was similarly supported by the weighted median method.Conclusion This study demonstrates significant associations between stroke and both DR and AMD.It provides the first genetic evidence suggesting a potential causal effect of DR on cardioembolic stroke and indicates that cardioembolic stroke may increase the risk of AMD.These findings offer new evidence for the comorbidity mechanisms underlying diabetic microvascular complications and cerebrovascular diseases,though their clinical implications require further validation through subsequent multicenter cohort studies.
Keywords：diabetic retinopathyage-related macular degenerationischemic strokeMendelian randomization analysiscross-sectional studiescardioembolic strokeNational Health and Nutrition Examination Surveygenome-wide association study
Publication Date：2026-02-28
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：10( 263-272 )