Antioxidant vitamin index and risk of age-related macular degeneration: multicenter validation and clinical translation

Abstract Age-related macular degeneration (AMD) is a leading cause of blindness in older adults, with oxidative stress as a central driver. We proposed the Antioxidant Vitamin Index (AVI), a composite indicator integrating vitamins A, C, and E to quantify systemic antioxidant nutritional status, and evaluated its association with AMD across three large cohorts: the UK Biobank, NHANES 2005–2008, and a Tianjin clinical cohort. Using Cox proportional hazards models for incident AMD in the UK Biobank and multivariable logistic regression for AMD prevalence in NHANES and Tianjin, complemented by restricted cubic splines, quartile analyses, and machine learning, we consistently observed that higher AVI was independently associated with a lower risk of AMD. Dose–response analyses showed a progressive decline in AMD risk with increasing AVI, and model performance improved when AVI was added to conventional risk factors. Machine learning and SHAP interpretation further identified age and AVI as dominant predictors of AMD. These findings support AVI as a biologically grounded, quantifiable metric with potential for early screening, risk stratification, and nutrition-based prevention of AMD.