Accelerated Biological Aging in Exfoliation Glaucoma Assessed by Fundus-Derived Predicted Age and Advanced Glycation End Products

Glaucoma is an age-related neurodegenerative disease characterized by progressive optic nerve damage. Accelerated biological aging, assessed using predicted age derived from fundus images, may serve as a biomarker for glaucoma progression. This study aimed to examine fundus-derived age acceleration among patients with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG), and controls, and to explore its biochemical basis through advanced glycation end products (AGEs). Fundus photographs from 237 participants (79 POAG, 79 EXG, and 79 age- and sex-matched controls) were analyzed using a deep learning model (EfficientNet) previously trained to predict biological age. AGE accumulation was assessed by measuring skin autofluorescence (sAF). Multivariate regression analyses were conducted to identify factors influencing predicted age acceleration, with stratification into age tertiles to control for age-related effects. EXG patients demonstrated significant accelerated biological aging compared to controls (<i>p</i> = 0.006), particularly evident in younger and middle-aged tertiles. AGE scores were significantly elevated in EXG relative to both POAG (<i>p</i> = 0.009) and control groups (<i>p</i> = 0.003). Predicted age and AGE scores were more strongly correlated than chronological age and AGEs, especially in the middle tertile (<i>p</i> = 0.002). Accelerated biological aging detected via fundus images occurs prominently in EXG, potentially reflecting underlying AGE accumulation. Fundus-derived predicted age could serve as a non-invasive biomarker for assessing glaucoma progression risk and warrants further exploration in clinical applications.