Association between the retinal age gap and systemic diseases in the Japanese population: the Nagahama study

Abstract

Purpose: To investigate the retinal age gap, defined as the difference between deep learning-predicted retinal age and chronological age, as a potential biomarker of systemic health in the Japanese population. Study design: Prospective cohort study. Methods: Data from the Nagahama Study, a large-scale Japanese cohort study, were used. Participants were divided into fine-tuning (n=2,261) and analysis (n=6,070) cohorts based on their visit status across the two periods. The fine-tuning cohort only included individuals without a history of systemic or cardiovascular diseases. A deep learning model, originally released in the Japan Ocular Imaging Registry, was fine-tuned using a fine-tuning cohort to predict retinal age from images. This refined model was then applied to the analysis cohort to calculate retinal age gaps. We conducted cross-sectional and longitudinal analyses to examine the association of these gaps with systemic and cardiovascular diseases. Results: The retinal age-prediction model achieved a mean absolute error of 3.00–3.42 years. Cross-sectional analysis revealed significant associations between the retinal age gap and a history of diabetes (β = 1.08, p < 0.001) and hyperlipidemia (β = –0.67, p < 0.001). Longitudinal analysis showed no significant association between the baseline retinal age gap and disease onset. However, onset of hypertension (β = 0.35, p = 0.049) and hyperlipidemia (β = 0.34, p = 0.035) showed marginal associations with an increase in retinal age gap over time. Conclusion: The retinal age gap is a promising biomarker for systemic health, particularly in relation to diabetes, hypertension, and hyperlipidemia.