High-accuracy retinal age prediction via fundus-based multitask learning reveals the effect of systemic disease

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Abstract
Background Accurate estimation of the retinal age, defined as the age predicted from fundus photographs by a deep-learning model trained on chronological age, provides a non-invasive biomarker of biological ageing and disease risk. Methods In this study, we trained an ensemble multitask learning model that integrates fundus photographs with glycated haemoglobin using 50,595 quality-controlled fundus photographs from 27,214 disease-free adults and validated it on an independent set of 7288 additional images from disease-free adults. Model performance was evaluated using mean absolute error. Prediction uncertainty was quantified by calculating the standard deviation across ensemble predictions for each eye, and eyes were stratified based on this standard deviation. Results Here we show that the model achieves mean absolute errors of 2.78 years in internal validation and 3.39 years and 8.63 years in two external cohorts comprising 135 and 4992 eyes, respectively. Eyes with ensemble standard deviations below the median demonstrate improved age-prediction accuracy (mean absolute error: 2.46 years internally; 2.87 years in the primary external cohort). In a systemic disease cohort of 8467 individuals, the retinal age gap (predicted minus chronological age) is significantly higher in participants with diabetes, cardiac disease, or stroke after adjustment for age and sex, indicating older-appearing retinas and supporting the biological relevance of retinal age. Conclusions Retinal age derived from a single fundus photograph provides a scalable and clinically deployed biomarker of biological ageing. This approach may enable opportunistic screening for cardiometabolic and other ageing-related diseases in other routine ocular imaging workflows.

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