Abstract
Traditional biomarkers, such as those obtained from blood tests, are essential for early disease detection, improving health outcomes and reducing healthcare costs. However, they often involve invasive procedures, specialized laboratory equipment or special handling of biospecimens. The retinal age gap (RAG) has emerged as a promising new biomarker that can overcome these limitations, making it particularly suitable for disease screening in low- and middle-income countries. This study aimed to evaluate the potential of the RAG as a biomarker for broad disease screening across a vast spectrum of diseases. Fundus images were collected from 86 522 UK Biobank participants aged 40-83 (mean age: 56.2 ± 8.3 years). A deep learning model was trained to predict retinal age using 17 791 images from healthy participants. The remaining images were categorized into disease/injury groups based on clinical codes. Additionally, 8524 participants from the Brazilian Multilabel Ophthalmological Dataset (BRSET) were used for external validation. Among the 159 disease/injury groups from the 2019 Global Burden of Disease Study, 56 groups (35.2%) exhibited RAG distributions significantly different from healthy controls. Notable examples included chronic kidney disease, cardiovascular disease, blindness, vision loss and diabetes. Overall, the RAG shows great promise as a cost-effective, non-invasive biomarker for early disease screening.