Evaluating the reproducibility of a deep learning algorithm for the prediction of retinal age

Recently, a deep learning algorithm (DLA) has been developed to predict the chronological age from retinal images. The Retinal Age Gap (RAG), a deviation between predicted age from retinal images (Retinal Age, RA) and chronological age, correlates with mortality and age-related diseases. This study evaluated the reliability and accuracy of RA predictions and analyzed various factors that may influence them. We analyzed two groups of participants: Intravisit and Intervisit, both imaged by color fundus photography. RA was predicted using an established algorithm. The Intervisit group comprised 26 subjects, imaged in two sessions. The Intravisit group had 41 subjects, of whom each eye was photographed twice in one session. The mean absolute test-retest difference in predicted RA was 2.39 years for Intervisit and 2.13 years for Intravisit, with the latter showing higher prediction variability. The chronological age was predicted accurately from fundus photographs. Subsetting image pairs based on differential image quality reduced test-retest discrepancies by up to 50%, but mean image quality was not correlated with retest outcomes. Marked diurnal oscillations in RA predictions were observed, with a significant overestimation in the afternoon compared to the morning in the Intravisit cohort. The order of image acquisition across imaging sessions did not influence RA prediction and subjective age perception did not predict RAG. Inter-eye consistency exceeded 3 years. Our study is the first to explore the reliability of RA predictions. Consistent image quality enhances retest outcomes. The observed diurnal variations in RA predictions highlight the need for standardized imaging protocols, but RAG could soon be a reliable metric in clinical investigations.