A Novel Foundation Model-Based Framework for Multimodal Retinal Age Prediction

Abstract

The retinal age gap (RAG; the difference between the retina’s biological and chronological age) has recently gained increased attention as a potential image-based, non-invasive, and accessible biomarker for a broad spectrum of ocular and non-ocular diseases. Traditionally, machine learning predictions of biological retinal age utilize convolutional neural network (CNN) architectures and data from color fundus photography (CFP). Despite being previously unexplored, the multimodal fusion of two-dimensional CFP with three-dimensional optical coherence tomography (OCT) data has significant potential to enhance retinal age prediction accuracy and the diagnostic utility of the RAG biomarker. Therefore, this work presents a novel foundation model-based framework for multimodal retinal age prediction. Technology or Method: Feature representations from CFP and OCT images were extracted using RETFound, a powerful foundation model for retinal image analysis. These representations were then combined using an innovative fusion strategy to train a lightweight linear regression head model for predicting retinal age. Training and evaluation of the developed multimodal retinal age prediction model was achieved using retinal images from over 80,000 participants in the UK Biobank. Results: The developed multimodal model sets a new benchmark in retinal age prediction (mean absolute error of 2.75 years), outperforming traditional CNN and single-modality approaches. Additionally, multimodal RAG values demonstrated superior performance in classifying patients with diabetes mellitus type 1, multiple sclerosis, and chronic kidney disease, highlighting the clinical relevance of the proposed multimodal approach for non-ocular disease detection. Conclusions: This work demonstrates that multimodal fusion of CFP and OCT significantly improves retinal age prediction and subsequent RAG-based analyses. By leveraging foundation models and multimodal retinal imaging, the proposed approach enhances disease classification accuracy and demonstrates the potential of integrating the RAG into clinical workflows as a scalable, non-invasive screening tool. Significance: The findings underscore the potential of multimodal retinal imaging to transform RAG into a clinically relevant and highly accessible biomarker for disease detection.