Artificial intelligence-enhanced retinal imaging as a biomarker for systemic diseases

Retinal images provide a non-invasive and accessible means to directly visualize human blood vessels and nerve fibers. Growing studies have investigated the intricate microvascular and neural circuitry within the retina, its interactions with other systemic vascular and nervous systems, and the link between retinal biomarkers and various systemic diseases. Using the eye to study systemic health, based on these connections, has been given a term as oculomics. Advancements in artificial intelligence (AI) technologies, particularly deep learning, have further increased the potential impact of this study. Leveraging these technologies, retinal analysis has demonstrated potentials in detecting numerous diseases, including cardiovascular diseases, central nervous system diseases, chronic kidney diseases, metabolic diseases, endocrine disorders, and hepatobiliary diseases. AI-based retinal imaging, which incorporates established modalities such as digital color fundus photographs, optical coherence tomography (OCT) and OCT angiography, as well as emerging technologies like ultra-wide field imaging, shows great promises in predicting systemic diseases. This provides a valuable opportunity for systemic diseases screening, early detection, prediction, risk stratification, and personalized prognostication. As the AI and big data research field grows, with the mission of transforming healthcare, they also face numerous challenges and limitations both in data and technology. The application of natural language processing framework, large language model, and other generative AI techniques presents both opportunities and concerns that require careful consideration. In this review, we not only summarize key studies on AI-enhanced retinal imaging for predicting systemic diseases but also underscore the significance of these advancements in transforming healthcare. By highlighting the remarkable progress made thus far, we provide a comprehensive overview of state-of-the-art techniques and explore the opportunities and challenges in this rapidly evolving field. This review aims to serve as a valuable resource for researchers and clinicians, guiding future studies and fostering the integration of AI in clinical practice.