Abstract: Age-related macular degeneration (AMD) is one of the leading causes of severe vision loss. Early detection, prompt intervention, and reliable assessment of treatment outcomes are essential to prevent irreversible vision loss from advanced AMD stages such as geographic atrophy (GA). Patients at higher risk of progression to GA would benefit from more frequent follow up visits, low vision referrals, and administration of therapeutic interventions. Deep learning (DL) techniques have recently been applied to diagnose, classify, and understand the progression trends of GA. However, a major limitation of DL is the need for large amounts of well curated datasets from a diverse sub-population for robust diagnostic or prognostic performance. Due to the overfitting on training data, the model tends to perform badly on external data (less generalizability of the model). Moreover, efforts towards large public centralized datasets for DL research are hindered by significant barriers to data sharing, privacy concerns, costs of image de-identification, and controls over how data would be used. In this project, we aim to demonstrate the utility of novel federated DL approaches, which enable gaining insights collaboratively, e.g., in the form of a consensus model, without moving patient data beyond the firewalls of the institutions in which they reside. This novel paradigm of DL model training focuses on distributing the training of DL models across institutions instead of sharing patient data and only the model parameters are shared with a central server. We specifically seek to build robust risk models for predicting the occurrence and growth of GA. Four data cohorts from the Stanford University, University of Illinois Chicago (UIC), Wake Forest University (Wake Forest), and National Taiwan University (NTU) will be used to test the hypothesis that the prognostic accuracy of the GA risk models using federated approach is more robust than models built on single institutional datasets. Our first aim is to establish a federated learning (FL) framework for GA prediction utilizing longitudinal multi-modal imaging and patient meta-data from four independent institutions (training and independent testing dataset from Stanford, UIC, Wake Forest, and NTU). Key success criterion of the aim 1 study is to demonstrate a robust and secure FL framework for GA risk model training within the multi-institutional environment. The second aim is to integrate a novel adversarial domain alignment (ADA) technique into the FL framework to tackle domain shift caused by heterogeneous data distribution at different institutions. To improve data representation learning, and model transferability and generalizability across sub-population data, a novel self-supervised contrastive learning (CL) based methods will be employed within the FL framework. Key success criterion of the aim 2 study is to establish protocols for integrating domain alignment into FL framework and evaluate the FL- trained GA prediction models deployed on new and previously unseen clinical data. Clinical deployment of such AI prediction tools will facilitate identification of high-risk AMD patients as candidates for more frequent screening and earlier treatment, leading to better clinical outcomes.

Public Health Relevance Statement Advanced age-related macular degeneration (AMD) in the form of geographic atrophy (GA) is a retinal disease that is a leading cause of severe vision loss worldwide. We are developing artificial intelligence (AI) based techniques to collaboratively build GA risk models using multi-institutional data cohorts with a diverse sub-population. Distributed deep learning will be used to build robust models to improve clinical management of AMD.