Collaboration provides valuable data for robust artificial intelligence (AI) model development. Federated learning (FL) is a privacy enhancing technology that allows collaboration while respecting privacy via the development of models without raw data transfer. However state-of-the-art FL models still face challenges in non-independent and identically distributed (non-i.i.d.) health care settings and remain susceptible to privacy breaches. We propose a novel FL framework coupled with blockchain technology to address these challenges.Retrospective multicohort study SUBJECTS AND METHODS: 27,145 images from Singapore, China and Taiwan were used to design a novel FL aggregation method for the detection of myopic macular degeneration (MMD) from fundus photographs and macular disease from optical coherence tomography (OCT) scans in feature distribution skew and label distribution imbalance scenarios. We further performed adversarial attacks (label flipping and clean label). As proof of concept, blockchain was incorporated into FL to demonstrate secure transfer of model updates across collaborating sites.We evaluated our FL model performance in MMD and OCT classification and compared our model against state-of the-art FL and centralized models.Our FL model showed robust performance with areas under the receiving operating characteristic curves (AUC) of 0.868±0.009 for MMD detection and 0.970±0.012 for OCT macular disease classification. In label flipping attack, our FL model had an AUC of 0.861±0.019, similar to the centralized model (AUC 0.856± 0.015) and higher than other FL models (AUC 0.578-0.819) In clean label attack, our FL model had an AUC of 0.878±0.006 which was comparable to the centralized model (AUC 0.878±0.001) and superior to other state-of-the-art FL models with AUC of 0.529-0.838. Simulation showed that the additional time with blockchain in one global epoch was around 5 seconds. The addition of blockchain to the FL framework was feasible with a minimal impact on model development time.Our proposed FL algorithm overcomes the shortcoming of the traditional FL in non i.i.d. situations and remains robust to against adversarial attacks. The integration of blockchain adds further security during the transfer of model updates. Blockchain-enabled FL can be a trusted platform for collaborative health AI research.Copyright © 2024. Published by Elsevier Inc.