OphMAE: Bridging Volumetric and Planar Imaging with a Foundation Model for Adaptive Ophthalmological Diagnosis

The advent of foundation models has heralded a new era in medical artificial intelligence (AI), enabling the extraction of generalizable representations from large-scale unlabeled datasets. However, current ophthalmic AI paradigms are predominantly constrained to single-modality inference, thereby creating a dissonance with clinical practice where diagnosis relies on the synthesis of complementary imaging modalities. Furthermore, the deployment of high-performance AI in resource-limited settings is frequently impeded by the unavailability of advanced three-dimensional imaging hardware. Here, we present the Ophthalmic multimodal Masked Autoencoder (OphMAE), a multi-imaging foundation model engineered to synergize the volumetric depth of 3D Optical Coherence Tomography (OCT) with the planar context of 2D en face OCT. By implementing a novel cross-modal fusion architecture and a unique adaptive inference mechanism, OphMAE was pre-trained on a massive dataset with of 183,875 paired OCT images derived from 32,765 patients. In a rigorous benchmark encompassing 17 diverse diagnostic tasks with 48,340 paired OCT images from 8,191 patients, the model demonstrated state-of-the-art performance, achieving an Area Under the Curve (AUC) of 96.9% for Age-related Macular Degeneration (AMD) and 97.2% for Diabetic Macular Edema (DME), consistently surpassing existing single-modal and multimodal foundation models. Crucially, OphMAE exhibits robust engineering adaptability: it maintains high diagnostic accuracy, such as 93.7\% AUC for AMD, even when restricted to single-modality 2D inputs, and demonstrates exceptional data efficiency by retaining 95.7% AUC with as few as 500 labeled samples. This work establishes a scalable and adaptable framework for ophthalmic AI, ensuring robust performance across different tasks.

SAIL: Structure-Aware Interpretable Learning for Anatomy-Aligned Post-hoc Explanations in OCT

Optical coherence tomography (OCT), a commonly used retinal imaging modality, plays a central role in retinal disease diagnosis by providing high-resolution visualization of retinal layers. While deep learning (DL) has achieved expert-level accuracy in OCT-based retinal disease detection, its "black box" nature poses challenges for clinical adoption, where explainability is essential for clinical trust and regulatory approval. Existing post-hoc explainable AI (XAI) methods often struggle to delineate fine-grained lesion structures, respect anatomical boundaries, or suppress noise, limiting the trustworthiness of their explanations. To bridge these gaps, we propose a Structure-Aware Interpretable Learning (SAIL) framework that integrates retinal anatomical priors at the representation level and couples them with semantic features via a fusion design. Without modifying standard post-hoc explainability methods, this representation yields sharper and more anatomically aligned attribution maps. Comprehensive experiments on diverse OCT datasets demonstrate that our structure-aware method consistently enhances interpretability, producing clinically meaningful and anatomy-aware explanations. Ablation studies further show that strong interpretability requires both structural priors and semantic features, and that properly fusing the two is critical to achieve the best explanation quality. Together, these results highlight structure-aware representations as a key step toward reliable explainability in OCT.