Evaluating Fundus-Specific Foundation Models for Diabetic Macular Edema Detection

Despite the widespread adoption of foundation models as feature extractors for medical imaging, relatively little is understood about how different pretraining strategies influence the transferability of learned representations to weakly supervised ophthalmic imaging tasks. We investigate this question in ultra-widefield (UWF) retinal imaging by evaluating foundation model representations within a patch-based multiple instance learning (MIL) framework for disease classification on UWF images. We compare Vision Transformer encoders pretrained with supervised, Masked Autoencoder (MAE), and self-distillation objectives, while keeping the downstream aggregation architecture unchanged. Within a controlled comparison of ViT-B encoders pretrained on ImageNet-1k, the choice of pretraining objective substantially influenced frozen representation transfer, with supervised and self-distillation-based models outperforming MAE. A contemporary DINOv3 model pretrained at a larger scale achieved the strongest overall performance, with a quadratic weighted kappa of 0.863 for five-class diabetic retinopathy grading, comparable with DINOv1. Attention analysis further revealed distinct patch-aggregation behaviours associated with the different pretrained representations, while partial fine-tuning substantially reduced the performance gap for MAE. These findings suggest that pretraining strategy influences both representation transferability and the subsequent aggregation of patch-level evidence within MIL, resulting in differences in downstream classification performance.

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.

Foundation models are used to extract transferable representations from large amounts of unlabeled data, typically via self-supervised learning (SSL). However, many of these models rely on architectures that offer limited interpretability, a critical issue in high-stakes domains such as medical imaging. We propose \model, a foundation model that is interpretable-by-design via a BagNet backbone whose small receptive fields generate class evidence maps that are faithful to the model's decision-making process. Additionally, \model{} incorporates a $2D$ projection layer during pretraining that enables direct visualization of the representation space, providing a dataset-level view of the learned structure including meaningful clinical clusters as well as potential spurious correlations. We trained \model{} on over 800,000 color fundus photographs from various sources to learn generalizable representations for different downstream tasks. Our model achieves performance comparable to RETFound, which has $16\times$ more parameters, while providing interpretable predictions on out-of-distribution data. These results suggest that large-scale SSL pretraining paired with inherent interpretability can lead to robust representations for retinal imaging. Code and pretrained models are available at \href{https://anonymous.4open.science/r/dual-ifm-3D5A/README.md}{www.anonymous.4open.science/dual-IFM}.