Ordinal Diffusion Models for Color Fundus Images

Diabetic Retinopathy (DR) progresses as a continuous and irreversible deterioration of the retina, following a well-defined clinical trajectory from mild to severe stages. However, most existing ordinal regression approaches model DR severity as a set of static, symmetric ranks, capturing relative order while ignoring the inherent unidirectional nature of disease progression. As a result, the learned feature representations may violate biological plausibility, allowing implausible proximity between non-consecutive stages or even reverse transitions. To bridge this gap, we propose Directed Ordinal Diffusion Regularization (D-ODR), which explicitly models the feature space as a directed flow by constructing a progression-constrained directed graph that strictly enforces forward disease evolution. By performing multi-scale diffusion on this directed structure, D-ODR imposes penalties on score inversions along valid progression paths, thereby effectively preventing the model from learning biologically inconsistent reverse transitions. This mechanism aligns the feature representation with the natural trajectory of DR worsening. Extensive experiments demonstrate that D-ODR yields superior grading performance compared to state-of-the-art ordinal regression and DR-specific grading methods, offering a more clinically reliable assessment of disease severity. Our code is available on https://github.com/HovChen/D-ODR.

Over the past decade, generative models have demonstrated success in enhancing fundus images. However, the evaluation of these models remains a challenge. A benchmark for fundus image enhancement is needed for three main reasons:(1) Conventional denoising metrics such as PSNR and SSIM fail to capture clinically relevant features, such as lesion preservation and vessel morphology consistency, limiting their applicability in real-world settings; (2) There is a lack of unified evaluation protocols that address both paired and unpaired enhancement methods, particularly those guided by clinical expertise; and (3) An evaluation framework should provide actionable insights to guide future advancements in clinically aligned enhancement models. To address these gaps, we introduce EyeBench-V2, a benchmark designed to bridge the gap between enhancement model performance and clinical utility. Our work offers three key contributions:(1) Multi-dimensional clinical-alignment through downstream evaluations: Beyond standard enhancement metrics, we assess performance across clinically meaningful tasks including vessel segmentation, diabetic retinopathy (DR) grading, generalization to unseen noise patterns, and lesion segmentation. (2) Expert-guided evaluation design: We curate a novel dataset enabling fair comparisons between paired and unpaired enhancement methods, accompanied by a structured manual assessment protocol by medical experts, which evaluates clinically critical aspects such as lesion structure alterations, background color shifts, and the introduction of artificial structures. (3) Actionable insights: Our benchmark provides a rigorous, task-oriented analysis of existing generative models, equipping clinical researchers with the evidence needed to make informed decisions, while also identifying limitations in current methods to inform the design of next-generation enhancement models.

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 DualIFM, 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, DualIFM 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 DualIFM 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 github.com/berenslab/interpretable_FM.