Lie Ju

Siyuan Yan, Xieji Li, Dan Mo et al.

Medical foundation models have shown promise in controlled benchmarks, yet widespread deployment remains hindered by reliance on task-specific fine-tuning. Here, we introduce DermFM-Zero, a dermatology vision-language foundation model trained via masked latent modelling and contrastive learning on over 4 million multimodal data points. We evaluated DermFM-Zero across 20 benchmarks spanning zero-shot diagnosis and multimodal retrieval, achieving state-of-the-art performance without task-specific adaptation. We further evaluated its zero-shot capabilities in three multinational reader studies involving over 1,100 clinicians. In primary care settings, AI assistance enabled general practitioners to nearly double their differential diagnostic accuracy across 98 skin conditions. In specialist settings, the model significantly outperformed board-certified dermatologists in multimodal skin cancer assessment. In collaborative workflows, AI assistance enabled non-experts to surpass unassisted experts while improving management appropriateness. Finally, we show that DermFM-Zero's latent representations are interpretable: sparse autoencoders unsupervisedly disentangle clinically meaningful concepts that outperform predefined-vocabulary approaches and enable targeted suppression of artifact-induced biases, enhancing robustness without retraining. These findings demonstrate that a foundation model can provide effective, safe, and transparent zero-shot clinical decision support.

Hyunmin Kim, Yukun Zhou, Rahul A. Jonas et al.

Oculomics - the concept of predicting systemic diseases, such as cardiovascular disease and dementia, through retinal imaging - has advanced rapidly due to the data efficiency of transformer-based foundation models like RETFound. Image-level mixed sample data augmentations, such as CutMix and MixUp, are frequently used for training transformers, yet these techniques perturb patient-specific attributes, such as medical comorbidity and clinical factors, since they only account for images and labels. To address this limitation, we propose a hierarchical sampling strategy, Oculomix, for mixed sample augmentations. Our method is based on two clinical priors. First (exam level), images acquired from the same patient at the same time point share the same attributes. Second (patient level), images acquired from the same patient at different time points have a soft temporal trend, as morbidity generally increases over time. Guided by these priors, our method constrains the mixing space to the patient and exam levels to better preserve patient-specific characteristics and leverages their hierarchical relationships. The proposed method is validated using ViT models on a five-year prediction of major adverse cardiovascular events (MACE) in a large ethnically diverse population (Alzeye). We show that Oculomix consistently outperforms image-level CutMix and MixUp by up to 3% in AUROC, demonstrating the necessity and value of the proposed method in oculomics.

Peng Xia, Ming Hu, Feilong Tang et al.

Diabetic Retinopathy (DR), induced by diabetes, poses a significant risk of visual impairment. Accurate and effective grading of DR aids in the treatment of this condition. Yet existing models experience notable performance degradation on unseen domains due to domain shifts. Previous methods address this issue by simulating domain style through simple visual transformation and mitigating domain noise via learning robust representations. However, domain shifts encompass more than image styles. They overlook biases caused by implicit factors such as ethnicity, age, and diagnostic criteria. In our work, we propose a novel framework where representations of paired data from different domains are decoupled into semantic features and domain noise. The resulting augmented representation comprises original retinal semantics and domain noise from other domains, aiming to generate enhanced representations aligned with real-world clinical needs, incorporating rich information from diverse domains. Subsequently, to improve the robustness of the decoupled representations, class and domain prototypes are employed to interpolate the disentangled representations while data-aware weights are designed to focus on rare classes and domains. Finally, we devise a robust pixel-level semantic alignment loss to align retinal semantics decoupled from features, maintaining a balance between intra-class diversity and dense class features. Experimental results on multiple benchmarks demonstrate the effectiveness of our method on unseen domains. The code implementations are accessible on https://github.com/richard-peng-xia/DECO.

Lie Ju, Sijin Zhou, Yukun Zhou et al.

Recent advances in medical vision-language models (VLMs) demonstrate impressive performance in image classification tasks, driven by their strong zero-shot generalization capabilities. However, given the high variability and complexity inherent in medical imaging data, the ability of these models to detect out-of-distribution (OOD) data in this domain remains underexplored. In this work, we conduct the first systematic investigation into the OOD detection potential of medical VLMs. We evaluate state-of-the-art VLM-based OOD detection methods across a diverse set of medical VLMs, including both general and domain-specific purposes. To accurately reflect real-world challenges, we introduce a cross-modality evaluation pipeline for benchmarking full-spectrum OOD detection, rigorously assessing model robustness against both semantic shifts and covariate shifts. Furthermore, we propose a novel hierarchical prompt-based method that significantly enhances OOD detection performance. Extensive experiments are conducted to validate the effectiveness of our approach. The codes are available at https://github.com/PyJulie/Medical-VLMs-OOD-Detection.

Yukun Zhou, Paul Nderitu, Jocelyn Hui Lin Goh et al.

Medical foundation models, pre-trained with large-scale clinical data, demonstrate strong performance in diverse clinically relevant applications. RETFound, trained on nearly one million retinal images, exemplifies this approach in applications with retinal images. However, the emergence of increasingly powerful and multifold larger generalist foundation models such as DINOv2 and DINOv3 raises the question of whether domain-specific pre-training remains essential, and if so, what gap persists. To investigate this, we systematically evaluated the adaptability of DINOv2 and DINOv3 in retinal image applications, compared to two specialist RETFound models, RETFound-MAE and RETFound-DINOv2. We assessed performance on ocular disease detection and systemic disease prediction using two adaptation strategies: fine-tuning and linear probing. Data efficiency and adaptation efficiency were further analysed to characterise trade-offs between predictive performance and computational cost. Our results show that although scaling generalist models yields strong adaptability across diverse tasks, RETFound-DINOv2 consistently outperforms these generalist foundation models in ocular-disease detection and oculomics tasks, demonstrating stronger generalisability and data efficiency. These findings suggest that specialist retinal foundation models remain the most effective choice for clinical applications, while the narrowing gap with generalist foundation models suggests that continued data and model scaling can deliver domain-relevant gains and position them as strong foundations for future medical foundation models.

Wenxue Li, Xinyu Xiong, Peng Xia et al.

Recent advances in large foundation models, such as the Segment Anything Model (SAM), have demonstrated considerable promise across various tasks. Despite their progress, these models still encounter challenges in specialized medical image analysis, especially in recognizing subtle inter-class differences in Diabetic Retinopathy (DR) lesion segmentation. In this paper, we propose a novel framework that customizes SAM for text-prompted DR lesion segmentation, termed TP-DRSeg. Our core idea involves exploiting language cues to inject medical prior knowledge into the vision-only segmentation network, thereby combining the advantages of different foundation models and enhancing the credibility of segmentation. Specifically, to unleash the potential of vision-language models in the recognition of medical concepts, we propose an explicit prior encoder that transfers implicit medical concepts into explicit prior knowledge, providing explainable clues to excavate low-level features associated with lesions. Furthermore, we design a prior-aligned injector to inject explicit priors into the segmentation process, which can facilitate knowledge sharing across multi-modality features and allow our framework to be trained in a parameter-efficient fashion. Experimental results demonstrate the superiority of our framework over other traditional models and foundation model variants.