Tobias Elze

Min Shi, Anagha Lokhande, Mojtaba S. Fazli et al. · harvard, stanford

Ophthalmic images and derivatives such as the retinal nerve fiber layer (RNFL) thickness map are crucial for detecting and monitoring ophthalmic diseases (e.g., glaucoma). For computer-aided diagnosis of eye diseases, the key technique is to automatically extract meaningful features from ophthalmic images that can reveal the biomarkers (e.g., RNFL thinning patterns) linked to functional vision loss. However, representation learning from ophthalmic images that links structural retinal damage with human vision loss is non-trivial mostly due to large anatomical variations between patients. The task becomes even more challenging in the presence of image artifacts, which are common due to issues with image acquisition and automated segmentation. In this paper, we propose an artifact-tolerant unsupervised learning framework termed EyeLearn for learning representations of ophthalmic images. EyeLearn has an artifact correction module to learn representations that can best predict artifact-free ophthalmic images. In addition, EyeLearn adopts a clustering-guided contrastive learning strategy to explicitly capture the intra- and inter-image affinities. During training, images are dynamically organized in clusters to form contrastive samples in which images in the same or different clusters are encouraged to learn similar or dissimilar representations, respectively. To evaluate EyeLearn, we use the learned representations for visual field prediction and glaucoma detection using a real-world ophthalmic image dataset of glaucoma patients. Extensive experiments and comparisons with state-of-the-art methods verified the effectiveness of EyeLearn for learning optimal feature representations from ophthalmic images.

Yan Luo, Yu Tian, Min Shi et al.

Fairness (also known as equity interchangeably) in machine learning is important for societal well-being, but limited public datasets hinder its progress. Currently, no dedicated public medical datasets with imaging data for fairness learning are available, though minority groups suffer from more health issues. To address this gap, we introduce Harvard Glaucoma Fairness (Harvard-GF), a retinal nerve disease dataset with both 2D and 3D imaging data and balanced racial groups for glaucoma detection. Glaucoma is the leading cause of irreversible blindness globally with Blacks having doubled glaucoma prevalence than other races. We also propose a fair identity normalization (FIN) approach to equalize the feature importance between different identity groups. Our FIN approach is compared with various the-state-of-the-art fairness learning methods with superior performance in the racial, gender, and ethnicity fairness tasks with 2D and 3D imaging data, which demonstrate the utilities of our dataset Harvard-GF for fairness learning. To facilitate fairness comparisons between different models, we propose an equity-scaled performance measure, which can be flexibly used to compare all kinds of performance metrics in the context of fairness. The dataset and code are publicly accessible via \url{https://ophai.hms.harvard.edu/datasets/harvard-glaucoma-fairness-3300-samples/}.

Yan Luo, Min Shi, Yu Tian et al.

Glaucoma is the number one cause of irreversible blindness globally. A major challenge for accurate glaucoma detection and progression forecasting is the bottleneck of limited labeled patients with the state-of-the-art (SOTA) 3D retinal imaging data of optical coherence tomography (OCT). To address the data scarcity issue, this paper proposes two solutions. First, we develop a novel generalization-reinforced semi-supervised learning (SSL) model called pseudo supervisor to optimally utilize unlabeled data. Compared with SOTA models, the proposed pseudo supervisor optimizes the policy of predicting pseudo labels with unlabeled samples to improve empirical generalization. Our pseudo supervisor model is evaluated with two clinical tasks consisting of glaucoma detection and progression forecasting. The progression forecasting task is evaluated both unimodally and multimodally. Our pseudo supervisor model demonstrates superior performance than SOTA SSL comparison models. Moreover, our model also achieves the best results on the publicly available LAG fundus dataset. Second, we introduce the Harvard Glaucoma Detection and Progression (Harvard-GDP) Dataset, a multimodal multitask dataset that includes data from 1,000 patients with OCT imaging data, as well as labels for glaucoma detection and progression. This is the largest glaucoma detection dataset with 3D OCT imaging data and the first glaucoma progression forecasting dataset that is publicly available. Detailed sex and racial analysis are provided, which can be used by interested researchers for fairness learning studies. Our released dataset is benchmarked with several SOTA supervised CNN and transformer deep learning models. The dataset and code are made publicly available via \url{https://ophai.hms.harvard.edu/datasets/harvard-gdp1000}.

Mohammad Eslami, Solale Tabarestani, Ehsan Adeli et al.

With the advent of sophisticated machine learning (ML) techniques and the promising results they yield, especially in medical applications, where they have been investigated for different tasks to enhance the decision-making process. Since visualization is such an effective tool for human comprehension, memorization, and judgment, we have presented a first-of-its-kind estimation approach we refer to as Visualized Learning for Machine Learning (VL4ML) that not only can serve to assist physicians and clinicians in making reasoned medical decisions, but it also allows to appreciate the uncertainty visualization, which could raise incertitude in making the appropriate classification or prediction. For the proof of concept, and to demonstrate the generalized nature of this visualized estimation approach, five different case studies are examined for different types of tasks including classification, regression, and longitudinal prediction. A survey analysis with more than 100 individuals is also conducted to assess users' feedback on this visualized estimation method. The experiments and the survey demonstrate the practical merits of the VL4ML that include: (1) appreciating visually clinical/medical estimations; (2) getting closer to the patients' preferences; (3) improving doctor-patient communication, and (4) visualizing the uncertainty introduced through the black box effect of the deployed ML algorithm. All the source codes are shared via a GitHub repository.

Yan Luo, Muhammad Osama Khan, Yu Tian et al.

Equity in AI for healthcare is crucial due to its direct impact on human well-being. Despite advancements in 2D medical imaging fairness, the fairness of 3D models remains underexplored, hindered by the small sizes of 3D fairness datasets. Since 3D imaging surpasses 2D imaging in SOTA clinical care, it is critical to understand the fairness of these 3D models. To address this research gap, we conduct the first comprehensive study on the fairness of 3D medical imaging models across multiple protected attributes. Our investigation spans both 2D and 3D models and evaluates fairness across five architectures on three common eye diseases, revealing significant biases across race, gender, and ethnicity. To alleviate these biases, we propose a novel fair identity scaling (FIS) method that improves both overall performance and fairness, outperforming various SOTA fairness methods. Moreover, we release Harvard-FairVision, the first large-scale medical fairness dataset with 30,000 subjects featuring both 2D and 3D imaging data and six demographic identity attributes. Harvard-FairVision provides labels for three major eye disorders affecting about 380 million people worldwide, serving as a valuable resource for both 2D and 3D fairness learning. Our code and dataset are publicly accessible at \url{https://ophai.hms.harvard.edu/datasets/harvard-fairvision30k}.

Mohammad Eslami, Dhanvinkumar Ganeshkumar, Saber Kazeminasab et al.

We present CataractSAM-2, a domain-adapted extension of Meta's Segment Anything Model 2, designed for real-time semantic segmentation of cataract ophthalmic surgery videos with high accuracy. Positioned at the intersection of computer vision and medical robotics, CataractSAM-2 enables precise intraoperative perception crucial for robotic-assisted and computer-guided surgical systems. Furthermore, to alleviate the burden of manual labeling, we introduce an interactive annotation framework that combines sparse prompts with video-based mask propagation. This tool significantly reduces annotation time and facilitates the scalable creation of high-quality ground-truth masks, accelerating dataset development for ocular anterior segment surgeries. We also demonstrate the model's strong zero-shot generalization to glaucoma trabeculectomy procedures, confirming its cross-procedural utility and potential for broader surgical applications. The trained model and annotation toolkit are released as open-source resources, establishing CataractSAM-2 as a foundation for expanding anterior ophthalmic surgical datasets and advancing real-time AI-driven solutions in medical robotics, as well as surgical video understanding.

Yu Tian, Min Shi, Yan Luo et al.

Fairness in artificial intelligence models has gained significantly more attention in recent years, especially in the area of medicine, as fairness in medical models is critical to people's well-being and lives. High-quality medical fairness datasets are needed to promote fairness learning research. Existing medical fairness datasets are all for classification tasks, and no fairness datasets are available for medical segmentation, while medical segmentation is an equally important clinical task as classifications, which can provide detailed spatial information on organ abnormalities ready to be assessed by clinicians. In this paper, we propose the first fairness dataset for medical segmentation named Harvard-FairSeg with 10,000 subject samples. In addition, we propose a fair error-bound scaling approach to reweight the loss function with the upper error-bound in each identity group, using the segment anything model (SAM). We anticipate that the segmentation performance equity can be improved by explicitly tackling the hard cases with high training errors in each identity group. To facilitate fair comparisons, we utilize a novel equity-scaled segmentation performance metric to compare segmentation metrics in the context of fairness, such as the equity-scaled Dice coefficient. Through comprehensive experiments, we demonstrate that our fair error-bound scaling approach either has superior or comparable fairness performance to the state-of-the-art fairness learning models. The dataset and code are publicly accessible via https://ophai.hms.harvard.edu/datasets/harvard-fairseg10k.

Farzin Soleymani, Mohammad Eslami, Tobias Elze et al.

We propose a Deep Variational Clustering (DVC) framework for unsupervised representation learning and clustering of large-scale medical images. DVC simultaneously learns the multivariate Gaussian posterior through the probabilistic convolutional encoder and the likelihood distribution with the probabilistic convolutional decoder; and optimizes cluster labels assignment. Here, the learned multivariate Gaussian posterior captures the latent distribution of a large set of unlabeled images. Then, we perform unsupervised clustering on top of the variational latent space using a clustering loss. In this approach, the probabilistic decoder helps to prevent the distortion of data points in the latent space and to preserve the local structure of data generating distribution. The training process can be considered as a self-training process to refine the latent space and simultaneously optimizing cluster assignments iteratively. We evaluated our proposed framework on three public datasets that represented different medical imaging modalities. Our experimental results show that our proposed framework generalizes better across different datasets. It achieves compelling results on several medical imaging benchmarks. Thus, our approach offers potential advantages over conventional deep unsupervised learning in real-world applications. The source code of the method and all the experiments are available publicly at: https://github.com/csfarzin/DVC

Liyin Chen, Nazlee Zebardast, Mengyu Wang et al.

Quantitative prediction of future retinal appearance from longitudinal imaging would support clinical decisions in progressive macular disease that currently rely on qualitative comparison or scalar progression scores. Recent methods have moved toward increasing generative complexity, but whether this complexity is necessary for slowly progressing retinal disease is unclear. We tested this through a controlled comparison of five conditioning configurations sharing one architecture and training dataset, spanning standard conditional diffusion, inference-aligned stochastic training, and deterministic regression. In our evaluation, aligning the training and inference input distributions produced large gains (delta-SSIM +0.082, SSIM +0.086, both p < 0.001), while the choice among aligned frameworks did not significantly affect any primary metric. Task-entropy and posterior-concentration analyses, replicated on two fundus autofluorescence (FAF) platforms, provided a mechanistic account: the predictable component of inter-visit change is small relative to time-invariant acquisition variability, leaving stochastic sampling with little width to exploit. Guided by these findings, we developed TRU (Temporal Retinal U-Net), a deterministic direct-regression model with continuous time-delta conditioning and multi-scale history aggregation. We evaluated TRU on 28,902 eyes across three imaging platforms: a mixed-disease Optos FAF cohort (9,942 eyes), zero-shot transfer to Stargardt macular dystrophy on Optos (288 eyes) and Heidelberg Spectralis (125 eyes), and a boundary evaluation on Cirrus en-face fundus images from a glaucoma cohort (18,547 eyes). TRU matched or exceeded delta-SSIM, SSIM, and PSNR in every FAF cohort against three state-of-the-art benchmarks, and its advantage grew monotonically with available history length.

Yan Luo, Min Shi, Muhammad Osama Khan et al.

Fairness is a critical concern in deep learning, especially in healthcare, where these models influence diagnoses and treatment decisions. Although fairness has been investigated in the vision-only domain, the fairness of medical vision-language (VL) models remains unexplored due to the scarcity of medical VL datasets for studying fairness. To bridge this research gap, we introduce the first fair vision-language medical dataset Harvard-FairVLMed that provides detailed demographic attributes, ground-truth labels, and clinical notes to facilitate an in-depth examination of fairness within VL foundation models. Using Harvard-FairVLMed, we conduct a comprehensive fairness analysis of two widely-used VL models (CLIP and BLIP2), pre-trained on both natural and medical domains, across four different protected attributes. Our results highlight significant biases in all VL models, with Asian, Male, Non-Hispanic, and Spanish being the preferred subgroups across the protected attributes of race, gender, ethnicity, and language, respectively. In order to alleviate these biases, we propose FairCLIP, an optimal-transport-based approach that achieves a favorable trade-off between performance and fairness by reducing the Sinkhorn distance between the overall sample distribution and the distributions corresponding to each demographic group. As the first VL dataset of its kind, Harvard-FairVLMed holds the potential to catalyze advancements in the development of machine learning models that are both ethically aware and clinically effective. Our dataset and code are available at https://ophai.hms.harvard.edu/datasets/harvard-fairvlmed10k.

Yang Bai, Haoran Cheng, Yang Zhou et al.

Despite the promise of foundation models in medical AI, current systems remain limited - they are modality-specific and lack transparent reasoning processes, hindering clinical adoption. To address this gap, we present EVLF-FM, a multimodal vision-language foundation model (VLM) designed to unify broad diagnostic capability with fine-grain explainability. The development and testing of EVLF-FM encompassed over 1.3 million total samples from 23 global datasets across eleven imaging modalities related to six clinical specialties: dermatology, hepatology, ophthalmology, pathology, pulmonology, and radiology. External validation employed 8,884 independent test samples from 10 additional datasets across five imaging modalities. Technically, EVLF-FM is developed to assist with multiple disease diagnosis and visual question answering with pixel-level visual grounding and reasoning capabilities. In internal validation for disease diagnostics, EVLF-FM achieved the highest average accuracy (0.858) and F1-score (0.797), outperforming leading generalist and specialist models. In medical visual grounding, EVLF-FM also achieved stellar performance across nine modalities with average mIOU of 0.743 and Acc@0.5 of 0.837. External validations further confirmed strong zero-shot and few-shot performance, with competitive F1-scores despite a smaller model size. Through a hybrid training strategy combining supervised and visual reinforcement fine-tuning, EVLF-FM not only achieves state-of-the-art accuracy but also exhibits step-by-step reasoning, aligning outputs with visual evidence. EVLF-FM is an early multi-disease VLM model with explainability and reasoning capabilities that could advance adoption of and trust in foundation models for real-world clinical deployment.

Yang Zhou, Chrystie Wan Ning Quek, Jun Zhou et al.

Current artificial intelligence models for medical imaging are predominantly single modality and single disease. Attempts to create multimodal and multi-disease models have resulted in inconsistent clinical accuracy. Furthermore, training these models typically requires large, labour-intensive, well-labelled datasets. We developed MerMED-FM, a state-of-the-art multimodal, multi-specialty foundation model trained using self-supervised learning and a memory module. MerMED-FM was trained on 3.3 million medical images from over ten specialties and seven modalities, including computed tomography (CT), chest X-rays (CXR), ultrasound (US), pathology patches, color fundus photography (CFP), optical coherence tomography (OCT) and dermatology images. MerMED-FM was evaluated across multiple diseases and compared against existing foundational models. Strong performance was achieved across all modalities, with AUROCs of 0.988 (OCT); 0.982 (pathology); 0.951 (US); 0.943 (CT); 0.931 (skin); 0.894 (CFP); 0.858 (CXR). MerMED-FM has the potential to be a highly adaptable, versatile, cross-specialty foundation model that enables robust medical imaging interpretation across diverse medical disciplines.