Daily Papers

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.

Diabetic retinopathy (DR) is a growing health problem worldwide and is a leading cause of visual impairment and blindness, especially among working people aged 20-65. Its incidence is increasing along with the number of diabetes cases, and it is more common in developed countries than in developing countries. Recent research in the field of diabetic retinopathy diagnosis is using advanced technologies, such as analysis of images obtained by ophthalmoscopy. Automatic methods for analyzing eye images based on neural networks, deep learning and image analysis algorithms can improve the efficiency of diagnosis. This paper describes an automatic DR diagnosis method that includes processing and analysis of ophthalmoscopic images of the eye. It uses morphological algorithms to identify the optic disc and lesions characteristic of DR, such as microaneurysms, hemorrhages and exudates. Automated DR diagnosis has the potential to improve the efficiency of early detection of this disease and contribute to reducing the number of cases of diabetes-related visual impairment. The final step was to create an application with a graphical user interface that allowed retinal images taken at cooperating ophthalmology offices to be uploaded to the server. These images were then analyzed using a developed algorithm to make a diagnosis.

Automatic diabetic retinopathy (DR) lesions segmentation makes great sense of assisting ophthalmologists in diagnosis. Although many researches have been conducted on this task, most prior works paid too much attention to the designs of networks instead of considering the pathological association for lesions. Through investigating the pathogenic causes of DR lesions in advance, we found that certain lesions are closed to specific vessels and present relative patterns to each other. Motivated by the observation, we propose a relation transformer block (RTB) to incorporate attention mechanisms at two main levels: a self-attention transformer exploits global dependencies among lesion features, while a cross-attention transformer allows interactions between lesion and vessel features by integrating valuable vascular information to alleviate ambiguity in lesion detection caused by complex fundus structures. In addition, to capture the small lesion patterns first, we propose a global transformer block (GTB) which preserves detailed information in deep network. By integrating the above blocks of dual-branches, our network segments the four kinds of lesions simultaneously. Comprehensive experiments on IDRiD and DDR datasets well demonstrate the superiority of our approach, which achieves competitive performance compared to state-of-the-arts.

Fundus images are widely used for diagnosing various eye diseases, such as diabetic retinopathy, glaucoma, and age-related macular degeneration. However, manual analysis of fundus images is time-consuming and prone to errors. In this report, we propose a novel method for fundus detection using object detection and machine learning classification techniques. We use a YOLO_V8 to perform object detection on fundus images and locate the regions of interest (ROIs) such as optic disc, optic cup and lesions. We then use machine learning SVM classification algorithms to classify the ROIs into different DR stages based on the presence or absence of pathological signs such as exudates, microaneurysms, and haemorrhages etc. Our method achieves 84% accuracy and efficiency for fundus detection and can be applied for retinal fundus disease triage, especially in remote areas around the world.

Deep learning is currently the state-of-the-art for automated detection of referable diabetic retinopathy (DR) from color fundus photographs (CFP). While the general interest is put on improving results through methodological innovations, it is not clear how good these approaches perform compared to standard deep classification models trained with the appropriate settings. In this paper we propose to model a strong baseline for this task based on a simple and standard ResNet-18 architecture. To this end, we built on top of prior art by training the model with a standard preprocessing strategy but using images from several public sources and an empirically calibrated data augmentation setting. To evaluate its performance, we covered multiple clinically relevant perspectives, including image and patient level DR screening, discriminating responses by input quality and DR grade, assessing model uncertainties and analyzing its results in a qualitative manner. With no other methodological innovation than a carefully designed training, our ResNet model achieved an AUC = 0.955 (0.953 - 0.956) on a combined test set of 61007 test images from different public datasets, which is in line or even better than what other more complex deep learning models reported in the literature. Similar AUC values were obtained in 480 images from two separate in-house databases specially prepared for this study, which emphasize its generalization ability. This confirms that standard networks can still be strong baselines for this task if properly trained.

Obtaining large pre-trained models that can be fine-tuned to new tasks with limited annotated samples has remained an open challenge for medical imaging data. While pre-trained deep networks on ImageNet and vision-language foundation models trained on web-scale data are prevailing approaches, their effectiveness on medical tasks is limited due to the significant domain shift between natural and medical images. To bridge this gap, we introduce LVM-Med, the first family of deep networks trained on large-scale medical datasets. We have collected approximately 1.3 million medical images from 55 publicly available datasets, covering a large number of organs and modalities such as CT, MRI, X-ray, and Ultrasound. We benchmark several state-of-the-art self-supervised algorithms on this dataset and propose a novel self-supervised contrastive learning algorithm using a graph-matching formulation. The proposed approach makes three contributions: (i) it integrates prior pair-wise image similarity metrics based on local and global information; (ii) it captures the structural constraints of feature embeddings through a loss function constructed via a combinatorial graph-matching objective; and (iii) it can be trained efficiently end-to-end using modern gradient-estimation techniques for black-box solvers. We thoroughly evaluate the proposed LVM-Med on 15 downstream medical tasks ranging from segmentation and classification to object detection, and both for the in and out-of-distribution settings. LVM-Med empirically outperforms a number of state-of-the-art supervised, self-supervised, and foundation models. For challenging tasks such as Brain Tumor Classification or Diabetic Retinopathy Grading, LVM-Med improves previous vision-language models trained on 1 billion masks by 6-7% while using only a ResNet-50.

Clinical diagnosis of the eye is performed over multifarious data modalities including scalar clinical labels, vectorized biomarkers, two-dimensional fundus images, and three-dimensional Optical Coherence Tomography (OCT) scans. Clinical practitioners use all available data modalities for diagnosing and treating eye diseases like Diabetic Retinopathy (DR) or Diabetic Macular Edema (DME). Enabling usage of machine learning algorithms within the ophthalmic medical domain requires research into the relationships and interactions between all relevant data over a treatment period. Existing datasets are limited in that they neither provide data nor consider the explicit relationship modeling between the data modalities. In this paper, we introduce the Ophthalmic Labels for Investigating Visual Eye Semantics (OLIVES) dataset that addresses the above limitation. This is the first OCT and near-IR fundus dataset that includes clinical labels, biomarker labels, disease labels, and time-series patient treatment information from associated clinical trials. The dataset consists of 1268 near-IR fundus images each with at least 49 OCT scans, and 16 biomarkers, along with 4 clinical labels and a disease diagnosis of DR or DME. In total, there are 96 eyes' data averaged over a period of at least two years with each eye treated for an average of 66 weeks and 7 injections. We benchmark the utility of OLIVES dataset for ophthalmic data as well as provide benchmarks and concrete research directions for core and emerging machine learning paradigms within medical image analysis.

Curating a large scale medical imaging dataset for machine learning applications is both time consuming and expensive. Balancing the workload between model development, data collection and annotations is difficult for machine learning practitioners, especially under time constraints. Causal analysis is often used in medicine and economics to gain insights about the effects of actions and policies. In this paper we explore the effect of dataset interventions on the output of image classification models. Through a causal approach we investigate the effects of the quantity and type of data we need to incorporate in a dataset to achieve better performance for specific subtasks. The main goal of this paper is to highlight the potential of causal analysis as a tool for resource optimization for developing medical imaging ML applications. We explore this concept with a synthetic dataset and an exemplary use-case for Diabetic Retinopathy image analysis.

Effectively representing medical images, especially retinal images, presents a considerable challenge due to variations in appearance, size, and contextual information of pathological signs called lesions. Precise discrimination of these lesions is crucial for diagnosing vision-threatening issues such as diabetic retinopathy. While visual attention-based neural networks have been introduced to learn spatial context and channel correlations from retinal images, they often fall short in capturing localized lesion context. Addressing this limitation, we propose a novel attention mechanism called Guided Context Gating, an unique approach that integrates Context Formulation, Channel Correlation, and Guided Gating to learn global context, spatial correlations, and localized lesion context. Our qualitative evaluation against existing attention mechanisms emphasize the superiority of Guided Context Gating in terms of explainability. Notably, experiments on the Zenodo-DR-7 dataset reveal a substantial 2.63% accuracy boost over advanced attention mechanisms & an impressive 6.53% improvement over the state-of-the-art Vision Transformer for assessing the severity grade of retinopathy, even with imbalanced and limited training samples for each class.

Fairness or equity in machine learning is profoundly important for societal well-being, but limited public datasets hinder its progress, especially in the area of medicine. It is undeniable that fairness in medicine is one of the most important areas for fairness learning's applications. Currently, no large-scale public medical datasets with 3D imaging data for fairness learning are available, while 3D imaging data in modern clinics are standard tests for disease diagnosis. In addition, existing medical fairness datasets are actually repurposed datasets, and therefore they typically have limited demographic identity attributes with at most three identity attributes of age, gender, and race for fairness modeling. To address this gap, we introduce our Eye Fairness dataset with 30,000 subjects (Harvard-EF) covering three major eye diseases including age-related macular degeneration, diabetic retinopathy, and glaucoma affecting 380 million patients globally. Our Harvard-EF dataset includes both 2D fundus photos and 3D optical coherence tomography scans with six demographic identity attributes including age, gender, race, ethnicity, preferred language, and marital status. We also propose a fair identity scaling (FIS) approach combining group and individual scaling together to improve model fairness. Our FIS approach is compared with various 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 Harvard-EF dataset for fairness learning. To facilitate fairness comparisons between different models, we propose performance-scaled disparity measures, which can be used to compare model fairness accounting for overall performance levels. The dataset and code are publicly accessible via https://ophai.hms.harvard.edu/datasets/harvard-ef30k.

Retinal imaging has emerged as a powerful, non-invasive modality for detecting and quantifying biomarkers of systemic diseases-ranging from diabetes and hypertension to Alzheimer's disease and cardiovascular disorders but current insights remain dispersed across platforms and specialties. Recent technological advances in optical coherence tomography (OCT/OCTA) and adaptive optics (AO) now deliver ultra-high-resolution scans (down to 5 {\mu}m ) with superior contrast and spatial integration, allowing early identification of microvascular abnormalities and neurodegenerative changes. At the same time, AI-driven and machine learning (ML) algorithms have revolutionized the analysis of large-scale retinal datasets, increasing sensitivity and specificity; for example, deep learning models achieve > 90 \% sensitivity for diabetic retinopathy and AUC = 0.89 for the prediction of cardiovascular risk from fundus photographs. The proliferation of mobile health technologies and telemedicine platforms further extends access, reduces costs, and facilitates community-based screening and longitudinal monitoring. Despite these breakthroughs, translation into routine practice is hindered by heterogeneous imaging protocols, limited external validation of AI models, and integration challenges within clinical workflows. In this review, we systematically synthesize the latest OCT/OCT and AO developments, AI/ML approaches, and mHealth/Tele-ophthalmology initiatives and quantify their diagnostic performance across disease domains. Finally, we propose a roadmap for multicenter protocol standardization, prospective validation trials, and seamless incorporation of retinal screening into primary and specialty care pathways-paving the way for precision prevention, early intervention, and ongoing treatment of life-threatening systemic diseases.

Foundation models, often pre-trained with large-scale data, have achieved paramount success in jump-starting various vision and language applications. Recent advances further enable adapting foundation models in downstream tasks efficiently using only a few training samples, e.g., in-context learning. Yet, the application of such learning paradigms in medical image analysis remains scarce due to the shortage of publicly accessible data and benchmarks. In this paper, we aim at approaches adapting the foundation models for medical image classification and present a novel dataset and benchmark for the evaluation, i.e., examining the overall performance of accommodating the large-scale foundation models downstream on a set of diverse real-world clinical tasks. We collect five sets of medical imaging data from multiple institutes targeting a variety of real-world clinical tasks (22,349 images in total), i.e., thoracic diseases screening in X-rays, pathological lesion tissue screening, lesion detection in endoscopy images, neonatal jaundice evaluation, and diabetic retinopathy grading. Results of multiple baseline methods are demonstrated using the proposed dataset from both accuracy and cost-effective perspectives.

Diabetic foot ulcers are a common manifestation of lesions on the diabetic foot, a syndrome acquired as a long-term complication of diabetes mellitus. Accompanying neuropathy and vascular damage promote acquisition of pressure injuries and tissue death due to ischaemia. Affected areas are prone to infections, hindering the healing progress. The research at hand investigates an approach on classification of infection and ischaemia, conducted as part of the Diabetic Foot Ulcer Challenge (DFUC) 2021. Different models of the EfficientNet family are utilized in ensembles. An extension strategy for the training data is applied, involving pseudo-labeling for unlabeled images, and extensive generation of synthetic images via pix2pixHD to cope with severe class imbalances. The resulting extended training dataset features 8.68 times the size of the baseline and shows a real to synthetic image ratio of 1:3. Performances of models and ensembles trained on the baseline and extended training dataset are compared. Synthetic images featured a broad qualitative variety. Results show that models trained on the extended training dataset as well as their ensemble benefit from the large extension. F1-Scores for rare classes receive outstanding boosts, while those for common classes are either not harmed or boosted moderately. A critical discussion concretizes benefits and identifies limitations, suggesting improvements. The work concludes that classification performance of individual models as well as that of ensembles can be boosted utilizing synthetic images. Especially performance for rare classes benefits notably.

Optical coherence tomography (OCT) is a non-invasive imaging technique with extensive clinical applications in ophthalmology. OCT enables the visualization of the retinal layers, playing a vital role in the early detection and monitoring of retinal diseases. OCT uses the principle of light wave interference to create detailed images of the retinal microstructures, making it a valuable tool for diagnosing ocular conditions. This work presents an open-access OCT dataset (OCTDL) comprising over 1600 high-resolution OCT images labeled according to disease group and retinal pathology. The dataset consists of OCT records of patients with Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), Epiretinal Membrane (ERM), Retinal Artery Occlusion (RAO), Retinal Vein Occlusion (RVO), and Vitreomacular Interface Disease (VID). The images were acquired with an Optovue Avanti RTVue XR using raster scanning protocols with dynamic scan length and image resolution. Each retinal b-scan was acquired by centering on the fovea and interpreted and cataloged by an experienced retinal specialist. In this work, we applied Deep Learning classification techniques to this new open-access dataset.

The retina is the only part of the human body in which blood vessels can be accessed non-invasively using imaging techniques such as digital fundus images (DFI). The spatial distribution of the retinal microvasculature may change with cardiovascular diseases and thus the eyes may be regarded as a window to our hearts. Computerized segmentation of the retinal arterioles and venules (A/V) is essential for automated microvasculature analysis. Using active learning, we created a new DFI dataset containing 240 crowd-sourced manual A/V segmentations performed by fifteen medical students and reviewed by an ophthalmologist, and developed LUNet, a novel deep learning architecture for high resolution A/V segmentation. LUNet architecture includes a double dilated convolutional block that aims to enhance the receptive field of the model and reduce its parameter count. Furthermore, LUNet has a long tail that operates at high resolution to refine the segmentation. The custom loss function emphasizes the continuity of the blood vessels. LUNet is shown to significantly outperform two state-of-the-art segmentation algorithms on the local test set as well as on four external test sets simulating distribution shifts across ethnicity, comorbidities, and annotators. We make the newly created dataset open access (upon publication).

WHO has declared that more than 2.2 billion people worldwide are suffering from visual disorders, such as media haze, glaucoma, and drusen. At least 1 billion of these cases could have been either prevented or successfully treated, yet they remain unaddressed due to poverty, a lack of specialists, inaccurate ocular fundus diagnoses by ophthalmologists, or the presence of a rare disease. To address this, the research has developed the Hybrid Trio-Network Model Algorithm for accurately diagnosing 12 distinct common and rare eye diseases. This algorithm utilized the RFMiD dataset of 3,200 fundus images and the Binary Relevance Method to detect diseases separately, ensuring expandability and avoiding incorrect correlations. Each detector, incorporating finely tuned hyperparameters to optimize performance, consisted of three feature components: A classical transfer learning CNN model, a two-stage CNN model, and a Siamese Network. The diagnosis was made using features extracted through this Trio-Model with Ensembled Machine Learning algorithms. The proposed model achieved an average accuracy of 97% and an AUC score of 0.96. Compared to past benchmark studies, an increase of over 10% in the F1-score was observed for most diseases. Furthermore, using the Siamese Network, the model successfully made predictions in diseases like optic disc pallor, which past studies failed to predict due to low confidence. This diagnostic tool presents a stable, adaptive, cost-effective, efficient, accessible, and fast solution for globalizing early detection of both common and rare diseases.

Scarcity of large publicly available retinal fundus image datasets for automated glaucoma detection has been the bottleneck for successful application of artificial intelligence towards practical Computer-Aided Diagnosis (CAD). A few small datasets that are available for research community usually suffer from impractical image capturing conditions and stringent inclusion criteria. These shortcomings in already limited choice of existing datasets make it challenging to mature a CAD system so that it can perform in real-world environment. In this paper we present a large publicly available retinal fundus image dataset for glaucoma classification called G1020. The dataset is curated by conforming to standard practices in routine ophthalmology and it is expected to serve as standard benchmark dataset for glaucoma detection. This database consists of 1020 high resolution colour fundus images and provides ground truth annotations for glaucoma diagnosis, optic disc and optic cup segmentation, vertical cup-to-disc ratio, size of neuroretinal rim in inferior, superior, nasal and temporal quadrants, and bounding box location for optic disc. We also report baseline results by conducting extensive experiments for automated glaucoma diagnosis and segmentation of optic disc and optic cup.

Diabetes, resulting from inadequate insulin production or utilization, causes extensive harm to the body. Existing diagnostic methods are often invasive and come with drawbacks, such as cost constraints. Although there are machine learning models like Classwise k Nearest Neighbor (CkNN) and General Regression Neural Network (GRNN), they struggle with imbalanced data and result in under-performance. Leveraging advancements in sensor technology and machine learning, we propose a non-invasive diabetes diagnosis using a Back Propagation Neural Network (BPNN) with batch normalization, incorporating data re-sampling and normalization for class balancing. Our method addresses existing challenges such as limited performance associated with traditional machine learning. Experimental results on three datasets show significant improvements in overall accuracy, sensitivity, and specificity compared to traditional methods. Notably, we achieve accuracies of 89.81% in Pima diabetes dataset, 75.49% in CDC BRFSS2015 dataset, and 95.28% in Mesra Diabetes dataset. This underscores the potential of deep learning models for robust diabetes diagnosis. See project website https://steve-zeyu-zhang.github.io/DiabetesDiagnosis/

The rise of imaging techniques such as optical coherence tomography (OCT) and advances in deep learning (DL) have enabled clinicians and researchers to streamline retinal disease staging. A popular DL approach is self-supervised learning (SSL), where models learn from vast amounts of unlabeled data, avoiding costly annotation. SSL has allowed the development of foundation models (FMs), large models that can be used for a variety of downstream tasks. However, existing FMs for OCT, trained solely on image data, lack a comprehensive and robust semantic understanding of images, as evidenced by their downstream performance (especially for complex tasks), and thus require supervised fine-tuning (which may be unfeasible) to better adapt to specific applications and populations. To address this, we propose RetFiner, an SSL vision-language refinement scheme that improves the representations of existing FMs and enables their efficient and direct adaptation to specific populations for improved downstream performance. Our method uses a diverse set of training objectives which take advantage of the rich supervisory signal found in textual data. We tested RetFiner on the retinal FMs RETFound, UrFound, and VisionFM, showing significant improvements in linear probing performance on seven highly diverse OCT classification tasks, with an average increase of 5.8, 3.9, and 2.1 percentage points over their baselines, respectively. Our code and model weights are publicly available at https://github.com/ronnief1/RetFiner.

Clinicians spend a significant amount of time reviewing medical images and transcribing their findings regarding patient diagnosis, referral and treatment in text form. Vision-language models (VLMs), which automatically interpret images and summarize their findings as text, have enormous potential to alleviate clinical workloads and increase patient access to high-quality medical care. While foundational models have stirred considerable interest in the medical community, it is unclear whether their general capabilities translate to real-world clinical utility. In this work, we show that foundation VLMs markedly underperform compared to practicing ophthalmologists on specialist tasks crucial to the care of patients with age-related macular degeneration (AMD). To address this, we initially identified the essential capabilities required for image-based clinical decision-making, and then developed a curriculum to selectively train VLMs in these skills. The resulting model, RetinaVLM, can be instructed to write reports that significantly outperform those written by leading foundation medical VLMs in disease staging (F1 score of 0.63 vs. 0.11) and patient referral (0.67 vs. 0.39), and approaches the diagnostic performance of junior ophthalmologists (who achieve 0.77 and 0.78 on the respective tasks). Furthermore, in a reader study involving two senior ophthalmologists with up to 32 years of experience, RetinaVLM's reports were found to be similarly correct (78.6% vs. 82.1%) and complete (both 78.6%) as reports written by junior ophthalmologists with up to 10 years of experience. These results demonstrate that our curriculum-based approach provides a blueprint for specializing generalist foundation medical VLMs to handle real-world clinical tasks.

The caliber and configuration of retinal blood vessels serve as important biomarkers for various diseases and medical conditions. A thorough analysis of the retinal vasculature requires the segmentation of the blood vessels and their classification into arteries and veins, typically performed on color fundus images obtained by retinography. However, manually performing these tasks is labor-intensive and prone to human error. While several automated methods have been proposed to address this task, the current state of art faces challenges due to manifest classification errors affecting the topological consistency of segmentation maps. In this work, we introduce RRWNet, a novel end-to-end deep learning framework that addresses this limitation. The framework consists of a fully convolutional neural network that recursively refines semantic segmentation maps, correcting manifest classification errors and thus improving topological consistency. In particular, RRWNet is composed of two specialized subnetworks: a Base subnetwork that generates base segmentation maps from the input images, and a Recursive Refinement subnetwork that iteratively and recursively improves these maps. Evaluation on three different public datasets demonstrates the state-of-the-art performance of the proposed method, yielding more topologically consistent segmentation maps with fewer manifest classification errors than existing approaches. In addition, the Recursive Refinement module within RRWNet proves effective in post-processing segmentation maps from other methods, further demonstrating its potential. The model code, weights, and predictions will be publicly available at https://github.com/j-morano/rrwnet.

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 https://ophai.hms.harvard.edu/datasets/harvard-gdp1000.

Introduction: Blood vessels can be non-invasively visualized from a digital fundus image (DFI). Several studies have shown an association between cardiovascular risk and vascular features obtained from DFI. Recent advances in computer vision and image segmentation enable automatising DFI blood vessel segmentation. There is a need for a resource that can automatically compute digital vasculature biomarkers (VBM) from these segmented DFI. Methods: In this paper, we introduce a Python Vasculature BioMarker toolbox, denoted PVBM. A total of 11 VBMs were implemented. In particular, we introduce new algorithmic methods to estimate tortuosity and branching angles. Using PVBM, and as a proof of usability, we analyze geometric vascular differences between glaucomatous patients and healthy controls. Results: We built a fully automated vasculature biomarker toolbox based on DFI segmentations and provided a proof of usability to characterize the vascular changes in glaucoma. For arterioles and venules, all biomarkers were significant and lower in glaucoma patients compared to healthy controls except for tortuosity, venular singularity length and venular branching angles. Conclusion: We have automated the computation of 11 VBMs from retinal blood vessel segmentation. The PVBM toolbox is made open source under a GNU GPL 3 license and is available on physiozoo.com (following publication).

Foundation vision-language models are currently transforming computer vision, and are on the rise in medical imaging fueled by their very promising generalization capabilities. However, the initial attempts to transfer this new paradigm to medical imaging have shown less impressive performances than those observed in other domains, due to the significant domain shift and the complex, expert domain knowledge inherent to medical-imaging tasks. Motivated by the need for domain-expert foundation models, we present FLAIR, a pre-trained vision-language model for universal retinal fundus image understanding. To this end, we compiled 37 open-access, mostly categorical fundus imaging datasets from various sources, with up to 97 different target conditions and 284,660 images. We integrate the expert's domain knowledge in the form of descriptive textual prompts, during both pre-training and zero-shot inference, enhancing the less-informative categorical supervision of the data. Such a textual expert's knowledge, which we compiled from the relevant clinical literature and community standards, describes the fine-grained features of the pathologies as well as the hierarchies and dependencies between them. We report comprehensive evaluations, which illustrate the benefit of integrating expert knowledge and the strong generalization capabilities of FLAIR under difficult scenarios with domain shifts or unseen categories. When adapted with a lightweight linear probe, FLAIR outperforms fully-trained, dataset-focused models, more so in the few-shot regimes. Interestingly, FLAIR outperforms by a large margin more generalist, larger-scale image-language models, which emphasizes the potential of embedding experts' domain knowledge and the limitations of generalist models in medical imaging.

With the rapid development of artificial intelligence (AI) in medical image processing, deep learning in color fundus photography (CFP) analysis is also evolving. Although there are some open-source, labeled datasets of CFPs in the ophthalmology community, large-scale datasets for screening only have labels of disease categories, and datasets with annotations of fundus structures are usually small in size. In addition, labeling standards are not uniform across datasets, and there is no clear information on the acquisition device. Here we release a multi-annotation, multi-quality, and multi-device color fundus image dataset for glaucoma analysis on an original challenge -- Retinal Fundus Glaucoma Challenge 2nd Edition (REFUGE2). The REFUGE2 dataset contains 2000 color fundus images with annotations of glaucoma classification, optic disc/cup segmentation, as well as fovea localization. Meanwhile, the REFUGE2 challenge sets three sub-tasks of automatic glaucoma diagnosis and fundus structure analysis and provides an online evaluation framework. Based on the characteristics of multi-device and multi-quality data, some methods with strong generalizations are provided in the challenge to make the predictions more robust. This shows that REFUGE2 brings attention to the characteristics of real-world multi-domain data, bridging the gap between scientific research and clinical application.

The oxygen saturation level in the blood (SaO2) is crucial for health, particularly in relation to sleep-related breathing disorders. However, continuous monitoring of SaO2 is time-consuming and highly variable depending on patients' conditions. Recently, optical coherence tomography angiography (OCTA) has shown promising development in rapidly and effectively screening eye-related lesions, offering the potential for diagnosing sleep-related disorders. To bridge this gap, our paper presents three key contributions. Firstly, we propose JointViT, a novel model based on the Vision Transformer architecture, incorporating a joint loss function for supervision. Secondly, we introduce a balancing augmentation technique during data preprocessing to improve the model's performance, particularly on the long-tail distribution within the OCTA dataset. Lastly, through comprehensive experiments on the OCTA dataset, our proposed method significantly outperforms other state-of-the-art methods, achieving improvements of up to 12.28% in overall accuracy. This advancement lays the groundwork for the future utilization of OCTA in diagnosing sleep-related disorders. See project website https://steve-zeyu-zhang.github.io/JointViT

The rapid advancement of large-scale vision-language models has showcased remarkable capabilities across various tasks. However, the lack of extensive and high-quality image-text data in medicine has greatly hindered the development of large-scale medical vision-language models. In this work, we present a diagnosis-guided bootstrapping strategy that exploits both image and label information to construct vision-language datasets. Based on the constructed dataset, we developed MedDr, a generalist foundation model for healthcare capable of handling diverse medical data modalities, including radiology, pathology, dermatology, retinography, and endoscopy. Moreover, during inference, we propose a simple but effective retrieval-augmented medical diagnosis strategy, which enhances the model's generalization ability. Extensive experiments on visual question answering, medical report generation, and medical image diagnosis demonstrate the superiority of our method.

Previous research on retinal vessel segmentation is targeted at a specific image domain, mostly color fundus photography (CFP). In this paper we make a brave attempt to attack a more challenging task of broad-domain retinal vessel segmentation (BD-RVS), which is to develop a unified model applicable to varied domains including CFP, SLO, UWF, OCTA and FFA. To that end, we propose Dual Convoltuional Prompting (DCP) that learns to extract domain-specific features by localized prompting along both position and channel dimensions. DCP is designed as a plug-in module that can effectively turn a R2AU-Net based vessel segmentation network to a unified model, yet without the need of modifying its network structure. For evaluation we build a broad-domain set using five public domain-specific datasets including ROSSA, FIVES, IOSTAR, PRIME-FP20 and VAMPIRE. In order to benchmark BD-RVS on the broad-domain dataset, we re-purpose a number of existing methods originally developed in other contexts, producing eight baseline methods in total. Extensive experiments show the the proposed method compares favorably against the baselines for BD-RVS.

Accurate retinal vessel (RV) segmentation is a crucial step in the quantitative assessment of retinal vasculature, which is needed for the early detection of retinal diseases and other conditions. Numerous studies have been conducted to tackle the problem of segmenting vessels automatically using a pixel-wise classification approach. The common practice of creating ground truth labels is to categorize pixels as foreground and background. This approach is, however, biased, and it ignores the uncertainty of a human annotator when it comes to annotating e.g. thin vessels. In this work, we propose a simple and effective method that casts the RV segmentation task as an image-level regression. For this purpose, we first introduce a novel Segmentation Annotation Uncertainty-Aware (SAUNA) transform, which adds pixel uncertainty to the ground truth using the pixel's closeness to the annotation boundary and vessel thickness. To train our model with soft labels, we generalize the earlier proposed Jaccard metric loss to arbitrary hypercubes for soft Jaccard index (Intersection-over-Union) optimization. Additionally, we employ a stable version of the Focal-L1 loss for pixel-wise regression. We conduct thorough experiments and compare our method to a diverse set of baselines across 5 retinal image datasets. Our empirical results indicate that the integration of the SAUNA transform and these segmentation losses led to significant performance boosts for different segmentation models. Particularly, our methodology enables UNet-like architectures to substantially outperform computational-intensive baselines. Our implementation is available at https://github.com/Oulu-IMEDS/SAUNA.

Postprandial hyperglycemia, marked by the blood glucose level exceeding the normal range after meals, is a critical indicator of progression toward type 2 diabetes in prediabetic and healthy individuals. A key metric for understanding blood glucose dynamics after eating is the postprandial area under the curve (PAUC). Predicting PAUC in advance based on a person's diet and activity level and explaining what affects postprandial blood glucose could allow an individual to adjust their lifestyle accordingly to maintain normal glucose levels. In this paper, we propose GlucoLens, an explainable machine learning approach to predict PAUC and hyperglycemia from diet, activity, and recent glucose patterns. We conducted a five-week user study with 10 full-time working individuals to develop and evaluate the computational model. Our machine learning model takes multimodal data including fasting glucose, recent glucose, recent activity, and macronutrient amounts, and provides an interpretable prediction of the postprandial glucose pattern. Our extensive analyses of the collected data revealed that the trained model achieves a normalized root mean squared error (NRMSE) of 0.123. On average, GlucoLense with a Random Forest backbone provides a 16% better result than the baseline models. Additionally, GlucoLens predicts hyperglycemia with an accuracy of 74% and recommends different options to help avoid hyperglycemia through diverse counterfactual explanations. Code available: https://github.com/ab9mamun/GlucoLens.

Automated segmentation of retinal optical coherence tomography (OCT) images has become an important recent direction in machine learning for medical applications. We hypothesize that the anatomic structure of layers and their high-frequency variation in OCT images make retinal OCT a fitting choice for extracting spectral-domain features and combining them with spatial domain features. In this work, we present Upsilon-Net, an architecture that combines the frequency domain features with the image domain to improve the segmentation performance of OCT images. The results of this work demonstrate that the introduction of two branches, one for spectral and one for spatial domain features, brings a very significant improvement in fluid segmentation performance and allows outperformance as compared to the well-known U-Net model. Our improvement was 13% on the fluid segmentation dice score and 1.9% on the average dice score. Finally, removing selected frequency ranges in the spectral domain demonstrates the impact of these features on the fluid segmentation outperformance.

Retinal foundation models aim to learn generalizable representations from diverse retinal images, facilitating label-efficient model adaptation across various ophthalmic tasks. Despite their success, current retinal foundation models are generally restricted to a single imaging modality, such as Color Fundus Photography (CFP) or Optical Coherence Tomography (OCT), limiting their versatility. Moreover, these models may struggle to fully leverage expert annotations and overlook the valuable domain knowledge essential for domain-specific representation learning. To overcome these limitations, we introduce UrFound, a retinal foundation model designed to learn universal representations from both multimodal retinal images and domain knowledge. UrFound is equipped with a modality-agnostic image encoder and accepts either CFP or OCT images as inputs. To integrate domain knowledge into representation learning, we encode expert annotation in text supervision and propose a knowledge-guided masked modeling strategy for model pre-training. It involves reconstructing randomly masked patches of retinal images while predicting masked text tokens conditioned on the corresponding retinal image. This approach aligns multimodal images and textual expert annotations within a unified latent space, facilitating generalizable and domain-specific representation learning. Experimental results demonstrate that UrFound exhibits strong generalization ability and data efficiency when adapting to various tasks in retinal image analysis. By training on ~180k retinal images, UrFound significantly outperforms the state-of-the-art retinal foundation model trained on up to 1.6 million unlabelled images across 8 public retinal datasets. Our code and data are available at https://github.com/yukkai/UrFound.

We present OCTCube-M, a 3D OCT-based multi-modal foundation model for jointly analyzing OCT and en face images. OCTCube-M first developed OCTCube, a 3D foundation model pre-trained on 26,685 3D OCT volumes encompassing 1.62 million 2D OCT images. It then exploits a novel multi-modal contrastive learning framework COEP to integrate other retinal imaging modalities, such as fundus autofluorescence and infrared retinal imaging, into OCTCube, efficiently extending it into multi-modal foundation models. OCTCube achieves best performance on predicting 8 retinal diseases, demonstrating strong generalizability on cross-cohort, cross-device and cross-modality prediction. OCTCube can also predict cross-organ nodule malignancy (CT) and low cardiac ejection fraction as well as systemic diseases, such as diabetes and hypertension, revealing its wide applicability beyond retinal diseases. We further develop OCTCube-IR using COEP with 26,685 OCT and IR image pairs. OCTCube-IR can accurately retrieve between OCT and IR images, allowing joint analysis between 3D and 2D retinal imaging modalities. Finally, we trained a tri-modal foundation model OCTCube-EF from 4 million 2D OCT images and 400K en face retinal images. OCTCube-EF attains the best performance on predicting the growth rate of geographic atrophy (GA) across datasets collected from 6 multi-center global trials conducted in 23 countries. This improvement is statistically equivalent to running a clinical trial with more than double the size of the original study. Our analysis based on another retrospective case study reveals OCTCube-EF's ability to avoid false positive Phase-III results according to its accurate treatment effect estimation on the Phase-II results. In sum, OCTCube-M is a 3D multi-modal foundation model framework that integrates OCT and other retinal imaging modalities revealing substantial diagnostic and prognostic benefits.

We propose a novel framework for retinal feature point alignment, designed for learning cross-modality features to enhance matching and registration across multi-modality retinal images. Our model draws on the success of previous learning-based feature detection and description methods. To better leverage unlabeled data and constrain the model to reproduce relevant keypoints, we integrate a keypoint-based segmentation task. It is trained in a self-supervised manner by enforcing segmentation consistency between different augmentations of the same image. By incorporating a keypoint augmented self-supervised layer, we achieve robust feature extraction across modalities. Extensive evaluation on two public datasets and one in-house dataset demonstrates significant improvements in performance for modality-agnostic retinal feature alignment. Our code and model weights are publicly available at https://github.com/MedICL-VU/RetinaIPA.

Although the preservation of shape continuity and physiological anatomy is a natural assumption in the segmentation of medical images, it is often neglected by deep learning methods that mostly aim for the statistical modeling of input data as pixels rather than interconnected structures. In biological structures, however, organs are not separate entities; for example, in reality, a severed vessel is an indication of an underlying problem, but traditional segmentation models are not designed to strictly enforce the continuity of anatomy, potentially leading to inaccurate medical diagnoses. To address this issue, we propose a graph-based approach that enforces the continuity and connectivity of anatomical topology in medical images. Our method encodes the continuity of shapes as a graph constraint, ensuring that the network's predictions maintain this continuity. We evaluate our method on two public benchmarks on retinal vessel segmentation, showing significant improvements in connectivity metrics compared to traditional methods while getting better or on-par performance on segmentation metrics.

Precise glucose level monitoring is critical for people with diabetes to avoid serious complications. While there are several methods for continuous glucose level monitoring, research on maintenance devices is limited. To mitigate the gap, we provide a novel neural control system for continuous glucose monitoring and management that uses differential predictive control. Our approach, led by a sophisticated neural policy and differentiable modeling, constantly adjusts insulin supply in real-time, thereby improving glucose level optimization in the body. This end-to-end method maximizes efficiency, providing personalized care and improved health outcomes, as confirmed by empirical evidence.

Multimodal large language models (MLLMs) demonstrate significant potential in the field of medical diagnosis. However, they face critical challenges in specialized domains such as ophthalmology, particularly the fragmentation of annotation granularity and inconsistencies in clinical reasoning logic, which hinder precise cross-modal understanding. This paper introduces FundusExpert, an ophthalmology-specific MLLM with integrated positioning-diagnosis reasoning capabilities, along with FundusGen, a dataset constructed through the intelligent Fundus-Engine system. Fundus-Engine automates localization and leverages MLLM-based semantic expansion to integrate global disease classification, local object detection, and fine-grained feature analysis within a single fundus image. Additionally, by constructing a clinically aligned cognitive chain, it guides the model to generate interpretable reasoning paths. FundusExpert, fine-tuned with instruction data from FundusGen, achieves the best performance in ophthalmic question-answering tasks, surpassing the average accuracy of the 40B MedRegA by 26.6%. It also excels in zero-shot report generation tasks, achieving a clinical consistency of 77.0%, significantly outperforming GPT-4o's 47.6%. Furthermore, we reveal a scaling law between data quality and model capability (L propto N^{0.068}), demonstrating that the cognitive alignment annotations in FundusGen enhance data utilization efficiency. By integrating region-level localization with diagnostic reasoning chains, our work develops a scalable, clinically-aligned MLLM and explores a pathway toward bridging the visual-language gap in specific MLLMs. Our project can be found at https://github.com/MeteorElf/FundusExpert.

Multimodal Large Language Models (MLLMs) have shown significant potential in medical image analysis. However, their capabilities in interpreting fundus images, a critical skill for ophthalmology, remain under-evaluated. Existing benchmarks lack fine-grained task divisions and fail to provide modular analysis of its two key modules, i.e., large language model (LLM) and vision encoder (VE). This paper introduces FunBench, a novel visual question answering (VQA) benchmark designed to comprehensively evaluate MLLMs' fundus reading skills. FunBench features a hierarchical task organization across four levels (modality perception, anatomy perception, lesion analysis, and disease diagnosis). It also offers three targeted evaluation modes: linear-probe based VE evaluation, knowledge-prompted LLM evaluation, and holistic evaluation. Experiments on nine open-source MLLMs plus GPT-4o reveal significant deficiencies in fundus reading skills, particularly in basic tasks such as laterality recognition. The results highlight the limitations of current MLLMs and emphasize the need for domain-specific training and improved LLMs and VEs.

A large-scale labeled dataset is a key factor for the success of supervised deep learning in computer vision. However, a limited number of annotated data is very common, especially in ophthalmic image analysis, since manual annotation is time-consuming and labor-intensive. Self-supervised learning (SSL) methods bring huge opportunities for better utilizing unlabeled data, as they do not need massive annotations. With an attempt to use as many as possible unlabeled ophthalmic images, it is necessary to break the dimension barrier, simultaneously making use of both 2D and 3D images. In this paper, we propose a universal self-supervised Transformer framework, named Uni4Eye, to discover the inherent image property and capture domain-specific feature embedding in ophthalmic images. Uni4Eye can serve as a global feature extractor, which builds its basis on a Masked Image Modeling task with a Vision Transformer (ViT) architecture. We employ a Unified Patch Embedding module to replace the origin patch embedding module in ViT for jointly processing both 2D and 3D input images. Besides, we design a dual-branch multitask decoder module to simultaneously perform two reconstruction tasks on the input image and its gradient map, delivering discriminative representations for better convergence. We evaluate the performance of our pre-trained Uni4Eye encoder by fine-tuning it on six downstream ophthalmic image classification tasks. The superiority of Uni4Eye is successfully established through comparisons to other state-of-the-art SSL pre-training methods.