Daily Papers

This investigation reports on the results of convolutional neural networks developed for the recently introduced PathologicAL Myopia (PALM) dataset, which consists of 1200 fundus images. We propose a new Optic Nerve Head (ONH)-based prediction enhancement for the segmentation of atrophy and fovea. Models trained with 400 available training images achieved an AUC of 0.9867 for pathological myopia classification, and a Euclidean distance of 58.27 pixels on the fovea localization task, evaluated on a test set of 400 images. Dice and F1 metrics for semantic segmentation of lesions scored 0.9303 and 0.9869 on optic disc, 0.8001 and 0.9135 on retinal atrophy, and 0.8073 and 0.7059 on retinal detachment, respectively. Our work was acknowledged with an award in the context of the "PathologicAL Myopia detection from retinal images" challenge held during the IEEE International Symposium on Biomedical Imaging (April 2019). Considering that (pathological) myopia cases are often identified as false positives and negatives in classification systems for glaucoma, we envision that the current work could aid in future research to discriminate between glaucomatous and highly-myopic eyes, complemented by the localization and segmentation of landmarks such as fovea, optic disc and atrophy.

The prevalence of vision-threatening eye diseases is a significant global burden, with many cases remaining undiagnosed or diagnosed too late for effective treatment. Large vision-language models (LVLMs) have the potential to assist in understanding anatomical information, diagnosing eye diseases, and drafting interpretations and follow-up plans, thereby reducing the burden on clinicians and improving access to eye care. However, limited benchmarks are available to assess LVLMs' performance in ophthalmology-specific applications. In this study, we introduce LMOD, a large-scale multimodal ophthalmology benchmark consisting of 21,993 instances across (1) five ophthalmic imaging modalities: optical coherence tomography, color fundus photographs, scanning laser ophthalmoscopy, lens photographs, and surgical scenes; (2) free-text, demographic, and disease biomarker information; and (3) primary ophthalmology-specific applications such as anatomical information understanding, disease diagnosis, and subgroup analysis. In addition, we benchmarked 13 state-of-the-art LVLM representatives from closed-source, open-source, and medical domains. The results demonstrate a significant performance drop for LVLMs in ophthalmology compared to other domains. Systematic error analysis further identified six major failure modes: misclassification, failure to abstain, inconsistent reasoning, hallucination, assertions without justification, and lack of domain-specific knowledge. In contrast, supervised neural networks specifically trained on these tasks as baselines demonstrated high accuracy. These findings underscore the pressing need for benchmarks in the development and validation of ophthalmology-specific LVLMs.

Optical coherence tomography (OCT) is a non-invasive imaging modality which is widely used in clinical ophthalmology. OCT images are capable of visualizing deep retinal layers which is crucial for early diagnosis of retinal diseases. In this paper, we describe a comprehensive open-access database containing more than 500 highresolution images categorized into different pathological conditions. The image classes include Normal (NO), Macular Hole (MH), Age-related Macular Degeneration (AMD), Central Serous Retinopathy (CSR), and Diabetic Retinopathy (DR). The images were obtained from a raster scan protocol with a 2mm scan length and 512x1024 pixel resolution. We have also included 25 normal OCT images with their corresponding ground truth delineations which can be used for an accurate evaluation of OCT image segmentation. In addition, we have provided a user-friendly GUI which can be used by clinicians for manual (and semi-automated) segmentation.

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.

Millions of melanocytic skin lesions are examined by pathologists each year, the majority of which concern common nevi (i.e., ordinary moles). While most of these lesions can be diagnosed in seconds, writing the corresponding pathology report is much more time-consuming. Automating part of the report writing could, therefore, alleviate the increasing workload of pathologists. In this work, we develop a vision-language model specifically for the pathology domain of cutaneous melanocytic lesions. The model follows the Contrastive Captioner framework and was trained and evaluated using a melanocytic lesion dataset of 42,512 H&E-stained whole slide images and 19,645 corresponding pathology reports. Our results show that the quality scores of model-generated reports were on par with pathologist-written reports for common nevi, assessed by an expert pathologist in a reader study. While report generation revealed to be more difficult for rare melanocytic lesion subtypes, the cross-modal retrieval performance for these cases was considerably better.

The scarcity of high-quality, labelled retinal imaging data, which presents a significant challenge in the development of machine learning models for ophthalmology, hinders progress in the field. Existing methods for synthesising Colour Fundus Photographs (CFPs) largely rely on predefined disease labels, which restricts their ability to generate images that reflect fine-grained anatomical variations, subtle disease stages, and diverse pathological features beyond coarse class categories. To overcome these challenges, we first introduce an innovative pipeline that creates a large-scale, captioned retinal dataset comprising 1.4 million entries, called RetinaLogos-1400k. Specifically, RetinaLogos-1400k uses the visual language model(VLM) to describe retinal conditions and key structures, such as optic disc configuration, vascular distribution, nerve fibre layers, and pathological features. Building on this dataset, we employ a novel three-step training framework, RetinaLogos, which enables fine-grained semantic control over retinal images and accurately captures different stages of disease progression, subtle anatomical variations, and specific lesion types. Through extensive experiments, our method demonstrates superior performance across multiple datasets, with 62.07% of text-driven synthetic CFPs indistinguishable from real ones by ophthalmologists. Moreover, the synthetic data improves accuracy by 5%-10% in diabetic retinopathy grading and glaucoma detection. Codes are available at https://github.com/uni-medical/retina-text2cfp.

The field of computational pathology has recently seen rapid advances driven by the development of modern vision foundation models (FMs), typically trained on vast collections of pathology images. Recent studies demonstrate that increasing the training data set and model size and integrating domain-specific image processing techniques can significantly enhance the model's performance on downstream tasks. Building on these insights, our work incorporates several recent modifications to the standard DINOv2 framework from the literature to optimize the training of pathology FMs. We also apply a post-training procedure for fine-tuning models on higher-resolution images to further enrich the information encoded in the embeddings. We present three novel pathology FMs trained on up to two orders of magnitude fewer WSIs than those used to train other state-of-the-art FMs while demonstrating a comparable or superior performance on downstream tasks. Even the model trained on TCGA alone (12k WSIs) outperforms most existing FMs and, on average, matches Virchow2, the second-best FM published to date. This suggests that there still remains a significant potential for further improving the models and algorithms used to train pathology FMs to take full advantage of the vast data collections.

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.

Vision-language models in pathology enable multimodal case retrieval and automated report generation. Many of the models developed so far, however, have been trained on pathology reports that include information which cannot be inferred from paired whole slide images (e.g., patient history), potentially leading to hallucinated sentences in generated reports. To this end, we investigate how the selection of information from pathology reports for vision-language modeling affects the quality of the multimodal representations and generated reports. More concretely, we compare a model trained on full reports against a model trained on preprocessed reports that only include sentences describing the cell and tissue appearances based on the H&E-stained slides. For the experiments, we built upon the BLIP-2 framework and used a cutaneous melanocytic lesion dataset of 42,433 H&E-stained whole slide images and 19,636 corresponding pathology reports. Model performance was assessed using image-to-text and text-to-image retrieval, as well as qualitative evaluation of the generated reports by an expert pathologist. Our results demonstrate that text preprocessing prevents hallucination in report generation. Despite the improvement in the quality of the generated reports, training the vision-language model on full reports showed better cross-modal retrieval performance.

Recent advances in vision language models (VLMs) have enabled broad progress in the general medical field. However, pathology still remains a more challenging subdomain, with current pathology specific VLMs exhibiting limitations in both diagnostic accuracy and reasoning plausibility. Such shortcomings are largely attributable to the nature of current pathology datasets, which are primarily composed of image description pairs that lack the depth and structured diagnostic paradigms employed by real world pathologists. In this study, we leverage pathology textbooks and real world pathology experts to construct high-quality, reasoning-oriented datasets. Building on this, we introduce Patho-R1, a multimodal RL-based pathology Reasoner, trained through a three-stage pipeline: (1) continued pretraining on 3.5 million image-text pairs for knowledge infusion; (2) supervised fine-tuning on 500k high-quality Chain-of-Thought samples for reasoning incentivizing; (3) reinforcement learning using Group Relative Policy Optimization and Decoupled Clip and Dynamic sAmpling Policy Optimization strategies for multimodal reasoning quality refinement. To further assess the alignment quality of our dataset, we propose PathoCLIP, trained on the same figure-caption corpus used for continued pretraining. Comprehensive experimental results demonstrate that both PathoCLIP and Patho-R1 achieve robust performance across a wide range of pathology-related tasks, including zero-shot classification, cross-modal retrieval, Visual Question Answering, and Multiple Choice Question. Our project is available at the Patho-R1 repository: https://github.com/Wenchuan-Zhang/Patho-R1.

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.

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.

The need for improved diagnostic methods in ophthalmology is acute, especially in the underdeveloped regions with limited access to specialists and advanced equipment. Therefore, we introduce VisionUnite, a novel vision-language foundation model for ophthalmology enhanced with clinical knowledge. VisionUnite has been pretrained on an extensive dataset comprising 1.24 million image-text pairs, and further refined using our proposed MMFundus dataset, which includes 296,379 high-quality fundus image-text pairs and 889,137 simulated doctor-patient dialogue instances. Our experiments indicate that VisionUnite outperforms existing generative foundation models such as GPT-4V and Gemini Pro. It also demonstrates diagnostic capabilities comparable to junior ophthalmologists. VisionUnite performs well in various clinical scenarios including open-ended multi-disease diagnosis, clinical explanation, and patient interaction, making it a highly versatile tool for initial ophthalmic disease screening. VisionUnite can also serve as an educational aid for junior ophthalmologists, accelerating their acquisition of knowledge regarding both common and underrepresented ophthalmic conditions. VisionUnite represents a significant advancement in ophthalmology, with broad implications for diagnostics, medical education, and understanding of disease mechanisms. The source code is at https://github.com/HUANGLIZI/VisionUnite.

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or image-caption data, disregarding pathology reports with more clinically authentic information from pathologists and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

Timely and accurate lymphoma diagnosis is essential for guiding cancer treatment. Standard diagnostic practice combines hematoxylin and eosin (HE)-stained whole slide images with immunohistochemistry, flow cytometry, and molecular genetic tests to determine lymphoma subtypes, a process requiring costly equipment, skilled personnel, and causing treatment delays. Deep learning methods could assist pathologists by extracting diagnostic information from routinely available HE-stained slides, yet comprehensive benchmarks for lymphoma subtyping on multicenter data are lacking. In this work, we present the first multicenter lymphoma benchmarking dataset covering four common lymphoma subtypes and healthy control tissue. We systematically evaluate five publicly available pathology foundation models (H-optimus-1, H0-mini, Virchow2, UNI2, Titan) combined with attention-based (AB-MIL) and transformer-based (TransMIL) multiple instance learning aggregators across three magnifications (10x, 20x, 40x). On in-distribution test sets, models achieve multiclass balanced accuracies exceeding 80% across all magnifications, with all foundation models performing similarly and both aggregation methods showing comparable results. The magnification study reveals that 40x resolution is sufficient, with no performance gains from higher resolutions or cross-magnification aggregation. However, on out-of-distribution test sets, performance drops substantially to around 60%, highlighting significant generalization challenges. To advance the field, larger multicenter studies covering additional rare lymphoma subtypes are needed. We provide an automated benchmarking pipeline to facilitate such future research.

Pathology foundation models substantially advanced the possibilities in computational pathology -- yet tradeoffs in terms of performance, robustness, and computational requirements remained, which limited their clinical deployment. In this report, we present Atlas 2, Atlas 2-B, and Atlas 2-S, three pathology vision foundation models which bridge these shortcomings by showing state-of-the-art performance in prediction performance, robustness, and resource efficiency in a comprehensive evaluation across eighty public benchmarks. Our models were trained on the largest pathology foundation model dataset to date comprising 5.5 million histopathology whole slide images, collected from three medical institutions Charité - Universtätsmedizin Berlin, LMU Munich, and Mayo Clinic.

Color fundus photography and Optical Coherence Tomography (OCT) are the two most cost-effective tools for glaucoma screening. Both two modalities of images have prominent biomarkers to indicate glaucoma suspected. Clinically, it is often recommended to take both of the screenings for a more accurate and reliable diagnosis. However, although numerous algorithms are proposed based on fundus images or OCT volumes in computer-aided diagnosis, there are still few methods leveraging both of the modalities for the glaucoma assessment. Inspired by the success of Retinal Fundus Glaucoma Challenge (REFUGE) we held previously, we set up the Glaucoma grAding from Multi-Modality imAges (GAMMA) Challenge to encourage the development of fundus \& OCT-based glaucoma grading. The primary task of the challenge is to grade glaucoma from both the 2D fundus images and 3D OCT scanning volumes. As part of GAMMA, we have publicly released a glaucoma annotated dataset with both 2D fundus color photography and 3D OCT volumes, which is the first multi-modality dataset for glaucoma grading. In addition, an evaluation framework is also established to evaluate the performance of the submitted methods. During the challenge, 1272 results were submitted, and finally, top-10 teams were selected to the final stage. We analysis their results and summarize their methods in the paper. Since all these teams submitted their source code in the challenge, a detailed ablation study is also conducted to verify the effectiveness of the particular modules proposed. We find many of the proposed techniques are practical for the clinical diagnosis of glaucoma. As the first in-depth study of fundus \& OCT multi-modality glaucoma grading, we believe the GAMMA Challenge will be an essential starting point for future research.

Rare cancers comprise 20-25% of all malignancies but face major diagnostic challenges due to limited expert availability-especially in pediatric oncology, where they represent over 70% of cases. While pathology vision-language (VL) foundation models show promising zero-shot capabilities for common cancer subtyping, their clinical performance for rare cancers remains limited. Existing multi-instance learning (MIL) methods rely only on visual features, overlooking cross-modal knowledge and compromising interpretability critical for rare cancer diagnosis. To address this limitation, we propose PathPT, a novel framework that fully exploits the potential of vision-language pathology foundation models through spatially-aware visual aggregation and task-specific prompt tuning. Unlike conventional MIL, PathPT converts WSI-level supervision into fine-grained tile-level guidance by leveraging the zero-shot capabilities of VL models, thereby preserving localization on cancerous regions and enabling cross-modal reasoning through prompts aligned with histopathological semantics. We benchmark PathPT on eight rare cancer datasets(four adult and four pediatric) spanning 56 subtypes and 2,910 WSIs, as well as three common cancer datasets, evaluating four state-of-the-art VL models and four MIL frameworks under three few-shot settings. Results show that PathPT consistently delivers superior performance, achieving substantial gains in subtyping accuracy and cancerous region grounding ability. This work advances AI-assisted diagnosis for rare cancers, offering a scalable solution for improving subtyping accuracy in settings with limited access to specialized expertise.

Although Vision Language Models (VLMs) have shown strong generalization in medical imaging, pathology presents unique challenges due to ultra-high resolution, complex tissue structures, and nuanced clinical semantics. These factors make pathology VLMs prone to hallucinations, i.e., generating outputs inconsistent with visual evidence, which undermines clinical trust. Existing RAG approaches in this domain largely depend on text-based knowledge bases, limiting their ability to leverage diagnostic visual cues. To address this, we propose Patho-AgenticRAG, a multimodal RAG framework with a database built on page-level embeddings from authoritative pathology textbooks. Unlike traditional text-only retrieval systems, it supports joint text-image search, enabling direct retrieval of textbook pages that contain both the queried text and relevant visual cues, thus avoiding the loss of critical image-based information. Patho-AgenticRAG also supports reasoning, task decomposition, and multi-turn search interactions, improving accuracy in complex diagnostic scenarios. Experiments show that Patho-AgenticRAG significantly outperforms existing multimodal models in complex pathology tasks like multiple-choice diagnosis and visual question answering. Our project is available at the Patho-AgenticRAG repository: https://github.com/Wenchuan-Zhang/Patho-AgenticRAG.

Spatial transcriptomics (ST) provides spatially resolved measurements of gene expression, enabling characterization of the molecular landscape of human tissue beyond histological assessment as well as localized readouts that can be aligned with morphology. Concurrently, the success of multimodal foundation models that integrate vision with complementary modalities suggests that morphomolecular coupling between local expression and morphology can be systematically used to improve histological representations themselves. We introduce Spatial Expression-Aligned Learning (SEAL), a vision-omics self-supervised learning framework that infuses localized molecular information into pathology vision encoders. Rather than training new encoders from scratch, SEAL is designed as a parameter-efficient vision-omics finetuning method that can be flexibly applied to widely used pathology foundation models. We instantiate SEAL by training on over 700,000 paired gene expression spot-tissue region examples spanning tumor and normal samples from 14 organs. Tested across 38 slide-level and 15 patch-level downstream tasks, SEAL provides a drop-in replacement for pathology foundation models that consistently improves performance over widely used vision-only and ST prediction baselines on slide-level molecular status, pathway activity, and treatment response prediction, as well as patch-level gene expression prediction tasks. Additionally, SEAL encoders exhibit robust domain generalization on out-of-distribution evaluations and enable new cross-modal capabilities such as gene-to-image retrieval. Our work proposes a general framework for ST-guided finetuning of pathology foundation models, showing that augmenting existing models with localized molecular supervision is an effective and practical step for improving visual representations and expanding their cross-modal utility.

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.

Glaucoma is one of the leading causes of irreversible but preventable blindness in working age populations. Color fundus photography (CFP) is the most cost-effective imaging modality to screen for retinal disorders. However, its application to glaucoma has been limited to the computation of a few related biomarkers such as the vertical cup-to-disc ratio. Deep learning approaches, although widely applied for medical image analysis, have not been extensively used for glaucoma assessment due to the limited size of the available data sets. Furthermore, the lack of a standardize benchmark strategy makes difficult to compare existing methods in a uniform way. In order to overcome these issues we set up the Retinal Fundus Glaucoma Challenge, REFUGE (https://refuge.grand-challenge.org), held in conjunction with MICCAI 2018. The challenge consisted of two primary tasks, namely optic disc/cup segmentation and glaucoma classification. As part of REFUGE, we have publicly released a data set of 1200 fundus images with ground truth segmentations and clinical glaucoma labels, currently the largest existing one. We have also built an evaluation framework to ease and ensure fairness in the comparison of different models, encouraging the development of novel techniques in the field. 12 teams qualified and participated in the online challenge. This paper summarizes their methods and analyzes their corresponding results. In particular, we observed that two of the top-ranked teams outperformed two human experts in the glaucoma classification task. Furthermore, the segmentation results were in general consistent with the ground truth annotations, with complementary outcomes that can be further exploited by ensembling the results.

In recent years, the incidence of vision-threatening eye diseases has risen dramatically, necessitating scalable and accurate screening solutions. This paper presents a comprehensive study on deep learning architectures for the automated diagnosis of ocular conditions. To mitigate the "black-box" limitations of standard convolutional neural networks (CNNs), we implement a pipeline that combines deep feature extraction with interpretable image processing modules. Specifically, we focus on high-fidelity retinal vessel segmentation as an auxiliary task to guide the classification process. By grounding the model's predictions in clinically relevant morphological features, we aim to bridge the gap between algorithmic output and expert medical validation, thereby reducing false positives and improving deployment viability in clinical settings.

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.

Artificial intelligence (AI) is vital in ophthalmology, tackling tasks like diagnosis, classification, and visual question answering (VQA). However, existing AI models in this domain often require extensive annotation and are task-specific, limiting their clinical utility. While recent developments have brought about foundation models for ophthalmology, they are limited by the need to train separate weights for each imaging modality, preventing a comprehensive representation of multi-modal features. This highlights the need for versatile foundation models capable of handling various tasks and modalities in ophthalmology. To address this gap, we present EyeFound, a multimodal foundation model for ophthalmic images. Unlike existing models, EyeFound learns generalizable representations from unlabeled multimodal retinal images, enabling efficient model adaptation across multiple applications. Trained on 2.78 million images from 227 hospitals across 11 ophthalmic modalities, EyeFound facilitates generalist representations and diverse multimodal downstream tasks, even for detecting challenging rare diseases. It outperforms previous work RETFound in diagnosing eye diseases, predicting systemic disease incidents, and zero-shot multimodal VQA. EyeFound provides a generalizable solution to improve model performance and lessen the annotation burden on experts, facilitating widespread clinical AI applications for retinal imaging.

Diabetic retinopathy (DR) is a leading cause of vision loss in working-age adults. While screening reduces the risk of blindness, traditional imaging is often costly and inaccessible. Artificial intelligence (AI) algorithms present a scalable diagnostic solution, but concerns regarding fairness and generalization persist. This work evaluates the fairness and performance of image-trained models in DR prediction, as well as the impact of disentanglement as a bias mitigation technique, using the diverse mBRSET fundus dataset. Three models, ConvNeXt V2, DINOv2, and Swin V2, were trained on macula images to predict DR and sensitive attributes (SAs) (e.g., age and gender/sex). Fairness was assessed between subgroups of SAs, and disentanglement was applied to reduce bias. All models achieved high DR prediction performance in diagnosing (up to 94% AUROC) and could reasonably predict age and gender/sex (91% and 77% AUROC, respectively). Fairness assessment suggests disparities, such as a 10% AUROC gap between age groups in DINOv2. Disentangling SAs from DR prediction had varying results, depending on the model selected. Disentanglement improved DINOv2 performance (2% AUROC gain), but led to performance drops in ConvNeXt V2 and Swin V2 (7% and 3%, respectively). These findings highlight the complexity of disentangling fine-grained features in fundus imaging and emphasize the importance of fairness in medical imaging AI to ensure equitable and reliable healthcare solutions.

Early detection of retinal diseases is one of the most important means of preventing partial or permanent blindness in patients. In this research, a novel multi-label classification system is proposed for the detection of multiple retinal diseases, using fundus images collected from a variety of sources. First, a new multi-label retinal disease dataset, the MuReD dataset, is constructed, using a number of publicly available datasets for fundus disease classification. Next, a sequence of post-processing steps is applied to ensure the quality of the image data and the range of diseases, present in the dataset. For the first time in fundus multi-label disease classification, a transformer-based model optimized through extensive experimentation is used for image analysis and decision making. Numerous experiments are performed to optimize the configuration of the proposed system. It is shown that the approach performs better than state-of-the-art works on the same task by 7.9% and 8.1% in terms of AUC score for disease detection and disease classification, respectively. The obtained results further support the potential applications of transformer-based architectures in the medical imaging field.

Glaucoma is the leading cause of irreversible blindness worldwide and poses significant diagnostic challenges due to its reliance on subjective evaluation. However, recent advances in computer vision and deep learning have demonstrated the potential for automated assessment. In this paper, we survey recent studies on AI-based glaucoma diagnosis using fundus, optical coherence tomography, and visual field images, with a particular emphasis on deep learning-based methods. We provide an updated taxonomy that organizes methods into architectural paradigms and includes links to available source code to enhance the reproducibility of the methods. Through rigorous benchmarking on widely-used public datasets, we reveal performance gaps in generalizability, uncertainty estimation, and multimodal integration. Additionally, our survey curates key datasets while highlighting limitations such as scale, labeling inconsistencies, and bias. We outline open research challenges and detail promising directions for future studies. This survey is expected to be useful for both AI researchers seeking to translate advances into practice and ophthalmologists aiming to improve clinical workflows and diagnosis using the latest AI outcomes.

Retinal imaging is fast, non-invasive, and widely available, offering quantifiable structural and vascular signals for ophthalmic and systemic health assessment. This accessibility creates an opportunity to study how quantitative retinal phenotypes relate to ocular and systemic diseases. However, such analyses remain difficult at scale due to the limited availability of public multi-label datasets and the lack of a unified segmentation-to-quantification pipeline. We present RetSAM, a general retinal segmentation and quantification framework for fundus imaging. It delivers robust multi-target segmentation and standardized biomarker extraction, supporting downstream ophthalmologic studies and oculomics correlation analyses. Trained on over 200,000 fundus images, RetSAM supports three task categories and segments five anatomical structures, four retinal phenotypic patterns, and more than 20 distinct lesion types. It converts these segmentation results into over 30 standardized biomarkers that capture structural morphology, vascular geometry, and degenerative changes. Trained with a multi-stage strategy using both private and public fundus data, RetSAM achieves superior segmentation performance on 17 public datasets. It improves on prior best methods by 3.9 percentage points in DSC on average, with up to 15 percentage points on challenging multi-task benchmarks, and generalizes well across diverse populations, imaging devices, and clinical settings. The resulting biomarkers enable systematic correlation analyses across major ophthalmic diseases, including diabetic retinopathy, age-related macular degeneration, glaucoma, and pathologic myopia. Together, RetSAM transforms fundus images into standardized, interpretable quantitative phenotypes, enabling large-scale ophthalmic research and translation.

Age-related macular degeneration (AMD) and choroidal neovascularization (CNV)-related conditions are leading causes of vision loss worldwide, with optical coherence tomography (OCT) serving as a cornerstone for early detection and management. However, deploying state-of-the-art deep learning models like ConvNeXtV2-Large in clinical settings is hindered by their computational demands. Therefore, it is desirable to develop efficient models that maintain high diagnostic performance while enabling real-time deployment. In this study, a novel knowledge distillation framework, termed KD-OCT, is proposed to compress a high-performance ConvNeXtV2-Large teacher model, enhanced with advanced augmentations, stochastic weight averaging, and focal loss, into a lightweight EfficientNet-B2 student for classifying normal, drusen, and CNV cases. KD-OCT employs real-time distillation with a combined loss balancing soft teacher knowledge transfer and hard ground-truth supervision. The effectiveness of the proposed method is evaluated on the Noor Eye Hospital (NEH) dataset using patient-level cross-validation. Experimental results demonstrate that KD-OCT outperforms comparable multi-scale or feature-fusion OCT classifiers in efficiency- accuracy balance, achieving near-teacher performance with substantial reductions in model size and inference time. Despite the compression, the student model exceeds most existing frameworks, facilitating edge deployment for AMD screening. Code is available at https://github.com/erfan-nourbakhsh/KD- OCT.

People with diabetes are at risk of developing an eye disease called diabetic retinopathy (DR). This disease occurs when high blood glucose levels cause damage to blood vessels in the retina. Computer-aided DR diagnosis is a promising tool for early detection of DR and severity grading, due to the great success of deep learning. However, most current DR diagnosis systems do not achieve satisfactory performance or interpretability for ophthalmologists, due to the lack of training data with consistent and fine-grained annotations. To address this problem, we construct a large fine-grained annotated DR dataset containing 2,842 images (FGADR). This dataset has 1,842 images with pixel-level DR-related lesion annotations, and 1,000 images with image-level labels graded by six board-certified ophthalmologists with intra-rater consistency. The proposed dataset will enable extensive studies on DR diagnosis. We set up three benchmark tasks for evaluation: 1. DR lesion segmentation; 2. DR grading by joint classification and segmentation; 3. Transfer learning for ocular multi-disease identification. Moreover, a novel inductive transfer learning method is introduced for the third task. Extensive experiments using different state-of-the-art methods are conducted on our FGADR dataset, which can serve as baselines for future research.

Despite being widely used to support clinical care, general-purpose large multimodal models (LMMs) have generally shown poor or inconclusive performance in medical image interpretation, particularly in pathology, where gigapixel images are used. However, prior studies have used either low-resolution thumbnails or random patches, which likely underestimated model performance. Here, we ask whether LMMs can be adapted to reason coherently and accurately in the evaluation of such images. In this study, we introduce Gigapixel Image Agent for Navigating Tissue (GIANT), the first framework that allows LMMs to iteratively navigate whole-slide images (WSIs) like a pathologist. Accompanying GIANT, we release MultiPathQA, a new benchmark, which comprises 934 WSI-level questions, encompassing five clinically-relevant tasks ranging from cancer diagnosis to open-ended reasoning. MultiPathQA also includes 128 questions, authored by two professional pathologists, requiring direct slide interpretation. Using MultiPathQA, we show that our simple agentic system substantially outperforms conventional patch- and thumbnail-based baselines, approaching or surpassing the performance of specialized models trained on millions of images. For example, on pathologist-authored questions, GPT-5 with GIANT achieves 62.5% accuracy, outperforming specialist pathology models such as TITAN (43.8%) and SlideChat (37.5%). Our findings reveal the strengths and limitations of current foundation models and ground future development of LMMs for expert reasoning in pathology.

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

Vision-language models hold considerable promise for ophthalmology, but their development depends on large-scale, high-quality image-text datasets that remain scarce. We present PubMed-Ophtha, a hierarchical dataset of 102,023 ophthalmological image-caption pairs extracted from 15,842 open-access articles in PubMed Central. Unlike existing datasets, figures are extracted directly from article PDFs at full resolution and decomposed into their constituent panels, panel identifiers, and individual images. Each image is annotated with its imaging modality -- color fundus photography, optical coherence tomography, retinal imaging, or other -- and a mark status indicating the presence of annotation marks such as arrows. Figure captions are split into panel-level subcaptions using a two-step LLM approach, achieving a mean average sentence BLEU score of 0.913 on human-annotated data. Panel and image detection models reach a mAP@0.50 of 0.909 and 0.892, respectively, and figure extraction achieves a median IoU of 0.997. To support reproducibility, we additionally release the human-annotated ground-truth data, all trained models, and the full dataset generation pipeline.

Diabetic retinopathy is a severe complication of diabetes that can lead to permanent blindness if not treated promptly. Early and accurate diagnosis of the disease is essential for successful treatment. This paper introduces a deep learning method for the detection and stage grading of diabetic retinopathy, using a single fundus retinal image. Our model utilizes transfer learning, employing two state-of-the-art pre-trained models as feature extractors and fine-tuning them on a new dataset. The proposed model is trained on a large multi-center dataset, including the APTOS 2019 dataset, obtained from publicly available sources. It achieves remarkable performance in diabetic retinopathy detection and stage classification on the APTOS 2019, outperforming the established literature. For binary classification, the proposed approach achieves an accuracy of 98.50, a sensitivity of 99.46, and a specificity of 97.51. In stage grading, it achieves a quadratic weighted kappa of 93.00, an accuracy of 89.60, a sensitivity of 89.60, and a specificity of 97.72. The proposed approach serves as a reliable screening and stage grading tool for diabetic retinopathy, offering significant potential to enhance clinical decision-making and patient care.

Deep learning has enabled the development of highly robust foundation models for various pathological tasks across diverse diseases and patient cohorts. Among these models, vision-language pre-training, which leverages large-scale paired data to align pathology image and text embedding spaces, and provides a novel zero-shot paradigm for downstream tasks. However, existing models have been primarily data-driven and lack the incorporation of domain-specific knowledge, which limits their performance in cancer diagnosis, especially for rare tumor subtypes. To address this limitation, we establish a Knowledge-enhanced Pathology (KEEP) foundation model that harnesses disease knowledge to facilitate vision-language pre-training. Specifically, we first construct a disease knowledge graph (KG) that covers 11,454 human diseases with 139,143 disease attributes, including synonyms, definitions, and hypernym relations. We then systematically reorganize the millions of publicly available noisy pathology image-text pairs, into 143K well-structured semantic groups linked through the hierarchical relations of the disease KG. To derive more nuanced image and text representations, we propose a novel knowledge-enhanced vision-language pre-training approach that integrates disease knowledge into the alignment within hierarchical semantic groups instead of unstructured image-text pairs. Validated on 18 diverse benchmarks with more than 14,000 whole slide images (WSIs), KEEP achieves state-of-the-art performance in zero-shot cancer diagnostic tasks. Notably, for cancer detection, KEEP demonstrates an average sensitivity of 89.8% at a specificity of 95.0% across 7 cancer types. For cancer subtyping, KEEP achieves a median balanced accuracy of 0.456 in subtyping 30 rare brain cancers, indicating strong generalizability for diagnosing rare tumors.

Vision Language Models (VLMs) like CLIP have attracted substantial attention in pathology, serving as backbones for applications such as zero-shot image classification and Whole Slide Image (WSI) analysis. Additionally, they can function as vision encoders when combined with large language models (LLMs) to support broader capabilities. Current efforts to train pathology VLMs rely on pathology image-text pairs from platforms like PubMed, YouTube, and Twitter, which provide limited, unscalable data with generally suboptimal image quality. In this work, we leverage large-scale WSI datasets like TCGA to extract numerous high-quality image patches. We then train a large multimodal model to generate captions for these images, creating PathGen-1.6M, a dataset containing 1.6 million high-quality image-caption pairs. Our approach involves multiple agent models collaborating to extract representative WSI patches, generating and refining captions to obtain high-quality image-text pairs. Extensive experiments show that integrating these generated pairs with existing datasets to train a pathology-specific CLIP model, PathGen-CLIP, significantly enhances its ability to analyze pathological images, with substantial improvements across nine pathology-related zero-shot image classification tasks and three whole-slide image tasks. Furthermore, we construct 200K instruction-tuning data based on PathGen-1.6M and integrate PathGen-CLIP with the Vicuna LLM to create more powerful multimodal models through instruction tuning. Overall, we provide a scalable pathway for high-quality data generation in pathology, paving the way for next-generation general pathology models.

Our research is motivated by the urgent global issue of a large population affected by retinal diseases, which are evenly distributed but underserved by specialized medical expertise, particularly in non-urban areas. Our primary objective is to bridge this healthcare gap by developing a comprehensive diagnostic system capable of accurately predicting retinal diseases solely from fundus images. However, we faced significant challenges due to limited, diverse datasets and imbalanced class distributions. To overcome these issues, we have devised innovative strategies. Our research introduces novel approaches, utilizing hybrid models combining deeper Convolutional Neural Networks (CNNs), Transformer encoders, and ensemble architectures sequentially and in parallel to classify retinal fundus images into 20 disease labels. Our overarching goal is to assess these advanced models' potential in practical applications, with a strong focus on enhancing retinal disease diagnosis accuracy across a broader spectrum of conditions. Importantly, our efforts have surpassed baseline model results, with the C-Tran ensemble model emerging as the leader, achieving a remarkable model score of 0.9166, surpassing the baseline score of 0.9. Additionally, experiments with the IEViT model showcased equally promising outcomes with improved computational efficiency. We've also demonstrated the effectiveness of dynamic patch extraction and the integration of domain knowledge in computer vision tasks. In summary, our research strives to contribute significantly to retinal disease diagnosis, addressing the critical need for accessible healthcare solutions in underserved regions while aiming for comprehensive and accurate disease prediction.

Deep learning based automated pathological diagnosis has markedly improved diagnostic efficiency and reduced variability between observers, yet its clinical adoption remains limited by opaque model decisions and a lack of traceable rationale. To address this, recent multimodal visual reasoning architectures provide a unified framework that generates segmentation masks at the pixel level alongside semantically aligned textual explanations. By localizing lesion regions and producing expert style diagnostic narratives, these models deliver the transparent and interpretable insights necessary for dependable AI assisted pathology. Building on these advancements, we propose PathMR, a cell-level Multimodal visual Reasoning framework for Pathological image analysis. Given a pathological image and a textual query, PathMR generates expert-level diagnostic explanations while simultaneously predicting cell distribution patterns. To benchmark its performance, we evaluated our approach on the publicly available PathGen dataset as well as on our newly developed GADVR dataset. Extensive experiments on these two datasets demonstrate that PathMR consistently outperforms state-of-the-art visual reasoning methods in text generation quality, segmentation accuracy, and cross-modal alignment. These results highlight the potential of PathMR for improving interpretability in AI-driven pathological diagnosis. The code will be publicly available in https://github.com/zhangye-zoe/PathMR.

Mitotic figure (MF) detection in histopathology images is challenging due to large variations in slide scanners, staining protocols, tissue types, and the presence of artifacts. This paper presents a collection of training techniques - a bag of tricks - that enable robust, real-time MF detection across diverse domains. We build on the efficient RTMDet single stage object detector to achieve high inference speed suitable for clinical deployment. Our method addresses scanner variability and tumor heterogeneity via extensive multi-domain training data, balanced sampling, and careful augmentation. Additionally, we employ targeted, hard negative mining on necrotic and debris tissue to reduce false positives. In a grouped 5-fold cross-validation across multiple MF datasets, our model achieves an F1 score between 0.78 and 0.84. On the preliminary test set of the MItosis DOmain Generalization (MIDOG) 2025 challenge, our single-stage RTMDet-S based approach reaches an F1 of 0.81, outperforming larger models and demonstrating adaptability to new, unfamiliar domains. The proposed solution offers a practical trade-off between accuracy and speed, making it attractive for real-world clinical adoption.

Considering the increased workload in pathology laboratories today, automated tools such as artificial intelligence models can help pathologists with their tasks and ease the workload. In this paper, we are proposing a segmentation model (DRU-Net) that can provide a delineation of human non-small cell lung carcinomas and an augmentation method that can improve classification results. The proposed model is a fused combination of truncated pre-trained DenseNet201 and ResNet101V2 as a patch-wise classifier followed by a lightweight U-Net as a refinement model. We have used two datasets (Norwegian Lung Cancer Biobank and Haukeland University Hospital lung cancer cohort) to create our proposed model. The DRU-Net model achieves an average of 0.91 Dice similarity coefficient. The proposed spatial augmentation method (multi-lens distortion) improved the network performance by 3%. Our findings show that choosing image patches that specifically include regions of interest leads to better results for the patch-wise classifier compared to other sampling methods. The qualitative analysis showed that the DRU-Net model is generally successful in detecting the tumor. On the test set, some of the cases showed areas of false positive and false negative segmentation in the periphery, particularly in tumors with inflammatory and reactive changes.

Optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) of the eye has become essential to ophthalmology and the emerging field of oculomics, thus requiring a need for transparent, reproducible, and rapid analysis of this data for clinical research and the wider research community. Here, we introduce OCTolyzer, the first open-source toolkit for retinochoroidal analysis in OCT/SLO data. It features two analysis suites for OCT and SLO data, facilitating deep learning-based anatomical segmentation and feature extraction of the cross-sectional retinal and choroidal layers and en face retinal vessels. We describe OCTolyzer and evaluate the reproducibility of its OCT choroid analysis. At the population level, metrics for choroid region thickness were highly reproducible, with a mean absolute error (MAE)/Pearson correlation for macular volume choroid thickness (CT) of 6.7mum/0.99, macular B-scan CT of 11.6mum/0.99, and peripapillary CT of 5.0mum/0.99. Macular choroid vascular index (CVI) also showed strong reproducibility, with MAE/Pearson for volume CVI yielding 0.0271/0.97 and B-scan CVI 0.0130/0.91. At the eye level, measurement noise for regional and vessel metrics was below 5% and 20% of the population's variability, respectively. Outliers were caused by poor-quality B-scans with thick choroids and invisible choroid-sclera boundary. Processing times on a laptop CPU were under three seconds for macular/peripapillary B-scans and 85 seconds for volume scans. OCTolyzer can convert OCT/SLO data into reproducible and clinically meaningful retinochoroidal features and will improve the standardisation of ocular measurements in OCT/SLO image analysis, requiring no specialised training or proprietary software to be used. OCTolyzer is freely available here: https://github.com/jaburke166/OCTolyzer.

Diagnosing a whole-slide image is an interactive, multi-stage process involving changes in magnification and movement between fields. Although recent pathology foundation models are strong, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. The blocker is data: scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not written in textbooks or online, and therefore absent from large language model training. We introduce the AI Session Recorder, which works with standard WSI viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands (inspect or peek at discrete magnifications) and bounding boxes. A lightweight human-in-the-loop review turns AI-drafted rationales into the Pathology-CoT dataset, a form of paired "where to look" and "why it matters" supervision produced at roughly six times lower labeling time. Using this behavioral data, we build Pathologist-o3, a two-stage agent that first proposes regions of interest and then performs behavior-guided reasoning. On gastrointestinal lymph-node metastasis detection, it achieved 84.5% precision, 100.0% recall, and 75.4% accuracy, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, this constitutes one of the first behavior-grounded agentic systems in pathology. Turning everyday viewer logs into scalable, expert-validated supervision, our framework makes agentic pathology practical and establishes a path to human-aligned, upgradeable clinical AI.

As advances in large language models (LLMs) and multimodal techniques continue to mature, the development of general-purpose multimodal large language models (MLLMs) has surged, offering significant applications in interpreting natural images. However, the field of pathology has largely remained untapped, particularly in gathering high-quality data and designing comprehensive model frameworks. To bridge the gap in pathology MLLMs, we present PathAsst, a multimodal generative foundation AI assistant to revolutionize diagnostic and predictive analytics in pathology. The development of PathAsst involves three pivotal steps: data acquisition, CLIP model adaptation, and the training of PathAsst's multimodal generative capabilities. Firstly, we collect over 207K high-quality pathology image-text pairs from authoritative sources. Leveraging the advanced power of ChatGPT, we generate over 180K instruction-following samples. Furthermore, we devise additional instruction-following data specifically tailored for invoking eight pathology-specific sub-models we prepared, allowing the PathAsst to effectively collaborate with these models, enhancing its diagnostic ability. Secondly, by leveraging the collected data, we construct PathCLIP, a pathology-dedicated CLIP, to enhance PathAsst's capabilities in interpreting pathology images. Finally, we integrate PathCLIP with the Vicuna-13b and utilize pathology-specific instruction-tuning data to enhance the multimodal generation capacity of PathAsst and bolster its synergistic interactions with sub-models. The experimental results of PathAsst show the potential of harnessing AI-powered generative foundation model to improve pathology diagnosis and treatment processes.

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.

Digital pathology enables automatic analysis of histopathological sections using artificial intelligence (AI). Automatic evaluation could improve diagnostic efficiency and help find associations between morphological features and clinical outcome. For development of such prediction models, identifying invasive epithelial cells, and separating these from benign epithelial cells and in situ lesions would be the first step. In this study, we aimed to develop an AI model for segmentation of epithelial cells in sections from breast cancer. We generated epithelial ground truth masks by restaining hematoxylin and eosin (HE) sections with cytokeratin (CK) AE1/AE3, and by pathologists' annotations. HE/CK image pairs were used to train a convolutional neural network, and data augmentation was used to make the model more robust. Tissue microarrays (TMAs) from 839 patients, and whole slide images from two patients were used for training and evaluation of the models. The sections were derived from four cohorts of breast cancer patients. TMAs from 21 patients from a fifth cohort was used as a second test set. In quantitative evaluation, a mean Dice score of 0.70, 0.79, and 0.75 for invasive epithelial cells, benign epithelial cells, and in situ lesions, respectively, were achieved. In qualitative scoring (0-5) by pathologists, results were best for all epithelium and invasive epithelium, with scores of 4.7 and 4.4. Scores for benign epithelium and in situ lesions were 3.7 and 2.0. The proposed model segmented epithelial cells in HE stained breast cancer slides well, but further work is needed for accurate division between the classes. Immunohistochemistry, together with pathologists' annotations, enabled the creation of accurate ground truths. The model is made freely available in FastPathology and the code is available at https://github.com/AICAN-Research/breast-epithelium-segmentation

The emergence of large multimodal models has unlocked remarkable potential in AI, particularly in pathology. However, the lack of specialized, high-quality benchmark impeded their development and precise evaluation. To address this, we introduce PathMMU, the largest and highest-quality expert-validated pathology benchmark for LMMs. It comprises 33,573 multimodal multi-choice questions and 21,599 images from various sources, and an explanation for the correct answer accompanies each question. The construction of PathMMU capitalizes on the robust capabilities of GPT-4V, utilizing approximately 30,000 gathered image-caption pairs to generate Q\&As. Significantly, to maximize PathMMU's authority, we invite six pathologists to scrutinize each question under strict standards in PathMMU's validation and test sets, while simultaneously setting an expert-level performance benchmark for PathMMU. We conduct extensive evaluations, including zero-shot assessments of 14 open-sourced and three closed-sourced LMMs and their robustness to image corruption. We also fine-tune representative LMMs to assess their adaptability to PathMMU. The empirical findings indicate that advanced LMMs struggle with the challenging PathMMU benchmark, with the top-performing LMM, GPT-4V, achieving only a 51.7\% zero-shot performance, significantly lower than the 71.4\% demonstrated by human pathologists. After fine-tuning, even open-sourced LMMs can surpass GPT-4V with a performance of over 60\%, but still fall short of the expertise shown by pathologists. We hope that the PathMMU will offer valuable insights and foster the development of more specialized, next-generation LLMs for pathology.

Vision foundation models (FMs) are accelerating the development of digital pathology algorithms and transforming biomedical research. These models learn, in a self-supervised manner, to represent histological features in highly heterogeneous tiles extracted from whole-slide images (WSIs) of real-world patient samples. The performance of these FMs is significantly influenced by the size, diversity, and balance of the pre-training data. However, data selection has been primarily guided by expert knowledge at the WSI level, focusing on factors such as disease classification and tissue types, while largely overlooking the granular details available at the tile level. In this paper, we investigate the potential of unsupervised automatic data curation at the tile-level, taking into account 350 million tiles. Specifically, we apply hierarchical clustering trees to pre-extracted tile embeddings, allowing us to sample balanced datasets uniformly across the embedding space of the pretrained FM. We further identify these datasets are subject to a trade-off between size and balance, potentially compromising the quality of representations learned by FMs, and propose tailored batch sampling strategies to mitigate this effect. We demonstrate the effectiveness of our method through improved performance on a diverse range of clinically relevant downstream tasks.

Fundus imaging such as CFP, OCT and UWF is crucial for the early detection of retinal anomalies and diseases. Fundus image understanding, due to its knowledge-intensive nature, poses a challenging vision-language task. An emerging approach to addressing the task is to post-train a generic multimodal large language model (MLLM), either by supervised finetuning (SFT) or by reinforcement learning with verifiable rewards (RLVR), on a considerable amount of in-house samples paired with high-quality clinical reports. However, these valuable samples are not publicly accessible, which not only hinders reproducibility but also practically limits research to few players. To overcome the barrier, we make a novel attempt to train a reasoning-enhanced fundus-reading MLLM, which we term Fundus-R1, using exclusively public datasets, wherein over 94\% of the data are annotated with only image-level labels. Our technical contributions are two-fold. First, we propose a RAG-based method for composing image-specific, knowledge-aware reasoning traces. Such auto-generated traces link visual findings identified by a generic MLLM to the image labels in terms of ophthalmic knowledge. Second, we enhance RLVR with a process reward that encourages self-consistency of the generated reasoning trace in each rollout. Extensive experiments on three fundus-reading benchmarks, i.e., FunBench, Omni-Fundus and GMAI-Fundus, show that Fundus-R1 clearly outperforms multiple baselines, including its generic counterpart (Qwen2.5-VL) and a stronger edition post-trained without using the generated traces. This work paves the way for training powerful fundus-reading MLLMs with publicly available data.

Microscopic interpretation of histopathology images underlies many important diagnostic and treatment decisions. While advances in vision-language modeling raise new opportunities for analysis of such images, the gigapixel-scale size of whole slide images (WSIs) introduces unique challenges. Additionally, pathology reports simultaneously highlight key findings from small regions while also aggregating interpretation across multiple slides, often making it difficult to create robust image-text pairs. As such, pathology reports remain a largely untapped source of supervision in computational pathology, with most efforts relying on region-of-interest annotations or self-supervision at the patch-level. In this work, we develop a vision-language model based on the BLIP-2 framework using WSIs paired with curated text from pathology reports. This enables applications utilizing a shared image-text embedding space, such as text or image retrieval for finding cases of interest, as well as integration of the WSI encoder with a frozen large language model (LLM) for WSI-based generative text capabilities such as report generation or AI-in-the-loop interactions. We utilize a de-identified dataset of over 350,000 WSIs and diagnostic text pairs, spanning a wide range of diagnoses, procedure types, and tissue types. We present pathologist evaluation of text generation and text retrieval using WSI embeddings, as well as results for WSI classification and workflow prioritization (slide-level triaging). Model-generated text for WSIs was rated by pathologists as accurate, without clinically significant error or omission, for 78% of WSIs on average. This work demonstrates exciting potential capabilities for language-aligned WSI embeddings.

Current vision-language models (VLMs) in medicine are primarily designed for categorical question answering (e.g., "Is this normal or abnormal?") or qualitative descriptive tasks. However, clinical decision-making often relies on quantitative assessments, such as measuring the size of a tumor or the angle of a joint, from which physicians draw their own diagnostic conclusions. This quantitative reasoning capability remains underexplored and poorly supported in existing VLMs. In this work, we introduce MedVision, a large-scale dataset and benchmark specifically designed to evaluate and improve VLMs on quantitative medical image analysis. MedVision spans 22 public datasets covering diverse anatomies and modalities, with 30.8 million image-annotation pairs. We focus on three representative quantitative tasks: (1) detection of anatomical structures and abnormalities, (2) tumor/lesion (T/L) size estimation, and (3) angle/distance (A/D) measurement. Our benchmarks show that current off-the-shelf VLMs perform poorly on these tasks. However, with supervised fine-tuning on MedVision, we significantly enhance their performance across detection, T/L estimation, and A/D measurement, demonstrating reduced error rates and improved precision. This work provides a foundation for developing VLMs with robust quantitative reasoning capabilities in medical imaging. Code and data are available at https://medvision-vlm.github.io.

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.

In recent years, a standard computational pathology workflow has emerged where whole slide images are cropped into tiles, these tiles are processed using a foundation model, and task-specific models are built using the resulting representations. At least 15 different foundation models have been proposed, and the vast majority are trained exclusively with tiles using the 20times magnification. However, it is well known that certain histologic features can only be discerned with larger context windows and requires a pathologist to zoom in and out when analyzing a whole slide image. Furthermore, creating 224times224 pixel crops at 20times leads to a large number of tiles per slide, which can be gigapixel in size. To more accurately capture multi-resolution features and investigate the possibility of reducing the number of representations per slide, we propose a region-level mixing encoder. Our approach jointly fuses image tile representations of a mixed magnification foundation model using a masked embedding modeling pretraining step. We explore a design space for pretraining the proposed mixed-magnification region aggregators and evaluate our models on transfer to biomarker prediction tasks representing various cancer types. Results demonstrate cancer dependent improvements in predictive performance, highlighting the importance of spatial context and understanding.

Optical Coherence Tomography (OCT) is essential for diagnosing conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration. Accurate retinal layer segmentation enables quantitative biomarkers critical for clinical decision-making, but manual segmentation is time-consuming and variable, while conventional deep learning models often lack interpretability. This work proposes an improved SegNet-based deep learning framework for automated and interpretable retinal layer segmentation. Architectural innovations, including modified pooling strategies, enhance feature extraction from noisy OCT images, while a hybrid loss function combining categorical cross-entropy and Dice loss improves performance for thin and imbalanced retinal layers. Gradient-weighted Class Activation Mapping (Grad-CAM) is integrated to provide visual explanations, allowing clinical validation of model decisions. Trained and validated on the Duke OCT dataset, the framework achieved 95.77% validation accuracy, a Dice coefficient of 0.9446, and a Jaccard Index (IoU) of 0.8951. Class-wise results confirmed robust performance across most layers, with challenges remaining for thinner boundaries. Grad-CAM visualizations highlighted anatomically relevant regions, aligning segmentation with clinical biomarkers and improving transparency. By combining architectural improvements, a customized hybrid loss, and explainable AI, this study delivers a high-performing SegNet-based framework that bridges the gap between accuracy and interpretability. The approach offers strong potential for standardizing OCT analysis, enhancing diagnostic efficiency, and fostering clinical trust in AI-driven ophthalmic tools.

Histopathology image analysis is fundamental to digital pathology, with hematoxylin and eosin (H&E) staining as the gold standard for diagnostic and prognostic assessments. While H&E imaging effectively highlights cellular and tissue structures, it lacks sensitivity to birefringence and tissue anisotropy, which are crucial for assessing collagen organization, fiber alignment, and microstructural alterations--key indicators of tumor progression, fibrosis, and other pathological conditions. To bridge this gap, we construct a polarization imaging system and curate a new dataset of over 13,000 paired Polar-H&E images. Visualizations of polarization properties reveal distinctive optical signatures in pathological tissues, underscoring its diagnostic value. Building on this dataset, we propose PolarHE, a dual-modality fusion framework that integrates H&E with polarization imaging, leveraging the latter ability to enhance tissue characterization. Our approach employs a feature decomposition strategy to disentangle common and modality specific features, ensuring effective multimodal representation learning. Through comprehensive validation, our approach significantly outperforms previous methods, achieving an accuracy of 86.70% on the Chaoyang dataset and 89.06% on the MHIST dataset. These results demonstrate that polarization imaging is a powerful and underutilized modality in computational pathology, enriching feature representation and improving diagnostic accuracy. PolarHE establishes a promising direction for multimodal learning, paving the way for more interpretable and generalizable pathology models.

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.

Rapid progress in computational pathology is increasingly driven by vision foundation models pretrained on vast histopathology datasets. While recent efforts have prioritized training on an ever-larger amount of patches, we take an alternative approach focused on data diversity. Our foundation model, Athena, was initialized from a pretrained model and trained on just 115 million tissue patches, several times fewer than recent histopathology foundation models. Rather than relying on patch volume or complex sampling heuristics, we maximize data diversity by randomly selecting only a moderate number of patches per whole-slide image from our diverse internal repository, which spans multiple countries, institutions, and scanner types. Evaluated on a single patch-level benchmark and four slide-level downstream tasks (two molecular and two morphological), Athena approaches the state-of-the-art and even surpasses several models trained on substantially larger datasets. This indicates that diversity across whole-slide images, rather than patch quantity alone, drives learning in histopathology foundation models.

The field of computational pathology has been transformed with recent advances in foundation models that encode histopathology region-of-interests (ROIs) into versatile and transferable feature representations via self-supervised learning (SSL). However, translating these advancements to address complex clinical challenges at the patient and slide level remains constrained by limited clinical data in disease-specific cohorts, especially for rare clinical conditions. We propose TITAN, a multimodal whole slide foundation model pretrained using 335,645 WSIs via visual self-supervised learning and vision-language alignment with corresponding pathology reports and 423,122 synthetic captions generated from a multimodal generative AI copilot for pathology. Without any finetuning or requiring clinical labels, TITAN can extract general-purpose slide representations and generate pathology reports that generalize to resource-limited clinical scenarios such as rare disease retrieval and cancer prognosis. We evaluate TITAN on diverse clinical tasks and find that TITAN outperforms both ROI and slide foundation models across machine learning settings such as linear probing, few-shot and zero-shot classification, rare cancer retrieval and cross-modal retrieval, and pathology report generation.

Throughout the different phases of a drug development program, randomized trials are used to establish the tolerability, safety, and efficacy of a candidate drug. At each stage one aims to optimize the design of future studies by extrapolation from the available evidence at the time. This includes collected trial data and relevant external data. However, relevant external data are typically available as averages only, for example from trials on alternative treatments reported in the literature. Here we report on such an example from a drug development for wet age-related macular degeneration. This disease is the leading cause of severe vision loss in the elderly. While current treatment options are efficacious, they are also a substantial burden for the patient. Hence, new treatments are under development which need to be compared against existing treatments. The general statistical problem this leads to is meta-analysis, which addresses the question of how we can combine datasets collected under different conditions. Bayesian methods have long been used to achieve partial pooling. Here we consider the challenge when the model of interest is complex (hierarchical and nonlinear) and one dataset is given as raw data while the second dataset is given as averages only. In such a situation, common meta-analytic methods can only be applied when the model is sufficiently simple for analytic approaches. When the model is too complex, for example nonlinear, an analytic approach is not possible. We provide a Bayesian solution by using simulation to approximately reconstruct the likelihood of the external summary and allowing the parameters in the model to vary under the different conditions. We first evaluate our approach using fake-data simulations and then report results for the drug development program that motivated this research.

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.

Deep learning brought boosts to auto diabetic retinopathy (DR) diagnosis, thus, greatly helping ophthalmologists for early disease detection, which contributes to preventing disease deterioration that may eventually lead to blindness. It has been proved that convolutional neural network (CNN)-aided lesion identifying or segmentation benefits auto DR screening. The key to fine-grained lesion tasks mainly lies in: (1) extracting features being both sensitive to tiny lesions and robust against DR-irrelevant interference, and (2) exploiting and re-using encoded information to restore lesion locations under extremely imbalanced data distribution. To this end, we propose a CNN-based DR diagnosis network with attention mechanism involved, termed lesion-aware network, to better capture lesion information from imbalanced data. Specifically, we design the lesion-aware module (LAM) to capture noise-like lesion areas across deeper layers, and the feature-preserve module (FPM) to assist shallow-to-deep feature fusion. Afterward, the proposed lesion-aware network (LANet) is constructed by embedding the LAM and FPM into the CNN decoders for DR-related information utilization. The proposed LANet is then further extended to a DR screening network by adding a classification layer. Through experiments on three public fundus datasets with pixel-level annotations, our method outperforms the mainstream methods with an area under curve of 0.967 in DR screening, and increases the overall average precision by 7.6%, 2.1%, and 1.2% in lesion segmentation on three datasets. Besides, the ablation study validates the effectiveness of the proposed sub-modules.

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.

Immunohistochemistry (IHC) provides information on protein expression in tissue sections and is commonly used to support pathology diagnosis and disease triage. While AI models for H\&E-stained slides show promise, their applicability to IHC is limited due to domain-specific variations. Here we introduce HPA10M, a dataset that contains 10,495,672 IHC images from the Human Protein Atlas with comprehensive metadata included, and encompasses 45 normal tissue types and 20 major cancer types. Based on HPA10M, we trained iSight, a multi-task learning framework for automated IHC staining assessment. iSight combines visual features from whole-slide images with tissue metadata through a token-level attention mechanism, simultaneously predicting staining intensity, location, quantity, tissue type, and malignancy status. On held-out data, iSight achieved 85.5\% accuracy for location, 76.6\% for intensity, and 75.7\% for quantity, outperforming fine-tuned foundation models (PLIP, CONCH) by 2.5--10.2\%. In addition, iSight demonstrates well-calibrated predictions with expected calibration errors of 0.0150-0.0408. Furthermore, in a user study with eight pathologists evaluating 200 images from two datasets, iSight outperformed initial pathologist assessments on the held-out HPA dataset (79\% vs 68\% for location, 70\% vs 57\% for intensity, 68\% vs 52\% for quantity). Inter-pathologist agreement also improved after AI assistance in both held-out HPA (Cohen's κ increased from 0.63 to 0.70) and Stanford TMAD datasets (from 0.74 to 0.76), suggesting expert--AI co-assessment can improve IHC interpretation. This work establishes a foundation for AI systems that can improve IHC diagnostic accuracy and highlights the potential for integrating iSight into clinical workflows to enhance the consistency and reliability of IHC assessment.

Artificial intelligence (AI) has become a fundamental tool for assisting clinicians in analyzing ophthalmic images, such as optical coherence tomography (OCT). However, developing AI models often requires extensive annotation, and existing models tend to underperform on independent, unseen data. Foundation models (FMs), large AI models trained on vast unlabeled datasets, have shown promise in overcoming these challenges. Nonetheless, available FMs for ophthalmology lack extensive validation, especially for segmentation tasks, and focus on a single imaging modality. In this context, we propose MIRAGE, a novel multimodal FM for the analysis of OCT and scanning laser ophthalmoscopy (SLO) images. Additionally, we propose a new evaluation benchmark with OCT/SLO classification and segmentation tasks. The comparison with general and specialized FMs and segmentation methods shows the superiority of MIRAGE in both types of tasks, highlighting its suitability as a basis for the development of robust AI systems for retinal OCT image analysis. Both MIRAGE and the evaluation benchmark are publicly available: https://github.com/j-morano/MIRAGE.

Pathological diagnosis remains the definitive standard for identifying tumors. The rise of multimodal large models has simplified the process of integrating image analysis with textual descriptions. Despite this advancement, the substantial costs associated with training and deploying these complex multimodal models, together with a scarcity of high-quality training datasets, create a significant divide between cutting-edge technology and its application in the clinical setting. We had meticulously compiled a dataset of approximately 45,000 cases, covering over 6 different tasks, including the classification of organ tissues, generating pathology report descriptions, and addressing pathology-related questions and answers. We have fine-tuned multimodal large models, specifically LLaVA, Qwen-VL, InternLM, with this dataset to enhance instruction-based performance. We conducted a qualitative assessment of the capabilities of the base model and the fine-tuned model in performing image captioning and classification tasks on the specific dataset. The evaluation results demonstrate that the fine-tuned model exhibits proficiency in addressing typical pathological questions. We hope that by making both our models and datasets publicly available, they can be valuable to the medical and research communities.

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.

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.

The complexity and variability inherent in high-resolution pathological images present significant challenges in computational pathology. While pathology foundation models leveraging AI have catalyzed transformative advancements, their development demands large-scale datasets, considerable storage capacity, and substantial computational resources. Furthermore, ensuring their clinical applicability and generalizability requires rigorous validation across a broad spectrum of clinical tasks. Here, we present PathOrchestra, a versatile pathology foundation model trained via self-supervised learning on a dataset comprising 300K pathological slides from 20 tissue and organ types across multiple centers. The model was rigorously evaluated on 112 clinical tasks using a combination of 61 private and 51 public datasets. These tasks encompass digital slide preprocessing, pan-cancer classification, lesion identification, multi-cancer subtype classification, biomarker assessment, gene expression prediction, and the generation of structured reports. PathOrchestra demonstrated exceptional performance across 27,755 WSIs and 9,415,729 ROIs, achieving over 0.950 accuracy in 47 tasks, including pan-cancer classification across various organs, lymphoma subtype diagnosis, and bladder cancer screening. Notably, it is the first model to generate structured reports for high-incidence colorectal cancer and diagnostically complex lymphoma-areas that are infrequently addressed by foundational models but hold immense clinical potential. Overall, PathOrchestra exemplifies the feasibility and efficacy of a large-scale, self-supervised pathology foundation model, validated across a broad range of clinical-grade tasks. Its high accuracy and reduced reliance on extensive data annotation underline its potential for clinical integration, offering a pathway toward more efficient and high-quality medical services.

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.

Optical coherence tomography angiography (OCTA) is a novel imaging modality that has been widely utilized in ophthalmology and neuroscience studies to observe retinal vessels and microvascular systems. However, publicly available OCTA datasets remain scarce. In this paper, we introduce the largest and most comprehensive OCTA dataset dubbed OCTA-500, which contains OCTA imaging under two fields of view (FOVs) from 500 subjects. The dataset provides rich images and annotations including two modalities (OCT/OCTA volumes), six types of projections, four types of text labels (age / gender / eye / disease) and seven types of segmentation labels (large vessel/capillary/artery/vein/2D FAZ/3D FAZ/retinal layers). Then, we propose a multi-object segmentation task called CAVF, which integrates capillary segmentation, artery segmentation, vein segmentation, and FAZ segmentation under a unified framework. In addition, we optimize the 3D-to-2D image projection network (IPN) to IPN-V2 to serve as one of the segmentation baselines. Experimental results demonstrate that IPN-V2 achieves an ~10% mIoU improvement over IPN on CAVF task. Finally, we further study the impact of several dataset characteristics: the training set size, the model input (OCT/OCTA, 3D volume/2D projection), the baseline networks, and the diseases. The dataset and code are publicly available at: https://ieee-dataport.org/open-access/octa-500.

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).

Vision disorders significantly impact millions of lives, altering how visual information is processed and perceived. In this work, a computational framework was developed using the BrokenEyes system to simulate five common eye disorders: Age-related macular degeneration, cataract, glaucoma, refractive errors, and diabetic retinopathy and analyze their effects on neural-like feature representations in deep learning models. Leveraging a combination of human and non-human datasets, models trained under normal and disorder-specific conditions revealed critical disruptions in feature maps, particularly for cataract and glaucoma, which align with known neural processing challenges in these conditions. Evaluation metrics such as activation energy and cosine similarity quantified the severity of these distortions, providing insights into the interplay between degraded visual inputs and learned representations.

Current fundus image analysis models are predominantly built for specific tasks relying on individual datasets. The learning process is usually based on data-driven paradigm without prior knowledge, resulting in poor transferability and generalizability. To address this issue, we propose MM-Retinal, a multi-modal dataset that encompasses high-quality image-text pairs collected from professional fundus diagram books. Moreover, enabled by MM-Retinal, we present a novel Knowledge-enhanced foundational pretraining model which incorporates Fundus Image-Text expertise, called KeepFIT. It is designed with image similarity-guided text revision and mixed training strategy to infuse expert knowledge. Our proposed fundus foundation model achieves state-of-the-art performance across six unseen downstream tasks and holds excellent generalization ability in zero-shot and few-shot scenarios. MM-Retinal and KeepFIT are available at https://github.com/lxirich/MM-Retinal.

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.

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.

Foundation models have recently achieved impressive success in computational pathology, demonstrating strong generalization across diverse histopathology tasks. However, existing models overlook the heterogeneous and non-uniform organization of pathological regions of interest (ROIs) because they rely on natural image backbones not tailored for tissue morphology. Consequently, they often fail to capture the coherent tissue architecture beyond isolated patches, limiting interpretability and clinical relevance. To address these challenges, we present Cross-modal Adaptive Region Encoder (CARE), a foundation model for pathology that automatically partitions WSIs into several morphologically relevant regions. Specifically, CARE employs a two-stage pretraining strategy: (1) a self-supervised unimodal pretraining stage that learns morphological representations from 34,277 whole-slide images (WSIs) without segmentation annotations, and (2) a cross-modal alignment stage that leverages RNA and protein profiles to refine the construction and representation of adaptive regions. This molecular guidance enables CARE to identify biologically relevant patterns and generate irregular yet coherent tissue regions, selecting the most representative area as ROI. CARE supports a broad range of pathology-related tasks, using either the ROI feature or the slide-level feature obtained by aggregating adaptive regions. Based on only one-tenth of the pretraining data typically used by mainstream foundation models, CARE achieves superior average performance across 33 downstream benchmarks, including morphological classification, molecular prediction, and survival analysis, and outperforms other foundation model baselines overall.

The VIP Cup offers a unique experience to undergraduates, allowing students to work together to solve challenging, real-world problems with video and image processing techniques. In this iteration of the VIP Cup, we challenged students to balance personalization and generalization when performing biomarker detection in 3D optical coherence tomography (OCT) images. Balancing personalization and generalization is an important challenge to tackle, as the variation within OCT scans of patients between visits can be minimal while the difference in manifestation of the same disease across different patients may be substantial. The domain difference between OCT scans can arise due to pathology manifestation across patients, clinical labels, and the visit along the treatment process when the scan is taken. Hence, we provided a multimodal OCT dataset to allow teams to effectively target this challenge. Overall, this competition gave undergraduates an opportunity to learn about how artificial intelligence can be a powerful tool for the medical field, as well as the unique challenges one faces when applying machine learning to biomedical data.

Multiple Instance learning (MIL) models have been extensively used in pathology to predict biomarkers and risk-stratify patients from gigapixel-sized images. Machine learning problems in medical imaging often deal with rare diseases, making it important for these models to work in a label-imbalanced setting. In pathology images, there is another level of imbalance, where given a positively labeled Whole Slide Image (WSI), only a fraction of pixels within it contribute to the positive label. This compounds the severity of imbalance and makes imbalanced classification in pathology challenging. Furthermore, these imbalances can occur in out-of-distribution (OOD) datasets when the models are deployed in the real-world. We leverage the idea that decoupling feature and classifier learning can lead to improved decision boundaries for label imbalanced datasets. To this end, we investigate the integration of supervised contrastive learning with multiple instance learning (SC-MIL). Specifically, we propose a joint-training MIL framework in the presence of label imbalance that progressively transitions from learning bag-level representations to optimal classifier learning. We perform experiments with different imbalance settings for two well-studied problems in cancer pathology: subtyping of non-small cell lung cancer and subtyping of renal cell carcinoma. SC-MIL provides large and consistent improvements over other techniques on both in-distribution (ID) and OOD held-out sets across multiple imbalanced settings.

Structural changes in retinal blood vessels are critical biomarkers for the onset and progression of glaucoma and other ocular diseases. However, current vessel segmentation approaches largely rely on supervised learning and extensive manual annotations, which are costly, error-prone, and difficult to obtain in optical coherence tomography angiography. Here we present BioVessel-Net, an unsupervised generative framework that integrates vessel biostatistics with adversarial refinement and a radius-guided segmentation strategy. Unlike pixel-based methods, BioVessel-Net directly models vascular structures with biostatistical coherence, achieving accurate and explainable vessel extraction without labeled data or high-performance computing. To support training and evaluation, we introduce RetinaMix, a new benchmark dataset of 2D and 3D OCTA images with high-resolution vessel details from diverse populations. Experimental results demonstrate that BioVessel-Net achieves near-perfect segmentation accuracy across RetinaMix and existing datasets, substantially outperforming state-of-the-art supervised and semi-supervised methods. Together, BioVessel-Net and RetinaMix provide a label-free, computationally efficient, and clinically interpretable solution for retinal vessel analysis, with broad potential for glaucoma monitoring, blood flow modeling, and progression prediction. Code and dataset are available: https://github.com/VikiXie/SatMar8.

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).

Histopathology plays a central role in clinical medicine and biomedical research. While artificial intelligence shows promising results on many pathological tasks, generalization and dealing with rare diseases, where training data is scarce, remains a challenge. Distilling knowledge from unlabeled data into a foundation model before learning from, potentially limited, labeled data provides a viable path to address these challenges. In this work, we extend the state of the art of foundation models for digital pathology whole slide images by semi-automated data curation and incorporating pathologist domain knowledge. Specifically, we combine computational and pathologist domain knowledge (1) to curate a diverse dataset of 103k slides corresponding to 750 million image patches covering data from different fixation, staining, and scanning protocols as well as data from different indications and labs across the EU and US, (2) for grouping semantically similar slides and tissue patches, and (3) to augment the input images during training. We evaluate the resulting model on a set of public and internal benchmarks and show that although our foundation model is trained with an order of magnitude less slides, it performs on par or better than competing models. We expect that scaling our approach to more data and larger models will further increase its performance and capacity to deal with increasingly complex real world tasks in diagnostics and biomedical research.

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.

The development of vision-language models (VLMs) is driven by large-scale and diverse multimodal datasets. However, progress toward generalist biomedical VLMs is limited by the lack of annotated, publicly accessible datasets across biology and medicine. Existing efforts are restricted to narrow domains, missing the full diversity of biomedical knowledge encoded in scientific literature. To address this gap, we introduce BIOMEDICA, a scalable, open-source framework to extract, annotate, and serialize the entirety of the PubMed Central Open Access subset into an easy-to-use, publicly accessible dataset.Our framework produces a comprehensive archive with over 24 million unique image-text pairs from over 6 million articles. Metadata and expert-guided annotations are also provided. We demonstrate the utility and accessibility of our resource by releasing BMCA-CLIP, a suite of CLIP-style models continuously pre-trained on the BIOMEDICA dataset via streaming, eliminating the need to download 27 TB of data locally.On average, our models achieve state-of-the-art performance across 40 tasks - spanning pathology, radiology, ophthalmology, dermatology, surgery, molecular biology, parasitology, and cell biology - excelling in zero-shot classification with a 6.56% average improvement (as high as 29.8% and 17.5% in dermatology and ophthalmology, respectively), and stronger image-text retrieval, all while using 10x less compute. To foster reproducibility and collaboration, we release our codebase and dataset for the broader research community.

Foundation models trained with self-supervised learning (SSL) on large-scale histological images have significantly accelerated the development of computational pathology. These models can serve as backbones for region-of-interest (ROI) image analysis or patch-level feature extractors in whole-slide images (WSIs) based on multiple instance learning (MIL). Existing pathology foundation models (PFMs) are typically pre-trained on Hematoxylin-Eosin (H&E) stained pathology images. However, images with special stains, such as immunohistochemistry, are also frequently used in clinical practice. PFMs pre-trained mainly on H\&E-stained images may be limited in clinical applications involving special stains. To address this issue, we propose StainNet, a specialized foundation model for special stains based on the vision transformer (ViT) architecture. StainNet adopts a self-distillation SSL approach and is trained on over 1.4 million patch images cropping from 20,231 publicly available special staining WSIs in the HISTAI database. To evaluate StainNet, we conduct experiments on an in-house slide-level liver malignancy classification task and two public ROI-level datasets to demonstrate its strong ability. We also perform few-ratio learning and retrieval evaluations, and compare StainNet with recently larger PFMs to further highlight its strengths. We have released the StainNet model weights at: https://huggingface.co/JWonderLand/StainNet.

Recent breakthroughs in self-supervised learning have enabled the use of large unlabeled datasets to train visual foundation models that can generalize to a variety of downstream tasks. While this training paradigm is well suited for the medical domain where annotations are scarce, large-scale pre-training in the medical domain, and in particular pathology, has not been extensively studied. Previous work in self-supervised learning in pathology has leveraged smaller datasets for both pre-training and evaluating downstream performance. The aim of this project is to train the largest academic foundation model and benchmark the most prominent self-supervised learning algorithms by pre-training and evaluating downstream performance on large clinical pathology datasets. We collected the largest pathology dataset to date, consisting of over 3 billion images from over 423 thousand microscopy slides. We compared pre-training of visual transformer models using the masked autoencoder (MAE) and DINO algorithms. We evaluated performance on six clinically relevant tasks from three anatomic sites and two institutions: breast cancer detection, inflammatory bowel disease detection, breast cancer estrogen receptor prediction, lung adenocarcinoma EGFR mutation prediction, and lung cancer immunotherapy response prediction. Our results demonstrate that pre-training on pathology data is beneficial for downstream performance compared to pre-training on natural images. Additionally, the DINO algorithm achieved better generalization performance across all tasks tested. The presented results signify a phase change in computational pathology research, paving the way into a new era of more performant models based on large-scale, parallel pre-training at the billion-image scale.

Optical Coherence Tomography Angiography (OCTA) and its derived en-face projections provide high-resolution visualization of the retinal and choroidal vasculature, which is critical for the rapid and accurate diagnosis of retinal diseases. However, acquiring high-quality OCTA images is challenging due to motion sensitivity and the high costs associated with software modifications for conventional OCT devices. Moreover, current deep learning methods for OCT-to-OCTA translation often overlook the vascular differences across retinal layers and struggle to reconstruct the intricate, dense vascular details necessary for reliable diagnosis. To overcome these limitations, we propose XOCT, a novel deep learning framework that integrates Cross-Dimensional Supervision (CDS) with a Multi-Scale Feature Fusion (MSFF) network for layer-aware vascular reconstruction. Our CDS module leverages 2D layer-wise en-face projections, generated via segmentation-weighted z-axis averaging, as supervisory signals to compel the network to learn distinct representations for each retinal layer through fine-grained, targeted guidance. Meanwhile, the MSFF module enhances vessel delineation through multi-scale feature extraction combined with a channel reweighting strategy, effectively capturing vascular details at multiple spatial scales. Our experiments on the OCTA-500 dataset demonstrate XOCT's improvements, especially for the en-face projections which are significant for clinical evaluation of retinal pathologies, underscoring its potential to enhance OCTA accessibility, reliability, and diagnostic value for ophthalmic disease detection and monitoring. The code is available at https://github.com/uci-cbcl/XOCT.

Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis suffers from limited reproducibility and diagnostic variability. To overcome these limitations, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on over 353 million multi-scale images from 210,043 H&E-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, protein expression status prediction, gene mutation prediction, and prognosis evaluation. We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.70% sensitivity across nine independent medical institutions. This work not only advances AI-driven precision pathology for GI diseases but also bridge critical gaps in histopathological practice.

Application of deep learning on histopathological whole slide images (WSIs) holds promise of improving diagnostic efficiency and reproducibility but is largely dependent on the ability to write computer code or purchase commercial solutions. We present a code-free pipeline utilizing free-to-use, open-source software (QuPath, DeepMIB, and FastPathology) for creating and deploying deep learning-based segmentation models for computational pathology. We demonstrate the pipeline on a use case of separating epithelium from stroma in colonic mucosa. A dataset of 251 annotated WSIs, comprising 140 hematoxylin-eosin (HE)-stained and 111 CD3 immunostained colon biopsy WSIs, were developed through active learning using the pipeline. On a hold-out test set of 36 HE and 21 CD3-stained WSIs a mean intersection over union score of 96.6% and 95.3% was achieved on epithelium segmentation. We demonstrate pathologist-level segmentation accuracy and clinical acceptable runtime performance and show that pathologists without programming experience can create near state-of-the-art segmentation solutions for histopathological WSIs using only free-to-use software. The study further demonstrates the strength of open-source solutions in its ability to create generalizable, open pipelines, of which trained models and predictions can seamlessly be exported in open formats and thereby used in external solutions. All scripts, trained models, a video tutorial, and the full dataset of 251 WSIs with ~31k epithelium annotations are made openly available at https://github.com/andreped/NoCodeSeg to accelerate research in the field.

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.

Task-specific deep learning models in histopathology offer promising opportunities for improving diagnosis, clinical research, and precision medicine. However, development of such models is often limited by availability of high-quality data. Foundation models in histopathology that learn general representations across a wide range of tissue types, diagnoses, and magnifications offer the potential to reduce the data, compute, and technical expertise necessary to develop task-specific deep learning models with the required level of model performance. In this work, we describe the development and evaluation of foundation models for histopathology via self-supervised learning (SSL). We first establish a diverse set of benchmark tasks involving 17 unique tissue types and 12 unique cancer types and spanning different optimal magnifications and task types. Next, we use this benchmark to explore and evaluate histopathology-specific SSL methods followed by further evaluation on held out patch-level and weakly supervised tasks. We found that standard SSL methods thoughtfully applied to histopathology images are performant across our benchmark tasks and that domain-specific methodological improvements can further increase performance. Our findings reinforce the value of using domain-specific SSL methods in pathology, and establish a set of high quality foundation models to enable further research across diverse applications.

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.

Histopathological cancer diagnostics has become more complex, and the increasing number of biopsies is a challenge for most pathology laboratories. Thus, development of automatic methods for evaluation of histopathological cancer sections would be of value. In this study, we used 624 whole slide images (WSIs) of breast cancer from a Norwegian cohort. We propose a cascaded convolutional neural network design, called H2G-Net, for semantic segmentation of gigapixel histopathological images. The design involves a detection stage using a patch-wise method, and a refinement stage using a convolutional autoencoder. To validate the design, we conducted an ablation study to assess the impact of selected components in the pipeline on tumour segmentation. Guiding segmentation, using hierarchical sampling and deep heatmap refinement, proved to be beneficial when segmenting the histopathological images. We found a significant improvement when using a refinement network for postprocessing the generated tumour segmentation heatmaps. The overall best design achieved a Dice score of 0.933 on an independent test set of 90 WSIs. The design outperformed single-resolution approaches, such as cluster-guided, patch-wise high-resolution classification using MobileNetV2 (0.872) and a low-resolution U-Net (0.874). In addition, segmentation on a representative x400 WSI took ~58 seconds, using only the CPU. The findings demonstrate the potential of utilizing a refinement network to improve patch-wise predictions. The solution is efficient and does not require overlapping patch inference or ensembling. Furthermore, we showed that deep neural networks can be trained using a random sampling scheme that balances on multiple different labels simultaneously, without the need of storing patches on disk. Future work should involve more efficient patch generation and sampling, as well as improved clustering.

Pathology, the microscopic examination of diseased tissue, is critical for diagnosing various medical conditions, particularly cancers. Traditional methods are labor-intensive and prone to human error. Digital pathology, which converts glass slides into high-resolution digital images for analysis by computer algorithms, revolutionizes the field by enhancing diagnostic accuracy, consistency, and efficiency through automated image analysis and large-scale data processing. Foundational transformer pretraining is crucial for developing robust, generalizable models as it enables learning from vast amounts of unannotated data. This paper introduces the Hibou family of foundational vision transformers for pathology, leveraging the DINOv2 framework to pretrain two model variants, Hibou-B and Hibou-L, on a proprietary dataset of over 1 million whole slide images (WSIs) representing diverse tissue types and staining techniques. Our pretrained models demonstrate superior performance on both patch-level and slide-level benchmarks, surpassing existing state-of-the-art methods. Notably, Hibou-L achieves the highest average accuracy across multiple benchmark datasets. To support further research and application in the field, we have open-sourced the Hibou-B model, which can be accessed at https://github.com/HistAI/hibou

Single cell analysis of human skeletal muscle (SM) tissue cross-sections is a fundamental tool for understanding many neuromuscular disorders. For this analysis to be reliable and reproducible, identification of individual fibres within microscopy images (segmentation) of SM tissue should be automatic and precise. Biomedical scientists in this field currently rely on custom tools and general machine learning (ML) models, both followed by labour intensive and subjective manual interventions to fine-tune segmentation. We believe that fully automated, precise, reproducible segmentation is possible by training ML models. However, in this important biomedical domain, there are currently no good quality, publicly available annotated imaging datasets available for ML model training. In this paper we release NCL-SM: a high quality bioimaging dataset of 46 human SM tissue cross-sections from both healthy control subjects and from patients with genetically diagnosed muscle pathology. These images include > 50k manually segmented muscle fibres (myofibres). In addition we also curated high quality myofibre segmentations, annotating reasons for rejecting low quality myofibres and low quality regions in SM tissue images, making these annotations completely ready for downstream analysis. This, we believe, will pave the way for development of a fully automatic pipeline that identifies individual myofibres within images of tissue sections and, in particular, also classifies individual myofibres that are fit for further analysis.

Histology review is often used as the `gold standard' for disease diagnosis. Computer aided diagnosis tools can potentially help improve current pathology workflows by reducing examination time and interobserver variability. Previous work in cancer grading has focused mainly on classifying pre-defined regions of interest (ROIs), or relied on large amounts of fine-grained labels. In this paper, we propose a two-stage attention-based multiple instance learning model for slide-level cancer grading and weakly-supervised ROI detection and demonstrate its use in prostate cancer. Compared with existing Gleason classification models, our model goes a step further by utilizing visualized saliency maps to select informative tiles for fine-grained grade classification. The model was primarily developed on a large-scale whole slide dataset consisting of 3,521 prostate biopsy slides with only slide-level labels from 718 patients. The model achieved state-of-the-art performance for prostate cancer grading with an accuracy of 85.11\% for classifying benign, low-grade (Gleason grade 3+3 or 3+4), and high-grade (Gleason grade 4+3 or higher) slides on an independent test set.

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.

Intraoperative pathology is pivotal to precision surgery, yet its clinical impact is constrained by diagnostic complexity and the limited availability of high-quality frozen-section data. While computational pathology has made significant strides, the lack of large-scale, prospective validation has impeded its routine adoption in surgical workflows. Here, we introduce CRISP, a clinical-grade foundation model developed on over 100,000 frozen sections from eight medical centers, specifically designed to provide Clinical-grade Robust Intraoperative Support for Pathology (CRISP). CRISP was comprehensively evaluated on more than 15,000 intraoperative slides across nearly 100 retrospective diagnostic tasks, including benign-malignant discrimination, key intraoperative decision-making, and pan-cancer detection, etc. The model demonstrated robust generalization across diverse institutions, tumor types, and anatomical sites-including previously unseen sites and rare cancers. In a prospective cohort of over 2,000 patients, CRISP sustained high diagnostic accuracy under real-world conditions, directly informing surgical decisions in 92.6% of cases. Human-AI collaboration further reduced diagnostic workload by 35%, avoided 105 ancillary tests and enhanced detection of micrometastases with 87.5% accuracy. Together, these findings position CRISP as a clinical-grade paradigm for AI-driven intraoperative pathology, bridging computational advances with surgical precision and accelerating the translation of artificial intelligence into routine clinical practice.

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.

With the advent of smartphone indirect ophthalmoscopy, teleophthalmology - the use of specialist ophthalmology assets at a distance from the patient - has experienced a breakthrough, promising enormous benefits especially for healthcare in distant, inaccessible or opthalmologically underserved areas, where specialists are either unavailable or too few in number. However, accurate teleophthalmology requires high-quality ophthalmoscopic imagery. This paper considers three feature families - statistical metrics, gradient-based metrics and wavelet transform coefficient derived indicators - as possible metrics to identify unsharp or blurry images. By using standard machine learning techniques, the suitability of these features for image quality assessment is confirmed, albeit on a rather small data set. With the increased availability and decreasing cost of digital ophthalmoscopy on one hand and the increased prevalence of diabetic retinopathy worldwide on the other, creating tools that can determine whether an image is likely to be diagnostically suitable can play a significant role in accelerating and streamlining the teleophthalmology process. This paper highlights the need for more research in this area, including the compilation of a diverse database of ophthalmoscopic imagery, annotated with quality markers, to train the Point of Acquisition error detection algorithms of the future.

Pathology is the study of microscopic inspection of tissue, and a pathology diagnosis is often the medical gold standard to diagnose disease. Pathology images provide a unique challenge for computer-vision-based analysis: a single pathology Whole Slide Image (WSI) is gigapixel-sized and often contains hundreds of thousands to millions of objects of interest across multiple resolutions. In this work, we propose PathoLogy Universal TransfOrmer (PLUTO): a light-weight pathology FM that is pre-trained on a diverse dataset of 195 million image tiles collected from multiple sites and extracts meaningful representations across multiple WSI scales that enable a large variety of downstream pathology tasks. In particular, we design task-specific adaptation heads that utilize PLUTO's output embeddings for tasks which span pathology scales ranging from subcellular to slide-scale, including instance segmentation, tile classification, and slide-level prediction. We compare PLUTO's performance to other state-of-the-art methods on a diverse set of external and internal benchmarks covering multiple biologically relevant tasks, tissue types, resolutions, stains, and scanners. We find that PLUTO matches or outperforms existing task-specific baselines and pathology-specific foundation models, some of which use orders-of-magnitude larger datasets and model sizes when compared to PLUTO. Our findings present a path towards a universal embedding to power pathology image analysis, and motivate further exploration around pathology foundation models in terms of data diversity, architectural improvements, sample efficiency, and practical deployability in real-world applications.

The advancement of Large Vision-Language Models (LVLMs) has propelled their application in the medical field. However, Medical LVLMs (Med-LVLMs) encounter factuality challenges due to modality misalignment, where the models prioritize textual knowledge over visual input, leading to hallucinations that contradict information in medical images. Previous attempts to enhance modality alignment in Med-LVLMs through preference optimization have inadequately mitigated clinical relevance in preference data, making these samples easily distinguishable and reducing alignment effectiveness. To address this challenge, we propose MMedPO, a novel multimodal medical preference optimization approach that considers the clinical relevance of preference samples to enhance Med-LVLM alignment. MMedPO curates multimodal preference data by introducing two types of dispreference: (1) plausible hallucinations injected through target Med-LVLMs or GPT-4o to produce medically inaccurate responses, and (2) lesion region neglect achieved through local lesion-noising, disrupting visual understanding of critical areas. We then calculate clinical relevance for each sample based on scores from multiple Med-LLMs and visual tools, and integrate these scores into the preference optimization process as weights, enabling effective alignment. Our experiments demonstrate that MMedPO significantly enhances factual accuracy in Med-LVLMs, achieving substantial improvements over existing preference optimization methods by averaging 14.2% and 51.7% across the Med-VQA and report generation tasks. Our code are available in https://github.com/aiming-lab/MMedPO.

Multimodal large language models (MLLMs) have recently demonstrated remarkable reasoning abilities with reinforcement learning paradigm. Although several multimodal reasoning models have been explored in the medical domain, most of them focus exclusively on basic reasoning, which refers to shallow inference based on visual feature matching. However, real-world clinical diagnosis extends beyond basic reasoning, demanding reasoning processes that integrate heterogeneous clinical information (such as chief complaints and medical history) with multimodal medical imaging data. To bridge this gap, we introduce MM-Retinal-Reason, the first ophthalmic multimodal dataset with the full spectrum of perception and reasoning. It encompasses both basic reasoning tasks and complex reasoning tasks, aiming to enhance visual-centric fundamental reasoning capabilities and emulate realistic clinical thinking patterns. Building upon MM-Retinal-Reason, we propose OphthaReason, the first ophthalmology-specific multimodal reasoning model with step-by-step reasoning traces. To enable flexible adaptation to both basic and complex reasoning tasks, we specifically design a novel method called Uncertainty-Aware Dynamic Thinking (UADT), which estimates sample-level uncertainty via entropy and dynamically modulates the model's exploration depth using a shaped advantage mechanism. Comprehensive experiments demonstrate that our model achieves state-of-the-art performance on both basic and complex reasoning tasks, outperforming general-purpose MLLMs, medical MLLMs, RL-based medical MLLMs, and ophthalmic MLLMs by at least 24.92\%, 15.00\%, 21.20\%, and 17.66\%. Project Page: https://github.com/lxirich/OphthaReason{link}.

In this paper we present a hybrid method for the automatic detection of dermatological pathologies in medical reports. We use a large language model combined with medical ontologies to predict, given a first appointment or follow-up medical report, the pathology a person may suffer from. The results show that teaching the model to learn the type, severity and location on the body of a dermatological pathology, as well as in which order it has to learn these three features, significantly increases its accuracy. The article presents the demonstration of state-of-the-art results for classification of medical texts with a precision of 0.84, micro and macro F1-score of 0.82 and 0.75, and makes both the method and the data set used available to the community.