Daily Papers

The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using 62,876 CFPs from 44,501 unique participants from the UK Biobank, DL models were trained to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability.

Retinal foundation models have significantly advanced retinal image analysis by leveraging self-supervised learning to reduce dependence on labeled data while achieving strong generalization. Many recent approaches enhance retinal image understanding using report supervision, but obtaining clinical reports is often costly and challenging. In contrast, metadata (e.g., age, gender) is widely available and serves as a valuable resource for analyzing disease progression. To effectively incorporate patient-specific information, we propose PRETI, a retinal foundation model that integrates metadata-aware learning with robust self-supervised representation learning. We introduce Learnable Metadata Embedding (LME), which dynamically refines metadata representations. Additionally, we construct patient-level data pairs, associating images from the same individual to improve robustness against non-clinical variations. To further optimize retinal image representation, we propose Retina-Aware Adaptive Masking (RAAM), a strategy that selectively applies masking within the retinal region and dynamically adjusts the masking ratio during training. PRETI captures both global structures and fine-grained pathological details, resulting in superior diagnostic performance. Extensive experiments demonstrate that PRETI achieves state-of-the-art results across diverse diseases and biomarker predictions using in-house and public data, indicating the importance of metadata-guided foundation models in retinal disease analysis. Our code and pretrained model are available at https://github.com/MICV-yonsei/PRETI

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.

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 retina offers a noninvasive window into neurodegenerative disease, capturing subtle structural patterns associated with a risk of future cognitive decline. Vision-language alignment frameworks such as REVEAL have shown that pairing retinal fundus images with structured clinical risk narratives improves early prediction of Alzheimer's disease (AD). A key design choice in these approaches is the use of phenotypic grouping, where individuals with similar risk profiles are treated as multi-positive pairs during contrastive learning. However, existing methods operationalize phenotypic similarity as a discrete construct, relying on hard group assignments that impose rigid supervision and decouple group formation from representation learning. We propose a continuous formulation of phenotypic structure within contrastive learning. Rather than assigning samples to fixed clusters, we model inter-subject similarity as a differentiable weighting function derived from intra-modality embedding similarities in both retinal images and risk profiles. These weights define soft multi-positive relationships through a continuous aggregation operator, enabling graded supervision that reflects the spectrum nature of disease risk. We further introduce a soft-target contrastive objective that jointly learns cross-modal alignment and phenotypic structure in an end-to-end manner. Evaluated on UK Biobank retinal imaging data for incident AD prediction, the proposed framework consistently outperforms discrete group-based contrastive learning and standard vision-language baselines. By treating phenotypic similarity as a learnable, continuous signal rather than a fixed grouping rule, our approach provides a principled and robust foundation for population-scale neurodegenerative risk modeling from multi-modal retinal and clinical data.

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.

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

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.

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.

Purpose: This study introduces the first adaptation of RETFound for joint optic disc (OD) and optic cup (OC) segmentation. RETFound is a well-known foundation model developed for fundus camera and optical coherence tomography images, which has shown promising performance in disease diagnosis. Methods: We propose FunduSegmenter, a model integrating a series of novel modules with RETFound, including a Pre-adapter, a Decoder, a Post-adapter, skip connections with Convolutional Block Attention Module and a Vision Transformer block adapter. The model is evaluated on a proprietary dataset, GoDARTS, and four public datasets, IDRiD, Drishti-GS, RIM-ONE-r3, and REFUGE, through internal verification, external verification and domain generalization experiments. Results: An average Dice similarity coefficient of 90.51% was achieved in internal verification, which outperformed all baselines, some substantially (nnU-Net: 82.91%; DUNet: 89.17%; TransUNet: 87.91%). In all external verification experiments, the average results were about 3% higher than those of the best baseline, and our model was also competitive in domain generalization. Conclusions: This study explored the potential of the latent general representations learned by RETFound for OD and OC segmentation in fundus camera images. Our FunduSegmenter generally outperformed state-of-the-art baseline methods. The proposed modules are general and can be extended to fine-tuning other foundation models. Translational Relevance: The model shows strong stability and generalization on both in-distribution and out-of-distribution data, providing stable OD and OC segmentation. This is an essential step for many automated tasks, from setting the accurate retinal coordinate to biomarker discovery. The code and trained weights are available at: https://github.com/JusticeZzy/FunduSegmenter.

The retinal vasculature provides important clues in the diagnosis and monitoring of systemic diseases including hypertension and diabetes. The microvascular system is of primary involvement in such conditions, and the retina is the only anatomical site where the microvasculature can be directly observed. The objective assessment of retinal vessels has long been considered a surrogate biomarker for systemic vascular diseases, and with recent advancements in retinal imaging and computer vision technologies, this topic has become the subject of renewed attention. In this paper, we present a novel dataset, dubbed RAVIR, for the semantic segmentation of Retinal Arteries and Veins in Infrared Reflectance (IR) imaging. It enables the creation of deep learning-based models that distinguish extracted vessel type without extensive post-processing. We propose a novel deep learning-based methodology, denoted as SegRAVIR, for the semantic segmentation of retinal arteries and veins and the quantitative measurement of the widths of segmented vessels. Our extensive experiments validate the effectiveness of SegRAVIR and demonstrate its superior performance in comparison to state-of-the-art models. Additionally, we propose a knowledge distillation framework for the domain adaptation of RAVIR pretrained networks on color images. We demonstrate that our pretraining procedure yields new state-of-the-art benchmarks on the DRIVE, STARE, and CHASE_DB1 datasets. Dataset link: https://ravirdataset.github.io/data/

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.

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.

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.

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.

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

Identifying cell types and understanding their functional properties is crucial for unraveling the mechanisms underlying perception and cognition. In the retina, functional types can be identified by carefully selected stimuli, but this requires expert domain knowledge and biases the procedure towards previously known cell types. In the visual cortex, it is still unknown what functional types exist and how to identify them. Thus, for unbiased identification of the functional cell types in retina and visual cortex, new approaches are needed. Here we propose an optimization-based clustering approach using deep predictive models to obtain functional clusters of neurons using Most Discriminative Stimuli (MDS). Our approach alternates between stimulus optimization with cluster reassignment akin to an expectation-maximization algorithm. The algorithm recovers functional clusters in mouse retina, marmoset retina and macaque visual area V4. This demonstrates that our approach can successfully find discriminative stimuli across species, stages of the visual system and recording techniques. The resulting most discriminative stimuli can be used to assign functional cell types fast and on the fly, without the need to train complex predictive models or show a large natural scene dataset, paving the way for experiments that were previously limited by experimental time. Crucially, MDS are interpretable: they visualize the distinctive stimulus patterns that most unambiguously identify a specific type of neuron.

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.

Vital to primary visual processing, retinal circuitry shows many similar structures across a very broad array of species, both vertebrate and non-vertebrate, especially functional components such as lateral inhibition. This surprisingly conservative pattern raises a question of how evolution leads to it, and whether there is any alternative that can also prompt helpful preprocessing. Here we design a method using genetic algorithm that, with many degrees of freedom, leads to architectures whose functions are similar to biological retina, as well as effective alternatives that are different in structures and functions. We compare this model to natural evolution and discuss how our framework can come into goal-driven search and sustainable enhancement of neural network models in machine learning.

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

Glaucoma is 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.

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.

Redundancies and correlations in the responses of sensory neurons seem to waste neural resources but can carry cues about structured stimuli and may help the brain to correct for response errors. To assess how the retina negotiates this tradeoff, we measured simultaneous responses from populations of ganglion cells presented with natural and artificial stimuli that varied greatly in correlation structure. We found that pairwise correlations in the retinal output remained similar across stimuli with widely different spatio-temporal correlations including white noise and natural movies. Meanwhile, purely spatial correlations tended to increase correlations in the retinal response. Responding to more correlated stimuli, ganglion cells had faster temporal kernels and tended to have stronger surrounds. These properties of individual cells, along with gain changes that opposed changes in effective contrast at the ganglion cell input, largely explained the similarity of pairwise correlations across stimuli where receptive field measurements were possible.

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.

From a falcon detecting prey to humans recognizing faces, many species exhibit extraordinary abilities in rapid visual localization and classification. These are made possible by a specialized retinal region called the fovea, which provides high acuity at the center of vision while maintaining lower resolution in the periphery. This distinctive spatial organization, preserved along the early visual pathway through retinotopic mapping, is fundamental to biological vision, yet remains largely unexplored in machine learning. Our study investigates how incorporating foveated retinotopy may benefit deep convolutional neural networks (CNNs) in image classification tasks. By implementing a foveated retinotopic transformation in the input layer of standard ResNet models and re-training them, we maintain comparable classification accuracy while enhancing the network's robustness to scale and rotational perturbations. Although this architectural modification introduces increased sensitivity to fixation point shifts, we demonstrate how this apparent limitation becomes advantageous: variations in classification probabilities across different gaze positions serve as effective indicators for object localization. Our findings suggest that foveated retinotopic mapping encodes implicit knowledge about visual object geometry, offering an efficient solution to the visual search problem - a capability crucial for many living species.

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.

Automatic extraction of retinal vascular biomarkers from color fundus images (CFI) is crucial for large-scale studies of the retinal vasculature. We present VascX, an open-source Python toolbox that extracts biomarkers from CFI artery-vein segmentations. VascX starts from vessel segmentation masks, extracts their skeletons, builds undirected and directed vessel graphs, and resolves vessel segments into longer vessels. A comprehensive set of biomarkers is derived, including vascular density, central retinal equivalents (CREs), and tortuosity. Spatially localized biomarkers may be calculated over grids placed relative to the fovea and optic disc. VascX is released via GitHub and PyPI with comprehensive documentation and examples. Our test-retest reproducibility analysis on repeat imaging of the same eye by different devices shows that most VascX biomarkers have moderate to excellent agreement (ICC > 0.5), with important differences in the level of robustness of different biomarkers. Our analyses of biomarker sensitivity to image perturbations and heuristic parameter values support these differences and further characterize VascX biomarkers. Ultimately, VascX provides an explainable and easily modifiable feature-extraction toolbox that complements segmentation to produce reliable retinal vascular biomarkers. Our graph-based biomarker computation stages support reproducible, region-aware measurements suited for large-scale clinical and epidemiological research. By enabling easy extraction of existing biomarkers and rapid experimentation with new ones, VascX supports oculomics research. Its robustness and computational efficiency facilitate scalable deployment in large databases, while open-source distribution lowers barriers to adoption for ophthalmic researchers and clinicians.

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.

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.

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.

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.

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

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

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.

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.

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.

Retinal detachment (RD) is a vision-threatening condition that requires timely intervention to preserve vision. Macular involvement -- whether the macula is still intact (macula-intact) or detached (macula-detached) -- is the key determinant of visual outcomes and treatment urgency. Point-of-care ultrasound (POCUS) offers a fast, non-invasive, cost-effective, and accessible imaging modality widely used in diverse clinical settings to detect RD. However, ultrasound image interpretation is limited by a lack of expertise among healthcare providers, especially in resource-limited settings. Deep learning offers the potential to automate ultrasound-based assessment of RD. However, there are no ML ultrasound algorithms currently available for clinical use to detect RD and no prior research has been done on assessing macular status using ultrasound in RD cases -- an essential distinction for surgical prioritization. Moreover, no public dataset currently supports macular-based RD classification using ultrasound video clips. We introduce Eye Retinal DEtachment ultraSound, ERDES, the first open-access dataset of ocular ultrasound clips labeled for (i) presence of retinal detachment and (ii) macula-intact versus macula-detached status. The dataset is intended to facilitate the development and evaluation of machine learning models for detecting retinal detachment. We also provide baseline benchmarks using multiple spatiotemporal convolutional neural network (CNN) architectures. All clips, labels, and training code are publicly available at https://osupcvlab.github.io/ERDES/.

We introduce VascX models, a comprehensive set of model ensembles for analyzing retinal vasculature from color fundus images (CFIs). Annotated CFIs were aggregated from public datasets for vessel, artery-vein, and disc segmentation; and fovea localization. Additional CFIs from the population-based Rotterdam Study were, with arteries and veins annotated by graders at pixel level. Our models achieved robust performance across devices from different vendors, varying levels of image quality levels, and diverse pathologies. Our models demonstrated superior segmentation performance compared to existing systems under a variety of conditions. Significant enhancements were observed in artery-vein and disc segmentation performance, particularly in segmentations of these structures on CFIs of intermediate quality, a common characteristic of large cohorts and clinical datasets. Our model outperformed human graders in segmenting vessels with greater precision. With VascX models we provide a robust, ready-to-use set of model ensembles and inference code aimed at simplifying the implementation and enhancing the quality of automated retinal vasculature analyses. The precise vessel parameters generated by the model can serve as starting points for the identification of disease patterns in and outside of the eye.

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.

Many keypoint detection and description methods have been proposed for image matching or registration. While these methods demonstrate promising performance for single-modality image matching, they often struggle with multimodal data because the descriptors trained on single-modality data tend to lack robustness against the non-linear variations present in multimodal data. Extending such methods to multimodal image matching often requires well-aligned multimodal data to learn modality-invariant descriptors. However, acquiring such data is often costly and impractical in many real-world scenarios. To address this challenge, we propose a modality-invariant feature learning network (MIFNet) to compute modality-invariant features for keypoint descriptions in multimodal image matching using only single-modality training data. Specifically, we propose a novel latent feature aggregation module and a cumulative hybrid aggregation module to enhance the base keypoint descriptors trained on single-modality data by leveraging pre-trained features from Stable Diffusion models. We validate our method with recent keypoint detection and description methods in three multimodal retinal image datasets (CF-FA, CF-OCT, EMA-OCTA) and two remote sensing datasets (Optical-SAR and Optical-NIR). Extensive experiments demonstrate that the proposed MIFNet is able to learn modality-invariant feature for multimodal image matching without accessing the targeted modality and has good zero-shot generalization ability. The source code will be made publicly available.

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.

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.

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.

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.

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.

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

Cats and humans differ in ocular anatomy. Most notably, Felis Catus (domestic cats) have vertically elongated pupils linked to ambush predation; yet, how such specializations manifest in downstream visual representations remains incompletely understood. We present a unified, frozen-encoder benchmark that quantifies feline-human cross-species representational alignment in the wild, across convolutional networks, supervised Vision Transformers, windowed transformers, and self-supervised ViTs (DINO), using layer-wise Centered Kernel Alignment (linear and RBF) and Representational Similarity Analysis, with additional distributional and stability tests reported in the paper. Across models, DINO ViT-B/16 attains the most substantial alignment (mean CKA-RBF approx0.814, mean CKA-linear approx0.745, mean RSA approx0.698), peaking at early blocks, indicating that token-level self-supervision induces early-stage features that bridge species-specific statistics. Supervised ViTs are competitive on CKA yet show weaker geometric correspondence than DINO (e.g., ViT-B/16 RSA approx0.53 at block8; ViT-L/16 approx0.47 at block14), revealing depth-dependent divergences between similarity and representational geometry. CNNs remain strong baselines but below plain ViTs on alignment, and windowed transformers underperform plain ViTs, implicating architectural inductive biases in cross-species alignment. Results indicate that self-supervision coupled with ViT inductive biases yields representational geometries that more closely align feline and human visual systems than widely used CNNs and windowed Transformers, providing testable neuroscientific hypotheses about where and how cross-species visual computations converge. We release our code and dataset for reference and reproducibility.

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).

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.

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.

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.

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.

We show the standard basis of transformer hidden states already provides a training-free, architecture-general feature basis. Individual dimensions encode semantic content via their signs (+/-1) and confidence via their magnitudes, acting as independent binary registers; a feature is a subset of dimensions with a consistent sign pattern, read by counting sign agreements with no learned rotation. We validate this Bag of Dims framework across seven models spanning language (Qwen 3.5-4B, Gemma 3-4B, Mistral 7B, Qwen3-32B), vision (DINOv2, ViT-Base), and audio (AST). Signs alone carry predictive content: unit-magnitude sign patterns preserve 60-93% top-5 next-token accuracy through the LM head, and decoder-free Hamming scoring reaches 80-90% top-4096. From a single-token cache (one forward pass per token, no context, no labels), we detect 175 categories at AUC 0.97-0.99 by sign agreement; a trained probe adds only +0.018 AUC and converges to axis-aligned weights. These features are causally operative: they survive the K/V attention projections, trace to the FFN neuron coalitions that write them (random-weight controls never reproduce this), and flipping a feature's signs during the live forward pass suppresses its concept across four language models, magnitude-matched and concept-specific. Dimensions stay independent throughout (pairwise mutual information below 0.006 bits). The structure is not specific to language: the same per-dimension signs appear in self-supervised vision (DINOv2, 9/12 ImageNet superclasses), supervised vision (ViT-Base, 11/12), and audio (AST, 50/50 ESC-50 categories), so it reflects transformer training in general, not the language-modeling objective. The standard basis already suffices for feature reading at one forward pass, no optimization, no GPU-days. The open problem shifts from finding the right rotation to cataloging what each dimension encodes.

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.

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.

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.

Computer vision foundation models, such as DINO or OpenCLIP, are trained in a self-supervised manner on large image datasets. Analogously, substantial evidence suggests that the human visual system (HVS) is influenced by the statistical distribution of colors and patterns in the natural world, characteristics also present in the training data of foundation models. The question we address in this paper is whether foundation models trained on natural images mimic some of the low-level characteristics of the human visual system, such as contrast detection, contrast masking, and contrast constancy. Specifically, we designed a protocol comprising nine test types to evaluate the image encoders of 45 foundation and generative models. Our results indicate that some foundation models (e.g., DINO, DINOv2, and OpenCLIP), share some of the characteristics of human vision, but other models show little resemblance. Foundation models tend to show smaller sensitivity to low contrast and rather irregular responses to contrast across frequencies. The foundation models show the best agreement with human data in terms of contrast masking. Our findings suggest that human vision and computer vision may take both similar and different paths when learning to interpret images of the real world. Overall, while differences remain, foundation models trained on vision tasks start to align with low-level human vision, with DINOv2 showing the closest resemblance.

Vision Transformers (ViTs) have emerged as the dominant architecture for visual processing tasks, demonstrating excellent scalability with increased training data and model size. However, recent work has identified the emergence of artifact tokens in ViTs that are incongruous with the local semantics. These anomalous tokens degrade ViT performance in tasks that require fine-grained localization or structural coherence. An effective mitigation of this issue is to the addition of register tokens to ViTs, which implicitly "absorb" the artifact term during training. Given the availability of various large-scale pre-trained ViTs, in this paper we aim at equipping them with such register tokens without the need of re-training them from scratch, which is infeasible considering their size. Specifically, we propose Post Hoc Registers (PH-Reg), an efficient self-distillation method that integrates registers into an existing ViT without requiring additional labeled data and full retraining. PH-Reg initializes both teacher and student networks from the same pre-trained ViT. The teacher remains frozen and unmodified, while the student is augmented with randomly initialized register tokens. By applying test-time augmentation to the teacher's inputs, we generate denoised dense embeddings free of artifacts, which are then used to optimize only a small subset of unlocked student weights. We show that our approach can effectively reduce the number of artifact tokens, improving the segmentation and depth prediction of the student ViT under zero-shot and linear probing.

Recent advances in Vision Transformers (ViTs) for face recognition (FR) have moved beyond the standard CLS-token paradigm. In this paradigm, a special classification token (CLS) is prepended to the patch embeddings and used as a representation of the input for downstream tasks. An alternative approach, Concatenated Patch Embeddings (CPE), instead leverages all patch tokens by concatenating them into a single vector, which is then projected into a compact face representation. CPE has been shown to improve recognition performance in comparison to CLS-based ones, but our qualitative analysis of attention maps showed the presence of artifacts that limit their interpretability. To address this issue, we incorporate register tokens, learnable tokens concatenated to the initial patch embeddings, and processed jointly through the ViT encoder blocks. This mechanism has been shown to produce more structured and interpretable attention maps compared to baseline ViT. We empirically demonstrate that these artifacts consistently appear across various ViT backbones, including small and large models, and that introducing register tokens effectively mitigates them. Adding four or eight registers significantly enhances interpretability, with eight registers providing the highest verification accuracies and smoothest attention structures. Our resulting model, ViT-8R, corresponds to a CPE-based ViT-B architecture augmented with eight register tokens achieves state-of-the-art performance among ViT-based FR models on large-scale IJB-B and IJB-C benchmarks. Also, ViT-8R produces substantially clearer attention maps compared with the baseline model, which offer deeper insight into the model's attention behavior (https://github.com/TaharChettaoui/ViT-FR-Registers)

As Vision Transformers (ViTs) become standard vision backbones, a mechanistic account of their computational phenomenology is essential. Despite architectural cues that hint at dynamical structure, there is no settled framework that interprets Transformer depth as a well-characterized flow. In this work, we introduce the Block-Recurrent Hypothesis (BRH), arguing that trained ViTs admit a block-recurrent depth structure such that the computation of the original L blocks can be accurately rewritten using only k ll L distinct blocks applied recurrently. Across diverse ViTs, between-layer representational similarity matrices suggest few contiguous phases. To determine whether these phases reflect genuinely reusable computation, we train block-recurrent surrogates of pretrained ViTs: Recurrent Approximations to Phase-structured TransfORmers (Raptor). In small-scale, we demonstrate that stochastic depth and training promote recurrent structure and subsequently correlate with our ability to accurately fit Raptor. We then provide an empirical existence proof for BRH by training a Raptor model to recover 96% of DINOv2 ImageNet-1k linear probe accuracy in only 2 blocks at equivalent computational cost. Finally, we leverage our hypothesis to develop a program of Dynamical Interpretability. We find i) directional convergence into class-dependent angular basins with self-correcting trajectories under small perturbations, ii) token-specific dynamics, where cls executes sharp late reorientations while patch tokens exhibit strong late-stage coherence toward their mean direction, and iii) a collapse to low rank updates in late depth, consistent with convergence to low-dimensional attractors. Altogether, we find a compact recurrent program emerges along ViT depth, pointing to a low-complexity normative solution that enables these models to be studied through principled dynamical systems analysis.

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.

In the field of medical imaging, the scarcity of large-scale datasets due to privacy restrictions stands as a significant barrier to develop large models for medical. To address this issue, we introduce SynFundus-1M, a high-quality synthetic dataset with over 1 million retinal fundus images and extensive disease and pathologies annotations, which is generated by a Denoising Diffusion Probabilistic Model. The SynFundus-Generator and SynFundus-1M achieve superior Frechet Inception Distance (FID) scores compared to existing methods on main-stream public real datasets. Furthermore, the ophthalmologists evaluation validate the difficulty in discerning these synthetic images from real ones, confirming the SynFundus-1M's authenticity. Through extensive experiments, we demonstrate that both CNN and ViT can benifit from SynFundus-1M by pretraining or training directly. Compared to datasets like ImageNet or EyePACS, models train on SynFundus-1M not only achieve better performance but also faster convergence on various downstream tasks.

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.

We reveal that feedforward network (FFN) layers, rather than attention layers, are the primary contributors to Vision Transformer (ViT) inference latency, with their impact signifying as model size increases. This finding highlights a critical opportunity for optimizing the efficiency of large-scale ViTs by focusing on FFN layers. In this work, we propose a novel channel idle mechanism that facilitates post-training structural reparameterization for efficient FFN layers during testing. Specifically, a set of feature channels remains idle and bypasses the nonlinear activation function in each FFN layer, thereby forming a linear pathway that enables structural reparameterization during inference. This mechanism results in a family of ReParameterizable Vision Transformers (RePaViTs), which achieve remarkable latency reductions with acceptable sacrifices (sometimes gains) in accuracy across various ViTs. The benefits of our method scale consistently with model sizes, demonstrating greater speed improvements and progressively narrowing accuracy gaps or even higher accuracies on larger models. In particular, RePa-ViT-Large and RePa-ViT-Huge enjoy 66.8% and 68.7% speed-ups with +1.7% and +1.1% higher top-1 accuracies under the same training strategy, respectively. RePaViT is the first to employ structural reparameterization on FFN layers to expedite ViTs to our best knowledge, and we believe that it represents an auspicious direction for efficient ViTs. Source code is available at https://github.com/Ackesnal/RePaViT.

Over the past decade, predictive modeling of neural responses in the primate visual system has advanced significantly, largely driven by various DNN approaches. These include models optimized directly for visual recognition, cross-modal alignment through contrastive objectives, neural response prediction from scratch, and large language model embeddings.Likewise, different readout mechanisms, ranging from fully linear to spatial-feature factorized methods have been explored for mapping network activations to neural responses. Despite the diversity of these approaches, it remains unclear which method performs best across different visual regions. In this study, we systematically compare these approaches for modeling the human visual system and investigate alternative strategies to improve response predictions. Our findings reveal that for early to mid-level visual areas, response-optimized models with visual inputs offer superior prediction accuracy, while for higher visual regions, embeddings from LLMs based on detailed contextual descriptions of images and task-optimized models pretrained on large vision datasets provide the best fit. Through comparative analysis of these modeling approaches, we identified three distinct regions in the visual cortex: one sensitive primarily to perceptual features of the input that are not captured by linguistic descriptions, another attuned to fine-grained visual details representing semantic information, and a third responsive to abstract, global meanings aligned with linguistic content. We also highlight the critical role of readout mechanisms, proposing a novel scheme that modulates receptive fields and feature maps based on semantic content, resulting in an accuracy boost of 3-23% over existing SOTAs for all models and brain regions. Together, these findings offer key insights into building more precise models of the visual system.

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.

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).

We present a simple mathematical model for the mammalian low visual pathway, taking into account its key elements: retina, lateral geniculate nucleus (LGN), primary visual cortex (V1). The analogies between the cortical level of the visual system and the structure of popular CNNs, used in image classification tasks, suggests the introduction of an additional preliminary convolutional module inspired to precortical neuronal circuits to improve robustness with respect to global light intensity and contrast variations in the input images. We validate our hypothesis on the popular databases MNIST, FashionMNIST and SVHN, obtaining significantly more robust CNNs with respect to these variations, once such extra module is added.

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.

Spatially variant dynamic convolution provides a principled approach of integrating spatial adaptivity into deep neural networks. However, mainstream designs in medical segmentation commonly generate dynamic kernels through average pooling, which implicitly collapses high-frequency spatial details into a coarse, spatially-compressed representation, leading to over-smoothed predictions that degrade the fidelity of fine-grained clinical structures. To address this limitation, we propose a novel Structure-Guided Dynamic Convolution (SGDC) mechanism, which leverages an explicitly supervised structure-extraction branch to guide the generation of dynamic kernels and gating signals for structure-aware feature modulation. Specifically, the high-fidelity boundary information from this auxiliary branch is fused with semantic features to enable spatially-precise feature modulation. By replacing context aggregation with pixel-wise structural guidance, the proposed design effectively prevents the information loss introduced by average pooling. Experimental results show that SGDC achieves state-of-the-art performance on ISIC 2016, PH2, ISIC 2018, and CoNIC datasets, delivering superior boundary fidelity by reducing the Hausdorff Distance (HD95) by 2.05, and providing consistent IoU gains of 0.99\%-1.49\% over pooling-based baselines. Moreover, the mechanism exhibits strong potential for extension to other fine-grained, structure-sensitive vision tasks, such as small-object detection, offering a principled solution for preserving structural integrity in medical image analysis. To facilitate reproducibility and encourage further research, the implementation code for both our SGE and SGDC modules has been is publicly released at https://github.com/solstice0621/SGDC.

Due to the capability of dynamic state space models (SSMs) in capturing long-range dependencies with linear-time computational complexity, Mamba has shown notable performance in NLP tasks. This has inspired the rapid development of Mamba-based vision models, resulting in promising results in visual recognition tasks. However, such models are not capable of distilling features across layers through feature aggregation, interaction, and selection. Moreover, existing cross-layer feature aggregation methods designed for CNNs or ViTs are not practical in Mamba-based models due to high computational costs. Therefore, this paper aims to introduce an efficient cross-layer feature aggregation mechanism for vision backbone networks. Inspired by the Retinal Ganglion Cells (RGCs) in the human visual system, we propose a new sparse cross-layer connection mechanism termed SparX to effectively improve cross-layer feature interaction and reuse. Specifically, we build two different types of network layers: ganglion layers and normal layers. The former has higher connectivity and complexity, enabling multi-layer feature aggregation and interaction in an input-dependent manner. In contrast, the latter has lower connectivity and complexity. By interleaving these two types of layers, we design a new family of vision backbone networks with sparsely cross-connected layers, achieving an excellent trade-off among model size, computational cost, memory cost, and accuracy in comparison to its counterparts. For instance, with fewer parameters, SparX-Mamba-T improves the top-1 accuracy of VMamba-T from 82.5\% to 83.5\%, while SparX-Swin-T achieves a 1.3\% increase in top-1 accuracy compared to Swin-T. Extensive experimental results demonstrate that our new connection mechanism possesses both superior performance and generalization capabilities on various vision tasks.

Vision Transformer (ViT) has emerged as a powerful architecture in the realm of modern computer vision. However, its application in certain imaging fields, such as microscopy and satellite imaging, presents unique challenges. In these domains, images often contain multiple channels, each carrying semantically distinct and independent information. Furthermore, the model must demonstrate robustness to sparsity in input channels, as they may not be densely available during training or testing. In this paper, we propose a modification to the ViT architecture that enhances reasoning across the input channels and introduce Hierarchical Channel Sampling (HCS) as an additional regularization technique to ensure robustness when only partial channels are presented during test time. Our proposed model, ChannelViT, constructs patch tokens independently from each input channel and utilizes a learnable channel embedding that is added to the patch tokens, similar to positional embeddings. We evaluate the performance of ChannelViT on ImageNet, JUMP-CP (microscopy cell imaging), and So2Sat (satellite imaging). Our results show that ChannelViT outperforms ViT on classification tasks and generalizes well, even when a subset of input channels is used during testing. Across our experiments, HCS proves to be a powerful regularizer, independent of the architecture employed, suggesting itself as a straightforward technique for robust ViT training. Lastly, we find that ChannelViT generalizes effectively even when there is limited access to all channels during training, highlighting its potential for multi-channel imaging under real-world conditions with sparse sensors. Our code is available at https://github.com/insitro/ChannelViT.

Vision transformers (ViTs) are quickly becoming the de-facto architecture for computer vision, yet we understand very little about why they work and what they learn. While existing studies visually analyze the mechanisms of convolutional neural networks, an analogous exploration of ViTs remains challenging. In this paper, we first address the obstacles to performing visualizations on ViTs. Assisted by these solutions, we observe that neurons in ViTs trained with language model supervision (e.g., CLIP) are activated by semantic concepts rather than visual features. We also explore the underlying differences between ViTs and CNNs, and we find that transformers detect image background features, just like their convolutional counterparts, but their predictions depend far less on high-frequency information. On the other hand, both architecture types behave similarly in the way features progress from abstract patterns in early layers to concrete objects in late layers. In addition, we show that ViTs maintain spatial information in all layers except the final layer. In contrast to previous works, we show that the last layer most likely discards the spatial information and behaves as a learned global pooling operation. Finally, we conduct large-scale visualizations on a wide range of ViT variants, including DeiT, CoaT, ConViT, PiT, Swin, and Twin, to validate the effectiveness of our method.

The task of localizing and categorizing objects in medical images often remains formulated as a semantic segmentation problem. This approach, however, only indirectly solves the coarse localization task by predicting pixel-level scores, requiring ad-hoc heuristics when mapping back to object-level scores. State-of-the-art object detectors on the other hand, allow for individual object scoring in an end-to-end fashion, while ironically trading in the ability to exploit the full pixel-wise supervision signal. This can be particularly disadvantageous in the setting of medical image analysis, where data sets are notoriously small. In this paper, we propose Retina U-Net, a simple architecture, which naturally fuses the Retina Net one-stage detector with the U-Net architecture widely used for semantic segmentation in medical images. The proposed architecture recaptures discarded supervision signals by complementing object detection with an auxiliary task in the form of semantic segmentation without introducing the additional complexity of previously proposed two-stage detectors. We evaluate the importance of full segmentation supervision on two medical data sets, provide an in-depth analysis on a series of toy experiments and show how the corresponding performance gain grows in the limit of small data sets. Retina U-Net yields strong detection performance only reached by its more complex two-staged counterparts. Our framework including all methods implemented for operation on 2D and 3D images is available at github.com/pfjaeger/medicaldetectiontoolkit.

The advent of large-scale vision foundation models, pre-trained on diverse natural images, has marked a paradigm shift in computer vision. However, how the frontier vision foundation models' efficacies transfer to specialized domains remains such as medical imaging remains an open question. This report investigates whether DINOv3, a state-of-the-art self-supervised vision transformer (ViT) that features strong capability in dense prediction tasks, can directly serve as a powerful, unified encoder for medical vision tasks without domain-specific pre-training. To answer this, we benchmark DINOv3 across common medical vision tasks, including 2D/3D classification and segmentation on a wide range of medical imaging modalities. We systematically analyze its scalability by varying model sizes and input image resolutions. Our findings reveal that DINOv3 shows impressive performance and establishes a formidable new baseline. Remarkably, it can even outperform medical-specific foundation models like BiomedCLIP and CT-Net on several tasks, despite being trained solely on natural images. However, we identify clear limitations: The model's features degrade in scenarios requiring deep domain specialization, such as in Whole-Slide Pathological Images (WSIs), Electron Microscopy (EM), and Positron Emission Tomography (PET). Furthermore, we observe that DINOv3 does not consistently obey scaling law in the medical domain; performance does not reliably increase with larger models or finer feature resolutions, showing diverse scaling behaviors across tasks. Ultimately, our work establishes DINOv3 as a strong baseline, whose powerful visual features can serve as a robust prior for multiple complex medical tasks. This opens promising future directions, such as leveraging its features to enforce multiview consistency in 3D reconstruction.

Recently two-stage detectors have surged ahead of single-shot detectors in the accuracy-vs-speed trade-off. Nevertheless single-shot detectors are immensely popular in embedded vision applications. This paper brings single-shot detectors up to the same level as current two-stage techniques. We do this by improving training for the state-of-the-art single-shot detector, RetinaNet, in three ways: integrating instance mask prediction for the first time, making the loss function adaptive and more stable, and including additional hard examples in training. We call the resulting augmented network RetinaMask. The detection component of RetinaMask has the same computational cost as the original RetinaNet, but is more accurate. COCO test-dev results are up to 41.4 mAP for RetinaMask-101 vs 39.1mAP for RetinaNet-101, while the runtime is the same during evaluation. Adding Group Normalization increases the performance of RetinaMask-101 to 41.7 mAP. Code is at:https://github.com/chengyangfu/retinamask

Positional embeddings (PE) play a crucial role in Vision Transformers (ViTs) by providing spatial information otherwise lost due to the permutation invariant nature of self attention. While absolute positional embeddings (APE) have shown theoretical advantages over relative positional embeddings (RPE), particularly due to the ability of sinusoidal functions to preserve spatial inductive biases like monotonicity and shift invariance, a fundamental challenge arises when mapping a 2D grid to a 1D sequence. Existing methods have mostly overlooked or never explored the impact of patch ordering in positional embeddings. To address this, we propose LOOPE, a learnable patch-ordering method that optimizes spatial representation for a given set of frequencies, providing a principled approach to patch order optimization. Empirical results show that our PE significantly improves classification accuracy across various ViT architectures. To rigorously evaluate the effectiveness of positional embeddings, we introduce the "Three Cell Experiment", a novel benchmarking framework that assesses the ability of PEs to retain relative and absolute positional information across different ViT architectures. Unlike standard evaluations, which typically report a performance gap of 4 to 6% between models with and without PE, our method reveals a striking 30 to 35% difference, offering a more sensitive diagnostic tool to measure the efficacy of PEs. Our experimental analysis confirms that the proposed LOOPE demonstrates enhanced effectiveness in retaining both relative and absolute positional information.

Despite their success, modern convolutional neural networks (CNNs) exhibit fundamental limitations, including data inefficiency, poor out-of-distribution generalization, and vulnerability to adversarial perturbations. These shortcomings can be traced to a lack of inductive biases that reflect the inherent geometric structure of the visual world. The primate visual system, in contrast, demonstrates superior efficiency and robustness, suggesting that its architectural and computational principles,which evolved to internalize these structures,may offer a blueprint for more capable artificial vision. This paper introduces Visual Cortex Network (VCNet), a novel neural network architecture whose design is informed by the macro-scale organization of the primate visual cortex. VCNet is framed as a geometric framework that emulates key biological mechanisms, including hierarchical processing across distinct cortical areas, dual-stream information segregation for learning disentangled representations, and top-down predictive feedback for representation refinement. We interpret these mechanisms through the lens of geometry and dynamical systems, positing that they guide the learning of structured, low-dimensional neural manifolds. We evaluate VCNet on two specialized benchmarks: the Spots-10 animal pattern dataset, which probes sensitivity to natural textures, and a light field image classification task, which requires processing higher-dimensional visual data. Our results show that VCNet achieves state-of-the-art accuracy of 92.1\% on Spots-10 and 74.4\% on the light field dataset, surpassing contemporary models of comparable size. This work demonstrates that integrating high-level neuroscientific principles, viewed through a geometric lens, can lead to more efficient and robust models, providing a promising direction for addressing long-standing challenges in machine learning.

Vision Transformers (ViTs) are normally regarded as a stack of transformer layers. In this work, we propose a novel view of ViTs showing that they can be seen as ensemble networks containing multiple parallel paths with different lengths. Specifically, we equivalently transform the traditional cascade of multi-head self-attention (MSA) and feed-forward network (FFN) into three parallel paths in each transformer layer. Then, we utilize the identity connection in our new transformer form and further transform the ViT into an explicit multi-path ensemble network. From the new perspective, these paths perform two functions: the first is to provide the feature for the classifier directly, and the second is to provide the lower-level feature representation for subsequent longer paths. We investigate the influence of each path for the final prediction and discover that some paths even pull down the performance. Therefore, we propose the path pruning and EnsembleScale skills for improvement, which cut out the underperforming paths and re-weight the ensemble components, respectively, to optimize the path combination and make the short paths focus on providing high-quality representation for subsequent paths. We also demonstrate that our path combination strategies can help ViTs go deeper and act as high-pass filters to filter out partial low-frequency signals. To further enhance the representation of paths served for subsequent paths, self-distillation is applied to transfer knowledge from the long paths to the short paths. This work calls for more future research to explain and design ViTs from new perspectives.

Convolutional neural networks (CNNs) have so far been the de-facto model for visual data. Recent work has shown that (Vision) Transformer models (ViT) can achieve comparable or even superior performance on image classification tasks. This raises a central question: how are Vision Transformers solving these tasks? Are they acting like convolutional networks, or learning entirely different visual representations? Analyzing the internal representation structure of ViTs and CNNs on image classification benchmarks, we find striking differences between the two architectures, such as ViT having more uniform representations across all layers. We explore how these differences arise, finding crucial roles played by self-attention, which enables early aggregation of global information, and ViT residual connections, which strongly propagate features from lower to higher layers. We study the ramifications for spatial localization, demonstrating ViTs successfully preserve input spatial information, with noticeable effects from different classification methods. Finally, we study the effect of (pretraining) dataset scale on intermediate features and transfer learning, and conclude with a discussion on connections to new architectures such as the MLP-Mixer.

We present a simple approach to make pre-trained Vision Transformers (ViTs) interpretable for fine-grained analysis, aiming to identify and localize the traits that distinguish visually similar categories, such as bird species. Pre-trained ViTs, such as DINO, have demonstrated remarkable capabilities in extracting localized, discriminative features. However, saliency maps like Grad-CAM often fail to identify these traits, producing blurred, coarse heatmaps that highlight entire objects instead. We propose a novel approach, Prompt Class Attention Map (Prompt-CAM), to address this limitation. Prompt-CAM learns class-specific prompts for a pre-trained ViT and uses the corresponding outputs for classification. To correctly classify an image, the true-class prompt must attend to unique image patches not present in other classes' images (i.e., traits). As a result, the true class's multi-head attention maps reveal traits and their locations. Implementation-wise, Prompt-CAM is almost a ``free lunch,'' requiring only a modification to the prediction head of Visual Prompt Tuning (VPT). This makes Prompt-CAM easy to train and apply, in stark contrast to other interpretable methods that require designing specific models and training processes. Extensive empirical studies on a dozen datasets from various domains (e.g., birds, fishes, insects, fungi, flowers, food, and cars) validate the superior interpretation capability of Prompt-CAM. The source code and demo are available at https://github.com/Imageomics/Prompt_CAM.

Recent self-supervised learning (SSL) methods have shown impressive results in learning visual representations from unlabeled images. This paper aims to improve their performance further by utilizing the architectural advantages of the underlying neural network, as the current state-of-the-art visual pretext tasks for SSL do not enjoy the benefit, i.e., they are architecture-agnostic. In particular, we focus on Vision Transformers (ViTs), which have gained much attention recently as a better architectural choice, often outperforming convolutional networks for various visual tasks. The unique characteristic of ViT is that it takes a sequence of disjoint patches from an image and processes patch-level representations internally. Inspired by this, we design a simple yet effective visual pretext task, coined SelfPatch, for learning better patch-level representations. To be specific, we enforce invariance against each patch and its neighbors, i.e., each patch treats similar neighboring patches as positive samples. Consequently, training ViTs with SelfPatch learns more semantically meaningful relations among patches (without using human-annotated labels), which can be beneficial, in particular, to downstream tasks of a dense prediction type. Despite its simplicity, we demonstrate that it can significantly improve the performance of existing SSL methods for various visual tasks, including object detection and semantic segmentation. Specifically, SelfPatch significantly improves the recent self-supervised ViT, DINO, by achieving +1.3 AP on COCO object detection, +1.2 AP on COCO instance segmentation, and +2.9 mIoU on ADE20K semantic segmentation.

Clinical decision-making relies heavily on understanding relative positions of anatomical structures and anomalies. Therefore, for Vision-Language Models (VLMs) to be applicable in clinical practice, the ability to accurately determine relative positions on medical images is a fundamental prerequisite. Despite its importance, this capability remains highly underexplored. To address this gap, we evaluate the ability of state-of-the-art VLMs, GPT-4o, Llama3.2, Pixtral, and JanusPro, and find that all models fail at this fundamental task. Inspired by successful approaches in computer vision, we investigate whether visual prompts, such as alphanumeric or colored markers placed on anatomical structures, can enhance performance. While these markers provide moderate improvements, results remain significantly lower on medical images compared to observations made on natural images. Our evaluations suggest that, in medical imaging, VLMs rely more on prior anatomical knowledge than on actual image content for answering relative position questions, often leading to incorrect conclusions. To facilitate further research in this area, we introduce the MIRP , Medical Imaging Relative Positioning, benchmark dataset, designed to systematically evaluate the capability to identify relative positions in medical images.

Vision foundation models, particularly the ViT family, have revolutionized image understanding by providing rich semantic features. However, despite their success in 2D comprehension, their abilities on grasping 3D spatial relationships are still unclear. In this work, we evaluate and enhance the 3D awareness of ViT-based models. We begin by systematically assessing their ability to learn 3D equivariant features, specifically examining the consistency of semantic embeddings across different viewpoints. Our findings indicate that improved 3D equivariance leads to better performance on various downstream tasks, including pose estimation, tracking, and semantic transfer. Building on this insight, we propose a simple yet effective finetuning strategy based on 3D correspondences, which significantly enhances the 3D correspondence understanding of existing vision models. Remarkably, even finetuning on a single object for just one iteration results in substantial performance gains. All code and resources will be made publicly available to support further advancements in 3D-aware vision models. Our code is available at https://github.com/qq456cvb/3DCorrEnhance.

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.

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.

Recent work has shown that the attention maps of the widely popular DINOv2 model exhibit artifacts, which hurt both model interpretability and performance on dense image tasks. These artifacts emerge due to the model repurposing patch tokens with redundant local information for the storage of global image information. To address this problem, additional register tokens have been incorporated in which the model can store such information instead. We carefully examine the influence of these register tokens on the relationship between global and local image features, showing that while register tokens yield cleaner attention maps, these maps do not accurately reflect the integration of local image information in large models. Instead, global information is dominated by information extracted from register tokens, leading to a disconnect between local and global features. Inspired by these findings, we show that the [CLS] token itself leads to a very similar phenomenon in models without explicit register tokens. Our work shows that care must be taken when interpreting attention maps of large ViTs. Further, by clearly attributing the faulty behavior to register and [CLS] tokens, we show a path towards more interpretable vision models.

There still remains an extreme performance gap between Vision Transformers (ViTs) and Convolutional Neural Networks (CNNs) when training from scratch on small datasets, which is concluded to the lack of inductive bias. In this paper, we further consider this problem and point out two weaknesses of ViTs in inductive biases, that is, the spatial relevance and diverse channel representation. First, on spatial aspect, objects are locally compact and relevant, thus fine-grained feature needs to be extracted from a token and its neighbors. While the lack of data hinders ViTs to attend the spatial relevance. Second, on channel aspect, representation exhibits diversity on different channels. But the scarce data can not enable ViTs to learn strong enough representation for accurate recognition. To this end, we propose Dynamic Hybrid Vision Transformer (DHVT) as the solution to enhance the two inductive biases. On spatial aspect, we adopt a hybrid structure, in which convolution is integrated into patch embedding and multi-layer perceptron module, forcing the model to capture the token features as well as their neighboring features. On channel aspect, we introduce a dynamic feature aggregation module in MLP and a brand new "head token" design in multi-head self-attention module to help re-calibrate channel representation and make different channel group representation interacts with each other. The fusion of weak channel representation forms a strong enough representation for classification. With this design, we successfully eliminate the performance gap between CNNs and ViTs, and our DHVT achieves a series of state-of-the-art performance with a lightweight model, 85.68% on CIFAR-100 with 22.8M parameters, 82.3% on ImageNet-1K with 24.0M parameters. Code is available at https://github.com/ArieSeirack/DHVT.

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.

Optical coherence tomography (OCT) imaging from different camera devices causes challenging domain shifts and can cause a severe drop in accuracy for machine learning models. In this work, we introduce a minimal noise adaptation method based on a singular value decomposition (SVDNA) to overcome the domain gap between target domains from three different device manufacturers in retinal OCT imaging. Our method utilizes the difference in noise structure to successfully bridge the domain gap between different OCT devices and transfer the style from unlabeled target domain images to source images for which manual annotations are available. We demonstrate how this method, despite its simplicity, compares or even outperforms state-of-the-art unsupervised domain adaptation methods for semantic segmentation on a public OCT dataset. SVDNA can be integrated with just a few lines of code into the augmentation pipeline of any network which is in contrast to many state-of-the-art domain adaptation methods which often need to change the underlying model architecture or train a separate style transfer model. The full code implementation for SVDNA is available at https://github.com/ValentinKoch/SVDNA.

Large-scale cell microscopy screens are used in drug discovery and molecular biology research to study the effects of millions of chemical and genetic perturbations on cells. To use these images in downstream analysis, we need models that can map each image into a feature space that represents diverse biological phenotypes consistently, in the sense that perturbations with similar biological effects have similar representations. In this work, we present the largest foundation model for cell microscopy data to date, a new 1.9 billion-parameter ViT-G/8 MAE trained on over 8 billion microscopy image crops. Compared to a previous published ViT-L/8 MAE, our new model achieves a 60% improvement in linear separability of genetic perturbations and obtains the best overall performance on whole-genome biological relationship recall and replicate consistency benchmarks. Beyond scaling, we developed two key methods that improve performance: (1) training on a curated and diverse dataset; and, (2) using biologically motivated linear probing tasks to search across each transformer block for the best candidate representation of whole-genome screens. We find that many self-supervised vision transformers, pretrained on either natural or microscopy images, yield significantly more biologically meaningful representations of microscopy images in their intermediate blocks than in their typically used final blocks. More broadly, our approach and results provide insights toward a general strategy for successfully building foundation models for large-scale biological data.

The goal of this work is to characterize the representational impact that foveation operations have for machine vision systems, inspired by the foveated human visual system, which has higher acuity at the center of gaze and texture-like encoding in the periphery. To do so, we introduce models consisting of a first-stage fixed image transform followed by a second-stage learnable convolutional neural network, and we varied the first stage component. The primary model has a foveated-textural input stage, which we compare to a model with foveated-blurred input and a model with spatially-uniform blurred input (both matched for perceptual compression), and a final reference model with minimal input-based compression. We find that: 1) the foveated-texture model shows similar scene classification accuracy as the reference model despite its compressed input, with greater i.i.d. generalization than the other models; 2) the foveated-texture model has greater sensitivity to high-spatial frequency information and greater robustness to occlusion, w.r.t the comparison models; 3) both the foveated systems, show a stronger center image-bias relative to the spatially-uniform systems even with a weight sharing constraint. Critically, these results are preserved over different classical CNN architectures throughout their learning dynamics. Altogether, this suggests that foveation with peripheral texture-based computations yields an efficient, distinct, and robust representational format of scene information, and provides symbiotic computational insight into the representational consequences that texture-based peripheral encoding may have for processing in the human visual system, while also potentially inspiring the next generation of computer vision models via spatially-adaptive computation. Code + Data available here: https://github.com/ArturoDeza/EmergentProperties

Unlike color photography images, which are consistently encoded into RGB channels, biological images encompass various modalities, where the type of microscopy and the meaning of each channel varies with each experiment. Importantly, the number of channels can range from one to a dozen and their correlation is often comparatively much lower than RGB, as each of them brings specific information content. This aspect is largely overlooked by methods designed out of the bioimage field, and current solutions mostly focus on intra-channel spatial attention, often ignoring the relationship between channels, yet crucial in most biological applications. Importantly, the variable channel type and count prevent the projection of several experiments to a unified representation for large scale pre-training. In this study, we propose ChAda-ViT, a novel Channel Adaptive Vision Transformer architecture employing an Inter-Channel Attention mechanism on images with an arbitrary number, order and type of channels. We also introduce IDRCell100k, a bioimage dataset with a rich set of 79 experiments covering 7 microscope modalities, with a multitude of channel types, and channel counts varying from 1 to 10 per experiment. Our proposed architecture, trained in a self-supervised manner, outperforms existing approaches in several biologically relevant downstream tasks. Additionally, it can be used to bridge the gap for the first time between assays with different microscopes, channel numbers or types by embedding various image and experimental modalities into a unified biological image representation. The latter should facilitate interdisciplinary studies and pave the way for better adoption of deep learning in biological image-based analyses. Code and Data to be released soon.

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.

Scientific archives now contain hundreds of petabytes of data across genomics, ecology, climate, and molecular biology that could reveal undiscovered patterns if systematically analyzed at scale. Large-scale, weakly-supervised datasets in language and vision have driven the development of foundation models whose internal representations encode structure (patterns, co-occurrences and statistical regularities) beyond their training objectives. Most existing methods extract structure only for pre-specified targets; they excel at confirmation but do not support open-ended discovery of unknown patterns. We ask whether sparse autoencoders (SAEs) can enable open-ended feature discovery from foundation model representations. We evaluate this question in controlled rediscovery studies, where the learned SAE features are tested for alignment with semantic concepts on a standard segmentation benchmark and compared against strong label-free alternatives on concept-alignment metrics. Applied to ecological imagery, the same procedure surfaces fine-grained anatomical structure without access to segmentation or part labels, providing a scientific case study with ground-truth validation. While our experiments focus on vision with an ecology case study, the method is domain-agnostic and applicable to models in other sciences (e.g., proteins, genomics, weather). Our results indicate that sparse decomposition provides a practical instrument for exploring what scientific foundation models have learned, an important prerequisite for moving from confirmation to genuine discovery.

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.

We introduce Image2Struct, a benchmark to evaluate vision-language models (VLMs) on extracting structure from images. Our benchmark 1) captures real-world use cases, 2) is fully automatic and does not require human judgment, and 3) is based on a renewable stream of fresh data. In Image2Struct, VLMs are prompted to generate the underlying structure (e.g., LaTeX code or HTML) from an input image (e.g., webpage screenshot). The structure is then rendered to produce an output image (e.g., rendered webpage), which is compared against the input image to produce a similarity score. This round-trip evaluation allows us to quantitatively evaluate VLMs on tasks with multiple valid structures. We create a pipeline that downloads fresh data from active online communities upon execution and evaluates the VLMs without human intervention. We introduce three domains (Webpages, LaTeX, and Musical Scores) and use five image metrics (pixel similarity, cosine similarity between the Inception vectors, learned perceptual image patch similarity, structural similarity index measure, and earth mover similarity) that allow efficient and automatic comparison between pairs of images. We evaluate Image2Struct on 14 prominent VLMs and find that scores vary widely, indicating that Image2Struct can differentiate between the performances of different VLMs. Additionally, the best score varies considerably across domains (e.g., 0.402 on sheet music vs. 0.830 on LaTeX equations), indicating that Image2Struct contains tasks of varying difficulty. For transparency, we release the full results at https://crfm.stanford.edu/helm/image2struct/v1.0.1/.

Object recognition plays a fundamental role in how biological organisms perceive and interact with their environment. While the human visual system performs this task with remarkable efficiency, reproducing similar capabilities in artificial systems remains challenging. This study investigates VisNet, a biologically inspired neural network model, and several enhanced variants incorporating radial basis function neurons, Mahalanobis distance based learning, and retinal like preprocessing for both general object recognition and symmetry classification. By leveraging principles of Hebbian learning and temporal continuity associating temporally adjacent views to build invariant representations. VisNet and its extensions capture robust and transformation invariant features. Experimental results across multiple datasets, including MNIST, CIFAR10, and custom symmetric object sets, show that these enhanced VisNet variants substantially improve recognition accuracy compared with the baseline model. These findings underscore the adaptability and biological relevance of VisNet inspired architectures, offering a powerful and interpretable framework for visual recognition in both neuroscience and artificial intelligence. Keywords: VisNet, Object Recognition, Symmetry Detection, Hebbian Learning, RBF Neurons, Mahalanobis Distance, Biologically Inspired Models, Invariant Representations

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}.

Vision Transformers (ViTs) have recently taken computer vision by storm. However, the softmax attention underlying ViTs comes with a quadratic complexity in time and memory, hindering the application of ViTs to high-resolution images. We revisit the attention design and propose a linear attention method to address the limitation, which doesn't sacrifice ViT's core advantage of capturing global representation like existing methods (e.g. local window attention of Swin). We further investigate the key difference between linear attention and softmax attention. Our empirical results suggest that linear attention lacks a fundamental property of concentrating the distribution of the attention matrix. Inspired by this observation, we introduce a local concentration module to enhance linear attention. By incorporating enhanced linear global attention and local window attention, we propose a new ViT architecture, dubbed L^2ViT. Notably, L^2ViT can effectively capture both global interactions and local representations while enjoying linear computational complexity. Extensive experiments demonstrate the strong performance of L^2ViT. On image classification, L^2ViT achieves 84.4% Top-1 accuracy on ImageNet-1K without any extra training data or label. By further pre-training on ImageNet-22k, it attains 87.0% when fine-tuned with resolution 384^2. For downstream tasks, L^2ViT delivers favorable performance as a backbone on object detection as well as semantic segmentation.

Though the success of CLIP-based training recipes in vision-language models, their scalability to more modalities (e.g., 3D, audio, etc.) is limited to large-scale data, which is expensive or even inapplicable for rare modalities. In this paper, we present ViT-Lens that facilitates efficient omni-modal representation learning by perceiving novel modalities with a pretrained ViT and aligning to a pre-defined space. Specifically, the modality-specific lens is tuned to project multimodal signals to the shared embedding space, which are then processed by a strong ViT that carries pre-trained image knowledge. The encoded multimodal representations are optimized toward aligning with the modal-independent space, pre-defined by off-the-shelf foundation models. A well-trained lens with a ViT backbone has the potential to serve as one of these foundation models, supervising the learning of subsequent modalities. ViT-Lens provides a unified solution for representation learning of increasing modalities with two appealing benefits: (i) Exploiting the pretrained ViT across tasks and domains effectively with efficient data regime; (ii) Emergent downstream capabilities of novel modalities are demonstrated due to the modality alignment space. We evaluate ViT-Lens in the context of 3D as an initial verification. In zero-shot 3D classification, ViT-Lens achieves substantial improvements over previous state-of-the-art, showing 52.0% accuracy on Objaverse-LVIS, 87.4% on ModelNet40, and 60.6% on ScanObjectNN. Furthermore, we enable zero-shot 3D question-answering by simply integrating the trained 3D lens into the InstructBLIP model without any adaptation. We will release the results of ViT-Lens on more modalities in the near future.

The emergence of powerful, general-purpose omnimodels capable of processing diverse data modalities has raised a critical question: can these ``jack-of-all-trades'' systems perform on par with highly specialized models in knowledge-intensive domains? This work investigates this question within the high-stakes field of medical image segmentation. We conduct a comparative study analyzing the zero-shot performance of a state-of-the-art omnimodel (Gemini 2.5 Pro, the ``Nano Banana'' model) against domain-specific deep learning models on three distinct tasks: polyp (endoscopy), retinal vessel (fundus), and breast tumor segmentation (ultrasound). Our study focuses on performance at the extremes by curating subsets of the ``easiest'' and ``hardest'' cases based on the specialist models' accuracy. Our findings reveal a nuanced and task-dependent landscape. For polyp and breast tumor segmentation, specialist models excel on easy samples, but the omnimodel demonstrates greater robustness on hard samples where specialists fail catastrophically. Conversely, for the fine-grained task of retinal vessel segmentation, the specialist model maintains superior performance across both easy and hard cases. Intriguingly, qualitative analysis suggests omnimodels may possess higher sensitivity, identifying subtle anatomical features missed by human annotators. Our results indicate that while current omnimodels are not yet a universal replacement for specialists, their unique strengths suggest a potential complementary role with specialist models, particularly in enhancing robustness on challenging edge cases.

Transformers yield state-of-the-art results across many tasks. However, their heuristically designed architecture impose huge computational costs during inference. This work aims on challenging the common design philosophy of the Vision Transformer (ViT) model with uniform dimension across all the stacked blocks in a model stage, where we redistribute the parameters both across transformer blocks and between different structures within the block via the first systematic attempt on global structural pruning. Dealing with diverse ViT structural components, we derive a novel Hessian-based structural pruning criteria comparable across all layers and structures, with latency-aware regularization for direct latency reduction. Performing iterative pruning on the DeiT-Base model leads to a new architecture family called NViT (Novel ViT), with a novel parameter redistribution that utilizes parameters more efficiently. On ImageNet-1K, NViT-Base achieves a 2.6x FLOPs reduction, 5.1x parameter reduction, and 1.9x run-time speedup over the DeiT-Base model in a near lossless manner. Smaller NViT variants achieve more than 1% accuracy gain at the same throughput of the DeiT Small/Tiny variants, as well as a lossless 3.3x parameter reduction over the SWIN-Small model. These results outperform prior art by a large margin. Further analysis is provided on the parameter redistribution insight of NViT, where we show the high prunability of ViT models, distinct sensitivity within ViT block, and unique parameter distribution trend across stacked ViT blocks. Our insights provide viability for a simple yet effective parameter redistribution rule towards more efficient ViTs for off-the-shelf performance boost.

Transformers have recently emerged as a powerful tool for learning visual representations. In this paper, we identify and characterize artifacts in feature maps of both supervised and self-supervised ViT networks. The artifacts correspond to high-norm tokens appearing during inference primarily in low-informative background areas of images, that are repurposed for internal computations. We propose a simple yet effective solution based on providing additional tokens to the input sequence of the Vision Transformer to fill that role. We show that this solution fixes that problem entirely for both supervised and self-supervised models, sets a new state of the art for self-supervised visual models on dense visual prediction tasks, enables object discovery methods with larger models, and most importantly leads to smoother feature maps and attention maps for downstream visual processing.

The problem of visual metamerism is defined as finding a family of perceptually indistinguishable, yet physically different images. In this paper, we propose our NeuroFovea metamer model, a foveated generative model that is based on a mixture of peripheral representations and style transfer forward-pass algorithms. Our gradient-descent free model is parametrized by a foveated VGG19 encoder-decoder which allows us to encode images in high dimensional space and interpolate between the content and texture information with adaptive instance normalization anywhere in the visual field. Our contributions include: 1) A framework for computing metamers that resembles a noisy communication system via a foveated feed-forward encoder-decoder network -- We observe that metamerism arises as a byproduct of noisy perturbations that partially lie in the perceptual null space; 2) A perceptual optimization scheme as a solution to the hyperparametric nature of our metamer model that requires tuning of the image-texture tradeoff coefficients everywhere in the visual field which are a consequence of internal noise; 3) An ABX psychophysical evaluation of our metamers where we also find that the rate of growth of the receptive fields in our model match V1 for reference metamers and V2 between synthesized samples. Our model also renders metamers at roughly a second, presenting a times1000 speed-up compared to the previous work, which allows for tractable data-driven metamer experiments.