Fundus Images

Despite significant progress in Multi-modal Large Language Models (MLLMs), their clinical reasoning capacity for multi-modal diagnosis remains largely unexamined. Current benchmarks, mostly single-modality data, can't evaluate progressive reasoning and cross-modal integration essential for clinical practice. We introduce the Cross-Modality Progressive Clinical Reasoning (X-PCR) benchmark, the first comprehensive evaluation of MLLMs through a complete ophthalmology diagnostic workflow, with two reasoning tasks: 1) a six-stage progressive reasoning chain spanning image quality assessment to clinical decision-making, and 2) a cross-modality reasoning task integrating six imaging modalities. The benchmark comprises 26,415 images and 177,868 expert-verified VQA pairs curated from 51 public datasets, covering 52 ophthalmic diseases. Evaluation of 21 MLLMs reveals critical gaps in progressive reasoning and cross-modal integration. Dataset and code: https://github.com/CVI-SZU/X-PCR.

We evaluated whether a glaucoma risk assessment (GRA) model trained on All of Us national data can identify patients at high probability of glaucoma using only systemic electronic health records (EHR) at an independent institution. In this cross-sectional study, 20,636 Stanford patients seen from November 2013 to January 2024 were included (15% with glaucoma). A pretrained GRA model was fine-tuned on the Stanford cohort and tested on a held-out set using demographics, systemic diagnoses, medications, laboratory results, and physical examination measurements as inputs. The best model achieved AUROC 0.883 and PPV 0.657. Calibration was consistent with clinical risk: the highest prediction decile showed the greatest glaucoma diagnosis rate (65.7%) and treatment rate (57.0%). Performance improved with more trainable layers up to 15 and with additional data. An EHR-only GRA model may enable scalable and accessible pre-screening without specialized imaging.

Diabetic retinopathy (DR) is a leading cause of vision impairment worldwide, and automated grading systems play a crucial role in large-scale screening programs. However, deep learning models often exhibit degraded performance when deployed across datasets acquired under different imaging conditions. This study presents a robust dual-resolution deep learning framework for DR grading that integrates attention-based feature fusion with ordinal regression to improve cross-dataset generalization. The proposed method employs two parallel EfficientNet backbones operating at different spatial resolutions to capture complementary retinal features. A learnable attention mechanism adaptively fuses multi-resolution representations, while an ordinal regression formulation based on the cumulative link model (CORAL) explicitly accounts for the ordered nature of DR severity levels. To mitigate domain discrepancies between datasets, a preprocessing strategy combining circular cropping, contrast enhancement, and histogram matching is applied. The model was trained on the APTOS 2019 dataset and evaluated on both an internal validation split and an external Messidor-2 test set. Experimental results demonstrate strong grading performance, achieving a quadratic weighted kappa (QWK) of 0.88 on the APTOS validation set and 0.68 on the unseen Messidor-2 dataset, indicating improved robustness for cross-dataset DR grading applications.

Automating medical reports for retinal images requires a sophisticated blend of visual pattern recognition and deep clinical knowledge. Current Large Vision-Language Models (LVLMs) often struggle in specialized medical fields where data is scarce, leading to models that overfit and miss subtle but critical pathologies. To address this, we introduce DREAM (Dynamic Retinal Enhancement with Adaptive Multi-modal Fusion), a novel framework for high-fidelity medical report generation that excels even with limited data. DREAM employs a unique two-stage fusion mechanism that intelligently integrates visual data with clinical keywords curated by ophthalmologists. First, the Abstractor module maps image and keyword features into a shared space, enhancing visual data with pathology-relevant insights. Next, the Adaptor performs adaptive multi-modal fusion, dynamically weighting the importance of each modality using learnable parameters to create a unified representation. To ensure the model's outputs are semantically grounded in clinical reality, a Contrastive Alignment module aligns these fused representations with ground-truth medical reports during training. By combining medical expertise with an efficient fusion strategy, DREAM sets a new state-of-the-art on the DeepEyeNet benchmark, achieving a BLEU-4 score of 0.241, and further demonstrates strong generalization to the ROCO dataset.

The advent of handheld fundus imaging devices has made ophthalmologic diagnosis and disease screening more accessible, efficient, and cost-effective. However, images captured from these setups often suffer from artifacts such as flash reflections, exposure variations, and motion-induced blur, which degrade image quality and hinder downstream analysis. While generative models have been effective in image restoration, most depend on paired supervision or predefined artifact structures, making them less adaptable to unstructured degradations commonly observed in handheld fundus images. To address this, we propose an unsupervised diffusion autoencoder that integrates a context encoder with the denoising process to learn semantically meaningful representations for artifact restoration. The model is trained only on high-quality table-top fundus images and infers to restore artifact-affected handheld acquisitions. We validate the restorations through quantitative and qualitative evaluations, and have shown that diagnostic accuracy increases to 81.17% on an unseen dataset and multiple artifact conditions

In this work, we propose Oph-Guid-RAG, a multimodal visual RAG system for ophthalmology clinical question answering and decision support. We treat each guideline page as an independent evidence unit and directly retrieve page images, preserving tables, flowcharts, and layout information. We further design a controllable retrieval framework with routing and filtering, which selectively introduces external evidence and reduces noise. The system integrates query decomposition, query rewriting, retrieval, reranking, and multimodal reasoning, and provides traceable outputs with guideline page references. We evaluate our method on HealthBench using a doctor-based scoring protocol. On the hard subset, our approach improves the overall score from 0.2969 to 0.3861 (+0.0892, +30.0%) compared to GPT-5.2, and achieves higher accuracy, improving from 0.5956 to 0.6576 (+0.0620, +10.4%). Compared to GPT-5.4, our method achieves a larger accuracy gain of +0.1289 (+24.4%). These results show that our method is more effective on challenging cases that require precise, evidence-based reasoning. Ablation studies further show that reranking, routing, and retrieval design are critical for stable performance, especially under difficult settings. Overall, we show how combining visionbased retrieval with controllable reasoning can improve evidence grounding and robustness in clinical AI applications,while pointing out that further work is needed to be more complete.

Foundation models are used to extract transferable representations from large amounts of unlabeled data, typically via self-supervised learning (SSL). However, many of these models rely on architectures that offer limited interpretability, a critical issue in high-stakes domains such as medical imaging. We propose \model, a foundation model that is interpretable-by-design via a BagNet backbone whose small receptive fields generate class evidence maps that are faithful to the model's decision-making process. Additionally, \model{} incorporates a $2D$ projection layer during pretraining that enables direct visualization of the representation space, providing a dataset-level view of the learned structure including meaningful clinical clusters as well as potential spurious correlations. We trained \model{} on over 800,000 color fundus photographs from various sources to learn generalizable representations for different downstream tasks. Our model achieves performance comparable to RETFound, which has $16\times$ more parameters, while providing interpretable predictions on out-of-distribution data. These results suggest that large-scale SSL pretraining paired with inherent interpretability can lead to robust representations for retinal imaging. Code and pretrained models are available at \href{https://anonymous.4open.science/r/dual-ifm-3D5A/README.md}{www.anonymous.4open.science/dual-IFM}.

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.

Diabetic Macular Edema (DME) is a leading cause of vision loss among patients with Diabetic Retinopathy (DR). While deep learning has shown promising results for automatically detecting this condition from fundus images, its application remains challenging due the limited availability of annotated data. Foundation Models (FM) have emerged as an alternative solution. However, it is unclear if they can cope with DME detection in particular. In this paper, we systematically compare different FM and standard transfer learning approaches for this task. Specifically, we compare the two most popular FM for retinal images-RETFound and FLAIR-and an EfficientNetB0 backbone, across different training regimes and evaluation settings in IDRiD, MESSIDOR-2 and OCT-and-Eye-FundusImages (OEFI). Results show that despite their scale, FM do not consistently outperform fine-tuned CNNs in this task. In particular, EfficientNet-B0 consistently achieves competitive or superior performance across evaluation settings, with FLAIR being the most competitive foundation model, consistently outperforming RETFound. These findings suggest that FMs do not necessarily provide an advantage for fine-grained ophthalmic tasks such as DME detection, even after fine-tuning, highlighting lightweight CNNs as strong baselines in data-scarce environments.

Multimodal large language models (MLLMs) have recently demonstrated remarkable reasoning abilities under reinforcement learning (RL) paradigm. However, most existing multimodal medical reasoning models focus on basic reasoning, which refers to shallow inference based on visual feature matching. In contrast, real-world clinical diagnosis extends beyond basic reasoning, demanding complex reasoning that integrates heterogeneous clinical information (such as chief complaints and medical history) with multimodal medical imaging data. To bridge this gap, we introduce MM-Retinal-Reason, an ophthalmic multimodal dataset covering the full spectrum of perception and reasoning. Specifically, it is the first dataset in ophthalmology to encompass both basic and complex reasoning tasks with Chain-of-Thought (CoT) trajectories, aiming to enhance visual-centric reasoning and emulate realistic clinical decision-making. Building upon MM-Retinal-Reason, we propose OphthaReason, the first RL-enhanced ophthalmic multimodal reasoning model with step-by-step reasoning traces. To enable flexible adaptation to both basic and complex reasoning tasks, we further introduce Uncertainty-Aware Dynamic Thinking (UADT), which estimates sample-level uncertainty via entropy and dynamically modulates exploration depth through a shaped advantage mechanism. Comprehensive experiments demonstrate the effectiveness of our model on both basic and complex reasoning tasks, outperforming general-purpose MLLMs, medical MLLMs, RL-based medical MLLMs, and ophthalmic MLLMs by at least 15.47%. Project Page: \href{https://github.com/lxirich/OphthaReason}{link}.

Early and accurate glaucoma detection is critical to prevent irreversible vision loss, yet existing AI methods often rely on unimodal inputs and lack interpretability. We present GlaBoost, a multimodal gradient boosting framework that unifies three complementary signals for glaucoma risk prediction: fundus image embeddings from a pretrained convolutional encoder,free-text neuroretinal rim assessments encoded by a transformer-based language model, and structured ophthalmic biomarkers. These modalities are fused into a single representation and classified by an enhanced XGBoost model.On two real-world annotated datasets, GlaBoost consistently outperforms unimodal and generic multimodal baselines. Feature importance analysis highlights the cup-to-disc ratio, rim thinning, and the ISNT rule as the dominant predictors, yielding clinically consistent and interpretable decisions. GlaBoost offers a transparent and scalable foundation for multimodal decision support in ophthalmology.

Even during fixation the human eye is constantly in low amplitude motion, jittering over small angles in random directions at up to 100Hz. This motion results in all features of the image on the retina constantly traversing a number of cones, yet objects which are stable in the world are perceived to be stable, and any object which is moving in the world is perceived to be moving. A series of experiments carried out over a dozen years revealed the psychophysics of visual stabilization to be more nuanced than might be assumed, say, from the mechanics of stabilization of camera images, or what might be assumed to be the simplest solution from an evolutionary perspective. The psychophysics revealed by the experiments strongly implies a specific set of operations on retinal signals resulting in the observed stabilization behavior. The presentation is in two levels. First is a functional description of the action of the mechanism that is very likely responsible for the experimentally observed behavior. Second is a more speculative proposal of circuit-level neural elements that might implement the functional behavior.

Artificial intelligence (AI) shows remarkable potential in medical imaging diagnostics, yet most current models require retraining when applied across different clinical settings, limiting their scalability. We developed GlobeReady, a deployment-oriented platform powered by the RetiGlobe foun- dation model and local feature augmentation. RetiGlobe was pretrained in two stages: 1) self-supervised learning using DINOv2 on 38 million synthetic ophthalmic images, and 2) contrastive learning using CLIP on 475,845 real image-text pairs spanning diverse ethnicities, imaging devices, and geographic regions worldwide. We evaluate GlobeReady on 488,448 ophthalmic images, including color fundus photographs (CFPs) and optical coherence tomography scans, from multi-centres in China, Singapore, Vietnam and the UK. Prospective testing included usability assessment with 31 ophthalmologists. Exploratory analyses evaluated domain generalisability, Bayesian uncertainty quantification, out-of-distribution (OOD) detection, and feature-based case retrieval.

Interpretability is crucial for utilizing machine learning models as clinical decision support tools for medical diagnostics. However, most state-of-the-art image classifiers based on neural networks are not interpretable. As a result, clinicians often resort to known biomarkers to guide diagnosis, although biomarker-based classification often suffers from drastic information loss compared to raw medical images. This work proposes a method that preserves the rich imaging information while simultaneously enhancing the interpretability of predictions for diabetic retinopathy staging from optical coherence tomography angiography (OCTA) images. The core contribution of our method is a novel biology-informed heterogeneous graph representation that models retinal vessel segments, intercapillary areas, and the foveal avascular zone (FAZ) in a human-interpretable way. This graph representation allows us to frame diabetic retinopathy staging as a graph-level classification task, which we solve using an established, efficient graph neural network architecture. We compare our method against established methods, including classical biomarker-based classifiers, convolutional neural networks (CNNs), and vision transformers in predicting the clinically assigned DR stage based on color fundus photography images. We find stage agreement rates of our method and alternative vision model based classifiers saturating at AUC-ROC values of 84%. Crucially, we use our biology-informed graph to provide explanations of great detail. Our approach surpasses existing methods in precisely localizing and identifying abnormal vessels and non-perfusion areas. Our approach sets the stage for the interpretable identification of patients who require special attention due to their traceable microvascular changes, only observable using the details of OCTA images.

Early detection of vision-threatening conditions such as diabetic retinopathy, glaucoma, and age-related macular degeneration depends on retinal fundus image analysis, but manual assessment is slow and expert-dependent. Automated convolutional neural networks classify fundus images accurately yet act as black boxes, and existing retinal vessel segmentation methods lose discriminative power under pathology and seldom exploit attention or transformer backbones. Using the FIVES and DRIVE fundus datasets, we develop a two-pipeline framework that pairs four-class disease classification with attention- and transformer-based vessel segmentation, organised in three stages: (1) FIVES images are augmented by rotation and horizontal and vertical flips and used to fine-tune eight ImageNet-pretrained CNNs: ResNet101, DenseNet169, Xception, InceptionV3, DenseNet121, InceptionResNetV2, ResNet50, and EfficientNetB0. (2) Five gradient-based explanation methods, Grad-CAM, Grad-CAM++, Score-CAM, Faster Score-CAM, and Layer-CAM, are computed on the final convolutional block of each classifier and compared qualitatively across architectures. (3) Ten U-Net variants are benchmarked for vessel segmentation: TransUNet (hybrid CNN--Transformer encoder) and Attention U-Net (gated skip connections), evaluated with ResNet50V2, ResNet101V2, and ResNet152V2 backbones, along with additional Attention U-Net configurations using DenseNet backbones, and the fully transformer-based Swin-UNet. ResNet101 gives the highest classification accuracy: 94.17% (F1 0.942) $>$ 88.33% for EfficientNetB0. For segmentation, the architecture ranking is consistent on both datasets: Attention U-Net $>$ TransUNet $>$ Swin-UNet. The strongest configuration is Attention U-Net with a ResNet101V2 backbone: FIVES IoU 0.722, Dice 0.838; DRIVE IoU 0.648, Dice 0.787, lifting DRIVE IoU 60.80 $\rightarrow$ 64.83 over a prior custom U-Net.

Hepatic vessels in computed tomography scans often suffer from image fragmentation and noise interference, making it difficult to maintain vessel integrity and posing significant challenges for vessel segmentation. To address this issue, we propose an innovative model: SegKAN. First, we improve the conventional embedding module by adopting a novel convolutional network structure for image embedding, which smooths out image noise and prevents issues such as gradient explosion in subsequent stages. Next, we transform the spatial relationships between Patch blocks into temporal relationships to solve the problem of capturing positional relationships between Patch blocks in traditional Vision Transformer models. We conducted experiments on a Hepatic vessel dataset, and compared to the existing state-of-the-art model, the Dice score improved by 1.78%. These results demonstrate that the proposed new structure effectively enhances the segmentation performance of high-resolution extended objects. Code will be available at https://github.com/goblin327/SegKAN