Fundus Images

Purpose: To develop and evaluate an interpretable artificial intelligence (AI) framework for glaucoma screening from low-cost portable, handheld retinal fundus photographs in a West African population and to compare its performance with clinical tabletop fundus imaging. Methods: We used data from a community-based study of 681 participants (1,362 eyes) in Nigeria, comprising 414 glaucoma, 478 glaucoma suspect, and 470 non-glaucoma eyes. Fundus photographs were acquired using the low-cost handheld, portable Volk Viva retinal camera and the Canon CR-2-AF tabletop camera. We fine-tuned component models separately to each device to perform vessel segmentation, cup and disc boundary segmentation, and feature extraction to detect optic nerve head features. A final classification model combined these components to classify scans as glaucoma, glaucoma suspect or non-glaucoma. Feature-weight analysis and Gradient-weighted Class Activation Mapping were used for interpretation. Results: The models performed well on both Volk Viva and Canon CR-2-AF images: Vessel segmentation: 0.98 Dice Coefficient (DC) (Volk) and 0.94 DC (Canon); Cup and disc segmentation: 0.95 DC (Volk) and 0.96 DC (Canon); Optic nerve head feature detection: area under the receiver operating characteristic curve (AUCs) of 0.83$\pm$0.03 (Volk) and 0.87$\pm$0.04 (Canon); Classification model: AUCs of 0.85$\pm$0.01 (Volk) and 0.93$\pm$0.01 (Canon). Reports for each image, present model decision confidence scores and decision-rationale visualizations to support clinical interpretation. Conclusions: Volk Viva results were reasonably comparable to Canon CR-2-AF in the component models and not far behind in classification. This shows that interpretable AI combined with low-cost, portable imaging may enhance community-level glaucoma screening, especially in settings with limited specialist access and resources.

Accurate retinal vessel segmentation is important for computer-aided ophthalmic analysis, yet thin vessels, low contrast, and severe foreground-background imbalance remain challenging for encoder-decoder networks. This paper presents U-PEN Mamba, a U-shaped retinal vessel segmentation architecture that couples progressive nonlinear feature expansion with selective state-space modeling. The proposed network enriches local vessel responses with progressive expansion, models long-range spatial dependencies through a Mamba Global Context (MGC) block with linear sequence complexity, and uses attention-based decoder fusion to recover fine vascular boundaries. We evaluate U-PEN Mamba on CHASE DB1 and DRIVE using a consistent patch-based preprocessing pipeline and compare it with convolutional, attention-based, transformer-based, and Mamba-based segmentation baselines. U-PEN Mamba obtains the best mean intersection over union among the compared methods, achieving 0.8394 on CHASE DB1 and 0.8221 on DRIVE, with Dice scores of 0.8187 and 0.8078, respectively, using 21.6M trainable parameters. Ablation studies show that the MGC block contributes the largest gain over the U-Net baseline, while projection dimension and state size provide practical accuracy-efficiency control. These results indicate that selective state-space modeling is a promising global-context mechanism for parameter-efficient retinal vessel segmentation. Code is available at: https://github.com/areyesan/UPEN_Mamba.

The inverse problem of reconstructing optical properties, specifically absorption and scattering coefficients, in layered biological media from time-domain reflectance measurements remains a significant challenge for traditional analytical models. Inverse solvers based on the diffusion equation often struggle with structural heterogeneity, frequently yielding poor accuracy for superficial absorption and deep-layers scattering. In this work, we propose a machine learning framework as an alternative approach to reconstruct the optical properties of a bilayered medium, benchmarking its efficiency and accuracy against model-based algorithms. To overcome the intrinsic approximations of diffusion theory and inverse reconstruction, we generated a robust synthetic dataset of forward DTOF using exact Monte Carlo simulations at multiple source-detector distances. A machine learning pipeline was then trained on this dataset and validated against state-of-the-art model-based reconstruction methods. Besides the significant reconstruction speed-up, the machine learning approach achieves higher accuracy than model-based inverse solvers, further providing an estimate of the parameter space dimensionality without requiring any a priori information about the number of layers in the investigated geometry. Further enhancements in the reconstruction accuracy can be expected in future extensions of this work, by training the pipeline over multiple DTOF curves from the same medium, in a joint multi-distance reconstruction approach.

High-frequency surgical maneuvers in ophthalmology necessitate high-fidelity temporal modeling, yet characterizing long-range procedural dependencies remains computationally prohibitive for attention-based architectures. Existing models often require aggressive temporal downsampling, which compromises the detection of fine-grained action boundaries and instrument-tissue interactions. To address these scalability constraints, we present OphBiWSSD, a framework that reformulates surgical temporal action localization leveraging Bidirectional State Space Duality. By employing a weight-tied selective scan mechanism that incorporates both preceding and succeeding surgical contexts, our approach facilitates the global synthesis of non-causal temporal cues with linear complexity. This streamlined architecture is well-suited to capture the bidirectional dependencies present in ophthalmic workflows, effectively bridging the gap between local boundary precision and long-range procedural context without incurring the quadratic memory overhead of traditional Transformers. Extensive experiments on the OphNet benchmark demonstrate that OphBiWSSD achieves state-of-the-art temporal localization performance, with mean Average Precisions of 44.42% on phases and 43.08% on operations, surpassing the baselines by 6.80% and 6.66%, respectively. Empirical validation indicates that our approach ensures precise temporal localization and offers a computationally viable pathway for deploying surgical intelligence systems in clinical environments. The code is publicly available at https://github.com/yo3nglau/OphBiWSSD.

Ultra-widefield (UWF) swept-source optical coherence tomography angiography (SS-OCTA) enables large-area retinal vascular imaging, yet vessel segmentation at this scale lacks dedicated public benchmarks and comprehensive evaluation for quantitative vascular analysis. We introduce WOIVES, to our knowledge the first publicly available UWF SS-OCTA vessel-segmentation dataset, comprising 206 eyes from 152 participants with a 24x20mm^2 field of view. WOIVES spans emmetropia to high myopia and provides soft probability vessel annotations. We further propose PG-Mamba, a visual state space model that enhances conventional directional scans with two complementary polar-coordinate scan orders. An auxiliary Dynamic FOV Gating module performs spatial modulation at the bottleneck. PG-Mamba outperformed seven competitive approaches on broad segmentation metrics under cross-validation. It achieved the lowest median absolute errors for vessel density, fractal dimension, and vessel length density. WOIVES is publicly available on Zenodo (DOI: 10.5281/zenodo.21904672), and the PG-Mamba code is available at https://github.com/syb1234567/PG-Mamba.

Pretrained diabetic retinopathy (DR) prediction models differ in their input fields, serialization formats, preprocessing requirements, and output semantics. Making these models accessible through a common clinical interface therefore requires explicit coordination between the user interface and the inference service. We designed and implemented DR-LabStack, a React-Flask web system integrating four externally developed pretrained models: RuleFit, Pruned RuleFit, Elaborative XGBoost, and Two-level Ensemble. A shared form retrieves ordered model features, renders model-specific numerical and categorical controls, and constructs a positional input vector. Backend adapters load heterogeneous artifacts and apply the ensemble's accompanying scaler, while a common JSON response supports binary classification display alongside method and source information. Functional evaluation on September 8, 2026 used copied application files and real model artifacts in a documented isolated environment. All four models loaded and exposed their 14-, 6-, 8-, and 25-field contracts. Sixty-two Flask test-client requests characterized service behavior; 12 limited-vector checks confirmed invocation-path and threshold consistency. Twenty-four browser-component scenarios with mocked transport verified input ordering and result rendering and characterized input-validation behavior. The resulting system demonstrates a reusable interaction and serving workflow for heterogeneous DR models. The contribution is web-system design, integration, and software functionality; clinical effectiveness and clinician usability require separate evaluation.

Robotic ophthalmic surgery offers high precision but introduces a "sensory gap" by decoupling the surgeon from their instrument, resulting in a loss of tactile feedback. This paper presents a novel haptic feedback system for subretinal injection tasks leveraging Scene Graphs (SG). The system bridges the sensory gap by analyzing a physically simulated intraoperative Optical Coherence Tomography (iOCT) feed to construct a real-time surgical SG. The SG serves as a semantic abstraction layer for the surgical scene, which is then utilized by a deterministic, rule-based engine to generate state-dependent haptic feedback on a robotic input device. The system was evaluated in a user study (N=16) using an anthropomorphic head phantom and a custom-built surgical robot. Results demonstrate that the SG-driven haptic feedback improved surgical precision, reducing needle alignment error by 14% (p = 0.044) and improving System Usability Scale (SUS) scores by 8% (p = 0.015), while maintaining comparable task completion times. A needle trajectory analysis revealed the emergence of a safer "Align-then-Approach" strategy, in which our haptic negative reinforcement prompted users to fine-tune the tool's trajectory before approaching the retinal target. This work suggests that SGs can effectively serve as the direct computational foundation for real-time, safety-enhancing context-aware haptic feedback in robotic microsurgery.

Accurate segmentation of corneal layers in optical coherence tomography (OCT) is essential for quantitative assessment of corneal morphology, including layer thickness and structural changes associated with disease or surgery. However, automatic segmentation remains challenging because corneal interfaces are thin, affected by speckle noise, and variable across acquisition devices. In this work, we propose ARCOS, a patch-based zero-shot boundary localization framework for corneal layer segmentation in clinical anterior-segment OCT images. Rather than performing conventional region classification, the method predicts boundary heatmaps for the main corneal interfaces from overlapping native-resolution patches. Patch-level predictions are stitched across the full B-scan and converted into boundary locations to obtain continuous, anatomically ordered layer segmentations. The network combines multi-scale feature fusion with a self-conditioned refinement module that uses intermediate boundary information to improve local heatmap predictions while preserving spatial detail. The method was evaluated on clinical OCT images acquired from multiple devices and compared with representative segmentation baselines using boundary localization and derived thickness metrics. The proposed method achieved an off-by-one boundary localization accuracy of 95.1% and a mean absolute boundary error of 0.514 pixels on the matched-device test set. In zero-shot cross-device evaluation, it maintained an average off-by-one accuracy of 84.3% and a mean absolute boundary error of 0.855 pixels across unseen acquisition devices, outperforming the baseline models. Thickness estimates derived from the predicted boundaries showed low error across corneal regions, supporting the method's use for quantitative corneal OCT analysis.

Accurate segmentation of vascular structures in digital subtraction angiography (DSA) images remains challenging due to the thin, elongated, and branching nature of blood vessels. Pixel-wise deep learning approaches such as U-Net achieve strong general-purpose segmentation performance but often produce fragmented or discontinuous predictions in fine vascular regions, since they do not explicitly enforce structural connectivity. Region growing algorithms preserve spatial context and topological continuity, but are highly sensitive to seed point initialization and can be computationally expensive. We propose UI-VISA (U-Net Initialized Vascular Image Segmentation Architecture), a hybrid pipeline that combines the complementary strengths of both approaches. UI-VISA uses U-Net's foreground predictions as informed seed points for a CNN-guided region growing algorithm, which then iteratively refines the segmentation by enforcing local connectivity and recovering fine vessel details that U-Net alone tends to miss or over-predict. We evaluate UI-VISA against standalone U-Net and a prior region-growing-based method (VISA) using 5-fold cross-validation on 26 DSA images. UI-VISA achieves the highest mean Dice and clDice scores across folds, and a paired Wilcoxon signed-rank test shows the improvement in clDice is statistically significant ($p=0.023$), consistent with the method's design goal of preserving vascular connectivity, while the improvement in Dice does not reach significance ($p=0.104$).

Patient identity errors can compromise longitudinal medical records, research databases, and downstream clinical decisions. We present a retinal biometric system for verifying claimed identities and retrieving the correct identity from color fundus images. We trained a 512-dimensional metric-learning encoder combining a ConvNeXtV2 backbone with ArcFace and triplet losses on 227,004 images from 21,851 patient-eye identities in the Rotterdam Study, spanning multiple imaging devices and up to 32.6 years of follow-up. The system was evaluated on held-out Rotterdam Study data and externally on the UK Biobank and Age-Related Eye Disease Study (AREDS). Before evaluation, we used the model to screen for identity inconsistencies and manually adjudicated flagged images, identifying incorrect assignments in 0.588% of Rotterdam Study images, 0.259% of UK Biobank images, and 0.164% of AREDS images. In retrospective-only verification after removing near-duplicate images, the system achieved AUROCs of 0.9998, 0.9997, and 0.9998 in the Rotterdam Study, UK Biobank, and AREDS, respectively. For identity retrieval using only previously acquired images, Recall@1 was 99.7%, 97.2%, and 97.6%, respectively, from galleries averaging 4436-8510 identities; the correct identity appeared among the top five results in at least 98.6% of cases. Performance remained robust across imaging devices and long follow-up intervals, while lower image quality and inconsistent retinal fields accounted for most failures. These findings establish retinal anatomy as a durable biometric signal, useful for safeguarding the integrity of longitudinal imaging records.

Surgical phase recognition is key to context-aware computer-assisted feedback in vitreoretinal procedures, yet the scarcity of synchronized multimodal intraoperative data, particularly microscope views and intraoperative OCT, limits approaches that aim to replicate the multimodal integration surgeons perform naturally. Surgical narration, by contrast, is abundantly available online and offers rich semantic supervision. Prior work has mainly explored pairwise contrastive learning (e.g., intraoperative OCT-microscope or microscope-narration), leaving the joint modeling of all three modalities largely unexplored. We introduce a framework that uses microscope views as a shared anchor to bridge surgical narrations and intraoperative OCT (iOCT) without requiring a fully synchronized tri-modal dataset, leveraging real microscope-narration videos and a synthetic dataset of synchronized microscope video and tool-aligned iOCT pairs. Contrastive alignment transfers structural priors from the synthetic domain to real videos lacking iOCT, and a dual-head MS-TCN++ integrates the resulting embeddings for joint macro- and micro-phase prediction. Evaluated on real vitreoretinal surgeries, our framework improves macro-phase recognition over a zero-shot baseline (mean F1 0.38 to 0.53) and provides an exploratory route to estimating fine-grained instrument-tissue measurements that are not directly observable in real microscope video alone; these micro-phase estimates are validated quantitatively on synthetic data and shown only qualitatively on real surgery. To our knowledge, this is the first work to unify microscope view, iOCT B-scans, and surgical narrations in a shared latent space for surgical phase recognition.

Clinical AI often optimizes predictive performance without engaging how clinicians decide where to look and what to write. We present Co-Annotator, which distills expert gaze and dictation into two guidance components: a gaze-aligned Vision Transformer producing fixation-aligned areas of interest (AOIs), and an ontology-bounded vision-language model (VLM) that pre-fills editable biomarker summaries for retinal optical coherence tomography (OCT). We first collect expert gaze and dictations (US1) to train the models, significantly improving diagnostic accuracy and biomarker generation. We then deploy the system with ophthalmology residents: a controlled resident study (US2) confirmed each modality is safe and independently beneficial, with AOI guidance producing lasting perceptual efficiency gains through post-guidance carryover and VLM guidance more than doubling biomarker documentation breadth. In a combined deployment across two academic institutions (US3), providing both modalities simultaneously produced efficiency gains that substantially exceeded either modality alone: correct diagnoses per minute increased by 40% and comment editing time fell by 67%, without compromising diagnostic accuracy. Notably, neither modality improved efficiency during guidance in US2, which makes the in-guidance efficiency gain under combined guidance in US3 the more striking result. Expert-distilled multimodal guidance can remove two distinct clinical workflow bottlenecks at once (visual search overhead and documentation burden) without compromising the diagnostic accuracy clinicians already achieve.

Reliable evaluation of vision-language models (VLMs) and medical vision-language models (Medical-VLMs) requires calibrated confidence, particularly under realistic clinical conditions. However, existing efforts mainly focused on improving accuracy, leaving calibration in the medical domain underexplored. To this end, we propose MVC-Bench, a calibration-centric benchmark for medical image classification with VLMs and Medical-VLMs. MVC-Bench assesses the calibration across three axes: (i) robustness to modality, backbone, and domain shift (ii) effectiveness of calibration strategies and prompt-tuning methods (iii) stability under prompt-template and random-seed variations. The benchmark covers eight different backbones, three medical modalities, including fundus imaging, histopathology, and chest X-ray under in-domain and domain shift settings. It compares post-hoc calibration, train-time calibration, and zero-shot inference methods, together with six prompt-tuning methods. Across more than 1638 controlled experiments, we report accuracy and Expected Calibration Error (ECE) as primary metrics, and further report results with complementary calibration measures, including Maximum Calibration Error (MCE) and Adaptive Calibration Error (ACE). We further investigate the underlying causes of miscalibration in VLMs and Medical-VLMs and propose a simple train-time calibration method, Multi-Class Margin (MCM) regularization, which achieves lowest ECE on 10 out of 12 settings in in-domain and remains competitive under domain shifts. Collectively, MVC-Bench provides a structured evaluation framework and actionable guidance for improving calibration in safety-critical medical workflows.

Age-related Macular Degeneration (AMD) is the major cause of blindness in the Western world. Its late dry phase is characterised by irreversible atrophic areas, namely Geographic Atrophy (GA). Longitudinal Fundus Autofluorescence (FAF) image acquisitions are currently the main tool for assessing lesion growth over time at the image level. However, due to its highly individualised progression, the evolution of late AMD remains poorly understood. In this work, we propose using Implicit Neural Representations (INRs) to model GA progression at the individual level in a low-data setting. Our approach generates both FAF and GA segmentation at both past and future time points. Among the comparison models, our method achieves competitive segmentation quality across different scenarios, yielding the lowest Mean Absolute Error (MAE) for the GA lesion area and the highest DICE score, without sacrificing FAF image quality. The code is available at https://github.com/SimoneSarrocco/ga-progression-with-inrs.

Retinal fundus images frequently exhibit multiple co-occurring pathologies, yet standard deep learning classifiers apply static, identical computation to every image regardless of the underlying disease distribution. We propose a novel architecture that resolves this via sparse conditional computation, pairing a Guided Context Gating (GCG) spatial attention front-end with a sparsely-routed Mixture-of-Experts (MoE) block operating over feature tokens. Crucially, this routing yields an interpretable, data-driven decomposition. Expert allocation is significantly disease-dependent (p < 0.001), with the healthy Normal state and morphologically distinct pathologies (e.g., ERM, AMD) isolating to dedicated experts. On a five-class, patient-disjoint 5-fold cross-validation benchmark, our model achieves 0.912 +/- 0.008 macro AUC and 0.653 +/- 0.014 macro F1. Furthermore, Grad-CAM++ and post-MoE t-SNE visualizations confirm that expert routing aligns with localized lesions and geometrically maps co-occurring cases between their constituent clusters, positioning sparse MoE as an interpretable approach to multi-disease retinal screening.

Myopia-induced posterior-pole remodeling is frequently accompanied by Optic Disc (OD) deformation and Peripapillary Atrophy (PPA), both of which provide clinically relevant structural biomarkers. In Cartesian fundus images, however, PPA often appears as an irregular and partially visible crescent adjacent to the OD, leading to fragmented segmentation and post-processing-dependent quantification. We propose UPolarSQ, a unified polar-domain framework for OD/PPA segmentation and biomarker quantification in myopic fundus images. UPolarSQ first maps an OD-centered region of interest into polar coordinates, where OD and PPA boundaries can be represented as radial profiles. It then employs UPolarSeg, a U-Net-based segmentation network enhanced with a Radial-Angular-Decoupled Module and boundary-aware auxiliary supervision to model anisotropic polar features and radial boundary transitions. Clinical biomarkers, including disc shape and PPA-width-related measurements, are deterministically extracted from the predicted polar masks, aligning segmentation and quantification within a shared geometric representation. Experiments on internal and external cohorts demonstrate that UPolarSQ improves OD/PPA segmentation and supports reliable polar-native biomarker estimation for myopic analysis.

Diabetic retinopathy (DR) remains a leading cause of vision loss among working-age adults worldwide, making reliable severity grading clinically important. Despite strong performance, most deep models formulate DR grading as image-level classification and do not explicitly model clinically grounded evidence, such as lesion types and spatial relations. In this paper, we propose PARAGraph, a Pathology-Anatomy-Aware Hierarchical Graph framework for DR grading. PARAGraph represents each image as a three-level hierarchical graph with lesion-level nodes, intermediate category and region nodes, and global anatomical and semantic nodes. To incorporate medical priors into nodes, we construct an optic disc-fovea-anchored coordinate frame that provides a scale- and rotation-normalized retinal reference system. Within this frame, lesion nodes are encoded with category, normalized area, and anatomical coordinates. To mitigate noisy lesion segmentation, PARAGraph uses a dual-fusion strategy that introduces global visual context into a graph semantic node and a decision-level prediction branch, improving robustness when lesion evidence is unreliable. Extensive experiments on Messidor-2, APTOS, and DDR show that PARAGraph achieves consistent DR grading performance over state-of-the-art methods. Interpretability and robustness analyses further demonstrate that its predictions are clinically grounded, closely associated with lesion evidence and robust to lesion segmentation noise.

Large language models (LLMs) show promise in medical image interpretation but suffer from hallucination, limited accuracy, and run-to-run inconsistency. We developed and validated an agentic AI framework integrating LLMs with specialized deep learning tools for glaucoma detection from fundus photography. The workflow had three steps: (1) LLM initial assessment; (2) function calling to invoke specialized tools for image quality (QAModel, FundaQ-8), glaucoma classification (SwinV2-Tiny), and optic disc/cup segmentation (SegFormer-B0); and (3) LLM reflection integrating the initial impression with tool outputs. Two LLMs (Gemini 2.5 Flash, GPT-5.4 mini) were evaluated on two public datasets (ORIGA, n=100; RIM-ONE-v3, n=100) under uncropped and cropped fields of view; all images were independently graded by a masked fellowship-trained glaucoma specialist. The agentic workflow improved classification accuracy by 16 to 47 percentage points across all conditions, reaching within 6 points of the specialist; on RIM-ONE-v3 the best configurations matched the specialist accuracy of 88%. LLM-alone approaches failed in two ways: GPT-5.4 mini showed positive bias (sensitivity 95-100%, specificity 0-5%), while Gemini 2.5 Flash varied stochastically between runs; the agentic workflow corrected both. Cup-to-disc ratio error fell 15-50% (MAE 0.156-0.228 to 0.104-0.132), and correlation with specialist grading rose from weak (r=0.12-0.39) to moderate-strong (r=0.59-0.84). Run-to-run consistency rose from near-random (kappa as low as -0.01) to near-perfect (kappa up to 0.96). Integrating LLMs with specialized tools addressed key limitations of LLM-alone approaches, including over-diagnosis and run-to-run variability. Gains held for both LLMs, suggesting generalizability across backbones, and may signal a shift from monolithic models toward orchestrated multi-agent systems in medical AI.

Spherical Equivalent Refraction (SER) and Axial Length (AL) are core indicators for pediatric myopia screening, yet their measurements require dedicated biometry and cycloplegic refraction. Fundus photography offers an accessible imaging modality, as myopia-related posterior-pole changes are visible in 45$^\circ$ fundus images. However, these cues are often low-contrast, spatially diffuse, and multi-scale. Moreover, AL, Sphere (SPH), and Cylinder (CYL) share partially overlapping but non-identical anatomical correlates. We propose SpecF2M, a spectral-aware multi-task network for estimating AL and SER components from pediatric fundus photographs. SpecF2M integrates a deterministic anatomy-guided enhancement module, a hybrid spatial--spectral backbone combining MixCNN and Hybrid Spectral Learning (HSL) blocks, and an expert-routing head for component-level estimation of AL, SPH, and CYL. On a pediatric cohort of 4,359 eligible child visits and 6,966 fundus images, SpecF2M outperforms controlled CNN/ViT baselines for AL and SPH estimation, achieving MAEs of 0.5347 mm and 0.7062 D, respectively. Component-level analysis further reveals asymmetric task coupling, where CYL exhibits weaker association with fundus-derived myopic patterns than AL/SPH. These results support fundus-based, screening-oriented estimation of pediatric myopia indicators, while external validation remains necessary before deployment.

There has been a tremendous amount of image processing and machine learning research to measure and classify disease progression from live optical coherence tomography (OCT) imaging of the retina. The images considered here are large, complex, three-dimensional (3-D) and difficult to visualize effectively. Many current supervised machine learning approaches, \emph{e.g.} neural networks, are non-metric meaning that any features or measurements generated can introduce systematic distortion that may be correlated with underlying non-meaningful physiological differences. Here we present a metric learning approach using the normalized compression distance (NCD) combined with anisotropic structure-enhancing filters to quantify and visualize the principal differences among a collection of 3-D retinal images. We validate the NCD-measured structural differences between pairs of images against the physician-measured change in visual field function, achieving a prediction error of $\sim$ 0.5 dB, more accurate than non-metric deep learning approaches. The normalized compression vectors (NCV) are proposed as a feature set measuring visual differences among a collection of 3-D microscopy images. The utility of the NCV for visualizing and measuring patterns of change is demonstrated for a human with moderate non-progressing glaucoma and for a non-human primate model using intraocular pressure setting manipulation. We conclude with a brief simulation of non-metric embedding features, \emph{e.g.} from neural networks, introducing class-correlated statistical distortion.

Scaling supervision for multi-turn medical agents is difficult because expert dialogue annotation is costly and clinical conversations are privacy-restricted. We introduce Guideline-as-Oracle (GAO), which compiles American Academy of Ophthalmology guidance into a 70-row operational rule table and uses it as the sole source of instance-level supervision for 3,000 training dialogues, reserving human labeling for evaluation. Because converting rules into dialogues is itself a design problem, we catalog eight construction strategies, including cited-row tier assignment, one-fact boundary pairs, metadata-only repair, and label repair, and characterize the evidential status of each: labeling mechanism, null, confounded, or evaluated only as a package. Fine-tuning a 9B backbone on this corpus yields GAO-Triage, improving agreement with a 201-case operational reference from 61.7% to 74.1% (exact McNemar p=0.0046) and emergent-case recall from 9.5% to 69.0%; the gains persist across a second seed and patient simulator. None of the seven general-purpose systems we test dominates GAO-Triage on both metrics, and GAO-Triage requires no frontier model at inference time. Permuting label-dialogue assignments collapses the model to a constant-routine predictor, indicating that the signal lies in guideline-derived assignment rather than dialogue surface form. Label repair coincides with the disappearance of a late-training safety degradation.

A large number of infants with congenital anomalies are born each year globally, especially in areas with underdeveloped medical resources. Currently, fetal ultrasound screening is the most common modality for early pregnancy anatomy detection. This modality can detect anomalies earlier and provide opportune treatment advice. However, the lack of an ultrasound dataset on early fetal gestation has slowed down the development of automated assisted diagnosis. In this work, we present a benchmark dataset for Fetal Ultrasound Screening in Early Pregnancy to facilitate intelligent ultrasound examination and assisted diagnosis called FUSEP. Our dataset consists of two ultrasound views recommended by the international guideline, i.e., Crown-rump Length (CRL) and Nuchal Translucency (NT) views in three hospitals, totaling 4,017 ultrasound images, with 45,820 box-level expert-level annotations. Our dataset and baseline present the following three contributions: 1) Our medical experts annotated a total of 14 key anatomical structures in two views using a box-level format; 2) Our data is collected extensively from different sonographers, devices, scanning angles, hospitals, etc; 3) We report the performance of the semi-supervised learning, fully supervised learning, unsupervised domain adaptation (UDA), and source-free UDA in ultrasound images multi-object detection. To the best of our knowledge, this is the first publicly available dataset and benchmark for fetal early pregnancy ultrasound screening. We believe that FUSEP and benchmark can contribute to the medical community in the development of multiple tasks such as standard plane recognition, quality control on ultrasound images, automated assisted diagnostics in early fetal pregnancy, medical multi-object detection, domain adaptation for object detection, etc.

Despite the widespread adoption of foundation models as feature extractors for medical imaging, relatively little is understood about how different pretraining strategies influence the transferability of learned representations to weakly supervised ophthalmic imaging tasks. We investigate this question in ultra-widefield (UWF) retinal imaging by evaluating foundation model representations within a patch-based multiple instance learning (MIL) framework for disease classification on UWF images. We compare Vision Transformer encoders pretrained with supervised, Masked Autoencoder (MAE), and self-distillation objectives, while keeping the downstream aggregation architecture unchanged. Within a controlled comparison of ViT-B encoders pretrained on ImageNet-1k, the choice of pretraining objective substantially influenced frozen representation transfer, with supervised and self-distillation-based models outperforming MAE. A contemporary DINOv3 model pretrained at a larger scale achieved the strongest overall performance, with a quadratic weighted kappa of 0.863 for five-class diabetic retinopathy grading, comparable with DINOv1. Attention analysis further revealed distinct patch-aggregation behaviours associated with the different pretrained representations, while partial fine-tuning substantially reduced the performance gap for MAE. These findings suggest that pretraining strategy influences both representation transferability and the subsequent aggregation of patch-level evidence within MIL, resulting in differences in downstream classification performance.

Background and Objective: Generating realistic medical images with anatomically accurate segmentation masks helps address the shortage of annotated data in medical imaging, particularly in optical coherence tomography (OCT) of mouse eyes, where manual retinal layer delineation is labour-intensive due to tiny structures and required expertise, resulting in scarce datasets. While diffusion models perform well in medical image synthesis, joint image-mask generation has relied mainly on U-Net-based denoisers, leaving diffusion transformers largely unexplored. Methods: We propose a conditional dual-output Diffusion Transformer (DualDiT) for joint synthesis of OCT B-scans and segmentation masks of the upper retinal cell layers in ex vivo mouse retina. DualDiT encodes both modalities into a shared latent space via a pretrained VAE, concatenates their latent representations, and performs conditional diffusion over the joint tensor. We compared DualDiT against two adapted diffusion baselines: DDPM and LDM. Generative quality was assessed via Fréchet Inception Distance (FID) and spatial FID (sFID); practical utility via synthetic data augmentation for downstream U-Net segmentation; and perceptual realism via evaluation by three domain experts. Results: DualDiT achieved the best generative quality (FID 56.14, sFID 114.35), outperforming DDPM and LDM. Expert panels misclassified 46% of synthetic samples as real and 42% of real samples as synthetic. Adding DualDiT-generated images and masks improved Dice and IoU scores on a held-out segmentation test set. Conclusions: DualDiT shows that transformer-based diffusion models can effectively learn the joint distribution of OCT images and segmentation masks, surpassing DDPM- and LDM-based baselines in generative fidelity, downstream utility, and perceptual realism, highlighting its potential for data augmentation in annotation-scarce medical imaging.

Multimodal medical anomaly detection identifies samples deviating from normal patterns, where scarce abnormal cases make normality modeling from normal data practical. In retinal Optical Coherence Tomography (OCT) and OCT Angiography (OCTA) anomaly detection, existing unsupervised methods rely on visual feature distributions, reconstruction residuals, or encoder-decoder discrepancies, making anomaly scores depend on appearance-level deviations, while multimodal normality also contains semantic organization described in normal medical reports. To this end, we propose Report-Guided Mixture-of-Experts (ReMoE), which distills normal report semantics into an image-to-text prior student, builds modality-aware priors, and uses Report-Guided Modality Modulation (RMM) to modulate features through mixture-of-experts routing. Experiments on a private OCT/OCTA dataset with paired normal reports and a public OCTA500-3MM setting using a fixed normal report demonstrate state-of-the-art performance.

Accurate evaluation of multimodal large language models (MLLMs) in dental panoramic radiography (orthopantomogram, OPG) is limited by the lack of fine-grained, clinically reliable benchmarks that reflect expert interpretation. This work introduces PanDent, a large-scale, clinically grounded OPG benchmark built upon fine-grained, expert-validated tooth-level annotations. The dataset comprises 9,524 high-quality OPGs, each associated with comprehensive structured annotations produced by experienced dentists and further validated by an oral and maxillofacial radiologist, providing clinically reliable supervision for tooth-level diagnosis and reasoning. Clinically consistent radiology reports are constructed from expert-validated findings using clinician-defined reporting logic, establishing explicit correspondence between structured clinical evidence and free-text descriptions. This design enables evaluation of whether MLLMs generate reports that are not only linguistically coherent but also clinically consistent with expert-validated tooth-level findings. Experiments are conducted on diverse MLLMs, including state-of-the-art (SOTA) proprietary models, general-domain open-source models, and medical-specific models. Results show that current MLLMs can generate fluent reports, yet fail to produce clinically consistent descriptions, exhibiting substantial errors in fine-grained localization and tooth-level diagnosis. Fine-tuning on PanDent significantly improves structure-language consistency, substantially enhancing visual localization accuracy and diagnostic correctness, and bringing model outputs closer to expert dental interpretation. These results establish PanDent as a rigorous benchmark for evaluating tooth-level clinical reasoning in MLLMs and a valuable resource for clinically grounded dental AI.

Deploying diabetic retinopathy (DR) screening models in primary care requires edge-efficient systems that remain accurate, safe, and reliable under domain shift. Multi-teacher knowledge distillation (KD) is a natural compression strategy, but existing approaches largely assume that all teachers provide equally trustworthy supervision. In our setting, this assumption fails: a strong CNN teacher (EfficientNet-B3, 0.876 QWK) and a weaker Transformer teacher (Swin-Base, 0.830 QWK) are complementary, yet the Transformer's logits can still mislead the student. We therefore propose OrthKD, a selective-trust distillation framework that transfers full supervision from the strong CNN, uses feature-only distillation from the weak ViT, and enforces orthogonality between teacher-specific student projections to encourage complementary rather than redundant evidence. This design preserves local lesion precision, injects global structural context, and improves robustness to distribution shift. On 132,049 retinal images, a 5.4M-parameter MobileNetV3 student reaches 0.885 QWK on EyePACS and improves zero-shot Messidor-2 performance from 0.507 to 0.728 QWK, while also achieving strong referral AUC and calibration. These results show that selectively distilling heterogeneous teachers can enable practical DR screening on resource-constrained devices.

Learning from minimal human supervision is a long-standing goal in medical image analysis, where dense expert annotations are costly. We study retinal vessel segmentation in an extreme semi-supervised setting with one annotated image and a pool of unlabeled images. We propose ESRVS, which selects a representative reference image for manual annotation and transfers vessel cues using target-domain-adapted DINOv3 features. ESRVS constructs a multi granular vessel prototype, combines prototype-similarity maps with a physics-inspired prior to generate initial pseudo-labels, and refines the transferred supervision through weighted pseudo-label training and adversarial refinement. Across eight public datasets, ESRVS achieves the best Dice and clDice on six datasets, and the best HD95 on all eight datasets among the compared semi-supervised methods, although those methods use 10 to 20% labeled data. With Mask2Former, ESRVS retains on average 93.7% of fully supervised Dice and 95.1% of fully supervised clDice. These results demonstrate the potential of foundation-model label propagation for highly label-efficient retinal vessel segmentation. Code is available at https://github.com/IAANNH/ESRVS.

Color Fundus Photography (CFP) is a primary non-invasive imaging modality for large-scale screening of ophthalmic and systemic diseases. Existing surveys mainly summarize task-specific algorithms, datasets, or preprocessing techniques independently, lacking a unified perspective on their co-evolution with modern artificial intelligence. This review provides an integrated overview of CFP AI through the interplay of dataset evolution, preprocessing paradigms, and modeling frameworks. We show that CFP datasets have evolved from small single-center collections with task-specific labels to large multi-center resources featuring multimodal pairings and longitudinal clinical records. Preprocessing has progressed from conventional image enhancement to neural data-engineering pipelines, hardware-aware token optimization, and self-supervised imputation for incomplete electronic health records (EHRs). Meanwhile, modeling has advanced from convolutional neural networks (CNNs) to vision foundation models, state space models (SSMs), and multimodal expert architectures. At the multimodal frontier, CFP is increasingly integrated with EHRs and longitudinal patient information, enabling more comprehensive clinical reasoning beyond isolated image analysis. We conclude that future progress depends on the collaborative optimization of datasets, preprocessing, and multimodal modeling, providing a roadmap toward robust clinical deployment, improved cross-domain generalization, and resource-efficient edge intelligence.

Vascular segmentation is a standard procedure for clinical diagnosis, yet the specific visual features determining model decisions remain poorly understood. This paper investigates the visual cues Convolutional Neural Networks (CNNs) use to segment blood vessels across two distinct imaging domains: fluorescence microscopy and retinal fundus photography. We employ a series of experiments to quantify the influence of shape, texture, and receptive field on segmentation performance. First, we isolate texture and intensity by evaluating performance on patches subjected to pixel shuffling and normalization. Second, we assess global shape relevance by training models on sparse contours and centerlines. Lastly, we quantify the required spatial context by systematically varying the network's theoretical and effective receptive fields. Within the scope of the evaluated datasets, we found that pixel intensity is more relevant than texture, though networks maintain surprisingly high accuracy even when both cues are removed. Furthermore, CNNs struggle to extrapolate full vessel geometry from shape cues alone, typically relying on a relatively small effective receptive field of around 20 pixels, though global context provides a modest benefit for fundus images. While specific to the modalities studied, this methodology offers a quantitative foundation to audit and refine deep learning systems in vascular imaging.

Automated detection of vision impairing retina-based ocular conditions from fundus images is important for early screening, timely referral and reducing dependency on specialist-only assessment, for which neural network-based deep learning (DL) models have been widely utilized. However, explainability of the DL frameworks remains a major bottleneck for clinical adoption, particularly when model decisions are not linked to retinal regions that are clinically meaningful. To address this issue, this study presents CounterFundus, a novel CycleGAN-driven counterfactual explainability framework, integrating EfficientNet-B5-based retinal disease detection with visually interpretable disease-to-normal fundus image translation. For each pathological image, the counterfactual yielded by the CycleGAN generator represents an estimated healthy counterpart and the resultant difference map is utilized to localize disease-associated retinal changes. Unlike conventional post-hoc saliency methods, CounterFundus provides counterfactual explanations through visually plausible disease-to-normal retinal translation. Thereafter, to quantify the spatial agreement between counterfactual difference maps and classifier saliency, the Counterfactual-Classifier Alignment Score (CCAS) is introduced, embedding Spearman correlation, binary IoU and pointing accuracy into a single assessment protocol. To this end, EigenCAM-aligned evaluation demonstrates that the generated counterfactual explanations remain spatially consistent with classifier-relevant retinal evidence across all CCAS dimensions. Along with that, ablation studies further confirm that CCAS-filtered counterfactual augmentation improves the downstream classification performance in fundus images, establishing CounterFundus as a clinically-grounded, explainable artificially intelligence (XAI) framework for retinal disease detection.

Diabetic retinopathy is a leading cause of preventable blindness; its early lesions are small, low contrast, and easily missed in manual screening. Most automated detectors handle the four non-proliferative DR lesions: microaneurysms, hemorrhages, hard exudates, and soft exudates, with a single multi-class model, even though these lesions differ sharply in size, color, morphology, and prevalence, so a shared model favors common, easy classes over rare, difficult ones. We present PRISM-DR, a lesion-specific pipeline that trains one single-class detector per lesion, each with its own configuration. From a raw fundus image, the pipeline applies region of interest cropping, fundus-specific preprocessing, four parallel YOLO detectors, tiling, per-lesion ensembling of five cross-validation folds, and an inter-lesion suppression step that resolves overlaps by physical lesion size and clinical priority rather than confidence. Per lesion, the best of five YOLO generations is selected, and augmentation is tuned by Bayesian optimization. Trained on IDRiD with stratified five-fold cross-validation, the system reaches a test mAP50 of 0.527 and F1 of 0.529, highest AP50 on hard exudates with 0.561. Without fine-tuning, the models transfer well where the imaging scale is close to IDRiD and degrade as field of view and resolution depart. These modest absolute results reflect a small single-source training set and a difficult task; however, treating each lesion as a separate detection problem is a practical alternative to a single multi-class model.

Detecting vessels engaging in illegal activities is of paramount importance for maritime security. One of the major goals is to detect dark vessels, ships that disable their transponders to evade surveillance. Deep Learning (DL) models can detect vessels in Synthetic Aperture Radar (SAR) images, enabling maritime traffic analysis regardless of weather or visibility conditions. However, to detect potential dark vessels, a DL model must select only those that are required to carry a transponder based on their Gross Tonnage (GT). Unfortunately, no public SAR dataset is available for training an end-to-end DL model for vessel detection and GT regression. In this work, we present a framework that leverages heterogeneous image and tabular datasets to solve this task. Our solution combines a multi-task DL framework for predicting the location, vessel type, and physical dimensions of ships, cascaded with a non-parametric model for predicting GT from vessel size and category. We perform GT regression by a KNN that measures sample similarity using a hybrid Euclidean and categorical distance. Experiments show that our solution can predict multiple outputs while remaining competitive with state-of-the-art models on individual subtasks, thus enabling the identification of dark vessels. We publish our code on GitHub https://github.com/PaltrinieriDavide/vesseldetection.

Volumetric segmentation of optical coherence tomography (OCT) images is essential for diagnosing ocular diseases but requires labor-intensive voxel-wise annotations. While semi-supervised learning (SSL) can reduce annotation costs, most existing methods process data slice by slice and fail to exploit the inherent 3D spatial context. We propose PC-Seg, a progressive cross-view consistency framework that learns high-accuracy 3D segmentation models from sparse 2D annotations. Unlike conventional multi-view approaches, PC-Seg uses a single 2D model to learn cross-view consistency from standard B-scans and orthogonal slices, thereby generating reliable volumetric pseudo-labels. These pseudo-labels are then distilled into a 3D model, followed by a co-training stage in which the 2D and 3D models mutually refine each other through ensemble pseudo-labeling. Experiments on the MSHC and Duke DME datasets demonstrate that PC-Seg achieves accuracy comparable to fully supervised learning while using labels for only about 0.7% of the training data, outperforming state-of-the-art semi-supervised and retinal layer segmentation methods. Our code is publicly available at https://github.com/gsisaoki/pc-seg-official.

Objective: To develop a low-cost automated cataract severity classification system operating on standard consumer-grade colour photographs of the eye, without specialised ophthalmic hardware. Methods: A hybrid framework was designed that fuses deep features from a Convolutional Neural Network (CNN) with five handcrafted Grey-Level Co-occurrence Matrix (GLCM) and intensity descriptors - mean intensity, uniformity, standard deviation, contrast, and energy - extracted from a Hough-circle-localised pupil Region of Interest (ROI). A multi-class Support Vector Machine (SVM) with Radial Basis Function (RBF) kernel classifies each image into one of four severity grades: normal, immature, mature, or hypermature cataract. Results: The proposed fused system achieved 95.0% accuracy, 93.8% sensitivity, and 96.1% specificity on an ophthalmologist-labelled test set drawn from 300 images (75 per class) collected at an ophthalmology clinic, outperforming texture-only (88.5%) and CNN-only (91.3%) baselines and surpassing recently published deep learning approaches. Conclusion: The CNN-GLCM-SVM fusion framework provides competitive four-class cataract grading without GPU acceleration or specialised cameras, making it suitable for primary-care and telemedicine deployment in resource-limited settings.

Background: Retinal fundus imaging is central to the early diagnosis of sight-threatening conditions including diabetic retinopathy, glaucoma, and retinal vein occlusion. Clinical utility of fundus images is routinely compromised by non-uniform illumination, motion blur, and low contrast - artefacts that increase the risk of diagnostic error. Effective image enhancement is therefore a prerequisite for reliable computer-aided ophthalmic diagnosis. Methods: This study proposes a two-stage image enhancement pipeline combining luminosity correction via HSV colour space decomposition with Contrast Limited Adaptive Histogram Equalization (CLAHE) applied exclusively to the Value (V) channel. Experiments are conducted on the publicly available DRIVE dataset (40 retinal fundus images, 584 x 565 pixels, Canon CR5 camera, ophthalmologist-annotated ground truth). Quantitative evaluation employs Peak Signal-to-Noise Ratio (PSNR), Structural Similarity Index (SSIM), and Contrast-to-Noise Ratio (CNR). Baseline comparisons include standard Histogram Equalization (HE) and Adaptive Histogram Equalization (AHE). A binary masking step is subsequently applied to isolate hyper-reflective regions consistent with vascular pathology. Results: The proposed method achieves PSNR = 29.3 dB, SSIM = 0.91, and CNR = 3.12 - outperforming HE (PSNR = 21.4 dB, SSIM = 0.74) and AHE (PSNR = 23.1 dB, SSIM = 0.79) across all metrics, with an average processing time of 0.14 seconds per image. Conclusions: The combined luminosity-CLAHE pipeline yields measurably superior contrast and structural fidelity compared to established baseline methods, with processing speed compatible with clinical screening workflows. Limitations and directions for deep-learning-based comparison are discussed.

Stream-processing systems increasingly operate across heterogeneous mobile edge--cloud infrastructures, where workload volatility, resource contention, and stringent quality-of-service (QoS) requirements complicate decentralized scheduling. This paper proposes \emph{MAS-DecStream}, whose main contribution is \emph{LLM-MR-CNP}: an extension of the classical Contract Net Protocol with semantic CFP formulation, progressive context disclosure, multi-round proposal revision, negotiation memory, and deterministic validation. Edge-cluster agents refine natural-language offloading proposals from local observations, predicted resource states, and qualitative runtime context, while hard resource and QoS constraints remain deterministic. Experiments derived from the Alibaba ASI Trace evaluate the extension at three levels: single- versus multi-round CNP, rule-based versus LLM-assisted refinement, and fixed-model single- versus multi-round negotiation. Under the evaluated configurations, MAS-DecStream reduces latency violations to 3%, eliminates resource overcommitment, reaches a conflict-resolution rate of 0.91 with 20 agents, and improves utility by up to 22% over the multi-round rule-based baseline. A separate 25-case evaluation shows model- and prompt-dependent accuracy--cost trade-offs. The results provide initial evidence that multi-round CNP refinement is the principal protocol-level gain, with LLM assistance adding value for qualitative and uncertain runtime context.

Optical coherence tomography (OCT) imaging is essential for the diagnosis and treatment of retinal diseases. Although multimodal large language models (MLLMs) have demonstrated considerable potential in medical image analysis, existing benchmarks largely reduce OCT understanding to coarse-grained disease classification or isolated visual question answering, leaving the complete cognitive process from visual perception to clinical reasoning insufficiently evaluated. To address this limitation, we introduce OCT-Bench, a comprehensive benchmark dedicated to OCT image understanding. OCT-Bench comprises 10,076 high-quality multiple-choice questions constructed from 4,137 OCT images across seven public datasets. Following the real-world clinical interpretation workflow, we establish a hierarchical capability taxonomy consisting of 20 fine-grained tasks across three dimensions: Perception, Cognition, and Reasoning. These tasks cover a broad range of capabilities, including imaging attributes, retinal anatomy, lesion characteristics, spatial relationships, disease assessment, therapeutic decision-making, and prognostic management. We systematically evaluate 20 representative MLLMs, including proprietary models, open-source general-purpose models, and medical-domain models. Experimental results demonstrate that current models remain substantially short of reliable OCT understanding. Moreover, neither medical-domain adaptation nor increased model scale consistently improves performance across capability levels. OCT-Bench enables comprehensive and fine-grained evaluation of MLLMs, providing a foundation for identifying capability bottlenecks and advancing clinically grounded OCT understanding.

Retinal layer segmentation in Optical Coherence Tomography (OCT) is a fundamental step for extracting quantitative biomarkers of retinal structure. Indeed, there is a growing interest in the analysis of OCTs in the context of neurodegenerative diseases. However, segmentation remains challenging due to speckle noise, shadowing artifacts, low contrast between adjacent layers, anatomical variability across subjects, and domain shifts arising from different acquisition protocols and clinical populations. While deep learning methods have achieved remarkable performance, their robustness and generalization across heterogeneous datasets remain limited. In this work, we investigate the role of spatial normalization as a preprocessing strategy to mitigate geometric domain shifts and improve the consistency of retinal layer segmentation. Inspired by standard practices in neuroimaging, we introduce a fovea-centered normalization framework that aligns OCT volumes into a common anatomical reference. We perform a comprehensive evaluation of state-of-the-art deep learning architectures. To provide a comprehensive assessment of segmentation quality, we combine conventional overlap-based metrics at B-scan level with topology-aware metrics at A-scan level and thickness-based measures at the en-face level. In cases where a ground truth is not available, we propose topology violation quantitative metrics that do not require ground truth annotations and a thickness-based qualitative assessment that captures structural consistency and clinically relevant patterns at the en-face level. The results demonstrate the importance of spatial normalization in OCT segmentation pipelines toward the development of robust and clinically meaningful retinal analysis tools, enabling reliable biomarker extraction and downstream computational analysis in neurodegenerative research.

Medical image classifiers are often trained within one source population, yet clinical deployment requires robustness to patients whose appearance, acquisition style, and disease prevalence differ from the source cohort. Existing fairness and robustness methods often require group supervision or treat appearance variation as an undifferentiated nuisance, which is insufficient when population-correlated low-level cues and lesion evidence share edge and texture structure. We study a strict source-only cross-population setting, where external populations are unseen during optimization, validation, scheduling, hyperparameter and model selection. We propose RED-Sphere, a plug-and-play robustness framework for image classification under unseen population shifts. It estimates shortcut-sensitive nuisance responses with an edge and feature energy prior, attenuates dominant responses through residual soft gating, regularizes masked nuisance views with counterfactual-inspired consistency and separation losses, and predicts labels with normalized spherical prototypes. It favours angular semantic evidence over source-correlated activation magnitude while preserving lesion structure. Although demonstrated on 2D Scanning Laser Ophthalmoscopy (SLO) fundus classification for Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR), RED-Sphere is not tied to retinal anatomy: the same principle can be adapted with modality-specific nuisance priors wherever appearance shortcuts and semantic evidence are entangled. Under a strict White-only Harvard-FairVision protocol, RED-Sphere improves held-out macro-F1 across all 20 task and backbone comparisons, with average gains of 1.28 and 2.98 F1 points on AMD and DR. Gains in AUC and PR-AUC, visual diagnostics, ablations, and sensitivity analyses further support stronger external semantic alignment and more stable angular disease geometry.

Measuring retinal fluid from optical coherence tomography (OCT) drives treatment decisions in macular disease, but manual annotation is slow and segmentation models trained on one scanner degrade on another. We present an attention-guided TransUNet that segments three fluid types across four independent OCT sources, combining a domain-adaptive normalisation scheme with an uncertainty estimate that flags unreliable pixels. The model reaches a mean fluid Dice of 0.78, and -- most usefully for clinicians -- its uncertainty is 1.34x higher exactly where expert graders disagree (p<10^-4), turning a raw segmentation map into an actionable clinical triage signal.

Deep models for retinal optical coherence tomography (OCT) classification report high accuracy but rarely report whether their confidence can be trusted -- a gap that matters when a wrong-but-confident reading delays sight-saving treatment. We pair a hybrid convolutional-Transformer encoder with a gradient-boosting (XGBoost) classification head and a three-part clinical safety layer: confidence calibration, out-of-distribution (OOD) rejection, and per-prediction uncertainty flagging. On four-class OCT (84,495 scans) the model reaches 95.4% accuracy while cutting calibration error twelve-fold (expected calibration error, ECE = 0.0024), so the confidence it reports tracks its true accuracy. To our knowledge this is the first OCT classifier to validate all three safety mechanisms jointly, with public weights and reproducible multi-seed evaluation.

Diabetic Retinopathy (DR) is a leading cause of preventable blindness worldwide, requiring automated lesion segmentation using deep learning models for early detection and monitoring. However, DR lesions vary dramatically in size from tiny microaneurysms to large hemorrhages and exudates. This variability creates conflicting demands on the model architecture and input resolution, posing a challenge for effective design. This work investigates the impact of input resolution on different lesion types. Through systematic experimentation with multiple architectures (U-Net, UNet++, Vision Transformers, DeepLabV3+) at $512 \times 512$ and $1024 \times 1024$ resolutions, we identify a critical, counter-intuitive phenomenon where increasing input resolution has opposing effects on different lesion types. We demonstrate that while higher resolution is essential for resolving fine-grained microaneurysms, it can unexpectedly degrade performance on larger hemorrhages. This finding challenges the common assumption that higher resolution is uniformly beneficial. To address this, we propose a novel Multi-Resolution Feature Stem, an input-level pyramid integrated with a UNet++ backbone. This architecture processes multiple scales in parallel, capturing fine-grained details without sacrificing contextual information. This work contributes crucial empirical evidence of this complex, resolution-dependent behavior and a practical, parameter-efficient architecture that successfully resolves this trade-off.

Squint and cataract are major ocular disorders that majorly affect visual perception and interaction capability. This paper proposes a real-time video-based automated detection system for squint and cataract detection based on computer vision and image processing methods. The proposed system uses a media-pipe face-mesh (a 478-point facial landmark detection model) to extract geometric ocular features for multi-class squint classification. Simultaneously, The presence and severity cataract is estimated through grayscale intensity and histogram-based lens opacity analysis. The system records short video sequences with standard laptop or mobile cameras, which can be deployed at low costs and on a large scale. The experimental performance has shown great accuracy in the detection of squint (98.39%) and classification of cataract (96.90%). Besides automatic ocular analysis, the proposed framework is also made accessible for visual impairment inference which will be integrated with future adaptive user interface and Web accessibility systems for people with visual impairment.

Background. Retinopathy of prematurity (ROP) is a preventable cause of childhood blindness, with rising burden in low- and middle-income countries where ROP-trained ophthalmologists are scarce. Plus disease, marked by retinal vessel dilation and tortuosity, triggers treatment but is subjective and variable. Automated screening could extend specialist reach, but African evidence remains limited. Methods. We analysed 121 Kenyan preterm infants, covering 237 eyes and 1,635 fundus images graded as No Plus, Pre-Plus or Plus. Vessel annotations from two graders supported segmentation training. Eleven configurations were evaluated for eye-level Plus detection using patient-grouped nested cross-validation, including image classifiers, multiple-instance learning, multi-task segmentation-classification, and segment-then-classify pipelines. Results. Vessel segmentation was feasible, achieving pooled Dice 0.533, IoU 0.368, sensitivity 0.623 and specificity 0.979 on held-out images. RGB classifiers were highly sensitive but over-referred, while segmentation-coupled models were more specific. Combining approaches improved performance: an OR-based screen achieved the highest sensitivity, an AND-based confirmation achieved the highest specificity, and a probability ensemble gave the best balanced performance, with sensitivity 0.692, specificity 0.914 and balanced accuracy 0.803, outperforming the vision classifier alone. Conclusions. Classification and vessel segmentation are complementary for ROP Plus detection in Kenyan data. Classifiers support sensitive case-finding, while segmentation improves specificity and reduces over-referral. African ROP AI systems should use combined workflows and undergo prospective multi-site validation.

Diabetic retinopathy (DR) is a local retinal lesion process and a visible manifestation of systemic microvascular injury. Modern retinal AI can grade images accurately, but often leaves unanswered how local lesion evidence, retinal vascular structure, and systemic disease pathways are connected. This paper introduces \emph{Causal-RetiGraph}, a compact biomedical informatics framework that links retinal graph phenotypes with NHANES-anchored pathway modelling. The retinal-image fold constructs an interpretable $X1234$ phenotype from vessel maps, lesion evidence, image embeddings, and AutoMorph biomarkers through spatial $X_{12}$ and Jacobian $X_{34}$ branches. The NHANES fold models systemic exposures, covariates, a same-subject retinal mediator family $R^*$, and downstream outcome families. $X1234$ is used for retinal support and pathway prioritisation, while $R^*$ is used for participant-level pathway summaries. On the retinal fold, $X1234$ achieves 0.9055 binary DR accuracy and 0.9711 AUROC, with graded DR QWK of 0.8312. The results show that lesion and biomarker streams improve contextual retinal representation under scarce and imbalanced data. In NHANES, HbA1c, urine albumin, pulse pressure, fasting glucose, and systolic blood pressure are the strongest binary DR anchors. Participant-level pathway analysis identifies glycaemic--renal and glycaemic--haemodynamic pathways as the clearest mediator-style signals. These results suggest that retinal graph phenotypes can help prioritise systemic pathways in DR while preserving the distinction between image-derived support and same-subject mediation.

Diabetic retinopathy (DR) is a leading cause of vision impairment worldwide, highlighting the need for accurate and accessible screening tools. Optical Coherence Tomography (OCT) provides high-resolution structural information of the retina, whereas OCT angiography (OCTA) offers complementary vascular information that is highly relevant for DR diagnosis. In this study, we propose a cross-modal fusion of OCT B-scans with single-channel en face OCTA using a bidirectional cross-modal attention network for automated DR classification. Two independent datasets, OCT500 and UIC, comprising 730 subjects in total, were utilized to evaluate performance under within-dataset, combined-dataset, and cross-dataset generalization settings. A ConvNeXt V2 model trained solely on OCT images served as the unimodal baseline. In addition to ground-truth (GT) OCTA, we explored the use of translated (TR) OCTA generated from OCT scans, eliminating the requirement for dedicated OCTA hardware. Experimental results demonstrate that cross-modal fusion consistently outperforms unimodal OCT classification across all evaluation scenarios. Fusion with GT OCTA improved classification accuracy and discriminative performance, while TR OCTA achieved comparable or superior results in most settings. Furthermore, TR OCTA improved sensitivity and cross-dataset generalization, indicating enhanced robustness to domain shifts. These findings demonstrate that attention-based OCT-OCTA en face fusion provides clinically meaningful improvements for DR detection and suggest that computationally generated OCTA can serve as a practical, low-cost alternative to hardware-acquired OCTA, enabling broader deployment of high-performance retinal screening systems in resource-limited clinical environments.

Microbial keratitis requires rapid pathogen identification to guide treatment, but culture- and PCR-based diagnostics are slow and resource-intensive. We developed a triple-phase multimodal framework for bacterial-versus-fungal keratitis classification using slit-lamp photographs acquired under blue-light, sclerotic-scatter, and white-light illumination, together with clinical metadata. The model combines cross-modality contrastive learning, modality-specific fine-tuning, and feature-level multimodal ensemble learning for patient-level prediction. We evaluated the framework on a multicenter dataset of 1,645 patients and 17,158 images from India and the United States. The model achieved 85.84% accuracy, 84.46% average F1-score, and 0.885 AUC. Site-specific evaluation showed that pooled results were overly optimistic, whereas resampling- and balance-based re-evaluation provided a more realistic assessment of cross-site generalization. Under all settings, our framework remained the top-performing approach. The code is available at https://github.com/yqwang01/TPMKA and dataset access will be provided subject to University of Michigan data-sharing clearance.

Purpose: Early screening for eye diseases is critical in low- and middle-income countries where access to care is limited. We investigate whether a confidence-guided, multi-image diabetic retinopathy diagnosis framework can integrate image filtering with confidence-aware predictions for reliable screening at capture. Methods: We develop a multi-image fusion method that aggregates retinal views to improve confidence and balanced accuracy. Our method uses confidence to identify unreliable predictions, prompting retakes when needed. We compare: (1) a cascaded image-quality and disease diagnosis pipeline using a single image per patient, (2) confidence-based prediction, and (3) our confidence-based multi-image fusion pipeline. All methods are evaluated using a RETFoundGreen backbone on the mBRSET (n = 1,234) and BRSET (n = 7,599) datasets. Results: At 70% coverage, our method achieves 91% balanced accuracy on mBRSET and 97% on BRSET, improvements of ~12% and ~6%, respectively, over cascade filtering. The image-quality cascade reaches sensitivities of 61% on mBRSET and 86% on BRSET, whereas our framework reaches 94% and 96%, respectively, at 50% coverage. Conclusions: Human-annotated quality labels are weakly associated with diagnostic performance, and confidence-based filtering consistently outperforms image quality-based cascaded pipelines. Translational Relevance: Using confidence-based multi-image fusion, patients receive more reliable predictions, reducing incorrect diagnoses during screening. The lightweight backbone and single inference pass per image make the framework compatible with low-latency mobile screening systems in resource-limited settings.

Glaucoma is a progressive eye disease that can lead to irreversible vision loss if not detected at an early stage. Conventional diagnostic procedures are often time-consuming and rely heavily on expert interpretation, limiting their scalability for large-scale screening. In this study, glaucoma detection is investigated under two evaluation settings: sample-wise, where individual samples are analyzed independently, and patient-wise, where data from each patient are aggregated for final prediction. An automated multimodal framework is proposed that integrates fundus images with clinical data. Under the sample-wise setting, detection is performed using fundus images and clinical features individually, as well as through their multimodal combination. Under the patient-wise setting, predictions are obtained by aggregating multiple fundus image representations with corresponding clinical information for each patient. Deep visual features are extracted using a Vision Transformer (ViT) architecture and classified using classical machine-learning models, with a stacking-based ensemble of the three best-performing classifiers employed to optimize performance. Experiments conducted on the publicly available PAPILA dataset demonstrate strong diagnostic performance, achieving 97.47% accuracy and a 97.50% F1-score for sample-wise multimodal classification, and 98.97% accuracy and F1-score for subject-wise detection. The proposed framework is further deployed as an end-to-end web-based platform to support automated glaucoma screening and clinical decision support.

Deep learning is widely applied in medical image analysis, but up to 10% of manually labelled images may be incorrect, degrading model performance. This paper proposes an automated method to identify incorrectly labelled medical images by analyzing sequences of loss functions from deep learning classification networks over multiple training epochs. Identified images can be reviewed and relabelled by experts, improving dataset quality and model performance. Two experiments validate the method on a fundus image dataset for referable diabetic retinopathy screening. In the first, 6% (648) of 10,788 gold-standard labels were intentionally flipped. The method identified 75.31% (488) of the flipped samples, with only 4.85% (492) false positives among correctly labelled samples. In the second, reviewing and correcting the 980 identified samples (9.1% of the dataset) and retraining the model improved best accuracy on an independent test set from 95.93% (with 6% label noise) to 96.50% (with 1.5% noise), approaching the ideal 96.57% (with 0% noise). The results demonstrate the method's effectiveness in improving model performance through automated label quality control.

Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) requires precise monitoring of relevant structural biomarkers to assess disease stage, progression, and treatment response. This paper presents a fully automated, deep learning-based framework for the high-precision, pixel-wise segmentation of key biomarkers in optical coherence tomography (OCT) imaging: retinal pigment epithelium (RPE) loss, ellipsoid zone (EZ) loss, and EZ thinning. The proposed pipeline uses three specialized semantic segmentation models to delineate RPE loss, EZ boundaries (including interruptions), and Bruch's membrane. To ensure robustness and generalizability, the models were developed on a diverse dataset of 298 SD-OCT volumes representing the full phenotypic spectrum of AMD (GA:222, intermediate AMD: 40, neovascular AMD: 17, healthy: 19) and validated on an independent external dataset (n=43). The comprehensive evaluation was further strengthened using additional datasets to assess repeatability, inter-reader reliability, the impact of B-scan density on measurement accuracy, and subgroup performance stratified by lesion size. Results demonstrated high segmentation accuracy (Dice RPE loss: 0.88, Dice EZ loss: 0.87, Pearson's r > 0.99). Total EZ thickness measurements exhibited a sub-pixel average deviation of 2.15 $μm$, and segmentation reliability was confirmed by a strong reproducibility score (ICC > 0.98). By accurately and consistently quantifying outer photoreceptor degeneration and RPE loss, this fully automated framework provides a highly reliable tool for GA assessment in both clinical trials and routine real-world ophthalmic care.

In recent years, most research on multimodal salient object detection (SOD) and camouflaged object detection (COD) typically aims to improve performance through complex cross-modal feature fusion and decoding structures. However, this approach leads to an excessively large model parameter scale and often fails to deliver satisfactory detection performance due to structural redundancy. In contrast, the human visual process is able to efficiently perform salient and camouflaged object identification without such complex structures. This contrast raises an important question: Can we draw conceptual inspiration from the human visual process to achieve a simpler modeling strategy, and still realize accurate and efficient object detection? To answer this question, we propose HVPNet, a simple yet general bio-inspired computational architecture. Drawing on the multi-layered information integration of the retina as a conceptual metaphor, we designed a Retinal Integration Module (RIM), which effectively integrates multimodal features through a level-specific multi-stage integration strategy. To fully exploit these features, we further design a cortical decoder (CD) that breaks down the decoding process into low- and high-level visual stages, abstracting the hierarchical processing in the human visual cortex. Benefiting from these designs, HVPNet can readily extend to seven tasks across four modalities. Without bells and whistles, it establishes an excellent accuracy-efficiency trade-off across 22 datasets spanning these seven tasks. Our code is available at https://github.com/jiaweiXu1029/HVPNet.

Color Fundus Photography (CFP) offers a low-cost and non-invasive route for ischemic heart disease (IHD) screening, but current studies are limited by scarce public benchmarks and ineffective fusion of retinal images with sparse clinical variables. We propose IDNet, a multimodal framework with a Cross-Modal Distillation Aggregator (CDA) that uses learnable queries to sequentially integrate left-eye, right-eye, and clinical features, mitigating the imbalance between high-dimensional visual features and low-dimensional tabular inputs. We also construct a reproducible UK Biobank benchmark with open-source curation and quality-control pipelines, yielding 50,410 images from 25,205 subjects. On this benchmark, IDNet outperforms image-only, clinical-only, and several multimodal baselines, and CDA consistently improves multiple visual encoders as a plug-in fusion module.

Color fundus photography (CFP) is the most common ophthalmic imaging modality for large-scale screening. However, it is highly susceptible to degradations, making robust fundus image quality assessment (FIQA) crucial. The criteria for what constitutes high-quality at the image level vary across clinical tasks, making FIQA dependent on expert knowledge. This motivated the development of automated methods and datasets. While existing datasets aim to standardize image-level quality, their criteria often differ. Furthermore, image-level labels preclude the quantitative evaluation of localized degradations, which is essential for trustworthy FIQA. We argue that pixel-level FIQA based on anatomical visibility represents a more task-agnostic, explainable approach. In this work, we introduce FunPiQ, the first FIQA benchmark to provide pixel-level quality annotations. In addition, we propose EFIQA-CP, an explainable-by-design (EBD) method that uses quality pseudo-labels based on anatomical visibility to train a CNN via Non-Negative Positive-Unlabeled learning. Extensive evaluations of classification methods with post-hoc explanations, anomaly detection methods, and EBD methods demonstrate the superior performance of the last and, particularly, of EFIQA-CP.

Learning causal models from fragmented biomedical data is challenging because clinical, molecular, and imaging variables are often incomplete or not jointly observed. We propose RetiSEM, a domain-constrained structural equation modelling (SEM) framework for causal graph recovery and mediation analysis under limited multimodal resources. This proposed work organises variables into biologically informed blocks, applies forbidden-edge constraints, and decomposes pathway-level effects into TE, NDE, and NIE components. We evaluate RetiSEM across ten synthetic benchmark scenarios that vary in dimensionality, nonlinearity, causal depth, and pathway structure, together with a fragmented real-world setting that combines NHANES clinical variables with externally derived retinal representations. This approach achieves lower structural error and higher causal accuracy than unconstrained baselines across the synthetic benchmarks. In the real-data analysis, retinal variables behave mainly as downstream biomarker-like indicators, with smaller but detectable indirect effects. These findings support our strategy as an interpretable framework for testing structured causal hypotheses in limited-resource biomedical AI. The code and resources for this work are publicly available at: https://github.com/Inamullah-Colab/ReitSEM.

Accurate pulmonary vessel segmentation remains challenging due to the sparse, tortuous, and multi-scale nature of vascular structures, where small branches are easily lost and topology integrity is difficult to preserve under voxel-wise supervision. Existing deep segmentation models primarily optimize binary masks, lacking explicit geometric constraints, thus struggling to recover continuous tubular morphology and fine vascular connectivity. In this study, we introduce MorVess, a morphology-aware segmentation framework that integrates differentiable geometric priors with large-scale foundation model adaptation to achieve fine-grained vascular parsing. MorVess jointly predicts vessel masks, distance maps, and thickness maps, providing explicit supervision for vascular boundaries, centerline consistency, and smooth diameter transitions. A lightweight 2.5D adapter bridges 3D spatial context and 2D SAM representations, while a global-local fusion block aggregates multi-level semantics and geometric cues for high-fidelity topology reconstruction. Across two challenging pulmonary CT benchmarks, MorVess delivers superior Dice, clDice, and HD95 scores, substantially improving small-vessel recovery and global connectivity. These results demonstrate that embedding geometric intelligence into pretrained vision models offers a principled and scalable pathway toward precise vessel analysis and clinically reliable structural quantification. Our source code is available at https://github.com/MaoFuyou/MorVess.

Automated diabetic retinopathy (DR) grading from colour fundus photographs can achieve strong predictive performance, but clinical interpretation requires more than an image-level label. It requires understanding how lesion evidence is distributed around retinal vessels and how this evidence relates to quantitative vascular biomarkers. We present a dual-edge spatial-Jacobian image graph for interpretable DR grading. Each fundus image is represented as a graph node with four aligned evidence streams: AutoMorph vessel information ($X_1$), DR-XAI-style lesion evidence maps ($X_2$), a 128-dimensional lesion-based contrastive image embedding ($X_3$), and AutoMorph morphometric biomarkers ($X_4$). The spatial edge branch ($X_{12}$) encodes vessel-lesion geometry, while the Jacobian branch ($X_{34}$) models embedding-biomarker sensitivity. Lightweight two-token attention fuses both edge families into a final image graph. On 2,910 matched non-augmented APTOS images, the full graph achieves 0.8076 accuracy, 0.8312 quadratic weighted kappa, 0.5915 macro-F1, and 0.9330 adjacent-grade accuracy; referable DR reaches 0.9055 accuracy and 0.9711 AUROC. The framework is positioned as an explainable representation-learning tool for lesion-biomarker hypothesis generation, rather than as a deployment-ready clinical classifier. The code is available at https://github.com/Inamullah-Colab/dual-edge-dr-graph-xai.

Large-scale pretrained foundation models have revolutionized general medical screening, but often falter on rare diseases because such conditions are underrepresented in real-world clinical datasets. While retrieval-augmented diagnosis attempts to mitigate this, conventional static methods frequently succumb to the hubness problem, retrieving visually similar but semantically incorrect common diseases. To address this, we propose Evo-RAD, a self-evolving agentic framework that transforms evidence acquisition into a dynamic decision-making task. We formulate retrieval as a Markov Decision Process (MDP) where a graphbased agent observes the reference set state and executes actions to purge discordant evidence (DELETE), acquire pathologically consistent samples (INSERT), or conclude the evolution (TERMINATE). Optimized via Group Relative Policy Optimization (GRPO) with a homogeneityaware reward, the agent learns to maximize the diagnostic homogeneity of the support reference set. Experiments on retinal disease benchmarks show that Evo-RAD substantially improves rare-disease diagnosis, outperforming retinal foundation models by +21.04%, while also surpassing retrieval-based and parameter-efficient fine-tuning methods by +3.56%. Code is available at https://github.com/SDH-Lab/Evo-RAD.

Automated frame selection for fetal biometry remains under addressed, with most prior work targeting generic quality assessment or downstream measurement pipelines that assume suitable frames are available. We introduce FetSelect, a task-specific framework that pairs a frozen vision foundation backbone with a hybrid multi-head design: a Task-Gated classification head and a Detection-derived quality head combined via learned fusion. We curate 6,486 expert-labeled frames across four targets: Crown-Rump Length (CRL), Nuchal Translucency (NT), Nasal Bone (NB), and Scalebar, and adapt the backbone with BYOL pretraining on 19,019 unlabeled images. On a held-out test set (974 frames), FetSelect achieves mean AUROC 0.956 and mean correlation 0.818 with expert quality annotations. Ablations confirm that hybrid fusion surpasses single-head variants, and ultrasound-specific self-supervision yields consistent gains. Evaluation on external clinical videos and 509 external CRL images demonstrates task-specific discrimination.