Interpretable Diabetic Retinopathy Grading

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.

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.

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.

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.

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.

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.

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.

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.

Diabetic Retinopathy (DR) is an aggressive retinal disease and a leading cause of global blindness, yet its clinical management is currently hindered by the black-box nature of diagnostic AI. While deep learning models achieve high classification accuracy, there is a critical lack of explainability methods capable of detailing the exact anatomical landmarks and lesion distributions that lead to a clinical decision for DR. Therefore, we propose HSQ-VLM, a novel quadrant segmentation pipeline on fundus images that utilizes a Landmark-Anchored Cartesian Cross-Attention mechanism to unify visual feature extraction with structured clinical reasoning. Unlike traditional methods that rely on arbitrary image partitioning, our pipeline implements 4-quadrant Topological Latent Partitioning (TLP) to dynamically align retinal features with a fovea-centered coordinate system. This allows the Vision-Language Model to generate natural language reports that quantify pathology with anatomical precision. On a dataset of 3,500 high-resolution fundus images, this innovative methodology achieved a lesion detection sensitivity of 99.6% for hemorrhages and 96.4% for microaneurysms, while demonstrating a significant reduction in boundary-ambiguity errors compared to standard segmentation baselines.

Long-term visual acuity (VA) outcomes after anti-VEGF therapy are central to patient counseling, expectation setting, and follow-up planning in diabetic macular edema (DME). However, in clinical practice, physicians must often estimate long-term visual trajectories based only on early post-treatment findings, making reliable prognostication difficult. Although prior OCT-based learning approaches have largely focused on short-term response or single-endpoint prediction, modeling VA trajectories across multiple future time points from early longitudinal observations remains insufficiently explored. In this study, we assembled a real-world cohort of 188 anti-VEGF--treated DME patients with paired baseline and month-1 OCT scans, along with tabular OCT-derived biomarkers and non-imaging clinical variables. Using only these early data, we formulate a multi-horizon VA forecasting problem aimed at predicting visual outcomes at 3, 6, 12, 18, and 24 months, reflecting clinically meaningful follow-up intervals. We propose \textbf{ReVA}, a response-aware multimodal framework that integrates structural features from baseline and month-1 OCT with the tabular variables to capture baseline disease status and early treatment response. ReVA uses spatial attention to preserve localized prognostic imaging features and a dependency-aware tabular encoder to model interactions among clinical variables. These multimodal representations are fused to predict patient-specific long-term visual acuity trajectories. The proposed framework achieves MAE $=0.1246$, RMSE $=0.1621$, and $R^2=0.6064$ for 24-month VA prediction, with consistent performance across all forecast horizons. Our findings show that incorporating early treatment-response signals enables clinically meaningful long-term visual acuity forecasting, supporting data-driven decision support for routine anti-VEGF management.

Retinal imaging provides a non-invasive window into systemic microvascular health and has emerged as a potential biomarker for systemic diseases. However, whether retinal features encode biologically meaningful systemic signals that can be reliably interpreted using explainable artificial intelligence (XAI) remains unclear. An explainable multi-task deep learning framework was developed to investigate associations between retinal microvascular features and systemic abnormalities in Type 2 Diabetes Mellitus. A total of 11,011 fundus images from 2,719 individuals were analysed using a shared neural network with task-specific heads for glycaemic status, kidney abnormality, and multi-system involvement. Model interpretability was evaluated using Gradient-weighted Class Activation Mapping (Grad-CAM), anatomical masking, and vessel alignment analysis. The framework demonstrated task-dependent predictive performance, with the best discrimination observed for kidney abnormality (AUC up to 0.63), whereas glycaemic status prediction showed limited performance (AUC = 0.49-0.61). Explainability analyses consistently localized model attention to retinal vessels and peripapillary regions. Masking experiments showed that occlusion of vascular regions caused the greatest performance decline, indicating that retinal vessels were the primary predictive source. Different architectures exhibited heterogeneous attention patterns, suggesting multiple representational pathways for systemic signal encoding. This pilot study demonstrates that retinal microvascular features contain measurable signals associated with systemic abnormalities, particularly microvascular damage. By integrating multi-task learning with quantitative XAI validation, this framework advances retinal imaging toward interpretable digital biomarkers for systemic risk stratification in diabetes.

Background: Type 2 diabetes mellitus (T2DM) is increasingly recognised as a systemic disease characterised by coordinated dysfunction across metabolic, renal, lipid, and inflammatory pathways. Existing clinical assessments often fail to capture this multi-dimensional burden. Methods: We conducted a retrospective study of 1,195 patients using routinely collected laboratory biomarkers. System-level abnormality indices were constructed to quantify organ-specific dysfunction, and multi-system involvement was defined as abnormalities in two or more systems. Supervised machine learning models, including logistic regression, random forest, and gradient boosting, were trained to predict multi-system dysregulation. Model interpretability was achieved using SHapley Additive exPlanations (SHAP). Results: The gradient boosting model demonstrated near-perfect discrimination (AUC = 1.000), significantly outperforming logistic regression (AUC = 0.925). Feature attribution analysis revealed that hyperglycaemia, renal impairment, dyslipidaemia, and inflammation were the dominant drivers of multi-system risk. Dose-response relationships observed in partial dependence analyses further supported the biological plausibility of model predictions. Conclusion: This study presents an interpretable, data-driven framework for quantifying systemic disease burden in T2DM. By linking routine biomarkers to multi-organ dysfunction, our approach provides both predictive accuracy and mechanistic insight, offering potential for improved risk stratification and precision medicine in diabetes care. The data and code used in this study are openly available on GitHub at: https://github.com/MiniHanWang/Type-2-Diabetes-1.git

Self-supervised learning (SSL) is now a standard way to pretrain medical image models, but performance is still mostly judged by downstream accuracy. For safety-critical screening tasks such as diabetic retinopathy grading, this is not enough: a model must also know when its predictions are unreliable and defer uncertain cases for clinical review. In this work, we examine how the length of SSL pretraining influences calibrated confidence and confidence-based abstention. We evaluate multiple SSL checkpoints under a fixed fine-tuning protocol and assess calibrated confidence, coverage, selective accuracy, and selective macro-F1. Across datasets and data regimes, SSL pretraining improves selective prediction compared to training from scratch. Unlike prior SSL studies that primarily evaluate downstream accuracy or AUROC, we analyze how SSL pretraining duration influences confidence behavior under calibrated confidence-based abstention. However, once accuracy saturates, selective performance can still change markedly across checkpoints, and longer pretraining does not consistently improve reliability. These results underscore the importance of abstention-aware evaluation and suggest that pretraining length should be treated as an important reliability-related design choice rather than only a computational detail. Code is available at GitHub.

Diabetic Retinopathy (DR) is one of the leading causes of preventable blindness, yet rural regions often lack the specialists and infrastructure needed for early detection. Although cloud-based deep learning systems offer high accuracy, they face significant challenges in these settings due to high latency, limited bandwidth, and high data transmission costs. To address these challenges, we propose a two-tier edge-cloud cascade on the public APTOS 2019 Blindness Detection dataset. Tier 1 runs a lightweight MobileNetV3-small model on a local clinic device to perform a binary triage between Referable DR (Classes 2-4) and Non-referable DR (Classes 0-1). Tier 2 runs a RETFoundDINOv2 model in the cloud for ordinal severity grading, but only on the subset of images flagged as referable by Tier 1. On a stratified APTOS test split of 733 images, Tier 1 reaches 98.99% sensitivity and 84.37% specificity at a validation-tuned high-sensitivity threshold. The default cascade forwards 49.52% of test images to Tier 2, reducing cloud calls by 50.48% relative to using a cloud-based model for all images. In the deployed 4-class output space (Class 0-1 / Class 2 / Class 3 / Class 4), the cascade obtains 80.49% accuracy and 0.8167 quadratic weighted kappa; the cloud-only baseline obtains 80.76% accuracy and 0.8184 quadratic weighted kappa. On APTOS, the cascade cuts cloud use by about half with a modest drop in grading performance. Index Terms: Diabetic Retinopathy, Edge-Cloud Cascade, MobileNetV3-small, RETFound-DINOv2, Retinal Screening, tele-ophthalmology

Diabetic Retinopathy (DR) is an art and science of recording and classifying the retinal images of a diabetic patient. DR classification deals with classifying retinal fundus image into five stages on the basis of severity of diabetes. One of the major issue faced while dealing with DR classification problem is the large and varying size of images. In this paper we propose and explore the use of several downscaling algorithms before feeding the image data to a Deep Learning Network for classification. For improving training and testing; we amalgamate two datasets: Kaggle and Indian Diabetic Retinopathy Image Dataset. Our experiments have been performed on a novel Multi Channel Inception V3 architecture with a unique self crafted preprocessing phase. We report results of proposed approach using accuracy, specificity and sensitivity, which outperform the previous state of the art methods. Index Terms: Diabetic Retinopathy, Downscaling Algorithms, Multichannel CNN Architecture, Deep Learning

Automated grading of diabetic retinopathy (DR) faces several critical challenges: subtle inter-grade visual distinctions in fine-grained lesion patterns, distributional discrepancies induced by heterogeneous imaging devices and acquisition conditions, and the inherent inability of purely visual approaches to exploit clinical semantic knowledge. In this paper, we propose CLIP-Guided Semantic Diffusion (CGSD), a DR grading framework that synergistically integrates vision-language pretraining with diffusion probabilistic modeling. We adopt a domain-specific vision-language model tailored for DR grading as the semantic guidance module and adapt it to the target domain via Low-Rank Adaptation (LoRA), effectively bridging the distributional gap between the pretrained model and the target dataset with only a minimal number of trainable parameters. Building on this foundation, we construct a cross-modal semantic conditioning vector by computing the dot product between image features and the text description features of each DR grade, yielding a joint representation that simultaneously encodes visual content and clinical-grade semantics. This vector serves as the conditioning signal for the diffusion denoising network, replacing the structurally complex dual-branch visual prior employed in existing diffusion-based classification methods. Experiments on the APTOS 2019 dataset demonstrate that the proposed approach achieves an accuracy of 87.5% and a macro-averaged F1 score of 0.731, outperforming a variety of representative methods. Ablation studies further validate the independent contribution of each constituent module.

Diabetic Retinopathy (DR) is a leading cause of preventable blindness among working-age adults worldwide, yet most automated screening systems are limited to image-level classification and lack clinically structured reporting. We propose Retina-RAG, a low-cost modular framework that jointly performs DR severity grading, macular edema (ME) detection, and report generation. The architecture decouples a high-performance retinal classifier and a parameter-efficient vision-language model (Qwen2.5-VL-7B-Instruct) adapted via Low-Rank Adaptation (LoRA), enabling flexible component integration. A retrieval-augmented generation (RAG) module injects curated ophthalmic knowledge together with structured classifier outputs at inference time to improve diagnostic consistency and reduce hallucinations. Retina-RAG achieves an F1-score of 0.731 for DR grading and 0.948 for ME detection, substantially outperforming zero-shot Qwen (0.096, 0.732) and MMed-RAG (0.541, 0.641) on a retinal disease detection dataset with captions. For report generation, Retina-RAG attains ROUGE-L 0.438 and SBERT similarity 0.884, exceeding all baselines. The full framework operates on a single consumer-grade GPU, demonstrating that clinically structured retinal AI can be achieved with modest computational resources.

Effectively stratifying patient risk in chronic diseases like glaucoma is a major clinical challenge. Clinicians need tools to identify patients at high risk of progression from sparse and irregularly-sampled electronic health records (EHRs). We propose a novel deep kernel learning (DKL) architecture that leverages a Gaussian Process (GP) backend. The GP's kernel is defined by a transformer-based feature extractor applied to clinical-BERT embeddings to model glaucoma patient trajectories from multimodal EHR data. Our method successfully identifies three clinically distinct patient subgroups. Crucially, the model learns to decouple disease progression from current severity, identifying a high-risk group with a worsening trajectory despite having better average visual acuity than a second, stably poor group. This reveals that the model learns to identify progression risk rather than just the current disease state. This ability to stratify patients based on their risk trajectory progression offers a powerful tool for clinical decision support, enabling targeted interventions for high-risk individuals and improving the management of glaucoma care.

The quality of diabetic retinopathy (DR) screening relies on the ability to correctly grade severity; however, many deep-learning (DL) classifiers cannot be easily interpreted in the clinical context. This study presents a methodology that combines strong discriminative models with multimodal explanations, converting retinal pixels into clinically interpretable outputs. Using the APTOS 2019 benchmark, we evaluated six representative CNN- and transformer-based backbones under a controlled protocol with stratified five-fold cross-validation. We then compared ensembling strategies (hard voting, weighted soft voting, stacking) and investigated a hybrid class-level fusion variant to exploit grade-specific advantages. For interpretability, we produced Grad-CAM++ visual attribution maps and short textual rationales using vision-language models (VLMs) conditioned on the fundus image and classifier outputs under conservative prompting constraints. Modern CNN backbones (ResNet-50 and ConvNeXt-Tiny) provided the strongest single-model baselines, with cross-validated QWK up to 0.919 and 0.914, respectively. Ensembling improved ordinal agreement, and weighted soft voting was the most consistent across folds (QWK 0.934 +/- 0.017). Hybrid class-level fusion was competitive but did not yield a statistically reliable improvement over standard fusion in paired fold comparisons (Holm-adjusted p >= 1.000). For explanation quality, Grad-CAM++ offered plausible but coarse localization, and VLM rationales were generally grade-consistent. Quantitatively, VLM variants showed a trade-off between clinical completeness and template-level semantic similarity (coverage 0.700 vs. BERTScore 0.072), while image-text alignment was comparable (CLIPScore approximately 0.34).

Reliable automated analysis of Optical Coherence Tomography (OCT) imaging is crucial for diagnosing retinal disorders but faces a critical barrier: the need for expensive, labor-intensive expert annotations. Supervised deep learning models struggle to generalize across diverse pathologies, imaging devices, and patient populations due to their restricted vocabulary of annotated abnormalities. We propose an unsupervised anomaly detection framework that learns the normative distribution of healthy retinal anatomy without lesion annotations, directly addressing annotation efficiency challenges in clinical deployment. Our approach leverages a discrete latent model trained on normal B-scans to capture OCT-specific structural patterns. To enhance clinical robustness, we incorporate retinal layer-aware supervision and structured triplet learning to separate healthy from pathological representations, improving model reliability across varied imaging conditions. During inference, anomalies are detected and localized via reconstruction discrepancies, enabling both image and pixel-level identification without requiring disease-specific labels. On the Kermany dataset (AUROC: 0.799), our method substantially outperforms VAE, VQVAE, VQGAN, and f-AnoGAN baselines. Critically, cross-dataset evaluation on Srinivasan achieves AUROC 0.884 with superior generalization, demonstrating robust domain adaptation. On the external RETOUCH benchmark, unsupervised anomaly segmentation achieves competitive Dice (0.200) and mIoU (0.117) scores, validating reproducibility across institutions.

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.

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.

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.