Fundus Imaging
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2 papers in the last four weeks, against 2 the four weeks before. 0.0% of all new papers.
Latest papers 31
Background: Artificial intelligence (AI)-based glaucoma detection from colour fundus photographs (CFP) offers scalable screening, but performance may decline on external datasets because of differences in ground-truth definitions, populations, and coexisting conditions such as high myopia (HM). We developed and validated a Vision Transformer-based deep learning (DL) model for glaucoma detection across multi-ethnic cohorts with and without HM. Methods: A ViT-B/16 model with predictive uncertainty estimation was developed using 56,483 CFPs (57.1% with myopia; 14.4% with HM). Glaucoma labels were standardised using clinical, imaging, and perimetry data. The model was validated on 16 independent datasets across three continents, including four datasets with explicit HM labels. Findings: Internal AUROC was 98.7% (95% CI 98.2-99.1%), with sensitivity 94.5% and specificity 97.3%. Across 16 external datasets from eight countries, AUROCs ranged from 86.4% to 99.6%. In HM eyes, internal AUROC was 97.8% (95% CI 96.1-99.2%), with sensitivity 94.8% and specificity 93.7%. External HM AUROCs were 86.5% in the Beijing Eye Study and 93.3%, 91.8%, and 85.5% in hospital-based datasets from Taiwan, Thailand, and South Korea. In an exploratory HM clinical evaluation, the model had higher CFP-only diagnostic accuracy than ophthalmologists and trained graders (92.0% vs 70.0%; p=0.008) and performed comparably to glaucoma specialists using full clinical information. Interpretation: The model showed robust glaucoma detection across myopic and non-myopic multi-ethnic populations and may support AI-assisted screening in settings with high HM prevalence.
Interpretable AI plus Handheld, Portable Retinal Photographs: A Low-Cost Glaucoma Screening Solution for West Africa
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 0.830.03 (Volk) and 0.870.04 (Canon); Classification model: AUCs of 0.850.01 (Volk) and 0.930.01 (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.
Modelling Geographic Atrophy Progression using Implicit Neural Representations
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.
Disentangling Co-Occurring Retinal Pathologies with Saliency-Guided Sparse Expert Routing
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.
UPolarSQ: Polar Representation Learning for Optic Disc and Peripapillary Atrophy Segmentation and Quantification in Fundus Photographs
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.
An Agentic AI Framework Overcomes Fundamental Limitations of Large Language Models for Glaucoma Detection from Fundus Photography
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.
SpecF2M: A Spectral-Aware Multi-task Network Estimating Axial Length and Refractive Error from Pediatric Fundus Photographs
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 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.
Color Fundus Photography Analysis: Co-evolution of Data, Preprocessing, and Modeling toward Multimodal AI
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.
Counterfactual Explainability Framework With CycleGAN And Counterfactual-Classifier Alignnment Score for Retinal Disease Classification
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.
Luminosity-Adaptive Contrast Enhancement Using CLAHE for Retinal Fundus Images with Quantitative Validation and Comparative Analysis
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.
RED-Sphere: Hyperspherical Residual Edge Debiasing for Cross-Population Fundus Disease Domain Generalization
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.
GlaKG: A Biomarker-Centric Fundus Knowledge Graph for Explainable Glaucoma Diagnosis and Risk Assessment
Glaucoma is a leading cause of irreversible blindness worldwide, yet most automated diagnosis systems rely on opaque deep-learning models that offer little clinical interpretability. We present GlaKG, a biomarker-centric fundus knowledge graph that integrates structural biomarkers, clinically grounded rules, and image features to produce traceable reasoning for glaucoma diagnosis and risk stratification. GlaKG encodes six entity types (Fundus Image, Optic Disc, Neural Rim, Pathology, Diagnosis, Risk Level), eight relation types, and 11 clinically validated rules into a unified graph, so that every prediction is accompanied by an explicit reasoning chain linking biomarker evidence to activated clinical rules. To keep knowledge-based reasoning strictly separate from label information, we adopt a post-processing fusion framework that combines ResNet50 image embeddings with a normalized KG reasoning-chain score via a tunable weight alpha, with all fitting confined to the training split. On a publicly available, AI-annotated fundus dataset, GlaKG reaches F1 = 0.9953 for binary glaucoma classification and 0.930 accuracy with 0.922 weighted F1 for four-class risk stratification; we report openly that the dataset's biomarker annotations are highly label-correlated, and therefore frame these figures as an upper bound attainable with clean structured biomarkers rather than as leakage-free image-only performance. Feature-importance analysis shows KG-derived and biomarker features contributing near-equally (51.1% vs. 48.9%), and the reasoning chain flags borderline cases by exposing low chain scores rather than failing silently. GlaKG's central contribution is therefore a clinically auditable reasoning framework that complements raw predictive performance by explicitly exposing the biomarker evidence and rule activations behind each decision.
Model Confidence-Guided Multi-Image Fusion of Fundus Images for Diabetic Retinopathy Diagnosis
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.
Cross-Modal Iteration Distillation for Robust IHD Screening: The IDNet Framework and A New Benchmark
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.
FunPiQ: A New Benchmark for Pixel-Level Quality Assessment in Fundus Images
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.
A Dual Edge Spatial Jacobian Image Graph for Interpretable Diabetic Retinopathy Grading
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 (), DR-XAI-style lesion evidence maps (), a 128-dimensional lesion-based contrastive image embedding (), and AutoMorph morphometric biomarkers (). The spatial edge branch () encodes vessel-lesion geometry, while the Jacobian branch () 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.
EFIQA: Explainable Fundus Image Quality Assessment via Anatomical Priors
Image quality control is vital for a wide range of downstream applications. Deep learning-based image quality assessment methods typically train classifiers on dataset-specific quality labels, inheriting two limitations: (1) generalization is tied to the labeling criteria of the training set and (2) these methods cannot provide spatial feedback on where the quality is degraded, lacking explainability. In this work, we propose EFIQA, a framework that requires no quality-related supervision and produces spatial quality maps by design. Rather than learning
what is degradation" from human-annotated labels, EFIQA learns what should be there" by leveraging anatomical priors. For fundus photography, we instantiate this as a two-stage approach, by first training an unsupervised anomaly detector via masked anatomical inpainting to identify regions of missing vasculature, and then distilling this prior knowledge into a shallow adapter mapping features of a frozen foundation model to precise quality maps. External-dataset evaluation demonstrates that this label-free approach with minimal adaptation achieves better performance and explainability compared with supervised methods across benchmarks with different quality criteria, highlighting its potential for real-world applications.Propagating Structural Guidance: Synthesizing Fluorescein Angiography from Fundus Images and Sparse OCT Scans
Fundus fluorescein angiography (FFA) is critical for assessing retinal vascular abnormalities, but its acquisition is invasive and not always feasible. In contrast, color fundus photography (CFP) is non-invasive and widely accessible, which has motivated studies on CFP-to-FFA synthesis. However, prior works rely solely on CFP surface texture, fundamentally limiting the ability to reconstruct functional vascular information and subtle pathological changes. To address this, we propose a novel framework that synthesizes FFA from CFP with structural guidance provided by optical coherence tomography (OCT). We construct a multi-modal retinal imaging dataset with paired CFP, FFA, and OCT from 3,676 patient eyes--the first tri-modally aligned dataset in retinal imaging. To bridge the spatial gap between OCT and fundus modalities, we propose a Spatially Aligned Cross-Modal Fusion (SACMF) module that projects depth-resolved OCT features onto the fundus plane and injects them into the CFP encoder via adaptive layer normalization. Beyond feature fusion, we further introduce Token-wise Cross-Modality Alignment (TCMA), a token-level contrastive learning strategy that explicitly aligns CFP and FFA representations at corresponding spatial positions. Our method achieves superior synthesis performance compared to state-of-the-art methods. Moreover, extensive experiments demonstrate that the FFA images synthesized by our approach bring greater improvements in downstream disease diagnosis performance than existing methods, highlighting the clinical potential of our approach as a non-invasive decision-support tool in routine workflows. The code is available at https://github.com/while-plus/OCT-guide-FFA-Syn.
Ellipse Meets Bit-Planes: A Novel Approach to RNFL based Glaucoma Detection Using Advanced Image Processing and Deep Learning
This work proposes an integrated pipeline for automatic glaucoma detection method from easily available colour fundas images based on an adaptive algorithm for ellipse-based polar transformation, to enhance the analysis of the Retinal Nerve Fiber Layer (RNFL) as the primary biomarker for observing glaucomatous changes, regardless of optic disc and macula position. Utilizing this transformation, we introduce two distinct frameworks tailored to different operational needs. The first framework, a deep learning-inspired feature fusion approach, achieves a 99.3% detection rate, ideal for settings where high precision is essential, despite higher computational demands. The second framework employs a novel image-processing algorithm based on bit-plane slicing, offering 92.31% accuracy and optimized for environments requiring rapid inference with minimal resource consumption. Both frameworks provide scalable and cost-effective solutions for early glaucoma detection. This study highlights the potential of RNFL-based diagnostic tools in addressing the global challenge of glaucoma, particularly in underserved regions.
EyeMVP: OCT-Informed Fundus Representation Learning via Paired CFP--OCT Pretraining
Color fundus photography (CFP) is the mainstay of large-scale retinal screening, but its diagnostic capacity is limited by the lack of depth-resolved structure, which optical coherence tomography (OCT) provides yet is less accessible at population scale. We present EyeMVP, a cross-modal retinal foundation model that uses paired CFP--OCT pretraining to learn OCT-informed CFP representations while requiring only CFP at inference. Pretrained on 674,893 same-eye same-day CFP--OCT triples from 112,642 patients across eight hospitals, EyeMVP uses cross-modal masked reconstruction to enrich CFP features with OCT-associated supervision, and combines source-constrained cross-attention with CFP-derived structural masks to accommodate the non-aligned geometry of en-face CFP and cross-sectional OCT. Across 15 dataset-level settings spanning classification and segmentation, under both full-data and few-shot regimes, EyeMVP performs on par with or better than representative retinal foundation models, with consistent gains on macular and optic-nerve tasks; it attains AUROCs of 0.923 for macular edema and 0.867 for myopic macular schisis, two conditions poorly resolved in CFP. In an exploratory reader study, EyeMVP surpasses junior and intermediate ophthalmologists but not seniors on macular edema, while exceeding all groups on myopic macular schisis. These results indicate that cross-modal reconstruction can enrich CFP representations with OCT-associated supervision, offering a practical route to stronger CFP-based screening.
Towards Clinically Interpretable Ophthalmic VQA via Spatially-Grounded Lesion Evidence
Visual Question Answering (VQA) holds great promise for clinical support, particularly in ophthalmology, where retinal fundus photography is essential for diagnosis. However, ophthalmic VQA benchmarks primarily emphasize answer accuracy, neglecting the explicit visual evidence necessary for clinical interpretability. In this work, we introduce FundusGround, a new benchmark for clinically interpretable ophthalmic VQA with spatially-grounded lesion evidence. Specifically, we propose a three-stage pipeline that collects 10,719 fundus images with 15,595 image-level meticulously annotated lesions. To ensure anatomical consistency and clinical validity, all lesions are spatially localized using the Early Treatment Diabetic Retinopathy Study (ETDRS) grid, enabling standardized mapping to nine clinically meaningful retinal regions. Built upon this structured lesion evidence, 72,706 questions are then generated spanning four formats: open-ended, closed-ended, single-choice, and multiple-choice. We further benchmark multiple general- and medical- large vision-language models using dual metrics for answer accuracy and lesion-level reasoning. The experiments demonstrate that incorporating lesion-level visual evidence consistently improves model performance and transparency, highlighting the necessity of explicit spatial grounding for reliable and explainable ophthalmic VQA.
ELEMENT: Multi-Modal Retinal Vessel Segmentation Based on a Coupled Region Growing and Machine Learning Approach
Vascular structures in the retina contain important information for the detection and analysis of ocular diseases, including age-related macular degeneration, diabetic retinopathy and glaucoma. Commonly used modalities in diagnosis of these diseases are fundus photography, scanning laser ophthalmoscope (SLO) and fluorescein angiography (FA). Typically, retinal vessel segmentation is carried out either manually or interactively, which makes it time consuming and prone to human errors. In this research, we propose a new multi-modal framework for vessel segmentation called ELEMENT (vEsseL sEgmentation using Machine lEarning and coNnecTivity). This framework consists of feature extraction and pixel-based classification using region growing and machine learning. The proposed features capture complementary evidence based on grey level and vessel connectivity properties. The latter information is seamlessly propagated through the pixels at the classification phase. ELEMENT reduces inconsistencies and speeds up the segmentation throughput. We analyze and compare the performance of the proposed approach against state-of-the-art vessel segmentation algorithms in three major groups of experiments, for each of the ocular modalities. Our method produced higher overall performance, with an overall accuracy of 97.40%, compared to 25 of the 26 state-of-the-art approaches, including six works based on deep learning, evaluated on the widely known DRIVE fundus image dataset. In the case of the STARE, CHASE-DB, VAMPIRE FA, IOSTAR SLO and RC-SLO datasets, the proposed framework outperformed all of the state-of-the-art methods with accuracies of 98.27%, 97.78%, 98.34%, 98.04% and 98.35%, respectively.
Scientific Domain Knowledge Improves Vision-Language Fundus Models
Vision-language models hold considerable promise for ophthalmology, but it remains unclear which training data source best conveys expert domain knowledge. Existing ophthalmic models are trained on fixed text templates, medical reports, or general biomedical literature, sources that have never been compared under matched conditions. To include domain-specific literature in this comparison, we present PubMed-Ophtha, a hierarchical dataset with high domain density of 102,023 panels with their subcaptions from 15,842 open-access articles in PubMed Central. We then finetuned identical CLIP models on each source, using a general biomedical literature model as baseline, and found that domain-specific literature achieved the best average performance across 110 clinical tasks, reaching a mean linear probing AUROC of 88.63% ahead of medical reports (85.68%). Restricting the dataset to fundus images, to the image count of the medical report dataset, or to articles unrelated to the evaluation datasets did not reduce performance, indicating that the gains likely stem from domain density. We release the dataset, the finetuned models, and the full generation pipeline.
Prediction of Alzheimer's Disease Risk Factors from Retinal Images via Deep Learning: Development and Validation of Biologically Relevant Morphological Associations in the UK Biobank
The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using 62,876 CFPs from 44,501 unique participants from the UK Biobank, DL models were trained to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability.
Training-inference input alignment outweighs framework choice in longitudinal retinal image prediction
Predicting disease progression from longitudinal imaging is useful for clinical decision making and trial design. Recent methods have moved toward increasing generative complexity, but the conditions under which this complexity is necessary remain unclear. We propose that generative complexity should match the entropy of the predictable component of a task's conditional posterior, with training-inference input alignment required in all regimes. Two model-light measurements, a task-entropy analysis on raw image pairs and a posterior-concentration analysis on a stochastic model, let practitioners assess the complexity a task warrants before committing to a modeling framework. We validated this framework on a fundus autofluorescence (FAF) dataset by contrasting five conditioning configurations, sharing one architecture and training set, spanning standard conditional diffusion, inference-aligned stochastic training, and deterministic regression. Training-inference alignment produced large gains (delta-SSIM +0.082, SSIM +0.086, both p < 0.001), while the choice among aligned frameworks produced no clinically meaningful difference across evaluated metrics. Across two FAF platforms, inter-visit change was dominated by time-invariant acquisition variability rather than disease progression, and the stochastic models' posteriors collapsed to an effective point, explaining the framework equivalence. We trained a deterministic Temporal Retinal U-Net (TRU) and evaluated it on 28,899 eyes across three manufacturers and two modalities (two FAF platforms and en-face SLO), with three independent cohorts evaluated zero-shot. TRU matched or exceeded three published baselines on delta-SSIM, SSIM, and PSNR. These findings show that when disease progression is slow compared with acquisition variability, a deterministic regression model matches or outperforms more complex stochastic alternatives.
Diffusion Autoencoder for Unsupervised Artifact Restoration in Handheld Fundus Images
The advent of handheld fundus imaging devices has made ophthalmologic diagnosis and disease screening more accessible, efficient, and cost-effective. However, images captured from these setups often suffer from artifacts such as flash reflections, exposure variations, and motion-induced blur, which degrade image quality and hinder downstream analysis. While generative models have been effective in image restoration, most depend on paired supervision or predefined artifact structures, making them less adaptable to unstructured degradations commonly observed in handheld fundus images. To address this, we propose an unsupervised diffusion autoencoder that integrates a context encoder with the denoising process to learn semantically meaningful representations for artifact restoration. The model is trained only on high-quality table-top fundus images and infers to restore artifact-affected handheld acquisitions. We validate the restorations through quantitative and qualitative evaluations, and have shown that diagnostic accuracy increases to 81.17% on an unseen dataset and multiple artifact conditions
Towards Interpretable Foundation Models for Retinal Fundus Images
Foundation models are used to extract transferable representations from large amounts of unlabeled data, typically via self-supervised learning (SSL). However, many of these models rely on architectures that offer limited interpretability, a critical issue in high-stakes domains such as medical imaging. We propose \model, a foundation model that is interpretable-by-design via a BagNet backbone whose small receptive fields generate class evidence maps that are faithful to the model's decision-making process. Additionally, \model{} incorporates a projection layer during pretraining that enables direct visualization of the representation space, providing a dataset-level view of the learned structure including meaningful clinical clusters as well as potential spurious correlations. We trained \model{} on over 800,000 color fundus photographs from various sources to learn generalizable representations for different downstream tasks. Our model achieves performance comparable to RETFound, which has more parameters, while providing interpretable predictions on out-of-distribution data. These results suggest that large-scale SSL pretraining paired with inherent interpretability can lead to robust representations for retinal imaging. Code and pretrained models are available at www.anonymous.4open.science/dual-IFM.
retinalysis-vascx: An explainable software toolbox for the extraction of retinal vascular biomarkers
Automatic extraction of retinal vascular biomarkers from color fundus images (CFI) is crucial for large-scale studies of the retinal vasculature. We present VascX, an open-source Python toolbox that extracts biomarkers from CFI artery-vein segmentations. VascX starts from vessel segmentation masks, extracts their skeletons, builds undirected and directed vessel graphs, and resolves vessel segments into longer vessels. A comprehensive set of biomarkers is derived, including vascular density, central retinal equivalents (CREs), and tortuosity. Spatially localized biomarkers may be calculated over grids placed relative to the fovea and optic disc. VascX is released via GitHub and PyPI with comprehensive documentation and examples. Our test-retest reproducibility analysis on repeat imaging of the same eye by different devices shows that most VascX biomarkers have moderate to excellent agreement (ICC > 0.5), with important differences in the level of robustness of different biomarkers. Our analyses of biomarker sensitivity to image perturbations and heuristic parameter values support these differences and further characterize VascX biomarkers. Ultimately, VascX provides an explainable and easily modifiable feature-extraction toolbox that complements segmentation to produce reliable retinal vascular biomarkers. Our graph-based biomarker computation stages support reproducible, region-aware measurements suited for large-scale clinical and epidemiological research. By enabling easy extraction of existing biomarkers and rapid experimentation with new ones, VascX supports oculomics research. Its robustness and computational efficiency facilitate scalable deployment in large databases, while open-source distribution lowers barriers to adoption for ophthalmic researchers and clinicians.
Evaluating Fundus-Specific Foundation Models for Diabetic Macular Edema Detection
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.
Clinician-Friendly Foundation Models for Ophthalmic Image Diagnostics without Fine-Tuning or Technical Barriers
Artificial intelligence (AI) shows remarkable potential in medical imaging diagnostics, yet most current models require retraining when applied across different clinical settings, limiting their scalability. We developed GlobeReady, a deployment-oriented platform powered by the RetiGlobe foun- dation model and local feature augmentation. RetiGlobe was pretrained in two stages: 1) self-supervised learning using DINOv2 on 38 million synthetic ophthalmic images, and 2) contrastive learning using CLIP on 475,845 real image-text pairs spanning diverse ethnicities, imaging devices, and geographic regions worldwide. We evaluate GlobeReady on 488,448 ophthalmic images, including color fundus photographs (CFPs) and optical coherence tomography scans, from multi-centres in China, Singapore, Vietnam and the UK. Prospective testing included usability assessment with 31 ophthalmologists. Exploratory analyses evaluated domain generalisability, Bayesian uncertainty quantification, out-of-distribution (OOD) detection, and feature-based case retrieval.