Retinal Disease Classification

Retinal fundus images frequently carry more than one disease, and public fundus datasets are heterogeneous and severely long-tailed. Clinical triage suggests a staged design, in which a screening gate, a disease-group router and group-specific classifiers operate in sequence, but it is unclear whether this hierarchy earns its complexity. We present a controlled comparison of three architectures on a unified 39-target label space built from RFMiD 1.0, RFMiD 2.0 and ODIR-5K (12,652 images): (i) a three-stage gated cascade of eight models, (ii) a flat model with 39 independent sigmoid outputs, and (iii) a label-correlation model that replaces the flat linear head with 39 learned label queries and a two-layer transformer decoder. All three share one Swin-V2-B backbone, one preprocessing pipeline and one training protocol, so differences are attributable to the architecture. Staging offers no consistent advantage: tracing every missed disease instance to the stage that lost it shows that the two coarse gates discard 34.2% of true instances while the fine-grained classifiers lose only 6.7%, and the gates' hard zeros depress the cascade's macro-AUC to 0.747. Label-correlation modeling gives the largest single gain, raising the detection rate from 0.621 to 0.682 (0.689 with test-time augmentation). Blending the flat and label-correlation models under four-view test-time augmentation is the best configuration on six of eight metrics (exact match 0.694, micro-F1 0.678, macro-F1 0.456, macro-AUC 0.972). On definition-matched class subsets it matches or exceeds four recent studies on macro- and micro-F1, most clearly on low-support pathologies. We also show that ensembling a gated cascade with continuous-output models is harmful, and that per-source negative sampling is needed to remove a dataset shortcut that otherwise yields a spurious AUC of 1.000.

Clinical screening for diabetic retinopathy proceeds in stages, yet most automated systems grade fundus images with a single black-box network. Three gaps remain: (i) lesions differ widely in size and contrast, but segmenters typically apply the same blocks to all; (ii) ungradable images are usually excluded or treated as an extra class, and lesion-aware graders seldom test whether lesions drive the grade; (iii) staged systems often report each stage only on the images reaching it, leaving propagated errors unmeasured. HierarchiRetina, a screening, segmentation and grading cascade with inspectable stage outputs, addresses each gap. First, HSMoE-AUNet is a U-Net whose skip, bottleneck and decoder blocks are sparse mixtures of heterogeneous experts, with lesion-matched types, counts and losses; SwinHRUNetPP, a dual-encoder vessel segmenter, uses a field-of-view-restricted loss. Second, LG-DRG separates gradability from ordinal severity and lets lesion masks query the image through gated cross-attention. Third, an end-to-end evaluation counts screening misses as errors and traces each error to its stage. Pooled Dice ranged from 0.184 (microaneurysms) to 0.579 (exudates); vessel Dice was 0.731. On 58,689 held-out images from six datasets, end-to-end quadratic weighted kappa was 0.804, with referral sensitivity 0.832 at specificity 0.947, and the screening gate caused 66% of errors. In ablations, the grade ignored the masks, even with the cross-attention gate started open. On all 4,105 official DDR test images, six-class accuracy was 85.6%, above the best published six-class result we found (83.8%). Staged screening systems should be evaluated end-to-end, with stage attribution and mask ablation, before clinical deployment.

Retinal foundation models have demonstrated strong performance across a wide range of ophthalmic tasks, yet relatively little is known about how disease-related information is represented within their learned embeddings and whether this distribution influences downstream prediction performance. In this work, we use Age-related Macular Degeneration (AMD) as a case study to investigate how disease severity is represented within the embedding space of RET-CLIP, a retinal vision-language foundation model, using bilateral fundus images from the AREDS dataset, benchmarked against non-retinal encoders. We first characterize the distribution of AMD severity within the learned representation space and then evaluate how this structure influences classification performance across three clinically relevant task formulations of increasing granularity. Finally, we analyze the most influential latent dimensions combining feature attribution, statistical phenotype association, and qualitative image analyses. Our results show that RET-CLIP represents AMD severity as a continuous spectrum rather than a set of discrete categories, with healthy and advanced disease stages exhibiting clearer separation than intermediate ones. This organization was reflected in downstream performance, which decreased from a balanced accuracy of 0.844 and 0.814 for binary AMD and Late-AMD detection respectively to 0.446 for six-class grading. Furthermore, the most influential latent dimensions were statistically associated to distinct retinal phenotypes, including drusen accumulation, pigmentary alterations, and advanced retinal lesions. These findings suggest that the structure of retinal foundation-model representations influences the difficulty of clinically relevant prediction tasks and demonstrate the potential of representation-level analysis for understanding disease organization and improving interpretability.

Progress in AI-based retinal image analysis has advanced with foundation models, yet evaluating their reliability remains challenging. Performance reported on a single dataset does not capture how models behave under dataset shift, across clinical definitions, or for different patient subgroups. This limitation is particularly critical in medical imaging analysis, where robustness, calibration, and fairness are essential for safe deployment. We introduce FOCUS (Foundation Ophthalmic Cross-Dataset Understanding under Shift), a cross-dataset benchmark for evaluating retinal fundus models that considers vision-only encoder models (VM), vision-language dual-encoder models (VLM), and multimodal large language models (MLLM). FOCUS harmonizes binary diabetic retinopathy, referable diabetic retinopathy, and glaucomatous optic neuropathy tasks across ten public datasets spanning diverse geographies, acquisition conditions, and label protocols. The benchmark evaluates models through a unified analysis layer that measures ranking performance, calibration, subgroup disparities, and image-quality robustness. We present a large-scale evaluation covering 532 base configurations and 228 MLLM configurations adapted through supervised fine-tuning with low-rank adaptation (LoRA). Results show that no model family consistently dominates across tasks and datasets: general VM encoders achieve the strongest average ranking performance, medical MLLMs are competitive but variable, and dual encoder VLMs benefit substantially from lightweight adaptation. Fine-tuning improves in-domain performance but exhibits heterogeneous transfer to external datasets, particularly in calibration. These findings demonstrate that retinal model evaluation is inherently multidimensional. FOCUS provides a practical framework and public benchmark to assess generalization, reliability, and robustness beyond single-dataset leaderboards

Diabetic retinopathy (DR) is a major cause of preventable blindness, creating a need for accurate and trustworthy automated screening. This study investigates an explainable DR classification framework using vision foundation models and multiple transfer learning strategies. Three backbones, DINOv2, CLIP, and Vision Transformer (ViT), were evaluated using full fine-tuning, linear probing, and Low-Rank Adaptation (LoRA). Models were trained and internally evaluated on the ODIR dataset and externally evaluated on APTOS to assess generalization. DINOv2-LoRA achieved the highest internal AUROC of 0.758, while DINOv2 full fine-tuning and ViT full fine-tuning achieved the highest external AUROC of 0.920. Calibration was further assessed using reliability analysis after isotonic regression. For explainability, Grad-CAM and HiResCAM were evaluated against expert-annotated lesion masks from the IDRiD dataset using Dice, Intersection over Union (IoU), and Pointing Game metrics. The results demonstrate that foundation models, particularly DINOv2, can provide strong predictive performance, while LoRA offers a parameter-efficient alternative to full fine-tuning. Quantitative evaluation of explanation maps further supports the assessment of whether model attention corresponds to clinically relevant retinal lesions.

Despite the growing number of public datasets, annotated medical images remain scarce. Supervised learning methods achieve strong performance on many benchmarks, however require large amounts of labeled data, which are costly and time-consuming to obtain in the medical domain. To address this limitation, contrastive self-supervised learning (SSL) has emerged as a promising alternative for learning useful representations from unlabeled data. In this work, we investigate two SSL frameworks, SimSiam and SimCLR, for retinal disease classification from fundus images. We focus on understanding how augmentation strategies and training parameters influence representation learning under resource-constrained settings. Given limited data and computational capacity, we explore the feasibility of training SSL models with small batch sizes incorporated with retinal-specific augmentation techniques. Through a series of experiments, we assess the quality of learned representations via linear evaluation and fine-tuning across downstream tasks, including multi-disease classification and diabetic retinopathy grading. Our results show that tailoring augmentation strategies to the characteristics of retinal images plays a critical role in improving performance. Even under constrained settings, lightweight SSL frameworks can learn transferable representations that reduce dependence on large annotated datasets and achieve competitive results.

Retinal fundus photography is widely used for screening and monitoring ocular diseases, but many modern classification pipelines rely on deep latent representations and provide limited interpretability. This study develops an interpretable fundus image classification framework based on a ring-structured representation of the retinal vasculature centered on the optic disc. The method quantifies vessel geometry, color appearance, oxygenation-related vascular appearance, and vessel--background entropy within concentric retinal regions. These physiologically motivated descriptors are derived from vessel masks, image intensities, and optical-density measurements and aggregated across rings to capture spatial variation in vascular properties. Using only quantitative vascular descriptors, the proposed method achieved strong classification performance across three public fundus datasets. On HRF, it achieved 91.1% accuracy using automatically generated vessel masks, matching RETFound, a vision transformer pretrained on large-scale retinal fundus image data, under the same evaluation setting. Additional analyses suggest that pretrained image models are sensitive to acquisition-related spatial cues, including fundus scale and retinal position within the field of view, as well as broader non-vessel image characteristics. This framework may support interpretable disease classification, quantitative retinal phenotyping, and retinal biomarker discovery without requiring large task-specific training datasets.

Retinal diseases are a leading cause of irreversible vision impairment, making early and accurate diagnosis essential for effective treatment. Optical Coherence Tomography (OCT) serves as a critical imaging modality for this purpose, yet its automated analysis is hindered by inherent speckle noise, varying lesion scales, and subtle inter-class similarities. To address these challenges, we propose a novel framework, RetiWave-Mamba, which integrates spatial-frequency domain learning with state-of-the-art state space models. The framework utilizes Discrete Wavelet Transform (DWT) to decompose OCT images into low- and high-frequency streams, enabling decoupled processing of structural context and fine-grained details. For the low-frequency branch, we design a Multi-scale Contextual Localization Module (MCLM), which synergizes multi-scale dilation with spatial attention to expand the global receptive field and precisely localize lesion regions. For the high-frequency branch, we introduce an Attention-Guided High-Resolution Network (AG-HRNet) equipped with an intelligent gating mechanism to suppress noise propagation during multi-scale interactions. Furthermore, a Feature-Adaptive Mamba Projector (FAMP) is incorporated to form complementary channel-wise feature paths and adaptively reweight them using Mamba-generated gates. Extensive experiments on the OCT-C8 dataset demonstrate that our approach achieves a state-of-the-art (SOTA) classification accuracy of 98.38, surpassing existing methods. These results highlight the effectiveness of RetiWave-Mamba in identifying retinal pathologies and support its potential for computer-aided OCT image analysis.

Automated five-stage diabetic retinopathy (DR) grading requires more than high accuracy alone. Medical-grade deployment calls for lesion-aware preprocessing, ordinal predictions, calibrated uncertainty, and explainability to support reliable diagnostic systems. We present a unified pipeline that addresses these requirements using a Ben-Graham-green-channel CLAHE feature representation, an EfficientNetV2-L ordinal regressor, and Monte Carlo dropout for uncertainty-driven referral. Grad-CAM provides visual explanations aligned with clinically relevant lesions. The proposed method achieves a QWK of 91.31% on the APTOS-2019 official test split, placing it within the near-perfect agreement band (>80%). At a 20% referral rate, 293 of 366 images are automatically graded with a QWK of 90.40%. More complex cases are referred for specialist assessment, demonstrating a practical trade-off among grading quality, automation, and patient safety in robust, reliable, and deployment-ready medical diagnostic systems.

The advanced retinal disease diagnosing imaging modality, optical coherence tomography (OCT), encounters a lack of automation because of the high expenses for annotations performed by specialists. The use of SSL solves the problem of insufficient annotations using unlabeled B-scans; however, most of the current techniques for generating pseudo-labels are based on prediction confidence without considering the asymmetry between different types of errors. This paper proposes TRIAGE, a risk-controlled semi-supervised framework for OCT scans classification, which uses the concept of a patient-level conformal risk controller with an asymmetric cost matrix. TRIAGE unites three crucial modules: a hierarchical classifier that is capable of working with partially abnormal supervision of the disease subtypes, a patient-grouped conformal risk controller with primal-dual coverage control, and a context-aware Transformer teacher for cross-slice verification. On the dataset from Noor Eye Hospital (16,822 B-scans, 161 patients, and 554 volumes) with a test set of unseen patients, TRIAGE demonstrates 89.66% scan-level accuracy, 0.8805 macro-F1, 0.9641 macro-AUC, and an 8.34% under-grading rate when using only 20% of the labeled data. With only 5% of the labeled data, TRIAGE keeps 76.88% accuracy and a 0.1656 under-grading rate. Compared with the other six state-of-the-art semi-supervised methods, TRIAGE significantly outperforms them with ablation study demonstrating the contribution of each module in the overall framework performance (by 42.7% in terms of under-grading rate comparing to fixed threshold methods). TRIAGE demonstrates 98.00% accuracy for 3-class classification with 1% labeled data and 95.94% accuracy for 8-class classification with 10% labeled data on the OCT-C8 dataset.

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.

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.

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 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 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.

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.

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.

Modern deep learning offers powerful tools for automated retinal screening, but it remains unclear how different visual model families compare in realistic multi-disease settings and under domain shift. In this work, we benchmark twelve architectures across four model families: convolutional neural networks, vision transformers, hybrid CNN-transformer backbones, and vision-language models, using the Retinal Fundus Multi-disease Image Dataset (RFMiD). We evaluate two tasks: binary screening for any retinal disease and multi-label classification across 28 disease classes. Using standardized training, calibration, and evaluation protocols, we report AUC, F1, precision, recall, and sensitivity at a clinically relevant operating point with specificity near 80%. On RFMiD, all architectures perform well on binary screening, with AUC above 84%, but attention-based models perform best. SwinTiny and the hybrid CoAtNet0 and MaxViTTiny models achieve the strongest binary screening results and improve macro and micro F1 in the multi-label setting. Vision-language models, including CLIP ViT-B/16 and SigLIP-Base384, are competitive with CNN baselines but do not surpass the best transformer and hybrid backbones. In external validation on Messidor-2 for referable diabetic retinopathy, AUC ranges from 66.8% to 84.7%, with hybrid and transformer models again showing strong performance. These results provide a reproducible reference for model selection in multi-disease retinal screening and guide future automated screening tools for clinical deployment.

Retinal diagnosis is inherently bilateral: clinicians compare homologous structures across eyes (e.g., optic disc asymmetry), yet most deep models operate on monocular representations. We investigate whether explicit structural correspondence improves diagnosis, and propose Anatomy-Slot to operationalize this hypothesis. Anatomy-Slot introduces an unsupervised anatomical bottleneck by decomposing patch tokens into a set of emergent, structurally-coherent slots that correspond to anatomical regions, then aligning these slots across eyes via bidirectional cross-attention. On ODIR-5K with $n=10$ seeds, the method improves AUC by $4.2$ points over a matched ViT-L baseline (95% CIs; Wilcoxon signed-rank test, $W=0$, $p=0.002$). Pairing disruption and stress testing under Gaussian noise provide controlled tests of correspondence dependence and robustness under corruption. We further report quantitative optic disc grounding on REFUGE and cross-attention localization analysis. Beyond the reported gains, these results indicate that object-centric anatomical correspondence offers a principled path toward interpretable diagnostic systems aligned with clinical bilateral comparison.

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.

Despite strong performance of deep learning models in retinal disease detection, most systems produce static predictions without clinical reasoning or interactive explanation. Recent advances in multimodal large language models (MLLMs) integrate diagnostic predictions with clinically meaningful dialogue to support clinical decision-making and patient counseling. In this study, OcularChat, an MLLM, was fine-tuned from Qwen2.5-VL using simulated patient-physician dialogues to diagnose age-related macular degeneration (AMD) through visual question answering on color fundus photographs (CFPs). A total of 705,850 simulated dialogues paired with 46,167 CFPs were generated to train OcularChat to identify key AMD features and produce reasoned predictions. OcularChat demonstrated strong classification performance in AREDS, achieving accuracies of 0.954, 0.849, and 0.678 for the three diagnostic tasks: advanced AMD, pigmentary abnormalities, and drusen size, significantly outperforming existing MLLMs. On AREDS2, OcularChat remained the top-performing method on all tasks. Across three independent ophthalmologist graders, OcularChat achieved higher mean scores than a strong baseline model for advanced AMD (3.503 vs. 2.833), pigmentary abnormalities (3.272 vs. 2.828), drusen size (3.064 vs. 2.433), and overall impression (2.978 vs. 2.464) on a 5-point clinical grading rubric. Beyond strong objective performance in AMD severity classification, OcularChat demonstrated the ability to provide diagnostic reasoning, clinically relevant explanations, and interactive dialogue, with high performance in subjective ophthalmologist evaluation. These findings suggest that MLLMs may enable accurate, interpretable, and clinically useful image-based diagnosis and classification of AMD.

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).

While deep learning has advanced automated glaucoma screening via color fundus photography, existing purely data-driven models often overfit to confounding imaging artifacts and struggle to capture unpredictable pathological cues located beyond predefined anatomical boundaries. To address these limitations, we propose a retinal knowledge-oriented framework that synergizes dynamic multi-scale feature learning with domain-specific anatomical priors. The proposed architecture adopts a tri-branch structure to jointly model the global retinal context, the structural characteristics of the optic cup and disc, and dynamically cropped pathological regions. Specifically, we devise a Dynamic Window Mechanism (DWM) that adaptively discovers diagnostically informative patches via image-level supervision. Furthermore, we introduce a Knowledge-Enhanced Convolutional Block Attention Module (KE-CBAM) that explicitly incorporates retinal priors from a pre-trained foundation model RETFound to guide spatial attention, preventing the network from assigning spurious weights to irrelevant background noise. Extensive evaluations on the large-scale AIROGS dataset demonstrate that our method achieves a state-of-the-art AUC of $98.5\%$ and an accuracy of $94.6\%$. More importantly, the integration of anatomical priors effectively mitigates the inherent class imbalance, significantly improving the detection of referable glaucoma cases. Additional validations on the SMDG-19 benchmark further confirm its superior cross-domain generalization, indicating that our contribution provides a robust, interpretable, and scalable solution for real-world clinical glaucoma diagnosis. Our code is available at https://github.com/magiczhuo/Glaucoma-Detection

Macular Holes, Central serous retinopathy and Diabetic Retinopathy are one of the most widespread maladies of the eyes responsible for either partial or complete vision loss, thus making it clear that early detection of the mentioned defects is detrimental for the well-being of the patient. This study intends to introduce the application of Vision Transformer and Support Vector Machine based hybrid architecture (ViT-SVM) and analyse its performance to classify the optical coherence topography (OCT) Scans with the intention to automate the early detection of these retinal defects.

Retinal diseases remain among the leading preventable causes of visual impairment worldwide. Automated screening based on fundus image analysis has the potential to expand access to early detection, particularly in underserved populations. This paper presents a reproducible deep learning pipeline for binary retinal disease risk classification from publicly available fundus photographs. We implement and compare a baseline convolutional neural network with a transfer learning approach using a pretrained VGG16 backbone and evaluate generalization on held-out data. To address class imbalance, we apply class weighting and report standard classification metrics including accuracy, precision, recall, F1-score, confusion matrices, and ROC-AUC. The VGG16 transfer learning model achieves 90.8% test accuracy with a weighted F1-score of 0.90, substantially outperforming the baseline CNN (83.1% accuracy). Results indicate that transfer learning improves discrimination compared to a baseline CNN, while also revealing remaining challenges in sensitivity to minority disease cases. We discuss practical limitations related to dataset characteristics, class imbalance, and threshold selection, and provide guidance for reproducibility and future improvements for clinically reliable screening

Diabetic retinopathy (DR) is a leading cause of preventable blindness, and automated fundus image grading can play an important role in large-scale screening. In this work, we investigate three CLIP-based approaches for five-class DR severity grading: (1) a zero-shot baseline using prompt engineering, (2) a hybrid FCN-CLIP model augmented with CBAM attention, and (3) a ranking-aware prompting model that encodes the ordinal structure of DR progression. We train and evaluate on a combined dataset of APTOS 2019 and Messidor-2 (n=5,406), addressing class imbalance through resampling and class-specific optimal thresholding. Our experiments show that the ranking-aware model achieves the highest overall accuracy (93.42%, AUROC 0.9845) and strong recall on clinically critical severe cases, while the hybrid FCN-CLIP model (92.49%, AUROC 0.99) excels at detecting proliferative DR. Both substantially outperform the zero-shot baseline (55.17%, AUROC 0.75). We analyze the complementary strengths of each approach and discuss their practical implications for screening contexts.

Early and accurate classification of retinal diseases is critical to counter vision loss and for guiding clinical management of retinal diseases. In this study, we proposed a deep learning method for retinal disease classification utilizing optical coherence tomography (OCT) images from the Retinal OCT Image Classification - C8 dataset (comprising 24,000 labeled images spanning eight conditions). Images were resized to 224x224 px and tested on convolutional neural network (CNN) architectures: Xception and InceptionV3. Data augmentation techniques (CutMix, MixUp) were employed to enhance model generalization. Additionally, we applied GradCAM and LIME for interpretability evaluation. We implemented this in a real-world scenario via our web application named RetinaVision. This study found that Xception was the most accurate network (95.25%), followed closely by InceptionV3 (94.82%). These results suggest that deep learning methods allow effective OCT retinal disease classification and highlight the importance of implementing accuracy and interpretability for clinical applications.

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

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