Balancing Accuracy and Efficiency: CNN Fusion Models for Diabetic Retinopathy Screening

Diabetic retinopathy (DR) remains a leading cause of preventable blindness, yet large-scale screening is constrained by limited specialist availability and variable image quality across devices and populations. This work investigates whether feature-level fusion of complementary convolutional neural network (CNN) backbones can deliver accurate and efficient binary DR screening on globally sourced fundus images. Using 11,156 images pooled from five public datasets (APTOS, EyePACS, IDRiD, Messidor, and ODIR), we frame DR detection as a binary classification task and compare three pretrained models (ResNet50, EfficientNet-B0, and DenseNet121) against pairwise and tri-fusion variants. Across five independent runs, fusion consistently outperforms single backbones. The EfficientNet-B0 + DenseNet121 (Eff+Den) fusion model achieves the best overall mean performance (accuracy: 82.89\%) with balanced class-wise F1-scores for normal (83.60\%) and diabetic (82.60\%) cases. While the tri-fusion is competitive, it incurs a substantially higher computational cost. Inference profiling highlights a practical trade-off: EfficientNet-B0 is the fastest (approximately 1.16 ms/image at batch size 1000), whereas the Eff+Den fusion offers a favorable accuracy--latency balance. These findings indicate that lightweight feature fusion can enhance generalization across heterogeneous datasets, supporting scalable binary DR screening workflows where both accuracy and throughput are critical.

Quadrant Segmentation VLM with Few-Shot Adaptation and OCT Learning-based Explainability Methods for Diabetic Retinopathy

Diabetic Retinopathy (DR) is a leading cause of vision loss worldwide, requiring early detection to preserve sight. Limited access to physicians often leaves DR undiagnosed. To address this, AI models utilize lesion segmentation for interpretability; however, manually annotating lesions is impractical for clinicians. Physicians require a model that explains the reasoning for classifications rather than just highlighting lesion locations. Furthermore, current models are one-dimensional, relying on a single imaging modality for explainability and achieving limited effectiveness. In contrast, a quantitative-detection system that identifies individual DR lesions in natural language would overcome these limitations, enabling diverse applications in screening, treatment, and research settings. To address this issue, this paper presents a novel multimodal explainability model utilizing a VLM with few-shot learning, which mimics an ophthalmologist's reasoning by analyzing lesion distributions within retinal quadrants for fundus images. The model generates paired Grad-CAM heatmaps, showcasing individual neuron weights across both OCT and fundus images, which visually highlight the regions contributing to DR severity classification. Using a dataset of 3,000 fundus images and 1,000 OCT images, this innovative methodology addresses key limitations in current DR diagnostics, offering a practical and comprehensive tool for improving patient outcomes.

NEURO-GUARD: Neuro-Symbolic Generalization and Unbiased Adaptive Routing for Diagnostics -- Explainable Medical AI

Accurate yet interpretable image-based diagnosis remains a central challenge in medical AI, particularly in settings characterized by limited data, subtle visual cues, and high-stakes clinical decision-making. Most existing vision models rely on purely data-driven learning and produce black-box predictions with limited interpretability and poor cross-domain generalization, hindering their real-world clinical adoption. We present NEURO-GUARD, a novel knowledge-guided vision framework that integrates Vision Transformers (ViTs) with language-driven reasoning to improve performance, transparency, and domain robustness. NEURO-GUARD employs a retrieval-augmented generation (RAG) mechanism for self-verification, in which a large language model (LLM) iteratively generates, evaluates, and refines feature-extraction code for medical images. By grounding this process in clinical guidelines and expert knowledge, the framework progressively enhances feature detection and classification beyond purely data-driven baselines. Extensive experiments on diabetic retinopathy classification across four benchmark datasets APTOS, EyePACS, Messidor-1, and Messidor-2 demonstrate that NEURO-GUARD improves accuracy by 6.2% over a ViT-only baseline (84.69% vs. 78.4%) and achieves a 5% gain in domain generalization. Additional evaluations on MRI-based seizure detection further confirm its cross-domain robustness, consistently outperforming existing methods. Overall, NEURO-GUARD bridges symbolic medical reasoning with subsymbolic visual learning, enabling interpretable, knowledge-aware, and generalizable medical image diagnosis while achieving state-of-the-art performance across multiple datasets.

WDT-MD: Wavelet Diffusion Transformers for Microaneurysm Detection in Fundus Images

Microaneurysms (MAs), the earliest pathognomonic signs of Diabetic Retinopathy (DR), present as sub-60 $μm$ lesions in fundus images with highly variable photometric and morphological characteristics, rendering manual screening not only labor-intensive but inherently error-prone. While diffusion-based anomaly detection has emerged as a promising approach for automated MA screening, its clinical application is hindered by three fundamental limitations. First, these models often fall prey to "identity mapping", where they inadvertently replicate the input image. Second, they struggle to distinguish MAs from other anomalies, leading to high false positives. Third, their suboptimal reconstruction of normal features hampers overall performance. To address these challenges, we propose a Wavelet Diffusion Transformer framework for MA Detection (WDT-MD), which features three key innovations: a noise-encoded image conditioning mechanism to avoid "identity mapping" by perturbing image conditions during training; pseudo-normal pattern synthesis via inpainting to introduce pixel-level supervision, enabling discrimination between MAs and other anomalies; and a wavelet diffusion Transformer architecture that combines the global modeling capability of diffusion Transformers with multi-scale wavelet analysis to enhance reconstruction of normal retinal features. Comprehensive experiments on the IDRiD and e-ophtha MA datasets demonstrate that WDT-MD outperforms state-of-the-art methods in both pixel-level and image-level MA detection. This advancement holds significant promise for improving early DR screening.

Stage Aware Diagnosis of Diabetic Retinopathy via Ordinal Regression

Diabetic Retinopathy (DR) has emerged as a major cause of preventable blindness in recent times. With timely screening and intervention, the condition can be prevented from causing irreversible damage. The work introduces a state-of-the-art Ordinal Regression-based DR Detection framework that uses the APTOS-2019 fundus image dataset. A widely accepted combination of preprocessing methods: Green Channel (GC) Extraction, Noise Masking, and CLAHE, was used to isolate the most relevant features for DR classification. Model performance was evaluated using the Quadratic Weighted Kappa, with a focus on agreement between results and clinical grading. Our Ordinal Regression approach attained a QWK score of 0.8992, setting a new benchmark on the APTOS dataset.

From Retinal Pixels to Patients: Evolution of Deep Learning Research in Diabetic Retinopathy Screening

Diabetic Retinopathy (DR) remains a leading cause of preventable blindness, with early detection critical for reducing vision loss worldwide. Over the past decade, deep learning has transformed DR screening, progressing from early convolutional neural networks trained on private datasets to advanced pipelines addressing class imbalance, label scarcity, domain shift, and interpretability. This survey provides the first systematic synthesis of DR research spanning 2016-2025, consolidating results from 50+ studies and over 20 datasets. We critically examine methodological advances, including self- and semi-supervised learning, domain generalization, federated training, and hybrid neuro-symbolic models, alongside evaluation protocols, reporting standards, and reproducibility challenges. Benchmark tables contextualize performance across datasets, while discussion highlights open gaps in multi-center validation and clinical trust. By linking technical progress with translational barriers, this work outlines a practical agenda for reproducible, privacy-preserving, and clinically deployable DR AI. Beyond DR, many of the surveyed innovations extend broadly to medical imaging at scale.

A Hybrid Framework Bridging CNN and ViT based on Theory of Evidence for Diabetic Retinopathy Grading

Diabetic retinopathy (DR) is a leading cause of vision loss among middle-aged and elderly people, which significantly impacts their daily lives and mental health. To improve the efficiency of clinical screening and enable the early detection of DR, a variety of automated DR diagnosis systems have been recently established based on convolutional neural network (CNN) or vision Transformer (ViT). However, due to the own shortages of CNN / ViT, the performance of existing methods using single-type backbone has reached a bottleneck. One potential way for the further improvements is integrating different kinds of backbones, which can fully leverage the respective strengths of them (\emph{i.e.,} the local feature extraction capability of CNN and the global feature capturing ability of ViT). To this end, we propose a novel paradigm to effectively fuse the features extracted by different backbones based on the theory of evidence. Specifically, the proposed evidential fusion paradigm transforms the features from different backbones into supporting evidences via a set of deep evidential networks. With the supporting evidences, the aggregated opinion can be accordingly formed, which can be used to adaptively tune the fusion pattern between different backbones and accordingly boost the performance of our hybrid model. We evaluated our method on two publicly available DR grading datasets. The experimental results demonstrate that our hybrid model not only improves the accuracy of DR grading, compared to the state-of-the-art frameworks, but also provides the excellent interpretability for feature fusion and decision-making.

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 EfficientNet-B0 backbone, across different training regimes and evaluation settings in IDRiD, MESSIDOR-2 and OCT-and-Eye-Fundus-Images (OEFI). Results show that despite their scale, FM do not consistently outperform fine-tuned CNNs in this task. In particular, an EfficientNet-B0 ranked first or second in terms of area under the ROC and precision/recall curves in most evaluation settings, with RETFound only showing promising results in OEFI. FLAIR, on the other hand, demonstrated competitive zero-shot performance, achieving notable AUC-PR scores when prompted appropriately. These findings reveal that FM might not be a good tool for fine-grained ophthalmic tasks such as DME detection even after fine-tuning, suggesting that lightweight CNNs remain strong baselines in data-scarce environments.

Simulating Clinical AI Assistance using Multimodal LLMs: A Case Study in Diabetic Retinopathy

Diabetic retinopathy (DR) is a leading cause of blindness worldwide, and AI systems can expand access to fundus photography screening. Current FDA-cleared systems primarily provide binary referral outputs, where this minimal output may limit clinical trust and utility. Yet, determining the most effective output format to enhance clinician-AI performance is an empirical challenge that is difficult to assess at scale. We evaluated multimodal large language models (MLLMs) for DR detection and their ability to simulate clinical AI assistance across different output types. Two models were tested on IDRiD and Messidor-2: GPT-4o, a general-purpose MLLM, and MedGemma, an open-source medical model. Experiments included: (1) baseline evaluation, (2) simulated AI assistance with synthetic predictions, and (3) actual AI-to-AI collaboration where GPT-4o incorporated MedGemma outputs. MedGemma outperformed GPT-4o at baseline, achieving higher sensitivity and AUROC, while GPT-4o showed near-perfect specificity but low sensitivity. Both models adjusted predictions based on simulated AI inputs, but GPT-4o's performance collapsed with incorrect ones, whereas MedGemma remained more stable. In actual collaboration, GPT-4o achieved strong results when guided by MedGemma's descriptive outputs, even without direct image access (AUROC up to 0.96). These findings suggest MLLMs may improve DR screening pipelines and serve as scalable simulators for studying clinical AI assistance across varying output configurations. Open, lightweight models such as MedGemma may be especially valuable in low-resource settings, while descriptive outputs could enhance explainability and clinician trust in clinical workflows.

XDR-LVLM: An Explainable Vision-Language Large Model for Diabetic Retinopathy Diagnosis

Diabetic Retinopathy (DR) is a major cause of global blindness, necessitating early and accurate diagnosis. While deep learning models have shown promise in DR detection, their black-box nature often hinders clinical adoption due to a lack of transparency and interpretability. To address this, we propose XDR-LVLM (eXplainable Diabetic Retinopathy Diagnosis with LVLM), a novel framework that leverages Vision-Language Large Models (LVLMs) for high-precision DR diagnosis coupled with natural language-based explanations. XDR-LVLM integrates a specialized Medical Vision Encoder, an LVLM Core, and employs Multi-task Prompt Engineering and Multi-stage Fine-tuning to deeply understand pathological features within fundus images and generate comprehensive diagnostic reports. These reports explicitly include DR severity grading, identification of key pathological concepts (e.g., hemorrhages, exudates, microaneurysms), and detailed explanations linking observed features to the diagnosis. Extensive experiments on the Diabetic Retinopathy (DDR) dataset demonstrate that XDR-LVLM achieves state-of-the-art performance, with a Balanced Accuracy of 84.55% and an F1 Score of 79.92% for disease diagnosis, and superior results for concept detection (77.95% BACC, 66.88% F1). Furthermore, human evaluations confirm the high fluency, accuracy, and clinical utility of the generated explanations, showcasing XDR-LVLM's ability to bridge the gap between automated diagnosis and clinical needs by providing robust and interpretable insights.