Interpretable Context-Aware Multi-Label Retinal Classification with Dual-Hub Heterogeneous Graph Neural Network

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.

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.

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.