Causal-RetiGraph: Cross-Cohort Retinal Support and Same-Subject Pathway Analysis for Diabetic Retinopathy

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 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.

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.