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.

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