Generating Realistic Counterfactuals for Retinal Fundus and OCT Images using Diffusion Models

Counterfactual reasoning is often used in a clinical setting to explain decisions or weigh alternatives. Therefore, for imaging based modalities such as ophthalmology, it would be beneficial to be able to create counterfactual images, illustrating the answer to the question: "If the subject had had diabetic retinopathy, how would the fundus image have looked?" Here, we demonstrate that using a diffusion model in combination with an adversarially robust classifier trained on retinal disease classification tasks enables generation of highly realistic counterfactuals of retinal fundus images and optical coherence tomorgraphy (OCT) B-scans. Ideally, these classifiers encode the salient features indicative for each disease class and can steer the diffusion model to show realistic disease signs or remove disease-related lesions in a realistic way. Importantly, in a user study, domain experts found the counterfactuals generated using our method significantly more realistic than counterfactuals generated from a previous method, and even indistiguishable from realistic images.