Generating Multi-frame Ultrawide-field Fluorescein Angiography from Ultrawide-field Color Imaging Improves Diabetic Retinopathy Stratification

Ultrawide-field fluorescein angiography (UWF-FA) facilitates diabetic retinopathy (DR) detection by providing a clear visualization of peripheral retinal lesions. However, the intravenous dye injection with potential risks hamper its application. We aim to acquire dye-free UWF-FA images from noninvasive UWF color fundus (UWF-CF) images using generative artificial intelligence (GenAI) and evaluate its effectiveness in DR screening. A total of 18,321 UWF-FA images of different phases were registered with corresponding UWF-CF images and fed into a generative adversarial networks (GAN)-based model for training. The quality of generated UWF-FA images was evaluated through quantitative metrics and human evaluation. The DeepDRiD dataset was used to externally assess the contribution of generated UWF-FA images to DR classification, using area under the receiver operating characteristic curve (AUROC) as outcome metrics. The generated early, mid, and late phase UWF-FA images achieved high authenticity, with multi-scale similarity scores ranging from 0.70 to 0.91 and qualitative visual scores ranging from 1.64 to 1.98 (1=real UWF-FA quality). In fifty randomly selected images, 56% to 76% of the generated images were difficult to distinguish from real images in the Turing test. Moreover, adding these generated UWF-FA images for DR classification significantly increased the AUROC from 0.869 to 0.904 compared to the baseline model using UWF-CF images (P < .001). The model successfully generates realistic multi-frame UWF-FA images without intravenous dye injection. The generated UWF-FA enhanced DR stratification.