To assess the feasibility of generating synthetic fluorescein angiography (FA) images from color fundus (CF) images using pixel-to-pixel generative adversarial network (pix2pixGANs) for clinical applications. Research questions addressed image realism to retinal specialists and utility for assessing macular edema (ME) in Retinal Vein Occlusion (RVO) eyes. We used a registration-guided pix2pixGANs method trained on the CF-FA dataset from Kham Eye Centre, Kandze Prefecture People's Hospital. A visual Turing test confirmed the realism of synthetic images without novel artifacts. We then assessed the synthetic FA images for assessing ME. Finally, we quantitatively evaluated the synthetic images using Fréchet Inception distance (FID) and structural similarity measures (SSIM). The raw development dataset had 881 image pairs from 349 subjects. Our approach is capable of generating realistic FA images because small vessels are clearly visible and sharp within one optic disc diameter around the macula. Two retinal specialists agreed that more than 85% of synthetic FA images have good or excellent image quality. For ME detection, accuracy was similar for real and synthetic images. FID demonstrated a 38.9% improvement over the previous state-of-the-art (SOTA), and SSIM reached 0.78 compared to the previous SOTA's 0.67. We developed a pix2pixGANs model translating FA images from label-free CF images, yielding reliable synthetic FA images. This suggests potential for noninvasive evaluation of ME in RVO eyes using pix2pix GANs techniques. Pix2pixGANs techniques have the potential to assist in the noninvasive clinical assessment of ME in RVO eyes.
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