Importance: Deep learning (DL) used for discriminative tasks in ophthalmology, such as diagnosing diabetic retinopathy or age-related macular degeneration (AMD), requires large image data sets graded by human experts to train deep convolutional neural networks (DCNNs). In contrast, generative DL techniques could synthesize large new data sets of artificial retina images with different stages of AMD. Such images could enhance existing data sets of common and rare ophthalmic diseases without concern for personally identifying information to assist medical education of students, residents, and retinal specialists, as well as for training new DL diagnostic models for which extensive data sets from large clinical trials of expertly graded images may not exist. Objective: To develop DL techniques for synthesizing high-resolution realistic fundus images serving as proxy data sets for use by retinal specialists and DL machines. Design, Setting, and Participants: Generative adversarial networks were trained on 133 821 color fundus images from 4613 study participants from the Age-Related Eye Disease Study (AREDS), generating synthetic fundus images with and without AMD. We compared retinal specialists' ability to diagnose AMD on both real and synthetic images, asking them to assess image gradability and testing their ability to discern real from synthetic images. The performance of AMD diagnostic DCNNs (referable vs not referable AMD) trained on either all-real vs all-synthetic data sets was compared. Main Outcomes and Measures: Accuracy of 2 retinal specialists' (T.Y.A.L. and K.D.P.) for diagnosing and distinguishing AMD on real vs synthetic images and diagnostic performance (area under the curve) of DL algorithms trained on synthetic vs real images. Results: The diagnostic accuracy of 2 retinal specialists on real vs synthetic images was similar. The accuracy of diagnosis as referable vs nonreferable AMD compared with certified human graders for retinal specialist 1 was 84.54% (error margin, 4.06%) on real images vs 84.12% (error margin, 4.16%) on synthetic images and for retinal specialist 2 was 89.47% (error margin, 3.45%) on real images vs 89.19% (error margin, 3.54%) on synthetic images. Retinal specialists could not distinguish real from synthetic images, with an accuracy of 59.50% (error margin, 3.93%) for retinal specialist 1 and 53.67% (error margin, 3.99%) for retinal specialist 2. The DCNNs trained on real data showed an area under the curve of 0.9706 (error margin, 0.0029), and those trained on synthetic data showed an area under the curve of 0.9235 (error margin, 0.0045). Conclusions and Relevance: Deep learning-synthesized images appeared to be realistic to retinal specialists, and DCNNs achieved diagnostic performance on synthetic data close to that for real images, suggesting that DL generative techniques hold promise for training humans and machines.
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