Background Spectral-domain optical coherence tomography (SDOCT) can be used to detect glaucomatous optic neuropathy, but human expertise in interpretation of SDOCT is limited. We aimed to develop and validate a three-dimensional (3D) deep-learning system using SDOCT volumes to detect glaucomatous optic neuropathy. MethodsWe retrospectively collected a dataset including 4877 SDOCT volumes of optic disc cube for training (60%), testing (20%), and primary validation (20%) from electronic medical and research records at the Chinese University of Hong Kong Eye Centre (Hong Kong, China) and the Hong Kong Eye Hospital (Hong Kong, China). Residual network was used to build the 3D deep-learning system. Three independent datasets (two from Hong Kong and one from Stanford, CA, USA), including 546, 267, and 1231 SDOCT volumes, respectively, were used for external validation of the deep-learning system. Volumes were labelled as having or not having glaucomatous optic neuropathy according to the criteria of retinal nerve fibre layer thinning on reliable SDOCT images with position-correlated visual field defect. Heatmaps were generated for qualitative assessments. Findings 6921 SDOCT volumes from 1 384 200 two-dimensional cross-sectional scans were studied. The 3D deeplearning system had an area under the receiver operation characteristics curve (AUROC) of 0•969 (95% CI 0•960-0•976), sensitivity of 89% (95% CI 83-93), specificity of 96% (92-99), and accuracy of 91% (89-93) in the primary validation, outperforming a two-dimensional deep-learning system that was trained on en face fundus images (AUROC 0•921 [0•905-0•937]; p<0•0001). The 3D deep-learning system performed similarly in the external validation datasets, with AUROCs of 0•893-0•897, sensitivities of 78-90%, specificities of 79-86%, and accuracies of 80-86%. The heatmaps of glaucomatous optic neuropathy showed that the learned features by the 3D deep-learning system used for detection of glaucomatous optic neuropathy were similar to those used by clinicians.Interpretation The proposed 3D deep-learning system performed well in detection of glaucomatous optic neuropathy in both primary and external validations. Further prospective studies are needed to estimate the incremental costeffectiveness of incorporation of an artificial intelligence-based model for glaucoma screening.

Citation: Russakoff DB, Mannil SS, Oakley JD, Ran AR, Cheung CY, Dasari S, Riyazzuddin M, Nagaraj S, Rao HL, Chang D, Chang RT. A 3D deep learning system for detecting referable glaucoma using full OCT macular cube scans. Trans Vis Sci Tech. 2020;9(2):12, https://doi.org/10. 1167/tvst.9.2.12 Purpose: The purpose of this study was to develop a 3D deep learning system from spectral domain optical coherence tomography (SD-OCT) macular cubes to differentiate between referable and nonreferable cases for glaucoma applied to real-world datasets to understand how this would affect the performance.Methods: There were 2805 Cirrus optical coherence tomography (OCT) macula volumes (Macula protocol 512 × 128) of 1095 eyes from 586 patients at a single site that were used to train a fully 3D convolutional neural network (CNN). Referable glaucoma included true glaucoma, pre-perimetric glaucoma, and high-risk suspects, based on qualitative fundus photographs, visual fields, OCT reports, and clinical examinations, including intraocular pressure (IOP) and treatment history as the binary (two class) ground truth. The curated real-world dataset did not include eyes with retinal disease or nonglaucomatous optic neuropathies. The cubes were first homogenized using layer segmentation with the Orion Software (Voxeleron) to achieve standardization. The algorithm was tested on two separate external validation sets from different glaucoma studies, comprised of Cirrus macular cube scans of 505 and 336 eyes, respectively. Results:The area under the receiver operating characteristic (AUROC) curve for the development dataset for distinguishing referable glaucoma was 0.88 for our CNN using homogenization, 0.82 without homogenization, and 0.81 for a CNN architecture from the existing literature. For the external validation datasets, which had different glaucoma definitions, the AUCs were 0.78 and 0.95, respectively. The performance of the model across myopia severity distribution has been assessed in the dataset from the United States and was found to have an AUC of 0.85, 0.92, and 0.95 in the severe, moderate, and mild myopia, respectively. Conclusions:A 3D deep learning algorithm trained on macular OCT volumes without retinal disease to detect referable glaucoma performs better with retinal segmentation preprocessing and performs reasonably well across all levels of myopia.Translational Relevance: Interpretation of OCT macula volumes based on normative data color distributions is highly influenced by population demographics and characteristics, such as refractive error, as well as the size of the normative database. Referable glaucoma, in this study, was chosen to include cases that should be seen by a specialist. This study is unique because it uses multimodal patient data for the glaucoma definition, and includes all severities of myopia as well as validates the algorithm with international data to understand generalizability potential.

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