Dan Milea1, Raymond P Najjar1, Jiang Zhubo1, Daniel Ting1, Caroline Vasseneix1, Xinxing Xu1, Masoud Aghsaei Fard1, Pedro Fonseca1, Kavin Vanikieti1, Wolf A Lagrèze1, Chiara La Morgia1, Carol Y Cheung1, Steffen Hamann1, Christophe Chiquet1, Nicolae Sanda1, Hui Yang1, Luis J Mejico1, Marie-Bénédicte Rougier1, Richard Kho1, Tran Thi Ha Chau1, Shweta Singhal1, Philippe Gohier1, Catherine Clermont-Vignal1, Ching-Yu Cheng1, Jost B Jonas1, Patrick Yu-Wai-Man1, Clare L Fraser1, John J Chen1, Selvakumar Ambika1, Neil R Miller1, Yong Liu1, Nancy J Newman1, Tien Y Wong1, Valérie Biousse1. 1. From the Singapore National Eye Center (D.M., D.T., S.S., C.-Y.C., T.Y.W.), Singapore Eye Research Institute (D.M., R.P.N., D.T., C.V., S.S., C.-Y.C., T.Y.W.), Duke-NUS Medical School (D.M., R.P.N., D.T., S.S., C.-Y.C., T.Y.W.), Institute of High Performance Computing, Agency for Science, Technology, and Research (J.Z., X.X., Y.L.), and Yong Loo Lin School of Medicine, National University of Singapore (S.S., T.Y.W.) - all in Singapore; Farabi Eye Hospital, Tehran University of Medical Science, Tehran, Iran (M.A.F.); the Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra, and the Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal (P.F.); the Department of Ophthalmology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (K.V.); the Eye Center, Medical Center, University of Freiburg, Freiburg (W.A.L.), and the Department of Ophthalmology, Ruprecht Karl University of Heidelberg, Mannheim (J.B.J.) - both in Germany; IRCCS Istituto delle Scienze Neurologiche di Bologna, Unità Operativa Complessa Clinica Neurologica, and Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy (C.L.M.); the Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong (C.Y.C.), and Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (H.Y.) - both in China; the Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Glostrup, Denmark (S.H.); the Department of Ophthalmology, University Hospital of Grenoble-Alpes, and Grenoble-Alpes University, HP2 Laboratory, INSERM Unité 1042, Grenoble (C.C.), Service d'Ophtalmologie, Unité Rétine-Uvéites-Neuro-Ophtalmologie, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux (M.-B.R.), the Department of Ophthalmology, Lille Catholic Hospital, Lille Catholic University, and INSERM Unité 1171, Lille (T.T.H.C.), the Department of Ophthalmology, University Hospital Angers, Angers (P.G.), and Rothschild Foundation Hospital, Paris (C.C.-V.) - all in France; the Department of Clinical Neurosciences, Geneva University Hospital, Geneva (N.S.); the Department of Neurology, SUNY Upstate Medical University, Syracuse, NY (L.J.M.); the American Eye Center, Mandaluyong City, Philippines (R.K.); Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, University College London, London (P.Y.-W.-M.), and Cambridge Eye Unit, Addenbrooke's Hospital, Cambridge University Hospitals, and Cambridge Centre for Brain Repair and Medical Research Council Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge (P.Y.-W.-M.) - all in the United Kingdom; the Save Sight Institute, Faculty of Health and Medicine, University of Sydney, Sydney (C.L.F.); the Department of Ophthalmology and Neurology, Mayo Clinic, Rochester, MN (J.J.C.); the Department of Neuro-ophthalmology, Sankara Nethralaya, Medical Research Foundation, Chennai, India (S.A.); the Departments of Ophthalmology, Neurology, and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore (N.R.M.); and the Departments of Ophthalmology and Neurology, Emory University School of Medicine, Atlanta (N.J.N., V.B.).
Abstract
BACKGROUND: Nonophthalmologist physicians do not confidently perform direct ophthalmoscopy. The use of artificial intelligence to detect papilledema and other optic-disk abnormalities from fundus photographs has not been well studied. METHODS: We trained, validated, and externally tested a deep-learning system to classify optic disks as being normal or having papilledema or other abnormalities from 15,846 retrospectively collected ocular fundus photographs that had been obtained with pharmacologic pupillary dilation and various digital cameras in persons from multiple ethnic populations. Of these photographs, 14,341 from 19 sites in 11 countries were used for training and validation, and 1505 photographs from 5 other sites were used for external testing. Performance at classifying the optic-disk appearance was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity, and specificity, as compared with a reference standard of clinical diagnoses by neuro-ophthalmologists. RESULTS: The training and validation data sets from 6779 patients included 14,341 photographs: 9156 of normal disks, 2148 of disks with papilledema, and 3037 of disks with other abnormalities. The percentage classified as being normal ranged across sites from 9.8 to 100%; the percentage classified as having papilledema ranged across sites from zero to 59.5%. In the validation set, the system discriminated disks with papilledema from normal disks and disks with nonpapilledema abnormalities with an AUC of 0.99 (95% confidence interval [CI], 0.98 to 0.99) and normal from abnormal disks with an AUC of 0.99 (95% CI, 0.99 to 0.99). In the external-testing data set of 1505 photographs, the system had an AUC for the detection of papilledema of 0.96 (95% CI, 0.95 to 0.97), a sensitivity of 96.4% (95% CI, 93.9 to 98.3), and a specificity of 84.7% (95% CI, 82.3 to 87.1). CONCLUSIONS: A deep-learning system using fundus photographs with pharmacologically dilated pupils differentiated among optic disks with papilledema, normal disks, and disks with nonpapilledema abnormalities. (Funded by the Singapore National Medical Research Council and the SingHealth Duke-NUS Ophthalmology and Visual Sciences Academic Clinical Program.).
BACKGROUND: Nonophthalmologist physicians do not confidently perform direct ophthalmoscopy. The use of artificial intelligence to detect papilledema and other optic-disk abnormalities from fundus photographs has not been well studied. METHODS: We trained, validated, and externally tested a deep-learning system to classify optic disks as being normal or having papilledema or other abnormalities from 15,846 retrospectively collected ocular fundus photographs that had been obtained with pharmacologic pupillary dilation and various digital cameras in persons from multiple ethnic populations. Of these photographs, 14,341 from 19 sites in 11 countries were used for training and validation, and 1505 photographs from 5 other sites were used for external testing. Performance at classifying the optic-disk appearance was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity, and specificity, as compared with a reference standard of clinical diagnoses by neuro-ophthalmologists. RESULTS: The training and validation data sets from 6779 patients included 14,341 photographs: 9156 of normal disks, 2148 of disks with papilledema, and 3037 of disks with other abnormalities. The percentage classified as being normal ranged across sites from 9.8 to 100%; the percentage classified as having papilledema ranged across sites from zero to 59.5%. In the validation set, the system discriminated disks with papilledema from normal disks and disks with nonpapilledema abnormalities with an AUC of 0.99 (95% confidence interval [CI], 0.98 to 0.99) and normal from abnormal disks with an AUC of 0.99 (95% CI, 0.99 to 0.99). In the external-testing data set of 1505 photographs, the system had an AUC for the detection of papilledema of 0.96 (95% CI, 0.95 to 0.97), a sensitivity of 96.4% (95% CI, 93.9 to 98.3), and a specificity of 84.7% (95% CI, 82.3 to 87.1). CONCLUSIONS: A deep-learning system using fundus photographs with pharmacologically dilated pupils differentiated among optic disks with papilledema, normal disks, and disks with nonpapilledema abnormalities. (Funded by the Singapore National Medical Research Council and the SingHealth Duke-NUS Ophthalmology and Visual Sciences Academic Clinical Program.).
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