A deep learning system for predicting time to progression of diabetic retinopathy

Ling Dai; Bin Sheng; Tingli Chen; Qiang Wu; Ruhan Liu; Chun Cai; Liang Wu; Dawei Yang; Haslina Hamzah; Yuexing Liu; Xiangning Wang; Zhouyu Guan; Shujie Yu; Tingyao Li; Ziqi Tang; Anran Ran; Haoxuan Che; Hao Chen; Yingfeng Zheng; Jia Shu; Shan Huang; Chan Wu; Shiqun Lin; Dan Liu; Jiajia Li; Zheyuan Wang; Ziyao Meng; Jie Shen; Xuhong Hou; Chenxin Deng; Lei Ruan; Feng Lu; Miaoli Chee; Ten Cheer Quek; Ramyaa Srinivasan; Rajiv Raman; Xiaodong Sun; Ya Xing Wang; Jiarui Wu; Hai Jin; Rongping Dai; Dinggang Shen; Xiaokang Yang; Minyi Guo; Cuntai Zhang; Carol Y Cheung; Gavin Siew Wei Tan; Yih-Chung Tham; Ching-Yu Cheng; Huating Li; Tien Yin Wong; Weiping Jia

doi:10.1038/s41591-023-02702-z

A deep learning system for predicting time to progression of diabetic retinopathy

Nat Med. 2024 Feb;30(2):584-594. doi: 10.1038/s41591-023-02702-z. Epub 2024 Jan 4.

Authors

Ling Dai^#^{1

2}, Bin Sheng^#^{3

4}, Tingli Chen^#⁵, Qiang Wu^#⁶, Ruhan Liu^#^{1

2}, Chun Cai¹, Liang Wu¹, Dawei Yang⁷, Haslina Hamzah⁸, Yuexing Liu¹, Xiangning Wang⁶, Zhouyu Guan¹, Shujie Yu¹, Tingyao Li^{1

2}, Ziqi Tang⁷, Anran Ran⁷, Haoxuan Che⁹, Hao Chen^{9

10}, Yingfeng Zheng¹¹, Jia Shu^{1

2}, Shan Huang^{1

2}, Chan Wu¹², Shiqun Lin¹², Dan Liu¹, Jiajia Li^{1

2}, Zheyuan Wang^{1

2}, Ziyao Meng^{1

2}, Jie Shen¹³, Xuhong Hou¹, Chenxin Deng¹⁴, Lei Ruan¹⁴, Feng Lu¹⁵, Miaoli Chee⁸, Ten Cheer Quek⁸, Ramyaa Srinivasan¹⁶, Rajiv Raman¹⁶, Xiaodong Sun¹⁷, Ya Xing Wang¹⁸, Jiarui Wu^{1

19}, Hai Jin¹⁵, Rongping Dai¹², Dinggang Shen^{20

21

22}, Xiaokang Yang², Minyi Guo¹, Cuntai Zhang¹⁴, Carol Y Cheung⁷, Gavin Siew Wei Tan^{8

23}, Yih-Chung Tham^{8

24}, Ching-Yu Cheng^{8

23

24}, Huating Li^#²⁵, Tien Yin Wong^{26

27}, Weiping Jia²⁸

Affiliations

¹ Shanghai Belt and Road International Joint Laboratory for Intelligent Prevention and Treatment of Metabolic Disorders, Department of Computer Science and Engineering, School of Electronic, Information, and Electrical Engineering, Shanghai Jiao Tong University, Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai, China.
² MOE Key Laboratory of AI, School of Electronic, Information, and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China.
³ Shanghai Belt and Road International Joint Laboratory for Intelligent Prevention and Treatment of Metabolic Disorders, Department of Computer Science and Engineering, School of Electronic, Information, and Electrical Engineering, Shanghai Jiao Tong University, Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai, China. shengbin@sjtu.edu.cn.
⁴ MOE Key Laboratory of AI, School of Electronic, Information, and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China. shengbin@sjtu.edu.cn.
⁵ Department of Ophthalmology, Huadong Sanatorium, Wuxi, China.
⁶ Department of Ophthalmology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
⁸ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
⁹ Department of Computer Science and Engineering, The Hong Kong University of Science and Technology, Hong Kong, China.
¹⁰ Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, China.
¹¹ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
¹² Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
¹³ Medical Records and Statistics Office, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁴ Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁵ National Engineering Research Center for Big Data Technology and System, Services Computing Technology and System Lab, Cluster and Grid Computing Lab, School of Computer Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
¹⁶ Shri Bhagwan Mahavir Vitreoretinal Services, Medical Research Foundation, Sankara Nethralaya, Chennai, India.
¹⁷ Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁸ Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China.
¹⁹ Center for Excellence in Molecular Science, Chinese Academy of Sciences, Shanghai, China.
²⁰ School of Biomedical Engineering, Shanghai Tech University, Shanghai, China.
²¹ Shanghai United Imaging Intelligence, Shanghai, China.
²² Shanghai Clinical Research and Trial Center, Shanghai, China.
²³ Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore.
²⁴ Centre for Innovation and Precision Eye Health; and Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
²⁵ Shanghai Belt and Road International Joint Laboratory for Intelligent Prevention and Treatment of Metabolic Disorders, Department of Computer Science and Engineering, School of Electronic, Information, and Electrical Engineering, Shanghai Jiao Tong University, Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai, China. huarting99@sjtu.edu.cn.
²⁶ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. wongtienyin@tsinghua.edu.cn.
²⁷ Tsinghua Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China. wongtienyin@tsinghua.edu.cn.
²⁸ Shanghai Belt and Road International Joint Laboratory for Intelligent Prevention and Treatment of Metabolic Disorders, Department of Computer Science and Engineering, School of Electronic, Information, and Electrical Engineering, Shanghai Jiao Tong University, Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai, China. wpjia@sjtu.edu.cn.

^# Contributed equally.

Abstract

Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754-0.846 and integrated Brier scores of 0.153-0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1-5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.

MeSH terms

Blindness
Deep Learning*
Diabetes Mellitus*
Diabetic Retinopathy* / diagnosis
Humans