Evaluating the utility of deep learning for predicting therapeutic response in diabetic eye disease.

• Authors: Vincent Dong, The Center for Computational Imaging and Personalized Diagnostics, Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH, United States.; Duriye D Sevgi, The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cleveland Clinic, Cleveland, OH, United States.; Sudeshna S Kar, The Center for Computational Imaging and Personalized Diagnostics, Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH, United States.; Sunil K Srivastava, The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cleveland Clinic, Cleveland, OH, United States.; Justis P Ehlers, The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cleveland Clinic, Cleveland, OH, United States.; Anant Madabhushi, Emory University
• Journal Title: Front Ophthalmol (Lausanne)
• Volume: Volume 2
• Publisher: Frontiers | 2022
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.3389/fopht.2022.852107
• Subjects: Engineering, Biomedical
• Keywords: deep learning; diabetic macular edema; diabetic retinopathy; optical coherence tomography; transfer learning; ultra-widefield fluorescein angiography

Abstract

PURPOSE: Deep learning (DL) is a technique explored within ophthalmology that requires large datasets to distinguish feature representations with high diagnostic performance. There is a need for developing DL approaches to predict therapeutic response, but completed clinical trial datasets are limited in size. Predicting treatment response is more complex than disease diagnosis, where hallmarks of treatment response are subtle. This study seeks to understand the utility of DL for clinical problems in ophthalmology such as predicting treatment response and where large sample sizes for model training are not available. MATERIALS AND METHODS: Four DL architectures were trained using cross-validated transfer learning to classify ultra-widefield angiograms (UWFA) and fluid-compartmentalized optical coherence tomography (OCT) images from a completed clinical trial (PERMEATE) dataset (n=29) as tolerating or requiring extended interval Anti-VEGF dosing. UWFA images (n=217) from the Anti-VEGF study were divided into five increasingly larger subsets to evaluate the influence of dataset size on performance. Class activation maps (CAMs) were generated to identify regions of model attention. RESULTS: The best performing DL model had a mean AUC of 0.507 ± 0.042 on UWFA images, and highest observed AUC of 0.503 for fluid-compartmentalized OCT images. DL had a best performing AUC of 0.634 when dataset size was incrementally increased. Resulting CAMs show inconsistent regions of interest. CONCLUSIONS: This study demonstrated the limitations of DL for predicting therapeutic response when large datasets were not available for model training. Our findings suggest the need for hand-crafted approaches for complex and data scarce prediction problems in ophthalmology.