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      A Review of Deep Learning for Screening, Diagnosis, and Detection of Glaucoma Progression

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          Abstract

          Because of recent advances in computing technology and the availability of large datasets, deep learning has risen to the forefront of artificial intelligence, with performances that often equal, or sometimes even exceed, those of human subjects on a variety of tasks, especially those related to image classification and pattern recognition. As one of the medical fields that is highly dependent on ancillary imaging tests, ophthalmology has been in a prime position to witness the application of deep learning algorithms that can help analyze the vast amount of data coming from those tests. In particular, glaucoma stands as one of the conditions where application of deep learning algorithms could potentially lead to better use of the vast amount of information coming from structural and functional tests evaluating the optic nerve and macula. The purpose of this article is to critically review recent applications of deep learning models in glaucoma, discussing their advantages but also focusing on the challenges inherent to the development of such models for screening, diagnosis and detection of progression. After a brief general overview of deep learning and how it compares to traditional machine learning classifiers, we discuss issues related to the training and validation of deep learning models and how they specifically apply to glaucoma. We then discuss specific scenarios where deep learning has been proposed for use in glaucoma, such as screening with fundus photography, and diagnosis and detection of glaucoma progression with optical coherence tomography and standard automated perimetry.

          Translational Relevance

          Deep learning algorithms have the potential to significantly improve diagnostic capabilities in glaucoma, but their application in clinical practice requires careful validation, with consideration of the target population, the reference standards used to build the models, and potential sources of bias.

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          Most cited references79

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          Efficacy of a Deep Learning System for Detecting Glaucomatous Optic Neuropathy Based on Color Fundus Photographs

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            Evaluation of retinal nerve fiber layer, optic nerve head, and macular thickness measurements for glaucoma detection using optical coherence tomography.

            To compare the ability of optical coherence tomography retinal nerve fiber layer (RNFL), optic nerve head, and macular thickness parameters to differentiate between healthy eyes and eyes with glaucomatous visual field loss. Observational case-control study. Eighty-eight patients with glaucoma and 78 healthy subjects were included. All patients underwent ONH, RNFL thickness, and macular thickness scans with Stratus OCT during the same visit. ROC curves and sensitivities at fixed specificities were calculated for each parameter. A discriminant analysis was performed to develop a linear discriminant function designed to identify and combine the best parameters. This LDF was subsequently tested on an independent sample consisting of 63 eyes of 63 subjects (27 glaucomatous and 36 healthy individuals) from a different geographic area. No statistically significant difference was found between the areas under the ROC curves (AUC) for the RNFL thickness parameter with the largest AUC (inferior thickness, AUC = 0.91) and the ONH parameter with largest AUC (cup/disk area ratio, AUC = 0.88) (P = .28). The RNFL parameter inferior thickness had a significantly larger AUC than the macular thickness parameter with largest AUC (inferior outer macular thickness, AUC = 0.81) (P = .004). A combination of selected RNFL and ONH parameters resulted in the best classification function for glaucoma detection with an AUC of 0.97 when applied to the independent sample. RNFL and ONH measurements had the best discriminating performance among the several Stratus OCT parameters. A combination of ONH and RNFL parameters improved the diagnostic accuracy for glaucoma detection using this instrument.
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              Development and Validation of a Deep Learning System to Detect Glaucomatous Optic Neuropathy Using Fundus Photographs

              How does a deep learning system compare with professional human graders in detecting glaucomatous optic neuropathy? In this cross-sectional study, the deep learning system showed a sensitivity and specificity of greater than 90% for detecting glaucomatous optic neuropathy in a local validation data set, in 3 clinical-based data sets, and in a real-world distribution data set. The deep learning system showed lower sensitivity when tested in multiethnic and website-based data sets. This assessment of fundus images suggests that deep learning systems can provide a tool with high sensitivity and specificity that might expedite screening for glaucomatous optic neuropathy. This cross-sectional study compares the sensitivity and specificity of automated classification of glaucomatous optic neuropathy on retinal fundus images by a deep-learning system with classification by human experts, using Chinese, multiethnic, and website-based data sets. A deep learning system (DLS) that could automatically detect glaucomatous optic neuropathy (GON) with high sensitivity and specificity could expedite screening for GON. To establish a DLS for detection of GON using retinal fundus images and glaucoma diagnosis with convoluted neural networks (GD-CNN) that has the ability to be generalized across populations. In this cross-sectional study, a DLS for the classification of GON was developed for automated classification of GON using retinal fundus images obtained from the Chinese Glaucoma Study Alliance, the Handan Eye Study, and online databases. The researchers selected 241 032 images were selected as the training data set. The images were entered into the databases on June 9, 2009, obtained on July 11, 2018, and analyses were performed on December 15, 2018. The generalization of the DLS was tested in several validation data sets, which allowed assessment of the DLS in a clinical setting without exclusions, testing against variable image quality based on fundus photographs obtained from websites, evaluation in a population-based study that reflects a natural distribution of patients with glaucoma within the cohort and an additive data set that has a diverse ethnic distribution. An online learning system was established to transfer the trained and validated DLS to generalize the results with fundus images from new sources. To better understand the DLS decision-making process, a prediction visualization test was performed that identified regions of the fundus images utilized by the DLS for diagnosis. Use of a deep learning system. Area under the receiver operating characteristics curve (AUC), sensitivity and specificity for DLS with reference to professional graders. From a total of 274 413 fundus images initially obtained from CGSA, 269 601 images passed initial image quality review and were graded for GON. A total of 241 032 images (definite GON 29 865 [12.4%], probable GON 11 046 [4.6%], unlikely GON 200 121 [83%]) from 68 013 patients were selected using random sampling to train the GD-CNN model. Validation and evaluation of the GD-CNN model was assessed using the remaining 28 569 images from CGSA. The AUC of the GD-CNN model in primary local validation data sets was 0.996 (95% CI, 0.995-0.998), with sensitivity of 96.2% and specificity of 97.7%. The most common reason for both false-negative and false-positive grading by GD-CNN (51 of 119 [46.3%] and 191 of 588 [32.3%]) and manual grading (50 of 113 [44.2%] and 183 of 538 [34.0%]) was pathologic or high myopia. Application of GD-CNN to fundus images from different settings and varying image quality demonstrated a high sensitivity, specificity, and generalizability for detecting GON. These findings suggest that automated DLS could enhance current screening programs in a cost-effective and time-efficient manner.
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                Author and article information

                Journal
                Transl Vis Sci Technol
                Transl Vis Sci Technol
                tvst
                TVST
                Translational Vision Science & Technology
                The Association for Research in Vision and Ophthalmology
                2164-2591
                22 July 2020
                July 2020
                : 9
                : 2
                : 42
                Affiliations
                [1 ]Vision, Imaging and Performance Laboratory (VIP), Duke Eye Center, Duke University, Durham, NC, USA
                Author notes
                Correspondence: Felipe A. Medeiros, Duke Eye Center, Department of Ophthalmology, Duke University, 2351 Erwin Rd, Durham, NC 27705, USA. e-mail: felipe.medeiros@ 123456duke.edu
                Article
                TVST-20-2490
                10.1167/tvst.9.2.42
                7424906
                32855846
                3dcec3a4-b054-42f2-9564-d42b757c7248
                Copyright 2020 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 21 May 2020
                : 06 April 2020
                Page count
                Pages: 19
                Categories
                Special Issue
                Special Issue

                glaucoma,deep learning,optical coherence tomography,visual fields

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