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      A 3D Deep Learning System for Detecting Referable Glaucoma Using Full OCT Macular Cube Scans

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          Abstract

          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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          Most cited references17

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          The relationship between glaucoma and myopia: the Blue Mountains Eye Study.

          To quantify the relationship between myopia and open-angle glaucoma, ocular hypertension (OH), and intraocular pressure (IOP) in a representative older population. Cross-sectional population-based study of 3654 Australians 49 to 97 years of age. Subjects with any myopia (> or =-1.0 diopter [D]) were identified by a standardized subjective refraction and categorized into low myopia (> or =-1.0 D to or =-3.0 D). Glaucoma was diagnosed from characteristic visual field loss, combined with optic disc cupping and rim thinning, without reference to IOP. Ocular hypertension was diagnosed when applanation IOP was greater than 21 mmHg in either eye in the absence of glaucomatous visual field and optic disc changes. General estimating equation models were used to assess associations between eyes with myopia and either glaucoma or OH. Glaucoma was present in 4.2% of eyes with low myopia and 4.4% of eyes with moderate-to-high myopia compared to 1.5% of eyes without myopia. The relationship between glaucoma and myopia was maintained after adjusting for known glaucoma risk factors, odds ratio (OR) of 2.3, and 95% confidence intervals (CI) of 1.3 to 4.1 for low myopia. It was stronger for eyes with moderate-to-high myopia (OR, 3.3; CI, 1.7-6.4). Only a borderline relationship was found with OH, OR of 1.8 (CI, 1.2-2.9) for low myopia, and OR of 0.9 (CI, 0.4-2.0) for moderate-to-high myopia. Mean IOP was approximately 0.5 mmHg higher in myopic eyes compared to nonmyopic eyes. This study has confirmed a strong relationship between myopia and glaucoma. Myopic subjects had a twofold to threefold increased risk of glaucoma compared with that of nonmyopic subjects. The risk was independent of other glaucoma risk factors and IOP.
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            Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study.

            The purpose of this study was to determine the prevalence of open-angle glaucoma and ocular hypertension in an Australian community whose residents are 49 years of age or older. There were 3654 persons, representing 82.4% of permanent residents from an area west of Sydney, Australia, who were examined. The population was identified by a door-to-door census of all dwellings and by closely matched findings from the national census. All participants received a detailed eye examination, including applanation tonometry, suprathreshold automated perimetry (Humphrey 76-point test), and Zeiss stereoscopic optic disc photography. Glaucoma suspects were asked to return for full threshold fields (Humphrey 30-2 test), gonioscopy, and repeat tonometry. A 5-point hemifield difference on the 76-point test was found in 616 persons (19% of people tested). Humphrey 30-2 tests were performed on 336 glaucoma suspects (9.2% of population), of whom 125 had typical glaucomatous field defects. Two hundred three persons had enlarged or asymmetric cup-disc ratios (> or = 0.7 in 1 or both eyes or a cup-disc ratio difference of > or = 0.3). Open-angle glaucoma was diagnosed when glaucomatous defects on the 30-2 test matched the optic disc changes, without regard to the intraocular pressure level. This congruence was found in 87 participants (2.4%), whereas an additional 21 persons (0.6%) had clinical signs of open-angle glaucoma but incomplete examination findings. Open-angle glaucoma was thus found in 108 persons, a prevalence of 3.0% (95% confidence interval [CI], 2.5-3.6), of whom 49% were diagnosed previously. An exponential rise in prevalence was observed with increasing age. Ocular hypertension, defined as an intraocular pressure in either eye greater than 21 mmHg, without matching disc and field changes, was present in 3.7% of this population (95% CI, 3.1-4.3), but there was no significant age-related increase in prevalence. The prevalence of glaucoma was higher in women after adjusting for age (odds ratio, 1.5; CI, 1.0-2.2). There was no sex difference in the age-adjusted prevalence of ocular hypertension. These data provide detailed age and sex-specific prevalence rates for open-angle glaucoma and ocular hypertension in an older Australian population.
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              Glaucoma diagnostic accuracy of ganglion cell-inner plexiform layer thickness: comparison with nerve fiber layer and optic nerve head.

              To determine the diagnostic performance of macular ganglion cell-inner plexiform layer (GCIPL) thickness measured with the Cirrus high-definition optical coherence tomography (HD-OCT) ganglion cell analysis (GCA) algorithm (Carl Zeiss Meditec, Dublin, CA) to discriminate normal eyes and eyes with early glaucoma and to compare it with that of peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) measurements. Evaluation of diagnostic test or technology. Fifty-eight patients with early glaucoma and 99 age-matched normal subjects. Macular GCIPL and peripapillary RNFL thicknesses and ONH parameters were measured in each participant, and their diagnostic abilities were compared. Area under the curve (AUC) of the receiver operating characteristic. The GCIPL parameters with the best AUCs were the minimum (0.959), inferotemporal (0.956), average (0.935), superotemporal (0.919), and inferior sector (0.918). There were no significant differences between these AUCs and those of inferior quadrant (0.939), average (0.936), and superior quadrant RNFL (0.933); vertical cup-to-disc diameter ratio (0.962); cup-to-disc area ratio (0.933); and rim area (0.910), all P>0.05. The ability of macular GCIPL parameters to discriminate normal eyes and eyes with early glaucoma is high and comparable to that of the best peripapillary RNFL and ONH parameters. Proprietary or commercial disclosure may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Transl Vis Sci Technol
                Transl Vis Sci Technol
                tvst
                tvst
                TVST
                Translational Vision Science & Technology
                The Association for Research in Vision and Ophthalmology
                2164-2591
                18 February 2020
                February 2020
                : 9
                : 2
                : 12
                Affiliations
                [1 ] Voxeleron LLC , San Francisco, CA, USA
                [2 ] Byers Eye Institute, Stanford University , Palo Alto, CA, USA
                [3 ] Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong , Hong Kong
                [4 ] Narayana Nethralaya Foundation , Bangalore-India
                Author notes
                Correspondence: Robert T. Chang, Department of Ophthalmology, Byers Eye Institute, Stanford University , 2452 Watson Ct, Palo Alto, CA 94303, USA. e-mail: viroptic@ 123456gmail.com
                Article
                TVST-19-2000
                10.1167/tvst.9.2.12
                7347026
                f16a9777-0c9d-48b8-8f79-1b363c90d338
                Copyright 2020 The Authors

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

                History
                : 10 December 2019
                : 01 October 2019
                Page count
                Pages: 14
                Categories
                Special Issue
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                machine learning,glaucoma,suspects
                machine learning, glaucoma, suspects

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