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A comparison of the diagnostic ability of vessel density and structural measurements of optical coherence tomography in primary open angle glaucoma

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      Abstract

      Purpose

      To compare the diagnostic abilities of vessel density measurements of the optic nerve head (ONH), peripapillary and macular regions on optical coherence tomography (OCT) angiography in eyes with primary open angle glaucoma (POAG) with that of the ONH rim area, peripapillary retinal nerve fiber layer (RNFL) thickness and the macular ganglion cell complex (GCC) thickness measurements.

      Methods

      In a cross sectional study, 78 eyes of 50 control subjects and 117 eyes of 67 POAG patients underwent vessel density and structural measurements with spectral domain OCT. POAG was diagnosed based on the masked evaluation of optic disc stereo photographs. Area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities of vessel densities in ONH, peripapillary and macular regions were compared with rim area, RNFL and GCC thickness.

      Results

      The AUC (sensitivity at 95% specificity) of average vessel densities within the ONH, peripapillary and macular region were 0.77 (31%), 0.85 (56%) and 0.70 (18%) respectively. The same of ONH rim area, average RNFL and GCC thickness were 0.94 (83%), 0.95 (72%) and 0.93 (62%) respectively. AUCs of vessel densities were significantly lower (p<0.05) than that of the corresponding structural measurements. Pre-treatment IOP (coefficient: 0.08) affected (p<0.05) the AUC of ONH vessel density but not of any other vessel density or structural measurements.

      Conclusions

      Diagnostic abilities of ONH, peripapillary and the macular vessel densities in POAG were significantly lower than ONH rim area, peripapillary RNFL and macular GCC measurements respectively. At fixed levels of glaucoma severity, the diagnostic ability of the ONH vessel density was significantly greater in eyes with higher pre-treatment IOP.

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      Most cited references 30

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      Primary open-angle glaucoma.

      Primary open-angle glaucoma is a progressive optic neuropathy and, perhaps, the most common form of glaucoma. Because the disease is treatable, and because the visual impairment caused by glaucoma is irreversible, early detection is essential. Early diagnosis depends on examination of the optic disc, retinal nerve fibre layer, and visual field. New imaging and psychophysical tests can improve both detection and monitoring of the progression of the disease. Recently completed long-term clinical trials provide convincing evidence that lowering intraocular pressure prevents progression at both the early and late stages of the disease. The degree of protection is related to the degree to which intraocular pressure is lowered. Improvements in therapy consist of more effective and better-tolerated drugs to lower intraocular pressure, and more effective surgical procedures. New treatments to directly treat and protect the retinal ganglion cells that are damaged in glaucoma are also in development.
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        The pathophysiology and treatment of glaucoma: a review.

        Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition. To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma. A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians. The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression. Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries.
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          Empirical evidence of design-related bias in studies of diagnostic tests.

          The literature contains a large number of potential biases in the evaluation of diagnostic tests. Strict application of appropriate methodological criteria would invalidate the clinical application of most study results. To empirically determine the quantitative effect of study design shortcomings on estimates of diagnostic accuracy. Observational study of the methodological features of 184 original studies evaluating 218 diagnostic tests. Meta-analyses on diagnostic tests were identified through a systematic search of the literature using MEDLINE, EMBASE, and DARE databases and the Cochrane Library (1996-1997). Associations between study characteristics and estimates of diagnostic accuracy were evaluated with a regression model. Relative diagnostic odds ratio (RDOR), which compared the diagnostic odds ratios of studies of a given test that lacked a particular methodological feature with those without the corresponding shortcomings in design. Fifteen (6.8%) of 218 evaluations met all 8 criteria; 64 (30%) met 6 or more. Studies evaluating tests in a diseased population and a separate control group overestimated the diagnostic performance compared with studies that used a clinical population (RDOR, 3.0; 95% confidence interval [CI], 2.0-4.5). Studies in which different reference tests were used for positive and negative results of the test under study overestimated the diagnostic performance compared with studies using a single reference test for all patients (RDOR, 2.2; 95% CI, 1.5-3.3). Diagnostic performance was also overestimated when the reference test was interpreted with knowledge of the test result (RDOR, 1.3; 95% CI, 1.0-1.9), when no criteria for the test were described (RDOR, 1.7; 95% CI, 1.1-2.5), and when no description of the population under study was provided (RDOR, 1.4; 95% CI, 1.1-1.7). These data provide empirical evidence that diagnostic studies with methodological shortcomings may overestimate the accuracy of a diagnostic test, particularly those including nonrepresentative patients or applying different reference standards.
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            Author and article information

            Affiliations
            [1 ]Narayana Nethralaya, Rajajinagar, Bangalore, India
            [2 ]Narayana Nethralaya, Hulimavu, Bangalore, India
            [3 ]Shiley Eye Institute, Hamilton Glaucoma Center and Department of Ophthalmology, University of California San Diego, San Diego, La Jolla, California, United States of America
            [4 ]Glaucoma Center, Montchoisi Clinic, Swiss Vision Network, Lausanne, Switzerland
            [5 ]Department of Ophthalmology, University of Colorado, Denver, Colorado, United States of America
            [6 ]University Eye Clinic Maastricht, University Medical Center, Maastricht, the Netherlands
            Bascom Palmer Eye Institute, UNITED STATES
            Author notes

            Competing Interests: HLR is a consultant for Pfizer, Santen and Cipla, RNW is a consultant for Aerie Pharmaceuticals, Allergan, Alcon, Bausch & Lomb, Eyenovia, and Unity., KM is a consultant for Santen and Sensimed, and CABW is a consultant for Allergan, MSD and Pfizer. RNW has received financial support in form of instruments or research funding from Topcon, Carl Zeiss, Neurovision, Optos, Heidelberg Engineering, Genentech and Quark, KM has received research funding from Topcon and Alcon, and CABW has received research funding from Alcon. We also confirm that this does not alter our adherence to PLOS ONE policies on sharing data and materials.

            • Conceptualization: HLR ZSP RNW MR JPV NKP DASR SDa SDe KM CABW.

            • Data curation: HLR ZSP MR SDa.

            • Investigation: HLR ZSP JPV NKP DASR SDe.

            • Project administration: HLR ZSP.

            • Supervision: HLR.

            • Validation: HLR ZSP RNW MR JPV NKP DASR SDa SDe KM CABW.

            • Visualization: HLR ZSP RNW MR JPV NKP DASR SDa SDe KM CABW.

            • Writing – original draft: HLR.

            • Writing – review & editing: HLR ZSP RNW MR JPV NKP DASR SDa SDe KM CABW.

            Contributors
            Role: Editor
            Journal
            PLoS One
            PLoS ONE
            plos
            plosone
            PLoS ONE
            Public Library of Science (San Francisco, CA USA )
            1932-6203
            13 March 2017
            2017
            : 12
            : 3
            28288185 5348011 10.1371/journal.pone.0173930 PONE-D-16-47526
            © 2017 Rao et al

            This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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            Figures: 3, Tables: 4, Pages: 13
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            Funding
            The authors received no specific funding for this work.
            Categories
            Research Article
            Biology and Life Sciences
            Anatomy
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            Medicine and Health Sciences
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            Ocular System
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            Ophthalmology
            Eye Diseases
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