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Quantitative optical coherence tomography angiography of macular vascular structure and foveal avascular zone in glaucoma

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      Abstract

      ObjectiveThe study aimed to evaluate the quantitative characteristics of the macular vessel density (VD) and foveal avascular zone (FAZ) in glaucoma using optical coherence tomography angiography (OCT-A).DesignCross-sectional, age- and sex-matched case–control study.MethodsFifty-two eyes of 52 patients with primary open angle glaucoma and 52 eyes from 52 healthy participants were recruited retrospectively. OCT-A was performed on a 3 x 3-mm macular region centered on the fovea. OCT-A scans were manually graded to define the FAZ. Parafoveal VD in superficial and deep retina were analyzed in the circular- and quadrant-segmented zone. The FAZ parameters included size, perimeter, and circularity index. The regression analysis among VD and FAZ-related parameters and ocular parameters was performed, and the diagnostic ability was calculated with refractive error adjusted.ResultsFor both groups, the mean age and the sex ratio was not different between groups. With refractive error adjusted, the average macular VD was lower in glaucoma than in the control group for superficial (P = 0.013), deep (P<0.001), and the whole retina (P = 0.002). There were increased FAZ perimeter and decreased FAZ circularity index in glaucoma when compared with controls (P<0.001). In the multivariate regression models, FAZ circularity index were significantly associated with decreased peripapillary RNFL thickness (P = 0.007) and macular GCIPL thickness (P = 0.009) measured by OCT. The refractive-error adjusted area under receiver operating characteristics was highest for FAZ circularity index (0.905; 95% CI, 0.844–0.966), followed by temporal deep retinal VD (0.870; 95% CI, 0.803–0.937) and FAZ perimeter (0.858; 95% CI, 0.784–0.932).ConclusionsDecreased macular VD, increased FAZ perimeter, and decreased FAZ circularity index were observed in eyes with glaucoma using OCT-A. With refractive error adjusted, these parameters showed considerable diagnostic value for glaucoma. FAZ circularity index may be a novel biomarker representing disruption of the parafoveal capillary network in glaucoma, as supported by its association with structural parameters.

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      Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.

      Methods of evaluating and comparing the performance of diagnostic tests are of increasing importance as new tests are developed and marketed. When a test is based on an observed variable that lies on a continuous or graded scale, an assessment of the overall value of the test can be made through the use of a receiver operating characteristic (ROC) curve. The curve is constructed by varying the cutpoint used to determine which values of the observed variable will be considered abnormal and then plotting the resulting sensitivities against the corresponding false positive rates. When two or more empirical curves are constructed based on tests performed on the same individuals, statistical analysis on differences between curves must take into account the correlated nature of the data. This paper presents a nonparametric approach to the analysis of areas under correlated ROC curves, by using the theory on generalized U-statistics to generate an estimated covariance matrix.
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        Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis.

         D Shweiki,  E Keshet,  A Itin (1992)
        Inefficient vascular supply and the resultant reduction in tissue oxygen tension often lead to neovascularization in order to satisfy the needs of the tissue. Examples include the compensatory development of collateral blood vessels in ischaemic tissues that are otherwise quiescent for angiogenesis and angiogenesis associated with the healing of hypoxic wounds. But the presumptive hypoxia-induced angiogenic factors that mediate this feedback response have not been identified. Here we show that vascular endothelial growth factor (VEGF; also known as vascular permeability factor) probably functions as a hypoxia-inducible angiogenic factor. VEGF messenger RNA levels are dramatically increased within a few hours of exposing different cell cultures to hypoxia and return to background when normal oxygen supply is resumed. In situ analysis of tumour specimens undergoing neovascularization show that the production of VEGF is specifically induced in a subset of glioblastoma cells distinguished by their immediate proximity to necrotic foci (presumably hypoxic regions) and the clustering of capillaries alongside VEGF-producing cells.
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          The impact of ocular blood flow in glaucoma.

          Two principal theories for the pathogenesis of glaucomatous optic neuropathy (GON) have been described--a mechanical and a vascular theory. Both have been defended by various research groups over the past 150 years. According to the mechanical theory, increased intraocular pressure (IOP) causes stretching of the laminar beams and damage to retinal ganglion cell axons. The vascular theory of glaucoma considers GON as a consequence of insufficient blood supply due to either increased IOP or other risk factors reducing ocular blood flow (OBF). A number of conditions such as congenital glaucoma, angle-closure glaucoma or secondary glaucomas clearly show that increased IOP is sufficient to lead to GON. However, a number of observations such as the existence of normal-tension glaucoma cannot be satisfactorily explained by a pressure theory alone. Indeed, the vast majority of published studies dealing with blood flow report a reduced ocular perfusion in glaucoma patients compared with normal subjects. The fact that the reduction of OBF often precedes the damage and blood flow can also be reduced in other parts of the body of glaucoma patients, indicate that the hemodynamic alterations may at least partially be primary. The major cause of this reduction is not atherosclerosis, but rather a vascular dysregulation, leading to both low perfusion pressure and insufficient autoregulation. This in turn may lead to unstable ocular perfusion and thereby to ischemia and reperfusion damage. This review discusses the potential role of OBF in glaucoma and how a disturbance of OBF could increase the optic nerve's sensitivity to IOP.
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            Author and article information

            Affiliations
            [1 ] Central Seoul Eye Center, Seoul, Republic of Korea
            [2 ] Department of Ophthalmology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Republic of Korea
            Bascom Palmer Eye Institute, UNITED STATES
            Author notes

            Competing Interests: The authors have declared that no competing interests exist.

            ‡ These authors also contributed equally to this work.

            Contributors
            Role: Conceptualization, Role: Data curation, Role: Formal analysis, Role: Investigation, Role: Methodology, Role: Project administration, Role: Resources, Role: Software, Role: Supervision, Role: Validation, Role: Visualization, Role: Writing – original draft, Role: Writing – review & editing
            Role: Data curation, Role: Formal analysis, Role: Resources, Role: Software, Role: Visualization
            Role: Data curation, Role: Formal analysis, Role: Resources, Role: Software, Role: Visualization
            Role: Supervision, Role: Validation, Role: Writing – review & editing
            Role: Data curation, Role: Resources, Role: Software
            ORCID: http://orcid.org/0000-0001-7407-596X, Role: Conceptualization, Role: Formal analysis, Role: Funding acquisition, Role: Investigation, Role: Project administration, Role: Resources, Role: Supervision, Role: Writing – review & editing
            Role: Editor
            Journal
            PLoS One
            PLoS ONE
            plos
            plosone
            PLoS ONE
            Public Library of Science (San Francisco, CA USA )
            1932-6203
            21 September 2017
            2017
            : 12
            : 9
            28934255
            5608222
            10.1371/journal.pone.0184948
            PONE-D-17-12573
            (Editor)
            © 2017 Choi 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: 5, Pages: 19
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            Funding
            The authors received no specific funding for this work.
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            Ophthalmology
            Eye Diseases
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