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      Clinical Factors Associated with Lamina Cribrosa Thickness in Patients with Glaucoma, as Measured with Swept Source Optical Coherence Tomography

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          Abstract

          Purpose

          To investigate the influence of various risk factors on thinning of the lamina cribrosa (LC), as measured with swept-source optical coherence tomography (SS-OCT; Topcon).

          Methods

          This retrospective study comprised 150 eyes of 150 patients: 22 normal subjects, 28 preperimetric glaucoma (PPG) patients, and 100 open-angle glaucoma patients. Average LC thickness was determined in a 3 x 3 mm cube scan of the optic disc, over which a 4 x 4 grid of 16 points was superimposed (interpoint distance: 175 μm), centered on the circular Bruch’s membrane opening. The borders of the LC were defined as the visible limits of the LC pores. The correlation of LC thickness with Humphrey field analyzer-measured mean deviation (MD; SITA standard 24–2), circumpapillary retinal nerve fiber layer thickness (cpRNFLT), the vertical cup-to-disc (C/D) ratio, and tissue mean blur rate (MBR) was determined with Spearman's rank correlation coefficient. The relationship of LC thickness with age, axial length, intraocular pressure (IOP), MD, the vertical C/D ratio, central corneal thickness (CCT), and tissue MBR was determined with multiple regression analysis. Average LC thickness and the correlation between LC thickness and MD were compared in patients with the glaucomatous enlargement (GE) optic disc type and those with non-GE disc types, as classified with Nicolela’s method.

          Results

          We found that average LC thickness in the 16 grid points was significantly associated with overall LC thickness (r = 0.77, P < 0.001). The measurement time for this area was 12.4 ± 2.4 minutes. Average LC thickness in this area had a correlation coefficient of 0.57 with cpRNFLT ( P < 0.001) and 0.46 ( P < 0.001) with MD. Average LC thickness differed significantly between the groups (normal: 268 ± 23 μm, PPG: 248 ± 13 μm, OAG: 233 ± 20 μm). Multiple regression analysis showed that MD (β = 0.29, P = 0.013), vertical C/D ratio (β = -0.25, P = 0.020) and tissue MBR (β = 0.20, P = 0.034) were independent variables significantly affecting LC thickness, but age, axial length, IOP, and CCT were not. LC thickness was significantly lower in the GE patients (233.9 ± 17.3 μm) than the non-GE patients (243.6 ± 19.5 μm, P = 0.040). The correlation coefficient between MD and LC thickness was 0.58 ( P < 0.001) in the GE patients and 0.39 ( P = 0.013) in the non-GE patients.

          Conclusion

          Cupping formation and tissue blood flow were independently correlated to LC thinning. Glaucoma patients with the GE disc type, who predominantly have large cupping, had lower LC thickness even with similar glaucoma severity.

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          Most cited references26

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          Optical coherence tomography angiography of optic disc perfusion in glaucoma.

          To compare optic disc perfusion between normal subjects and subjects with glaucoma using optical coherence tomography (OCT) angiography and to detect optic disc perfusion changes in glaucoma.
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            Myopia as a risk factor for open-angle glaucoma: a systematic review and meta-analysis.

            To determine the association between myopia and open-angle glaucoma. Systematic review and meta-analysis of observational studies. Thirteen studies involving 48 161 individuals. Articles published between 1994 and 2010 were identified in PubMed, Embase, and reference lists. Study-specific odds ratios (ORs) were pooled using a random effects model. Odds ratios with 95% confidence intervals (CIs) of myopia as a risk factor for open-angle glaucoma. Data from 11 population-based cross-sectional studies were included in the main analyses. The pooled OR of the association between myopia and glaucoma based on 11 risk estimates was 1.92 (95% CI, 1.54-2.38). On the basis of 7 risk estimates, the pooled ORs of the associations between low myopia (myopia up to -3 D) and glaucoma and between high myopia (≤-3 D myopic) and glaucoma were 1.65 (1.26-2.17) and 2.46 (1.93-3.15), respectively. There was considerable heterogeneity among studies that reported an association between any myopia and glaucoma (I(2)=53%) and low myopia and glaucoma (I(2)=29%), but not for high myopia and glaucoma (I(2)=0%). After omitting studies that contributed significantly to the heterogeneity, the pooled ORs were 1.88 (1.60-2.20) for any myopia and glaucoma and 1.77 (1.41-2.23) for low myopia and glaucoma. Individuals with myopia have an increased risk of developing open-angle glaucoma. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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              Risk factors for open-angle glaucoma in a Japanese population: the Tajimi Study.

              To identify the risk factors associated with primary open-angle glaucoma (POAG) in the Tajimi Study. Population-based cross-sectional epidemiologic study. One hundred nineteen POAG patients and 2755 controls. Univariate and multivariate comparison of ocular factors and systemic factors between POAG patients and controls. Difference in factors between POAG patients and controls, factors associated with POAG patients, and their odds ratio (OR). Intraocular pressure (IOP), age, myopia, and history of hypertension differed between POAG patients and controls in univariate analyses. Multivariate analysis with logistic regression with stepwise selection of variables demonstrated that higher IOP (OR, 1.12 [95% confidence interval (CI), 1.04-1.21]), myopia (ORs, 1.85 [95% CI, 1.03-3.31] for low myopia and 2.60 [95% CI, 1.56-4.35] for moderate to high myopia), and older age (OR, 1.06 [95% CI, 1.04-1.08]) were associated with an increased risk of having POAG. Although the majority (92%) of POAG patients diagnosed in the Tajimi Study had IOP within the normal range, IOP was still identified as a significant risk factor for POAG. Together with IOP, myopia and age were significant risk factors for having POAG.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                21 April 2016
                2016
                : 11
                : 4
                : e0153707
                Affiliations
                [1 ]Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan
                [2 ]Topcon Corporation, Tokyo, Japan
                [3 ]Department of Retinal Disease Control, Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan
                [4 ]Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
                Massachusetts Eye & Ear Infirmary, Harvard Medical School, UNITED STATES
                Author notes

                Competing Interests: Co-authors AM, TK, and MA are employed by Topcon Corporation, a commercial company. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: KO AM MA TN. Performed the experiments: KO ST AM. Analyzed the data: KO ST AM SM TK NH HT KM HK. Contributed reagents/materials/analysis tools: AM TK MA. Wrote the paper: KO TN.

                Article
                PONE-D-16-04257
                10.1371/journal.pone.0153707
                4839731
                27100404
                ad16fa4a-1359-4355-a0b7-72ddf16bc3ae
                © 2016 Omodaka 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.

                History
                : 13 February 2016
                : 3 April 2016
                Page count
                Figures: 7, Tables: 3, Pages: 18
                Funding
                Funded by: the JST Center for Revitalization Promotion
                Award Recipient :
                Funded by: a JST grant from JSPS KAKENHI Grants-in-Aid for Exploratory Research
                Award ID: 26670751
                Award Recipient :
                Funded by: a JST grant from JSPS KAKENHI Grants-in-Aid for Scientific Research (B)
                Award ID: 26293372
                Award Recipient :
                Topcon Corporation provided support in the form of salaries for authors AM, TK, and MA, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This paper was supported in part by a JST grant from JSPS KAKENHI Grants-in-Aid for Scientific Research (B) (TN 26293372) and for Exploratory Research (TN 26670751), and by the JST Center for Revitalization Promotion.
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