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      Schlemm’s Canal and Trabecular Meshwork in Eyes with Primary Open Angle Glaucoma: A Comparative Study Using High-Frequency Ultrasound Biomicroscopy

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          Abstract

          We investigated in vivo changes in Schlemm’s canal and the trabecular meshwork in eyes with primary open angle glaucoma (POAG). Relationships between Schlemm’s canal diameter, trabecular meshwork thickness, and intraocular pressure (IOP) were examined. Forty POAG patients and 40 normal individuals underwent 80-MHz Ultrasound Biomicroscopy examinations. The Schlemm’s canal and trabecular meshwork were imaged in superior, inferior, nasal and temporal regions. Normal individuals had an observable Schlemm’s canal in 80.3% of sections, a meridional canal diameter of 233.0±34.5 μm, a coronal diameter of 44.5±12.6 μm and a trabecular meshwork thickness of 103.9±11.1 μm, in POAG patients, Schlemm’s canal was observable in 53.1% of sections, a meridional canal diameter of 195.6±31.3 μm, a coronal diameter of 35.7±8.0 μm, and a trabecular meshwork thickness of 88.3±13.2 μm, which significantly differed from normal (both p <0.001). Coronal canal diameter (r = -0.623, p < 0.001) and trabecular meshwork thickness (r = -0.663, p < 0.001) were negatively correlated with IOP, but meridional canal diameter was not (r = -0.160, p = 0.156). Schlemm’s canal was observable in 50.5% and 56.6% of POAG patients with normal (<21 mmHg) and elevated (>21 mmHg) IOP, respectively (χ = 1.159, p = 0.282). Coronal canal diameter was significantly lower in the elevated IOP group (32.6±4.9 μm) than in the normal IOP group (35.7±8.0 μm, p < 0.001). This was also true of trabecular meshwork thickness (81.9±10.0 μm vs. 97.1±12.0 μm, p < 0.001). In conclusion, eyes with POAG had fewer sections with an observable Schlemm’s canal. Canal diameter and trabecular meshwork thickness were also lower than normal in POAG patients. Schlemm’s canal coronal diameter and trabecular meshwork thickness were negatively correlated with IOP.

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          Extracellular matrix in the trabecular meshwork.

          The extracellular matrix (ECM) of the trabecular meshwork (TM) is thought to be important in regulating intraocular pressure (IOP) in both normal and glaucomatous eyes. IOP is regulated primarily by a fluid resistance to aqueous humor outflow. However, neither the exact site nor the identity of the normal resistance to aqueous humor outflow has been established. Whether the site and nature of the increased outflow resistance, which is associated with open-angle glaucoma, is the same or different from the normal resistance is also unclear. The ECMs of the TM beams, juxtacanalicular region (JCT) and Schlemm's canal (SC) inner wall are comprised of fibrillar and non-fibrillar collagens, elastin-containing microfibrils, matricellular and structural organizing proteins, glycosaminoglycans (GAGs) and proteoglycans. Both basement membranes and stromal ECM are present in the TM beams and JCT region. Cell adhesion proteins, cell surface ECM receptors and associated binding proteins are also present in the beams, JCT and SC inner wall region. The outflow pathway ECM is relatively dynamic, undergoing constant turnover and remodeling. Regulated changes in enzymes responsible for ECM degradation and biosynthetic replacement are observed. IOP homeostasis, triggered by pressure changes or mechanical stretching of the TM, appears to involve ECM turnover. Several cytokines, growth factors and drugs, which affect the outflow resistance, change ECM component expression, mRNA alternative splicing, cellular cytoskeletal organization or all of these. Changes in ECM associated with open-angle glaucoma have been identified.
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            Intraocular pressure fluctuation a risk factor for visual field progression at low intraocular pressures in the advanced glaucoma intervention study.

            To investigate the relationship of intraocular pressure (IOP) fluctuation and mean IOP to visual field (VF) progression in patients enrolled in the Advanced Glaucoma Intervention Study (AGIS). Retrospective analysis of a prospective randomized clinical trial. Three hundred one eyes of 301 patients enrolled in the AGIS were included. Eyes with more than one surgical intervention were excluded. Worsening of the VF was detected with pointwise linear regression. Long-term IOP fluctuation was defined as the standard deviation of IOP (millimeters of mercury) at all visits after initial intervention until the time of VF worsening or end of follow-up, whichever came first. A multivariate linear regression model was performed to identify predictors of VF progression. Terciles of mean IOP were identified, and the average IOP fluctuation in each stratum was calculated. Terciles of long-term IOP fluctuation were similarly evaluated. The proportion of eyes showing VF progression in each stratum was determined and compared. Visual field progression. Visual field progression was detected in 78 eyes (26%). There were statistically significant differences, between progressing and nonprogressing eyes, for mean IOP (P = 0.006), IOP fluctuation (P<0.001), mean length of follow-up (P = 0.013), mean number of VFs (P = 0.005), and mean number of medications (P = 0.006). Three variables were associated with a higher probability of VF progression: greater IOP fluctuation (P = 0.009), argon laser trabeculoplasty (P = 0.004), and older age (P = 0.05). In this model, mean IOP was of borderline statistical significance (P = 0.09). Within the lower and upper terciles of mean IOP, IOP fluctuation was associated with VF progression in the low mean IOP group (P = 0.002) but not in the high mean IOP group (P = 0.2). When subjects were stratified according to IOP fluctuation, there was a statistically significant difference between lower and upper terciles of IOP fluctuation with respect to progression (P = 0.05). There was a weak correlation between mean IOP and IOP fluctuation (r(2) = 0.025, P = 0.01). In the AGIS, long-term IOP fluctuation is associated with VF progression in patients with low mean IOP but not in patients with high mean IOP.
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              Experimental aqueous perfusion in enucleated human eyes.

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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
                4 January 2016
                2016
                : 11
                : 1
                : e0145824
                Affiliations
                [001]Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
                Duke University, UNITED STATES
                Author notes

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

                Conceived and designed the experiments: HZ. Performed the experiments: XY YS. Analyzed the data: XY YS. Contributed reagents/materials/analysis tools: HZ ZC YZ XY YS ML. Wrote the paper: XY YS ML.

                Article
                PONE-D-15-35112
                10.1371/journal.pone.0145824
                4699705
                26726880
                17d84ab1-ecc5-4267-8408-b09f52215bdc
                © 2016 Yan 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
                : 12 August 2015
                : 9 December 2015
                Page count
                Figures: 4, Tables: 5, Pages: 15
                Funding
                Support was provided by grants No 81170842 from the Natural Science Foundation of China [ http://isisn.nsfc.gov.cn/egrantindex/funcindex/prjsearch-list] to HZ, and by grants No 81300760 from the Natural Science Foundation of China [ http://isisn.nsfc.gov.cn/egrantindex/funcindex/prjsearch-list] to ZC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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