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      Association between systemic oxidative stress and visual field damage in open-angle glaucoma

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          Abstract

          Local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage may be involved in the pathogenesis of glaucoma. We reported previously that a lower level of systemic antioxidative capacity is associated with IOP elevation in open-angle glaucoma (OAG). We assessed the correlation between the visual field sensitivity value, i.e., mean deviation (MD), and systemic levels of prooxidants and antioxidants by analyzing the blood biochemistry in 202 patients with glaucoma. Serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured using the diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free-radical analyzer. Univariate and multivariate analyses suggested a positive correlation between MD and BAP (R = 0.005 and P = 0.0442 by a multiple regression model adjusted for seven demographic parameters), but no significant associations between the MD and the dROM (R = 0.002 and P = 0.8556) and SH tests (R = −0.001 and P = 0.8280). Use of more antiglaucoma medication and primary OAG rather than normal tension glaucoma also were associated significantly with worse visual field damage. This large and comprehensive assessment of the association between systemic redox status and visual field damage in OAG suggests that lower systemic antioxidant capacity measured by ferric-reducing activity is associated with more severe visual field damage in OAG that partly explained its roles in IOP elevation.

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          Prevalence and causes of low vision and blindness in a Japanese adult population: the Tajimi Study.

          To determine the prevalence and causes of low vision and blindness in a Japanese adult population. Population-based cross-sectional study. Randomly selected residents (n = 3870) of Tajimi City, Japan, who were 40 years of age or older. Of the 3021 study participants (78.1% of 3870 eligible persons), 2977 (76.9%) underwent a complete ophthalmologic examination including measurement of the best-corrected visual acuity (BCVA) with full subjective refraction using a Landolt ring chart at 5 m. Age- and gender-specific prevalence rates of low vision and blindness were estimated and causes were identified. Low vision and blindness were defined as BCVA in the better eye worse than 20/60 to a lower limit of 20/400 and worse than 20/400, respectively (World Health Organization [WHO] criteria) and worse than 20/40 but better than 20/200 and 20/200 or worse, respectively (United States criteria). The overall prevalence of blindness according to the WHO or U.S. criteria was 0.14% (n = 4; 95% confidence interval [CI], 0.06-0.32). The primary causes were optic atrophy, myopic macular degeneration, retinitis pigmentosa, and uveitis. The overall prevalence of low vision according to the WHO criteria was 0.39% (95% CI, 0.18%-0.60%) and according to the U.S. criteria was 0.98% (95% CI, 0.66%-1.30%), which was significantly greater in women and in the older half of the participants than in the younger half (P = 0.0079 and <0.0001, respectively). The leading causes of low vision in descending order were cataract followed by glaucoma, and those of monocular blindness were myopic macular degeneration, glaucoma, and trauma. The prevalence of low vision and blindness in Japanese adults was one of the lowest among those reported. The major causes of low vision were cataract and glaucoma, and the leading cause of monocular blindness was myopic macular degeneration.
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            The impact of Vision 2020 on global blindness.

            Recent data suggest that there are 37 million blind people and 124 million with low vision, excluding those with uncorrected refractive errors. The main causes of global blindness are cataract, glaucoma, corneal scarring (from a variety of causes), age-related macular degeneration, and diabetic retinopathy. It would appear that the global Vision 2020 initiative is having an impact to reduce avoidable blindness particularly from ocular infections, but more needs to be done to address cataract, glaucoma, and diabetic retinopathy.
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              Oxidative deoxyribonucleic acid damage in the eyes of glaucoma patients.

              Little is known about the molecular mechanisms responsible for the development of glaucoma, the leading cause of irreversible blindness worldwide. Some investigators have hypothesized that oxidative damage may be involved. We evaluated oxidative deoxyribonucleic acid (DNA) damage, in terms of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the eyes of glaucoma patients. Levels of 8-OH-dG were measured in the trabecular meshwork region from 42 patients with glaucoma and 45 controls of similar age and sex. Genotypes of glutathione S-transferase isoenzymes (GSTM1 and GSTT1) were assessed by polymerase chain reaction in the same DNA samples. Levels of 8-OH-dG were significantly higher in glaucoma patients than in controls. Oxidative DNA damage in patients with glaucoma correlated significantly with intraocular pressure; in patients with primary open-angle glaucoma, it also correlated with visual field defects. GSTT1 was similar in the two groups, and had no effect on 8-OH-dG levels. Conversely, 8-OH-dG levels were significantly higher in GSTM1-null than in GSTM1-positive subjects. The GSTM1-null genotype was significantly more common in patients with primary open-angle glaucoma than in controls. Oxidative DNA damage is significantly increased in the trabecular meshwork of glaucoma patients. GSTM1 gene deletion, which has been associated with an increased risk of cancer at various sites and molecular lesions in atherosclerosis, predisposes to more severe oxidative DNA damage in glaucoma patients. These findings may contribute to understanding the pathogenesis of glaucoma and may be useful in the prevention and treatment of this disease.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                11 May 2016
                2016
                : 6
                : 25792
                Affiliations
                [1 ]Department of Ophthalmology, Shimane University Faculty of Medicine , 89-1 Enya, Izumo, Shimane, 693-8501, Japan
                [2 ]Division of Ophthalmology, Matsue Red Cross Hospital , 200 Horo-machi, Matsue, Shimane, 690-8506, Japan
                Author notes
                Article
                srep25792
                10.1038/srep25792
                4863173
                27165400
                32897f25-4e2b-481d-81b8-cd1f6b846bd4
                Copyright © 2016, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 08 January 2016
                : 22 April 2016
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