{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T21:11:31Z","timestamp":1781730691842,"version":"3.54.5"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20H03838"],"award-info":[{"award-number":["JP20H03838"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Grant-in-Aid for Challenging Exploratory Research","award":["JP21K19548"],"award-info":[{"award-number":["JP21K19548"]}]},{"name":"Grant-in-Aid for Early-Career Scientists","award":["JP21K16866"],"award-info":[{"award-number":["JP21K16866"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>To investigate the association of systemic oxidative stress markers and optic nerve head (ONH) blood flow in normal-tension glaucoma (NTG) patients, as well as sex differences in this association.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This was a cross-sectional study of 235 eyes with NTG of 134 patients (56 male, 78 female; mean age, 60.9\u00b114.1 years). Laser speckle flowgraphy (LSFG) was used to measure ONH blood flow (mean blur rate in the tissue area of the ONH; MBR-T) and LSFG pulse-waveform parameters, including flow acceleration index in the tissue area of the ONH (FAI-T). Oxidative stress markers, diacron-reactive oxygen metabolites (d-ROMs), and biological antioxidant potential (BAP) were measured with a free radical elective evaluator. Spearman\u2019s rank correlation test and a multivariate linear mixed-effect model were used to investigate factors associated with ONH blood flow.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>MBR-T was significantly correlated with age (rs = -0.28, p &lt; 0.001), mean arterial pressure (rs = -0.20, p = 0.002), intraocular pressure (rs = 0.24, p &lt; 0.001), peripapillary retinal nerve fiber layer thickness (rs = 0.62, p &lt; 0.001), and disc area (rs = -0.26, p &lt; 0.001), but not with serum d-ROM level. Separate analyses of the subjects divided by sex showed that BAP was positively correlated to MBR-T (rs = 0.21, p = 0.036) and FAI-T (rs = 0.36, p &lt; 0.001) only in male subjects. Similarly, BAP was significantly associated with MBR-T (\u03b2 = 0.25, p = 0.026) and FAI-T (\u03b2 = 0.37, p &lt; 0.001) in male subjects in a multivariate linear mixed-effect model.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>A lower serum antioxidant level, as indicated by BAP, was associated with reduced ONH blood flow only in male NTG patients. Our findings suggest that there are sex differences in the involvement of oxidative stress in the pathogenesis of reduced ocular blood flow in NTG.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0282047","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T18:42:21Z","timestamp":1677264141000},"page":"e0282047","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Sex differences in the association between systemic oxidative stress status and optic nerve head blood flow in normal-tension glaucoma"],"prefix":"10.1371","volume":"18","author":[{"given":"Masataka","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Himori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5591-4155","authenticated-orcid":true,"given":"Toru","family":"Nakazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"pone.0282047.ref001","article-title":"Epidemiology of Glaucoma: The Past, Present, and Predictions for the Future","author":"K Allison","year":"2020","journal-title":"Cureus"},{"issue":"1","key":"pone.0282047.ref002","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S1350-9462(98)00014-7","article-title":"Neuronal death in glaucoma","volume":"18","author":"HA Quigley","year":"1999","journal-title":"Prog Retin Eye Res"},{"issue":"4","key":"pone.0282047.ref003","doi-asserted-by":"crossref","first-page":"271","DOI":"10.7326\/0003-4819-158-4-201302190-00008","article-title":"Comparative effectiveness of treatments for open-angle glaucoma: a systematic review for the U.S. Preventive Services Task Force","volume":"158","author":"MV Boland","year":"2013","journal-title":"Ann Intern Med"},{"issue":"1","key":"pone.0282047.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13104-015-1339-x","article-title":"Characteristics of patients with primary open angle glaucoma and normal tension glaucoma at a university hospital: A cross-sectional retrospective study","volume":"8","author":"Y Yokoyama","year":"2015","journal-title":"BMC Res Notes"},{"key":"pone.0282047.ref005","doi-asserted-by":"crossref","first-page":"023","DOI":"10.17352\/2455-1414.000088","article-title":"Normal tension glaucoma: Prevalence, etiology and treatment","author":"A George","year":"2021","journal-title":"J Clin Res Ophthalmol"},{"issue":"9","key":"pone.0282047.ref006","first-page":"1641","article-title":"The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study","volume":"111","author":"A Iwase","year":"2004","journal-title":"Ophthalmology"},{"issue":"1","key":"pone.0282047.ref007","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/APO.0000000000000183","article-title":"Ocular Blood Flow and Influencing Factors for Glaucoma","volume":"5","author":"T. 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