Sex Differences in the Association Between Systemic Oxidative Stress Status and Optic Nerve Head Blood Flow in Normal-tension Glaucoma

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2023 Feb 24

PMID 36827337

Authors

Masataka Sato

Masayuki Yasuda

Nana Takahashi

Kazuki Hashimoto

Noriko Himori

Toru Nakazawa

Affiliations

Soon will be listed here.

Abstract

Purpose: 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.

Methods: This was a cross-sectional study of 235 eyes with NTG of 134 patients (56 male, 78 female; mean age, 60.9±14.1 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's rank correlation test and a multivariate linear mixed-effect model were used to investigate factors associated with ONH blood flow.

Results: MBR-T was significantly correlated with age (rs = -0.28, p < 0.001), mean arterial pressure (rs = -0.20, p = 0.002), intraocular pressure (rs = 0.24, p < 0.001), peripapillary retinal nerve fiber layer thickness (rs = 0.62, p < 0.001), and disc area (rs = -0.26, p < 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 < 0.001) only in male subjects. Similarly, BAP was significantly associated with MBR-T (β = 0.25, p = 0.026) and FAI-T (β = 0.37, p < 0.001) in male subjects in a multivariate linear mixed-effect model.

Conclusion: 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.

Citing Articles

Systemic oxidative stress levels and their associations with the risk of neovascular age-related macular degeneration and treatment response.

Abe M, Kunikata H, Aizawa N, Yasuda M, Nitta F, Abe T Int J Retina Vitreous. 2025; 11(1):16.

PMID: 39930486 PMC: 11809058. DOI: 10.1186/s40942-025-00632-1.

The association between intraocular pressure dynamics during dark-room prone testing and intraocular pressure over a relatively long-term follow-up period in primary open-glaucoma patients.

Sato M, Kiyota N, Yabana T, Maekawa S, Tsuda S, Omodaka K Graefes Arch Clin Exp Ophthalmol. 2023; 262(3):949-956.

PMID: 37864634 PMC: 10907413. DOI: 10.1007/s00417-023-06257-0.

Factors Associated With Visual Acuity Decline in Glaucoma Patients With Loss of Ganglion Cell Complex Thickness.

Takahashi N, Omodaka K, Kikawa T, Ninomiya T, Kiyota N, Tsuda S Transl Vis Sci Technol. 2023; 12(7):2.

PMID: 37395706 PMC: 10324415. DOI: 10.1167/tvst.12.7.2.

References

Asano Y, Himori N, Kunikata H, Yamazaki M, Shiga Y, Omodaka K . Age- and sex-dependency of the association between systemic antioxidant potential and glaucomatous damage. Sci Rep. 2017; 7(1):8032. PMC: 5556047. DOI: 10.1038/s41598-017-08624-4. View

Vajaranant T, Nayak S, Wilensky J, Joslin C . Gender and glaucoma: what we know and what we need to know. Curr Opin Ophthalmol. 2010; 21(2):91-9. PMC: 4326058. DOI: 10.1097/ICU.0b013e3283360b7e. View

Yokoyama Y, Maruyama K, Konno H, Hashimoto S, Takahashi M, Kayaba H . Characteristics of patients with primary open angle glaucoma and normal tension glaucoma at a university hospital: a cross-sectional retrospective study. BMC Res Notes. 2015; 8:360. PMC: 4541728. DOI: 10.1186/s13104-015-1339-x. View

Signorelli S, Scuto S, Marino E, Xourafa A, Gaudio A . Oxidative Stress in Peripheral Arterial Disease (PAD) Mechanism and Biomarkers. Antioxidants (Basel). 2019; 8(9). PMC: 6770183. DOI: 10.3390/antiox8090367. View

Masai S, Ishida K, Anraku A, Takumi T, Tomita G . Pulse Waveform Analysis of the Ocular Blood Flow Using Laser Speckle Flowgraphy before and after Glaucoma Treatment. J Ophthalmol. 2019; 2019:1980493. PMC: 6794986. DOI: 10.1155/2019/1980493. View

Shiga Y, Omodaka K, Kunikata H, Ryu M, Yokoyama Y, Tsuda S . Waveform analysis of ocular blood flow and the early detection of normal tension glaucoma. Invest Ophthalmol Vis Sci. 2013; 54(12):7699-706. DOI: 10.1167/iovs.13-12930. View

Mazza M, Marano G, Traversi G, Bria P, Mazza S . Primary cerebral blood flow deficiency and Alzheimer's disease: shadows and lights. J Alzheimers Dis. 2010; 23(3):375-89. DOI: 10.3233/JAD-2010-090700. View

Himori N, Inoue Yanagimachi M, Omodaka K, Shiga Y, Tsuda S, Kunikata H . The Effect of Dietary Antioxidant Supplementation in Patients with Glaucoma. Clin Ophthalmol. 2021; 15:2293-2300. PMC: 8183457. DOI: 10.2147/OPTH.S314288. View

Himori N, Kunikata H, Shiga Y, Omodaka K, Maruyama K, Takahashi H . The association between systemic oxidative stress and ocular blood flow in patients with normal-tension glaucoma. Graefes Arch Clin Exp Ophthalmol. 2015; 254(2):333-41. DOI: 10.1007/s00417-015-3203-z. View

10.

Takayanagi Y, Takai Y, Kaidzu S, Tanito M . Evaluation of Redox Profiles of the Serum and Aqueous Humor in Patients with Primary Open-Angle Glaucoma and Exfoliation Glaucoma. Antioxidants (Basel). 2020; 9(12). PMC: 7765903. DOI: 10.3390/antiox9121305. View

11.

Hall J . Endocrinology of the Menopause. Endocrinol Metab Clin North Am. 2015; 44(3):485-96. PMC: 6983294. DOI: 10.1016/j.ecl.2015.05.010. View

12.

Boland M, Ervin A, Friedman D, Jampel H, Hawkins B, Vollenweider D . Comparative effectiveness of treatments for open-angle glaucoma: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 158(4):271-9. DOI: 10.7326/0003-4819-158-4-201302190-00008. View

13.

Tanito M, Kaidzu S, Takai Y, Ohira A . Association between systemic oxidative stress and visual field damage in open-angle glaucoma. Sci Rep. 2016; 6:25792. PMC: 4863173. DOI: 10.1038/srep25792. View

14.

Luft N, Wozniak P, Aschinger G, Fondi K, Bata A, Werkmeister R . Ocular Blood Flow Measurements in Healthy White Subjects Using Laser Speckle Flowgraphy. PLoS One. 2016; 11(12):e0168190. PMC: 5154568. DOI: 10.1371/journal.pone.0168190. View

15.

Xing D, Nozell S, Chen Y, Hage F, Oparil S . Estrogen and mechanisms of vascular protection. Arterioscler Thromb Vasc Biol. 2009; 29(3):289-95. PMC: 2700771. DOI: 10.1161/ATVBAHA.108.182279. View

16.

Mursch-Edlmayr A, Luft N, Podkowinski D, Ring M, Schmetterer L, Bolz M . Laser speckle flowgraphy derived characteristics of optic nerve head perfusion in normal tension glaucoma and healthy individuals: a Pilot study. Sci Rep. 2018; 8(1):5343. PMC: 5871884. DOI: 10.1038/s41598-018-23149-0. View

17.

Iwase A, Suzuki Y, Araie M, Yamamoto T, Abe H, Shirato S . The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study. Ophthalmology. 2004; 111(9):1641-8. DOI: 10.1016/j.ophtha.2004.03.029. View

18.

Izzotti A, Bagnis A, Sacca S . The role of oxidative stress in glaucoma. Mutat Res. 2006; 612(2):105-14. DOI: 10.1016/j.mrrev.2005.11.001. View

19.

Shiga Y, Kunikata H, Aizawa N, Kiyota N, Maiya Y, Yokoyama Y . Optic Nerve Head Blood Flow, as Measured by Laser Speckle Flowgraphy, Is Significantly Reduced in Preperimetric Glaucoma. Curr Eye Res. 2016; 41(11):1447-1453. DOI: 10.3109/02713683.2015.1127974. View

20.

Kiyota N, Shiga Y, Ichinohasama K, Yasuda M, Aizawa N, Omodaka K . The Impact of Intraocular Pressure Elevation on Optic Nerve Head and Choroidal Blood Flow. Invest Ophthalmol Vis Sci. 2018; 59(8):3488-3496. DOI: 10.1167/iovs.18-23872. View