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      Optic Disc Perfusion in Primary Open Angle and Normal Tension Glaucoma Eyes Using Optical Coherence Tomography-Based Microangiography

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          Abstract

          Purpose

          To investigate optic disc perfusion differences in normal, primary open-angle glaucoma (POAG), and normal tension glaucoma (NTG) eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique.

          Design

          Cross-sectional, observational study.

          Subjects

          Twenty-eight normal, 30 POAG, and 31 NTG subjects.

          Methods

          One eye from each subject was scanned with a 68 kHz Cirrus HD-OCT 5,000-based OMAG prototype system centered at the optic nerve head (ONH) (Carl Zeiss Meditec Inc, Dublin, CA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program.

          Main Outcome Measures

          Optic disc perfusion, quantified as flux, vessel area density, and normalized flux (flux normalized by the vessel area) within the ONH.

          Results

          Glaucomatous eyes had significantly lower optic disc perfusion in preLC in all three perfusion metrics (p<0.0001) compared to normal eyes. The visual field (VF) mean deviation (MD) and pattern standard deviation (PSD) were similar between the POAG and NTG groups, and no differences in optic disc perfusion were observed between POAG and NTG. Univariate analysis revealed significant correlation between optic disc perfusion and VF MD, VF PSD, and rim area in both POAG and NTG groups (p≤0.0288). However, normalized optic disc perfusion was correlated with some structural measures (retinal nerve fiber layer thickness and ONH cup/disc ratio) only in POAG eyes.

          Conclusions

          Optic disc perfusion detected with OMAG was significantly reduced in POAG and NTG groups compared to normal controls, but no difference was seen between POAG and NTG groups with similar levels of VF damage. Disc perfusion was significantly correlated with VF MD, VF PSD, and rim area in glaucomatous eyes. Vascular changes at the optic disc as measured using OMAG may provide useful information for diagnosis and monitoring of glaucoma.

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          Most cited references44

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          The impact of ocular blood flow in glaucoma.

          Josef Flammer, Selim Orgül, Vital P. Costa … (2002)
          Two principal theories for the pathogenesis of glaucomatous optic neuropathy (GON) have been described--a mechanical and a vascular theory. Both have been defended by various research groups over the past 150 years. According to the mechanical theory, increased intraocular pressure (IOP) causes stretching of the laminar beams and damage to retinal ganglion cell axons. The vascular theory of glaucoma considers GON as a consequence of insufficient blood supply due to either increased IOP or other risk factors reducing ocular blood flow (OBF). A number of conditions such as congenital glaucoma, angle-closure glaucoma or secondary glaucomas clearly show that increased IOP is sufficient to lead to GON. However, a number of observations such as the existence of normal-tension glaucoma cannot be satisfactorily explained by a pressure theory alone. Indeed, the vast majority of published studies dealing with blood flow report a reduced ocular perfusion in glaucoma patients compared with normal subjects. The fact that the reduction of OBF often precedes the damage and blood flow can also be reduced in other parts of the body of glaucoma patients, indicate that the hemodynamic alterations may at least partially be primary. The major cause of this reduction is not atherosclerosis, but rather a vascular dysregulation, leading to both low perfusion pressure and insufficient autoregulation. This in turn may lead to unstable ocular perfusion and thereby to ischemia and reperfusion damage. This review discusses the potential role of OBF in glaucoma and how a disturbance of OBF could increase the optic nerve's sensitivity to IOP.
          Article 0 comments Cited 416 times – based on 0 reviews     Review now
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            Optical coherence tomography angiography of optic disc perfusion in glaucoma.

            Yali Jia, Eric Wei, Xiaogang Wang … (2014)
            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.
            Article 0 comments Cited 229 times – based on 0 reviews     Review now
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              Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey.

              A Sommer, J Tielsch, J. Katz … (1991)
              A detailed ocular examination, including perimetry, was conducted on 5308 black and white subjects aged 40 years and older in a population-based prevalence survey in east Baltimore, Md. Repeated, detailed examinations were carried out on selected subjects. Roughly half of all subjects with optic nerve damage from primary open angle glaucoma, regardless of race, were unaware that they had the condition. The average intraocular pressure (IOP) among black patients with glaucoma who were receiving treatment was virtually identical to that in those black patients who were not receiving treatment (median IOP, 20 mm Hg); treated eyes of white patients had a lower IOP than those eyes of white patients who were not receiving treatment (mean [+/- SD] IOP, 18.69 +/- 3.23 mm Hg vs 24.15 +/- 5.23 mm Hg; P less than .001). The risk of glaucomatous optic nerve damage increased with the height of the screening IOP, particularly at levels of 22 to 29 and 30 mm Hg and above (relative rate compared with IOP of 15 mm Hg or lower, 12.8 and 40.1 mm Hg, respectively). More than half of all glaucomatous eyes had a screening IOP below 21 mm Hg, whether these eyes were receiving treatment or not. The IOP in glaucomatous eyes tended to rise on follow-up, in contrast with nonglaucomatous eyes in which the IOP was as likely to rise as to fall. Results confirmed that IOP is an important factor in glaucoma, but did not support the traditional distinction between "normal" and "elevated" pressure, nor its corollaries, "low-tension" glaucoma and "high-tension" glaucoma.
              Article 0 comments Cited 156 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Demetrios G. Vavvas: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 5 May 2016
                Publication date Collection: 2016
                Volume: 11
                Issue: 5
                Electronic Location Identifier: e0154691
                Affiliations
                [1 ]Department of Ophthalmology, University of Washington, Seattle, Washington, United States of America
                [2 ]Department of Bioengineering, University of Washington, Seattle, Washington, United States of America
                [3 ]Department of Ophthalmology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
                Massachusetts Eye & Ear Infirmary, Harvard Medical School, UNITED STATES
                Author notes

                Competing Interests: The authors have read the journal's policy and have the following competing interests: CLC, QZ, and RKW received research support from Carl Zeiss Meditec, Inc.; MAJ is a consultant for Healonics, Sensimed, Ivantis, Cascade Ophthalmics, and receives royalties from intellectual property owned by Allergan; RKW has significant financial interest in the intellectual property of OMAG technology, owned by Oregon Health & Science University; KDB, JCW, CX, DG, RCM, and PPC: None. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: KDB CLC JCW QZ CX DG RCM MAJ RKW PPC. Performed the experiments: KDB CLC JW DG. Analyzed the data: KDB, CHC. Contributed reagents/materials/analysis tools: KDB CLC JCW QZ CX DG RCM MAJ RKW PPC. Wrote the paper: KDB CLC JCW QZ CX DG RCM MAJ RKW PPC.

                Article
                Publisher ID: PONE-D-16-06066
                DOI: 10.1371/journal.pone.0154691
                PMC ID: 4858256
                PubMed ID: 27149261
                SO-VID: 48a73583-8f31-47f0-9c7a-13661af21f66
                Copyright © © 2016 Bojikian et al
                License:

                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
                Date received : 11 February 2016
                Date accepted : 18 April 2016
                Page count
                Figures: 3, Tables: 5, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000053, National Eye Institute;
                Award ID: R01-EY024158
                Award Recipient :
                Funded by: Carl Zeiss Meditec Inc
                Funded by: funder-id http://dx.doi.org/10.13039/100001818, Research to Prevent Blindness;
                This study was supported in part by the National Institutes of Health contract NEI R01-EY024158; Carl Zeiss Meditec Inc.; Research to Prevent Blindness (New York, NY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Head
                Subject: Eyes
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Head
                Subject: Eyes
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Ocular System
                Subject: Eyes
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Ocular System
                Subject: Eyes
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Ocular System
                Subject: Ocular Anatomy
                Subject: Optic Disc
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Ocular System
                Subject: Ocular Anatomy
                Subject: Optic Disc
                Subject: Medicine and Health Sciences
                Subject: Ophthalmology
                Subject: Eye Diseases
                Subject: Glaucoma
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Body Fluids
                Subject: Blood
                Subject: Blood Flow
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Body Fluids
                Subject: Blood
                Subject: Blood Flow
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Body Fluids
                Subject: Blood
                Subject: Blood Flow
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Body Fluids
                Subject: Blood
                Subject: Blood Flow
                Subject: Medicine and Health Sciences
                Subject: Hematology
                Subject: Blood
                Subject: Blood Flow
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Blood Pressure
                Subject: Research and Analysis Methods
                Subject: Computational Techniques
                Subject: Biometrics
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Diagnostic Radiology
                Subject: Tomography
                Subject: Research and Analysis Methods
                Subject: Imaging Techniques
                Subject: Diagnostic Radiology
                Subject: Tomography
                Subject: Medicine and Health Sciences
                Subject: Radiology and Imaging
                Subject: Diagnostic Radiology
                Subject: Tomography
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Ocular System
                Subject: Optic Nerve
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Ocular System
                Subject: Optic Nerve
                Custom metadata
                Data Availability All relevant data are within the paper.

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