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 Table of Contents  
Year : 2020  |  Volume : 113  |  Issue : 2  |  Page : 46-53

Assessment of radial peripapillary capillary and macular vascular density in primary open angle glaucoma

Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission08-Mar-2020
Date of Acceptance03-Apr-2020
Date of Web Publication10-Jul-2020

Correspondence Address:
MD Haitham Y Al-Nashar
Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig, 44511
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ejos.ejos_11_20

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Purpose The aim was to assess radial peripapillary capillary (RPC) and macular vascular density in eyes with primary open angle glaucoma (POAG).
Patients and methods This observational cross-sectional study included 60 eyes of normal person and 67 eyes with POAG. Glaucomatous eyes were subdivided into three groups according to visual field findings; mild, moderate, and severe glaucoma (14, 27, and 26 eyes, respectively). Both RPC and macular vascular density were measured using optical coherence tomography angiography (OCTA). Visual field mean deviation was analyzed. Retinal nerve fiber layer (NFL) thickness and ganglion cell complex thickness were determined using OCT in all eyes.
Results Peripapillary retinal NFL (thickness and ganglion cell complex thickness were significantly different between glaucomatous and normal eyes (P<0.001). In eyes with POAG, RPC vascular density was significantly less than normal ones (P<0.001) and was correlated with glaucoma severity (P=0.02). A significant correlation was found between RPC vascular density and visual field mean deviation and NFL thickness. Macular vascular density was significantly less in glaucomatous eyes (P<0.001) with significant correlation with the degree of glaucoma severity (P=0.01).
Conclusion OCTA has the ability of visualization and quantification of RPC and macula vessel density and may be useful in measuring retinal ganglion cell damage in open angle glaucoma.

Keywords: ganglion cell, optical coherence tomography angiography, vascular density

How to cite this article:
Al-Nashar HY, El-Haig WM, Al-Naimy MA. Assessment of radial peripapillary capillary and macular vascular density in primary open angle glaucoma. J Egypt Ophthalmol Soc 2020;113:46-53

How to cite this URL:
Al-Nashar HY, El-Haig WM, Al-Naimy MA. Assessment of radial peripapillary capillary and macular vascular density in primary open angle glaucoma. J Egypt Ophthalmol Soc [serial online] 2020 [cited 2021 Jun 20];113:46-53. Available from: http://www.jeos.eg.net/text.asp?2020/113/2/46/289485

  Introduction Top

Primary open angle glaucoma (POAG) is a progressive chronic optic neuropathy in which there is damage of retinal ganglion cells (RGCs) causes thinning of retinal nerve fiber layer (RNFL) [1],[2]. Since the mechanical theory fails to explain the glaucomatous optic nerve damage associated with normal-tension/low-tension glaucoma, factors other than elevated intraocular pressure (IOP) have been implicated, including glaucoma genes and dysfunction of optic nerve blood flow [3],[4]. There is compelling evidence suggesting that glaucoma pathogenesis can be partly attributed to vascular dysfunction of the head of optic nerve and peripapillary retina [5]. The radial peripapillary capillary (RPC) layer is a distinct capillary network located within the RNFL, which supplies taxons of RGCs [6]. RPC lies between the internal limiting membrane and the nerve fiber layer (NFL) [7].

Ganglion cell complex (GCC) represents the inner-most layer of the retina which includes the RNFL, the ganglion cell layer, and the inner plexiform layer [8].

Macula contains more than 30% of total RGCs. High metabolic requirements of these RGCs depend on the macular capillary vasculature [9]. Apoptotic RGC death has been suggested due to insufficient ocular blood flow, so assessment of macular vessel density may have a role in early detection of glaucomatous damage [10]. Many techniques such as fluorescein angiography, laser speckle flowgraphy, and laser Doppler flowmetry were used in the evaluation of ocular and retinal blood flow [11],[12]. With the introduction of optical coherence tomography angiography (OCTA), researchers and clinicians are now able to assess in a rapid and noninvasive way the RPC and macular vasculatures, which satisfy metabolic and nutritional demands of RGC axons [13]. Recently, quantitative assessment of RPCs and macular vascular density were achieved by OCTA. A reliable and reproducible estimation of RPC and macular vascular density can be given with the release of the new software which gives an accurate numerical data [14],[15].

This study aimed to assess RPC and macular vascular density in patients with POAG with detection of its correlation with thickness of RNFL and GCC and visual field indices.

  Patients and methods Top

This observational cross-sectional study was conducted on consecutive Egyptian individuals. The study was done according to the tenets of the Declaration of Helsinki with a written informed consent.

The study included 127 eyes (70 persons) that were divided into two groups: the first group included 60 normal eyes and the second group included 67 eyes with POAG. The glaucomatous eyes were subdivided into three subgroups depending on glaucoma severity as detected by visual field findings: mild, moderate, and severe groups [(mean deviation (MD)>−6.0 dB, from −6 to −12.0 dB and >−12.0 dB, respectively] [16].

Inclusion criteria for glaucomatous eyes were: glaucomatous optic disk changes (cupping), RNFL defect, glaucomatous pattern of visual field, and opened normal angle. There is no previous history of ocular or systemic diseases affecting the optic nerve. Inclusion criteria for normal eyes: normal visual field test, IOP of less than 20 mmHg, no history of topical or systemic use of steroids, no optic disk cupping, and normal RNFL.

Exclusion criteria: individuals younger than 20 years or older than 70 years, errors of refraction more than ±6.00 D, previous intraocular surgery or inflammation, topical or systemic steroids treatment, retinal pathology or retinopathy, and eyes with media opacity.

All eyes included in this study underwent a complete eye examination; visual acuity (best corrected), refraction, anterior segment examination using a slit-lamp biomicroscope, gonioscopy using Goldman 3-mirror lens (Ocular instruments, Bellevue, Washington, USA), IOP measurement by applanation tonometer, and posterior segment examination.

Visual field testing was done for all eyes by a Humphrey Visual Field Analyzer II (Carl Zeiss Meditec Inc., Dublin, California, USA) set for the 24-2 threshold test, size III white stimulus, and standard SITA algorithm.

Spectral domain OCT system (RTVue OCT; Optovue Inc., Fremont, California, USA) of 840-nm wavelength was used to scan the optic disk and the macula in all eyes. Peripapillary NFL thickness was measured from the traditional optic nerve head scan (12 radial scans of 3.4 mm in length centered on the optic disk). The GCC scan was done in all eyes with a square grid centered on the macula. GCC thickness was measured from the inner limiting membrane to the posterior boundary of the inner plexiform layer.

OCTA scans were done by RTVue-XR Avanti (software version 2017, 1, 0,151; Optovue Inc.). For measuring RPC vessel density, OCT scanning is centered on the optic disc. Vascular density in the RPC layer was obtained from the scan with a size of 4.5×4.5 mm centered on the optic disc and expressed in numerical form as percentage of large vessels and microvasculature. RPC vascular density was measured in whole image and in the peripapillary region (superior, nasal, inferior, and temporal quadrants) ([Figure 1]).
Figure 1 Optovue AngioVue imaging of the optic disk. (a) Different angiographic slabs (from left to right) SLO image, vitreous/retina slab, RPC layer, and choroid layer. (b) Peripapillary capillary density map. (c) RPC vascular density percentage (capillaries and large vessels). (d) Peripapillary capillary density in different regions; hemisuperior, hemi-inferior, superior, nasal inferior, and temporal quadrants. RPC, radial peripapillary capillary; SLO, scanning laser ophthalmoscope.

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For measuring macular vessel density, macula 6×6 mm scans center on the macula were done by the same OCTA system. Macular vascular density was automatically measured and represented as a vessel density map with quantitative percentage measures. Perifoveal and parafoveal vascular density were measured. Both parafoveal and perifoveal regions are divided into four regions (temporal, superior, nasal, and inferior) ([Figure 2]).
Figure 2 Optovue AngioVue imaging of the macula. (a) OCTA image of the superficial capillary layer (ring diameters of 1, 3, and 6 mm). (b) Superficial vessel density map. (c) Macula vessel density (%) in different regions. OCTA, optical coherence tomography angiography.

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All statistical analyses were done using the SPSS software (version 20.0; SPSS, Chicago, IL, USA). Data are presented as mean±SD values. P less than 0.05 is considered significant. Analysis of variance test with post-hoc analysis was done to compare data between normal and glaucomatous eyes.

  Results Top

RPC and macular vascular density were investigated in 60 normal and 67 glaucomatous eyes. The glaucomatous eyes included 14 eyes with mild disease, 27 eyes with moderate, and 26 eyes with severe glaucoma according to the Glaucoma staging system.

Clinical data of each group is summarized in [Table 1]; no significant differences were found in age and IOP between different groups (P=0.31 and 0.42, respectively). In comparison with normal eyes, the glaucomatous eyes showed significant loss of field of vision with higher MD and PSD values (P<0.001). Glaucomatous patients treated with antiglaucoma agents, though no significant difference in IOP was detected between tglaucomatous and normal persons. In glaucomatous eyes, 15 eyes received one glaucoma medication, 38 treated by two agents, and 14 by three medications.
Table 1 Baseline clinical characteristics of different study groups

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RNFL thickness measured in all eyes included in the study with significant difference between glaucomatous and normal eyes (P<0.001). GCC thickness was measured also in all eyes with significant difference between both normal and glaucomatous eyes (P<0.001). These data are presented in [Table 2].
Table 2 Glaucoma parameters for normal and primary open angle glaucoma patients

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The PRC vessel density was significantly lower in glaucomatous eyes compared with normal ones (P<0.001). And with post-hoc analysis and pairwise comparison between glaucomatous eyes groups, a significant difference was found in RPC vascular density.

RPC vascular density was significantly decreased with the degree of glaucoma severity(P<0.001). These data are presented in [Table 3] and [Figure 3].
Table 3 Radial peripapillary capillary vascular density (measured %)

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Figure 3 Decreased RPC vascular density in glaucomatous eyes compared with normal. RPC vascular density is decreased with the severity of glaucoma: (a) normal; (b) mild POAG; (c) moderate POAG; (d) severe POAG. POAG, primary open angle glaucoma; RPC, radial peripapillary capillary.

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Similar results are obtained with a measurement of macular vessel density. Macular vascular density was measured in both perifoveal (3 mm) and parafoveal (6 mm) centered on the fovea. Macular vascular density showed significant difference between normal and glaucomatous eyes (P<0.001). Also, macular vascular density had a significant correlation with the degree of glaucoma severity (P<0.001). These data are presented in [Table 4] and [Figure 4].
Table 4 Macular vascular density (measured %)

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Figure 4 Decreased macular vascular density in glaucomatous eyes compared with normal. Macular vessel density is decreased with the severity of glaucoma. (a) normal; (b) mild POAG; (c) moderate POAG; (d) severe POAG. POAG, primary open angle glaucoma.

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In eyes included in the study, univariate regression analysis showed that the RPC and the macular vascular density had a significant correlation with thickness of both RNFL and GCC, respectively. RPC vascular density was also significantly correlated with visual field MD ([Table 5]).
Table 5 Correlation between RPC and macular vascular density and both structural (GCC and NFLT) and functional (MD) glaucoma parameters

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  Discussion Top

POAG is a disease in which progressive optic nerve degeneration occurs with RGCs loss and the corresponding defect in visual field [17]. There are different theories for the pathophysiology of glaucoma; the mechanical theory postulated that the ganglion cell axons damage based mainly on increased IOP, and vascular theory explains this damage by other factors besides increased IOP as compromised optic nerve blood flow. Now, optic nerve head vascular insufficiency is considered an essential factor in the development of POAG [18],[19].

Current indices which are used to diagnose glaucomatous optic nerve changes include visual field analysis, measurement of RNFL thickness, and GCC analysis [20],[21].

Analysis of optic nerve head vasculature appears to be a useful adjunctive tool for both diagnosis and evaluation of glaucoma. They correlate well with previous functional and structural indices [22].RGCs are damaged in eyes with glaucoma. One-third of RGCs is present in the macula. So, macular perfusion may be considered as a good tool for the detection of glaucoma and assessment of disease severity [23]. Combination of both conventional OCT and OCTA allows simultaneous evaluation of RNFL structure, GCC thickness, optic disk, and macular perfusion [24].

Previous studies [25],[26],[27],[28],[29],[30],[31] used OCTA to investigate the changes in ONH and macular vasculature in glaucomatous patients. Their results showed that ONH and macular vascular density were reduced in glaucomatous patients as in comparison with normal control individuals. They found a significant correlation between ONH vessel density and RNFL, GCC, and VF indices.

This study used OCTA for the assessment of vascular density in both macula and RPCs layer. RPC layer is considered the most important one as it is responsible for perfusion of RNFL. Results of the present study demonstrate a significant reduction in RPC and macular vascular density in glaucomatous eyes in comparison with normal ones. The RPC and macular vascular vessel density showed a significant correlation with the degree of glaucoma severity.

Also, a significant correlation between RPC vessel density and both RNFL thickness and visual field MD was found. Macular vessel density was significantly correlated with GCC thickness.

Previous studies had a limitation of difficult numerical quantification of the blood flow.

This study used the software that gives a numerical data for measuring both RPC and macular vascular density. In addition, our study scanned a wider area of macula (6×6 mm), so it evaluated both perifovea and parafovea areas.

  Conclusion Top

In conclusion, data of this study suggest that quantitative OCTA can help in the diagnosis of glaucoma depending on the reduction of both RPC and macular vascular density. RPC and macular vessel density measured by OCTA have a correlation with structural (thickness of both RNFL and GCC) and functional (visual field MD) parameters.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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