November 2016
Volume 57, Issue 14
Open Access
Glaucoma  |   November 2016
OCT Angiography of the Peripapillary Retina in Primary Open-Angle Glaucoma
Author Affiliations & Notes
  • Eun Ji Lee
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Kyoung Min Lee
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Seung Hyen Lee
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Tae-Woo Kim
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Correspondence: Tae-Woo Kim, Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam, Gyeonggi-do 463-707, Korea; twkim7@snu.ac.kr
Investigative Ophthalmology & Visual Science November 2016, Vol.57, 6265-6270. doi:10.1167/iovs.16-20287
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      Eun Ji Lee, Kyoung Min Lee, Seung Hyen Lee, Tae-Woo Kim; OCT Angiography of the Peripapillary Retina in Primary Open-Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(14):6265-6270. doi: 10.1167/iovs.16-20287.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The purpose of this study was to investigate the topographic relationship between the decreased parapapillary retinal microvasculature as assessed by optical coherence tomography angiography (OCTA) and retinal nerve fiber layer (RNFL) defect in eyes with primary open-angle glaucoma (POAG) and a localized RNFL defect.

Methods: The peripapillary retinal circulation was evaluated using the OCTA centered on the optic nerve head in 98 POAG eyes having a localized RNFL defect and 45 healthy control eyes. A vascular impairment (VI) was identified in OCTA by the presence of a sign indicating decreased microvasculature. The frequencies of VI were compared between the POAG and control groups, and the topographic correlation between the VI and the RNFL defect identified in red-free fundus photographs was determined in the POAG group.

Results: The VI was observed as an area of decreased density of the microvascular network of the retina in 100% of the POAG eyes. The VI exactly coincided with the RNFL defect evident in red-free fundus photographs in terms of both the location and extent (Pearson's correlation coefficient = 0.997 and 0.988, respectively, all P < 0.001). None of the control eyes exhibited VI in OCTA.

Conclusions: Decreased parapapillary microvasculature of the retina determined by OCTA was found at the location of RNFL defect in POAG patients. This finding suggests that the decreased retinal microvasculature is likely secondary loss or closure of capillaries at the area of glaucomatous RNFL atrophy.

Studies have shown that peripapillary retinal blood flow1,2 and retinal vessel caliber3,4 are reduced in glaucoma patients compared with healthy subjects, using laser Doppler flowmetry,1 Doppler optical coherence tomography (OCT),2 and measurements of retinal vessel caliber.36 Decreased retinal perfusion has also been demonstrated angiographically in glaucoma patients using fluorescein angiography.710 These findings has raised the interest in the potential role of decreased ocular perfusion as an etiopathogenic factor for the glaucomatous optic neuropathy (GON), together with epidemiologic or clinical data that demonstrated the association of low blood pressure1113 or nocturnal blood pressure dips1416 with glaucoma. In contrast, Quigley et al.17 demonstrated that the density of capillaries remained constant across a wide range of neural tissue losses within the optic nerve head (ONH) in both experimental and human glaucoma eyes. In addition, Cull et al.18 showed that the ONH blood flow measured by laser speckle flowgraphy increased during the earliest stage of glaucoma followed by a linear decline that was strongly correlated with thickness reduction of the retinal nerve fiber layer (RNFL) thickness. These findings suggest that the reduced retinal perfusion could simply result from ONH degeneration and a consequently diminished metabolic demand.1,2,46 It therefore remains unclear whether the decreases in retinal and ONH blood flows in glaucoma are the cause or result of GON. 
Optical coherence tomography angiography (OCTA) is a new imaging technique that enables visualization of the retinal and choroidal microvasculatures. Yu et al.19 and Mase et al.20 demonstrated that the retinal vessel density shown in OCTA was correlated with the thicknesses of the inner retina and the RNFL in healthy subjects, respectively. Liu et al.21 evaluated peripapillary retinal perfusion in 12 glaucomatous eyes and 12 age-matched control eyes using OCTA and demonstrated a reduced parapapillary retinal perfusion in glaucomatous eyes. The decreased microvascular density was more severe in the inferior region in eyes with more superior visual field (VF) defect and vice versa. Similarly, Yarmohammadi et al.22 and Chen et al.23 reported that the vessel density within the RNFL was lower in eyes with primary open-angle glaucoma (POAG) than in glaucoma suspects and healthy eyes. Akagi et al.24 showed that the parapapillary retinal vessel density was reduced in the corresponding hemi-field in POAG eyes with hemi-field VF defect. These findings from the OCTA studies again shed light on the potential role of vascular factors in glaucoma. However, similar to the previous findings describing decreased retinal perfusion in glaucoma, it is unknown whether the decreased retinal microvascularity identified on OCTA is a cause or effect of glaucomatous damage. 
We hypothesized that determination of the topographic relationship between the structural damage of peripapillary retina and the decreased density of peripapillary microvasculature may give a clue to determine the causal relationship between the decreased microvasculature/retinal circulation and GON. If decreased retinal vascularity is an effect of primary vascular change (e.g., reduction of large retinal vessel caliber due to lack of autoregulation25 or local vasospasm26), the area of decreased vessel density would follow the territory of the retinal vessels. On the contrary, if it is the result of the GON (i.e., capillary dropout at the area of RNFL defect), the decreased vessel density would be observed only at the area of RNFL defect. Therefore, we performed this study to characterize the OCTA findings of the retinal layer in POAG eyes having localized RNFL defect compared with healthy control eyes and to topographically correlate the OCTA findings with RNFL defect shown in the red-free fundus photographs. 
Methods
This prospective study investigated the peripapillary retinal circulation using OCTA in consecutive POAG patients who were enrolled in the Investigating Glaucoma Progression Study, which is an ongoing prospective study of glaucoma patients at the Seoul National University Bundang Hospital Glaucoma Clinic. Healthy control subjects were recruited from patients who visited the clinic because of an incipient cataract. Written informed consent to participate was obtained from all subjects, and the study protocol was approved by the Seoul National University Bundang Hospital Institutional Review Board. The study protocol followed the tenets of the Declaration of Helsinki. 
All participants underwent comprehensive ophthalmic examinations that included best-corrected visual acuity (BCVA), Goldmann applanation tonometry, a refraction test, slit-lamp biomicroscopy, gonioscopy, stereo disc photography and red-free fundus photography (EOS D60 digital camera; Canon, Utsunomiyashi, Tochigiken, Japan), central corneal thickness measurement (Orbscan II; Bausch & Lomb Surgical, Rochester, NY, USA), axial length measurement (IOLMaster version 5; Carl Zeiss Meditec, Dublin, CA, USA), spectral-domain OCTA (Spectralis; Heidelberg Engineering, Heidelberg, Germany), standard automated perimetry (Humphrey Field Analyzer II 750, 24-2 Swedish interactive threshold algorithm; Carl Zeiss Meditec), and OCTA (AngioVue; Optovue, Fremont, CA, USA). 
Primary open-angle glaucoma was defined as the presence of an open iridocorneal angle, GON (i.e., neuroretinal rim thinning, notching, or an RNFL defect), and a glaucomatous VF defect. A glaucomatous VF defect was defined as a defect conforming with one or more of the following criteria: (1) outside normal limits on a glaucoma hemifield test; (2) three abnormal points with a P < 5% probability of being normal and one abnormal point with P < 1% by pattern deviation; or (3) a pattern standard deviation of P < 5% confirmed on two consecutive reliable tests (fixation loss rate of ≤20% and false-positive and false-negative error rates of ≤25%). The normal controls had an intraocular pressure (IOP) of ≤21 mm Hg, no history of increased IOP, an optic disc with a normal appearance, and a normal VF. 
Eyes included in the POAG group were required to have a record of untreated IOP, which was measured prior to the initiation of ocular hypotensive treatment or identified in the referral notes. In patients with an untreated IOP of ≤21 mm Hg, the diurnal variation was measured during office hours (9 AM to 5 PM). In patients who were undergoing treatment with ocular hypotensive medication at the time of the initial visit, the diurnal variation was measured after a 4-week washout period. Eyes were also required to have a localized RNFL defect that was clearly visible in red-free fundus photography. This criterion was implemented because the purpose of the present study was to determine the topographic correlation between a glaucomatous RNFL defect and the area of impaired perfusion, and it is often difficult to delineate the border of an RNFL defect in eyes with diffuse RNFL atrophy. The exclusion criteria were eyes with a BCVA worse than 20/40, a spherical equivalent of <–6.0 or >+3.0 diopters (D), a cylinder correction >±3.0 D, a history of intraocular surgery with the exception of uneventful cataract surgery or trabeculectomy, or retinal or neurologic diseases. When both eyes were eligible, one eye was randomly selected for inclusion in the study. 
Optical Coherence Tomography Angiography
The optic nerve and peripapillary area were imaged using a commercially available OCTA device (AngioVue; Optovue). Each image set comprised two raster volumetric patterns (one with vertical priority and one with horizontal priority) that covered an area of 4.5 × 4.5 mm centered on the optic disc. Each volume comprised 216 line-scan locations at which five consecutive B-scans were obtained. Each B-scan contained 216 A-scans. The AngioVue OCTA system used a patented Split Spectrum Amplitude Decorrelation Angiography software algorithm,27 which compares the consecutive B-scans at the same location to detect flow based on motion contrast. An en face angiogram was obtained using the maximum flow (decorrelation value) projection. The OCTA images were coregistered with OCT B-scans that were obtained concurrently to enable visualization of both the vasculature and structure in tandem. 
Using the internal limiting membrane as a plane of reference, a slab with a uniform thickness that included the RNFL, ganglion cell layer, and inner plexiform layer (from the internal limiting membrane to the outer border of the inner plexiform layer) was manually determined from the entire OCTA data sets using the coregistered OCT B-scans in each eye. 
The vascular impairment (VI) in OCTA was assessed by determining the presence of a region of decreased vascularity in the inner retina using the en face angiogram. The VI was indicated by a clearly demarcated darker area with decreased capillary density relative to the adjacent area. Two independent observers (E.J.L and S.H.L.) identified the VI while being blinded to the clinical information of the subjects. Each observer recorded the presence or absence of VI. When VI was present, its sectoral location was recorded as superotemporal, inferotemporal, inferonasal, or superonasal. Agreements between observers were accepted only when both observers determined that VI was present in the same sectoral location. Disagreements between these two observers were resolved by a third adjudicator (T.W.K.). When the quality of the OCTA images was poor (i.e., blurred images that hampered the delineation of the vascular defect), the eye was excluded from the analysis. 
Determination of the Circumferential Location and the Extent of the RNFL Defect and VI
In POAG eyes, the circumferential location and extent of the RNFL defect and VI were determined to investigate their topographic correlation, using the red-free fundus photography and OCTA images, respectively. The circumferential location and extent were measured as the angular deviation of the midpoint of the RNFL defect or VI relative to the foveal–disc axis and as the angular extent of the RNFL defect or VI, respectively (Fig. 1). These measurements were made by first identifying the two points at which the borders of an RNFL defect or VI area met the clinical optic disc margin. Lines connecting the disc center and the two points were then drawn, and these lines were used to measure the angular location and extent. To determine the foveal–disc center axis in OCTA images, these images were superimposed and manually aligned on the red-free fundus photographs using commercial software (Photoshop CC; Adobe Systems, Mountain View, CA, USA). 
Figure 1
 
Red-free fundus photographs (A, C, E) and OCTA images obtained at inner-retinal layer (B, D, F) in three glaucomatous eyes. Note that the vascular impairments (Vis) in the retinal layer shown by OCTA appear to be identical to the RNFL defects evident in red-free photographs (arrowheads). The topographic correlation between the RNFL defect and VI was determined by measuring their angular extent (α, B-2) and angular location relative to the foveal–disc axis (β, B-3). The angular extent (α) was measured by identifying the two points at which the borders of an RNFL defect or VI area met the clinical optic disc margin. Lines were then drawn that connected the disc center and the two points (light green lines, B-2), and the angular distance between these two lines was defined as the angular extent of the RNFL defect or VI (α, B-2). To determine the foveal-disc axis in OCTA images, these images were superimposed and manually aligned on the red-free fundus photographs using commercial software (Photoshop CC; Adobe Systems) (B-4). The locations of the RNFL defect and the VI (β) were determined as the angular distance between the foveal-disc axis and the midline dividing the light green lines indicating the angular extent of the RNFL defect or the VI, respectively (yellow lines, B-3).
Figure 1
 
Red-free fundus photographs (A, C, E) and OCTA images obtained at inner-retinal layer (B, D, F) in three glaucomatous eyes. Note that the vascular impairments (Vis) in the retinal layer shown by OCTA appear to be identical to the RNFL defects evident in red-free photographs (arrowheads). The topographic correlation between the RNFL defect and VI was determined by measuring their angular extent (α, B-2) and angular location relative to the foveal–disc axis (β, B-3). The angular extent (α) was measured by identifying the two points at which the borders of an RNFL defect or VI area met the clinical optic disc margin. Lines were then drawn that connected the disc center and the two points (light green lines, B-2), and the angular distance between these two lines was defined as the angular extent of the RNFL defect or VI (α, B-2). To determine the foveal-disc axis in OCTA images, these images were superimposed and manually aligned on the red-free fundus photographs using commercial software (Photoshop CC; Adobe Systems) (B-4). The locations of the RNFL defect and the VI (β) were determined as the angular distance between the foveal-disc axis and the midline dividing the light green lines indicating the angular extent of the RNFL defect or the VI, respectively (yellow lines, B-3).
The locations and extents of the RNFL defect and VI were measured by two observers (E.J.L. and K.M.L.), who were blinded to the subjects' clinical information. Each observer measured the values twice, and the mean of the four values was used for the analysis. 
Data Analysis
The interobserver agreement regarding confirmation of the presence of VI was assessed using κ statistics (κ value). The interobserver reproducibility in the determination of the circumferential location and extent of the localized RNFL defect and VI was assessed by calculating intraclass correlation coefficients (ICCs). The topographic correlation between VI and a localized RNFL defect was assessed using Pearson's correlation coefficient. All statistical analyses were performed using SPSS software (version 19.0; SPSS, Chicago, IL, USA). The data are presented as the mean ± SD values except where stated otherwise, and the cutoff for statistical significance was set at P < 0.05. 
Results
One hundred twenty POAG eyes and 47 healthy control eyes were initially included. Of these eyes, five POAG eyes and two control eyes were excluded due to poor-quality angiography images. Seventeen of the 115 POAG eyes were additionally excluded due to diffuse RNFL atrophy being evident in red-free photography. The baseline characteristics of the remaining 98 POAG eyes and 45 control eyes are provided in the Table
Table
 
Baseline Characteristics of the Participants
Table
 
Baseline Characteristics of the Participants
Parapapillary Retinal VI
The segmentation depth from the internal limiting membrane to the outer border of the inner plexiform layer was 98.3 ± 13.5 μm in POAG eyes and 113.6 ± 11.1 μm in healthy eyes. The VI was identified in 98 of the 98 POAG eyes (100%). It was observed as an area of decreased microvessel density of the parapapillary area (Fig. 1). The VI was identified as a well-demarcated wedge-shaped area whose appearance was similar to that of the RNFL defect evident in the red-free fundus photographs (Fig. 1). None of the eyes in the control group exhibited reduced vascularity in the OCTA images (Fig. 2). 
Figure 2
 
Red free fundus photograph (A) and OCTA images in the inner retinal layer (B). Dashed ellipses indicate the optic disc margin. Note that the OCTA image (B) does not show signs of retinal microvascular impairment.
Figure 2
 
Red free fundus photograph (A) and OCTA images in the inner retinal layer (B). Dashed ellipses indicate the optic disc margin. Note that the OCTA image (B) does not show signs of retinal microvascular impairment.
There was excellent interobserver agreement regarding the detection of VI, with κ = 0.984 (Supplementary Table S1 is a contingency table for the determination of the presence of VI by the two observers). 
Topographic Correlation Between the VI on Angiography and the RNFL Defect on Red-Free Photography
In the 98 POAG eyes, the VI exhibited nearly complete topographic correlations with the RNFL defect in terms of both the circumferential location (Pearson's correlation coefficient = 0.997, P < 0.001; Fig. 3A) and the extent (Pearson's correlation coefficient = 0.988, P < 0.001; Fig. 3B). 
Figure 3
 
Scatter plots showing the topographic correlations between the vascular impairment shown by optical coherence tomography angiography (VI) and the RNFL defects evident in red-free fundus photographs. Positive and negative values of the locations of the RNFL defect and VI indicate the locations that are superior and inferior relative to the foveal–disc axis, respectively.
Figure 3
 
Scatter plots showing the topographic correlations between the vascular impairment shown by optical coherence tomography angiography (VI) and the RNFL defects evident in red-free fundus photographs. Positive and negative values of the locations of the RNFL defect and VI indicate the locations that are superior and inferior relative to the foveal–disc axis, respectively.
The interobserver ICCs (95% CIs) in measuring the circumferential location and extent of the VI and the localized RNFL defect were 0.990 (0.985–0.993) and 0.961 (0.943–0.974) for VI and 0.996 (0.993–0.997) and 0.995(0.993–0.997) for RNFL defect, respectively. 
Discussion
This study investigated the peripapillary retinal circulation using OCTA in POAG eyes and healthy control eyes. Decreased microvascular density (i.e., VI) of parapapillary retina was identified in 100% of the POAG eyes at the location of glaucomatous damage, whereas none of the healthy control eyes exhibited reduced vascularity. 
The retinal microvasculature was evaluated using the en face image of a slab that included the inner retinal layer. In this process, a slab with a uniform thickness was chosen for each eye: this was because AngioVue did not allow selection of varied thickness for each B-scan. Therefore, the defined slab included deeper layers in the periphery in cases where the inner retinal layer was thinner than the juxtapapillary area. This could result in visualizing not only the radial peripapillary capillaries but also the inner vascular plexus.20,28 However, in our experience, including retinal layers that are below the inner plexiform layer does not substantially affect the visualization of the retinal vasculature. In addition, the en face image obtained using our method provided better contrast between the areas of decreased and intact vascularity than the enface image obtained from the RNFL only. 
Localized attenuation of the microvascular network was found in the parapapillary retina by OCTA in virtually all of the POAG patients. This finding is in line with Liu et al.21 and Akagi et al.,24 reporting that focal retinal vessel defects had a hemifield concordance with the location of functional deterioration: eyes with superior VF loss had a decreased inferior parapapillary vessel density. However, hemifield concordance between the retinal vessel defect and the VF defect does not necessarily indicate that the location and extent of the two changes coincide each other. In the present study, we examined the topographic relationship of the localized VI with structural glaucomatous damage (i.e., RNFL defect), and found that VI almost perfectly coincided with the localized RNFL defect identified using red-free photography. 
Studies have suggested that vascular factors can play a pathogenic role in glaucoma. It is of great interest to know whether the decreased peripapillary retinal vasculature identified by OCTA is one manifestation of compromised ocular perfusion that may contribute to the development of GON. In the present study, we identified a universal presence of inner-retinal hypoperfusion, which coincided with the RNFL defect identified via red-free photography. This finding suggests that the decreased density of retinal microvasculature probably represents the closure or degeneration of capillaries that occurs along with the RNFL loss. If it was due to the primary reduction of retinal perfusion, the area of VI should not necessarily coincide with the RNFL defect. Rather, it should have followed the territory of the retinal arterial branches, as was demonstrated in cases of branched retinal arterial occlusion.29 However, the present study did not definitively address the causal relationship between the decreased blood flow and GON. A longitudinal study is needed to clarify whether the decreased capillary density of the peripapillary retina is the result or cause of GON. 
The decreased vascularity in the area of an RNFL defect found in the present study is in line with the other OCTA studies that have found correlations between the density of retinal vessels and the thickness of the inner retinal layer or the RNFL.19,20 It appears that the capillaries within the RNFL or the inner retina become involuted as the neural tissue degenerates. This finding has also been demonstrated within the ONH neural tissue in eyes with glaucoma. Quigley et al.17 demonstrated that the loss of capillary volume was proportional to the loss of neural tissue within the ONH in both experimental and human glaucoma eyes. 
One limitation of the current study was the absence of blood flow quantification. The current version of commercially available OCTA devices does not provide software for measuring the blood flow index. However, the interobserver agreement was found to be nearly perfect in determinations of the location and extent of VI. In addition, these parameters were successfully used in this study to demonstrate the topographic correlation with the RNFL defect. The second limitation is that only eyes with a localized RNFL defect were included. Thus, the results of the current study are not directly applicable to eyes with diffuse RNFL atrophy. In other words, it remains to be elucidated whether the relationship between the decreased vascularity and the RNFL damage in such eyes is different from that in eyes with localized RNFL defect. 
In conclusion, a decreased parapapillary retinal microvasculature was universally identified using OCTA in POAG eyes with a localized RNFL defect, with an excellent topographic relationship with the area of RNFL defect. The finding suggests that the decreased microvasculature identified in OCTA probably represents the secondary loss or closure of capillaries, which occur along with the glaucomatous RNFL loss. Further longitudinal studies are required to confirm the relationship between the development of an RNFL defect and decreases in the retinal microvasculature. 
Acknowledgments
Supported by Grant 02-2016-023 from the Seoul National University Bundang Hospital Research Fund. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 
Disclosure: E.J. Lee, None; K.M. Lee, None; S.H. Lee, None. T.-W. Kim, None 
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Figure 1
 
Red-free fundus photographs (A, C, E) and OCTA images obtained at inner-retinal layer (B, D, F) in three glaucomatous eyes. Note that the vascular impairments (Vis) in the retinal layer shown by OCTA appear to be identical to the RNFL defects evident in red-free photographs (arrowheads). The topographic correlation between the RNFL defect and VI was determined by measuring their angular extent (α, B-2) and angular location relative to the foveal–disc axis (β, B-3). The angular extent (α) was measured by identifying the two points at which the borders of an RNFL defect or VI area met the clinical optic disc margin. Lines were then drawn that connected the disc center and the two points (light green lines, B-2), and the angular distance between these two lines was defined as the angular extent of the RNFL defect or VI (α, B-2). To determine the foveal-disc axis in OCTA images, these images were superimposed and manually aligned on the red-free fundus photographs using commercial software (Photoshop CC; Adobe Systems) (B-4). The locations of the RNFL defect and the VI (β) were determined as the angular distance between the foveal-disc axis and the midline dividing the light green lines indicating the angular extent of the RNFL defect or the VI, respectively (yellow lines, B-3).
Figure 1
 
Red-free fundus photographs (A, C, E) and OCTA images obtained at inner-retinal layer (B, D, F) in three glaucomatous eyes. Note that the vascular impairments (Vis) in the retinal layer shown by OCTA appear to be identical to the RNFL defects evident in red-free photographs (arrowheads). The topographic correlation between the RNFL defect and VI was determined by measuring their angular extent (α, B-2) and angular location relative to the foveal–disc axis (β, B-3). The angular extent (α) was measured by identifying the two points at which the borders of an RNFL defect or VI area met the clinical optic disc margin. Lines were then drawn that connected the disc center and the two points (light green lines, B-2), and the angular distance between these two lines was defined as the angular extent of the RNFL defect or VI (α, B-2). To determine the foveal-disc axis in OCTA images, these images were superimposed and manually aligned on the red-free fundus photographs using commercial software (Photoshop CC; Adobe Systems) (B-4). The locations of the RNFL defect and the VI (β) were determined as the angular distance between the foveal-disc axis and the midline dividing the light green lines indicating the angular extent of the RNFL defect or the VI, respectively (yellow lines, B-3).
Figure 2
 
Red free fundus photograph (A) and OCTA images in the inner retinal layer (B). Dashed ellipses indicate the optic disc margin. Note that the OCTA image (B) does not show signs of retinal microvascular impairment.
Figure 2
 
Red free fundus photograph (A) and OCTA images in the inner retinal layer (B). Dashed ellipses indicate the optic disc margin. Note that the OCTA image (B) does not show signs of retinal microvascular impairment.
Figure 3
 
Scatter plots showing the topographic correlations between the vascular impairment shown by optical coherence tomography angiography (VI) and the RNFL defects evident in red-free fundus photographs. Positive and negative values of the locations of the RNFL defect and VI indicate the locations that are superior and inferior relative to the foveal–disc axis, respectively.
Figure 3
 
Scatter plots showing the topographic correlations between the vascular impairment shown by optical coherence tomography angiography (VI) and the RNFL defects evident in red-free fundus photographs. Positive and negative values of the locations of the RNFL defect and VI indicate the locations that are superior and inferior relative to the foveal–disc axis, respectively.
Table
 
Baseline Characteristics of the Participants
Table
 
Baseline Characteristics of the Participants
Supplement 1
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