SUBJECTS

This cross-sectional study was approved by the institutional review and ethics board of the Akita University Graduate School of Medicine, Akita, Japan, and followed the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants.

We recruited consecutive patients who visited the glaucoma clinic of the Akita University Graduate School of Medicine between May 2018 and July 2020. All participants underwent a comprehensive ophthalmic assessment, including best-corrected visual acuity, central corneal thickness, and axial length by pachymetry (SP-3000 model; Tomey Corp, Nagoya, Japan), Goldmann applanation tonometry, slit-lamp biomicroscopy, gonioscopy, dilated fundus stereoscopic examination, fundus color stereo photography (Canon, Tokyo, Japan), standard automated perimetry (Humphrey Field Analyzer II model 750; 24-2 Swedish interactive threshold algorithm; Carl Zeiss Meditec, Dublin, California, USA), OCT angiography (Plex Elite 9000 model; Zeiss, Oberkochen, Germany), and SD-OCT (Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany). SD-OCT was performed within 3 months of the VF test.

This study included eyes with open-angle glaucoma and angle-closure glaucoma that presented with glaucomatous optic disc changes such as localized or diffuse rim thinning and RNFLDs and glaucomatous VFDs corresponding to the glaucomatous structural changes. Glaucomatous VFDs were defined by the presence of at least 3 continuous test points within the same hemifield, on the pattern deviation plot at P <5%, with at least 1 of these points at P <1%, which was confirmed by 2 consecutive reliable tests (fixation loss rate: ≤20%; and false-positive and false-negative error rates: ≤15% each). Exclusion criteria were as follows: 1) myopic eyes with an axial length ≥24.0 mm, in order to eliminate the effects of myopic deformation of the ONH, as myopia alone is reported to cause ONH deformations that may affect position of the CRV ; 2) eyes with poor-quality OCT images (quality score ≤15) for more than 5 sections in serial ONH scans; 3) retinal or neuro-ophthalmologic disease that may affect the VF; and 4) congenital ONH abnormalities and suspected anomalies. Normal eyes were included as controls when they exhibited an intraocular pressure ≤21 mm Hg, an open iridocorneal angle, an optic disc that appeared normal, and no VFDs.

SD-OCT was performed using the enhanced depth imaging (EDI) technique, which improves the visualization of deep structures. ^, The magnification error was corrected using the formula provided by the manufacturer according to autorefraction keratometry results and the focus setting during image acquisition. The scale of the OCT images was corrected to 1:1 μm before evaluation. Measurements were performed by an experienced glaucoma specialist (Y.S.) who was masked to the clinical information of the participants.

IDENTIFYING THE ENTRY POINT OF THE CENTRAL RETINAL VESSEL INTO AND ITS EXIT POINT FROM THE LAMINA CRIBROSA

The path of the CRV within the LC was identified using EDI OCT by the following process. First, horizontal scans of the ONH were acquired by aligning with the line connecting the fovea and the BMO center ( Figure 1 A). The horizontal scans were set 30 μm apart, and each B-scan was constructed using 35 frames. ^{, ,} Based on those horizontal scans, the point at which the CRV exited the LC and emerged on the surface of the ONH was identified ( Figure 1 C, red star). The point was plotted at the corresponding position on the ONH in the infrared (IR) fundus image ( Figure 1 D).

Capture of the passage of the CRV within the LC, using spectral-domain optical coherence tomography. (A) Horizontal scans of the ONH were obtained by aligning with the line connecting the fovea with the Bruch’s membrane opening center (yellow arrows). (B) From the horizontal scans, a line that captured the point at which the CRV exited the LC and emerged on the ONH surface was identified (yellow arrow). (C) B-scan image obtained at the scan line shown in (B). The red star indicates the point at which the CRV exits LC and emerges on the ONH surface. (D) The exit point of the CRV is plotted at the corresponding position on the ONH in the IR fundus image (red star). (E) Radial scans of the ONH centered on the exit point of the CRV identified in the horizontal scans (red star) were obtained. (F) Among the radial scans, a line capturing the passage of the CRV within the LC is identified (green arrow). (G) B-scan image captures the passage of the CRV within the LC obtained in the scan line shown in (F). In this image, the point at which the CRV enters the LC from the retrolaminar ONH region is identified (blue star). (H) The entry point of the CRV into the LC is plotted at the corresponding position on the ONH in the IR image (blue star) together with the exit position from the LC on the ONH (red star). The yellow arrow indicates the displacement of the CRV from the entry position to the exit position during its passage through the deformed LC. CRV = central retinal vessel; IR = infrared; LC = lamina cribrosa; ONH = optic nerve head.

Next, radial scans of the ONH centered on the point at which the CRV exited the ONH, as identified in the horizontal scans, were acquired ( Figure 1 E). The radial scans included 48 B-scan images, 3.75 degrees apart, with each B-scan constructed using 42 frames. Based on these radial scans, a scan line that captured the path of the CRV within the LC was obtained ( Figure 1 F). This line passes through the central hump of the LC, which is a thick, mounded area at the center of the LC that embeds the CRV. ^, In the B-scan image obtained at this line, the point at which the CRV entered the LC from the retrolaminar ONH region was identified as the point at which the CRV changed its direction from perpendicular to nasal ( Figure 1 G, blue star). The point was plotted at the corresponding position on the ONH in the IR image ( Figure 1 H, blue star). In Figure 1 H, the yellow arrow indicates displacement of the CRV during its passage through the deformed LC from the entry position into the LC to the exit position from it.

The CRVs consist of the central retinal artery and vein. Although the retinal artery was easily identified throughout the LC in most eyes, retinal vessels sometimes appeared collapsed and thin, and its entire path was difficult to identify in some eyes. Therefore, in the present study, we assessed the position of the central retinal vessel as the position of the central retinal artery.

ASSESSMENT OF THE COORDINATE OF THE ENTRY AND EXIT POSITIONS OF THE CENTRAL RETINAL VESSEL IN THE OPTIC NERVE HEAD

The coordinates of the position of the CRV in the ONH were assessed vertically and horizontally ( Figure 2 ).

Assessment of the coordinate of the CRV within the ONH. (A) Infrared fundus image. (B) Assessment of the vertical coordinate. Yellow arrow indicates fovea-BMO center line. The entry position of the CRV into the LC was assessed in the OCT scan line passing through the entry position (blue arrow). The blue star indicates the entry position, and the white dots indicate the superior and inferior Bruch’s membrane opening (BMO). The vertical exit position from the LC was obtained using the OCT scan line passing through the exit position (red arrow). (C) Assessment of the horizontal coordinate. Yellow arrow indicates fovea-BMO center line. The entry position of the CRV into the LC was assessed in the OCT scan line passing through the entry position (blue arrow). The blue star indicates the entry position, and the white dots indicate the BMO. The horizontal exit position of the CRV from the LC was obtained using the OCT scan line passing through the exit position (red arrow).

BMO = Bruch’s membrane opening; CRV = central retinal vessel; I = inferior; LC = lamina cribrosa; N = nasal; OCT = optical coherence tomography; ONH = optic nerve head; S = superior; T = temporal.

The vertical coordinate of the entry position of the CRV into the LC was assessed relative to the fovea-BMO center line ( Figure 2 B, yellow arrow). Serial vertical OCT scans were obtained perpendicular to the fovea-BMO center line, and a scan line passing through the entry position of the CRV was identified among them ( Figure 2 B, blue arrow). Superior and inferior BMOs were identified in the B-scan image obtained at the scan line and plotted on the corresponding locations in the IR fundus image ( Figure 2 B, white dots on the blue arrow), which was defined as the ONH margin. The vertical coordinate of the entry position of the CRV (V-coordinate _entry ) was calculated by the following formula:

Therefore, if the entry position was in the superior (inferior) region of the BMO, the V- coordinate _entry was presented as <50% (≤50%). The vertical coordinate of the exit position of the CRV from the LC was obtained in the same way, using the scan line passing through the exit position ( Figure 2 B, red arrow).

The horizontal coordinate of the entry position of the CRV (H-coordinate _entry ) was assessed using OCT scan lines parallel to the fovea-BMO center line ( Figure 2 C, yellow arrow). Among them, a scan line passing through the entry position of the CRV was identified ( Figure 2 C, blue arrow). Temporal and nasal BMOs were identified in the B-scan image obtained at the scan line, and they were plotted on the corresponding locations in the IR fundus image ( Figure 2 C, white dots on the blue arrow). The H-coordinate _entry was calculated by the following formula:

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