Study Subjects

For inclusion in the present study, subjects had to have myopia with refraction < –0.5 D or axial length (AXL) > 24 mm. High myopia was defined as refraction < –6.0 D or AXL > 26 mm. POAG was defined as including the presence of glaucomatous optic disc changes such as focal notching and thinning, RNFL defects on disc stereo photography and red-free fundus photography, glaucomatous visual field (VF) defect, and an open angle confirmed by gonioscopic examination. Glaucomatous VF defect was defined as (1) glaucoma hemifield test values outside the normal limits or (2) three or more abnormal points with a probability of being normal of P < 5%, of which at least one point has a pattern deviation of P < 1%, or (3) a pattern standard deviation of P < 5%. The VF defects were confirmed on two consecutive reliable tests (fixation loss rate ≤ 20%, false-positive and false-negative error rates ≤ 25%). Subjects were deemed to be healthy when no definite RNFL defect was found on red-free RNFL photography and they were found to be within normal limits on a glaucoma hemifield test of the standard automated perimetry.

The subjects initially underwent complete ophthalmic examinations including a medical history review, best-corrected visual acuity (BCVA), phakic status, refraction, slit-lamp biomicroscopy, Goldmann applanation tonometry, gonioscopy, dilated fundus examination, stereo optic-disc photography, red-free RNFL photography (VISUCAM, Carl Zeiss Meditec), and standard automated perimetry (HVF, Humphrey C 24-2 SITA-Standard visual field; Carl Zeiss Meditec). Also, the central corneal thickness (CCT) (Pocket II; Quantel Medical, Clermont-Ferrand, France) and AXL (AXIS-II Ultrasonic Biometer; Quantel Medical S.A., Bozeman, MT, USA) were measured.

The present study excluded subjects with a history of any ocular surgery such as glaucoma surgery, or a history of any retinal disease (e.g., diabetic retinopathy, uveitis, retinal vein occlusion, epiretinal membrane, or age-related macular degeneration). Eyes with ambiguous RNFL on red-free RNFL photography also were excluded. If both eyes were eligible for the present study, one eye was selected randomly.

SD-OCT and SS-OCT Imaging

The subjects underwent SD-OCT (Cirrus HD-OCT, Carl-Zeiss Meditec) and SS-OCT (DRI OCT Triton, Topcon) imaging in random order on the same day. All eyes were dilated (1% tropicamide, 2.5% phenylephrine) before undergoing OCT imaging. For Cirrus HD-OCT, a 200×200 macular cube scan and a 200×200 optic disc cube scan were obtained. The following macular GCIPL and peripapillary RNFL thicknesses were measured automatically by the built-in software (Cirrus HD-OCT Review Software, Ver. 10.0): average and sectoral (superotemporal, superior, superonasal, inferonasal, inferior, inferotemporal) measurements for GCIPL and average, sectoral (superior, nasal, inferior, and temporal) and 12 clock-hour measurements for RNFL thickness. For DRI OCT Triton, a 12×9 mm 3D Wide scan were obtained. The 3D Wide scan in DRI OCT Triton provides a 12×9 mm wide-field thickness map, a thickness surface map, and SuperPixel maps for the RNFL, GCL++ and GCL+ layers. The thickness surface map is displayed in 3D for selected layers (RNFL, GCL++, or GCL+) and can be rotated or zoomed-in and -out by mouse operation ( Figure 1 ). The SuperPixel-200 map consists of 26×26 grids within a 5.2×5.2 mm ² peripapillary area and 30×30 grids within a 6.0×6.0 mm ² macular area, thereby providing a significance map based on the built-in normative database. The side length of each grid is 200 μm. The uncolored pixels indicate the normal range, whereas the yellow-colored or red-colored pixels indicate abnormality at P = 1%-5% and P < 1% of the normal level, respectively. The average, sectoral (superior, nasal, inferior, and temporal), and 12 clock-hour peripapillary RNFL thicknesses and average and sectoral (superotemporal, superior, superonasal, inferonasal, inferior, inferotemporal) GCL++ and GCL+ thicknesses were measured automatically by the built-in review program (IMAGEnet 6 Version 1.25, Topcon). All of the analyses were performed according to the right-eye orientation.

Wide-Field Map Provided by DRI OCT Triton. Representative Atlas of wide-field map of retinal nerve fiber layer (RNFL, A–D), GCL++ (RNFL + ganglion cell-inner plexiform layer [GCIPL], E–H), and GCL+ (GCIPL, I–L) provided by DRI OCT Triton for right eye of 52-year-old male with primary open-angle glaucoma (POAG). The wide-field map can be featured in the thickness map (A, E, I) and thickness surface map (B, F, J), which are provided in a three-dimensional (3D) manner and can be zoomed-in and -out (C, G, K), and SuperPixel maps (D, H, L). (M) Red-free RNFL photography captured by DRI OCT Triton. (N) Combined SuperPixel map of RNFL and GCL++ (D+H). (O) Combined SuperPixel map of RNFL and GCL+ (D+L).

Additionally excluded from the present study were eyes with motion or blink artifacts ( n = 14), defocus ( n = 12), algorithm segmentation failure ( n = 12), a signal strength < 6 ( n = 16) or image quality < 30 ( n = 3) on OCT scans, or any abnormalities (e.g., large peripapillary atrophy in the circumpapillary region that affected the scan circle where the OCT RNFL thickness measurement was obtained) ( n = 4).

Definition of Glaucomatous Structural Defect

Detailed definitions of RNFL defect on red-free photography, Cirrus HD-OCT, and DRI OCT Triton have been provided elsewhere. ^, RNFL defects for red-free RNFL photography have been defined as diverging, arched or wedge-shaped, wider than the main retinal vessel at a distance of 1-disc diameter from the edge of the disc.

RNFL defect on the Cirrus HD-OCT thickness map was defined as a wedge-shaped dark-blue area surrounding an abrupt color-scale change. RNFL defect on the deviation map was defined as the presence of a wedge-shaped area of at least 20 contiguous yellow/red pixels along with RNFL thinning. On both maps, the width of the defect increased from the disc toward the edge of the map, and the minimum defect size was larger than the diameter of the major retinal vessel. GCIPL defects on the Cirrus HD-OCT thickness map were defined as the presence of a blue/black region. For the deviation map, it was defined as the presence of an area coded in yellow/red, the size of which is greater than 10 pixels.

Defect on the DRI OCT Triton wide-field thickness map was defined as an arcuate or wedge-shaped diverging dark-blue (for RNFL and GCL+) or light-blue (for GCL++) area surrounding an abrupt color-scale change. The minimum defect size was larger than the diameter of a major retinal vessel. The wide-field thickness surface map was used to cross-check the three-dimensional (3D) thickness difference with the surrounding tissues. Defect on the SuperPixel-200 map was defined as the presence of a wedge-shaped area of at least 20 contiguous yellow/red pixels.

When RNFL defect on the red-free RNFL photography was not subsequently identified on the OCT maps, it was classified as a false-negative. If a defect on the OCT map did not match a defect on the red-free RNFL photography and/or HVF test results, it was classified as a false-positive. The inter-rater agreement for assessment of glaucomatous structural defect was obtained from three glaucoma specialists (YWK, JHL, and JSK) by estimation of Fleiss’ kappa. If the readings did not match each other, they were determined by consensus of the three readers.

Data Analysis

Continuous variables were compared between the two groups by student t-test. Categorical variables were compared using a chi-square test. The accuracy for glaucomatous structural defect was measured according to the following equation: Accuracy = (true-positive + true-negative) / (true-positive + false-positive + true-negative + false-negative). McNemar’s test was used to compare the sensitivity and specificity for detection of glaucomatous structural defect between the two OCT devices. The diagnostic performance of each parameter from the two OCT devices for the detection of myopic glaucoma was determined by calculating the area under receiver operating characteristic (AUROC) curve. The best cut-off value was selected according to the Youden index value (which maximizes the value of ‘sensitivity + specificity – 1’). A receiver operating characteristic (ROC) analysis was performed using the “pROC” package in the open-platform R software. The AUCs were compared using the “ROCtest” function in the “pROC” package, based on the method introduced by DeLong et al. The false discovery rate (FDR) was controlled for using the Benjamini-Hochberg method. Except where stated otherwise, the data are presented as mean ± standard deviations, and the level of statistical significance was set at P < 0.05.

Subject Demographics

The present study enrolled 150 myopic glaucoma eyes and 100 healthy myopic eyes. The average age was 54.8 ± 12.8 years for myopic glaucoma and 51.8 ± 13.4 years for healthy myopic eyes (the controls), respectively ( P = 0.11). There were no significant differences in age, gender, BCVA, phakic status, IOP, SE, disc area, AXL or CCT between the two groups ( Table 1 ). The range of disc area was 1.03–3.55 mm ² for myopic glaucoma and 1.04–3.22 mm ² for healthy myopia. There was no difference in the microdisc proportion (disc area < 1.63 mm ² ) between myopic glaucoma (n = 49, 32.7%) and healthy myopia (n = 27, 27%) ( P = 0.42). The mean deviation (MD) of VF was –4.23 ± 5.68 dB for myopic glaucoma and 0.23 ± 1.83 dB for the healthy controls ( P < 0.001). Among the myopic glaucoma eyes, 39 (26.0%) had RNFL defect in the inferotemporal region, 31 (20.7%) in the superotemporal region, and 80 (53.3%) in both the inferotemporal and superotemporal regions. The detailed demographic data are provided in Table 1 .

Table 1

Subject Demographics

	Myopic POAG (n = 150)	Healthy Myopia (n = 100)	P -value
Age, yr	54.8 ± 12.8	51.8 ± 13.4	0.11 a
Gender, female, n (%)	65 (43.3)	52 (52.0)	0.27 b
BCVA, logMAR	0.04 ± 0.12	0.02 ± 0.12	0.37
Phakia, n (%)	139 (92.7)	95 (95.0)
IOP, mmHg	13.3 ± 2.7	13.6 ± 2.6	0.44 a
SE, D	–3.78 ± 3.07	–3.14 ± 2.66	0.13 a
AXL, mm	25.26 ± 1.17	24.89 ± 1.21	0.09 a
High myopia, n (%)	46 (30.7)	21 (21.0)	0.12 b
CCT, μm	546.6 ± 36.6	544.5 ± 37.2	0.68 a
RNFL thickness, μm	73.5 ± 10.8	87.3 ± 9.6	<0.001 a
Rim area, mm 2	0.84 ± 0.23	1.12 ± 0.23	<0.001 a
Disc area, mm 2	1.89 ± 0.51	1.91 ± 0.41	0.68 a
Average C/D	0.72 ± 0.12	0.61 ± 0.15	<0.001 a
Vertical C/D	0.73 ± 0.12	0.57 ± 0.15	<0.001 a
Cup volume, mm 3	0.425 ± 0.281	0.284 ± 0.222	<0.001 a
Average GCIPL thickness, μm	69.6 ± 8.4	79.9 ± 6.3	<0.001 a
Minimum GCIPL thickness, μm	59.9 ± 11.7	75.3 ± 11.4	<0.001 a
MD. dB	–4.23 ± 5.68	0.23 ± 1.83	<0.001 a
PSD, dB	5.94 ± 4.52	1.84 ± 1.03	<0.001 a
VFI, %	87.1 ± 16.5	98.9 ± 2.2	<0.001 a

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