Initially, 194 eyes were recruited, however, eyes were excluded: 74 eyes due to less than 10° difference between the two layers, 33 eyes due to lack of presence of the VDs in the both layers, and 15 eyes whose image quality score less than 50. The rest of 72 eyes of 72 patients with NTG who satisfied the inclusion and exclusion criteria were included for further study.
Patient’s characteristics are in Table 1. The widths for the superficial and the deep layers of the SVD group were 46.56±21.86°, and 32.16±17.20°, respectively. Those for the DVD group were 35.11±18.83°, and 59.97±24.87°, respectively. The DVD group was significantly older than the SVD group (P, 0.023). Regarding the degree of visual field defects, the SVD group showed substantially progressed status not only in mean deviations (MD) but also in pattern standard deviation (PSD), and visual field index (VFI) (all Ps ≤0.002). In addition, the DVD group showed a higher proportion of the paracentral VF defect, compared to the SVD group (% of paracentral VF defects, 47.6%, 28.1%, respectively, P 0.008).
With regard to the OCT parameters (Table 1), there were no noticeable differences in average RNFL thickness (RNFLT), average cup-to-disc (C/D) ratio, average ganglion cell inner plexiform layer thickness (GCIPLT).
Table 1
|
Wider SVD
(N,32)
|
Wider DVD
(N,42)
|
P value
|
OCTA SSI
|
67.34 ± 5.42
|
64.98 ± 7.21
|
0.127 a
|
Width of Superficial defects (°)
|
46.56±21.86
|
35.11±18.83
|
0.018a
|
Width of
Deep defects (°)
|
32.16±17.20
|
59.97±24.87
|
< 0.001a
|
Age (year)
|
52.06±11.99
|
58.48±11.63
|
0.023a
|
Sex
(Male, no. (%))
|
10 (31.3%)
|
18 (42.9%)
|
0.308b
|
Laterality
(OD, no. (%))
|
19 (59.4%)
|
16 (38.1%)
|
0.069b
|
HTN
(Yes, no. (%))
|
2 (6.3%)
|
9 (21.4%)
|
0.101b
|
DM
(Yes, no. (%))
|
2 (6.3%)
|
3 (7.1%)
|
1.000b
|
Cardiovascular disease
(Yes, no. (%))
|
1 (3.1%)
|
4 (9.5%)
|
0.639b
|
Migraine
(Yes, no. (%))
|
1 (3.1%)
|
3 (7.1%)
|
0.629b
|
Cold extremities (Yes, no. (%))
|
1 (3.1%)
|
4 (9.5%)
|
0.639b
|
Baseline IOP (mmHg)
|
15.23±3.95
|
15.40±3.31
|
0.834a
|
Treated IOP (mmHg)
|
13.66±3.30
|
14.71±3.56
|
0.195a
|
CCT (㎛)
|
529.70±45.70
|
527.71±32.29
|
0.830a
|
AL (mm)
|
24.51±5.23
|
25.06±1.57
|
0.540a
|
MD (dB)
|
-4.71±3.05
|
-2.52±2.35
|
0.001a
|
PSD (dB)
|
6.66±3.72
|
3.72±2.85
|
0.001a
|
VFI (%)
|
88.16±9.42
|
94.67±6.11
|
0.002a
|
Presence of Paracentral VFD (Yes, no. (%))
|
9 (28.1%)
|
20 (47.6%)
|
0.008b
|
Average RNFLT (㎛)
|
73.25±9.20
|
76.62±8.75
|
0.113 a
|
Average CD ratio
|
.72± .11
|
.69± .15
|
0.334 a
|
Average GCIPLT (㎛)
|
67.41±8.05
|
70.05±6.99
|
0.136 a
|
SVD; superficial vessel defect; DVD = deep vessel defect; n = number; OCTA = optical coherence tomography angiography; SSI = signal strength index; HTN = hypertension; DM = diabetes mellitus; IOP = intraocular pressure; CCT = central corneal thickness; AL = axial length; MD = mean deviation; dB = decibel; PSD = pattern standard deviation; VFI = visual field index; VFD = visual field defect; RNFLT = retinal nerve fiber layer thickness; CD = cup disc; GCIPLT = ganglion cell inner plexiform layer thickness. |
Mean values are presented with standard deviations
Bold font indicates significant p values (p < 0.05).
a Student’s t-test
b Chi-squared test
The Pearson correlation analysis was performed between clinical parameters and the width of the VDs in the superficial and the deep layers in the total eyes (Table 2). The average GCIPLT showed a marked correlation with the widths of the VD in the superficial layer (r, -0.335, P, 0.004). MD and average RNFLT showed borderline correlation with the width of the superficial VD (r, -0.226, P, 0.054, r, -0.213, P, 0.068, respectively). Meanwhile, treated IOP showed a significant correlation with the width of the deep VD (r, 0.300, P, 0.009), and baseline IOP was marginally correlated with the width of the deep VD (r, 0.219, P, 0.063). In Fig. 1, the width of the superficial VD increases as average RNFLT and average GCIPLT decreases (R2, 0.045, P, 0.068, R2, 0.112, P,0.04, respectively), yet these relationships were attenuated with the width of the deep VD (R2, 0.048, P, 0.914, R2, 0.0002, P, 0.415, respectively). Nonetheless, the width of deep VD increases as baseline and treated IOP increases (Fig. 2). These relationships between the IOPs and the width of deep VD were not found with the width of superficial VD. (R2, 0.048, P, 0.063, R2, 0.004, P,0.616, respectively, for baseline IOP, R2, 0.048, P, 0.009, R2, 0.004, P,0.571, respectively, for treated IOP)
Further analyses were carried out with patients whose MDs were worse than − 3dB and better than − 6dB (Table 3). The average GCIPLT was the only factor which correlated with the width of the superficial VD (r, -0.325, P, 0.041), while the IOP factors including baseline and treated IOP, and central corneal thickness (CCT) showed significant correlations with the width of the deep VD (r, 0.0447, P, 0.004, r, 0.382, P, 0.015, and r, 0.377, P, 0.018, respectively).
Table 2
Correlation Coefficients between the Width of Vessel Defect in each layer and Structural or Functional Parameters in all eyes
|
Width of SVD
|
P
|
Width of DVD
|
P
|
Age
|
-0.097
|
0.410
|
0.162
|
0.167
|
Baseline IOP
|
0.060
|
0.616
|
0.219
|
0.063
|
Treated IOP
|
0.067
|
0.571
|
0.300
|
0.009
|
CCT
|
-0.023
|
0.852
|
0.065
|
0.593
|
Axial Length
|
0.042
|
0.737
|
0.038
|
0.764
|
MD
|
-0.226
|
0.054
|
0.096
|
0.418
|
PSD
|
0.092
|
0.439
|
-0.166
|
0.160
|
VFI
|
-0.187
|
0.112
|
0.108
|
0.365
|
Average RNFLT
|
-0.213
|
0.068
|
0.013
|
0.914
|
Average CD ratio
|
0.159
|
0.177
|
0.065
|
0.583
|
Average GCIPLT
|
-0.335
|
0.004
|
-0.096
|
0.415
|
Table 3
Correlation Coefficients between the Width of Vessel Defect in each layer and Structural or Functional Parameters in Eyes with MD < -3dB
|
Width of SVD
|
P
|
Width of DVD
|
P
|
Age
|
-0.088
|
0.591
|
0.288
|
0.071
|
Baseline IOP
|
-0.060
|
0.715
|
0.447
|
0.004
|
Treated IOP
|
0.022
|
0.891
|
0.382
|
0.015
|
CCT
|
0.024
|
0.886
|
0.377
|
0.018
|
Axial Length
|
-0.048
|
0.783
|
0.054
|
0.755
|
MD
|
-0.158
|
0.330
|
0.086
|
0.596
|
PSD
|
-0.003
|
0.988
|
-0.058
|
0.724
|
VFI
|
-0.041
|
0.800
|
0.137
|
0.399
|
Average RNFLT
|
-0.240
|
0.136
|
-0.031
|
0.851
|
Average CD ratio
|
0.007
|
0.964
|
0.002
|
0.990
|
Average GCIPLT
|
-0.325
|
0.041
|
0.061
|
0.709
|
Abbreviations: SVD; superficial vessel defect; DVD = deep vessel defect; IOP = intraocular pressure; CCT = central corneal thickness; MD = mean deviation; PSD = pattern standard deviation; VFI = visual function index; RNFLT = retinal nerve fiber layer thickness; CD = cup to disc; GCIPLT = ganglion cell inner plexiform layer thickness.
Bold font indicates significant p values (p < 0.05).
Pearson correlation analysis was used.
Linear regression analysis was adopted to identify factors associated with the width of VD in each layer (Table 4). Both baseline and treated IOPs were associated with the width of the deep VD (β, 1.582, P, 0.063, β, 2.236, P, 0.009, respectively) in the univariate analysis, however, in the multivariate analysis, only the baseline IOP showed a significant association (β, 3.900, P, 0.014). As for the width of the superficial VD (Table 5), structural factors including average RNFLT and average GCIPLT and MD, a functional component, were associated with the width of the superficial VD. Nevertheless, in the multivariate analysis, average GCIPLT turned out to be the sole factor.
Table 4
Linear Regression analysis to Determine the Correlation between Variables and Width of Deep Vascular Defect in All eyes (N, 72)
|
Univariate
|
|
Multivariate
|
|
|
Beta
|
P
|
Beta
|
P
|
Age
|
0.345
|
0.167
|
|
|
Baseline IOP
|
1.582
|
0.063
|
3.900
|
0.014
|
Treated IOP
|
2.236
|
0.009
|
|
|
CCT
|
0.044
|
0.593
|
|
|
Axial Length
|
0.282
|
0.764
|
|
|
MD
|
0.860
|
0.418
|
|
|
PSD
|
-1.203
|
0.160
|
|
|
VFI
|
0.333
|
0.365
|
|
|
Average RNFLT
|
0.036
|
0.914
|
|
|
Average CD ratio
|
12.369
|
0.583
|
|
|
Average GCIPLT
|
-0.330
|
0.415
|
|
|
Table 5
Linear Regression analysis to Determine the Correlation between Variables and Width of Superficial Vascular Defect in All eyes (N, 72)
|
Univariate
|
|
Multivariate
|
|
|
Beta
|
P
|
Beta
|
P
|
Age
|
-0.167
|
0.410
|
|
|
Baseline IOP
|
0.351
|
0.616
|
|
|
Treated IOP
|
0.403
|
0.571
|
|
|
CCT
|
-0.013
|
0.852
|
|
|
Axial Length
|
0.251
|
0.737
|
|
|
MD
|
-1.653
|
0.054
|
|
|
PSD
|
0.544
|
0.439
|
|
|
VFI
|
-0.475
|
0.112
|
|
|
Average RNFLT
|
-0.492
|
0.068
|
|
|
Average CD ratio
|
24.427
|
0.177
|
|
|
Average GCIPLT
|
-0.928
|
0.004
|
-0.935
|
0.004
|
SVD; superficial vessel defect; DVD = deep vessel defect; IOP = intraocular pressure; CCT = central corneal thickness; MD = mean deviation; PSD = pattern standard deviation; VFI = visual function index; RNFLT = retinal nerve fiber layer thickness; CD = cup to disc; GCIPLT = ganglion cell inner plexiform layer thickness.
Only variables with a P value < 0.10 in the univariate analysis were included in the multivariate model.
Bold font indicates significant p values (p < 0.05).
Table 6 illustrates the results of logistic regression analysis to identify factors related to presence of wider DVD. In multivariate analysis, older age and PSD showed significance (Both Ps, 0.001).
Table 6
Logistic Regression Analysis of Factors associated with the Presence of Wider Deep Vascular Defect
|
Univariate
|
Multivariate
|
β (95% CI)
|
P value
|
β (95% CI)
|
P value
|
Age (year)
|
0.046
(1.005–1.091)
|
0.027
|
0.047
(1.001–1.097)
|
0.001
|
Baseline IOP (mmHg)
|
0.014
(0.889–1.157)
|
0.831
|
|
|
Treated IOP (mmHg)
|
0.091
(0.955–1.256)
|
0.194
|
|
|
CCT (㎛)
|
-0.001
(0.986–1.011)
|
0.827
|
|
|
Axial Length (mm)
|
0.045
(0.903–1.212)
|
0.549
|
|
|
Presence of Paracentral VFD (Yes)
|
0.799
(0.831–5.944)
|
0.112
|
|
|
MD (dB)
|
0.312
(1.110–1.682)
|
0.003
|
|
|
PSD (dB)
|
-0.262
(0.658–0.900)
|
0.001
|
-0.268
(0.652–0.897)
|
0.001
|
VFI (%)
|
0.122
(1.040–1.227)
|
0.004
|
|
|
Average RNFLT (㎛)
|
0.043
(0.989–1.102)
|
0.117
|
|
|
Average CD ratio
|
-1.836
(0.004–6.714)
|
0.336
|
|
|
Average GCIPLT (㎛)
|
0.048
(0.984–1.119)
|
0.139
|
|
|
CI, confidence interval; IOP, intraocular pressure; CCT, central corneal thickness; VFD, visual field defect; MD, mean deviation; PSD, pattern standard deviation; VFI, visual field index; RNFLT, retinal nerve fiber layer thickness; CD, cup disc; GCIPLT, ganglion cell inner plexiform layer thickness.
Variables with P < 0.10 were included in the multivariate analysis.
Factors with statistical significance are shown in bold.
Representative cases are shown in Figs. 3 and 4. A 63-year-old man with NTG and hypertension had a paracentral VFD, and a localized inferotemporal RNFL defect (Fig. 3A, C-D). In his OCTA examination, we found a large DVD at the site of inferotemporal RNFL defect, which was wider than the SVD (Fig. 3B-1 and B-2). In the other case, a 45-year-old male NTG patient had a prominent inferotemporal RFNL defect and a superior peripheral VFD (Fig. 4A, C-D). The OCTA exam showed that the width of SVD was noticeably greater than that of DVD (Fig. 4B-1 and B-2).