Optical Coherence Tomography Angiography (OCTA) Differences in Vessel Perfusion Density and Flux Index of the Optic Nerve and Peri-Papillary Area in Healthy, Glaucoma Suspect and Glaucomatous Eyes

Figures & data

Figure 1 The optic nerve and peri-papillary area; (A) OCTA and segmentation into superior inferior nasal and temporal quadrants, (B) disc photography, (C) peri-papillary OCT retinal nerve fiber layer thickness.

Table 1 Demographic and Clinical Characteristics of Subjects in the Healthy, Glaucoma Suspected and Glaucomatous Groups

	Healthy	Glaucoma Suspected	Glaucomatous	p-value*
No. of Participants/Eyes	33/56	52/79	64/103 Early (n=56) Moderate (n=27) Severe (n=20)
Age (yr)	55.58 ± 15.19	61.12 ± 9.24	64.78 ± 7.22	<0.001^ab
Male	8 (24.2%)	18 (34.6%)	24 (37.5%)	0.405
Female	25 (75.8%)	34 (65.4%)	40 (62.5%)
Pulse rate (beats/min)	78.41 ± 11.67	77.43 ± 11.37	74.13 ± 12.04	0.194
Systolic blood pressure (mmHg)	128.44 ± 20.46	133.96 ± 19.53	136.56 ± 18.56	0.171
Diastolic blood pressure (mmHg)	76.50 ± 8.91	79.66 ± 11.94	80.00 ± 13.56	0.389
Mean arterial pressure (mmHg)	93.81 ± 11.29	97.76 ± 12.34	98.85 ± 12.78	0.176
Underlying diseases
-Diabetic Mellitus	3 (9.1%)	9 (17.3%)	15 (23.4%)	0.207
-Essential Hypertension	10 (30.3%)	28 (53.8%)	34 (53.1%)	0.070
-Heart disease	1 (3.0%)	2 (3.8%)	3 (4.7%)	1.000
-Dyslipidemia	5 (15.2%)	11 (21.2%)	10 (15.6%)	0.727
IOP (mmHg)	14.82 ± 3.1	16.23 ± 3.1	15.15 ± 3.9	0.839
Central corneal thickness (CCT)(μm)	521.39 ± 75.30	532.90 ± 33.79	511.17 ± 32.54	0.008^c
Axial length (mm)	23.28 ± 1.00	23.37 ± 0.81	23.25 ± 0.96	0.677

Notes: *Continuous data compared by one-way analysis of variance (ANOVA) and categorical data by chi-square tests, ^a Statistically significance difference between healthy and glaucoma suspected eyes, ^b Statistically significance difference between healthy and glaucomatous eyes, ^c Statistically significance difference between glaucoma suspected and glaucomatous eyes.

Table 2 Ocular Parameters in Healthy, Glaucoma Suspected and Glaucomatous Groups and in Glaucomatous Eyes Differing by Severity (Adjusted for Age)

Data	Healthy (1) (n=56)	Glaucoma Suspected (2) (n=79)	Glaucoma: (3) (n=103)				p-value* (1) vs (2)	p-value* (1) vs (3)	p-value* (2) vs (3)
			All (n=103)	Early (n=56)	Moderate (n=27)	Severe (n=20)
Vessel perfusion density (%), mean ± SD
Average	45.40 ± 0.19	45.05 ± 0.22	42.89 ± 0.32	43.99 ± 0.32^a	42.63 ± 0.43^b	39.27 ± 0.48^c	0.224	<0.001	<0.001
Superior	43.93 ± 0.39	43.63 ± 0.27	41.43 ± 0.51	43.10 ± 0.52	41.17 ± 0.71^b	35.92 ± 0.79^c	0.514	<0.001	<0.001
Nasal	44.29 ± 0.30	45.53 ± 0.39	43.61 ± 0.38	44.35 ± 0.43	43.32 ± 0.61^b	40.74 ± 0.71	0.010	0.167	<0.001
Inferior	45.05 ± 0.34	44.76 ± 0.33	40.57 ± 0.52	42.56 ± 0.53^a	39.60 ± 0.74^b	35.10 ± 0.82^c	0.526	<0.001	<0.001
Temporal	47.93 ± 0.49	46.20 ± 0.40	45.68 ± 0.32	45.77 ± 0.39	46.67 ± 0.56^b	44.36 ± 0.64	0.006	<0.001	0.300
Flux index, mean ± SD
Average	0.4210 ± 0.0055	0.4105 ± 0.0039	0.3801 ± 0.0048	0.3908 ± 0.005 ^a	0.3563 ± 0.0076	0.3419 ± 0.0088^c	0.124	<0.001	<0.001
Superior	0.4119 ± 0.0050	0.4015 ± 0.0035	0.3742 ± 0.0045	0.3849 ± 0.0051^a	0.3547 ± 0.0074	0.3354 ± 0.0085^c	0.091	<0.001	<0.001
Nasal	0.4197 ± 0.0064	0.4159 ± 0.0050	0.3808 ± 0.0050	0.3892 ± 0.0054^a	0.3555 ± 0.0081	0.3420 ± 0.0096^c	0.644	<0.001	<0.001
Inferior	0.4156 ± 0.0057	0.4093 ± 0.0033	0.3747 ± 0.0054	0.3911 ± 0.0053^a	0.3476 ± 0.0076	0.3312 ± 0.0086^c	0.343	<0.001	<0.001
Temporal	0.4357 ± 0.0064	0.4129 ± 0.0050	0.3886 ± 0.0055	0.3967 ± 0.0065^a	0.3655 ± 0.0093	0.3529 ± 0.0107^c	0.006	<0.001	0.001
Optical coherence tomography retinal nerve fiber layer thickness, mean ± SD
Average	105.80 ± 2.27	104.54 ± 1.74	76.46 ± 1.58	84.09 ± 1.91^a	72.57 ± 2.54^b	52.21 ± 2.82^c	1.000	<0.001	<0.001
Superior	139.42 ± 5.19	132.29 ± 3.97	104.79 ± 3.62	116.81 ± 4.43^a	99.74 ± 5.86^b	66.87 ± 6.49^c	0.785	<0.001	<0.001
Nasal	78.37 ± 2.45	77.26 ± 1.88	59.41 ± 1.71	63.87 ± 2.32	57.64 ± 3.24^b	45.48 ± 3.63^c	1.000	<0.001	<0.001
Inferior	150.17 ± 5.22	140.15 ± 3.99	98.37 ± 3.65	110.28 ± 3.90^a	87.38 ± 5.32^b	54.09 ± 5.92^c	0.349	<0.001	<0.001
Temporal	79.04 ± 2.30	75.69 ± 1.76	63.25 ± 1.60	67.43 ± 1.98	63.26 ± 2.68^b	50.87 ± 2.98^c	0.718	<0.001	<0.001
Optical coherence tomography ganglion cell analysis, mean ± SD
Sector 1	81.19 ± 1.69	77.01 ± 1.33	73.11 ± 1.18	73.26 ± 1.71	69.84 ± 2.10	66.80 ± 2.31^c	0.110	<0.001	0.027
Sector 2	81.13 ± 1.64	78.40 ± 1.29	75.15 ± 1.15	74.49 ± 1.64	71.61 ± 2.08	69.55 ± 2.30	0.476	0.005	0.074
Sector 3	83.55 ± 1.66	81.64 ± 1.31	77.19 ± 1.17	77.10 ± 1.66	74.75 ± 2.01	71.53 ± 2.21	0.982	0.003	0.006
Sector 4	82.65 ± 1.49	78.53 ± 1.18	74.52 ± 1.07	72.45 ± 1.46	73.52 ± 1.71^b	68.76 ± 1.87	0.048	<0.001	0.004
Sector 5	78.20 ± 1.56	74.87 ± 1.23	70.77 ± 1.11	69.95 ± 1.44	67.08 ± 1.89	63.30 ± 2.09^c	0.191	<0.001	0.005
Sector 6	80.76 ± 1.69	77.24 ± 1.33	70.11 ± 1.17	71.70 ± 1.63^a	64.11 ± 2.15	63.04 ± 2.38^c	0.256	<0.001	<0.001
Average	81.12 ± 1.45	78.16 ± 1.14	73.36 ± 1.01	73.41 ± 1.40	70.08 ± 1.78	66.86 ± 1.97^c	0.255	<0.001	0.001
Min	74.05 ± 1.96	72.66 ± 1.54	66.59 ± 1.38	66.21 ± 1.79	61.70 ± 2.40	57.88 ± 2.66^c	1.000	0.003	0.001
Humphrey visual field 24–2, mean ± SD
MD (dB)	−2.93 ± 0.83	−2.54 ± 0.64	−7.37 ± 0.59	−4.66 ± 0.77	−6.58 ± 1.17^b	−18.89 ± 1.36^c	1.000	<0.001	<0.001
PSD (dB)	2.65 ± 0.44	2.74 ± 0.34	4.96 ± 0.31	3.38 ± 0.39 ^a	5.71 ± 0.56 ^b	9.88 ± 0.64 ^c	1.000	<0.001	<0.001
VFI (%)	96.78 ± 2.34	95.36 ± 1.81	83.64 ± 1.67	92.94 ± 1.92^a	82.60 ± 2.60^b	52.20 ± 2.94^c	1.000	<0.001	<0.001

Notes: Data presented as mean (standard error) adjusted for age. *Generalized estimating equation (GEE), ^aStatistically significant difference between early and moderate glaucoma, ^bStatistically significant difference between moderate and severe glaucoma, ^cStatistically significant difference between early and severe glaucoma.

Figure 2 OCTA results in healthy (A), glaucoma suspected (B), and glaucomatous eyes (C).

Figure 3 OCTA results in early (A), moderate (B), and severe glaucomatous eyes (C).

Table 3 Correlations Among Vessel Perfusion Density, Flux Index, Optical Coherence Tomography Retinal Nerve Fiber Layer Thickness (OCT RNFL), Optical Coherence Tomography Ganglion Cell Complex (OCT GCC) and Humphrey Visual Field Test 24–2 (HVF 24–2)

Pearson’s Correlation	OCT RNFL	Average	Superior	Nasal	Inferior	Temporal	HVF 24–2	MD (dB)	PSD (dB)	VFI (%)
Vessel perfusion density (%)
Average		0.736**	0.659**	0.493**	0.647**	0.439**		0.630**	−0.505**	0.597**
Superior		0.744**	0.737**	0.515**	0.538**	0.435**		0.651**	−0.393**	0.584**
Nasal		0.374**	0.402**	0.300**	0.238*	0.222*		0.338**	−0.196	0.331**
Inferior		0.639**	0.487**	0.394**	0.696**	0.323**		0.535**	−0.600**	0.564**
Temporal		0.319**	0.264**	0.181	0.322**	0.303**		0.241*	−0.193	0.167
Flux index
Average		0.514**	0.424**	0.204*	0.499**	0.411**		0.424**	−0.343**	0.464**
Superior		0.550**	0.459**	0.246*	0.499**	0.441**		0.424**	−0.319**	0.455**
Nasal		0.464**	0.393**	0.198*	0.465**	0.327**		0.374**	−0.255*	0.407**
Inferior		0.536**	0.445**	0.228*	0.560**	0.353**		0.481**	−0.426**	0.538**
Temporal		0.462**	0.359**	0.142	0.431**	0.431**		0.368**	−0.330**	0.406**
Pearson’s correlation	OCT GCA	Sector 1	Sector 2	Sector 3	Sector 4	Sector 5	Sector 6	Average	min
Vessel perfusion density (%)
Mean		0.192	0.135	0.143	0.217*	0.196*	0.222*	0.220*	0.231*
Superior		0.338**	0.322**	0.239*	0.215*	0.193	0.231*	0.314**	0.264**
Nasal		0.027	−0.072	−0.039	0.037	−0.048	−0.003	−0.028	0.002
Inferior		0.086	0.004	0.036	0.191	0.277**	0.292**	0.183	0.250*
Temporal		0.022	0.102	0.155	0.139	0.032	0.010	0.078	0.032
Pearson’s correlation	OCT GCA	Sector 1	Sector 2	Sector 3	Sector 4	Sector 5	Sector 6	Average	min
Flux index
Mean		0.283**	0.252*	0.218*	0.281*	0.360**	0.305**	0.332**	0.324**
Superior		0.299**	0.269**	0.226*	0.282**	0.322**	0.276**	0.332**	0.307**
Nasal		0.262**	0.194	0.180	0.229*	0.305**	0.278**	0.284**	0.285**
Inferior		0.233*	0.169	0.135	0.222*	0.354**	0.299**	0.281**	0.309**
Temporal		0.306**	0.307**	0.271**	0.326**	0.388**	0.319**	0.369**	0.341**

Notes: **p < 0.01, *p < 0.05.

Abbreviations: MID, mean deviate; PSD, pattern standard deviation; VFI, visual field index.

Table 4 Rates of Change per Year in Vessel Perfusion Density, Flux Index, Retinal Nerve Fiber Layer Thickness, Ganglion Cell Complex and Humphrey Visual Field 24–2 in Glaucomatous Eyes with and without Progression

Yearly Rate of Change	Progression			Stable			p-value^b
	GEE Coefficient	95% CI	p-value^a	GEE Coefficient	95% CI	p-value^a
Vessel perfusion density (%)
Mean	−0.555	−1.406, −0.298	0.027*	−0.305	−0.485, 0.126	0.051	0.901
Superior	−1.198	−1.436, −0.959	<0.001*	−0.238	−1.077, 0.601	0.578	0.123
Nasal	−0.786	−1.563, −0.009	0.047*	0.088	−0.185, 0.362	0.528	0.036*
Inferior	−0.535	−1.286, 0.216	0.163	−1.199	−1.817, −0.581	<0.001*	0.935
Temporal	0.382	−0.470, 1.234	0.379	1.143	−1.708, 2.578	0.055	0.302
Flux index
Mean	−0.008	−0.016, 0.001	0.054	−0.002	−0.005, 0.010	0.511	0.053
Superior	−0.012	−0.020, −0.005	0.002*	−0.001	−0.007, 0.007	0.981	0.002*
Nasal	−0.004	−0.014, 0.005	0.359	−0.001	−0.008, 0.010	0.832	0.079
Inferior	−0.008	−0.016, −0.001	0.045*	−0.003	−0.002, 0.008	0.175	0.007*
Temporal	0.001	−0.002, 0.004	0.529	0.001	−0.009, 0.012	0.810	0.074
Retinal nerve fiber layer (RNFL) thickness (μm)
Mean	−1.207	−2.991, −0.577	0.018*	−0.794	−3.479, 1.890	0.562	0.002*
Superior	−5.375	−11.680, −0.930	0.045*	−0.131	−2.147, 1.885	0.899	0.005*
Nasal	−3.315	−4.447, −2.183	<0.001*	−1.009	−2.022, 0.003	0.051	0.335
Inferior	−5.439	−10.071, −0.806	0.021*	−1.309	−3.268, 0.651	0.191	0.013*
Temporal	−1.308	−3.492, −0.875	0.024*	−1.052	−1.981, −0.123	0.026*	0.001*
Humphrey visual field 24–2 (HVF 24–2)
MD (dB)	−0.877	−1.425, −0.330	0.002*	0.262	−0.003, 0.528	0.053	0.006*
PSD (dB)	−0.276	−0.873, 0.321	0.365	0.006	−0.152, 0.163	0.942	0.113
VFI (%)	−0.972	−2.320, 0.377	0.158	1.635	−0.952, 4.223	0.215	0.036*
Ganglion cell analysis (GCA) (μm)
Sector 1	−0.995	−2.626, 0.636	0.232	−1.674	−4.982, 1.634	0.321	0.034*
Sector 2	−2.384	−7.910, −2.859	0.001*	−0.367	−2.441, 3.175	0.798	0.005*
Sector 3	−3.638	−4.559, −2.718	<0.001*	−0.363	−6.326, −0.400	0.006*	0.035*
Sector 4	−5.475	−7.720, −3.230	<0.001*	−5.485	−8.252, −2.719	<0.001*	0.001*
Sector 5	−5.586	−11.542, 0.370	0.066	−1.899	−4.009, 0.212	0.078	0.182
Sector 6	−3.519	−4.815, −2.223	<0.001*	−0.049	−2.552, 2.650	0.971	0.339
Average	−4.386	−5.309, −3.462	<0.001*	−2.216	−4.605, 0.173	0.069	0.053
Min	−4.510	−5.910, −3.110	<0.001*	−2.043	−5.285, 1.198	0.217	0.035*

Notes: ^asignificantly different from zero, ^b significantly different between groups, *p < 0.05.

Abbreviations: AUROC, areas under receiver operating characteristic curves; BP, blood pressure; FI, flux index; GCA, ganglion cell analysis; GEE, generalized estimating equations; GPA, guided progression analysis; IOP, intraocular pressure; MAP, mean arterial pressure; MD, mean deviation; OCT, optical coherence tomography; OCTA, optical coherence tomography angiography; PSD, pattern standard deviation; RNFL, retinal nerve fiber layer thickness; SD, standard deviation; VPD, vascular perfusion density; VFI, visual field index.