Association of Retinal Neurovascular Impairment with Disease Severity in Patients with Major Depressive Disorder: An Optical Coherence Tomography Angiography Study

Figures & data

Table 1 Demographic, Clinical, and Ocular Characteristics of Healthy Controls and Major Depressive Disorder Groups

	Healthy Controls (n=60)	Major Depressive Disorder (n=74)	p value
Demographic Characteristics
Age (years), mean (SD)	34.00 (12.62)	34.24 (14.85)	0.924
Sex (female, %)	28 (51.90%)	56 (75.70%)	0.005*
SBP (mmHg), mean (SD)	114.76 (11.27)	108.10 (15.52)	0.016*
DBP (mmHg), mean (SD)	73.54 (7.80)	72.36 (10.27)	0.516
BMI, mean (SD)	22.90 (3.40)	21.55 (3.70)	0.048*
Questionnaire scores, mean (SD)
HAMD score	–	22.16 (12.27)
MoCA score	–	23.96 (3.07)
HAMA score	–	18.88 (10.87)
ISI score	–	13.03 (8.96)
Ocular characteristics
VA, mean (SD)	0.56 (0.38)	0.44 (0.41)	0.274
SE, mean (SD)	−1.87 (1.91)	−2.64 (3.75)	0.138
BCVA (log MAR), mean (SD)	0.97 (0.16)	0.98 (0.21)	0.734
IOP (mmHg), mean (IQR)	14.96 (3.05)	14.46 (3.90)	0.315

Note: *p<0.05 is considered statistically significant.

Abbreviations: SD, standard deviation; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; HAMD, Hamilton Depression Scale; HAMA, Hamilton anxiety scale; MoCA, Montreal Cognitive Assessment; ISI, Insomnia Severity Index; VA, visual acuity; SE, spherical equivalent; BCVA, the best-corrected visual acuity; IOP, intraocular pressure; IQR, interquartile range;

Table 2 Comparison of Retinal Neurovascular Parameters Between Healthy Controls and Major Depressive Disorder Groups

	Healthy Controls (n=60)	Major Depressive Disorder (n=74)	p value
Retinal microvascular parameters
SCP VD (%), mean (SD)
Whole Image	51.43 (2.31)	50.80 (2.52)	0.139
Fovea	20.62 (6.67)	20.51 (6.83)	0.923
ParaFovea	54.02 (2.80)	53.10 (3.24)	0.088
PeriFovea	52.29 (2.51)	51.32 (2.53)	0.029*
DCP VD (%), mean (SD)
Whole Image	54.37 (4.49)	51.32 (5.00)	<0.001*
Fovea	36.51 (7.66)	36.97 (7.70)	0.732
ParaFovea	57.62 (3.33)	56.20 (3.80)	0.025*
PeriFovea	56.02 (4.81)	52.58 (5.34)	<0.001*
Overall QI	8.65 (0.61)	8.14 (0.87)	<0.001*
Retinal neural parameters
GCC, mean (SD)
Inner retina average	100.20 (5.78)	97.36 (5.88)	0.008*
Superior	100.17 (6.29)	97.35 (6.38)	0.015*
Inferior	100.26 (5.74)	97.34 (5.77)	0.005*
S-I Avg	−0.09 (3.33)	0.02 (2.30)	0.848
FLV	0.55 (0.55)	0.78 (0.83)	0.082
GLV	1.55 (1.80)	2.31 (2.19)	0.040*
Avg SSI^a	79.49 (5.30)	73.67 (6.63)	<0.001*
ONH, mean (SD)
Area C-D ratio	0.29 (0.15)	0.33 (0.12)	0.101
H C-D ratio	0.59 (0.18)	0.63 (0.15)	0.204
V C-D ratio	0.46 (0.17)	0.52 (0.12)	0.045*
Cup Area	0.66 (0.40)	0.72 (0.33)	0.381
Rim Area	1.55 (0.34)	1.37 (0.32)	0.005*
ONH Volume	0.37 (0.16)	0.30 (0.11)	0.005*
Avg RNFL	108.30 (9.28)	105.26 (8.80)	0.076
Sup RNFL	110.18 (9.60)	107.84 (10.00)	0.208
Inf RNFL	106.42 (10.69)	102.68 (9.16)	0.047*
Avg SSI^b	77.54 (6.70)	75.00 (7.37)	0.059

Notes: ^aSignal strength index of GCC mode of OCTA image. ^bSignal strength index of ONH mode of OCTA image. *p<0.05 is considered statistically significant.

Abbreviations: SCP, superficial capillary plexus; VD, vessel density; SD, standard deviation; DCP, deep capillary plexus; Overall QI, overall quality index; GCC, ganglion cell complex; Avg, average; S-I Avg, Superior Avg-Inferior Avg; FLV, focal loss volume; GLV, global loss volume; SSI, signal strength index; ONH, optic nerve head; C-D ratio, cup/disc ratio; H C-D ratio, horizontal cup/disc ratio; V C-D ratio, vertical cup/disc ratio; RNFL, retinal nerve fibre layer; Sup, superior; Inf, inferior.

Figure 1 Comparison of retinal neurovascular parameters of healthy controls and major depressive disorder groups. (A) Comparison of DCP VD and GCC parameters between controls and MDD; (B) Comparison of GLV and optic nerve head volume between controls and MDD; For all figures, *p<0.05; **p<0.01; ***p<0.001.

Abbreviations: MDD, major depressive disorder; DCP, deep capillary plexus; VD, vessel density; GCC, ganglion cell complex; RNFL, retinal nerve fibre layer; GLV, global loss volume.

Table 3 Comparison of Retinal Neurovascular Parameters of Healthy Controls and Major Depressive Disorder Groups After Adjusting for Confounding Variables^a

	β	95% CI	p value
Retinal microvascular parameters
SCP VD
Whole Image	−0.14	−1.05 to 0.77	0.758
Fovea	0.65	−2.28 to 3.58	0.661
ParaFovea	0.33	−0.809 to 1.46	0.569
PeriFovea	−0.24	−1.20 to 0.7	0.629
DCP VD
Whole Image	−2.50	−4.20 to −0.80	0.004*
Fovea	0.969	−2.39 to 4.33	0.568
ParaFovea	−1.56	−2.85 to −0.28	0.017*
PeriFovea	−2.65	−4.42 to −0.87	0.004*
Retinal neural parameters
GCC
Inner retina average	−4.00	−6.83 to −1.18	0.006*
Superior	−4.34	−7.40 to −1.29	0.006*
Inferior	−3.73	−6.52 to −0.93	0.010*
S-I Avg	−0.62	−2.12 to 0.893	0.418
GLV	1.22	0.28 to 2.17	0.012*
FLV	0.32	−0.01 to 0.66	0.057
ONH
Area C-D ratio	0.06	−0.01 to 0.12	0.082
H C-D ratio	0.06	−0.01 to 0.14	0.089
V C-D ratio	0.06	−0.01 to 0.14	0.087
Cup Area	0.11	−0.07 to 0.29	0.225
Rim Area	−0.14	−0.29 to 0.01	0.060
ONH Volume	−0.07	−0.14 to −0.01	0.027*
Avg RNFL	−4.95	−9.05 to −0.86	0.018*
Sup RNFL	−3.96	−8.44 to 0.52	0.083
Inf RNFL	−5.55	−10.12 to −0.97	0.018*

Notes: ^aAdjustment for confounding variables including age, sex, SBP, BMI, and image quality. *p<0.05 is considered statistically significant.

Abbreviations: CI, confidence interval; SCP, superficial capillary plexus; VD, vessel density; DCP, deep capillary plexus; GCC, ganglion cell complex; Avg, average; S-I Avg, Superior Avg-Inferior Avg; FLV, focal loss volume; GLV, global loss volume; ONH, optic nerve head; C-D ratio, cup/disc ratio; H C-D ratio, horizontal cup/disc ratio; V C-D ratio, vertical cup/disc ratio; RNFL, retinal nerve fibre layer; Sup, superior; Inf, inferior.

Figure 2 Correlation analyses between the retinal neural parameters and questionnaire scores. The cup area (A), cup volume (B) and disc area (C) were positively correlated with HAMD scores; (D) The thickness of RNFL was positively correlated with ISI scores.

Abbreviations: HAMD, Hamilton Depression Scale; ISI, Insomnia Severity Index; I-Hemi RNFL, the thickness of the retinal nerve fibre layer in the inferior-hemifield of the peri-disc.

Table 4 Comparison of Retinal Neurovascular Parameters in Female and Male Subjects Separately After Adjusting for Confounding Variables^a

	Female (n=87)			Male (n=47)
	β	95% CI	p value	β	95% CI	p value
Retinal microvascular parameters
DCP VD
Whole Image	−2.61	−4.94 to −0.28	0.029*	−1.26	−3.33 to 0.81	0.222
ParaFovea	−2.02	−3.68 to −0.36	0.018*	0.13	−1.70 to 1.96	0.887
PeriFovea	−2.99	−5.44 to −0.54	0.018*	−1.06	−3.15 to 1.04	0.309
Retinal neural parameters
GCC
Inner retina average	−2.77	−6.21 to −0.67	0.113	−3.35	−8.50 to 1.81	0.194
Superior Avg	−3.79	−7.51 to −0.07	0.046*	−3.78	−9.20 to 1.65	0.165
Inferior Avg	−3.42	−6.86 to 0.01	0.051	−2.91	−8.08 to 2.25	0.257
GCC-GLV	1.36	0.05 to 2.67	0.042*	1.16	−0.01 to 2.33	0.051
ONH
V C-D ratio	0.04	−0.05 to 0.12	0.386	0.11	−0.04 to 0.26	0.136
Rim area	−0.15	−0.33 to 0.03	0.104	−0.17	−0.46 to 0.14	0.269
ONH volume	−0.08	−0.16 to −0.002	0.044*	−0.06	−0.19 to 0.06	0.289
Inf RNFL	−4.58	−9.98 to 0.82	0.095	−5.67	−13.89 to 2.54	0.167

Notes: ^aAdjustment for confounding variables including age, SBP, BMI, and image quality. *p<0.05 is considered statistically significant.

Abbreviations: CI, confidence interval; DCP, deep capillary plexus; VD, vessel density; GCC, ganglion cell complex; Avg, average; GLV, global loss volume; ONH, optic nerve head; V C-D ratio, vertical cup/disc ratio; Inf, inferior; RNFL, retinal nerve fibre layer.

Table 5 Comparison of Retinal Neurovascular Parameters in Aged ≤40 Years and >40 Years Subjects Separately After Adjusting for Confounding Variables^a

	≤40 y (n=89)			>40 y (n=45)
	β	95% CI	p value	β	95% CI	p value
Retinal microvascular parameters
DCP VD
Whole Image	−2.36	−4.94 to −0.28	0.025*	−2.02	−5.97 to 1.94	0.305
ParaFovea	−1.12	−2.76 to 0.52	0.176	−1.64	−6.12 to 1.00	0.213
PeriFovea	−2.51	−4.67 to −0.34	0.024*	−2.09	−3.15 to 1.94	0.297
Retinal neural parameters
GCC
Inner Retina Average	−2.94	−6.08 to 0.20	0.066	−1.48	−7.88 to 1.81	0.639
Superior Avg	−3.10	−6.43 to 0.22	0.067	−6.24	−13.41 to 0.93	0.085
Inferior Avg	−2.90	−6.11 to 0.32	0.077	−4.29	−10.28 to 1.70	0.153
GCC-GLV	1.20	0.26 to 2.14	0.013*	1.78	−0.87 to 4.43	0.178
ONH
V C-D ratio	0.06	−0.03 to 0.15	0.166	0.07	−0.89 to 0.26	0.431
Rim area	−0.07	−0.26 to 0.12	0.471	−0.34	−0.64 to −0.05	0.025*
ONH volume	−0.06	−0.13 to −0.02	0.150	−0.15	−0.30 to 0.01	0.054
Inf RNFL	−3.22	−8.67 to −2.23	0.241	−9.95	−17.62 to −2.29	0.013*

Notes: ^aAdjustment for confounding variables including sex, SBP, BMI, and image quality. *p<0.05 is considered statistically significant.

Abbreviations: CI, confidence interval; DCP, deep capillary plexus; VD, vessel density; GCC, ganglion cell complex; Avg, average; GLV, global loss volume; ONH, optic nerve head; V C-D ratio, vertical cup/disc ratio; Inf, inferior; RNFL, retinal nerve fibre layer.

Table 6 Comparison of Retinal Neurovascular Parameters of MDD Patients with Different Years of Use for Antidepressants

	<6m (n=25)	6m-1y (n=23)	>1y (n=26)	p value
Retinal microvascular parameters
DCP VD (%), mean (SD)
Whole Image	51.67 (5.07)	52.16 (5.79)	50.24 (4.11)	0.268
ParaFovea	56.31 (3.77)	56.84 (4.78)	55.53 (2.75)	0.209
PeriFovea	53.00 (5.39)	53.34 (6.17)	51.51 (4.48)	0.290
Retinal neural parameters
GCC, mean (SD)
Inner Retina Average	98.28 (5.35)	97.01 (5.15)	97.39 (6.63)	0.445
Superior Avg	98.77 (5.33)	97.17 (5.65)	97.01 (7.07)	0.273
Inferior Avg	97.80 (5.52)	96.87 (4.94)	97.65 (6.73)	0.567
GCC-GLV	2.13 (2.24)	2.18 (1.81)	2.22 (1.76)	0.715
ONH, mean (SD)
V C-D ratio	0.52 (0.13)	0.50 (0.14)	0.52 (0.11)	0.503
Rim area	1.34 (0.40)	1.45 (0.34)	1.36 (0.21)	0.619
ONH volume	0.28 (0.13)	0.32 (0.12)	0.30 (0.09)	0.473
Inf RNFL	105.44 (10.77)	103.32 (8.84)	101.74 (7.64)	0.231

Abbreviations: MDD, major depressive disorder; DCP, deep capillary plexus; VD, vessel density; SD, standard deviation; GCC, ganglion cell complex; Avg, average; GLV, global loss volume; ONH, optic nerve head; V C-D ratio, vertical cup/disc ratio; Inf, inferior; RNFL, retinal nerve fibre layer.