Non-linear relationship between age and subfoveal choroidal thickness in Chinese patients with proliferative diabetic retinopathy

Table 1 Baseline characteristics of participants

Item	mean ± SD/n (%)
Age (year)	55.60 ± 10.03
SBP (mmHg)	136.98 ± 20.75
DBP (mmHg)	82.92 ± 10.90
Height (cm)	161.72 ± 8.16
Weight (kg)	62.91 ± 10.83
BMI (kg/m2)	23.99 ± 3.07
Duration of diabetes (year)	12.27 ± 6.80
Visual acuity (logMAR)	0.73 ± 0.53
IOP (mmHg)	16.28 ± 4.16
Fasting blood glucose (mmol/L)	7.40 ± 2.87
Serum urea nitrogen (mmol/L)	8.47 ± 4.39
Serum creatinine, µmol/L	145.98 ± 182.39
eGFR (mL/minutes × 1.73 m2)	66.95 ± 30.47
Uric acid (mmol/L)	377.59 ± 87.59
Triglyceride (mmol/L)	1.50 ± 0.75
Total cholesterol (mmol/L)	4.60 ± 1.19
HDL-C (mmol/L)	1.31 ± 0.41
LDL-C (mmol/L)	2.68 ± 1.02
HbA1c (%)	7.73 ± 1.74
Ocular axial length (mm)	23.17 ± 0.99
CMT (μm)	283.76 ± 122.66
SFCT (μm)	264.70 ± 83.28
Gender
Female	99 (42.31)
Male	135 (57.69)
Education level
Junior high school or below	147 (63.64)
Senior high school	40 (17.32)
College or above	44 (19.05)
Hypertension history
No	126 (53.85)
Yes	108 (46.15)
Diabetic nephropathy history
No	188 (80.34)
Yes	46 (19.66)
Stroke history
No	222 (94.87)
Yes	12 (5.13)
Anemia history
No	162 (69.23)
Yes	72 (30.77)
Heart disease history
No	222 (94.87)
Yes	12 (5.13)
PRP
None	111 (47.44)
Partial	43 (18.38)
Whole	80 (34.19)
Anti-VEGF therapy
No	175 (74.79)
Yes	59 (25.21)
Insulin treatment
No	113 (48.29)
Yes	121 (51.71)
Oral glucose-lowering drugs
No	59 (25.21)
Yes	175 (74.79)
Calcium antagonists
No	183 (78.54)
Yes	50 (21.46)

SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BMI: Body mass index; HbA1c: Hemoglobin A1c; logMAR: Logarithmic minimum resolution angle; IOP: Intraocular pressure; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; eGFR: Estimated glomerular filtration rate; CMT: Central macular thickness; SFCT: Subfoveal choroidal thickness; VEGF: Vascular endothelial growth factor; PRP: Pan-retinal photocoagulation.

Table 2 Univariate linear regression analysis of subfoveal choroidal thickness measurements by enhanced depth imaging-optical coherence tomography

	β, 95%CI	P value
Male vs female	31.08 (9.81 to 52.36)	0.0046
Age, per 1-year increase	-2.44 (-3.46 to -1.42)	< 0.0001
Education level
Junior high school or below	Reference
Senior high school	-19.95 (-48.87 to 8.97)	0.1778
College or above	2.39 (-25.48 to 30.26)	0.8666
SBP, per 1 mmHg increase	0.42 (-0.11 to 0.95)	0.1222
DBP, per 1 mmHg increase	1.27 (0.26 to 2.27)	0.0141
Height, per 1 cm increase	1.74 (0.41 to 3.08)	0.0111
Weight, per 1 cm increase	1.17 (0.17 to 2.17)	0.0234
BMI, per 1 kg/m2 increase	1.96 (-1.63 to 5.55)	0.2865
Duration of diabetes, per 1-year increase	-0.40 (-1.99 to 1.20)	0.6269
Hypertension vs absent	-2.97 (-24.42 to 18.48)	0.7862
Diabetic nephropathy history vs absent	40.23 (13.83 to 66.64)	0.0031
Stroke history vs absent	2.07 (-46.41 to 50.55)	0.9333
Anemia vs absent	12.80 (-10.31 to 35.91)	0.2788
Heart disease vs absent	-19.42 (-67.84 to 28.99)	0.4325
PRP
None	Reference
Partial	4.02 (-24.99 to 33.03)	0.7861
Whole	31.00 (7.32 to 54.69)	0.0109
Anti-VEGF therapy vs absent	30.55 (6.24 to 54.86)	0.0145
Insulin vs absent	23.81 (2.63 to 44.99)	0.0286
Oral glucose-lowering drugs vs absent	-28.96 (-53.31 to -4.62)	0.0205
Calcium antagonists vs absent	40.49 (14.86 to 66.13)	0.0022
Visual acuity, per 1 LogMAR increase	-12.24 (-32.49 to 8.01)	0.2374
IOP, per 1 mmHg increase	2.27 (-0.32 to 4.86)	0.0876
Fasting blood glucose, per 1 mmol/L increase	-2.34 (-6.06 to 1.39)	0.2201
Serum urea nitrogen, per 1 mmol/L increase	1.63 (-0.81 to 4.06)	0.1910
Serum creatinine, per 1 μmol/L increase	0.08 (0.02 to 0.14)	0.0092
eGFR, per 1 mL/minutes × 1.73m2 increase	-0.15 (-0.50 to 0.20)	0.3938
Uric acid, per 1 mmol/L	-0.01 (-0.14 to 0.11)	0.8322
Triglyceride, per 1 mmol/L increase	-3.01 (-24.36 to 18.34)	0.7828
Total cholesterol, per 1 mmol/L increase	-16.08 (-29.25 to -2.91)	0.0181
HDL-C, per 1 mmol/L increase	-42.66 (-81.44 to -3.89)	0.0329
LDL-C, per 1 mmol/L increase	-15.27 (-30.72 to 0.17)	0.0548
HbA1c, per 1 % increase	-5.36 (-16.77 to 6.04)	0.3590
CMT, per 1 μm increase	0.02 (-0.06 to 0.11)	0.5839
Ocular axial length, per 1 mm increase	-18.57 (-34.96 to -2.18)	0.0282

CI: Confidence interval; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BMI: Body mass index; HbA1c: Hemoglobin A1c; logMAR: Logarithmic minimum resolution angle; IOP: Intraocular pressure; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; eGFR: Estimated glomerular filtration rate; CMT: Central macular thickness; SFCT: Subfoveal choroidal thickness; VEGF: Vascular endothelial growth factor; PRP: Pan-retinal photocoagulation.

Table 3 Relationship between age and subfoveal choroidal thickness in different models

Exposure	Model I		Model II		Model III
	β (95%CI)	P value	β (95%CI)	P value	β (95%CI)	P value
Age (year)	-2.23 (-3.29 to -1.18)	< 0.0001	-1.96 (-3.03 to -0.90)	0.0004	-1.68 (-2.97 to -0.39)	0.0117

Model I adjusted for sex and ocular axial length; Model II adjusted for sex, ocular axial length, anti-vascular endothelial growth factor (VEGF) therapy, pan-retinal photocoagulation (PRP), insulin treatment, oral glucose-lowering drugs, and calcium antagonists; Model III adjusted for sex, ocular axial length, anti-VEGF therapy, PRP, insulin treatment, oral glucose-lowering drugs, calcium antagonists, diastolic blood pressure, hemoglobin A1c, duration of diabetes, serum creatinine, and total cholesterol. CI: Confidence interval; DBP: Diastolic blood pressure; HbA1c: Hemoglobin A1c; SFCT: Subfoveal choroidal thickness; VEGF: Vascular endothelial growth factor; PRP: Pan-retinal photocoagulation.

Table 4 Non-linearity addressed by a two-piecewise linear regression model

For exposure: Age	SFCT (μm)
Outcome, Model	β	95%CI	P value
Fitting model by standardized linear regression	-1.68	-2.97 to -0.39	0.0117
Fitting model by two-piecewise linear regression
Inflection point of age	54.00
≤ 54	2.00	-0.16 to 4.17	0.0712
> 54	-4.89	-6.87 to -2.90	< 0.0001
Log likelihood ratio test			< 0.0010

The adjustment strategy was the same as the adjusted Model III.

Table 5 Results of stratified analysis between age and subfoveal choroidal thickness in patients with proliferative diabetic retinopathy

Y = SFCT, μm	n	β, 95%CI	P value
Gender
Female	99	-0.38 (-2.39 to 1.64)	0.7157
Male	135	-2.63 (-4.51 to -0.74)	0.0074
Hypertension history
No	126	-1.19 (-2.65 to 0.27)	0.1137
Yes	108	-3.27 (-5.42 to -1.12)	0.0037
Education level
Junior high school or below	147	-2.13 (-3.90 to -0.36)	0.0198
Senior high school	40	-0.72 (-4.44 to 3.00)	0.7086
College or above	44	-2.09 (-5.23 to 1.06)	0.2054
Diabetic nephropathy history
No	188	-1.76 (-3.06 to -0.46)	0.0089
Yes	46	-1.29 (-6.51 to 3.94)	0.6341
Stroke history
No	222	-1.48 (-2.80 to -0.16)	0.0294
Yes	12	Not applicable
Heart disease history
No	222	-1.61 (-2.90 to -0.32)	0.0153
Yes	12	Not applicable
Anemia history
No	162	-2.62 (-4.15 to -1.08)	0.0011
Yes	72	1.16 (-1.62 to 3.93)	0.4176
PRP
None	111	0.05 (-1.78 to 1.87)	0.9602
Partial	43	-3.64 (-6.62 to -0.66)	0.0257
Whole	80	-4.56 (-7.00 to -2.11)	0.0006
Anti-VEGF therapy
No	175	-1.03 (-2.56 to 0.50)	0.1891
Yes	59	-3.95 (-6.57 to -1.32)	0.0055
Insulin treatment
No	113	-1.16 (-2.82 to 0.49)	0.1711
Yes	121	-2.34 (-4.42 to -0.25)	0.0304
Oral glucose-lowering drugs
No	59	-2.85 (-5.15 to -0.56)	0.0180
Yes	175	-2.13 (-3.27 to -0.99)	0.0003
Calcium antagonists
No	183	-1.27 (-2.56 to 0.02)	0.0550
Yes	50	-3.00 (-7.47 to 1.48)	0.1993
Total cholesterol group (mmol/L)
< 6.22	119	-1.78 (-3.74 to 0.18)	0.0788
≥ 6.22	12	Not applicable
eGFR group (mL/minutes × 1.73 m2)
< 30	30	-3.83 (-8.33 to 0.68)	0.1198
≥ 30, < 60	61	-3.45 (-7.12 to 0.22)	0.0719
≥ 60, < 90	81	-1.47 (-4.21 to 1.27)	0.2976
≥ 90	62	0.11 (-1.87 to 2.08)	0.9161

Not applicable means that the model failed because of the small sample size. The adjustment strategy for each stratification was identical to that of Model III except for the stratification factor. CI: Confidence interval; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; eGFR: Estimated glomerular filtration rate; SFCT: Subfoveal choroidal thickness; VEGF: Vascular endothelial growth factor; PRP: Pan-retinal photocoagulation.