Foveal Avascular Zone Does Not Correspond to Choroidal Characteristics in Patients with Diabetic Retinopathy: A Single-Center Cross-Sectional Analysis

Figures & data

Figure 1 Representative fluorescein angiograms with FAZ outlines: (A) grade ≤2; (B) grade ≥3 according to the ETDRS report number 11.¹⁵ The same angiograms with FAZ area boundaries and sizes: (C and D).

Figure 2 Representative OCT scan across the fovea. ILM and BM were detected automatically, while the choroidal-scleral junction was marked manually. SFCT was defined as the distance between the BM and the choroidal-scleral junction at the fovea (blue arrow b). The SFCT was obtained as a difference between the total thickness (retinal + choroidal thickness, from the ILM to the choroidal-scleral junction) (yellow arrow c) and the central foveal thickness (red arrow a). Analogically, the choroidal thickness outside the fovea (blue arrow e) was calculated by subtracting the retinal thickness (red arrow d) from the total thickness (retinal + choroidal thickness, from the ILM to the choroidal-scleral junction) (yellow arrow f).

Table 1 Baseline Characteristics of Patients with Diabetic Retinopathy

	Overall	FAZ Outline		p	CSME		p
		Grade ≤2	Grade ≥3		Absent	Present
Number of patients	152	63	89		60	92
Number of eyes	210	93	117		76	134
Age, years, mean ± SD	60.73±12.40	62.18±12.06	59.71±12.61	0.225	60.80±13.01	59.95±12.73	0.704
Sex, female, n (%)	75 (49.3)	28 (44.4)	47 (52.8)	0.395	30 (50.0)	45 (48.9)	>0.999
Spherical equivalent, mean ± SD	0.30±1.02	0.42±0.95	0.20±1.07	0.107	0.14±0.83	0.39±1.11	0.076
DR severity, n (%)
NPDR	135 (64.3)	78 (83.9)	57 (48.7)	<0.001	49 (64.5)	86 (64.2)	>0.999
PDR	75 (35.7)	15 (16.1)	60 (51.3)		27 (35.5)	48 (35.8)
CSME, n (%)
Present	134 (63.8)	55 (59.1)	79 (67.5)	0.267	–	–	–
Absent	76 (36.2)	38 (40.9)	38 (32.5)		–	–
PRP, n (%)
No	138 (65.7)	72 (77.4)	66 (56.4)	0.002	51 (67.1)	87 (64.9)	0.866
Yes	72 (34.3)	21 (22.6)	51 (43.6)		25 (32.9)	47 (35.1)
FAZ area, mm^2, median (Q1; Q3)	0.36 (0.25;0.51)	0.32 (0.10;0.75)	0.41 (0.28;0.59)	<0.001	0.42 (0.29;0.53)	0.35 (0.24;0.49)	0.034
FAZ outline, n, (%)
Grade ≤2	93 (44.3)	–	–	–	38 (50.0)	55 (41.0)	0.267
Grade ≥3	117 (55.7)	–	–		38 (50.0)	79 (59.0)

Notes: Groups compared with the chi-square test for nominal variables and with t-test or Mann–Whitney U-test (FAZ area) for continuous variables.

Abbreviations: FAZ, foveal avascular zone; CSME, clinically significant macular edema; DR, diabetic retinopathy; NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; PRP, panretinal photocoagulation.

Table 2 Choroidal Parameters in Patients with Diabetic Retinopathy

Characteristic	Total Group	FAZ Outline		FAZ Area (mm^2)
		Grade ≤2	Grade ≥3	<0.355	>0.355
Choroidal thickness (µm):
Outer T	246.64±50.99	240.82±56.25	249.76±47.86	251.89±53.55	241.35±47.95
Inner T	256.75±55.06	251.82±62.94	259.37±50.41	261.07±57.61	252.43±52.30
Central macular	260.06±56.19	252.47±64.44	264.11±51.04	262.47±57.14	257.66±55.38
Inner N	250.23±61.33	240.81±65.74	255.25±58.48	252.22±62.24	248.24±60.64
Outer N	222.36±63.89	213.93±65.66	226.85±62.70	224.11±64.34	220.60±63.68
Outer S	263.91±53.76	259.72±59.59	266.14±50.48	267.10±54.62	260.69±52.96
Inner S	265.41±53.13	261.34±62.42	267.58±47.56	267.04±55.08	263.78±51.33
Inner I	254.22±60.01	244.66±66.34	259.32±55.93	256.78±60.65	251.67±59.54
Outer I	243.82±61.14	238.15±64.00	246.91±59.55	248.01±62.11	239.59±60.16
SFCT	260.07±58.57	251.11±64.85	264.85±54.58	263.10±58.59	257.05±58.67
Choroidal volume (mm^3):
Outer T	1.31±0.27	1.28±0.30	1.32±0.25	1.33±0.28	1.28±0.25
Inner T	0.41±0.09	0.40±0.10	0.41±0.08	0.41±0.09	0.40±0.09
Central macular	0.20±0.04	0.20±0.05	0.21±0.04	0.21±0.04	0.20±0.04
Inner N	0.39±0.10	0.38±0.11	0.40±0.09	0.40±0.10	0.39±0.10
Outer N	1.17±0.34	1.13±0.34	1.20±0.33	1.18±0.34	1.16±0.34
Outer S	1.40±0.28	1.38±0.31	1.41±0.27	1.42±0.29	1.38±0.28
Inner S	0.42±0.08	0.41±0.10	0.42±0.07	0.42±0.09	0.41±0.08
Inner I	0.40±0.09	0.38±0.10	0.41±0.09	0.40±0.10	0.40±0.09
Outer I	1.29±0.32	1.26±0.34	1.30±0.31	1.31±0.33	1.26±0.31
Total	6.99±1.49	6.81±1.66	7.09±1.39	7.09±1.52	6.89±1.46
Other choroidal parameters:
CVI	0.59±0.06	0.59±0.06	0.59±0.06	0.59±0.06	0.59±0.05
LA (mm^2)	1.35±0.40	1.27±0.40	1.37±0.38	0.13±0.42	1.34±0.37
SA (mm^2)	0.91±0.23	0.87±0.23	0.94±0.22	0.93±0.24	0.90±0.22
TCA (mm^2)	2.25±0.56	2.13±0.56	2.31±0.55	2.27±0.59	2.23±0.53

Note: Data presented as means ± SD.

Abbreviations: FAZ, foveal avascular zone; T, temporal; I, inferior; N, nasal; S, superior; SFCT, subfoveal choroidal thickness; CVI, choroidal vascularity index; LA, luminal area; SA, stromal area; TCA, total choroidal area; conventional ETDRS grid with nine subfields, central macular field (central field within a 500 µm radius), four inner subfields (within a 500–1500 µm radius) and four outer subfields (within a 1500–3000 µm radius).

Table 3 Univariate Models to Analyze Relationships Between Choroidal Parameters and FAZ Outline in Patients with Diabetic Retinopathy

Characteristic	Univariate Models			Univariate models (Sex, Age, CSME, PRP, DR Severity as Covariates)
	β	SE	p	β	SE	p
Choroidal thickness (µm):
Outer T	5.17	6.93	0.456	−1.79	6.75	0.790
Inner T	2.86	8.04	0.723	−3.92	7.94	0.622
Central macular	9.29	8.01	0.248	2.67	7.93	0.644
Inner N	12.30	8.52	0.150	5.97	8.53	0.485
Outer N	13.38	8.53	0.118	7.97	8.56	0.353
Outer S	2.85	7.56	0.706	−2.54	7.36	0.730
Inner S	7.69	7.50	0.307	1.21	7.46	0.871
Inner I	11.75	8.44	0.165	6.27	8.39	0.456
Outer I	4.20	8.36	0.616	−0.56	8.16	0.945
SFCT	7.41	8.66	0.394	1.94	8.51	0.820
Choroidal volume (mm^3):
Outer T	0.03	0.04	0.422	−0.01	0.04	0.829
Inner T	0.008	0.01	0.522	−0.004	0.01	0.782
Central macular	0.007	0.006	0.264	0.003	0.006	0.638
Inner N	0.02	0.01	0.206	0.01	0.01	0.332
Outer N	0.08	0.04	0.082	0.05	0.04	0.246
Outer S	0.02	0.04	0.705	−0.01	0.04	0.748
Inner S	0.01	0.01	0.367	0.001	0.01	0.908
Inner I	0.02	0.02	0.172	0.009	0.01	0.467
Outer I	0.02	0.04	0.601	−0.002	0.04	0.962
Total	0.25	0.19	0.182	0.10	0.19	0.593
Other choroidal parameters:
CVI	0.003	0.009	0.682	0.004	0.009	0.595
LA (mm^2)	0.04	0.06	0.522	0.006	0.06	0.912
SA (mm^2)	0.02	0.03	0.614	−0.009	0.04	0.810
TCA (mm^2)	0.05	0.08	0.553	−0.008	0.08	0.924

Notes: Only patients with DR were included, 210 eyes (93 eyes with FAZ grade ≤2 and 117 eyes with FAZ grade ≥3). Covariates: age in years, sex (male/female), CSME (absent/present), PRP (no/yes), DR severity (NPDR/PDR).

Abbreviations: β, coefficient from regression model; SE, standard error; CSME, clinically significant macular edema; PRP, panretinal photocoagulation; T, temporal; I, inferior; N, nasal; S, superior; SFCT, subfoveal choroidal thickness; CVI, choroidal vascularity index; LA, luminal area; SA, stromal area; TCA, total choroidal area; conventional ETDRS grid with nine subfields, central macular field (central field within a 500 µm radius), four inner subfields (within a 500–1500 µm radius) and four outer subfields (within a 1500–3000 µm radius).

Table 4 Correlations Between FAZ Area and Choroidal Parameters in Patients with Diabetic Retinopathy Overall and in Patients with CSME and Without

Characteristic	Overall		CSME Absent		CSME Present
	rho	p	rho	p	rho	p
Choroidal thickness (µm):
Outer T	−0.10	0.273	−0.14	0.389	−0.10	0.380
Inner T	−0.11	0.260	−0.17	0.301	−0.07	0.531
Central macular	−0.05	0.618	−0.16	0.331	−0.03	0.815
Inner N	−0.05	0.598	−0.14	0.399	0.01	0.956
Outer N	−0.01	0.876	−0.11	0.487	0.06	0.590
Outer S	−0.06	0.481	−0.14	0.398	−0.01	0.913
Inner S	−0.04	0.699	−0.12	0.454	0.02	0.896
Inner I	−0.04	0.641	−0.14	0.388	0.02	0.893
Outer I	−0.10	0.295	−0.16	0.316	−0.04	0.719
SFCT	−0.04	0.681	−0.09	0.571	−0.02	0.841
Choroidal volume (mm^3):
Outer T	−0.10	0.283	−0.15	0.371	−0.10	0.402
Inner T	−0.07	0.440	−0.11	0.488	−0.05	0.649
Central macular	−0.05	0.559	−0.15	0.341	−0.03	0.784
Inner N	−0.04	0.708	−0.09	0.575	0.01	0.972
Outer N	−0.04	0.695	−0.11	0.482	0.03	0.810
Outer S	−0.06	0.491	−0.14	0.391	−0.01	0.918
Inner S	−0.07	0.435	−0.13	0.438	−0.04	0.717
Inner I	−0.03	0.748	−0.11	0.516	0.02	0.886
Outer I	−0.10	0.295	−0.16	0.318	−0.04	0.727
Total	−0.09	0.316	−0.16	0.345	−0.05	0.680
Other choroidal parameters:
CVI	0.16	0.087	−0.12	0.466	0.27	0.020
LA (mm^2)	0.05	0.622	−0.12	0.478	0.12	0.298
SA (mm^2)	−0.13	0.180	−0.01	0.932	−0.16	0.164
TCA (mm^2)	−0.01	0.908	−0.06	0.721	0.03	0.772

Notes: Only patients with DR were included, solely single eyes, n=116. Since the data set included a single eye from each patient, there was no violation of the independence assumption between observations for correlation analysis.

Abbreviations: rho, Spearman correlation coefficient; CSME, clinically significant macular edema; T, temporal; I, inferior; N, nasal; S, superior; SFCT, subfoveal choroidal thickness; CVI, choroidal vascularity index; LA, luminal area; SA, stromal area; TCA, total choroidal area; conventional ETDRS grid with nine subfields, central macular subfield (central field within a 500 µm radius), four inner subfields (within a 500–1500 µm radius) and four outer subfields (within a 1500–3000 µm radius).

Table 5 Univariate Mixed-Effect Models to Compare Choroidal Parameters in Patients with Diabetic Retinopathy and FAZ Area >0.355 and <0.355mm²

Characteristic	Univariate Models			Univariate Models (Sex, Age, CSME, PRP, DR Severity as Covariates)
	β	SE	p	β	SE	p
Choroidal thickness (µm):
Outer T	−4.30	5.71	0.453	−2.27	5.41	0.675
Inner T	−4.11	6.97	0.556	−0.92	6.62	0.889
Central macular	−2.52	6.75	0.709	0.83	6.44	0.897
Inner N	−5.51	6.99	0.432	−2.52	6.75	0.709
Outer N	0.19	6.88	0.977	2.16	6.63	0.745
Outer S	−2.28	6.25	0.716	0.83	5.91	0.888
Inner S	0.14	6.27	0.983	2.98	6.00	0.620
Inner I	−1.12	6.98	0.872	1.95	6.69	0.771
Outer I	−0.60	6.72	0.929	1.74	6.42	0.787
SFCT	−6.35	7.57	0.403	−2.03	7.16	0.777
Choroidal volume (mm^3):
Outer T	−0.02	0.03	0.504	−0.01	0.03	0.740
Inner T	−0.003	0.01	0.779	0.002	0.01	0.841
Central macular	−0.002	0.005	0.775	0.001	0.005	0.823
Inner N	−0.009	0.01	0.441	−0.004	0.001	0.750
Outer N	0.001	0.03	0.986	0.01	0.03	0.797
Outer S	−0.01	0.03	0.741	0.005	0.03	0.870
Inner S	−0.001	0.01	0.924	0.003	0.009	0.740
Inner I	−0.002	0.01	0.836	0.003	0.01	0.789
Outer I	−0.004	0.03	0.904	0.005	0.03	0.869
Total	−0.03	0.15	0.829	0.02	0.14	0.903
Other choroidal parameters:
CVI	0.006	0.007	0.432	0.009	0.007	0.220
LA (mm^2)	0.02	0.05	0.589	0.04	0.04	0.375
SA (mm^2)	−0.005	0.03	0.878	−0.001	0.03	0.963
TCA (mm^2)	0.03	0.07	0.687	0.05	0.07	0.512

Notes: Only patients with DR were included, 210 eyes (105 eyes with FAZ area <0.355mm² and 105 eyes with FAZ area >0.355mm²). Covariates: age in years, sex (male/female), CSME (absent/present), PRP (no/yes), DR severity (NPDR/PDR).

Abbreviations: β, coefficient from regression model; SE, standard error; CSME, clinically significant macular edema; PRP, panretinal photocoagulation; T, temporal; I, inferior; N, nasal; S, superior; SFCT, subfoveal choroidal thickness; CVI, choroidal vascularity index; LA, luminal area; SA, stromal area; TCA, total choroidal area; conventional ETDRS grid with nine subfields, central macular subfield (central field within a 500 µm radius), four inner subfields (within a 500–1500 µm radius) and four outer subfields (within a 1500–3000 µm radius).

Early Treatment Diabetic Retinopathy Study Research Group. Classification of diabetic retinopathy from fluorescein angiograms. ETDRS report number 11. Ophthalmology . 1991;98(5 Suppl):807–822. doi:10.1016/S0161-6420(13)38013-0 2062514

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