Effects of Intravitreous Aflibercept Injection in Pachychoroid Neovasculopathy: Comparison with Typical Neovascular Age-Related Macular Degeneration

Figures & data

Figure 1 Treatment protocol. Intervention schedule for patients with pachychoroid neovasculopathy and neovascular age-related macular degeneration.

Aflibercept injection (2 mg);

clinical data collection;

efficacy endpoint.

Table 1 Patient Characteristics at Baseline and 12 Months After Intravitreous Injection of Aflibercept

	Pachychoroid Neovasculopathy			Neovascular AMD
	Baseline	12 Months	P value	Baseline	12 Months	P value
Age, years	74.4 ± 8.1			78.5 ± 7.3
Sex (male/female)	22/5			37/26
Number of eyes	27			63
BCVA, logMAR (range)	0.28 (0.13–0.44)	0.14 (0.11–0.27)	0.001*	0.40 (0.31–0.50)	0.29 (0.19–0.39)	< 0.001*
GLD, µm (range)	3294 ± 1649 (2642–3947)	3033 ± 1729 (2350–3717)	0.090*	3885 ± 1739 (3447–4323)	3356 ± 1569 (2961–3751)	0.001*
Lesion size, mm2 (range)	5.17 ± 3.92 (3.62–6.72)	5.01 ± 4.76 (3.13–6.89)	0.811*	9.95 ± 13.18 (6.63–13.27)	6.08 ± 5.46 (4.70–7.45)	0.013*
CRT, µm (range)	346 ± 132 (294–399)	197 ± 56 (174–219)	< 0.001*	380 ± 180 (335–426)	206 ± 119 (176–236)	< 0.001*
SFCT, µm (range)	338 ± 66 (312–364)	303 ± 81 (271–335)	< 0.001*	223 ± 90 (200–246)	192 ± 88 (170–215)	< 0.001*
Intact foveal ELM (±)	13/14	21/6	0.008**	18/45	30/33	0.004**
Intact foveal EZ (±)	1/26	12/15	0.001**	5/58	13/50	0.021**
Vitreoretinal adhesion (±)	5/22	3/24	0.500**	16/47	12/51	0.289**
Presence of polyps (±)	13/14	5/22	0.039**	32/31	14/49	< 0.001**

Notes: Data are presented as mean ± standard deviation or number of patients. *Paired t-test, **McNemar’s test.

Abbreviations: AMD, age-related macular degeneration; BCVA, best-corrected visual acuity; logMAR, logarithm of minimal angle of resolution; GLD, greatest lesion diameter; CRT, central retinal thickness; SFCT, subfoveal choroidal thickness; ELM, external limiting membrane; EZ, ellipsoid zone.

Table 2 Comparison of Baseline Characteristics Between Patients with Pachychoroid Neovasculopathy and Neovascular AMD

	Pachychoroid Neovasculopathy	Neovascular AMD	P value
Age, years	74.4 ± 8.1	78.5 ± 7.3	0.023*
Sex (male/female)	22/5	37/26	0.037**
BCVA logMAR	0.28 ± 0.39	0.40 ± 0.38	0.709^†
GLD, µm	3294 ± 1649	3885 ± 1739	0.123^†
Lesion size, mm2	5.17 ± 3.92	9.95 ± 13.18	0.245^†
CRT, µm	346 ± 132	380 ± 180	0.839^†
SFCT, µm	338 ± 66	223 ± 90	<0.001^†
Intact foveal ELM (±)	13/14	18/45	0.073**
Intact foveal EZ (±)	1/26	5/58	0.461**
Vitreoretinal adhesion (±)	5/22	16/47	0.480**
Presence of Polyps (±)	13/14	32/31	0.818**

Notes: Data are presented as mean ± standard deviation or number of patients. *Unpaired t-test, **Chi-square test, ^†ANCOVA (adjusted for age and sex).

Abbreviations: AMD, age-related macular degeneration; BCVA, best-corrected visual acuity; logMAR, logarithm of minimal angle of resolution; GLD, greatest lesion diameter; CRT, central retinal thickness; SFCT, subfoveal choroidal thickness; ELM, external limiting membrane; EZ, ellipsoid zone.

Figure 2 A case with pachychoroid neovasculopathy (before treatment). Images of the left eye of a 70-year-old man with pachychoroid neovasculopathy without any treatment history. The best-corrected visual acuity was 20/50. (A) Color fundus photograph shows subretinal hemorrhage and serous retinal detachment. Note that drusen are absent. (B) Optical coherence tomography (OCT) angiography image shows choroidal neovascularization (CNV). (C) Late-phase fluorescein angiography image shows leakage suggesting occult CNV. (D) Late-phase indocyanine green angiography image. (E) Enhanced-depth imaging OCT image shows serous retinal detachment and elevation of the retinal pigment epithelium, suggesting CNV. The choroid is thick throughout the macula, and choroidal vessels are dilated. Subfoveal choroidal thickness = 387 μm, central retinal thickness = 317 μm.

Figure 3 A case with pachychoroid neovasculopathy (after treatment). Images of the same patient as in Figure 2, acquired 12 months after initial treatment. The best-corrected visual acuity had improved to 20/16. (A) Color fundus photograph shows resolution of subretinal hemorrhage and serous retinal detachment. (B) Optical coherence tomography (OCT) angiography image shows choroidal neovascularization. (C) Late-phase fluorescein angiography image shows reduction of leakage. (D) Late-phase indocyanine green angiography image. (E) Enhanced-depth imaging OCT image shows resolution of serous retinal detachment. Subfoveal choroidal thickness = 348 μm, central retinal thickness = 206 μm.

Table 3 Changes in Visual Acuity, Subfoveal Choroidal Thickness, and Central Retinal Thickness During Intravitreal Aflibercept Injection Treatment for Pachychoroid Neovasculopathy

	Baseline	3 Months	6 Months	9 Months	12 Months	Difference Between Baseline and 12 Months (95% CI)	P value*
BCVA, logMAR
Mean ± SD	0.28 ± 0.39	0.17 ± 0.32	0.15 ± 0.31	0.14 ± 0.35	0.14 ± 0.33	0.14 (0.06–0.21)	<0.001
Median	0.15	0.05	0.05	0.10	0.10
Subfoveal choroidal thickness, µm
Mean ± SD	338 ± 66	301 ± 85	307 ± 76	299 ± 81	303 ± 81	35 (16–51)	<0.001
Median	341	315	328	313	315
Decrease from baseline (%)		10.9	9.3	11.5	10.3
Central retinal thickness, µm
Mean ± SD	346 ± 132	217 ± 127	207 ± 65	193 ± 59	197 ± 56	149 (91–208)	<0.001
Median	317	183	203	184	191
Decrease from baseline (%)		37.2	40.4	44.2	43.2

Note: *Repeated measures ANOVA.

Abbreviations: CI, confidence interval; BCVA, best-corrected visual acuity; logMAR, logarithm of minimal angle of resolution; SD, standard deviation.

Table 4 Changes in Visual Acuity, Subfoveal Choroidal Thickness, and Central Retinal Thickness During Intravitreal Aflibercept Injection Treatment for Neovascular Age-Related Macular Degeneration

	Baseline	3 Months	6 Months	9 Months	12 Months	Difference Between Baseline and 12 Months (95% CI)	P value*
BCVA, logMAR
Mean ± SD	0.40 ± 0.38	0.33 ± 0.41	0.32 ± 0.41	0.31 ± 0.42	0.29 ± 0.41	0.12 (0.05–0.17)	<0.001
Median	0.30	0.30	0.22	0.22	0.15
Subfoveal choroidal thickness (µm)
Mean ± SD	223 ± 90	193 ± 88	193 ± 88	189 ± 88	192 ± 88	30 (23–37)	<0.001
Median	210.5	167.5	166.5	171	177
Decrease from baseline (%)		13.4	13.7	15.1	13.7
Central retinal thickness (µm)
Mean ± SD	380 ± 180	202 ± 105	190 ± 85	190 ± 84	206 ± 119	174 (130–218)	<0.001
Median	338	174	164	170	172
Decrease from baseline (%)		46.9	49.9	50.1	45.8

Note: *Repeated measures ANOVA.

Abbreviations: CI, confidence interval; BCVA, best-corrected visual acuity; logMAR, logarithm of minimal angle of resolution; SD, standard deviation.

Table 5 Patients Classified with Pachychoroid Neovasculopathy

	Polypoidal Lesion (+) Group (n=11)	Polypoidal Lesion (–) Group (n=16)	P value
Gender (men/women)	10/1	12/4	0.618**
Age (years), mean ± SD	69.9 ± 8.6	73.3 ± 7.2	0.417*
Initial conditions
BCVA (logMAR), mean ± SD	0.22 ± 0.26	0.35 ± 0.44	0.480*
Lesion area (mm2), mean ± SD	2.99 ± 2.77	5.18 ± 4.13	0.030*
GLD (µm), mean ± SD	2602 ± 1398	3686 ± 1611	0.094*
CRT (µm), mean ± SD	349.7 ± 99.3	343.7 ±147.1	0.911*
SFCT (µm), mean ± SD	338.1 ± 48.7	338.3 ± 74.2	0.993*
Final conditions
BCVA (logMAR), mean ± SD	−0.01 ± 0.16	0.25 ± 0.36	0.042*
CRT (µm), mean ± SD	174.2 ± 26.1	212.1 ± 63.8	0.085*

Notes: *Unpaired t-test, **Chi-square test.

Abbreviations: SD, standard deviation; BCVA, best-corrected visual acuity; GLD, greatest linear dimension; CRT, central retinal thickness; SFCT, subfoveal choroidal thickness.

Table 6 Prevalence of Dry Macula in Patients with Pachychoroid Neovasculopathy and AMD Treated with Aflibercept

	3 Months	6 Months	9 Months	12 Months
Overall (95% CI)	0.66 (0.56–0.76)	0.71 (0.57–0.77)	0.75 (0.66–0.85)	0.70 (0.60–0.79)
Pachychoroid Neovasculopathy	0.66 (0.48–0.86)	0.74 (0.56–0.92)	0.81 (0.66–0.97)	0.77 (0.61–0.95)
Neovascular AMD	0.66 (0.55–0.79)	0.69 (0.58–0.81)	0.73 (0.62–0.84)	0.68 (0.56–0.80)

Abbreviations: AMD, age-related macular degeneration; CI, confidence interval.