One-year outcome of intravitreal aflibercept injection for age-related macular degeneration resistant to ranibizumab: rapid morphologic recovery and subsequent visual improvement

Figures & data

Figure 1 The efficacy of aflibercept for treating AMD resistant to ranibizumab (patient 3 with occult CNV).

Notes: A fundus photograph at baseline (A) and SD-OCT images prior to the initial IVR injection (B), at baseline (C), 1 month after the initial IVA injection (D), 3 months after the initial IVA injection (E), and 12 months after the initial IVA injection (F) in a 66-year-old man with occult CNV are shown. Marked SRF and a slight PED have improved at 1-month follow-up examination, and the retinal structure has been maintained over 12 months.
Abbreviations: AMD, age-related macular degeneration; CNV, choroidal neovascularization; IVA, intravitreal aflibercept; IVR, intravitreal ranibizumab; PED, pigment epithelial detachment; SD-OCT, spectral domain optical coherence tomography; SRF, subretinal fluid.

Figure 2 The efficacy of aflibercept for AMD refractory to ranibizumab (patient 8 with PCV).

Notes: A fundus photograph at baseline (A) and SD-OCT images prior to the initial IVR injection (B), at baseline (C), 1 month after the initial IVA injection (D), 3 months after the initial IVA injection (E), and 12 months after the initial IVA injection (F) in a 72-year-old man with PCV are shown. Slight SRF and prominent subfoveal PED have resolved completely at 1-month follow-up examination, and the improved anatomic condition has been maintained over 12 months.
Abbreviations: AMD, age-related macular degeneration; IVA, intravitreal aflibercept; IVR, intravitreal ranibizumab; PCV, polypoidal choroidal vasculopathy; PED, pigment epithelial detachment; SD-OCT, spectral domain optical coherence tomography; SRF, subretinal fluid.

Table 1 Demographics of 14 patients with AMD

Patient number	Age	Sex	Eye	AMD subtype	Number of previous IVR injections	Number of IVA injections over 12 months
1	82	M	R	Occult CNV	4	6
2	70	M	R	Occult CNV	12	8
3	66	M	L	Occult CNV	9	8
4	83	M	R	Occult CNV	9	7
5	95	F	L	Occult CNV	5	11
6	83	F	L	Occult CNV	6	7
7	96	M	L	Occult CNV	10	6
8	72	M	R	PCV	27	5
9	76	F	L	PCV	6	7
10	70	M	R	PCV	10	10
11	77	F	R	PCV	12	4
12	66	F	L	PCV	41	12
13	74	M	R	PCV	15	7
14	78	M	R	PCV	7	10
Mean ± SD	77.7±9.4				12.4±10.0	7.7±2.3

Abbreviations: AMD, age-related macular degeneration; CNV, choroidal neovascularization; IVA, intravitreal aflibercept; IVR, intravitreal ranibizumab; PCV, polypoidal choroidal vasculopathy; SD, standard deviation; L, left; R, right; M, male; F, female.

Figure 3 The efficacy of aflibercept assessed based on the visual acuity and central macular thickness in 14 patients with AMD (seven patients with occult CNV and seven subjects with PCV).

Notes: The efficacy of aflibercept is assessed based on visual acuity converted to logMAR (A) and the central macular thickness measured by SD-OCT (B). Data obtained at 1 month (1 M), 3 months (3 M), 6 months (6 M), and 12 months (12 M) after the first IVA injection are compared with baseline data. Subcategorical data based on the subtype classifications are also demonstrated (seven patients with occult CNV and seven subjects with PCV). The line charts of the mean data for occult CNV, PCV, and the total cohort are shown in different colors. Statistical significance was defined as P<0.05. Asterisks indicate significant differences (Wilcoxon signed-rank test, ^*=occult CNV, ^**=PCV, ^***=total cohort).
Abbreviations: AMD, age-related macular degeneration; CNV, choroidal neovascularization; IVA, intravitreal aflibercept; logMAR, logarithm of minimum angle of resolution; PCV, polypoidal choroidal vasculopathy; SD-OCT, spectral domain optical coherence tomography.

Table 2 Best-corrected visual acuity of 14 patients treated with IVA injection

Patient number	AMD subtype	BCVA (logMAR)
		Baseline	1 month	3 months	6 months	12 months
1	Occult CNV	0.52	0.52	0.40	0.40	0.30
2	Occult CNV	0.52	0.70	0.52	0.40	0.52
3	Occult CNV	0.40	0.40	0.40	0.40	0.40
4	Occult CNV	0.22	0.10	0.00	0.15	0.30
5	Occult CNV	0.52	0.52	0.30	0.22	0.40
6	Occult CNV	0.40	0.30	0.30	0.22	0.40
7	Occult CNV	1.00	1.00	0.82	NA	1.10
Mean ± SD (Pt 1–7)		0.51±0.24	0.50±0.29	0.39±0.25	0.30±0.11	0.49±0.28
P-value			P=0.462	P=0.028*	P=0.027*	P=0.397
8	PCV	0.15	0.10	0.05	0.22	0.00
9	PCV	0.15	0.15	0.00	0.05	0.00
10	PCV	0.05	0.05	0.00	−0.08	−0.08
11	PCV	0.30	0.22	0.15	NA	0.15
12	PCV	0.40	0.52	0.40	0.40	0.52
13	PCV	0.82	0.70	0.70	0.70	0.70
14	PCV	0.15	0.15	0.00	0.10	0.00
Mean ± SD (Pt 8–14)		0.29±0.26	0.27±0.24	0.19±0.27	0.23±0.28	0.18±0.30
P-value			P=0.248	P=0.028*	P=0.116	P=0.027*
Mean ± SD (Pt 1–14)		0.40±0.27	0.39±0.28	0.29±0.27	0.26±0.21	0.34±0.32
P-value			P=0.209	P=0.002*	P=0.006*	P=0.018*

Notes: Statistical analysis was performed with the Wilcoxon signed-rank test.

* Significant difference was defined as P<0.05 comparing BCVA (logMAR) at each visit with baseline.

Abbreviations: AMD, age-related macular degeneration; BCVA, best-corrected visual acuity; CNV, choroidal neovascularization; IVA, intravitreal aflibercept; logMAR, logarithm of the minimum angle of resolution; NA, not applicable; PCV, polypoidal choroidal vasculopathy; Pt, patient; SD, standard deviation.

Table 3 Central macular thickness of 14 patients treated with IVA

Patient number	AMD subtype	CMT (μm)
		Baseline	1 month	3 months	6 months	12 months
1	Occult CNV	330	222	226	225	225
2	Occult CNV	397	214	185	NA	NA
3	Occult CNV	315	185	180	259	181
4	Occult CNV	297	306	305	265	251
5	Occult CNV	245	226	217	239	219
6	Occult CNV	322	272	264	278	262
7	Occult CNV	219	202	198	NA	183
Mean ± SD (Pt 1–7)		303.1±59.0	232.4±42.1	225.0±45.4	253.2±21.1	220.2±33.6
P-value			P=0.028*	P=0.028*	P=0.043*	P=0.028*
8	PCV	214	194	186	220	187
9	PCV	246	170	NA	202	174
10	PCV	NA	NA	NA	NA	NA
11	PCV	304	210	207	NA	250
12	PCV	184	165	175	213	179
13	PCV	175	156	155	151	144
14	PCV	306	196	282	222	243
Mean ± SD (Pt 8–14)		238.2±57.5	181.8±21.1	201.0±49.0	201.6±29.3	196.2±41.7
P-value			P=0.027*	P=0.043*	P=0.345	P=0.028*
Mean ± SD (Pt 1–14)		273.2±65.2	209.1±42.0	215.0±46.4	227.4±36.3	208.2±38.2
P-value			P=0.002*	P=0.003*	P=0.028*	P=0.002*

Notes: Statistical analysis was performed with the Wilcoxon signed rank test.

* Significant difference was defined as P<0.05 comparing CMT at each visit with baseline.

Abbreviations: AMD, age-related macular degeneration; CMT, central macular thickness; CNV, choroidal neovascularization; NA, not applicable; PCV, polypoidal choroidal vasculopathy; Pt, patient; SD, standard deviation.

Table 4 Anatomical response to IVA treatment in 14 patients with AMD

Patient number	AMD subtype	Baseline		1 month		3 months		6 months		12 months		Complete resolution of SRF/PED (month)	Anatomic improvement assessed by OCT
		SRF	PED	SRF	PED	SRF	PED	SRF	PED	SRF	PED
1	Occult CNV	++	++	−	−	−	−	−	−	−	−	+/+ (1/1)	+
2	Occult CNV	++	++	+	−	−	+	−	−	−	−	+/+ (3/1)	+
3	Occult CNV	++	++	−	++	−	−	+	+	−	−	+/+ (1/3)	+
4	Occult CNV	++	++	+	+	+	+	−	+	−	+	+/− (6/−)	+
5	Occult CNV	−	++	−	+	−	+	+	+	−	+	*/−	+
6	Occult CNV	++	++	−	+	−	+	+	+	+	+	+/− (1/−)	+
7	Occult CNV	++	++	−	+	−	+	NA	NA	−	−	+/+ (1/12)	+
8	PCV	−	++	−	−	−	−	+	+	−	−	*/+ (*/1)	+
9	PCV	++	++	−	−	−	−	+	+	−	−	+/+ (1/1)	+
10	PCV	++	++	−	+	−	+	−	+	−	+	+/− (1/−)	+
11	PCV	++	++	−	−	−	−	NA	NA	−	−	+/+ (1/1)	+
12	PCV	−	++	−	+	−	+	−	+	−	+	*/−	+
13	PCV	++	++	−	−	−	−	−	−	−	−	+/+ (1/1)	+
14	PCV	++	++	+	+	+	+	+	+	+	+	−/−	+

Notes: Anatomic response was determined with spectral domain optical coherence tomography by assessing change in subretinal fluid or subretinal pigment epithelial fluid. SRF and PED observed by OCT: ++ = detected at baseline/− = not detected at baseline; ++ = no change, + = improved (from ++) or newly appeared (from −), − = not detected at 1, 3, 6, and 12 months. Anatomic OCT change: + = improved. Complete resolution of SRF/PED: + = completely resolved, − = not completely resolved,

* = not detectable at baseline.

Abbreviations: AMD, age-related macular degeneration; CNV, choroidal neovascularization; IVA, intravitreal aflibercept; PCV, polypoidal choroidal vasculopathy; PED, pigment epithelial detachment; OCT, optical coherence tomography; SRF, subretinal fluid.