Significance of Early Visual Responses to Anti-Vascular Endothelial Growth Factor in Age-related Macular Degeneration

Hee Jun Song; Ji Ho Yang; Do Gyun Kim

doi:10.3341/jkos.2018.59.11.1030

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Song, Yang, and Kim: Significance of Early Visual Responses to Anti-Vascular Endothelial Growth Factor in Age-related Macular Degeneration

Original Article

J Korean Ophthalmol Soc 2018;59(11):1030-1038.

Published online: 25 September 2018

DOI: https://doi.org/10.3341/jkos.2018.59.11.1030

Significance of Early Visual Responses to Anti-Vascular Endothelial Growth Factor in Age-related Macular Degeneration

Hee Jun Song, MD, Ji Ho Yang, MD, Do Gyun Kim, MD, PhD

Department of Ophthalmology, Myongji Hospital, Goyang, Korea

Address reprint requests to Do Gyun Kim, MD, PhD Department of Ophthalmology, Myongji Hospital, #55 Hwasu-ro 14beon-gil, Deokyang-gu, Goyang 10475, Korea Tel: 82-31-810-6250, Fax: 82-31-810-0500 E-mail: Kimdk89@empas.com

Received 12 July 2018 Revised 10 August 2018 Accepted 22 October 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To evaluate whether early visual acuity response at 4 weeks after the first intravitreal anti-vascular endothelial growth factor (VEGF) injection or 4 weeks after the third injection in neovascular age-related macular degeneration (nAMD) is associated with 12-month follow-up outcome.

Methods

Thirty treatment-naive patients (30 eyes) with nAMD, treated with intravitreal anti-VEGF, were retrospectively included. Initially, all patients were injected at least three times for three consecutive months and followed up with a pro re nata regimen for at least 12 months. The relationship between 4 weeks after the first and third anti-VEGF injections in visual acuity response was explored, including the mean change from baseline in best-corrected visual acuity (BCVA). The mean change in BCVA was classified into three groups according to visual improvement: <1, 1‒<3, or ≥ 3 logMAR line(s) in BCVA. The associations among baseline characteristics (gender, age, duration of symptoms, initial BCVA, central macular thickness, and intraocular pressure) and visual acuity responses 4 weeks after the first and third anti-VEGF injections were also assessed.

Results

The proportions of eyes with <1, 1–<3, and ≥ 3-line(s) improvement at 4 weeks after the first injection were 6 eyes (20%), 7 eyes (23.3%), and 17 eyes (56.6%), respectively. The proportions of eyes with <1, 1–<3, and ≥ 3-line(s) improvement at 4 weeks after the third injection were 9 eyes (30%), 9 eyes (30%), and 12 eyes (40%), respectively. A BCVA response ≥3-lines improvement at 4 weeks after the third injection showed significant associations with ≥ 3-lines improvement and BCVA response at 12 months in multiple logistic and linear regression analyses (p = 0.04).

Conclusions

In this study, BCVA response ≥ 3-lines improvement at 4 weeks after the third injection showed a significant association with ≥ 3-lines improvement and BCVA response at 12 months.

Keywords: Anti-vascular endothelial growth factor, Early response, Neovascular age-related macular degeneration, Visual response

References

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Figure 1.

The visual acuity (VA) response category (≥3 line improvement, 1-<3 line improvement, <1 line improvement) at year 1 by the early VA response category at 1 month after 1st anti-VEGF injection or at 1 month after 3rd anti-VEGF injection. VA response category at 1 year by VA response at 1 month after 1st anti-VEGF injection (A), and VA response category at 1 year by VA response at 1 month after 3rd anti-VEGF injection (B). VEGF = vascular endothelial growth factor.

Table 1.

Distribution of initial 3 consecutive intravitreal anti-VEGF injections, categorized by additional anti-VEGF injections

	Additional anti-VEGF injections
	No	Ranibizumab	Aflibercept	Bevacizumab
Initial anti-VEGF injections
Ranibizumab	16 (53.3)	12 (75)	4 (25)	0 (0)
Aflibercept	11 (36.7)	4 (36.4)	7 (63.6)	0 (0)
Bevacizumab	3 (10.0)	2 (66.7)	0 (0)	1 (33.3)
Total	30 (100)	18 (60.0)	11 (36.7)	1 (3.3)

Values are presented as number (%).

VEGF = vascular endothelial growth factor.

Table 2.

Demographics and baseline characteristics of pooled study eyes, categorized by BCVA response at 1 month after the 1st an-ti-VEGF injection

	BCVA changes from baseline at 1 month after the first anti-VEGF injection			p-value
	<1 line improvement (n = 6)	1-<3 line improvement (n = 7)	≥3 line improvement (n = 17)	p-value
Gender (male/female)	4/2	4/3	10/7	0.78^*
Age (years)	68.50 ± 8.31	72.85 ± 5.84	74.17 ± 4.79	0.14^†
Duration of symptom (months)	2.00 ± 0.89	2.42 ± 1.13	1.70 ± 0.68	0.17^†
Baseline BCVA (logMAR)	0.56 ± 0.16	0.56 ± 0.13	0.57 ± 0.16	0.61^†‡
Baseline CMT (μ m)	387.11 ± 52.93	407.35 ± 42.34	422.10 ± 33.42	0.35^†
IOP (mmHg)	12.72 ± 3.43	13.21 ± 1.62	12.94 ± 2.15	0.47^†

Values are presented as mean ± SD unless otherwise indicate. BCVA = best-corrected visual acuity; VEGF = vascular endothelial growth factor; logMAR = logarithm of the minimal angle of resolution; CMT = central macular thickness; IOP = intraocular pressure.

^* Pearson's chi-square test

^† One way analysis of variance (ANOVA) test

^‡ Post-hoc test (Tukey method) between group comparison. <1 line improvement vs. ≥3 lines improvement, p = 0.98. 1-<3 line improvement vs. ≥3 lines improvement, p = 0.98.

Table 3.

Demographics and baseline characteristics of pooled study eyes, categorized by BCVA response at 1 month after the 3rd an-ti-VEGF injection

	BCVA changes from baseline at 1 month after the third anti-VEGF injection			p-value
	<1 line improvement (n = 9)	1-<3 line improvement (n = 9)	≥3 line improvement (n = 12)	p-value
Gender (male/female)	5/3	6/3	7/6	0.16^*
Age (years)	74.11 ± 5.75	73.00 ± 6.24	71.50 ± 6.38	0.73^†
Duration of symptom (months)	1.55 ± 0.52	1.88 ± 0.92	2.16 ± 0.93	0.29^†
Baseline BCVA (logMAR)	0.34 ± 0.08	0.51 ± 0.07	0.63 ± 0.06	0.11^†‡
Baseline CMT (μ m)	418.11 ± 25.47	415.00 ± 41.48	402.08 ± 52.14	0.35^†
IOP (mmHg)	13.21 ± 3.33	12.43 ± 1.42	12.92 ± 2.22	0.53^†

^* Pearson's chi-square test

^† One way analysis of variance (ANOVA) test

^‡ Post-hoc test (Tukey method) between group comparison. <1 line improvement vs. ≥3 lines improvement, p = 0.45. 1-<3 line improvement vs. ≥3 lines improvement, p = 0.98.

Table 4.

Association of visual acuity response at 1 month after 1st anti-VEGF injection or at 1 month after 3rd anti-VEGF injection with visual acuity response at year 1

Visual acuity change	No	Visual acuity change from baseline at year 1
Visual acuity change	No	<1 line improvement	1-<3 line improvement	≥3 line improvement
From baseline at 1 month after 1st anti-VEGF injection
<1 line improvement	6	3 (50.0)	2 (33.3)	1 (16.6)
1-<3 line improvement	7	2 (28.5)	4 (57.1)	1 (14.2)
≥3 line improvement	17	5 (29.4)	5 (29.4)	7 (41.1)
Total	30	10 (33.3)	11 (36.6)	9 (30.0)
From baseline at 1 month after 3rd anti-VEGF injection
<1 line improvement	9	4 (44.4)	3 (33.3)	2 (22.2)
1-<3 line improvement	9	4 (44.4)	4 (44.4)	1 (11.1)
≥3 line improvement	12	2 (16.6)	2 (16.6)	8 (66.6)
Total	30	10 (33.3)	9 (30)	11 (36.6)

Values are presented as number (%).

VEGF = vascular endothelial growth factor.

Table 5.

Logistic regression analysis of 3 lines or more visual improvement at 12 months

	Logistic regression of ≥3 lines improvement in BCVA at 12 months
	Univariated		Multivariated
	Odds ratio	p-value^*	Odds ratio	p-value^*
Age (years)	0.05	0.72
Male:Female	2.22	0.45
Baseline BCVA (logMAR)	0.15	0.62
Baseline CMT (μ m)	0.99	0.43
BCVA change ≥3 lines at 1 month after first anti-VEGF injection	12.29	0.50	19.26	0.13
BCVA change ≥3 lines at 1 month after third anti-VEGF injection	886.54	0.04	25.66	0.02
Cumulative number of anti-VEGF injection	2.00	0.24
Symptom duration	0.53	0.24

BCVA = best-corrected visual acuity; logMAR = logarithm of the minimal angle of resolution; CMT = central macular thickness; VEGF = vascular endothelial growth factor.

^* Univariate logistic regression

^† Multivariate logistic regression.

Table 6.

Linear regression analysis of changes from baseline in BCVA at 12 months

	Linear regression of BCVA response at 12 months
	Univariated		Multivariated
	Estimate^*	p-value^†	Estimate^*	p-value^‡
Age (years)	−0.06	0.75	0.03	0.18
Male:Female	−0.23	0.21	−0.13	0.48
Baseline BCVA (logMAR)	0.33	0.07	0.12	0.57
Baseline CMT (μ m)	−0.97	0.60	0.01	0.84
BCVA change ≥3 lines at 1 month after first anti-VEGF injection	0.20	0.27	0.08	0.66
BCVA change ≥3 lines at 1 month after third anti-VEGF injection	0.58	0.01	0.52	0.02
Cumulative number of anti-VEGF injection	0.11	0.54	0.04	0.80
Symptom duration	0.14	0.44	−0.09	0.61

BCVA = best-corrected visual acuity; logMAR = logarithm of the minimal angle of resolution; CMT = central macular thickness; VEGF = vascular endothelial growth factor.

^* β-coefficient

^† Univariate logistic regression

^‡ Multivariate linear regression.

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