Significance of Early Visual Responses to Bevacizumab for Macular Edema in Branch Retinal Vein Occlusion

Ryu Gahyung; Noh Donghyoun; Lee Junyeop; Sagong Min

doi:10.3341/jkos.2017.58.8.937

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Gahyung, Donghyoun, Junyeop, and Min: Significance of Early Visual Responses to Bevacizumab for Macular Edema in Branch Retinal Vein Occlusion

Original Article

J Korean Ophthalmol Soc 2017;58(8):937-946.

Published online: 8 September 2017

DOI: https://doi.org/10.3341/jkos.2017.58.8.937

Significance of Early Visual Responses to Bevacizumab for Macular Edema in Branch Retinal Vein Occlusion

Ryu Gahyung, M.D., Noh Donghyoun, M.D., Lee Junyeop, M.D., PhD, Sagong Min, M.D., PhD

Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea

Address reprint requests to Min Sagong, MD, PhD Department of Ophthalmology, Yeungnam University Hospital,#170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea Tel: 82-53-620-3443, Fax: 82-53-626-5936 E-mail: msagong@ynu.ac.kr

* Conflicts of Interest: The authors have no conflicts to disclose.

Received 23 March 201716 May 2017 Accepted 17 July 2017

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 determine whether early visual acuity response to intravitreal bevacizumab in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) is associated with 12-month follow-up outcome.

Methods

Sixty treatment-naïve patients (60 eyes) with ME secondary to BRVO treated with intravitreal bevacizumab (1.25 mg) were retrospectively included. Initially, all patients were injected monthly to achieve fluid resolution and followed up with a pro re nata regimen for at least 12 months. The relationship between early (month 1) and late (month 12) visual acuity response (mean change from baseline in best-corrected visual acuity [BCVA]; categorized improvement [<1, 1‒3, or ≥3 logMAR lines in BCVA]) was explored.

Results

The proportions of eyes with <1, 1-<3, and ≥3-line improvements at 1 month were 19 eyes (31.7%), 17 eyes (28.3%), and 24 eyes (40%), respectively. Within each of the three response categories, the mean BCVA change from baseline at 12 months and onward did not vary by more than 1 line from the observed mean BCVA improvement at 1 month. Inter-cohort differ-ences across the three response categories in mean BCVA change from baseline were statistically significant at each time point. Early BCVA response at 1 month showed significant associations with ≥3 line improvement and BCVA response at 12 months in multiple logistic and linear regression analyses.

Conclusions

Early BCVA responses to bevacizumab are associated with subsequent responses over the entire 12-month duration of treatment.

Keywords: Bevacizumab, Branch retinal vein occlusion, Early response, Macular edema, Visual response

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Figure 1.

Mean best-corrected visual acuity (BCVA) changes from baseline over time, categorized by BCVA response at 1 month after the first bevacizumab injection. Within the groups, the mean BCVA changes from baseline did not vary by more than 1 line af-ter 1 month over the entire period. Inter-co-hort differences were significant at each time point. Post-hoc test (Tukey method) between group comparison. <1 line im-provement vs. ≥3 lines Improvement, p < 0.001, at each time point. 1-<3 line im-provement vs. ≥3 lines Improvement, p < 0.001, p = 0.016, p = 0.022, p = 0.011.

Figure 2.

Frequency distribution of best-corrected visual acuity (BCVA) improvement, categorized by BCVA response at 1 month. (A) Within the subset of eyes with < 1 line BCVA improvement at 1 month, approx-imately one-third of eyes continued to show < 1 line BCVA improve-ment at each time point. (B) Within the subset of eyes with 1 -< 3 lines BCVA improvement at 1 month, most eyes showed ≥ 1 line BCVA improvement at each time point. (C) Within the subset of eyes with a pro-nounced initial BCVA response (≥ 3 lines improvement) at 1 month, most eyes maintained this response over the entire period.

Figure 3.

Mean central macular thickness (CMT) over time, categorized by best-cor-rected visual acuity response at 1 month after the first bevacizumab injection. There were no inter-cohort differences in mean CMT at each time point (p = 0.061, p = 0.651, p = 0.600, p = 0.420, p = 0.353, at each time point).

Supplementary Figure 1.

Structural changes of external limiting membrane (ELM) and ellipsoid zone (EZ) integrity over time, cate-gorized by best-corrected visual acuity (BCVA) response at 1 month. No significant difference in distribution of ELM and EZ re-storation amongh three groups at each time point. (A) ELM integrity over time in <1 line BCVA improvement group. (B) EZ in-tegrity over time in <1 line BCVA improvement group. (C) ELM integrity over time in 1-< 3 lines BCVA improvement group. (D) EZ integrity over time in 1-< 3 lines BCVA improvement group. (E) ELM integrity over time in ≥3 lines BCVA improvement group. (F) EZ integrity over time in ≥3 lines BCVA improvement group.

Table 1.

Demographic and baseline characteristics of pooled study eyes, categorized by BCVA response at 1 month after the first bevacizumab injection

	BCVA changes from baseline at 1 month
	<1 line improvement	1-<3 lines improvement	≥3 lines improvement	p-value
	(n = 19)	(n = 17)	(n = 24)
Age (years)	62.3 ± 8.8	60.8 ± 10.7	61.8 ± 11.1	0.900^*
Male: Female	8:11	7:10	13:11	0.640^†
Hypertension	6	7	8	0.877^†
Lens status (phakic:pseudophakic)	16:3	12:5	22:2	0.202^†
Symptom duration (months)	3.8 ± 2.1	4.3 ± 2.9	1.6 ± 0.4	0.872^‡
Baseline BCVA (logMAR)	0.45 ± 0.05	0.52 ± 0.07	0.68 ± 0.06	0.004^‡^§
Baseline CMT (μ m)	352.2 ± 47.3	475.7 ± 44.9	449.5 ± 25.0	0.061^‡
Foveal ischemia	1	4	3	0.274^†
Hyper-reflective foci
Intra-retinal	3.6 ± 4.9	2.9 ± 5.0	1.1 ± 1.6	0.259^*
Outer-retinal	2.6 ± 3.6	4.2 ± 5.5	2.3 ± 3.0	0.477^*
Sub-retinal	0.2 ± 0.7	1.1 ± 2.0	0.3 ± 0.9	0.226^*

Values are presented as mean ± SD unless otherwise indicate.

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

^* One way analysis of variance (ANOVA) test.

^† Pearson’s chi-square test.

^‡ Kruskal-Wallis Test.

^§ Post-hoc test (Tukey method) between group comparison. <1 line improvement vs. ≥3 lines Improvement, p = 0.013. 1-<3 line improvement vs. ≥3 lines Improvement, p = 0.011.

Table 2.

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)	0.976	0.366
Male: Female	0.832	0.726
Baseline BCVA (logMAR)	44.992	0.006	11.179	0.097
Baseline CMT (μ m)	1.003	0.289
BCVA change ≥ 3 lines at 1 month	11.000	0.001	7.568	0.006
Absence of fluid at 1 month	1.800	0.352
Cumulative number of bevacizumab injection	0.848	0.356
Symptom duration	0.892	0.146

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

Table 3.

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

	Linear regression of BCVA response at 12 months
	Univariated		Multivariated
	Estimate	p-value	Estimate	p-value
Age	-0.001	0.813	0.002	0.682
Male: Female	-0.003	0.966	0.050	0.632
Baseline BCVA (logMAR)	0.300	0.077	0.089	0.739
Baseline CMT (μ m)	0.001	0.120	0.001	0.858
BCVA change ≥ 3 lines at 1 month	0.325	<0.001	0.234	0.046
Absence of fluid at 1 month	-0.025	0.788	-0.089	0.388
Cumulative number of bevacizumab injection	0.001	0.997	0.015	0.680
Symptom duration	-0.009	0.084	-0.003	0.831

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

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