Effects of Intravitreal Injection of Bevacizumab or Ranibizumab on Systemic Circulation

Myung Hun Yoon; Young Jun Kim; So Young Lee; Kang Won Lee; Hee Seung Chin

doi:10.3341/jkos.2016.57.3.429

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Yoon, Kim, Lee, Lee, and Chin: Effects of Intravitreal Injection of Bevacizumab or Ranibizumab on Systemic Circulation

Original Article

J Korean Ophthalmol Soc 2016;57(3):429-437.

Published online: 3 September 2016

DOI: https://doi.org/10.3341/jkos.2016.57.3.429

Effects of Intravitreal Injection of Bevacizumab or Ranibizumab on Systemic Circulation

Myung Hun Yoon, MD, Young Jun Kim, MD, So Young Lee, BD, Kang Won Lee, MD, Hee Seung Chin, MD, PhD

Department of Ophthalmology, Inha University School of Medicine, Incheon, Korea

Address reprint requests to Hee Seung Chin, MD, PhD, Department of Ophthalmology, Inha University Hospital, #27 Inhang-ro, Jung-gu, Incheon 22332, Korea, Tel: 82-32-890-2400, Fax: 82-32-890-2417, E-mail: hschin@inha.ac.kr

Received 10 July 2015 Revised 2 October 2015 Accepted 9 December 2015

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

The purpose of this study was to evaluate the systemic effects of ranibizumab and bevacizumab by examining the plasma levels of anti-vascular endothelial growth factor (anti-VEGF) and VEGF before and after a single intravitreal injection.

Methods

Twenty-eight eyes of 28 patients with various retinal diseases were enrolled. Seventeen eyes received an injection of intravitreal bevacizumab, and 11 eyes received an injection of ranibizumab. Blood samples were collected just before and 1 day, 1 week, and 1 month after injection. Concentrations of anti-VEGF and VEGF in plasma were measured using enzyme-linked immunosorbent assay (ELISA).

Results

In the bevacizumab group, anti-VEGF concentration before the injection was 91.0 ng/mL, while those at 1 day, 1 week, and 1 month post-injection increased to 153.6, 196.3, and 140.3 ng/mL, respectively (p < 0.05 for all). VEGF concentration before the injection was 93.9 pg/mL, while those 1 day, 1 week, and 1 month post-injection were reduced to 40.1, 24.7, and 33.5 pg/mL, respectively (p < 0.05 for all). However, in the ranibizumab group, no significant reductions in anti-VEGF concentration were observed. The anti-VEGF concentration before the injection was 177.6 ng/mL, while those at 1 day, 1 week, and 1 month post-injection were 177.5, 160.7, 175.3 ng/mL, respectively (p > 0.05 for all). VEGF level also showed no significant change. VEGF concentration before the injection was 80.9 pg/mL, while those at 1 day, 1 week and 1 month post-injection were 96.7, 106.3, 106.1 pg/mL, respectively (p > 0.05 for all).

Conclusions

Contrary to ranibizumab, intravitreal bevacizumab significantly lowers plasma VEGF level in patients with various retinal diseases. The study suggests the consideration of the systemic effects of intravitreal bevacizumab injection.

Keywords: Anti-vascular endothelial growth factor (anti-VEGF), Bevacizumab, Ranibizumab, Vascular endothelial growth factor (VEGF)

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Figure 1.

Plasma levels of anti-vascular endothelial growth factor (VEGF) and VEGF before and after an intravitreal injection of bevacizumab. (A) Anti-VEGF concentrations before and 1 day, 1 week, and 1 month after injection were; 91.0, 153.6, 196.3, and 140.3 ng/mL (p = 0.001, 0.000, 0.001, respectively).(B) VEGF concentrations before and 1 day, 1 week, and 1 month after injection were 93.9, 40.1, 24.7, 33.5 pg/mL (p = 0.006, 0.001, 0.002, respectively). ^*p < 0.05.

Figure 2.

Schematic graphs of plasma levels of anti-vascular endothelial growth factor (VEGF) and VEGF before and over 1 month after an intravitreal injection of bevacizumab. As anti-VEGF level increased, VEGF level decreased.

Figure 3.

Plasma levels of anti-vascular endothelial growth factor (VEGF) and VEGF before and after an intravitreal injection of ranibizumab. (A) Anti-VEGF concentrations before injection and 1 day, 1 week, and 1 month after injection were 177.6, 177.5, 160.7, and 175.3 ng/mL (p = 0.646, 0.110, 0.477, respectively). (B) VEGF concentrations before injection and 1 day, 1 week, and 1 month after injection were 80.9, 96.7, 106.3, and 106.1 pg/mL (p = 0.504, 0.328, 0.203, respectively).

Figure 4.

Schematic graphs of plasma levels of anti-vascular endothelial growth factor (VEGF) and VEGF before and for one month after an intravitreal injection of ranibizumab. No significant change is observed in anti-VEGF or VEGF levels.

Table 1.

Demographic data

Case	Sex	Age (years)	Retinopathy	VEGF	Drug	Laterality
1	M	60	CNV d/t AMD	46.5	Ranibizumab	OS
2	M	75	CNV d/t AMD	27.1	Ranibizumab	OD
3	M	74	CNV d/t AMD	30.5	Ranibizumab	OD
4	M	67	CNV d/t AMD	97.1	Ranibizumab	OD
5	M	61	CNV d/t AMD	72.4	Ranibizumab	OD
6	M	62	CNV d/t AMD	59.2	Ranibizumab	OS
7	F	71	DR	127.4	Bevacizumab	OS
8	M	88	CNV d/t AMD	38.3	Ranibizumab	OS
9	F	56	DR	17.8	Bevacizumab	OS
10	M	37	CRVO	174.6	Bevacizumab	OD
11	M	71	CNV d/t AMD	22.0	Ranibizumab	OD
12	F	77	DR	240.6	Bevacizumab	OS
13	F	55	DR	57.7	Bevacizumab	OS
14	F	34	Myopic CNV	27.3	Bevacizumab	OD
15	F	57	Myopic CNV	154.3	Bevacizumab	OD
16	F	31	Myopic CNV	121.8	Bevacizumab	OS
17	F	24	Myopic CNV	27.7	Bevacizumab	OS
18	F	39	Myopic CNV	17.0	Bevacizumab	OD
19	M	45	BRVO	34.8	Bevacizumab	OD
20	M	45	DR	280.1	Bevacizumab	OD
21	M	62	BRVO	54.7	Bevacizumab	OD
22	M	84	CNV d/t AMD	39.2	Ranibizumab	OS
23	M	63	BRVO	70.0	Bevacizumab	OS
24	M	50	DR	32.0	Bevacizumab	OS
25	F	73	CNV d/t AMD	221.0	Ranibizumab	OS
26	F	62	CNV d/t AMD	236.9	Ranibizumab	OS
27	F	43	PDR	44.0	Bevacizumab	OD
28	F	49	BRVO	116.0	Bevacizumab	OS

Concentrations of VEGF are in picograms of VEGF per milliliter (pg/mL).

VEGF = vascular endothelial growth factor; M = male; F = female; CNV = choroidal neovascularization; d/t = due to; AMD = age-related macular degeneration; OS = oculus sinister; OD = oculus dexter; DR = diabetic retinopathy; CRVO = central retinal vein occlusion; BRVO = branch retinal vein occlusion; PDR = proliferative diabetic retinopathy.

Table 2.

Plasma concentrations of anti-VEGF and VEGF in the bevacizumab group

	N	Mean	SD	Percentile		p-value^*
	N	Mean	SD	25th	75th	p-value^*
Anti-VEGF
Before	17	91.0	67.3	40.2	107.6
After 1 day	17	153.6	94.4	82.0	221.6	0.001
After 1 week	17	196.3	89.7	127.1	249.1	0.000
After 1 month	17	140.3	82.8	93.5	159.7	0.001
VEGF
Before	17	93.9	80.0	29.8	140.8
After 1 day	17	40.1	39.6	13.4	57.2	0.006
After 1 week	17	24.7	12.4	13.4	31.4	0.001
After 1 month	17	33.5	31.9	10.6	38.8	0.002

Concentrations of anti-VEGF are in nanograms of anti-VEGF per milliliter (ng/mL). Concentrations of VEGF are in picograms of VEGF per milliliter (pg/mL).

VEGF = vascular endothelial growth factor; N = number; SD = standard deviation.

^* Wilcoxon's Signed Ranks Test. p-values are for comparisons of values before versus after injection.

Table 3.

Plasma concentrations of anti-VEGF and VEGF in the ranibizumab group

	N	Mean	SD	Percentile		p-value^*
	N	Mean	SD	25th	75th	p-value^*
Anti-VEGF
Before	11	177.6	76.5	129.1	220.8
After 1 day	11	177.5	73.6	139.8	205.4	0.646
After 1 week	11	160.7	82.5	97.6	225.5	0.110
After 1 month	11	175.3	62.2	139.2	207.4	0.477
VEGF
Before	11	80.9	76.4	30.5	97.1
After 1 day	11	96.7	137.6	21.0	102.2	0.504
After 1 week	11	106.3	82.1	28.4	131.9	0.328
After 1 month	11	106.1	89.0	27.1	190.7	0.203

Concentrations of anti-VEGF are in nanograms of ranibizumab per milliliter. Concentrations of VEGF are in picograms of VEGF per milliliter.

VEGF = vascular endothelial growth factor; N = number; SD = standard deviation.

^* Wilcoxon's Signed Ranks Test. p-values are for comparisons of values before versus after injection.

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