Meta-analysis of Intravitreal Injection of Anti-vascular Endothelial Growth Factors for Diabetic Macular Edema

Hajin Tchoe; Sang Jin Shin; Jae Kyung Suh; Songhee Cho; Jangmi Yang; Min Joo Kang; Donghyun Jee

doi:10.3341/jkos.2019.60.2.144

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Tchoe, Shin, Suh, Cho, Yang, Kang, and Jee: Meta-analysis of Intravitreal Injection of Anti-vascular Endothelial Growth Factors for Diabetic Macular Edema

Original Article

Journal of the Korean Ophthalmological Society 2019; 60(2): 144-151.

Published online: 15 February 2019

DOI: https://doi.org/10.3341/jkos.2019.60.2.144

Meta-analysis of Intravitreal Injection of Anti-vascular Endothelial Growth Factors for Diabetic Macular Edema

Hajin Tchoe, MPharm¹, Sang Jin Shin, PhD¹, Jae Kyung Suh, PhD¹, Songhee Cho, MPH¹, Jangmi Yang, MPH¹, Min Joo Kang, MS¹, Donghyun Jee, MD, PhD, MPH²

¹Office of Economic Evaluation Research, National Evidence Based Healthcare Collaborating Agency, Seoul, Korea.

²Department of Ophthalmology and Visual Science, St. Vincent Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Address reprint requests to Donghyun Jee, MD, PhD, MPH. Department of Ophthalmology and Visual Science, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, #93 Jungbudae-ro, Paldal-gu, Suwon 16247, Korea. Tel: 82-31-249-7343, Fax: 82-31-249-6225, doj087@mail.catholic.ac.kr

Received 3 May 2018 Revised 19 June 2018 Accepted 24 January 2019

The Korean Ophthalmological Society

(open-access):

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

Intravitreal aflibercept, ranibizumab, bevacizumab, and dexamethasone are the most widely used drugs in the treatment of diabetic macular edema (DME). The aim of this study was to compare the efficacy and safety of anti-vascular endothelial growth factors and dexamethasone for the treatment of DME.

Methods

There were nine previous systematic reviews on this topic; we updated these high-quality reviews. Seven studies were added to two studies following a literature search. Efficacy outcomes were 1) average improvement in visual acuity, 2) proportion of patients who experienced an improvement in vision (an increase in best-corrected visual acuity (BCVA) of ≥ 15 in the Early Treatment Diabetic Retinopathy Study [ETDRS]), and 3) proportion of patients who experienced worsening vision (a decrease in BCVA of ≥ 15 in the ETDRS). Safety outcomes included systemic adverse events and ocular-related adverse events.

Results

The mean difference in the BCVA for ranibizumab versus bevacizumab treatment was 0.16 (95% confidence interval [CI]: −0.02, 0.34), and that for ranibizumab versus aflibercept was −0.08 (95% CI: −0.26, 0.10). The mean difference in the change of BCVA for aflibercept versus ranibizumab was −0.20 (95% CI: −0.40, −0.01), and that for aflibercept versus bevacizumab was −0.34 (95% CI: −0.53, −0.14). Other efficacy outcomes showed similar trends, and there was no significant difference between treatments. There was also no significant difference in both systemic and ocular adverse events rates between the treatments.

Conclusions

In DME patients, the efficacy of aflibercept was found to be higher with respect to BCVA changes compared with ranibizumab or bevacizumab. However, there were no significant difference in terms of visual acuity improvement or visual acuity of more than 15 letters, nor in terms of anti-vascular endothelial growth factors (as a safety outcome).

Keywords: Aflibercept, Anti-vascular endothelial growth factor, Diabetic macular edema, Ranibizumab

Figures and Tables

Table 1

PICO of the study

PICO = population intervention comparator outcome; BCVA = best-corrected visual acuity; ETDR = early treatment diabetic retinopathy study; ATE = arterial thromboembolic events; VTE = venous thromboembolic events; IOP = increased intraocular pressure.

Table 2

Assessment of risk of bias

Table 3

Studies included in the final analysis

Table 4

Results of meta-analysis of anti-vascular endothelial growth factor for diabetic macular edema

BCVA = best-corrected visual acuity; ETDR = early treatment diabetic retinopathy study.

Table 5

Results of network meta-analysis of anti-vascular endothelial growth factor

CI = confidence interval; P = probability; MD = mean difference.

Table 6

Results of network meta-analysis of anti-vasclar endothelial growth factor: increase of BCVA >ETDRs 15 letter

BCVA = best-corrected visual acuity; ETDR = early treatment diabetic retinopathy study.

Table 7

Results of network meta-analysis of anti-vasclar endothelial growth factor: increase of BCVA <ETDRs 15 letter

BCVA = best-corrected visual acuity; ETDR = early treatment diabetic retinopathy study.

Notes

The authors acknowledge the financial support of the National Research Foundation of Korea Grant funded by the Korean government (MSIP) (No NRF-2016R1D1A1B03932606), and of the National Evidence-based Healthcare Collaborating Agency of Korea (NECA-A-17-003).

^{Conflicts of Interest} The authors have no conflicts to disclose.

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