Journal List > J Korean Ophthalmol Soc > v.60(2) > 1116276

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

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).

Figures and Tables

Table 1

PICO of the study

jkos-60-144-i001

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

jkos-60-144-i002
Table 3

Studies included in the final analysis

jkos-60-144-i003
Table 4

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

jkos-60-144-i004

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

Table 5

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

jkos-60-144-i005

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

jkos-60-144-i006

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

jkos-60-144-i007

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.

References

1. Hendrick AM, Gibson MV, Kulshreshtha A. Diabetic retinopathy. Prim Care. 2015; 42:451–464.
crossref pmid
2. Frank RN. Diabetic retinopathy and systemic factors. Middle East Afr J Ophthalmol. 2015; 22:151–156.
crossref pmid pmc
3. Jee D, Lee WK, Kang S. Prevalence and risk factors for diabetic retinopathy: the Korea National Health and Nutrition Examination Survey 2008-2011. Invest Ophthalmol Vis Sci. 2013; 54:6827–6833.
crossref pmid
4. Ashraf M, Souka AAR. Aflibercept in age-related macular degeneration: evaluating its role as a primary therapeutic option. Eye (Lond). 2017; 31:1523–1536.
crossref pmid pmc
5. Villegas VM, Aranguren LA, Kovach JL, et al. Current advances in the treatment of neovascular age-related macular degeneration. Expert Opin Drug Deliv. 2017; 14:273–282.
crossref pmid
6. Zhang Y, Chioreso C, Schweizer ML, Abràmoff MD. Effects of aflibercept for neovascular age-related macular degeneration: a systematic review and meta-analysis of observational comparative studies. Invest Ophthalmol Vis Sci. 2017; 58:5616–5627.
pmid pmc
7. Gemenetzi M, Patel PJ. A systematic review of the treat and extend treatment regimen with anti-vegf agents for neovascular age-related macular degeneration. Ophthalmol Ther. 2017; 6:79–92.
crossref pmid pmc
8. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015; 372:1193–1203.
crossref pmid pmc
9. Jampol LM, Glassman AR, Bressler NM, et al. Anti-vascular endothelial growth factor comparative effectiveness trial for diabetic macular edema: additional efficacy post hoc analyses of a randomized clinical trial. JAMA Ophthalmol. 2016; 134:1429–1434.
10. Nepomuceno AB, Takaki E, Paes de Almeida FP, et al. A prospective randomized trial of intravitreal bevacizumab versus ranibizumab for the management of diabetic macular edema. Am J Ophthalmol. 2013; 156:502–510.
pmid
11. Fouda SM, Bahgat AM. Intravitreal aflibercept versus intravitreal ranibizumab for the treatment of diabetic macular edema. Clin Ophthalmol. 2017; 11:567–571.
crossref pmid pmc
12. Abouammoh MA. Ranibizumab injection for diabetic macular edema: meta-analysis of systemic safety and systematic review. Can J Ophthalmol. 2013; 48:317–323.
crossref pmid
13. Leveziel N, Ragot S, Gand E, et al. Association between diabetic macular edema and cardiovascular events in type 2 diabetes patients: a multicenter observational study. Medicine (Baltimore). 2015; 94:e1220.
14. Kwon JW, Jee D, La TY. The association between myocardial infarction and intravitreal bevacizumab injection. Medicine (Baltimore). 2018; 97:e0198.
crossref
15. Anothaisintawee T, Leelahavarong P, Ratanapakorn T, Teerawattananon Y. The use of comparative effectiveness research to inform policy decisions on the inclusion of bevacizumab for the treatment of macular diseases in Thailand's pharmaceutical benefit package. Clinicoecon Outcomes Res. 2012; 4:361–374.
pmid pmc
16. Ford JA, Elders A, Shyangdan D, et al. The relative clinical effectiveness of ranibizumab and bevacizumab in diabetic macular oedema: an indirect comparison in a systematic review. BMJ. 2012; 345:e5182.
crossref
17. Korobelnik JF, Kleijnen J, Lang SH, et al. Systematic review and mixed treatment comparison of intravitreal aflibercept with other therapies for diabetic macular edema (DME). BMC Ophthalmol. 2015; 15:52.
crossref pmid pmc
18. Régnier S, Malcolm W, Allen F, et al. Efficacy of anti-VEGF and laser photocoagulation in the treatment of visual impairment due to diabetic macular edema: a systematic review and network metaanalysis. PLoS One. 2014; 9:e102309.
crossref
19. Mohamed QA, Fletcher EC, Buckle M. Diabetic retinopathy: intravitreal vascular endothelial growth factor inhibitors for diabetic macular oedema. BMJ Clin Evid. 2016; 2016.
20. Virgili G, Parravano M, Evans JR, et al. Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis. Cochrane Database Syst Rev. 2017; 6:Cd007419.
crossref
21. Ollendorf DA, Colby JA, Pearson SD. Comparative effectiveness of anti-VEGF agents for diabetic macular edema. Int J Technol Assess Health Care. 2013; 29:392–401.
crossref pmid
22. Zhang L, Wang W, Gao Y, et al. The efficacy and safety of current treatments in diabetic macular edema: a systematic review and network meta-analysis. PLoS One. 2016; 11:e0159553.
crossref
23. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology. 2016; 123:1351–1359.
pmid pmc
24. Wells JA, Glassman AR, Jampol LM, et al. Association of baseline visual acuity and retinal thickness with 1-year efficacy of aflibercept, bevacizumab, and ranibizumab for diabetic macular edema. JAMA Ophthalmol. 2016; 134:127–134.
crossref pmid pmc
25. Callanan DG, Loewenstein A, Patel SS, et al. A multicenter, 12-month randomized study comparing dexamethasone intravitreal implant with ranibizumab in patients with diabetic macular edema. Graefes Arch Clin Exp Ophthalmol. 2017; 255:463–473.
crossref
26. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012; 119:789–801.
pmid
27. Ekinci M, Ceylan E, Çakıcı Ö, et al. Treatment of macular edema in diabetic retinopathy: comparison of the efficacy of intravitreal bevacizumab and ranibizumab injections. Expert Rev Ophthalmol. 2014; 9:139–143.
crossref
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