OBJECTIVES : Diabetes mellitus is a global epidemic and poses major public health issue for the complications involved, of which diabetic retinopathy is most common. Diabetic macular oedema (DMO) is the leading cause of adult-onset blindness in diabetic retinopathy. Laser photocoagulation has been the standard treatment for DMO until anti-vascular endothelial growth factors (anti-VEGFs) replaced it as treatment mainstay, based on encouraging results from recent studies. However, there is a dearth of evidence on the comparative benefit of anti-VEGF modalities. The objective, therefore, is to compare the efficacy and safety of anti-VEGF monotherapies for DMO adults by conducting systematic review and network meta-analysis (NMA).

METHODS : Qualified studies were identified in a search of MEDLINE, Embase, CENTRAL, and clinicaltrials.gov databases, from inception to April 2020. Randomized controlled trials assessing gain of ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, improvement in best corrected visual acuity (BCVA), and occurrence of adverse events (AEs) and serious AEs at one year were considered. Outcomes were analyzed using Bayesian NMA adopting a fixed-effect model (lower DIC values), using Openbugs v3.2.3 and R v3.6.1. Mean differences in change from baseline and mean odds ratios (OR) with 95% credible intervals (CrIs) were calculated.

RESULTS : The review identified 35 relevant studies that were subject to feasibility assessment, of which 22 studies were included in the NMA. Patients receiving aflibercept were more likely to gain ≥ 15 ETDRS letters compared to ranibizumab (OR: 1.91; 95%CrI: 1.20, 3.03) and pegaptanib (OR: 4.94; 95% CrI: 1.31, 20.35). Aflibercept, bevacizumab and pegaptanib were all comparable with respect to ranibizumab since no differences in mean BCVA change were noted. The anti-VEGFs had similar safety profile with no significant differences observed.

CONCLUSIONS : Aflibercept was more effective in improving visual acuity in DMO as compared to other anti-VEGFs. However, no difference in overall safety between the four monotherapies was observed.