This highlights the importance of using robust methodologies that adjust for potential effect modifiers in comparisons of RCTs. Drawing conclusions based on raw data may be misleading. The results of the analysis were robust to changes in the included RCTs and treatment arms. Including REVEAL, excluding READ-2 and including the ranibizumab plus deferred laser arm from DRCR.net Protocol I did not substantially modify the results: in all three scenarios, ranibizumab had the highest probability of being the most efficacious treatment in the network, although not significantly better than aflibercept bimonthly. In the base case, the probability that ranibizumab plus laser or aflibercept monotherapy are the most efficacious treatment in the network was 12% and 14% respectively. A strength of the current analysis is the inclusion of baseline BCVA and CRT as covariates in the models to account for differences in baseline visual acuity and disease progression among the patient populations of different RCTs. In particular, baseline BCVA varied among patient populations: the inclusion criterion for BCVA in VIVID and VISTA was 24–73 letters compared with 39–78 letters in RESTORE. Adjusting for baseline visual acuity and disease progression among the patient populations is critical in comparisons among RCTs because gains in BCVA with antiVEGF therapy in patients with DME and other retinal diseases such as neovascular age-related macular degeneration have been shown to be greater in patients with a worse baseline BCVA than in patients with a better BCVA. The coefficient reflecting the impact of baseline BCVA on the logarithm of the odds of gaining at least 10 letters BCVA was consistent with a negative correlation between baseline BCVA and gain in BCVA as a result of treatment. The random treatment effects model including baseline BCVA provided a good fit because the posterior mean of the total residual deviance was 19.0 versus 19.0 unconstrained points. This study has some limitations. The analysis included a relatively small number of RCTs, of which three are not yet published in full and although the RCTs included in the metaanalysis were, in general, of good quality, the use of masking was not clearly reported in READ-2. Exclusion of READ-2 during sensitivity analyses suggested that this did not have a substantial effect on the results. Finally, the RESOLVE RCT was a dose finding study with starting doses of 0.3 and 0.5 mg; after month 1 there was no true 0.5 mg treatment arm as the dose could be doubled. Consistent with the RESOLVE Reversine publication, we used the pooled results in the analysis since they “are considered to be representative for treatment with 0.5-mg injections”. Given the substantial burden of VI due to DME and the evolving options for treatment, it is important to regularly compare the relative efficacy of the available first-line therapies. This study is the first comparative network meta-analysis comparing anti-VEGF therapy with laser photocoagulation to include phase III data for aflibercept.