Letter to the Editor Regarding “Aflibercept 8 mg versus Faricimab Treat-and-Extend for Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration: A Bayesian Fixed-Effect Network Meta-analysis of Clinical Trials”

neovascular age-related macular degeneration (nAMD).However, several methodological issues warrant a more guarded interpretation of the authors' conclusions.My main concern is that the reported advantage in injection frequency may be driven, at least in part, by structural differences in trial design rather than by a true comparative durability signal.The aflibercept 8 mg studies and the faricimab studies did not use equivalent treatment algorithms.The loading phases differed, with fewer initial injections in the aflibercept 8 mg programme, and the maximum extension interval also differed, reaching up to 24 weeks for aflibercept 8 mg but only up to 16 weeks for faricimab.In addition, the interval-adjustment criteria were not aligned across the trials.Under such conditions, comparing cumulative injection numbers risks conflating protocol architecture with therapeutic effect.A second issue concerns the assumptions underlying the network meta-analysis itself.The network was sparse, with only three trials contributing to each disease-specific comparison, and there were no closed loops.Although the authors justify the use of a fixed-effect model on statistical grounds, the underlying clinical heterogeneity remains substantial.Differences in eligibility criteria, prior treatment exposure, disease activity rules and timing of outcome assessment challenge the transitivity assumption required for valid indirect comparison.