Evaluation of real-world early response of DMO to aflibercept therapy to inform future clinical trial design of novel investigational agents

New clinical trials for diabetic macular oedema (DMO) are being designed to prove superiority over aflibercept when this agent is already very effective in improving visual acuity (VA) and DMO. The aim of this study was to determine the optimal inclusion–exclusion criteria for trials to aim for superiority in visual outcomes with newer agents. As Phase 1 studies are short duration, we aimed to evaluate the early response of aflibercept in a real-world cohort initiated on monthly aflibercept for 3 consecutive injections and observed the effects at 4 months. The sub-optimal responders were pre-defined based on different cut-offs for VA and central sub-field thickness (CST). 200 patients with treatment naïve DMO treated with 3 loading doses of aflibercept were included in the study. We found that those presenting with baseline VA of 35–54 ETDRS letters (n = 43) had higher proportion of sub-optimal responders compared to other categories (p < 0.001). Patients with baseline CST of less than 400 µm (n = 96) responded less well functionally and anatomically to loading dose than eyes with baseline CST of 400 µm or more (n = 104, p = 0.02), indicating that eyes with CST ≥ 400 µm is another inclusion criteria. There was minimal correlation between change in CST and change in VA at 4 months (r = − 0.27), suggesting that both these inclusion criteria are non-exclusive. However, for maximal efficacy, patients that meet both these inclusion criteria are more likely to show benefit from an alternative intervention. New trials should aim to include patients with treatment naïve DMO with VA between 35–54 letters and CST of 400 µm or more when aflibercept is used as the comparator.