Real-World Longitudinal Outcomes of First-Line Aflibercept 8 mg for Treatment-Naïve Diabetic Macular Edema

We sought to evaluate longitudinal visual and anatomical outcomes in treatment-naïve eyes with diabetic macular edema (DME) treated with aflibercept 8 mg in routine clinical practice. Treatment-naïve eyes with DME receiving aflibercept 8 mg as first-line therapy under an observe-and-plan regimen were evaluated. Medical records were retrospectively reviewed, collecting data on best-corrected visual acuity (BCVA), central retinal thickness (CRT), and follow-up visits. Longitudinal changes in BCVA and CRT were analyzed using linear mixed-effects models with random effects to account for repeated measurements. Analyses were restricted to the first 300 days after baseline. A total of 95 eyes from 77 patients were eligible for evaluation. In the linear mixed-effect model, the estimated marginal mean BCVA improved by 3.6 ETDRS letters (95% CI 1.7–5.6) at 300 days, with eyes with a baseline BCVA ≤ 60 ETDRS achieving a 16.2 ETDRS letter gain (95% CI 12.2–20.1). In the mixed-effect model, the mean CRT decreased by 84.9 µm (95% CI − 103.1 to − 66.6) at 300 days while a CRT decline of 170.1 µm (95% CI −199.2 to −141.1) was achieved in severe DME (baseline CRT ≥ 400 µm). The estimated marginal probability of center-involving macular edema was 0.70 (95% CI 0.55–0.82) at 90 days, 0.65 (95% CI 0.51–0.77) at 180 days, and 0.76 (CI 95% 0.62–0.86) at 300 days. The median last completed injection interval at 300 days was 5.1 weeks (IQR 4.1–6.3 weeks). No adverse event was reported. Aflibercept 8 mg resulted in a meaningful improvement in BCVA and significant reduction in CRT. The estimated marginal probability of center-involving macular edema suggests that sustained therapy is required during the first 300 days of treatment. The study highlights the need for the development of real-world strategies to reach long injection intervals.