Extended-interval outcomes with aflibercept 8 mg in diabetic macular edema: Real-world evidence from naïve and switch cohorts

Objectives: To evaluate the safety, efficacy and durability of intravitreal aflibercept 8 mg (IVA 8 mg) in treatment-naïve and previously treated patients with diabetic macular edema (DME) of Indian origin in a retrospective analysis in the real-world clinical setting. Material and Methods: This retrospective, multicenter observational study included adult patients with center-involving DME who received IVA 8 mg in routine clinical practice. Both treatment-naïve patients and those switched from prior anti-vascular endothelial growth factor therapy (faricimab or brolucizumab) were included. All patients completed 52 weeks of follow-up. The primary endpoint was the incidence and characterization of treatment-emergent adverse events (TEAEs). Secondary endpoints included changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), proportion of eyes achieving clinically meaningful visual gains, improvement in diabetic retinopathy severity scale (DRSS), and treatment interval extension over 1 year. Results: Seventy patients (70 eyes), including 28 treatment-naïve and 42 previously treated patients (30 switched from faricimab and 12 from brolucizumab), were analyzed, with the treatment naïve cohort analyzed separately from the switch patients, as pairwise comparisons would be interpreted differently in switch patients, as would tests of significance with appropriate corrections. The mean age was 57.9 ± 9.1 years. Drug-related TEAEs were infrequent across cohorts, and no new safety signals were identified. Most adverse events were ocular and mild. Serious adverse events were uncommon (≤16.7%), with no treatment-related events resulting in permanent vision loss or death. Intraocular pressure remained stable. At week 52, mean BCVA improved by +12.3 letters in treatment-naïve patients, +8.4 letters in the faricimab-switch group, and +8.5 letters in the brolucizumab-switch group. Mean CRT reductions were −197 µm, −164 µm, and −198 µm, respectively. ≥15-letter gains were achieved in over half of the treatment-naïve patients and approximately one-quarter of switch patients. ≥2-step DRSS improvement occurred in 50% of naïve patients and over half of switch patients. The mean number of injections was ~5 over 52 weeks. Most of the patients achieved ≥12-week intervals, with many extending to 16 weeks. Conclusion: IVA 8 mg demonstrated a safety profile consistent with previously reported data, with no new safety signals identified over 52 weeks. It was also associated with improvements in visual and anatomical outcomes, as well as extension of treatment intervals in both treatment-naïve and previously treated patients with DME.