Switching to High-Dose Aflibercept (8 mg) with Pro Re Nata Reduces Treatment Burden in Diabetic Macular Edema: A Real-World Pilot Study

TL;DR

Switching to high-dose aflibercept with on-demand dosing in diabetic macular edema maintained vision and reduced treatment frequency in a small real-world study.

Contribution

This pilot study provides real-world evidence that switching to aflibercept 8 mg with pro re nata dosing is effective and reduces treatment burden in diabetic macular edema.

Findings

Mean central retinal thickness significantly decreased in the first four months after switching to aflibercept 8 mg.

Twenty-five percent of patients required only a single additional injection over six months.

No intraocular inflammation or retinal vasculitis was observed during the study period.

Abstract

Background/Objectives: The PHOTON trial established the efficacy of aflibercept 8 mg using fixed-interval dosing in treatment-naïve patients; however, real-world evidence regarding pro re nata (PRN) regimens in switch cases remains limited. This pilot study evaluated the short-term efficacy and safety of switching to aflibercept 8 mg with PRN dosing in eyes with DME. Methods: This retrospective study included 20 eyes from 12 patients with DME who switched to aflibercept 8 mg and were followed for 6 months. Patients received initial induction doses (1–3 injections based on predetermined anatomical and functional criteria) followed by PRN dosing based on clinical findings. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Treatment intervals and injection frequency were also analyzed. Results: Mean logMAR BCVA was maintained from baseline (0.242 ± 0.252) throughout the follow-up period: 0.164 ± 0.218 at 1 month, 0.138 ± 0.241 at 2 months, 0.145 ± 0.204 at 3 months, 0.143 ± 0.181 at 4 months, 0.149 ± 0.166 at 5 months, and 0.180 ± 0.224 at 6 months. No statistically significant changes in BCVA from baseline were observed at any time point. Mean CRT decreased from baseline (369.6 ± 138.3 μm) at all follow-up time points: 251.5 ± 82.1 μm at 1 month, 269.1 ± 104.5 μm at 2 months, 255.8 ± 67.8 μm at 3 months, 275.2 ± 76.6 μm at 4 months, 301.4 ± 81.2 μm at 5 months, and 302.7 ± 86.8 μm at 6 months. Statistically significant reductions in CRT were observed at 1 through 4 months (1 month: p = 0.000010; 2 months: p = 0.000243; 3 months: p = 0.000035; 4 months: p = 0.000597), whereas the reductions at 5 months (p = 0.0317) and 6 months (p = 0.0424) were not statistically significant. The mean number of injections over 6 months was 1.45 ± 1.05 (median 1; range 1–4), with 70% of eyes achieving treatment intervals ≥ 4 months. Five eyes (25%) required only the switching dose with no additional treatment during follow-up. No intraocular inflammation or retinal vasculitis was observed. Conclusions: Switching to aflibercept 8 mg with PRN dosing provided sustained anatomical improvement and maintained visual acuity in DME, with one quarter of the cases maintaining these outcomes with only a single additional injection. These real-world findings from a pilot study suggest that the PRN approach appears feasible and effective in real-world practice, offering a practical treatment option that may help reduce treatment burden while maintaining disease control.

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