Evaluation of Very High- and Very Low-Dose Intravitreal Aflibercept in Patients with Neovascular Age-Related Macular Degeneration

Purpose: To determine bioactivity and duration of effect of intravitreal aflibercept injection (also known as vascular endothelial growth factor Trap-Eye) for neovascular age-related macular degeneration (AMD). Methods: In this double-masked, phase 1 study, 28 patients with lesions <= 12 disc areas, >= 50% active choroidal neovascularization (CNV), and best corrected visual acuity (BCVA) <= 20/40 were randomized 1: 1 to a single intravitreal injection of aflibercept 0.15 or 4 mg. The primary end point was the change from baseline in central retinal/lesion thickness (CR/LT) at week-8. Secondary outcomes were the change from baseline BCVA, the change in CNV lesion size and area of leakage, and proportion of patients requiring repeat injection at 8 weeks. Results: Mean percent decrease in CR/LT for the 4-mg and 0.15-mg groups was, respectively, 34.2 versus 13.3 at week 4 (P = 0.0065), 23.8 versus 5.9 at week 6 (P = 0.0380), and 25.2% versus 11.3% at week 8 (P = 0.150). The 4-mg group gained a mean of 4.5 letters in BCVA (6/14 patients gaining >= 10 letters) versus 1.1 letters in 0.15-mg group (1/14 gaining >= 10 letters) at week 8. Fewer patients needed retreatment in the 4-mg group at week 8. No serious adverse event or ocular inflammation was reported in either group. Conclusions: Intravitreal aflibercept 4 mg had a safety profile similar to that of the very low dose 0.15 mg, and was well-tolerated. The 4-mg dose significantly reduced foveal thickening at weeks 4 and 6, significantly improved BCVA at weeks 6, and reduced the need for repeat injection after 8 weeks compared with intravitreal aflibercept 0.15mg in neovascular AMD patients.