Aflibercept Rescue of Bevacizumab- or Ranibizumab-Resistant Choroidal Neovascularization in Age-Related Macular Degeneration

Abstract

Purpose: To evaluate the effect of intravitreal aflibercept on patients with neovascular age-related macular degeneration (AMD) that developed resistance to bevacizumab or ranibizumab treatment.

Methods: This is a consecutive interventional case series. Eyes that were treated with every four weeks (Q4W) bevacizumab or ranibizumab that did not respond to treatment were switched to aflibercept 2 mg (0.5 mL) every 8 weeks (Q8W) (no induction). Resistance was defined as multiple recurrences or persistence of intraretinal (IRF) or subretinal fluid (SRF). Imaging was performed monthly initially and semi monthly thereafter. We determined changes in visual acuity, and retinal thickness and area. A subgroup of patients was tested with the Vimetrics instrument, which is a time-based vision, contrast and glare acuity test with read out in ETDRS notation.

Results: Forty-one eyes of 34 patients were treated. The mean age was 80.1 years old (range, 67-90) and there were an equal number of males and females. Mean number of prior bevacizumab or ranibizumab injections was 17.5 (range, 2-39). Mean best-corrected visual acuity (BCVA) at baseline was 20/112.5 on ETDRS. Maximum retinal thickness at baseline was 452 μm which significantly improved to 330 μm at 1-month (p<0.001) and to 376 μm at 2 months (p=0.004) after an initial injection. Seventy-seven percent of eyes had good response (i.e. showing >90% resorption of SRF and IRF) at 1 month. All the rest except for 1 eye had evidence of response to the initial injection. Of the eyes that showed good response at 1 month, 61% remained stable and maintained the initial response at 2 months. Mean BCVA improved to 20/74 at 1 month post-injection and this was maintained at 2 months (20/79), with a corresponding improvement in contrast sensitivity.

Conclusions: Alfibercept is an effective treatment even in bevacizumab- or ranibizumab-resistant patients and even given at a pharmacokinetically equivalent dose to bevacizumab or ranibizumab (i.e. bevacizumab or ranibizumab Q4W and aflibercept Q8W). This suggests that the potency of aflibercept overcomes bevacizumab or ranibizumab resistance and that much of this resistance is due to inadequate anti-VEGF activity. We’re continuing to follow this cohort of patients with semi-monthly aflibercept injections and data on durability of response and need for more frequent injections will be present.

Keywords: 453 choroid: neovascularization • 412 age-related macular degeneration • 748 vascular endothelial growth factor