Aflibercept as a Second Line Therapy for Neovascular Age Related Macular Degeneration in Israel (ASLI) study

Abstract

PurposeThe purpose of this study is to evaluate an early switch to aflibecept in eyes with neovascular age-related macular degeneration (nvAMD) showing partial or lack of response for initial therapy with bevacizumab.MethodsThe Aflibercept as a Second Line Therapy for Neovascular Age Related Macular Degeneration in Israel (ASLI) was a prospective, multicenter, single-arm clinical trial. Eyes with nvAMD having incomplete response to 3-9 prior bevacizumab injections were recruited. Three monthly intravitreal aflibercept (2 mg) injections were administered, followed by two bi-monthly injections and a final examination at week 28. An optional injection was allowed at week 20.ResultsForty-seven eyes of 46 patients (mean±SD age 76±8 years) were recruited. The mean number of prior bevacizumab injections was 5.5±2.9. The mean visual acuity improved from 60.3±10 ETDRS letters at baseline to 63.1±15 letters at week 28 (P=0.02, paired t-test). The central subfield thickness (CST) reduced from 409±127 micron at baseline to 330±110 microns at week 4 (P=0.0002; paired t-test), and 277±70 microns at week 28 (P=0.00002; paired t-test). Twenty-two eyes had three to five prior bevacizumab injections (mean 5.1±0.7), and 25 eyes had six to nine prior injections (7.32±1.2). Both groups had reduced CST from baseline to week 28 (P=0.0004 and P=0.0007; paired t-test, respectively). Thirty-five (75%) eyes required the optional additional aflibercept injection at week 20.ConclusionsThe ASLI study demonstrated improved BCVA and reduced CST following an early switch to aflibercept therapy in eyes with prior incomplete response to initial therapy with three to nine bevacizumab injections.

Figure 1

The mean change in CST in microns according to OCT during 28 weeks of follow-up (n=47; a). (b–c) A subgroup analysis of CST changes during the study. (b) CST changes in eyes that received additional injection at week 20 (n=35) and eyes without additional injection (n=12). There were similar CST changes in both groups. (c) CST changes along the study according to the number of bevacizumab injections prior to enrollment to the study. There were similar CST changes in both groups. *P<0.05 for the comparison of baseline vs follow-up examination in the same group. Error bars represent SEM.

Figure 2

The mean change in BCVA measured by ETDRS letters (n=47) during the study period (a). (b–c) A subgroup analysis of the mean change in BCVA during the study. (b) BCVA changes in eyes that received additional injection at week 20 (n=35), and in eyes without additional injection (n=12). (c) BCVA changes along the study according to the number of bevacizumab injections prior to enrollment to the study. There were similar BCVA changes in both groups. *P<0.05 for the comparison of current vs follow-up examination. Error bars represent SEM.

Figure 3

Seventy-four-year-old female who previously received five bevacizumab injections had SRF, IRF, and PED at baseline (a). Following the first aflibercept injection there was complete absorption of the IRF and minimal remnants of SRF (b), which resolved at week 8 (c). However, after the first bi-monthly interval, at week 16 there was recurrence of SRF and IRF (d). At week 20 there was a resolution of the fluid (e) and the macula remained dry until the end of the study under monthly therapy.