Comparative efficacy of bevacizumab and aflibercept in the rabbit DL-AAA model of chronic retinal neovascularization

Abstract

Purpose : Intravitreal administration of DL-α-aminoadipic acid (DL-AAA) induces chronic retinal neovascularization (RNV). Here we compared efficacy of biosimilar bevacizumab and aflibercept against RNV induced by DL-AAA in Dutch Belted rabbits.

Methods : Adult Dutch-Belted rabbits (DB) were selected, randomized and sorted into 3 treatment groups: DL-AAA followed by 1) intravitreal (IVT) administration of aflibercept at a dose of 250 µg/eye, 2) IVT administration of bevacizumab at a dose of 1 250 µg/eye, and 3) IVT administration of saline.
The animals were monitored prior to RNV induction and during the whole 21 week follow-up period post-induction using in vivo imaging, spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA). RNV was induced in DB rabbits by intravitreal injections of DL-AAA. DL-AAA-characteristics changes of RNV were monitored using in vivo imaging at 1 week post- injection and every 2 weeks at later time points. At 13 weeks post-induction bevacizumab, aflibercept or saline were intravitreally injected. The animals were followed for the additional 8 weeks.

Results : The RNV-associated leakage was detected already on the first week in all DB rabbits that received DL-AAA injection. The mean leakage area was 41.9 µm ² ± 20.9 µm². At weeks 5-7 post-induction the RNV leakage peaked to 56.9 µm² ± 25.6 µm² and remained unchanged until week 13. Intravitreal administration of bevacizumab decreased the leakage area by 11.4 µm² ± 8.6 µm² and aflibercept treatment decreased the leakage area by 7.2 µm² ± 5 µm² at 2 weeks post-treatment administration as compared to saline-treated eyes.
At later time points the RNV leak again increased to 30.2 µm² ± 7.4 µm² in the aflibercept group and to 61.9 µm² ± 23.6 µm² in the bevacizumab group. The saline/treated eyes had a leakage of 56.7 µm² ± 12.5 µm².

Conclusions : Both bevacizumab and aflibercept significantly decreased the leakage area after intravitreal administration equally well. However, in a long term aflibercept was more efficacious to decrease RNV leak as compared to bevacizumab.

This is a 2020 ARVO Annual Meeting abstract.