Comparison of the effects of intravitreal aflibercept, bevacizumab, and ranibizumab on the retinal function and vasculature after oxygen-induced retinopathy

Abstract

Purpose: Vascular endothelial growth factor (VEGF) level plays a critical role on progression of retinopathy of prematurity (ROP). Anti-VEGF therapies including aflibercept, bevacizumab or ranibizumab have been used as treatment for Advance ROP. Although the efficacy and effectiveness of these drugs on ROP are well recognized, its effect on the retinal function is largely unknown. Therefore, the effects of these 3 drugs on the retinal function and vasculature in ROP were investigated using the mouse oxygen-induced retinopathy (OIR) model Methods: 75% oxygen was provided to C57Bl/6J mice at postnatal day (P) 7 to P12, which were then returned to room air (RA). Intravitreal injection of PBS (control), aflibercept (3.33mg/kg), bevacizumab (5.18mg/kg), or ranibizumab (2.06mg/kg) was performed on one eye on P14. On P21, retinal function was analyzed by scotopic electroretinogram (ERG) and retinal tissue was collected for retinal vasculature visualization using isolectin (GS-IB4) immunohistochemical staining . Results: Three anti-VEGF drugs showed similar effects on the retinal function after OIR. There was increase of a-wave and b-wave amplitudes on P21 in the ipsilateral eyes but none in the contralateral eyes. Similar implicit times of a-wave and longer implicit time in b-wave was observed in ipsilateral eyes receiving the drugs. Meanwhile, there were longer implicit times of both a-wave and b-wave in the contralateral eyes. Although these 3 drugs showed similar effects on retinal function after OIR, a slight difference was noted in the retinal vasculature. Smaller central avascular zone was observed in the aflibercept-treated eyes. Moreover, eyes receiving the 3 drugs showed a reduction of neovascular area, with the largest decrease in the ranibizumab-treated eyes Conclusions: Aflibercept, bevacizumab and ranibizumab displayed similar effects with small difference on retinal function and retinal vascular development in the mouse OIR model, suggesting small difference may exist between these 3 types of anti-VEGF for ROP treatment. Our results provided evidence to support the short-term beneficial effects of these 3 anti-VEGF drugs.