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Sarina Mahesh Amin, Swati Agarwal, W. Clay Smith, Jade Gieseke Guevara; The efficacy of aflibercept in treating retinopathy of prematurity in the mouse model of oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):193.
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© ARVO (1962-2015); The Authors (2016-present)
Many studies have reported on bevacizumab for the treatment of retinopathy of prematurity (ROP); however, there is a scarcity of literature on the efficacy and safety of aflibercept in the treatment of ROP despite anecdotal evidence of promising outcomes in human neonates. The goal of this study was to assess the efficacy of aflibercept in regression of neovascularization in the mouse model of oxygen-induced retinopathy.
In this study, 14 mice (n=28 eyes) were included and randomly assigned to a room air control (n=10) or hyperoxic conditions with 75% oxygen (n=18). The mice exposed to hyperoxia were assigned to one of two groups: 0 ng (n=8) or 10 ng (n=10) of aflibercept. Intravitreal injections were administered to hyperoxia groups on day 14 of life. Two days post-injection, eyes were enucleated and retinas were extracted. Samples were stained with anti-collagen IV antibody to highlight vasculature. Flat mount preparations were photographed, and areas of perfusion and non-perfusion were quantified using ImageJ software. Statistical analysis was performed using one-way ANOVA with Bonferroni correction.
A significant difference (p<0.05) in vascular and avascular surface areas was noted between the room air control and the hyperoxia groups. Curiously, hyperoxic eyes treated with aflibercept showed increased neovascularization compared to the untreated hyperoxic eyes (p<0.05). There was a notable trend towards reduction of avascular surface area in the aflibercept-treated eyes, although the difference did not reach statistical significance (p=0.06).
Mice exposed to hyperoxic conditions displayed increased vascularity compared with room air controls. Aflibercept-treated eyes showed more vascularity than non-treated eyes possibly due to inadequate dosing or to the short time from injection to enucleation not allowing for treatment effect. Although non-significant, a clear trend was noted for reduced avascular surface area in eyes treated with aflibercept compared with the hyperoxic control. This study will be expanded to increase sample size and to include groups treated with higher doses of aflibercept. This study will help clarify the doses of aflibercept associated with the adverse effect of persistent avascular retina, and ultimately this study can help establish aflibercept as a potential treatment alternative in human neonates with ROP.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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