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Jade Gieseke Gieseke Guevara, Andres Gonzalez, Clay Clay Smith, Swati Agarwal-Sinha, Sarina Amin; Aflibercept does not inhibit normal retinal vascular development in the mouse model of oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):772.
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Literature on the efficacy and safety of aflibercept in the treatment of retinopathy of prematurity (ROP) is scarce despite promising outcomes in animal models. The goal of this study is to determine if the drug has a detrimental effect on normal vascular development.
81 mouse eyes were randomly assigned to a room air control (n=21) or hyperoxic conditions with 75% oxygen (n=60). The hyperoxia eyes were assigned to one of three groups: 0 ng (n=13), 100 ng (n=25), or 1000 ng (n=22) of aflibercept. Intravitreal aflibercept injections were administered on day 14 of life. The eyes were randomly assigned to be enucleated 3 days (P17) or 12 days post-injection (P25). The retinas were extracted and stained with anti-collagen IV antibody to highlight vasculature. Flat mount preparations were photographed, and areas of perfusion and non-perfusion were quantified using Image J software. The ratios between average nonperfused area of the hyperoxic groups and average perfused area of the control groups were determined and a two-sample test for equality of ratios was performed to determine statistical significance.
There was no significant difference in the ratio of nonperfused area between the hyperoxic control and the 100 ng and 1000 ng treatment eyes, or between the 100 ng and 1000 ng treatment eyes in the P17 group. For the P25 group, the hyperoxic control eyes had a larger ratio of nonperfusion compared to the 1000 ng eyes which was statistically significant (p<0.05). Otherwise, there was no significant difference between ratios in the P25 group between the hyperoxic control, 100 ng, and 1000 ng treatment groups. When comparing the P17 and P25 groups, there was a statistically significant decrease (p<0.05) in the ratio of nonperfusion for the 1000 ng treatment dose in the P25 group compared to the P17 group.
In the P25 group, eyes treated with 1000 ng aflibercept had a significantly lower ratio of retinal nonperfusion compared to the untreated hyperoxic control. The P25 100 ng eyes did not show significant difference in ratio of nonperfusion compared to the untreated hyperoxic control eyes. These results suggest the effect of aflibercept dissipates between 3 and 12 days post-injection, and that normal retinal vasculature is not completely inhibited at the 1000 ng dose by day 12 post-injection.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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