Efficacy of Aflibercept Treatment and its Effect on the Retinal Perfusion in the Oxygen-Induced Retinopathy Mouse Model of Retinopathy of Prematurity.

INTRODUCTION Bevacizumab and ranibizumab, which are anti-VEGF medications, are used frequently in the treatment for retinopathy of prematurity (ROP) in infants. Aflibercept, or VEGF-trap, has been used anecdotally but translation and clinical studies are lacking. OBJECTIVE This study investigates the efficacy of aflibercept at reducing areas of non-perfused retina and studies its effect on normal angiogenesis in the oxygen-induced retinopathy (OIR) mouse model of ROP. METHODS C57BL/6J mice were assigned to room air control (n=21 eyes) or hyperoxia with 75% oxygen (n=84 eyes). The hyperoxic mice were assigned to one of three groups: 0 ng (n=14 eyes), 100 ng (n=35 eyes), or 1000 ng (n=35 eyes) of intravitreal aflibercept administered on postnatal day 14 (PN14). Eyes were enucleated at PN17 and PN25 post-injection. Retinas were stained with anti-collagen IV antibody and photographed with microscopy. Areas of perfused and non-perfused retina were quantified using ImageJ software. Statistical comparisons were made using analysis of variance (ANOVA) with Tukey post-hoc comparisons. RESULTS At PN17, there was no significant difference in the area of non-perfused retina between the hyperoxic control and the 100ng and 1000ng aflibercept groups. At PN25, the 100ng (p<0.05) and 1000ng (p=0.008) treatment group displayed less non-perfusion compared to hyperoxic controls. At the 1000ng dose, there was increased non-perfusion compared to the 100ng dose (p=0.02). There was reduced non-perfusion by PN25 compared to PN17 for the 100ng group (p<0.05) with no difference in the 1000ng group. CONCLUSIONS The study shows that area of non-perfused retina decreases effectively with aflibercept at PN25 with 100ng dosage. With the 1000ng dosage, there is an inhibition of the physiological angiogenesis with a higher area of non-perfused retina.