Multimodal Imaging to Detect in vivo Responses to Aflibercept Therapy in a Mouse Model of Type 3 Neovascularization

Abstract

<b><i>Purpose:</i></b> The aim of this study was to characterize the response to aflibercept in a mouse model of type 3 neovascularization, the neoretinal vascularization (NRV) 2 mouse line. <b><i>Methods:</i></b> Twelve NRV2 mice were assigned to one of the following groups: (1) 6 mice were injected with aflibercept 3 µg/g at postnatal day (P) 15 (“aflibercept” group), and (2) the remaining 6 mice did not receive any treatment (“placebo” group). The mice were examined at P30 and P44. <b><i>Results:</i></b> The NRV mice’s retinas were characterized by regions of depigmentation that were topographically associated with hyperfluorescent lesions seen on fluorescein angiography (FA) images. On optical coherence tomography images, intraretinal neovascularizations were visualized as hyperreflective lesions mainly localized within the outer plexiform and outer nuclear layers. The average number of intraretinal neovascular lesions visualized on FA at P30 was 5.0 ± 2.2 in the aflibercept group and 20.7 ± 2.4 in the placebo group (<i>p</i> &#x3c; 0.0001). At P44, the average number of intraretinal lesions was still lower in the aflibercept group, although this difference was not statistically significant (<i>p</i> = 0.088). <b><i>Conclusion:</i></b> Aflibercept therapy was effective in inhibiting pathologic angiogenesis in the NRV2 mouse model. However, the successive treatment washout resulted in an increase in the number of lesions.