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Ruta Maciulaitiene, Symantas Ragauskas, Anna Mari Haapaniemi, Simon Kaja, Ingrida Januleviciene, Giedrius Kalesnykas; Aflibercept shows strong dose-dependency when administered intravitreally in the mouse CNV model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2631. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To study the efficacy and dose-dependency of aflibercept (Eylea®) on retinal leakage in the mouse choroidal neovascularization (CNV) model.
The growth of subretinal blood vessels from the choroid was induced by perforating Bruch’s membrane using a 532 nm diode laser in 8-week old male C57Bl/6J mice (N=24). The successful damage of Bruch’s membrane was verified by fluorescein angiography (FA) and spectral domain optical coherence tomography (SD-OCT). Aflibercept (Eylea®, Bayer AG) was intravitreally administered at a dose of 4 µg, 40 µg and 80 µg per eye (2 µl injection volume) immediately after CNV induction. These doses were chosen with 4 µg representing equivalent of human dose normalized to estimated vitreous volume. Longitudinal in vivo imaging was performed on days 5, 10 and 14. Two weeks after CNV induction mice were sacrificed and isolectin GS-IB4 fluorescence on choroidal flatmounts was quantified using Image J (NIH).
CNV results in significant retinal leakage at all laser sites. Intravitreal administration of aflibercept at high doses (40 µg and 80 µg) completely prevented CNV formation and vascular leak on Day 5, whereas 4 µg significantly decreased CNV formation and vascular leak as compared to saline-injected eyes on Day 5 (One-Way ANOVA, P<0.05). At longer follow-up time on Day 10 and Day 14, retinal leak was significantly increased in all aflibercept-treated eyes as compared to Day 5. However, 4 ug, 40 ug and 80 ug aflibercept treatment showed a statistically significant difference from saline-treated groups at the level of retinal leak and histological assessment of vascular growth from post-laser day 14 (P<0.05 for all).
Aflibercept shows strong dose-dependency in preventing CNV formation and retinal vascular leak in the mouse CNV model. Our data provide relevant insight for study of novel combination therapies for angiogenic disorders of the eye.
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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