Selective Immunotherapy for Choroidal Neovascularization with Intravitreal Factor VII–Fc Chimeric Antibody (ICON)

Abstract

Abstract: : Purpose: To test the efficacy of intravitreal mouseICON to selectively ablate laser–induced choroidal neovascularization in the pig. Methods. Subretinal neovascularization was induced by laser photocoagulphotocoagulation in four Yucatan miniature pigs (Sus scrofa). An indirect double–frequency YAG laser (532 nm) was used to deliver 15–25 spots per eye (0.1 seconds, 1.0 W) using a 2.2 D lens.150 µg mouseICON in 100 µl of PBS was injected into the midvitreous cavity either at the time of laser photocoagulation or on day 10. The same amount of PBS was injected into the control fellow eye. At day 14 animals were sacrificed and confocal microscopy was used to determine the presence of choroidal neovascularization. Results: Injection of mouseICON at the time of laser photocoagulation did not decrease the frequency of choroidal neovascularization (47% in the control group vs. 34% in the treatment group), in contrast to injection on day 10 (56% in the control group vs. 25% in the treatment group). No ocular side effects developed within the observation period. Conclusions: MouseICON can selectively obliterate already established laser–induced choroidal neovascularization. Its preferential efficacy on established choroidal neovascularization is probably due to the fact that Factor VII in the immunoconjugate selectively targets Tissue Factor, which is uniquely expressed on the vascular endothelia of choroidal neovascularization.

Keywords: age–related macular degeneration • choroid: neovascularization • neovascularization