Trans-scleral delivery of polyamine analogs for ocular neovascularization

Periocular injections of the polyamine analog CGC-11144 three times a week causes regression of choroidal neovascularization. This regimen was selected to maximize chances of success for proof of concept, but is not ideal for clinical application. In this study we explored other regimens for periocular delivery of CGC-11144, and 2 other polyamine analogs, CGC-11047 and CGC-11093. A single periocular injection of 200 μg of CGC-11144, 2 mg of CGC-11047, or 1.5 mg of CGC-11093 caused significant suppression and regression of laser-induced choroidal neovascularization. An injection of 2 mg of CGC-11047 or 1.5 mg of CGC-11093 one or two weeks before, but not 3 weeks before, rupture of Bruch's membrane also caused significant suppression. Periocular injection of polyamine analogs also caused strong inhibition of retinal or subretinal neovascularization in mice with oxygen-induced ischemic retinopathy or Rhodopsin promoter/VEGF transgenic mice, respectively. These data suggest that periocular injection of one of 3 different polyamine analogs inhibits retinal or choroidal neovascularization and a single injection provides inhibitory activity for at least 2 to 3 weeks, which could provide the basis for a feasible treatment regimen for clinical trials.