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Ofra Benny, Zai-Long Chi, Lauren Bazinet, Robert D'Amato; Periocular injection of a broad spectrum antiangiogenic therapy regresses choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4657.
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Current therapies with intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents for intraocular neovascularization suppress neovascularization and vessel leakage. However, nearly half of AMD patients do not respond to this therapy, and those that do require injections repeatedly and chronically, poising them for clinical ocular complications. The purpose of our study is to develop a less invasive, local treatment that can safely be administered chronically, as a means of simultaneously improving the potency of treatment and reducing the burden for patients with AMD.
Lodamin is a polyethylenglycol-poly lactic acid (PEG-PLA) conjugate of the antiangiogenic drug TNP-470, a Methionine aminopeptidase 2 (MetAp2) inhibitor and selective cytostatic agent of endothelial cells. A laser-induced CNV model was used in C57/Bl mice, with 6 lesions inflicted per retina. Average CNV size was measured following isolectin IB4 staining of retinal vessels.
Lodamin was administered as a single retrobulbar or peribulbar injection (100ug per eye) on the day of laser treatment. By day 7, 42% inhibition and 34% inhibition in CNV size was recorded, respectively. Additionally, experiments were performed with established CNV lesions where treatment was given on Day 7 post-laser. In these cases, Lodamin was able to regress CNV by 45% as measured on day 14 post CNV induction.
We have previously demonstrated Lodamin to be a potent broad-spectrum antiangiogenic drug in multiple angiogenic models. Lodamin was effective in treating CNV when administered orally. However in the interest of reducing systemic exposure, local administration (intravitreal) was explored, yielding positive results. We now show that Lodamin is also effective when given by periocular administration, thus minimizing the risks clinically associated with intravitreal injection. Lodamin’s ability to regress preexisting neovascularization together with its improved delivery may change the paradigm of patient therapy and improve current disease treatment.
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