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Y. Fu, L. Ponce, M. Thill, P. Yuan, N. Wang, K. Csaky; Inhibition of Laser-Induced Choroidal Neovascularization by a Sustained Delivery of an Integrin Antagonist EMD 478761. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5813.
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To evaluate the inhibitory effects of an integrin antagonist in a laser-induced choroidal neovascularization (CNV) using an intravitreal sustained release implant.
CNV was induced in Brown Norway rats with a diode laser. Polyvinyl alcohol (PVA)-based reservoir type microimplants (A and B) releasing EMD 478761 at different rates (18.1, 11.5ug/day) were designed. The microimplants measuring 1x1x2 mm consisted of a compressed drug core embedded within a PVA matrix. In vitro release rates were measured by assaying drug concentrations over time using an HPLC. In the current study, an EMD microimplant or sham implant was placed within the vitreous chamber of the right eye and the left eye served as laser control. The rats were sacrificed 1 week or 2 weeks after laser, perfused with FITC-dextran and choroidal flatmounts were generated. Areas of CNV were examined and quantified.
Both types of EMD microimplants inhibited CNV relative to sham controls in a statistically significant fashion. 7 days after laser, in the eyes that received EMD microimplants A and B, the mean CNV areas of lesions decreased 58% and 60% respectively as compared to those of sham implant treated eyes. Similarly, 14 days after laser, the CNV areas from microimplant A and B treated eyes were reduced by 63% and 65%, respectively, compared to those treated with sham implants. In addition, there was no significant difference between sham implant and laser controls.
EMD microimplants demonstrated antiangiogenic properties in a rat model of CNV. This study provided evidence that EMD may be useful in the treatment of eye diseases associated with neovascularization via long acting sustained release intraocular implants.
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