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CL Rowe-Rendleman, A Higa, S Iwai, A Ellis, K Hecker, D Armstrong; Prophylactic Intra-Scleral Injection of Steroid Compounds in Rabbit Model of Retinal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3872.
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Purpose: The 18:2 form of lipid hydroperoxide (LHP) forms free radicals in cells and produces retinal neovascularization (NV) when injected intra-ocularly at the retinal-vitreous border in rabbits (Ueda et al., Angiogenesis 1997; 1:174-1). We developed a technique to deliver drugs to the retina via the sclera and evaluated the deposition of 18:2 LHP as a biomarker after intra-scleral injection in rabbits and investigated whether prophylactic intra-scleral injection of steroids could retard LHP-mediated NV in rabbits. Methods: Intra-scleral injections of medroxyprogesterone, triamcinolone, and fluocinolone at doses known to be tolerated in the eye were made OS on days 1-3. An intra-ocular injection of LHP was introduced to the steroid-treated eye on day 4. The sister eye was left untreated or received LHP as an internal control. Fluorescein angiograms (FAG) and fundus photography were used to confirm the diffusion of LHP and blood vessel leakage. IOP was monitored before and after the injections with LHP. The animals were sacrificed at either 2 or 4 weeks after LHP injection. Retinal anatomy was evaluated with histology. Results: Fundus photography, FAG, and histology taken after steroid injection indicated that intra-scleral delivery of steroids alone was not damaging to retinal anatomy. IOP did not increase in animals injected with steroid. Intra-scleral injections of LHP alone produced localized degeneration in the RPE and ONL. Histological examination after intra-ocular injection of LHP to form NV indicated minimal capillary proliferation, degeneration of photoreceptors and loss of 2-3 rows of cells in the ONL at 2 weeks and fibroplasia and scarring that involved 1/4 -1/2 of the retina at 4 weeks. Eyes that had received both LHP and steroid had no capillary proliferation, but more extensive degeneration of the retina, RPE and inner layer of the choroid. Conclusions: Steroids and similar drugs may be safely injected directly into the scleral matrix near diseased or cellular targets in the posterior segment. A practical and minimally invasive method of drug delivery now in development uses a micro-surgical approach to pierce the epi-sclera and deposit drug directly in the sclera for diffusion to the choroid, RPE, and retina. In this model, the prophylactic introduction of steroids through the sclera enhances the damaging effects of LHP in the retina, most likely through additional reactive species generated in the choroid and retina.
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