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F. Froussart, G. Renard, S. Ponsart, F. Behar-Cohen; Viscous Poly (Orthoester) for the Slow Intravitreal Release of Dexamethasone and 5 FU in a Vitreo Retinal Proliferation Model in the Rabbit . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3598.
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Background : Poly(orthoester) have been shown to be well tolerated in the rabbit eye, by either sub conjunctival, intravitreal or supra choroidal injection. POE have many advantages such as a zero kinetic order for drug release, being injectable, biodegradable and possibility to modulate the release rate. Purpose : evalue potential of POE for the slow release of Dexamethasone or 5-FU to prevent vitreo retinal proliferation in a rabbit model. Materials and methods : VPR was obtained by intravitreal injection of dispase in albinos rabbits. VRP was observed at 1 month after injection. POE was used naked or also combined to 5FU or dexamethasone. In a first experiment, 1% 5FU POE (0.1 and 0.2 ml) was injected at one day after the dispase injection, by either sub-conjuntival or intravitreal route. Clinical and histological analysis were performed at either day 15 or 30. In a second experiment, POE was injected only by intravitreal route to compare the efficacy of both drugs and their combination ; clinical examination was completed by a direct macroscopic analysis post mortem at day 30. Results : After subconjonctival injection of POE with 5FU, VRP is reduced at 15 or 30 with only focal folds and a reduced intraretinal desorganisation. Dexamethasone POE injected sub conjunctivally resulted in a minimal VRP reaction a preserved retinal structure. The intravitreal injection of naked POE in normal rabbits resulted in no inflammatory reaction and no histological damage of eye tissues. In the group 5FU or dexamethasone only local retinal folds can could be observed but no retinal detachments. The macroscopic post mortem analysis of the rabbits’ eyes in the second protocol confirm that PVR is maximal in the group POE alone, decrescendo in the group POE 5Fu or POE dexamethasone and is finally minimal in the group POE 5FU combined to dexamethasone. 5FU and dexamehasone seem to have different effects on VRP development and the combination of both drugs, released by a single intravitreal injection of POE, prevented VRP. Conclusions : Combination of 5FU and dexamethasone in a polymeric biodegradable matrix such as POE is efficient in the rabbit model of PVR created by dispase intravitreal injection. POE is a soft injectable biodegradable polymer which offers advantages compares to solid implantable devices.
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