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CJ Cheng, JJ Huang, EM Shrier, M Nissen; Pharmacologic Agents for Prevention and Treatment of Proliferative VitreoRetinopathy in the Rabbit Model . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4507.
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Purpose: Proliferative vitreoretinopathy (PVR) is the most feared complication of vitreoretinal surgery. It is a major cause for the failure of retinal detachment (RD) surgery, often requiring re-operation. The pathogenesis of PVR is unclear and multi-factorial consisting of (1) a retinal break, (2) the release of retinal pigment epithelium (RPE) cells, (3) migration of RPE cells, glial cells, and fibrocytes to the vitreoretinal surface with membrane formation, (4) and contraction with new retinal breaks and tractional RD, (5) and formation of collagen. There are no reliable methods for the induction of PVR in animals. A new model of PVR, utilizing dispase, a bacterial neutral protease (enzyme) isolated from bacillus sp., allows for the study of PVR by induction of native cells, without creation of a retinal break, addition of exogenous cells, or growth factors. This model of PVR is technically simple, with a clear view of the retina, and is highly reliable. Using dispase, we can consistently reproduce an animal model of PVR. Our goal is to develop new pharmacologic modalities for the treatment and prevention PVR. Methods: After one week of habituation to their environment, all animal eyes will be injected with dispase. Drugs, such as steroids, retinoic acid, and anti-metabolites may be given at time of dispase injection to alleviate the development of PVR. Upon detection of PVR, the animal eyes will undergo a standard three-port, trans-pars plana vitrectomy (TPPV). The course of surgery will be varied depending upon degree of PVR; membranes will be cut, segmented and removed where possible. Conventional non-toxic perfluorocarbon liquid and purified air (20-25 cc) will also be utilized. Several modified vitreous substitutes will be used with drug agents to assist the prevention of RD and recurrent PVR. Results: Eyes will be examined every other day by ophthalmoscopy and post-operatively. Vitreous may be sampled weekly for statistical treatment data. The disease process will be graded with clinical examination, photos, observer scoring, success of reattachment, and histopathologic findings. ERG and ultrasound may be used to assess retinal function and quantify disease progression. Conclusion: Proliferative vitreoretinopathy complicates all retinal surgeries and often necessitate re-operation. Pharmacologic agents with the ability intra-operatively to prevent the development of PVR can greatly facilitate the success of all vitreoretinal surgery. Many of the agents can be combined with vitreous substitute for a time-delayed drug delivery system.
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