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MB Goddard, P O'Rourke, S Sherman, W Bell, A Lim, S McGuire, V Budz, A Geltzer, W Tao; Safety, Tolerability and Toxicology Evaluation of Encapsulated Cell Based Intraocular Delivery of CNTF in Minipigs . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2306.
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Purpose: The objective of the current study was to evaluate the safety, tolerability and toxicology of continuous, low dose administration of CNTF delivered via encapsulated cells directly into the vitreous of the eye in minipigs. The dose-range effect and time course of the treatment were investigated. Methods: Polymer membrane capsules (1.0 cm in length and 1.0 mm in diameter) were loaded with mammalian cells that were genetically engineered to secrete CNTF. The cell containing capsules were then surgically implanted into the vitreous of one eye of each minipig. The contralateral eyes were not treated. The capsules remained in the eyes for either 3 months or 6 months. Clinical monitoring and blood chemistry evaluation were conducted 2 weeks post implantation and at monthly intervals thereafter. At the end of the studies, the capsules were explanted and CNTF output and cell viability were evaluated. The eyes and all major tissues were examined at necropsy and processed histologically for microscopic examinations. Results: The surgical procedure for implantation of the capsules was well tolerated with no signs of postoperative discomfort and no complications noted. No systemic adverse effects were observed, including fever, weight loss, and changes in blood chemistry. No major adverse effects to the cornea, lens and retina in the treated eyes were observed. In some animals (∼20%), intraocular implantation of a CNTF secreting capsule was associated with transient redness and vascular engorgement of the iris, peaking at 2-4 weeks post implant and subsiding thereafter. Preliminary histologic evaluation indicates that this finding is not associated with inflammatory changes to the iris or new vessel formation. In some cases, small focal lens opacities (not affecting visualization of the fundus) were seen in the equatorial region of the posterior capsule, possibly associated with direct contact by the device or high CNTF dose. Conclusion: Continuous, low dose administration of CNTF delivered via encapsulated cells directly into the vitreous of the eye appears to be safe. The surgically implanted, cell containing capsules were well tolerated during the 3-6 months implantation intervals. Toxicologic findings based on clinical pathology, histopathology and clinical exams were benign.
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