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R Buddi, SL Perkins, JM Burke, DP Han; Intravitreal Injection of Human Immune Globulin in Rabbit eyes: Histopathology and Immunohistochemical Localization . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4443.
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Purpose: To determine the histopathological changes and immunohistochemical localization following intravitreal injection of human immune globulin (HIG) in rabbit eyes. This study is preliminary to a larger study determining the efficacy of HIG in staphylococcal exotoxin induced intraocular inflammation. Methods: Twenty four rabbit eyes were injected in the vitreous with 0.5, 2.5, 10, 20 and 30 mg of commercially available HIG (Gamimune, N). The eyes were harvested on post-injection day 1, 2, 3, and 5. Formalin fixed, paraffin embedded sections were used for H & E and immunoperoxidase staining with a human IgG specific antibody. Controls included normal rabbit eyes, eyes injected with diluent, and human tonsil (positive control). Results: Ten of the twenty-four eyes showed minimal mononuclear cell infiltration. This was predominantly pre-papillary or pre-retinal, appeared on day 2, and was independent of HIG dose. Intense HIG labeling was localized to the vitreous, posterior epithelial layer of the iris, inner layer of the ciliary epithelium, retina (predominantly inner nuclear layer and outer segments layer), and retinal pigment epithelium. This staining was noted at all time points. Ten eyes also showed linear focal staining in the outer choroids anterior to the equator. Intense staining was also noted in collagenous septae of the optic nerve head. Conclusion: Intravitreal injection of HIG induces minimal or no inflammation in rabbit eyes for the duration studied. In a normal eye, HIG persists in the vitreous cavity as well as other ocular structures for at least 5 days post-injection. High doses of intravitreal HIG can cross the intact retina, and in some eyes cross into the choroid. Recent studies by others suggest that periocular IgG molecules can cross an intact sclera, choroid, and retina. Trans-retinal migration of HIG could be secondary to the large amounts injected, and may therapeutically benefit toxin mediated intraocular inflammation such as in endophthalmitis.
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