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L. Feiner, Y.B. Shui, J. Wickens, E.E. Barr, D.P. Joseph, N.S. Holekamp, M.A. Brantley, Jr.; Evaluation of the Safety of Intravitreal Injection of Avastin in Rabbits and Humans . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5228.
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Avastin, a full length monoclonal IgG antibody with high affinity for vascular endothelial growth factor (VEGF), is FDA approved for intravenous administration in patients with metastatic colorectal cancer. This same preparation is being used off–label for the treatment of exudative age related macular degeneration, macular edema in diabetes and retinovascular disease, and neovascularization secondary to retinal ischemia. To determine the safety of this route of administration, we have injected Avastin at two different dosages into rabbit eyes and performed ERGs and histology at 1 and 5 weeks post injection. We have also retrospectively collected data on adverse events in 38 patients injected with 1.25mg of Avastin at the Barnes Retina Institute.
We have injected one eye of New Zealand white rabbits with either control antibody (a biotinylated horse anti pig IgG; n=2 eyes) or 1.25mg (n=3 eyes) or 5.0mg of Avastin(n=3 eyes). Scotopic and photopic ERGs were performed at approximately 1 and 5 weeks post injection. Hematoxylin and eosin stained sections of control and injected eyes were compared at 1 and 5 weeks post injection. The retinal penetration of control IgG and Avastin was determined using streptavidin or anti–human secondary antibodies in fresh frozen sections. Retrospective chart review in 38 patients injected by a single physician was performed to determine the number of adverse events related to intravitreal injection in humans.
At both concentrations injected, there was no significant difference in scotopic or photopic b–wave amplitudes in in control vs. injected eyes. Initial immunohistochemical studies suggest that Avastin can penetrate the retina. In the 38 patients injected with Avastin, five mild adverse events(foreign body sensation and subconjunctival hemorrhage) and one serious adverse event(hospitalization for bowel stricture in a patient with a history of bowel surgery) were reported.
Avastin does not appear to alter retinal morphology or compromise retinal function in rabbits based on electroretinography and histology. The retinal penetration of full length of IgG supports the biological plausibility that Avastin may have efficacy in treating exudative age related macular degeneration and other retinal diseases. In limited clinical experience, Avastin appears safe. Larger randomized clinical trials studying the safety and efficacy of Avastin versus other anti–VEGF therapies is warranted.
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