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A.S. Kitzmann, K.H. Baratz, B.G. Mohney, J.S. Pulido, J.D. Cameron, E.S. Lee, R.J. Marler, K.M. Johnson, L.E. Dixon, E.B. Leof; Intraocular Toxicity of Imatinib Mesylate and Rituximab in Rabbits . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4258.
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To evaluate the intraocular toxicity of the protein–tyrosine kinase inhibitor, imatinib mesylate, and the monoclonal antibody, rituximab, in rabbit eyes.
Intravitreal injections of 0.1 mL solutions of imatinib mesylate, rituximab or balanced salt solution were performed on the right eyes of 25 Dutch belted rabbits. All left eyes received no injection. Twelve rabbits were euthanized and enucleated one week after injection of balanced salt solution (2 eyes), or imatinib mesylate 1.65 mg (4 eyes), 16.5 mcg (2 eyes), and 165 mcg (4 eyes). Thirteen rabbits injected with imatinib mesylate 165 mcg (5 eyes), 825 mcg (5 eyes), or rituximab 1 mg (3 eyes) were enucleated one month later. Eyes were preserved in 10% formalin and stained with hematoxylin and eosin prior to microscopic examination.
All 4 eyes injected with 1.65 mg of imatinib mesylate and enucleated at one week had full thickness retinal necrosis and inflammation in the posterior pole, posterior subcapsular cataract and vitritis. One of the 2 eyes injected with 16.5 mcg and enucleated at 1 week revealed focal areas of subretinal fluid and retinal undulations suggestive of retinal edema. All 4 eyes injected with 165 mcg and enucleated at one week showed no ocular toxicity. Of the 10 eyes injected with imatinib mesylate and enucleated at one month, one eye (825 mcg dose) had focal chorioretinal adhesion with intraretinal gliosis in the absence of retinal inflammation or vitritis. One eye (165 mcg dose) had rupture of the posterior lens capsule. Findings in these two eyes were suggestive of injection–related trauma rather than toxicity. No toxicity was observed in the three eyes injected with rituximab. No eyes at any dose had toxicity involving any other intraocular tissue. No abnormalities were noted in any left eyes or the two eyes injected with balanced salt solution.
Imatinib mesylate 1.65 mg caused extensive retinal toxicity in rabbit eyes. In contrast, lower doses did not appear to cause toxicity, except for one eye with retinal edema at the 16.5 mcg dose. Rituximab 1 mg did not cause toxicity. These data will be helpful in establishing non–toxic, intraocular doses of these anti–neoplastic agents.
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