Histologic studies of the intraocular toxicity of imatinib mesylate in rabbits

Abstract

Purpose: To evaluate histologic signs of toxicity of the protein tyrosine kinase inhibitor, imatinib mesylate, in rabbit eyes. Methods: Twenty Dutch-belted rabbits underwent intravitreal injections of 0.1ml solutions of imatinib mesylate. Ten rabbits were killed and enucleated 1 week after injection of imatinib mesylate (1.65mg (four eyes), 165μg (four eyes), and 16.5μg (two eyes)). Ten rabbits injected with imatinib mesylate (165μg (five eyes) and 825μg (five eyes)) were enucleated 1 month later. Eyes were fixed in 10% formalin and stained with haematoxylin and eosin for microscopic examination. Results: All four eyes injected with 1.65 mg of imatinib mesylate and enucleated at 1 week demonstrated ocular toxicity. All four eyes injected with 165μg and enucleated at 1 week showed no ocular toxicity. One of the two eyes injected with 16.5μg and enucleated at 1 week revealed focal areas of subretinal fluid and retinal undulations, suggestive of retinal oedema. None of the 10 eyes injected with imatinib mesylate at either the 165 or 825μg dose and enucleated at 1 month showed ocular toxicity. Conclusions: Imatinib mesylate at 1.65 mg caused extensive retinal toxicity in rabbit eyes. In contrast, lower doses did not appear to cause toxicity, but may be associated with retinal oedema.