Evaluation of toxicity after periocular and intravitreal administration of carboplatin in rabbit eyes

The aim of this study was to characterize the extent of toxicity of focal carboplatin administration and to identify the dose limiting toxicity in rabbit eyes depending on administered concentrations. New Zealand white male rabbits (n = 18) were treated with 1 of 3 regimens: a single periocular injection of 15 mg of carboplatin (group I), a single periocular injection of 30 mg of carboplatin (group II) and a single transcorneal intravitreal injection of 0.05 mg of carboplatin (group III). Ophthalmologic examinations and vitreous samplings were performed under dissociative anaesthesia at regular intervals during next 2 (groups I and III) or 3 (group II) weeks. Carboplatin concentrations in vitreous samples were assessed by atomic absorption spectroscopy. At the end of experiments, all rabbit eyes were obtained for histopathologic examination. Clinical and histological evidence of toxicity was graded into four grades according to anatomical structures of the rabbit eye. The dose limiting toxicity was reached in group II after periocular injection of 30 mg of carboplatin and in group III after intravitreal injection of 0.05 mg of carboplatin. No systemic toxicity was observed in any group. Focal carboplatin administration may decrease systemic exposure to this cytotoxic drug in the retinoblastoma treatment. This moreover suggests that focal carboplatin administration is a promising approach and challenge for advanced retinoblastoma chemotherapy.