Subconjunctival Carboplatin Therapy and Cryotherapy in the Treatment of Transgenic Murine Retinoblastoma

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Abstract
Objectives: To determine the efficacy and dose response of subconjunctival carboplatin with and without cryotherapy in the treatment of murine transgenic hereditary retinoblastoma. Methods: Fifty-one 5-week-old transgenic BLH SV-40 (Charles Rivers Laboratories, Boston, Mass) T-antigen-positive mice with retinoblastoma were administered 6 subconjunctival injections of carboplatin in 1 eye at drug doses of 10, 15, 20, 25, 62.5, 125, and 250 μg. Six control eyes received 6 subconjunctival injections of balanced salt solution. Fourteen of the 51 subconjunctivally treated eyes received a single application of transconjunctival cryotherapy immediately prior to each carboplatin injection. Six control eyes received 6 single applications of transconjunctival cryotherapy using the above schedule but did not receive carboplatin. All experimental and control eyes were obtained at 16 weeks of age for histopathologic examination. Results: A dose-dependent inhibition of intraocular tumor growth by subconjunctivally delivered carboplatin was observed in these transgenic retinoblastoma mice. Tumor development was inhibited in 50% of the mouse eyes at doses of 180 μg. In animals treated with cryotherapy alone, no tumor control was noted (0 of 6). In animals treated with subconjunctival carboplatin coupled with cryotherapy, a tumor control dose of 417 pg was found. No evidence of histopathologic treatment toxicity was noted. Conclusions: Subconjunctival delivery of carboplatin in serial doses effectively inhibits intraocular tumor growth in a dose-dependent fashion in a transgenic murine retinoblastoma model. Cryotherapy does not increase tumor control in this murine retinoblastoma model.