Subconjunctival carboplatin therapy and cryotherapy in the treatment of transgenic murine retinoblastoma

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 mu g. 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 mu g In animals treated with cryotherapy alone, no tumor control was noted (O of 6). In animals treated with subconjunctival carboplatin coupled with cryotherapy, a tumor control dose of 417 mu g 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.