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K.R. Van Quill, P.K. Dioguardi, C.T. Tong, J.A. Gilbert, T.M. Aaberg, Jr, H.E. Grossniklaus, H.F. Edelhauser, J.M. O'Brien; Subconjunctival Carboplatin in Fibrin Sealant in the Treatment of Transgenic Murine Retinoblastoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1108.
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Purpose:Fibrin sealant is a human protein–derived surgical adhesive that provides a biodegradable, semi–solid medium for sustained transscleral drug delivery. We evaluated the efficacy of subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma. Methods:Three groups of eleven 10–week–old LHß–Tag transgenic mice were treated with a single 30 µl injection of fibrin sealant in the subconjunctival space of one eye; the opposite eye was left untreated as an internal control. Group 1 (low–dose group) received 37.5 mg/ml calculated concentration of carboplatin in fibrin sealant (0.66 mg measured total dose). Group 2 (high–dose group) received 75 mg/ml calculated concentration of carboplatin in fibrin sealant (1.23 mg measured total dose). Group 3 (control group) received fibrin sealant only. Mice were sacrificed on day 22 post–treatment. Eyes were serially sectioned, and ocular tumor burden was quantified by histopathologic analysis. Results:The best therapeutic results were obtained in eyes treated with low–dose carboplatin in fibrin sealant, where no histopathologic evidence of toxicity was observed and 6 of 11 eyes had zero tumor burden. Tumor burden in the remaining five eyes in this group was minimal (4 eyes) or moderate (1 eye) in comparison to mean control values. Mean tumor burden in this low–dose group was significantly smaller than mean tumor burden in untreated eyes from the same mice (p<.004), sealant–treated eyes in the control group (p<.004), and untreated eyes in the control group (p<.002). While a similar reduction in mean tumor burden was observed in eyes treated with high–dose carboplatin in fibrin sealant, 5 of 10 eyes analyzed in this group also demonstrated histopathologic evidence of severe toxicity. Conclusions:Subconjunctival carboplatin in fibrin sealant is effective in the treatment of transgenic murine retinoblastoma. A single injection of low–dose carboplatin in fibrin sealant was sufficient to induce complete or near–complete intraocular tumor regression in 10 of 11 eyes (91%), with no associated histological evidence of toxicity. These results suggest that subconjunctival carboplatin in fibrin sealant provides sustained release and could have clinical utility in the treatment of intraocular retinoblastoma.
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