Subconjunctival Carboplatin in Fibrin Sealant in the Treatment of Transgenic Murine Retinoblastoma
Received 5 August 2004; accepted 29 November 2004. published online 09 May 2005.
Purpose
To evaluate the efficacy of subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma.
Design
Experimental study using LHβ-Tag transgenic mice in a randomized controlled trial.
Participants and Controls
Thirty-three 10-week-old LHβ-Tag transgenic mice: 22 carboplatin-treated animals and 11 control animals.
Methods
Three groups of 11 mice were treated with a single, 30 μl injection of fibrin sealant in the subconjunctival space of 1 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 killed on day 22 after treatment. Eyes were serially sectioned, and retinal tumor burden was quantified by histopathologic analysis. For statistical analysis of treatment effects, eyes were divided into 6 groups: low-dose group, sealant-treated eyes; low-dose group, untreated eyes; high-dose group, sealant-treated eyes; high-dose group, untreated eyes; control group, sealant-treated eyes; and control group, untreated eyes.
Main Outcome Measures
Main outcome measure was mean tumor burden per level per eye in each experimental group.
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 5 eyes in this group was minimal (4 eyes) or moderate (1 eye) compared with mean control values. Mean tumor burden in this group was significantly smaller than mean tumor burden in untreated eyes from the same mice (P<0.004), sealant-treated eyes in the control group (P<0.004), and untreated eyes in the control group (P<0.002). Although 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 histologic evidence of toxicity. These results suggest that subconjunctival carboplatin in fibrin sealant provides sustained release and could have clinical use in the treatment of intraocular retinoblastoma.
1Ocular Oncology Unit, Department of Ophthalmology, University of California at San Francisco, San Francisco, California
2Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia
Reprint requests to Joan M. O’Brien, MD, Director, Ocular Oncology Unit, UCSF Department of Ophthalmology, 10 Koret Way, Box 0730, San Francisco, CA 94143.
Manuscript no. 240606.
Supported by a grant from Foundation Fighting Blindness, Owings Mills, Maryland (HFE); That Man May See Foundation, Inc., San Francisco, California (JMO); and the National Eye Institute, Bethesda, Maryland (grant no.: EY13812 [JMO], core grant no.: EY02162).
None of the authors has any commercial or proprietary interest in any of the materials used in the study.
⁎ Mr Van Quill and Dr Dioguardi contributed equally to this study.
ABSTRACT