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November 1996

Penetration of Chemotherapy Into Vitreous Is Increased by Cryotherapy and Cyclosporine in Rabbits

Author Affiliations

From the Department of Pediatric Ophthalmology (Dr Wilson) and the Janet Weis Research Center (Mr Heydt and Dr Frey), Geisinger Medical Center, University of Pennsylvania, Danville; the Divisions of Hematology/Oncology (Dr Chan) and Immunology and Cancer Research (Drs Gallie and Chan), The Hospital for Sick Children Research Institute, and the Departments of Ophthalmology, Molecular and Medical Genetics (Dr Gallie), and Pediatrics (Dr Chan), The Hospital for Sick Children and the University of Toronto; and Occupational Health Laboratory, Ontario Ministry of Labour (Ms Moselhy); Toronto, Ontario. None of the authors has proprietary interest in the development or marketing of the agents that were used in the study.

Arch Ophthalmol. 1996;114(11):1390-1395. doi:10.1001/archopht.1996.01100140590011

Objective:  To investigate whether cryotherapy, which induces a serous effusion in retina, might increase access of systemic chemotherapy into the vitreous.

Methods:  The right eyes of 18 rabbits were treated with triple or single freeze-thaw cryotherapy at 1 or 2 locations, 1 day before administering intravenous carboplatin with or without cyclosporine. Control left eyes received no cryotherapy. The rabbits were killed 2 or 24 hours after chemotherapy, and carboplatin concentrations were measured in the vitreous of each eye and in blood.

Results:  A significant increase was found in intravit-real carboplatin concentrations when cryotherapy was applied (P<.001) or high-dose cyclosporine was administered (P<.001) and if 2 locations were frozen compared with 1 location frozen (P=.02). Intravitreal carboplatin concentrations were always significantly greater after cryotherapy, either when the corresponding blood carboplatin concentrations were high (2 hours after completing treatment) or when they had dropped to much lower levels (at 24 hours). The triple freeze-thaw technique did not yield significantly better results than a single freeze-thaw technique.

Conclusion:  Cryotherapy administered 24 hours before chemotherapy significantly increased the intravit-real penetration of carboplatin, and this strategy may enhance the capacity of chemotherapy to cure intraocular retinoblastoma, particularly avascular tumors such as vitreous seeds.

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