Penetration of chemotherapy into vitreous is increased by cryotherapy and cyclosporine in rabbits
T. W. Wilson, H. S. Chan, G. M. Moselhy, D. D. Heydt Jr, C. M. Frey and B. L. Gallie
Department of Pediatric Ophthalmology, Geisinger Medical Center, University of Pennsylvania, Danville, USA.
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 intravitreal 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 intravitreal penetration of
carboplatin, and this strategy may enhance the capacity of chemotherapy to
cure intraocular retinoblastoma, particularly avascular tumors such as
vitreous seeds.