Abstract
Abstract: :
Purpose: To evaluate subconjunctivally injected carboplatin in fibrin sealant as a possible treatment for retinoblastoma, ERGs were performed on rabbits to test for retinal toxicity. Methods: One group of rabbits received a unilateral subconjunctival injection of carboplatin (Paraplatin®) impregnated in fibrin sealant (Hemaseel APR®), which had a final concentration of 20.4 ± 7.3 mg/mL. Another group of rabbits received 11.2 ± 0.8 mg/mL of carboplatin in balanced salt solution (BSS), the currently used vehicle. Two additional control groups of rabbits were similarly injected with fibrin sealant and BSS without carboplatin. Baseline ERGs were performed on all rabbits prior to injection and at 2 days, 1, 2, and 3 weeks after injection. During each testing session, the animals were dark adapted for two hours, anesthetized, and pupils were dilated with 1% tropicamide and 2.5% phenylephrine HCl. The ERG was recorded with a Jet contact lens electrode with a 6mm Grass cup reference electrode placed in the mouth and a 1 cm needle ground electrode placed subcutaneously in the trunk. Signals were amplified (.01 to 1,000 Hz), averaged and stored using a Diagnosys Espion System. Flash stimuli were presented in order of increasing intensity to both dark-adapted eyes using a bifurcated fiber optic cable with a Diagnosys hand-held ganzfeld. Following 10 minutes of light adaptation, a light-adapted intensity series was presented to isolate cone function. Atomic absorption spectrophotometry was used to confirm the concentration of carboplatin in each injection. Results: Both dark and light-adapted ERG amplitudes and implicit times showed no significant changes from control eyes at any time after treatment with carboplatin in either vehicle or in the vehicles alone. Conclusion: At the current concentrations, the use of locally administered carboplatin in fibrin sealant does not adversely affect retinal function and remains a feasible approach in delivering carboplatin in a time-released fashion for the treatment of retinoblastoma. Support: NEI Core Grant P30-EY06360, Knights Templar Educational Foundation, Foundation Fighting Blindness, RPB, Inc., and Department of Veterans Affairs.
Keywords: 390 drug toxicity/drug effects • 396 electroretinography: non-clinical • 569 retinoblastoma