A High Dose Rate Palladium (103Pd) Applicator Safety and Feasibility Study Using Normal Rabbit Eyes

Abstract

Abstract: : Purpose: The rabbit eye was used for safety testing of a ¹⁰³Pd high dose rate device being developed by Theragenics Corporation (Buford, GA) for potential use in treatment of Age-Related Macular Degeneration (ARMD). Methods: In this pilot study, conducted at the Charles River Laboratories (Worcester, MA), the right eye of four groups of male New Zealand White rabbits were irradiated with a 0, 10, 20, or 50 Gy dose in a single 5 to 25 minute fraction. A 5 mm aperture ¹⁰³Pd applicator was positioned adjacent to the optic nerve and held in place to deliver the prescribed dose to a depth of 3 mm into the eye. The left eye of each rabbit was used as a control. During the study, daily clinical observations, weekly ophthalmic observations and body weights were recorded. An electroretinogram and a final ophthalmic examination were performed on each rabbit at the end of the 29 day study. On Day 29, all rabbits were euthanized, and both eyes were enucleated and submitted for histopathologic examination. The eyes were fixed in Davidson's fixative. A central calotte that included the treatment site from each eye was processed, embedded in paraffin, and sectioned. The glass slides were stained with hematoxylin and eosin, and then evaluated by light microscopy. Results: On day 5, the rabbit eyes in all treatment groups regardless of delivered radiation dose had mild conjunctival injection attributed to the treatment procedure. Electroretinograms were comparable for both eyes (treated and untreated) of all but two rabbits. In both of these rabbits, the low A-B amplitude was thought to have been a preexisting condition. Final ophthalmic findings for two rabbit eyes in the high-dose group (50 Gy) revealed chorioretinal hypovascularization that appeared to be treatment related. Two retinal detachments were noted in untreated eyes during the final ophthalmic examination. Histopathologic examination of the additional rabbit eye in the high dose group showed focal retinal atrophy involving the outer nuclear and photoreceptor layers of the retina in the posterior portion of the globe. No lenticular or scleral side effects were noted. Conclusion: The rabbit eye was used as an ocular model for safety testing of the ¹⁰³Pd high dose rate applicator. No adverse events could be attributed to the treatment methodology or the physical parameters of the device. An acute vascular effect within the choroid and retina appeared at a treatment dose of 50 Gy.

Keywords: age-related macular degeneration • radiation therapy • animal model