Evaluation of Effects of Intraocular Delivery of Beta–Radiation

Abstract

Abstract: : Purpose: To evaluate and quantify the acute effects of focal intraocular delivery of beta radiation on retinal and subretinal tissue over a prescribed dose range. Methods: Forty rabbits underwent pars plana vitrectomy and received controlled intraocular strontium⁹⁰ beta–radiation using a novel radiation probe. Four study groups of 10 rabbits each, received 2 dosages in different retinal locations. The following dosages were evaluated: 0, 26, 51, 77, 82, 164, 246 Gy. Rabbits were followed for 3 (N=20) and 6 months (N=20). Main outcome measures included changes in the fundus appearance, fluorescein angiography (FA), electroretinography (ERG) and histology. Primary tissues of interest are the neural retina, retinal pigment epithelium (RPE), Bruch’s membrane/choriocapillaris complex, and choroid. Results: Controlled intraocular delivery of beta–radiation was achieved in all eyes. No intra–operative or peri–operative complications were observed. No detectable change was observed on electroretinography in any of the rabbits at 3 and 6 months. No abnormalities in fundus appearance, FA, or light microscopy were observed in any animals receiving 77 Gy or less. However, in subgroups receiving 82 Gy or more, changes were observed including retinal vascular attenuation, myelin atrophy, retinal vessel obliteration, RPE atrophy, and RPE proliferation on biomicroscopy (and in color photographs). In addition, FA in these animals revealed retinal vascular non–perfusion, abnormal hyperfluorescence, and delayed choroidal filling. Light microscopy disclosed changes in the outer nuclear layer and subretinal space, including retinal gliosis, RPE proliferation, decreased pigmentation or hyperpigmentation of RPE, RPE loss, RPE atrophy and RPE hypertrophy. No progression of these acute toxic effects was observed between 3 and 6 months after radiation exposure. Conclusions: Short–term toxicity data demonstrates that the minimum threshold for acute damage with this approach is above 82 Gy. Further studies to evaluate the role of local delivery of strontium⁹⁰ beta–radiation in the treatment of AMD are warranted.

Keywords: age-related macular degeneration • choroid: neovascularization • radiation therapy