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: Eighty rabbits underwent pars plana vitrectomy and received controlled intraocular strontium90 beta–radiation using a novel radiation probe. Eight study groups of 10 rabbits each, received 2 dosages in different retinal locations. The following dosages were evaluated: 0, 13, 19, 26, 32, 38, 41, 51, 62, 77, 82, 103, 123, 164, and 246 Gy. Rabbits were followed for 1 (N=40) or 2 months (N=40). 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 4 and 8 weeks. No abnormalities in fundus appearance, FA, or light microscopy were observed in any animals receiving 103 Gy or less. However, in subgroups receiving 123 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 4 and 8 weeks after radiation exposure. Conclusions: Short–term toxicity data demonstrates that the minimum threshold for acute damage with this approach is above 103 Gy. Further studies to evaluate the role of local delivery of strontium90 beta–radiation in the treatment of AMD are warranted.
Keywords: radiation therapy • pathology: experimental • retina