Dose response of rat retinal microvessels to proton dose schedules used clinically: a pilot study.

PURPOSE: This preclinical rat pilot study quantifies retinal microvessel, endothelial, and pericyte population changes produced by proton irradiation METHODS AND MATERIALS: The left eyes of rats were irradiated with single doses of 8, 14, 20, and 28 Gy protons; right eyes, with two fractions. Animals were euthanized, and eyes were removed; elastase digests were prepared, and cell populations were counted in sample fields. Results were compared with unirradiated controls. RESULTS: Progressive time- and dose-dependent endothelial cell loss occurred following all schedules. Cell loss was significantly different from control values (p < 0.001) following 28 Gy and following 20 Gy (p < 0.05) in a single dose. Endothelial cell loss was the same for single- and split-dose schedules. Progressive endothelial cell loss produced vessel collapse and acellular vessel strands. Endothelial cells were in the G(0) phase of the mitotic cycle. 28 Gy produced photoreceptor cell loss. CONCLUSION: The retinal digest is an elegant bioassay to quantify the microvessel population response. Single- and split-dose schedules appear to yield similar outcomes, in terms of endothelial cell density.

Proton beam irradiation of subfoveal choroidal neovascularisation in age-related macular degeneration.

PURPOSE: To assess the safety and potential toxicity of proton beam radiation in the treatment of subfoveal choroidal neovascular membrane (CNVM) due to age-related manner degeneration (ARMD) in a prospective, non-randomised study. METHODS: Forty-eight eyes of 46 consecutive patients with subfoveal CNVM due to ARMD, not amenable to laser photocoagulation, were treated prospectively with a single proton beam exposure. Two dose regimens were evaluated: 8 CGE (Cobalt Gray Equivalent) and 14 CGE. Patients were followed for an average of 22.1 months after proton beam treatment. RESULTS: At the 12 month follow-up, 44% of eyes in the 8 CGE group and 75% of the eyes in the 14 CGE group had stabilized or improved visual acuity. Complex size in the 8 CGE group as measured on standard fluorescein angiography (FA), decreased or had no change initially but showed less effect over time, while the eyes treated with 14 CGE maintained decreased leakage over the follow-up period of 12 months. However, 11 eyes in the 14 CGE group experienced radiation retinopathy, with the onset between 3 and 30 months. Seven of these 11 eyes have demonstrated some visual loss but only 1 eye developed severe visual loss at 15 months after proton treatment. CONCLUSIONS: To date, 14 CGE has suggested a favourable influence on visual function and growth inhibition of CNVM. Proton beam irradiation appears to inhibit CNVM growth. The 14 CGE dose regimen appears to have a longer effect of CNVM growth than does 8 CGE, with overall stabilisation of visual function and growth inhibition. Radiation retinopathy has developed over time, but severe visual loss has been limited. On the basis of the incidence of radiation retinopathy, adjustments in the total radiation dosage and/or fractionation of the dosage should be considered.