Endothelial cell loss in irradiated optic nerves

Radiation optic neuropathy usually occurs months to years after exposure of the anterior visual pathways to ionizing radiation. It is characterized by high signal on gadolinium-enhanced T1-weighted magnetic resonance imaging. Radiation-induced endothelial cell damage resulting in blood-nerve barrier breakdown is hypothesized to produce this pattern, but histologic evidence of this in the optic nerve is lacking. We attempted to evaluate the effect of radiation on endothelial cells in the optic nerve.

Case-controlled histologic study.

We studied the optic nerves of 16 enucleated eyes from patients with uveal melanoma treated with proton beam irradiation, 6 from normal eyes and 5 from eyes with unirradiated uveal melanomas. Binding of Ulex europaeus agglutinin I (UEA-I) lectin was used to identify endothelial cells in single paraffin sections. Transverse and longitudinal sections of vessels were counted in masked fashion.

There were 49.4+/-6.9 transversely sectioned endothelial cells per millimeter of nerve in 6 optic nerves exposed to 0 to 1000 cGyE ("low-dose") compared with 17.3+/-5.3 in 10 nerves exposed to 5500 to 7000 cGyE ("high-dose") (P = 0.002). Longitudinally sectioned vessels stained with UEA-I were separately identified, with 11.5+/-2.1 in the low-dose group and 5.6+/-1.6 in the high-dose group (P = 0.044). The thickness and staining of the endothelial cell layer appeared greater in the high-dose group. Endothelial cell counts did not correlate with age, gender, acuity, or interval after irradiation.

Increased radiation dosage to the optic nerve correlates with smaller numbers of endothelial cells.