Experimental optic cup enlargement caused by endothelin-1-induced chronic optic nerve head ischemia

Purpose: Vascular insufficiency of the optic nerve bead may contribute to glaucomatous optic neuropathy, especially in normal-tension glaucoma. We investigated the effect of chronic optic nerve head ischemia, created by repeated intravitreal injection of endothelin-1 (ET-1), on the morphology and function of the optic nerve, Methods: In pigmented rabbits, we injected ET-1 (10(-6) M, 10 mu L) into the posterior vitreous of one eye twice a week for 4 weeks (N = 7). The vehicle for ET-1 was injected into the contralateral eye as a control (N = 7). The subsequent observation period was set at 8 weeks. The microcirculation of the optic nerve head was noninvasively monitored with a laser speckle circulation analyzer. To evaluate the changes of visual function, visual-evoked potentials were recorded. Morphologic changes of the optic nerve head were analyzed with stereography, and the ratio of cup area (CA) to disk, area (DA) was measured by calculating the number of pixels in each area with a microcomputer. Results: Capillary blood flow in the optic nerve head was continuously below 80% of the baseline throughout the study. The visual-evoked potential latency was significantly delayed in ET-1-treated eyes. The CA/DA ratio was significantly increased relative to baseline in the ET-1 treated eyes. Histologic examination showed axonal loss and demyelination affecting the prelaminar portion of the optic nerve. The intraocular pressure was not significantly different from the control value. Conclusion: Optic nerve head ischemia could contribute to the enlargement and excavation of the disk cup independent of the intraocular pressure level. (Surv Ophthalmol 44 [Suppl 1]:S74-S84, 1999. (C) 1999 by Elsevier Science Inc. All rights reserved.).