Peripapillary Edema Is Associated with Nerve Fiber Layer Atrophy in a Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

Abstract

Purpose: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic nerve disorder of persons over 50. The pathophysiology of this disorder is poorly understood, aside from the fact that optic nerve head (ONH) infarction follows a disruption of circulation in the optic nerve head and retrolaminar capillaries. We developed a non-human primate model of NAION (pNAION)* to identify mechanisms of damage in this disorder with the hope that strategies can be developed that target these mechanisms and prevent severe vision loss in patients with NAION. For this paper, we tested the hypothesis that peripapillary edema in pNAION results in eventual nerve fiber layer (NFL) atrophy.

Methods: pNAION was induced in four rhesus monkeys using a method described previously*, in which the animal is injected IV with Rose Bengal, a dye that, when stimulated, generates O₂ radicals that damage the endothelial cell walls of the ONH, closing capillaries and resulting in infarction. Laser energy having subthermal fluence is used to stimulate the dye. We performed spectral-domain optical coherence tomography (OCT) in these animals using a Heidelberg OCT, and evaluated the thickness of the NFL prior to inducing infarction and repeatedly over a period of 2 months post infarction.

Results: In our most affected animal, NFL thickness measured at 1 day post pNAION induction was linearly correlated with NFL thinness measured at weeks 6 and 7 post induction (r = 0.928). The slope of the regression line was -1.59, suggesting that for this animal, every unit of edema resulted in one and a half units of atrophy. Data from the other three monkeys confirmed this main effect but were more variable because they were mildly treated and consequently developed mild cases of NAION.

Conclusions: The severity of peripapillary edema in pNAION is associated with eventual NFL atrophy, with the severity of the edema correlating with the severity of atrophy. Limiting edema in this disorder may prevent or reduce ultimate visual loss. *Chen, C, Johnson, MA, Flower, RA, Slater, BJ, Miller, NR, Bernstein, SL: A primate model of non-arteritic anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2985-92.

Keywords: 610 nerve fiber layer • 613 neuro-ophthalmology: optic nerve • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)