Nonarteritic anterior ischemic optic neuropathy (NAION): a misnomer. Rearranging pieces of a puzzle to reveal a nonischemic papillopathy caused by vitreous separation.

Nonarteritic anterior ischemic optic neuropathy (NAION) has been the subject of numerous publications and editorials. Yet, meaningful progress toward understanding the pathogenesis of this entity has been limited. As the term “ischemic” would indicate, investigators have focused their efforts on defending a vascular cause. What is the evidence for ischemia in this entity that, by histopathologic and observational ophthalmology, first affects the prelaminar optic disc? The fact that vascular abnormalities such as disc hemorrhages and swelling are present at the time of visual loss, followed by peripapillary vascular narrowing and ensuing disc pallor, is enticing, but not etiologically conclusive. Unlike ischemic neuropathy in giant cell arteritis in which short posterior ciliary arteries are affected, with loss of supplied tissue leading to increased laminar cupping, such findings have never been demonstrated in NAION. Fluorescein and indocyanine green angiography demonstrate changes at the prelaminar disc surface alone, uncorrelated to changes in visual field or in neural tissue, and not at the deeper levels supplied by the ciliochoroidal and central retinal vasculature. Whiteness with disc swelling has been accepted as a sign of ischemia, but there is both optic disc and retinal evidence that such whiteness is indicative of axoplasmic stasis (cotton wool spots) that may also occur simply from anatomic distortion of axons rather than occlusion of vessels. This may also occur from fracture of the axonal cytoskeleton and frank membrane disruption with axoplasmic “leakage.” In giant cell arteritis, retrolaminar vascular occlusion will cause axoplasmic accumulation anteriorly, with a white appearance at the level of the optic disc. If disc ischemia were prelaminar, however, white axoplasmic accumulation and swelling would develop upstream predominately in peripapillary retina. The immediate development of prelaminar disc changes with the onset of clinical symptomatology precludes slow orthograde axoplasmic accumulation as responsible. The search for a systemic vascular denominator for this disease has been futile. With so little to show for it, it seems worth questioning the underlying presumption of ischemia as an etiologic factor for so-called NAION. When the name of an entity itself may be a misnomer, it can be especially difficult to escape erroneous interpretations of pathophysiology. Indeed, the mechanism of this disease needs to be reanalyzed in a completely different direction.