Nonarteritic Anterior Ischemic Optic Neuropathy

A discussion of its clinical features, diagnosis and treatment.

OMAR S. PUNJABI, MD ∙ ANGELO P. TANNA, MD ∙ MICHAEL A. ROSENBERG, MD

Ischemic optic neuropathies (IONs) are classified, on the basis of the location of the ischemic damage, as anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy and, based on the etiology, as arteritic ION and nonarteritic ION (NAION). Arteritic ION is less common than NAION and is often associated with giant cell arteritis (GCA), although other conditions such as polyarteritis nodosa and systemic lupus erythematosis can be associated.¹

NAION is most often idiopathic, but its development is strongly associated with vasculopathic risk factors. NAION comprises the majority of cases of AION (95%)² and is the most common acute optic neuropathy in patients over 50 years of age, with an estimated annual incidence in the United States of two to 10 per 100,000 members of the population.³ The incidence is significantly higher among Caucasians than among African-American or Latino individuals.² The mean age at onset in most studies ranges from 57 to 65 years.^2,4

PATHOPHYSIOLOGY

Although the exact pathogenesis of NAION remains unknown, ischemic occlusion of the vessels supplying the prelaminar layers of the optic disc likely occurs (Figure 1). In the acute phase of NAION, fluorescein angiography may show delayed filling of the prelaminar layers of the edematous optic disc, suggesting that hypoperfusion of the optic disc occurs.⁵ Indocyanine green angiography (ICGA) studies of the choroidal flow can show substantial slowing in arteritic ION but not in NAION, suggesting that extensive vascular occlusion in the short posterior ciliary arteries occurs in arteritic ION.

While structurally small, “crowded” optic discs are associated with NAION, the mechanism by which this contributes to ischemia has not been elucidated. Mechanical effects of structural crowding may potentiate obstruction to axoplasmic flow, with resultant intracellular axonal swelling from minimal microvascular ischemia leading to more severe axonal swelling, more extensive ischemia, and further neuronal damage. In addition, an abnormally stiff cribriform plate may potentiate compression in the laminar area, further compromising axonal function.⁶

Vasculopathic risk factors, such as systemic hypertension, diabetes mellitus, cigarette smoking, hyperlipidemia and radiation injury, could possibly contribute to the development of NAION.¹² Reports have also linked elevated plasma homocysteine to the development of NAION, but this association remains controversial.⁷

NAION has been associated infrequently with a multitude of additional factors and disorders that may be causative, either due to optic disc structure or to other features that might affect optic disc perfusion pressure. These include hyperopia, optic disc drusen, elevated intraocular pressure, cataract surgery, migraine, embolism, obstructive sleep apnea and medications for erectile dysfunction.^8,9

Figure 1. Combined anterior ischemic optic neuropathy (swollen optic disc with hemorrhages) and central retinal artery occlusion (pallid swelling of the retina with cherry red spot). IMAGE FROM DISORDERS OF THE ANTERIOR VISUAL PATHWAYS . J NEUROL NEUROSURG PSYCHIATRY. 2004;75:IV12-IV19, REPRINTED WITH PERMISSION OF BMJ JOURNALS.

CLINICAL PRESENTATION

Nonarteritic anterior ischemic optic neuropathy typically presents with painless loss of vision occurring over hours to days, often described as blurring, dimness, or cloudiness in the affected region of the visual field. Headache and other symptoms associated with GCA are usually absent. The initial course is usually static, with little or no fluctuation in the severity of the loss of visual function or, rarely, progressive vision loss, with either episodic, stepwise decrements or steady decline of vision over weeks prior to eventual stabilization.

It has been noted that color vision loss in NAION tends to parallel visual acuity loss, as opposed to that in optic neuritis or optic nerve compression, in which color loss is often disproportionately greater than visual acuity loss. Visual field defects in NAION are usually inferior altitudinal but may follow any pattern of optic nerve damage: arcuate, central, cecocentral, paracentral, etc. Optic disc edema is present during the initial event of NAION, and the edema may be diffuse or segmental but typically shows some segmental involvement.

Peripapillary retinal hemorrhages are seen in approximately 72% of patients.¹⁰ Peripapillary cotton wool spots may be present. The optic disc in the contralateral eye is often small in diameter¹¹ and demonstrates a small or absent physiologic cup.⁶ The disc appearance in such fellow eyes has been described as the “disc at risk.”

CLINICAL COURSE

Most cases of NAION show no significant improvement or deterioration over time after the initial event,^12,13 although rare cases are progressive. Approximately 30% of cases may show some improvement in visual field loss, but not in visual acuity.

The optic disc becomes pale, either in a sectoral or diffuse pattern, usually within four to six weeks of the initial event. Persistence of edema past this point or significant deterioration of visual function should prompt consideration of an alternate diagnosis and necessitates neuro-imaging and neuro-ophthalmological consultation.

Eventual involvement of the fellow eye has been reported in 24% to 39% of patients.^14,15 A history of diabetes and baseline visual acuity of 20/200 or worse in the affected eye, but not age, sex, or smoking, were significant risk factors for the development of NAION in the fellow eye.¹⁵

Occurrence in the second eye produces the clinical appearance of the “pseudo–Foster Kennedy syndrome,” in which the previously affected disc is atrophic and the currently involved nerve head is edematous. Significantly impaired visual function in the eye with disc edema distinguishes this condition from the true Foster Kennedy syndrome, in which disc edema is due to elevated intracranial pressure (often from an intracranial tumor) and therefore does not produce visual loss acutely in the edematous eye.

DIFFERENTIAL DIAGNOSIS

It is critical to rule out AION due to GCA in order to initiate prompt treatment and prevent visual loss in the contralateral eye. NAION must also be differentiated from idiopathic optic neuritis, syphilitic and sarcoid-related optic nerve inflammation, particularly in patients under 50 years of age; infiltrative optic neuropathies; anterior orbital lesions producing optic nerve compression; and idiopathic forms of optic disc edema, including diabetic papillopathy. Other conditions, such as optic disc drusen, can cause elevation of the optic disc margins that can be mistaken for disc edema in NAION. However, optic disc hemorrhages are typically absent, and ultrasound testing may show the presence of drusen. These clinical entities do not fit the typical presentation of NAION described above. Differentiation is typically made based on patient history, clinical suspicion, laboratory testing and imaging.

DIAGNOSTIC TESTING AND THERAPY

In patients with a typical presentation of NAION, without symptoms or signs to suggest GCA, and with normal erthyrocyte sedimentation rates (ESR) and C-reactive protein (CRP) levels, additional testing is not routinely performed. The upper limit of normal values of ESR (in mm/hour) are age ÷ 2 in males and (age + 10) ÷ 2 in females.^16,17 The value of CRP varies among laboratories, but <1.0 mg/dL is usually considered normal. Evaluation by a primary care physician for evidence and control of risk factors, such as hypertension, diabetes and hyperlipidemia, is essential. Neuro-imaging is not necessary unless the patient has an atypical course, such as pain, prolonged optic disc edema, or progressive or recurrent visual loss.

There is no effective therapy for NAION. Several therapies have been attempted, including anticoagulation, subTenon injections of vasodilators, intravenous IOP-lowering agents, thrombolytic agents, stellate ganglion block, hyperbaric oxygen, oral corticosteroids, and aspirin.^18-20 None of these treatments has been shown to be effective.

The Ischemic Optic Neuropathy Decompression Trial demonstrated no benefit with optic nerve sheath decompression surgery. Improvement in visual acuity of at least three lines was observed in 33% of treated patients vs 43% of untreated patients. There was a significantly greater risk of deterioration of visual acuity of ≥3 lines in the surgery group.¹⁰

PREVENTION

Although aspirin has a proven effect in reducing the risk of stroke and myocardial infarction in patients at risk, published data regarding its role in decreasing the severity of optic neuropathy²¹ and the incidence of fellow-eye involvement after the initial episode of NAION have been controversial. One study found that fellow eye involvement occurred in 17% of patients treated with aspirin vs 50% in untreated patients.²² Seventy percent of fellow-eye involvement cases occurred during the first year. It is recommended, therefore, that patients should take aspirin if there is no contraindication for its use after they have had an initial event of NAION, primarily because these patients frequently have other underlying vasculopathic risk factors for which the use of aspirin has a proven benefit. RP

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