NAION Secondary to IIH

Article initiated by:

Andrew Go Lee, MD, Noor Laylani, MD, Peter W. Mortensen, MD, Ryung Lee

All authors and contributors:

Andrew Go Lee, MD, Peter W. Mortensen, MD, Nagham Al-Zubidi, MD, Noor Laylani, MD

Assigned editor:

Mary Labowsky, MD

Review:

Assigned status Update Pending

 by Mary Labowsky, MD on July 29, 2023.

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Contributing Editors:	add

Disease Entity

Ischemic optic neuropathy (ION) is an optic neuropathy due to lack of perfusion to the optic nerve blood supply. ION has two ophthalmoscopic presentations, an anterior form characterized by optic disc edema (AION) and a less common posterior form characterized by a normal disc at onset (PION). The primary visual complaint in Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) is a painless loss of vision in the affected eye associated with the eye findings of an ipsilateral relative afferent pupillary defect (RAPD) in unilateral or bilateral but asymmetric cases and a swollen optic nerve. Often the fellow eye has a small cup-to-disc ratio (the “structural disc at risk”). The visual acuity loss in NAION ranges from none (20/20) to no light perception (NLP) but most often better than 20/200. The visual field loss is typically in a nerve fiber layer pattern (e.g., arcuate, altitudinal) or central pattern. Multiple vasculopathic risk factors have been associated with the NAION including hypertension, sleep apnea, diabetes mellitus, and certain medications. Although vasculopathic risk factors are most commonly associated with NAION, this EyeWiki will review the association of Idiopathic Intracranial Hypertension (IIH) as a risk factor for NAION producing a permanent visual loss. Table 1 summarizes the cases reported in the literature of the disease presentation.

Table 1: Cases Reported in the Literature of Non-Arteritic Anterior Ischemic Optic Neuropathy with Idiopathic Intracranial Hypertension.

Study	Patient Presentation	Neuro-Ophthalmic Findings
Pirouzmand et al (2022)	48-year-old man with blurry vision and bilateral papilledema.	Severe flattening of the posterior sclera and enhancement of optic nerve head DWI restricted diffusion within the optic nerve head on MRI orbits.
Ma et al (2020)	A 29-year-old obese woman presented to the emergency room with horizontal binocular diplopia, new headaches, and transient visual obscurations.	Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) showed signs of raised intracranial pressure. Superior altitudinal visual field defect on Humphrey 24-2.
Amit Kumar Deb (2021)	A 28-year-old female presented with a history of sudden onset painless diminution of vision in both eyes associated with headache and vomiting for one day.	Fundus examination showed bilateral diffuse pallid disc edema and peri-papillary superficial splinter hemorrhages. Lumbar puncture was done carefully, and CSF examination showed an opening pressure of 84 cm H2O.

Epidemiology

Concurrent IIH and NAION are not as common as either entity alone. Typical NAION affects between 2.3 and 10.3 people per 100,000 individuals per year. There are approximately 6000 new cases per year. Men and women are nearly equally affected and the mean age at symptom onset varies between 57 and 65 years. In contrast, papilledema in idiopathic intracranial hypertension (IIH) commonly affects obese women of childbearing age, with a prevalence of 7.9-20 per 100,000 in overweight women. Male patients with hypertension or patients presenting with papilledema from a hypertensive emergency are likely more susceptible to permanent and severe visual loss from combined NAION and papilledema (including IIH). Populations predisposed to obstructive sleep apnea may also be at risk due to common pathologic mechanisms for both NAION and IIH.

Pathophysiology

NAION is believed to be hypoperfusion in the blood supply to the optic nerve (e.g., short posterior ciliary arteries) but the precise mechanism remains ill-defined. A small crowded optic disc predisposes individuals to typical NAION (i.e., the “disc at risk”). Papilledema in IIH may produce atrophy of the optic disc or blockage of optic nerve axoplasmic flow. Therefore, an optic disc obscuration due to papilledema may predispose individuals, especially those with underlying vasculopathic risk factors, to anterior optic nerve ischemia.

Diagnosis

Signs and Symptoms

Typical NAION occurs as an isolated, sudden, painless, monocular vision loss with optic disc edema. Vision field loss, such as inferior nasal, central, or altitudinal defects may be present or an enlarged blind spot from underlying optic atrophy or nerve damage. In addition, patients with increased intracranial pressure may have headaches, tinnitus, and nausea/vomiting. RAPD is present in NAION while absent in bilateral symmetric papilledema due to IIH, therefore in acute cases, new RAPD will be present. Additionally, sector or diffuse optic disc edema or pallor will be seen in NAION with attenuated bilateral disc edema.

Diagnostic Procedures/Investigations

Patients with suspected papilledema should have an assessment of the blood pressure as well as the intracranial pressure as a hypertensive emergency can present with papilledema (grade IV hypertensive retinopathy) without the other retinal findings of systemic hypertension. For patients with a hypertensive emergency, the presence of optic disc edema is evidence of target-end organ dysfunction and typically requires admission to the hospital. A slow rather too rapid reduction of blood pressure (e.g., 25% in the first few hours) is recommended to avoid precipitating NAION or stroke.

Neuroimaging with magnetic resonance imaging (MRI) and MR venography (MRV) is recommended for papilledema with or without concomitant NAION. Diffuse restriction of the optic nerve head is present in both acute NAION and chronic papilledema. Automated perimetry (e.g., Humphrey visual field) to define the extent and severity of the visual field deficit and optical coherence tomography (OCT) can be helpful in differentiating cases of papilledema (e.g., enlarged blind spot) from NAION with papilledema.

Specifically, in the early stages of optic disc edema, OCT of the retinal nerve fiber layer (RNFL) may show thickening relative to the fellow eye. The RNFL thickening decreases rapidly in the subacute phase and then typically progresses to RNFL loss and optic atrophy. At this point, differentiating post-papilledema optic atrophy from NAION in such cases may be difficult. Fluorescein angiography may be useful to demonstrate sector non-perfusion in the optic disc or delay in filling in a disc segment in NAION but may be of limited value in severe papilledema where disc leakage may be severe.

If etiology is unclear following neuroimaging, a lumbar puncture may be performed once life-threatening causes of NAION are accounted for. Elevated opening pressure may further support the diagnosis of IIH. Lumbar puncture is typically not recommended if a diagnosis of NAION is highly probable.

Differential diagnosis

The differential diagnosis includes conditions that elevated intracranial pressure that can coexist with NAION including:

•Intracranial Masses

•Malignant Hypertension

•Venous Sinus Thrombosis

Management

The treatment of NAION with IIH is centered on treating the underlying risk factors. Medical management and surgical intervention if indicated for papilledema may reduce ICP and thus reduce the risk for secondary NAION. There remains no proven treatment for NAION but management of vasculopathic risk factors is recommended. Many therapies have been recommended in the past, but none have proven to be effective (e.g. anti-platelet agents and anticoagulants; vasopressors; optic nerve surgery (Transvitreal optic neurotomy, optic nerve fenestration); and neuroprotective agents).

Treatments for underlying IIH (see EyeWiki on IIH) include both medical (e.g., carbonic anhydrase inhibitors (Acetazolamide or Topiramate) or Loop diuretics (Furosemide) or surgical intervention (e.g., venous stenosis stenting; optic nerve sheath fenestration, cerebrospinal fluid diversion (ventriculoperitoneal shunt) or bariatric surgery).

Prognosis

The visual prognosis for NAION in papilledema is variable and depends on the underlying risk factors, severity at onset, and duration of the disease. Improvements in visual acuity may be demonstrated following the resolution of edema and underlying risk factors. Vision loss stabilizes following several months but patients with acute and severe IIH (i.e., fulminant IIH) have a significant permanent visual loss of acuity and/or visual field without aggressive treatment of the elevated ICP (e.g., lumbar drain, high dose medical therapy, and surgical intervention). The presumed mechanism of the visual loss in this setting is likely multifactorial.

Summary

Visual loss due to NAION or IIH both present with optic disc edema and the two conditions can occur simultaneously in the same patient. The precise mechanism for papilledema-related visual loss remains ill-defined but likely involves local optic disc head ischemia with disc crowding. This type of NAION related to IIH should be differentiated from typical NAION which is usually acute, painless, and unilateral. One common pathogenic mechanism, however, in both NAION and IIH is systemic hypertension, and blood pressure should be assessed in both conditions. Hypertensive urgency can be defined by papilledema and avoiding over-aggressive reduction of the blood pressure acutely can help mitigate iatrogenic NAION in such cases.