NAION Secondary to IIH

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Article initiated by:

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

All contributors:

Andrew Go Lee, MD, Peter W. Mortensen, MD, Nagham Al-Zubidi, MD, Noor Laylani, M.D., Mary Labowsky, MD

Assigned editor:

Mary Labowsky, MD

Review:

Assigned status Update Pending

 by Mary Labowsky, MD on November 15, 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; it is classified as either anterior (AION) characterized by presence of optic disc edema on exam and posterior (PION) in the absence of disc edema. The latter is exceeding rare and seen only in specific clinical contexts (excessive blood loss, prolonged prone spine surgery, giant cell arteritis).

ION is further classified by entity, with arteritic anterior ischemic optic neuropathy (AION) referring to ION secondary to giant cell arteritis, and non-arteritic anterior ischemic optic neuropathy (NAION) referring to ION unrelated to giant cell arteritis. This article will be focused on the latter.

NAION presents with painless loss of vision in the affected eye, with associated findings of an optic neuropathy including an ipsilateral relative afferent pupillary defect (RAPD) and a swollen optic nerve, which is necessary for the diagnosis. 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 it is most often better than 20/200. The visual field loss is typically in a nerve fiber layer pattern - classically altitudinal field loss, but can also be an arcuate, nasal step, or central pattern.

Vasculopathic risk factors (hypertension, sleep apnea, diabetes mellitus) and certain medications have been associated with NAION, but this article will focus on the association of Idiopathic Intracranial Hypertension (IIH). 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, following severe blood loss from an obstetric procedure.	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.
Jiraskova et al (2012)	A 58-year-old female with IIH presented 3 months after treatment for IIH, with left AION.
Green et al (1980)	A 40 year-old woman presented with 5 days of headache, TVOs, and vision loss in the left eye.	Visual field testing showed an enlarged blind spot in the right eye, and an inferior altitudinal defect in the left eye. Exam showed bilateral optic disc edema; the left eye had sectoral pallid edema. Fluorescein angiogram suggested evidence of optic nerve ischemia. Opening pressure on spinal tap was 47.5 mm

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. 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.

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

Patients with increased intracranial pressure may have headaches, tinnitus, and nausea/vomiting.

NAION occurs as a sudden, painless, monocular vision loss with optic disc edema. Vision field loss, such as inferior nasal, central, or altitudinal defects may be present; when superimposed on papilledema, an enlarged blind spot from underlying optic atrophy or nerve damage may be present.

An RAPD is present in NAION while absent in bilateral, symmetric papilledema due to IIH.

Sector or diffuse optic disc edema or pallor will be seen in NAION with attenuated bilateral disc edema.

Diagnostic Procedures/Investigations

Blood Pressure. Hypertensive emergency can present with papilledema 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 (meeting criteria for grade IV hypertensive retinopathy). A gradual reduction of blood pressure (e.g., 25% in the first few hours) is recommended to avoid causing ischemic events (including stroke and iatrogenic NAION) which can be precipitated by aggressive lowering of perfusion pressure.

Ancillary testing.

Automated perimetry (e.g., Humphrey visual field) to define the extent and severity of the visual field deficit and can be helpful in differentiating cases of papilledema (e.g., enlarged blind spot) from NAION superimposed on papilledema.

In the early stages of optic disc edema, OCT of the retinal nerve fiber layer (RNFL) may show thickening relative to the fellow eye, and may show a sectoral pattern. 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.

Neuroimaging. 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.

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

NAION and Papilledema related to IIH both present with painless vision loss and optic nerve edema, and can occur simultaneously in the same patient. The precise mechanism for papilledema-related ION remains ill-defined but likely involves local optic disc head ischemia with disc crowding. NAION related to IIH should be differentiated from typical NAION which is usually acute, painless, and unilateral. Both NAION and Papilledema can be caused by systemic hypertension, and blood pressure should be assessed in both conditions, particularly as the presence of papilledema is diagnostic of hypertensive emergency.