Field defects typical of ischemic optic neuropathy were probably first described by Knapp in 1875. Miller and Smith first used the term ischemic optic neuropathy in 1966, and Hayreh later added the term anterior. In 1924, Uhthoff first described severe visual loss, with field defects and swollen optic discs.[1]
Anterior ischemic optic neuropathy (AION) is the most common cause of acute optic neuropathy in older age groups. It can be nonarteritic (nonarteritic anterior ischemic optic neuropathy [NAION]) or arteritic, the latter being associated with giant cell arteritis (GCA; often termed temporal arteritis). AION is characterized by visual loss associated with optic disc swelling of a pallid nature, sometimes with flame hemorrhages on the swollen disc or nearby neuroretinal layer, and sometimes with nearby cotton-wool exudates. Visual loss is usually sudden or develops over a few days at most and is commonly unilateral, although second eye involvement may occur later. The visual loss is usually permanent, with some recovery possibly occurring within the first weeks or months. Optic atrophy of varying degrees ensues within the next few week as a result of the hypoxic episode and is usually generalized but may be sectorial in NAION.
Although the pathophysiology differs in the arteritic form of AION, ischemia is the end result, as the results on vision are the same. According to Rucker, temporal arteritis probably was first described very early by Ali Ibn Isa (AD 940-1010).[2] In modern times (1890), Hutchinson described a disease of this nature, and, in 1932, Horton and colleagues at the Mayo Clinic used the term temporal arteritis.[3, 4] To better describe the histologic features, Gilmour suggested the term giant cell arteritis in 1941. As a result of understanding that the mechanism for GCA was inflammatory and not just localized to findings of optic nerve ischemia, treatment of GCA with steroids was started at the Mayo Clinic in 1949.
Examples of anterior optic neuropathy are shown in the images below.
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Anterior ischemic optic neuropathy of the right eye. Swollen pale disc that can be seen in stereo by converging the eyes and fusing the central image.
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Sectorial optic atrophy of the right eye as a late finding resulting from anterior ischemic optic neuropathy. Atrophy has supervened, and the atrophic....
Anterior ischemic optic neuropathy (AION) is thought to be an ischemic process affecting the posterior circulation of the globe, principally vessels (ie, short posterior ciliary arteries) supplying the optic nerve at its exit from the eye. Only glial cells support the optic disc at this site, and it is the only site in which swelling can occur. More posterior ischemia results in a similar condition, without visible swelling, and is termed posterior ischemic optic neuropathy.
Early observations of optic disc photographs suggested that patients with congenitally smaller discs having smaller or nonexistent cups have an anatomical predisposition for nonarteritic anterior ischemic optic neuropathy (NAION). As an ischemic episode evolves, the swelling compromises circulation within a presumable already more compact disc, with a spiral of ischemia resulting in further neuronal damage. This type of structural/ischemic spiral is less implicated in the arteritic type of AION, in which the entire ophthalmic arterial circulation to the eye and orbit may be compromised.
Patients with both arteritic and nonarteritic forms of anterior ischemic optic neuropathy (AION) are usually older than 50 years, with females predominating in the arteritic group. The incidence of nonarteritic anterior ischemic optic neuropathy (NAION) is 2.3-10.3 per 100,000 in the United States, and, for the arteritic type, it is 0.36 per 100,000. In the arteritic group, the incidence increases almost exponentially with advanced age. The literature seems to support the notion that whites are affected more commonly than blacks in the nonarteritic group, and people of Scandinavian or European ancestry are the most commonly affected ethnic group in the arteritic type.
International
In the nonarteritic group, incidence is higher in whites and uncommon in other races. The countries with the highest incidence of arteritic AION are the Scandinavian countries (ie, Norway, Denmark, Sweden), followed by Germany. The arteritic form is not as well recognized in non-whites. In the future, genetic evidence may help to explain this incidence.
Mortality/Morbidity
Although NAION may not be associated with conditions such as hypertension, diabetes, and myocardial infarction, many individuals with NAION do not have such life-threatening vascular diseases. The role of smoking in this disease is unclear. By contrast, the arteritic form of AION as significantly more nonocular morbidity since it is associated with giant cell (cranial) arteritis. This condition affects many organs of the body, and the incidence of death associated with it is higher than that of the general population. Late-onset abdominal aortic aneurysms contribute to the morbidity and mortality of giant cell arteritis (GCA).
Bilateral visual loss is more common in the arteritic form of the disease, especially if treatment is delayed, and approximates 50% in some earlier series. By contrast, bilateral visual loss may be seen in 12-19% of nonarteritic anterior ischemic optic neuropathy (NAION), and it usually occurs sequentially instead of simultaneously.
Progressive visual loss in the contralateral eye can occur in either form of AION, despite steroids, anticoagulation, or hyperbaric oxygen. Progressive visual loss is less common and usually stabilizes in a few days.
Race
Nonarteritic anterior ischemic optic neuropathy (NAION) is most common in whites (95%); it is less common in blacks (2%), Asians (3%), and Hispanics (1%). The arteritic form of the disease is predominantly described among whites of European descent, particularly Scandinavian and German.
A past misconception was that black patients did not succumb to GCA. However, numerous documented cases of GCA in blacks are noted; GCA in black patients is not uncommon.
Sex
Females dominate the incidence in both forms of AION, but only slightly in the nonarteritic form (1.2:1) compared with the arteritic type (2:1).
Age
Both disorders are found in older age groups. In the nonarteritic group, age ranges from the late 40s and older. The arteritic group almost always is older than 50 years, with an exponential increase with advanced age (90% of patients are >60 y). Rare cases of AION occur before 40 years, and the differentiation from optic neuritis associated with demyelinating disease is important in this crossover age group.
Visual loss is painless in at least 90% of patients with nonarteritic anterior ischemic optic neuropathy (NAION). The vision loss is often noticed upon awakening, perhaps due to nocturnal hypotension. NAION can occur after procedures such as spinal fusion surgery. Risk factors for NAION after spinal fusion surgery include obesity, male sex, Wilson frame use, longer anesthetic duration, greater estimated blood loss, and decreased percent colloid administration.[5]
Patients with arteritic anterior ischemic optic neuropathy (AION) often have symptoms other than visual loss, such as malaise, headache, scalp tenderness and tender temporal arteries, jaw pain on mastication (jaw claudication), generalized muscle aches and swelling.
The earlier manifestations of arteritic AION include malaise, weight loss, fever, vague abdominal or GI pains, and anorexia.
Late manifestations of arteritic AION, often years later, include a much higher incidence of abdominal aortic aneurysm.
Nonarteritic anterior ischemic optic neuropathy (NAION) has typical findings of visual loss and field loss in an otherwise asymptomatic individual.
A small cup disc ratio is usually noted. Initially, the optic disc is swollen and pale, often in a generalized or diffuse manner.
Sectorial disc edema, especially of the superior disc, is classic. Altitudinal visual field loss is common.
Visual loss with NAION is not usually as severe as with arteritic anterior ischemic optic neuropathy (AION), but vision loss as severe as no light perception has been described.
Arteritic anterior ischemic optic neuropathy
In patients with arteritic AION, the disc is classically described as chalky white, pale, and swollen.
Ischemia in multiple vascular territories is not uncommon (eg, central retinal artery occlusion, choroidal infarction, anterior segment ischemia, extraocular muscle ischemia causing diplopia).
The temporal arteries may be quite prominent, ropey, and tender.
Oral, tongue, or even scalp ulcers may rarely be seen.
Anterior ischemic optic neuropathy (AION) is an ischemic disease, but the cause is yet to be found definitively. In nonarteritic ischemic optic neuropathy (NAION), atherosclerosis is assumed to be the basis, with its effect on the circulation of the optic nerve head. The posterior ciliary arteries feed the optic nerve head, and, despite variable results in animal primate models with ligation of the posterior ciliary arteries, their susceptibility to atherosclerosis and arteriosclerosis in a widespread manner seems to be the underlying cause. In the arteritic form, the basis for the ischemia is identical in pattern, with a giant cell arteritis (GCA) involving most of the orbital vessels, including the central retinal artery, and the posterior ciliary arteries. Involvement of the branch retinal arterioles is rare presumably because of the lack of internal elastic lamina.
Elucidating the genetic predisposition to GCA has yet to be completed but has promise. Incidence in families of Scandinavian origin is high, and genetically determining persons who are predisposed to this disorder may be possible. Human leukocyte antigen (HLA) haplotypes may also provide some interesting relationships, as there are very rare instances of GCA in patients with true rheumatoid arthritis. The proximity of the gene locus in these 2 diseases seems to preclude the expression of both diseases in the same individual.
According to Miller's edition of Walsh and Hoyt's Clinical Neuro-ophthalmology, the causes and associated conditions of AION are as follows.[6]
The erythrocyte sedimentation rate (ESR) is commonly obtained in patients with anterior ischemic optic neuropathy (AION). In patients with arteritic AION, the ESR is usually elevated, although 10% of patients may have a normal ESR. In nonarteritic anterior ischemic optic neuropathy (NAION), the ESR is more likely to be normal, assuming no comorbid condition is present. The Westergren ESR is thought to be more reliable than the Wintrobe ESR.
A hematology group is useful. Mild anemia may be present.
Other blood tests, such as the C-reactive protein (CRP), have been found useful in diagnosing giant cell arteritis (GCA). In a few patients with GCA, the CRP level has been shown to be elevated despite the finding of a normal ESR.
Ultrasonography of the temporal arteries and ocular Doppler ultrasonography have been described, but the utility of ultrasonographic evaluation in the differentiation between arteritic anterior ischemic optic neuropathy (AION) and nonarteritic anterior ischemic optic neuropathy (NAION) has not been proven.
Ocular plethysmography (OPG) findings have been described as being abnormal in patients with arteritic AION.
MRI is useful in younger individuals in identifying unilateral visual loss of optic nerve with possible demyelinating disease. It is not useful in older age groups, in either the arteritic or nonarteritic form of AION.
CT scanning is not useful in either the arteritic or nonarteritic form of AION.
Fluorescein angiography has been suggested as a possible method of distinguishing arteritic AION from NAION. With arteritic AION, a markedly prolonged choroidal filling time is usually present.
Angiography of the cerebral circulation has been useful in giant cell arteritis (GCA), showing segmental stenosis or even occlusion of the extracranial vessels. However, angiography is rarely used because of its invasive nature. CT angiography has been described as sometimes revealing segmental stenosis in GCA.
Optical coherence tomography (OCT) has been used in patients with AION with success.[7]
Temporal artery biopsy is used to diagnose giant cell arteritis (GCA). It is especially useful in patients with any of the symptoms of GCA or in patients with visual loss and a high ESR. A normal result of the temporal artery biopsy is often used to exclude the diagnosis of GCA in older patients with anterior ischemic optic neuropathy (AION).
Whenever possible, a biopsy specimen of at least 2-3 cm should be obtained to minimize the possibility of skip lesions. Bilateral temporal artery biopsies increase the yield of positive results. A second temporal artery biopsy should be considered if GCA is still suspected despite an initial negative result of the first temporal artery biopsy. Delaying the second side a few weeks may improve the yield of a positive biopsy result on that second side.
Biopsy should generally be performed either before or soon after the initiation of steroid therapy, although positive biopsy results can sometimes be obtained months after steroids have begun.
The idiopathic form of ischemic optic neuropathy has no characteristic pathology other than obliterative occlusion of the cilioretinal arteries and ischemic necrosis of the optic nerve head in variable degree.
Giant cell arteritis (GCA) has a characteristic inflammatory infiltrate that has a granulomatous appearance, sometimes with giant cells. Complete occlusion of the ophthalmic artery within the orbit may result in ischemic changes of the globe in its entirety. The use of frozen section for temporal artery biopsy is very useful in determining arteritis, and it may establish the diagnosis with a single temporal artery biopsy. Rarely, if the initial temporal artery biopsy result is negative, the contralateral biopsy result may be positive due to minimal involvement or skip areas. Inflammatory infiltrate in the adventitia often is considered to be sufficient evidence for diagnosis, even with the elastica intact.
Comanagement of anterior ischemic optic neuropathy (AION) with an internist, especially a rheumatologist, is helpful in patients with giant cell arteritis (GCA). Control of blood pressure and diabetes, often comorbid conditions, is helpful in the general sense, but it is of little use in the recovery of visual loss.
In GCA, the steroid regimen is as follows:
The initial dose is 40-60 mg/d of prednisone, depending on the size of the patient and the severity of the disease. If starting at 40 mg/d, hold for 2-4 weeks; then, reduce as below. If starting at 60 mg/d, reduce by 10 mg every 2 weeks to 40 mg, followed by 5-mg reductions every 1-2 weeks to 20 mg/d, and then 2.5 mg every 1-2 weeks. Below 10 mg/d, reduce 1 mg per month. The reduction schedule depends of the course on the patient.
Obtain erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) at monthly intervals to monitor the course of the patient. Brief interviews at monthly intervals are helpful. If recurrences develop, the reduction schedule needs to be delayed, and, sometimes, small increments need to be given again for flare-ups. Avoid large increments for flare-ups if possible.
Some authors have advocated larger doses, even intravenous doses of 1 gram daily for several days, followed by the standard treatment as above. Support for this is currently lacking, but, in an ongoing study at the Mayo Clinic, a double-masked study is underway to determine if intravenous doses accelerate the recovery and shorten the need for months of long-term steroids.
At a later stage in the steroid management, it is sometimes useful to add antimetabolites, such as methotrexate or cyclosporine, to reduce the dosage of steroids, particularly if adverse effects are becoming a problem. Careful monitoring of liver function and blood counts is essential and is best left to the rheumatologist.
Most scientific data do not support corticosteroid treatment for nonarteritic anterior ischemic optic neuropathy (NAION), although a 27-year prospective study by Hayreh and Zimmerman suggested that NAION eyes treated during the acute phase with systemic corticosteroids resulted in a significantly higher probability of improved visual acuity (P = 0.001) and visual field (P = 0.005) than in the untreated group. Both visual acuity and visual fields improved up to 6 months after onset of NAION.[8]
When the diagnosis is in question, a short-term trial is warranted. Once temporal arteritis has been ruled out, continuing is unnecessary because the long-term complications of steroids are considerable.
The Ischemic Optic Neuropathy Decompression Trial (IONDT)[9, 10] showed that optic nerve decompression has no effect in the treatment of ischemic optic neuropathy.
Temporal artery biopsy is warranted for diagnosis when arteritis is a possibility.
Oral steroids are of little or no use in nonarteritic anterior ischemic optic neuropathy (NAION). Systemic steroids must be initiated early in the case of giant cell arteritis (GCA), especially if one eye is involved. Usually, the treatment prevents the second eye from becoming involved, but, sometimes, vision is lost despite steroids.[11, 12, 13]
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli. In those cases that overlap with the optic neuritis (inflammatory, demyelinating) group (ie, patients in their fourth to fifth decade), a trial of steroids (intravenous) is useful.
Systemic steroids, ranging from 100 mg of prednisone daily to lower doses that are tolerated more easily on a long-term basis, may be indicated. Alternate day steroid therapy is not recommended, especially in the acute treatment of arteritic anterior ischemic optic neuropathy (AION). Titration of dosage with clinical symptoms and ESR seems to be the best regimen.
Treatment may be continued for a year or more, and it may be augmented by other antimetabolites, such as Imuran or methotrexate. Ultimately, a low dose of 2.5-5 mg daily, which is very close to physiologic secretion by the adrenals, is desirable.
No medications of known value are available in the prevention of anterior ischemic optic neuropathy (AION) in the other eye. Currently, most practitioners advise use of an aspirin daily in patients who can tolerate this medication. Its long-term efficacy is not proven.
Other than visual loss in the second eye, which may occur simultaneously with that in the first eye, few ocular complications accompany anterior ischemic optic neuropathy (AION). Ocular palsies in the arteritic form of the disease and ischemia of the entire globe associated with GCA have been reported. Rarely, scalp necrosis can occur.
Steroids have well-known and significant adverse effects. Such adverse effects are beyond the scope of this article, and an internist or a rheumatologist best manages them.
Occasional complications of temporal artery biopsy include hemorrhage or wound infection. Rare complications of temporal artery biopsy include facial nerve palsy, scalp necrosis, and cerebrovascular accident (if the superficial temporal artery supplies a critical collateral to the internal carotid circulation).
Prognosis for visual recovery generally is poor. However, in the IONDT study, more recovery of vision and visual field occurred than was expected. Part of this finding may be explained by adaptation, but the measured visual acuity and parameters of the fields did seem to improve substantially in many cases.
A second attack of nonarteritic ischemic optic neuropathy (NAION) has never been documented in an eye that has already suffered one attack. Thus, vision in a patient with NAION, even if both eyes have been affected, should remain stable. However, a second attack in the same eye has been found on occasion with the arteritic form of ischemic optic neuropathy associated with giant cell arteritis (GCA).
Anterior ischemic optic neuropathy (AION) is a very frustrating disease, to both patients and physicians, because little can be performed to treat it. Investigation of large vessel diseases, scanning of the brain, and treatment modalities have proven fruitless. Once visual loss has occurred, little can be performed to restore it.
Awareness of the entity of giant cell arteritis (GCA) is important to both physicians and patients, as the intervention of steroids may prevent loss of vision in the other eye, as well as prevention of considerable comorbidity in other organ systems.
General health measures (eg, control of blood pressure, obesity, and diabetes; not smoking) are important, but bear little result in recovery of vision that is already lost.
Andrew A Dahl, MD, FACS, Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Disclosure: Nothing to disclose.
Additional Contributors
Brian R Younge, MD, Professor of Ophthalmology (Retired), Mayo Clinic School of Medicine
Disclosure: Nothing to disclose.
Edsel Ing, MD, MPH, FRCSC, Associate Professor, Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine; Active Staff, Michael Garron Hospital (Toronto East Health Network); Consulting Staff, Hospital for Sick Children and Sunnybrook Hospital, Canada
Disclosure: Nothing to disclose.
References
Uhtoff W. Zu den entzundlichen sehnerven: Affectionen bei arteriosklerose. Ber Dtsch Ophthalmol Gesampte. 1924. 44:196-198.
Ali Ibn Isa. Memorandum Book of a Tenth-Century Oculist. (Translated by CA Wood). Chicago: Northwestern University; 1936.
Hutchinson J. Diseases of the arteries. Arch Surg (London). 1890. 1:323.
Horton BT, Magath TB, Brown GE. An undescribed form of arteritis of the temporal vessels. Proc Staff Meet Mayo Clinic. 1932. 7:700.
Anterior ischemic optic neuropathy of the right eye. Swollen pale disc that can be seen in stereo by converging the eyes and fusing the central image.
Sectorial optic atrophy of the right eye as a late finding resulting from anterior ischemic optic neuropathy. Atrophy has supervened, and the atrophic pale disc with a more pronounced cup can be seen in stereo.
Anterior ischemic optic neuropathy of the right eye. Swollen pale disc that can be seen in stereo by converging the eyes and fusing the central image.
Sectorial optic atrophy of the right eye as a late finding resulting from anterior ischemic optic neuropathy. Atrophy has supervened, and the atrophic pale disc with a more pronounced cup can be seen in stereo.
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