Acute Optic Neuritis

Most patients with optic neuritis are women between 25 and 45 years of age, although this condition can also develop in children and older patients. Optic neuritis is characterized in more than 95% of cases by the sudden onset of pain, often quite severe, behind or around the eye, followed shortly thereafter by decreased central vision and, in many cases, by central field loss.² The loss of central vision is variable. It may be extremely mild or quite severe; indeed, in some cases, all vision is lost. Affected patients have decreased color vision that may be worse than the acuity would suggest. A relative afferent pupillary defect is always present unless the patient has experienced a previous attack of optic neuritis or has some other optic neuropathy in the opposite eye or the acute process is bilateral. The affected optic disc appears normal in about two thirds of cases; in the other one third, it is swollen (Fig. 23-5).

Figure 23-5 Acute optic neuritis. Note swelling of optic disc associated with perivascular sheathing.

Most cases of optic neuritis are idiopathic or demyelinating in origin; however, rare cases are caused by such inflammatory or infectious conditions as sarcoid, syphilis, Lyme disease, and cat-scratch disease.²

The natural history of demyelinating or idiopathic optic neuritis is to improve vision to 20/20 or better without treatment. Although a 3-day course of high-dose (1g/day) methylprednisolone followed by a 2-week course of low-dose (1 mg/kg/day) prednisone may speed recovery by several weeks to a month, this treatment does not affect the ultimate visual outcome. The use of low-dose steroids without first use of high-dose steroids in a patient with acute optic neuritis increases the risk of recurrent optic neuritis in the affected eye and the risk of an attack of acute optic neuritis in the other eye.

Patients who experience an attack of acute optic neuritis have an increased risk of developing multiple sclerosis, depending in large part on whether white-matter lesions are visible on magnetic resonance images at the time of the acute attack (Fig. 23-6). The presence of even one lesion doubles a patient’s risk of developing multiple sclerosis over the subsequent 10 years.³ Fortunately, there is evidence that the use of interferon β-1a reduces the risk of developing multiple sclerosis in these patients.⁴

Figure 23-6 Magnetic resonance images are two different levels showing multiple white-matter lesions in a patient with isolated acute optic neuritis.

Patients who experience an attack of optic neuritis in one eye have a 10% to 20% risk of developing a similar event in the opposite eye.² Risk factors for second-eye involvement include white-matter lesions on magnetic resonance images, a family history of multiple sclerosis, and neurological symptoms.

A variant of optic neuritis that has a very different prognosis from the demyelinating or idiopathic form is neuroretinitis.⁵ This condition begins as an apparently straightforward anterior optic neuritis in which vitreous cells may or may not be present; however, within 1 to 3 weeks, a macular star develops that often persists after the optic disc swelling resolves (Fig. 23-7). Neuroretinitis may be caused by cat-scratch disease, sarcoid, syphilis, tuberculosis, or Lyme disease; however, it is never caused by multiple sclerosis.

Figure 23-7 Acute neuroretinitis. Note swelling of optic disc associated with macular star appearance composed of lipid.

Ischemic Optic Neuropathy

The second major cause of acute visual loss with and without optic disc swelling is ION.⁶ This condition occurs in three main settings: (1) as a complication of systemic noninflammatory vascular diseases, such as diabetes mellitus, hypertension, and hypercholesterolemia; (2) in the perioperative period, most often after cardiac surgery or back surgery in the prone position; and (3) as a complication of vasculitis, most often temporal (giant cell) arteritis.

Nonarteritic ION usually occurs in patients older than 55; equal numbers of men and women are affected. At least one underlying systemic vasculopathy is usually present, but it may or may not have been identified at the time vision is lost.

Nonarteritic ION is usually painless. When eye pain is present, it is usually mild, and pain on eye movement is very rare. As in the case of optic neuritis, the degree of visual loss in patients with nonarteritic ION is variable, ranging from 20/20 to hand motion vision or worse. Color vision usually mirrors acuity; the worse the central vision is, the worse the color vision is. The visual field usually shows an altitudinal or arcuate field defect. A relative afferent pupillary defect is always present if the condition is unilateral and there is no optic neuropathy in the opposite eye.

Nonarteritic ION may be of the anterior or the retrobulbar variety.⁷ In anterior ION, which constitutes about 90% of all cases, the optic disc is usually hyperemic, and peripapillary flame-shaped hemorrhages are often present (Fig. 23-8); however, soft exudates (cotton-wool spots) are usually absent. The opposite optic disc is almost always small with little or no cup (see Fig. 23-8), and this morphological anomaly is believed to predispose the nerve to ischemia by causing crowding of the optic nerve axons. Patients with retrobulbar ION have a normal-appearing optic disc. Because this condition is rare in comparison with anterior ION, retrobulbar ION should be considered a diagnosis of exclusion: that is, other causes of retrobulbar optic neuropathy, particularly an intracranial mass, should be considered.

Figure 23-8 Acute nonarteritic anterior ischemic optic neuropathy. Note hyperemic optic disc and flame-shaped hemorrhages (left). Opposite optic disc (right) is small and has no cup (disc at risk).

In about 40% of patients with nonarteritic ION, the condition improves spontaneously, although visual acuity is more likely to improve than is visual field.⁶ No treatment exists for patients whose vision does not recover. In addition, patients who experience an attack of nonarteritic ION are at risk for subsequent cerebrovascular and cardiovascular events, and such patients have an increased rate of mortality in comparison with age- and gender-matched control subjects.

Patients who experience an attack of nonarteritic ION have a 10% to 20% risk of experiencing a similar attack in the opposite eye.⁸ Risk factors for opposite eye involvement include advanced age, severe vascular disease, and persistent poor visual acuity in the affected eye.

Perioperative ION occurs most often after back surgery in the prone position and after cardiac surgery in which cardiopulmonary bypass is used. The rates vary from 0.06% to 0.1% after cardiac surgery and from 0.1% to 0.01% after back surgery in the prone position.^9,10

The major factors leading to this complication appear to be operative and perioperative anemia and hypotension, although there are cases in which neither of these factors appears to be in evidence.

Perioperative ION is often, although not invariably, bilateral; visual acuity in the affected eye is usually very poor, and the optic discs may be swollen or normal in appearance. Spontaneous improvement is rare. There is no proved treatment, but the author believes that anemia and hypotension should be corrected immediately, because there is indirect evidence from cases of nonsurgical anemia or hypotension that vision could improve with this treatment. Nevertheless, the author is unaware of any cases of perioperative ION in which vision has substantially improved after this treatment.

Arteritic ION is the least common type of ION. It is usually associated with temporal (giant cell) arteritis,⁶ but other vasculitides can be responsible, such as periarteritis nodosa. Patients with this condition do not experience eye pain, but they may have headache, scalp tenderness, jaw pain, ear pain, or a combination of these manifestations. Thus, the physician evaluating a patient with possible arteritic ION must ask specifically about these symptoms.

The visual manifestations of arteritic ION are typical. Many affected patients have experienced episodes of transient visual loss preceding permanent loss of vision. The episodes are identical with those experienced by patients with carotid artery disease, usually lasting between 15 seconds and one minute or two. The episodes are unilateral, but both eyes may be affected. Once an attack of arteritic ION occurs, the visual acuity loss is usually profound. Many patients become completely blind in the affected eye, and in almost all, vision is worse than 20/400. The condition is usually unilateral, but bilateral simultaneous ION is not uncommon, and bilateral sequential ION is the rule if the condition is not diagnosed correctly and treated within a short time. As with other unilateral optic neuropathies, patients with arteritic ION always have an ipsilateral relative afferent pupillary defect. The absence of this finding in a patient with presumed arteritic ION should raise concern regarding subclinical involvement of the contralateral eye.

As with nonarteritic and perioperative ION, arteritic ION may be of the anterior or retrobulbar variety. When the condition is of the anterior type, the optic disc usually shows pallid rather than hyperemic swelling, which indicates a true infarction of the nerve, and one or more soft exudates (cotton-wool spots) are often present (Fig. 23-9). Indeed, in the appropriate clinical setting, the presence of such exudates in a patient with an acute anterior optic neuropathy is almost pathognomonic of arteritic ION.

Figure 23-9 Arteritic anterior ischemic optic neuropathy. Note pallid swelling, indicating an infarction of the disc substance. Also note peripapillary soft exudate (cotton-wool spot).

In most patients, regardless of treatment, arteritic ION does not improve. Nevertheless, a small percentage do experience improvement; these are usually patients treated with high-dose systemic corticosteroids (methylprednisolone [Solu-Medrol], 1g/day). Of more importance, perhaps, is that this treatment substantially reduces, although it does not eliminate, the risk of second-eye involvement and also may protect the patient against other complications of the vasculitis, including stroke, heart attack, and renal failure. Thus, it is crucial to diagnose and treat unilateral arteritic ION as soon as possible.

Leber’s Hereditary Optic Neuropathy

LHON can occur at any age but typically manifests in young adults; about eight times more men than women are affected.¹¹ Visual loss is bilateral and simultaneous in about one half the cases; in the remainder, one eye is affected initially, and the other eye becomes affected, in most cases, within 1 month. Whether unilateral or bilateral, the visual loss is always painless, and this distinguishes the condition from acute optic neuritis, which is almost always associated with pain behind or around the eye, often worsening with eye movement (see previous discussion). The rate of visual loss in LHON is slower than that caused by optic neuritis but faster than that caused by most compressive lesions. The nadir, typically about 20/400, is usually reached within 3 to 6 months. The visual loss is associated with marked color vision loss; a central or cecocentral scotoma with preservation of the peripheral field in most but not all cases; and either a normal-appearing optic disc or the triad of hyperemic “pseudoedema” of disc, telangiectatic vessels on the disc and in the peripapillary region, and no evidence of leakage on fluorescein angiogram (Fig. 23-10).

Figure 23-10 Leber’s hereditary optic neuropathy. Note dilated vessels on disc surface and in the peripapillary region in both fundi.

LHON is a mitochondriopathy. It is, therefore, maternally inherited; more than 90% of cases are caused by mutations at sites 11778 (the most common site), 14484, and 3460. There are a number of other sites at which mutations are responsible for small numbers of cases. Approximately 20% of patients with the pathogenic mutations that cause LHON become symptomatic, but it is not known which factors cause some patients but not others to lose vision. Alcohol abuse, tobacco abuse, and metabolic stress have all been postulated to play a role, but none has been proved to do so.¹²

The natural history of LHON varies with the site of the mutation.¹¹ Patients with the 11778 mutation have the worst visual prognosis, with a 4% improvement rate, whereas 25% to 40% of patients with mutations at sites 14484 and 3460 experience improvement, often to 20/20 or better. Improvement is associated with breaking up of the central field defects.

Unfortunately, there is no definitive treatment for LHON. Although it has been suggested that idebenone, a form of coenzyme Q, may be helpful, there are few data to support this contention, and other “cocktails” of various vitamins and enzymes have not been found to successfully treat or prevent the condition.

The diagnosis of LHON should be considered in any patient, young or old, who experiences painless, relatively rapid (too slow for optic neuritis and too fast for most compressive lesions) visual loss in one or both eyes in association with normal-appearing optic discs what appears to be minimal disc swelling (i.e., hyperemic disc) without hemorrhages or exudates.

Compressive Optic Neuropathy

A compressive optic neuropathy may be unilateral or bilateral.¹³ When it is unilateral, the optic disc may be swollen or normal in appearance. When it is swollen, the mass is almost always located within the anterior or middle portion of the orbit (Fig. 23-11). When the disc appears normal, the lesion is located in the posterior orbit, in the optic canal, or intracranially. When the visual loss is bilateral, the lesion is almost always intracranial or in the paranasal sinuses, and the optic discs appear normal, at least initially.

Figure 23-11 Compressive anterior optic neuropathy. Left, Optic disc is moderately swollen. Note absence of hemorrhages. Right, Computed tomographic scan shows intraconal mass. Note compression and medial deviation of the optic nerve by the mass.

Regardless of their location, lesions that compress the optic nerve can produce any level of visual loss and any type of field defect. In most cases, color vision is diminished in the affected eye, and the severity of color deficit may be more than expected in comparison with the severity of visual loss. A relative afferent pupillary defect is present in every patient with a unilateral process.

Patients suspected of having a compressive optic neuropathy require neuroimaging. When an orbital or paranasal sinus process is suspected, computed tomographic scanning is the optimum imaging modality, whereas intracranial lesions are best detected with magnetic resonance imaging. The treatment of a compressive lesion of the optic nerve depends on the nature of the lesion, as well as its location. Whether a patient improves after successful elimination of the compression process depends in part on how long symptoms have been present and the severity of visual dysfunction before treatment.

Infiltrative Optic Neuropathy

Like compressive optic neuropathies, infiltrative optic neuropathies may be unilateral or bilateral.¹³ Any level of visual loss can occur, and any type of visual field defect can be present. As with other optic neuropathies, a relative afferent pupillary defect is always present in unilateral cases. Patients with an infiltrative optic neuropathy may have an optic disc that is truly swollen, a disc that appears swollen but that is actually infiltrated with the underlying lesion, or a normal disc. Disorders most likely to produce an infiltrative optic neuropathy include reticuloendothelial disorders, such as leukemia and lymphoma; inflammatory conditions, such as sarcoidosis; and metastatic tumors, particularly carcinomas (Fig. 23-12).

Figure 23-12 Infiltrative optic neuropathy. Optic disc has a fluffy appearance, which is consistent with infiltration, rather than true swelling.

The diagnosis of an infiltrative optic neuropathy may be difficult; however, in many cases, magnetic resonance imaging reveals diffuse or focal enlargement and enhancement of the affected nerve. Both treatment and prognosis depend on the nature and severity of the process.

Toxic and Deficiency Optic Neuropathies

These conditions are almost always bilateral, although one eye may be affected days to weeks before the other.¹⁴ The loss of vision occurs slowly, usually over one month or more. The eventual nadir is usually about 20/400, except with methanol toxicity, which can cause complete blindness. The visual loss in patients with toxic or deficiency optic neuropathies is virtually always accompanied by bilateral severe loss of color vision, bilateral central or cecocentral scotomas, and optic discs that appear normal or perhaps slightly swollen (Fig. 23-13). Hemorrhages and exudates are almost never seen. Because of the bilaterality of the process, a relative afferent pupillary defect is almost never present. The substances that can cause a toxic optic neuropathy include both common and uncommon medications (Table 23-1).

Figure 23-13 Toxic optic neuropathy in a patient taking ethambutol and isoniazid for pulmonary tuberculosis. Both right (left) and left (right) optic discs appear slightly swollen.

TABLE 23-1 Some Reported Causes of Toxic Optic Neuropathy

Traumatic Optic Neuropathy

The diagnosis of traumatic optic neuropathy is usually quite easy to establish.¹⁶ It usually occurs in the setting of blunt head trauma, in which there is often a period of loss of consciousness. The majority of cases appear to result from damage to the optic nerve within the optic canal, where traumatic hemorrhage and swelling produce severe damage to the optic nerve and its blood supply. The severity of visual loss is variable, from mild loss of visual acuity to no light perception. Although some physicians advocate treatment with systemic corticosteroids and others advocate decompression of the optic nerve within the optic canal, there is no evidence that any intervention is better than the natural history of the process.

Radiation-Induced Optic Neuropathy

This condition occurs in 10% to 15% of cases in which the optic nerves have received at least 5000cGy.¹⁷ The only exceptions appear to be patients with diabetes mellitus and patients receiving chemotherapy for cancer at the time of the irradiation, in which case the condition can occur with smaller doses. A transient type of optic neuropathy can occur during the irradiation itself and is believed to be related to acute swelling of the nerve. This form of optic neuropathy is usually self-limited, and treatment consists of systemic corticosteroids. Most cases of radiation-induced optic neuropathy, however, occur 1 to 8 years after irradiation and consist of a relatively rapid progression of visual loss in one or both eyes, usually associated with an initially normal-appearing optic disc that gradually becomes pale. Neuroimaging in such cases may reveal enhancement and enlargement of one or both optic nerves, but this is not a universal finding (Fig. 23-14).

Figure 23-14 Neuroimaging of radiation-induced optic neuropathy. Magnetic resonance image shows enlargement and enhancement of the left optic nerve.

There is no proved treatment for radiation-induced optic neuropathy. Corticosteroids, anticoagulants, and hyperbaric oxygen all have their supporters, but none of these treatments has proved successful in the majority of cases.