Optic Neuritis

Typical optic neuritis is an inflammatory optic neuropathy caused by demyelinating disease (Balcer, 2006) (Fig. 15.5). Visual loss in the affected eye typically occurs rapidly over several hours to a few days. Decreased color vision and contrast sensitivity are highly characteristic (Baier et al., 2005; Trobe et al., 1996). In addition, pain with eye movements precedes the vision loss in approximately 90% of cases (Optic Neuritis Study Group, 1991). The pain typically lasts 3 to 5 days; if it persists for longer than 7 days, optic neuritis should be considered less likely, and further workup should be pursued. Visual field defects commonly are present; they can be either diffuse or discrete scotomas and are nonspecific. Fundus examination reveals mild disc swelling in approximately one-third of affected eyes, which is considerably less prominent than the disc swelling associated with papilledema (Balcer, 2006; Beck, 1998) (Fig. 15.6). In the majority of patients, the fundus appearance is normal.

Fig. 15.5 Axial T1-weighted post-gadolinium MRI with fat saturation in a patient with right optic neuritis. Note swelling and enhancement of the right optic nerve (black arrow) consistent with inflammation.

(Reprinted with permission from Prasad et al., 2010.)

Fig. 15.6 Fundus photograph of the right eye in a patient with acute right optic neuritis. Note mild nerve fiber layer swelling, greatest at the temporal portion of the disc (black arrow), without hemorrhages or cotton-wool spots.

(Reprinted with permission from Prasad et al., 2010.)

The prognosis for recovery of vision generally is good but is in relation to the severity of the initial deficit. Recovery typically begins within 1 month. The likelihood of progression of optic neuritis to multiple sclerosis (MS) is best predicted by brain magnetic resonance imaging (MRI) at the time of diagnosis. In the Optic Neuritis Treatment Trial, the risk of developing MS within 15 years was 72% among patients with one or more characteristic brain lesions, whereas it was 25% if the MRI was normal (Optic Neuritis Study Group, 2008). With features that are atypical for optic neuritis, however (e.g., painless visual loss, severe disc edema, disc or peripapillary hemorrhages, macular exudate), the risk of developing MS is significantly lower (Beck et al., 2003).

Following an episode of optic neuritis, the optic nerve often demonstrates pallor, suggesting that axonal loss has accompanied the episode of demyelination (Fig. 15.7). Optical coherence tomography (OCT) is a noninvasive imaging method that quantifies the atrophy of the nerve fiber layer (Balcer, 2006). It provides a reliable structural marker that complements clinical assessments of visual function.

Fig. 15.7 Top, Fundus photographs of the left eye in a patient with prior left optic neuritis, demonstrating mild temporal pallor (black arrow). Below, Optical coherence tomography (OCT) measurement of retinal nerve fiber layer thickness confirms and quantifies temporal nerve fiber layer thinning (corresponding to the papillomacular bundle). Thickness measurement is shown in black line, with normal range depicted in green zone; measurements within the yellow zone are borderline, and within the red zone are abnormally low.

(Reprinted with permission from Prasad et al., 2010.)

Neuromyelitis optica (NMO), or Devic disease, is characterized by necrotizing demyelinating lesions of bilateral optic nerves and the spinal cord (Wingerchuk, 2006). It is believed to be a humorally mediated disease distinct from MS. The spinal lesion characteristic of NMO often extends contiguously over three or more vertebral segments. A serum antibody, neuromyelitis optica immunoglobulin G (NMO-IgG), which targets the autoantigen aquaporin 4 (AQP4), may be a useful marker in diagnosing the condition, although the exact specificity remains unknown (Jarius et al., 2008). Treatment with rituximab, a chemotherapeutic monoclonal antibody, may be of particular benefit in this group of patients (Wingerchuk, 2006).

Treating optic neuritis with high-dose intravenous (IV) corticosteroids reduces the risk of developing MS over the following 2 years (Beck et al., 1992). In the long term, however, this acute treatment is unlikely to affect the likelihood of progression to MS. In addition, IV corticosteroid treatment may hasten visual recovery, particularly for visual fields and contrast sensitivity, but does not significantly affect long-term visual outcomes. Because low-dose oral corticosteroids may be associated with an increased risk of recurrence of optic neuritis, this therapy should be avoided (Beck et al., 1992). In addition to IV corticosteroids, recent studies support the early use of immunomodulating treatments for high-risk patients to reduce the likelihood of progression to MS within 2 to 5 years (Balcer, 2006).

Ischemic Optic Neuropathy

Arteritic anterior ischemic optic neuropathy (AAION) is usually related to giant cell arteritis (GCA), also referred to as temporal arteritis. Its incidence increases with age, with most patients being older than 70.

GCA typically affects the extracranial medium- to large-caliber arteries, because they possess elastic lamina, which is the initial site of inflammation in this disorder (Salvarani et al., 2008). The condition is associated with polymyalgia rheumatica, consisting of proximal muscle ache, arthralgia, and stiffness, as well as with jaw claudication, fever, malaise, and scalp tenderness. The diagnosis is suggested by an elevated erythrocyte sedimentation rate and C-reactive protein and is confirmed by evidence of giant cells and endovascular inflammation on temporal artery biopsy. Acute vision loss is the presenting symptom in 7% to 60% of cases and is generally more severe than in NAION. In approximately 25% of cases, vision is limited to hand motion perception or worse (Balcer et al., 2003). In suspected cases, treatment with corticosteroids should not be delayed until a biopsy is obtained. Intraveous corticosteroids may help delay the progression of visual loss and decrease the likelihood of fellow eye involvement. The prognosis for recovery in the affected eye, however, is poor despite treatment (Hall and Balcer, 2004).

The optic disc in AAION typically has a chalky-white edematous appearance, and disc hemorrhages are likely to be present (Fig. 15.8). Coexisting retinal ischemia with cotton-wool spots is very typical for AAION. Fluorescein angiography reveals choroidal hypoperfusion (Fig. 15.9). Occasionally, GCA can be limited to the retro-orbital nerve and present without disc swelling; this situation is termed arteritic posterior ischemic optic neuropathy (PION).

Fig. 15.8 Fundus photograph of the right eye in a patient with ischemic optic neuropathy from temporal arteritis. Note blurring of the nasal disc margin, with pallor and swelling of the nerve head (black arrow). The patient also has inner retinal ischemia evidenced by large cotton-wool spots (black asterisks).

(Reprinted with permission from Prasad et al., 2010.)

Fig. 15.9 Late-phase fluorescein angiography of the left eye in a patient with giant cell arteritis, revealing nonperfused choroid (black asterisks) consistent with occlusion of posterior ciliary vessels.

(Reprinted with permission from Prasad et al., 2010.)

Nonarteritic AION is the most common cause of unilateral optic nerve swelling in adults older than 50 and is commonly associated with vascular risk factors such as diabetes or hypertension (Fontal et al., 2007). Other risk factors include a crowded optic nerve head and nocturnal hypotension, possibly precipitated by antihypertensive therapy (Arnold, 2003; Mathews, 2005). Swelling of a crowded optic nerve within the scleral canal may provoke a cycle of further vascular compression, ischemia, and swelling.

Although the clinical profile of NAION may occasionally overlap with the findings of optic neuritis (Rizzo et al., 1991), typical features of NAION include nerve fiber hemorrhages, altitudinal visual field loss, moderate to severe disc edema, and the absence of pain (Figs. 15.10 and 15.11). Because the optic nerve head is supplied by an end-arterial system of short posterior ciliary arteries and the circle of Zinn-Haller, sectoral ischemic disc swelling is common. NAION may follow ocular surgery, because an associated increase in intraocular pressure may compromise optic nerve head perfusion (Fontal et al., 2007).

Fig. 15.10 Fundus photographs in a patient with acute nonarteritic ischemic optic neuropathy in the right eye, demonstrating peripapillary edema (black arrows) with a small cup-to-disc ratio in the left eye (white arrow), suggesting a “disc at risk.”

(Reprinted with permission from Prasad et al., 2010.)

Fig. 15.11 Fundus photographs of the right eye in a patient with right nonarteritic anterior ischemic optic neuropathy. Note blurring of the disc margin and swelling of the optic nerve head (black arrows), splinter hemorrhages (white arrows), as well as dilated capillaries and luxury perfusion of the nerve head (asterisk).

(Reprinted with permission from Prasad et al., 2010.)

Many patients with NAION will have a stable deficit, although one minority may experience visual loss progressing over one month. Spontaneous improvement may occur in the first 6 months, although in many patients this reflects improved ability with eccentric fixation (Hayreh and Zimmerman, 2008). In 30% to 40% of patients, subsequent involvement of the fellow eye also occurs, and this rate is increased by the presence of vascular risk factors. When the second eye is affected in AION, optic atrophy has already developed in one eye, and acute disc edema occurs in the fellow eye; this clinical presentation is called the pseudo–Foster Kennedy syndrome. (A true Foster Kennedy syndrome is produced by optic atrophy due to compression, typically from an expanding tumor, and papilledema in the fellow eye secondary to increased ICP.) Occasionally, premonitory disc swelling in an asymptomatic eye will be noted, which may progress to frank visual loss or remit spontaneously (Hayreh and Zimmerman, 2007). Recurrence of NAION in an affected eye, however, is rare, possibly because optic nerve atrophy following the initial event decompresses the nerve. There does not appear to be a significantly higher rate of stroke in patients with nonarteritic ischemic optic neuropathy, suggesting that its pathophysiology may differ from simple vasoocclusion (Arnold and Levin, 2002).

Other Causes

Inflammatory conditions are an important cause of subacute optic neuropathy. Optic discs may appear swollen or normal, the latter indicating retrobulbar involvement. Optic nerve involvement is common in neurosarcoidosis, which can be accompanied by anterior uveitis or posterior segment vitritis (Prasad et al., 2008) (Fig. 15.12). Visual loss due to this condition is often steroid responsive. Optic neuropathy and retinal involvement may also occur with other inflammatory disorders, such as systemic lupus erythematosus and Sjögren disease (Fig. 15.13). Occasionally, optic nerve infiltration produces optic disc edema without affecting visual function, but more often there is a decrease in visual acuity and visual field loss.

Fig. 15.12 Coronal T1-weighted post-gadolinium MRI in a patient with left optic neuropathy from neurosarcoidosis. Note swelling and enhancement of right optic nerve (white arrow).

(Reprinted with permission from Prasad et al., 2010.)

Fig. 15.13 Optic disc pallor and multiple cotton-wool spots in a patient with systemic lupus erythematosus.

Infectious conditions are another frequent cause of optic neuropathy (March and Lessell, 1996). Neuroretinitis, in which optic neuropathy coexists with characteristic peripapillary or macular exudates, should be distinguished from acute demyelinating optic neuritis (Fig. 15.14