Optic neuritis typically begins with rapid, but not sudden, loss of vision, usually unilateral. The onset of visual loss is relatively acute and progresses over hours or days (Glaser 1990). It is associated with pain (90%) in or behind the eye. Pain may precede visual loss and lasts for days to weeks. An afferent pupillary defect is expected, unless the other eye is also involved.
Visual loss is usually monocular, but 19% to 50% of adults (Hutchinson 1976; Beck et al 1993a; 1993d) and 60% of children have bilateral loss. With unilateral optic neuritis, the “normal” fellow eye has decreased visual acuity in 70%, but this resolves quickly (Foroozan et al 2002). Thus, bilateral optic neuritis is common, even if unapparent. Bilateral loss is associated with infections, with acute disseminated encephalomyelomyelitis, and is more common in people of Korean (Hwang et al 2002) and black South African descent (Pokroy et al 2001); these authors may have been describing Devic disease. Children with bilateral visual loss have a better prognosis than adults (Parkin et al 1984).
Bilateral visual loss is most likely following a virus infection (chickenpox, human herpes virus-6B) or vaccination (Kennedy 1960; Farris and Pickard 1990; Good et al 1992), or in Devic disease (80% get optic neuritis as the first symptom; 20% of these are bilateral) (Merle et al 2006) and acute disseminated encephalomyelitis. It can also complicate acute renal failure. It is sometimes idiopathic.
Deficit in the central field of vision is commonly mentioned by the patients and detectable in 97%; but on formal testing, central vision is preferentially diminished in only 10%. The central scotoma is described as blurring or a dark patch, and visual acuity is not improved when looking through a pinhole. Diffuse loss is more common and is seen in 50% of affected eyes (Keltner et al 1993; Foroozan et al 2002). Paracentral or peripheral field defects are less common. Chiasmal neuritis is a variant of optic neuritis, which is similar in clinical course except that visual field defects are bitemporal or junctional, and pain is less prevalent (Pula and Reder 2009). Altitudinal defects are typical with ischemic arterial disease, but also appear in 6% to 20% of patients with optic neuritis (Keltner et al 1993).
Contrast sensitivity is abnormal in nearly 90% of patients with normal visual acuity (Foroozan et al 2002). Low-contrast testing is more sensitive than regular contrast.
Visual acuity can be normal even with significant axonal loss; 20/20 vision requires only 44% of normal foveal axons; 20/70 vision requires only 5% (Miller 1982). Bilateral field loss with normal visual acuity, however, suggests multiple sclerosis plaques in posterior visual pathways.
Visual function is worst at 7 to 10 days. It usually begins to improve rapidly after 2 weeks, and resolution continues over several months. Complete recovery of visual acuity is common, even after near blindness, and functional levels of sight are the rule (Glaser 1990). Almost all patients with a moderate defect recover completely or to near normal within a year; 40% of those with total or severe blindness recover to normal (Celesia et al 1990). Evoked potentials and contrast sensitivity improve for 2 years (in some studies but not others), likely from ion channel reorganization, less inflammation, and remyelination. With time, however, the insidious effects of continual low-grade demyelination and axonal degeneration usually become more evident (Brusa and Jones 2001) as optic atrophy evolves over several years. Progressive visual worsening for more than 2 weeks, or no recovery after 8 weeks, suggests the diagnosis may not be optic neuritis (Kaur and Bennett 2007). The risk of developing multiple sclerosis is discussed in the Prognosis and complications section of this clinical summary.
Other disturbances of vision such as reduced contrast sensitivity and stereopsis often persist, even when acuity has returned to normal. Patients may complain of visual "blurring" but have normal visual acuity on testing. Colors are often drab, even in 30% of patients whose visual acuity is normal. Red desaturation is traditionally expected, but loss of blue hues may be as common as red (Frederiksen et al 1991; Katz 1995). Six months after vision in the affected eye has recovered to 20/30 or better, there remains abnormal color vision (57%), contrast sensitivity (72%), perimetry (26%), stereo acuity (80%), light brightness (89%), papillary reaction (89%), and optic disc appearance (77%) (Fleishman et al 1987). The non-affected eye (acuity = 20/20) sometimes has problems with color vision (21%), visual contrast (33%), and disc appearance (5%). Improvement in visual acuity and visual fields is correlated with the physical length of nerve enhancement on MRI (shorter is better) (Hickman et al 2004).
Apparent light intensity is reduced in the affected eye, and this corresponds to a Marcus Gunn pupillary response (ie, relative afferent papillary defect, APD) in the swinging flashlight test. Quicker redilation indicates a subtle afferent papillary defect. Retinal disease or bilateral optic neuritis can negate the test. A neutral density filter can amplify the defect from optic neuritis (eg, the normal eye at 20/20 is reduced to 20/40 with the filter. In the affected eye, however, 20/40 drops to 20/100). The filter can help differentiate optic neuritis from ischemic optic neuropathy, retinal disease, and functional defects where the change with the filter is minimal or absent.
Depth perception is impaired in 80% of patients with a history of optic neuritis, and this alters the trajectory of moving objects (Pulfrich phenomenon, in which a swinging pendulum seems to bend toward the eye with slower conduction velocity). Even in multiple sclerosis patients with no history of optic neuritis and 20/20 vision, Randot stereoacuity testing shows binocular depth perception defects in 74% of patients (Sobaci et al 2009). The horizontal disparity that gives rise to depth perception (binocular integration) requires input from both optic nerve and the inferior temporal cortex. Depth perception can be easily tested at the patient’s bedside with a swinging black pen (Mojon et al 1998) or formally with stereopsis grids. Impaired depth perception could interfere with driving.
Bright lights cause a prolonged afterimage; for example, lights of an oncoming car at night cause a lingering phantasm of headlights. This "flight of colors" is as common as slowed visual evoked potentials (Swart and Millac 1980). Eye movements sometimes cause fleeting flashes of light (movement phosphenes); the mechanism corresponds to that of Lhermitte sign from cervical cord lesions in multiple sclerosis (Davis et al 1976). The critical flicker fusion frequency is reduced. All of these symptoms are amplified by increased body temperature (Uhthoff sign) and by acidosis from exercise, sometimes without a rise in body temperature. Visual evoked potentials are slowed in normal optic nerves by a rise in temperature of 1.6°C. In eyes with prior optic neuritis, even minimal heat or exercise can diminish visual acuity, sometimes within minutes (Scherokman et al 1985; Selhorst and Saul 1995). Half of patients with multiple sclerosis and optic neuritis have visual temperature sensitivity, and only 16% had resolution of visual Uhthoffs (Fraser et al 2012).
Retro-orbital pain is common (80% to 90%) and may precede visual loss (Hutchinson 1976; Foroozan et al 2002). The sheath of the optic nerve is pain-sensitive, unlike most of the deep cerebral areas that are demyelinated in multiple sclerosis. Pain is felt in the eye or ophthalmic division of the trigeminal nerve in more than 90% of patients with MRI lesions in the orbital optic nerve but in only 30% of patients with lesions of intracranial pathways (Fazzone et al 2003). Pain and disc swelling is most likely when there is Gadolinium enhancement in the anterior orbital optic nerve (Hickman 2004). Pain can be present at rest, with pressure on the globe, and with voluntary movement. The pain in the globe or brow is worse with eye movement because of traction of the superior and medial recti on the optic nerve sheath at the orbital apex (Lepore 1991). Severe, persistent pain suggests another disorder such as posterior scleritis, infection, sarcoidosis, or granulomatous optic neuropathy. Headache is present in nearly one third of children with optic neuritis (Kennedy 1960).
The fundus is often normal (60%), especially when the inflammation is retrobulbar (Hutchinson 1976). The fundus sometimes appears blurred, possibly from prior optic neuritis, or shows papillitis with swelling of the optic nerve head and peripheral hemorrhages (17% to 40%; severe in 5%) (Bradley and Whitty 1968; Hutchinson 1976). Papillitis is more common in children (65% to 70%) (Kennedy 1960; Riikonen et al 1988; Good et al 1992). With papillitis, inflammation of the anterior optic nerve causes disc swelling, and sometimes hemorrhages, cells in the vitreous, and deep retinal exudates. It can cause loss of normal spontaneous venous pulsations. Swelling is from inflammation and edema, obstruction of axonal transport, and venous congestion.
After the neuritis resolves, the disc is often pale (optic pallor), most commonly in the temporal aspect. Optic pallor appears when axons drop out; the transparent nerve fiber bundles are no longer able to conduct light. This light normally would pass into the disc and pass through capillaries. Instead, it is reflected from glial cells and appears white instead of pink, usually in the temporal area.
Atrophy is seen over time, especially after lesions that cause poor visual acuity and slowed evoked potentials. Distal axons degenerate completely with 7 days, but the cell body and proximal axon appear normal for 3 to 4 weeks. These then degenerate rapidly, and by 6 to 8 weeks there are no more viable cells among the affected retinal ganglion cells (Miller 1982). Imaging with ocular coherence tomography (OCT) can accurately define the loss. Visual evoked potential amplitude (axonal dysfunction) and visual acuity improve over 4 months, but VEP latency (demyelination) and motion perception remain impaired (Raz et al 2012), interfering with walking and driving.
Lesions are often disseminated beyond the eye. Idiopathic chiasmal lesions in 20 patients, in whom 6 had associated white matter lesions, evolved to multiple sclerosis in 40% over 1 to 5 years (Kawasaki and Purvin 2009). Between 25% and 75% of patients with optic neuritis have abnormal MRI scans. In 70% of optic neuritis patients with disseminated brain lesions on MRI, attention and information processing speed are reduced (Feinstein et al 1992), an indication of diffuse central nervous system dysfunction. Similarly, blood flow in the affected occipital cortex is reduced on functional MRI (Toosy et al 2002) and magnetization transfer (Audoin et al 2006), and activation of extra-occipital areas is increased (Toosy et al 2002). Conversely, 31% of army recruits with multiple sclerosis had optic signs (Kurtzke 1970).
Less commonly recognized phenomena such as slit-like defects in the peripapillary nerve fiber layer are described in patients with multiple sclerosis, with or without a history of acute optic neuritis (Frisen and Hoyt 1974; Elbol and Work 1990). With red-free light, retinal nerve fiber layer defects and an abnormally small neuroretinal rim are often visible, and are sometimes present when visual evoked potentials are normal (MacFadyen et al 1988). These defects are due to axonal pathology and suggest optic nerve damage.
Periphlebitis retinae (perivenous sheathing) and pars planitis are more common during active multiple sclerosis than in optic neuritis. Twelve percent of patients with optic neuritis have retinal venous sheathing. These patients are more likely to develop multiple sclerosis (Lightman et al 1987), but the sheathing does not predict clinical disease course. Periphlebitis retinae consist of glistening cuffs of immune cells around segments of retinal veins. After infiltration of the walls of veins by lymphocytes and plasma cells, thick hyaline material in concentric lamellae replaces the normal lacy periventricular connective tissue. The residual fine lines of scarring and venous sheathing around veins are easily seen with an ophthalmoscope (Engell et al 1999). There is leakage on fluorescein angiography. Because there is no myelin in the retina, some vascular changes may be independent of demyelination.
Between 1% and 50% of patients with pars planitis have multiple sclerosis. In those with multiple sclerosis, it is associated with HLA-DR2. Seven percent will develop optic neuritis; 16% to 33% will develop multiple sclerosis (Malinowski et al 1993; Prieto et al 2001). Pars planitis is difficult to detect; this difficulty is one explanation for the huge range in incidence. This form of uveitis is restricted to the area behind the iris, the pars plana of the ciliary body. It is not an anterior uveitis (in the anterior chamber or iris) or a posterior uveitis (in vitreous, choroid, retina, or optic nerve). An angled lens or slit lamp helps visualize protein and cells that have settled to the bottom of the vitreous and formed “snowballs” from an inflammatory attack against the highly vascular uvea (iris, ciliary body, and retinal pigment epithelium). The local antigen that is a target of the immune attack remains unknown, but similar inflammation is seen with bacterial, viral, and protozoal infections, and with autoimmune diseases (Brazis et al 2004).