The n e w e ng l a n d j o u r na l of m e dic i n e

clinical practice

Optic Neuritis
Laura J. Balcer, M.D., M.S.C.E.

This Journal feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal guidelines,
when they exist. The article ends with the author’s clinical recommendations.

A 25-year-old woman presents with a one-week history of blurred vision in the left eye.
One day before the onset of visual loss, she noted a dull ache in the left periorbital
region accompanied by pain on eye movement. Her symptoms progressed for three
days but have not worsened since. The patient has no history of other visual or neuro-
logic symptoms. Examination reveals visual acuity of 20/40 in the left eye when tested
with a Snellen chart, reduced color perception, and a left afferent pupillary defect
(i.e., a poor response of the left pupil to light stimulation as compared with the right
pupil, on a swinging flashlight test). There is no visible swelling of the optic disk or
pallor of the optic nerve, and a neurologic examination is normal. How should she be
evaluated and treated?

The Cl inic a l Probl e m

Optic neuritis is a condition involving primary inflammation of the optic nerve. It From the Division of Neuro-ophthalmol-
may be associated with a variety of systemic autoimmune disorders, but the most ogy, Departments of Neurology and Oph-
thalmology, University of Pennsylvania
common form, acute demyelinating optic neuritis, is best known for its association School of Medicine, Philadelphia. Address
with multiple sclerosis.1-4 Acute demyelinating optic neuritis is the presenting fea- reprint requests to Dr. Balcer at the De-
ture (i.e., the first clinical demyelinating event) in 15 to 20 percent of patients with partment of Neurology, 3 East Gates,
3400 Spruce St., Philadelphia, PA 19104,
multiple sclerosis, and it occurs at some time during the course of the disease in 50 or at lbalcer@mail.med.upenn.edu.
percent of patients.5-8 During a 10-year follow-up, multiple sclerosis was diagnosed
in 38 percent of patients with a first episode of optic neuritis who were enrolled in N Engl J Med 2006;354:1273-80.
Copyright © 2006 Massachusetts Medical Society.
the Optic Neuritis Treatment Trial (ONTT), a multicenter study of the effects of
high-dose corticosteroid treatment on visual outcome.4 The risk was greatest among
patients who had one or more demyelinating lesions on magnetic resonance imag-
ing (MRI) of the brain at baseline but was not influenced over the long term by
corticosteroid treatment.4,9 Additional data from natural-history studies indicate an
even higher rate of multiple sclerosis among patients during a longer follow-up
period after the first demyelinating events.10
Recurrences of optic neuritis after a single isolated episode are not uncommon.
Among patients in the placebo group of the ONTT, the risk of at least one recurrence
was 31 percent during the 10-year follow-up period and was greatest among those
in whom multiple sclerosis had developed (48 percent in patients with multiple
sclerosis vs. 24 percent in patients without multiple sclerosis).11
The high risk of multiple sclerosis associated with optic neuritis, combined with
data from clinical trials demonstrating a reduction in this risk with early therapy
among selected patients, underscores the importance of accurate diagnosis and
management.12-15

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 The n e w e ng l a n d j o u r na l of m e dic i n e

S t r ategie s a nd E v idence Worsening beyond one week or failure of recov-

ery to begin within four weeks is considered sus-
Diagnosis picious for other diagnoses (Table 1).5-8,16,17 Al-
History and Physical Examination though the majority of patients recover their
Acute demyelinating optic neuritis is a clinical visual acuity, subtle symptoms may persist. Even
diagnosis that is made on the basis of the history patients whose visual acuity recovers to 20/20 or
and clinical features (Table 1). Patients report better may report that their vision seems blurred,
subacute visual loss and difficulty perceiving col- washed out, or “not right.”24
ors; objects, particularly red ones, appear “washed Examination of patients with acute demye-
out.” Pain on eye movement is common and was linating optic neuritis reveals evidence of optic
reported by 92 percent of the participants in the neuropathy (e.g., impaired visual acuity and color
ONTT.1,21 Visual loss is usually monocular but vision, visual-field loss, and afferent pupillary de-
may involve both eyes, particularly in children, fect).21 The visual acuity in affected eyes ranges
and typically progresses to its nadir over a period from 20/20 or better to no light perception. An
of hours to days. In the placebo group of the afferent pupillary defect is almost always present
ONTT, median visual acuity in affected eyes was in the affected eye and is assessed by stimulating
20/60 at baseline but improved to 20/25 by day 15 each pupil with a bright light in an alternating
and to 20/20 by one month of follow-up.22,23 pattern; even mild dysfunction of the optic nerve

Table 1. Clinical Features and Differential Diagnosis of Acute Demyelinating Optic Neuritis.

Acute Demyelinating Anterior Ischemic Leber’s Hereditary

Characteristic Optic Neuritis* Optic Neuropathy Optic Neuropathy
Age (yr) 20 to 50 >50 26 to 37
Male sex (%) 33 50 80 to 90

Pain Present in >90% of patients; exacerbated by Present in <10% of patients; accompa- Not usually present; occasionally
eye movement; resolves within 1 wk nied by headache in patients with accompanied by headache
temporal arteritis
Visual loss Progresses over a period of hours to days Sudden onset, often noted by patients Progresses over a period of weeks
(maximum of 10 days); unilateral in on awakening; unilateral in adult pa- to months; involves both eyes
adult patients; signs of optic neuropathy tients; signs of optic neuropathy (e.g., sequentially; signs of optic
(e.g., visual-field loss and impaired visual visual-field loss and impaired visual neuropathy (e.g., visual-field
acuity and color vision)†‡ acuity and color vision) loss and impaired visual acu-
ity and color vision)
Optic disk Swelling present in one third of patients; Swelling present; sectoral involvement May be pale or hyperemic; often
hemorrhages and retinal exudates of optic-nerve head and hemorrhages telangiectatic vessels present
rareठpossible; optic disk in the fellow eye
is crowded with a small or no cup
Visual-field loss Typically central but may be arcuate (radiat- Typically altitudinal (involving area Caused by central or cecocentral
ing from physiological blind spot), ceco- above or below horizontal) scotomas
central (involving central vision and
physiologic blind spot), hemianopic
(involving area to right or left of vertical)
Recovery of Begins within 2 to 4 weeks and generally Improves by 3 or more lines on a Snellen Occurs to some degree in approx-
visual acuity reaches 20/20 or better in 75% of pa- chart over a period of months in ap- imately 33% of patients
tients with normal vision at baseline proximately 40% of patients¶

* Absence of these typical features should suggest other causes of inflammatory optic neuropathy or alternative diagnoses (e.g., sarcoidosis,
systemic lupus and other vasculitides, paraneoplastic disease, syphilis, Lyme disease, Bartonella henselae infection [associated with cat
scratch neuroretinitis], ischemic optic neuropathy, or Leber’s hereditary optic neuropathy).5-8,11,16,17
† The time course of symptom onset distinguishes demyelinating optic neuritis from other inflammatory or compressive optic neuropathies in
which visual function may worsen relentlessly over a period of weeks to months (e.g., sarcoid neuropathy, meningioma, or pituitary adenoma).
‡ Optic neuritis is more frequently bilateral in children than in adults and is more commonly associated with optic-disk swelling in children
than in adults.18-20
§ These ophthalmoscopic findings were associated with an extremely low risk or no risk of multiple sclerosis within 10 years of follow-up
among patients in the Optic Neuritis Treatment Trial.4
¶ Data are from the Ischemic Optic Neuropathy Decompression Trial.16

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 clinical pr actice

results in reduced constriction of the affected anterior ischemic optic neuropathy (Table 1 and
and contralateral pupils in reaction to light when Fig. 1C).4 Lipid deposits, called retinal exudates,
the affected eye is stimulated during the swing- that result from optic-disk edema are rare and
ing flashlight test. Absence of this finding in pa- suggest a diagnosis of neuroretinitis. After weeks
tients with acute visual loss suggests retinal dis- of follow-up, clinically observable atrophy of the
ease (e.g., central serous retinopathy) or coincident optic-nerve head and thinning of the nerve-fiber
optic-nerve dysfunction in the other eye.5-8 layer of the surrounding retina may develop de-
Visual-field loss is typical of acute demyelin- spite recovery of visual acuity.30
ating optic neuritis.21,25-27 Central scotomas are
classic, but a more broad spectrum of patterns
A
typically occurs, including diffuse defects (i.e.,
generalized depression of the entire central 30
degrees of the visual field) and focal defects.26,27
Altitudinal defects (visual-field loss above or be-
low the horizontal meridian) are less common
and should prompt consideration of a diagnosis
of anterior ischemic optic neuropathy (Table 1).
In addition to assessing visual acuity and the vi-
sual field, low-contrast letter acuity (perception of
light gray letters of progressively smaller size on
a white background) and contrast sensitivity B
(minimum contrast level or shade of gray at which
patients can perceive letters of a single large size)
are methods used to detect visual dysfunction in
patients with acute optic neuritis and multiple
sclerosis.28-30 Although these tests are not rou-
tinely performed in clinical practice, reductions
in the scores for these measures have been dem-
onstrated even in patients with visual acuities of
20/20 or better according to a Snellen chart.
The optic disk appears normal in two thirds
of patients with optic neuritis; these patients are
said to have retrobulbar optic neuritis (Fig. 1A).21
When swelling (papillitis) is present in patients
with optic neuritis (Fig. 1B), hemorrhages are
uncommon. The presence of hemorrhages with
swelling suggests alternative diagnoses, such as C

Figure 1. The Optic Disk in Acute Demyelinating Optic

Neuritis.
In two thirds of cases, the optic disk appears normal
(Panel A) and the patients are said to have retrobulbar
optic neuritis. When optic-disk swelling (papillitis) is
present (Panel B), it is mild and diffuse; there are no
peripapillary hemorrhages, cotton-wool spots, or retinal
exudates (lipid deposits) in this setting. Peripapillary
hemorrhages, such as those seen in anterior ischemic
optic neuropathy (Panel C, arrows), are associated with
an extremely low risk or no risk of multiple sclerosis in
patients with optic neuritis as a first demyelinating event
and normal MRI of the brain.4 (Courtesy of Dr. Nicholas
J. Volpe, Department of Ophthalmology, University of
Pennsylvania School of Medicine, Scheie Eye Institute,
Philadelphia.)

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Several features of the history and examina-

tion are predictive of the risk of multiple sclero- A
sis. Among patients in the ONTT who had optic
neuritis as their first clinical demyelinating event
and no white-matter lesions on MRI of the brain,
the features associated with no risk or an ex-
tremely low risk of the development of multiple
sclerosis within the 10-year follow-up period in-
cluded hemorrhage of the optic disk or surround-
ing retina and the absence of pain. Severe disk
swelling, no light perception, and retinal exudates
were also associated with a low risk of multiple
sclerosis; patients with these findings may have B
had alternative diagnoses.4

MRI
MRI of the brain should be performed routinely,
preferably within two weeks after the onset of
symptoms.9 Gadolinium-enhanced MRI (with fat
saturation) of the orbits shows enhancement and
enlargement of the optic nerve (Fig. 2A). More
important is determining whether there are le-
sions indicating a high risk of multiple sclerosis.
Characteristic demyelinating lesions in patients at
risk for multiple sclerosis are 3 mm or larger in
diameter, are ovoid, are located in periventricular
areas of the white matter, and radiate toward the
ventricular spaces (Fig. 2B).12-15 In the ONTT,
the risk of multiple sclerosis within 10 years after
the first episode of optic neuritis was 56 percent
among patients with one or more characteristic
white-matter lesions at baseline, as compared with Figure 2. MRI of Brain and Orbits in a Patient with Acute
22 percent among patients with no lesions.4 Demyelinating Optic Neuritis.
A T1-weighted gadolinium-enhanced axial image of the
orbits with fat-saturation techniques (Panel A) shows
Other Methods of Diagnosis
diffuse enhancement of the left optic nerve (arrows).
Oligoclonal banding of proteins in the cerebro- In patients with optic neuritis as a first demyelinat-
spinal fluid is a useful predictor of the risk of mul- ing event, T2 -weighted and T1-weighted gadolinium-
tiple sclerosis. This is true particularly among pa- enhanced MRI of the brain are also recommended to
tients with normal findings on brain MRI31 but identify white-matter lesions, which would indicate a
high risk of multiple sclerosis. Characteristic demye-
also among patients with abnormal findings that
linating lesions have been defined in clinical trials as
are not classic for demyelination (e.g., small, punc- 3 mm or larger in diameter, with at least one periven-
tate lesions that are not periventricular or ovoid). tricular or ovoid lesion (Panel B, arrows).4,12-15 The
Tests of visual evoked potentials may be help- T2 -weighted axial MRI in Panel B shows multiple areas
ful in patients in whom the diagnosis of acute of increased signal intensity in the periventricular white
matter of the cerebral hemispheres. In the ONTT, the
demyelinating optic neuritis is in question. Ab-
presence of one characteristic lesion at the time of
normal findings (e.g., increased latencies and re- acute visual loss more than doubled the risk of multiple
duced amplitudes of waveform) are consistent sclerosis, as compared with the risk among patients
with demyelination in the afferent visual path- with a normal MRI scan of the brain.4
ways and are observed in more than 65 percent

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 clinical pr actice

of patients with optic neuritis.32,33 However, such prednisone and 16.7 percent among those re-
testing is not routinely indicated, and abnormal ceiving placebo. Among patients with two or
findings may also occur with other conditions, more white-matter lesions, the rate of multiple
such as optic-nerve compression, infiltration, and sclerosis at two years was 16.2 percent in the
nondemyelinating inflammation. Multifocal vi- group receiving intravenous methylprednisolone,
sual evoked potentials can be a more sensitive 32.4 percent in the group receiving prednisone,
and specific tool for detecting demyelinating op- and 35.9 percent in the placebo group.24 How-
tic neuritis, although the technique is not widely ever, the benefits of methylprednisolone did not
available for routine use.33 persist on assessments beyond two years.
Optical coherence tomography is a noninvasive Oral prednisone alone was associated with a
technique that uses near-infrared light to deter- significantly increased risk of recurrent optic
mine the thickness of retinal tissues. In research neuritis among patients in the first 2 years (30
studies, it has been used to demonstrate thin- percent, vs. 13 percent for patients receiving in-
ning of the nerve-fiber layer of the retina in pa- travenous methylprednisolone and 16 percent for
tients with a history of acute demyelinating optic those receiving placebo); the risk of recurrent
neuritis, as well as in patients with multiple scle- disease continued to appear higher in the oral
rosis who have no known history of optic neuri- prednisone group at 10 years of follow-up, al-
tis.34,35 This technique currently is not used rou- though the differences between groups were no
tinely in practice to assess patients with optic longer significant.24 Similarly, a randomized trial
neuritis. in Japan showed quicker recovery of visual acuity
among patients receiving intravenous methyl-
Short-Term Treatment prednisolone as compared with those receiving a
Intravenous methylprednisolone hastens recovery control drug (methylcobalamin) but no long-term
of visual function but does not affect long-term effect on visual outcome.36
visual outcome.1,5-8,11 In the ONTT, patients were
randomly assigned within 8 days after the onset Long-Term Therapy
of symptoms to receive oral prednisone (1 mg per Interferon beta-1a and interferon beta-1b have
kilogram of body weight per day for 14 days, with been shown to reduce the development of multi-
subsequent tapering over a period of 4 days), intra- ple sclerosis in patients with acute demyelinating
venous methylprednisolone (250 mg every 6 hours optic neuritis and two or more characteristic de-
for 3 days) followed by oral prednisone (1 mg per myelinating lesions on MRI of the brain. Three
kilogram per day for 11 days, with subsequent randomized trials have suggested a role for early
tapering over a period of 4 days), or oral placebo.1 treatment in the setting of a first clinical demye-
Treatment with intravenous methylprednisolone linating event.12-15
resulted in more rapid recovery of visual function The Controlled High-Risk Subjects Avonex
to normal, particularly for visual fields (P<0.001 Multiple Sclerosis Prevention Study (CHAMPS)
for the comparison with both of the other groups) included 383 patients with acute optic neuritis or
and contrast sensitivity (P = 0.02 for the compari- other first demyelinating events who were at high
son with both of the other groups).1 Differences risk for multiple sclerosis according to MRI evi-
were greatest 4 and 15 days after the first episode dence (two or more white-matter lesions).12 All
of optic neuritis and remained significant at the patients received 1 g per day of intravenous meth-
6-month follow-up for contrast sensitivity and ylprednisolone for 3 days; 193 patients were ran-
color vision. At one year of follow-up and beyond, domly assigned within 27 days to receive weekly
visual outcomes did not differ significantly be- intramuscular injections of 30 μg of interferon
tween groups.11,22,23 beta-1a (Avonex) and 190 were randomly assigned
The rate of multiple sclerosis at two years of to weekly injections of placebo. Patients treated
follow-up among patients who received intrave- with interferon beta-1a had a reduced three-year
nous methylprednisolone was 7.5 percent, as com- cumulative probability of multiple sclerosis as
pared with 14.7 percent among patients receiving compared with those receiving placebo (35 per-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

cent vs. 50 percent); they also had a lower rate of associated with an increased risk of recurrence,
new lesions on MRI. Results were similar in the suggesting that this therapy be avoided.1,11 A
subgroup of patients who presented with optic study of patients who received higher doses of oral
neuritis.13 An extension study (Controlled High- methylprednisolone (500 mg per day for 5 days,
Risk Avonex Multiple Sclerosis Prevention Study followed by a 10-day period of tapering) showed
in Ongoing Neurological Surveillance, known as that recovery from visual symptoms, as assessed
CHAMPIONS) showed that patients randomly as- with the use of a visual-analogue scale, was has-
signed initially to interferon beta-1a still had a tened, but the study did not provide sufficient data
lower probability of multiple sclerosis at five years regarding the risk of recurrent optic neuritis.38
of follow-up (21 percent) as compared with pa-
tients who initially had received placebo but had Interferon Therapy
begun to receive active treatment at two to three Interferon therapy has been investigated only in
years of follow-up (35 percent).37 patients with acute demyelinating optic neuritis
In the Early Treatment of Multiple Sclerosis as a first clinical demyelinating event and two or
study, 308 patients with first clinical demyelin- more white-matter lesions on MRI of the brain.12-15
ating events (98 of whom had acute optic neuritis) However, in longitudinal studies, the presence of
were randomly assigned to receive either 22 μg one demyelinating lesion was associated with a
weekly of interferon beta-1a (Rebif) subcutaneous- risk of multiple sclerosis similar to the risk as-
ly or placebo.14 Treatment was initiated within sociated with multiple lesions.10 Evidence is lack-
three months; 39 percent of patients had evidence ing regarding the benefits of long-term treatment
of two or more central nervous system lesions at of patients with one lesion on MRI, but early ther-
presentation. Seventy percent of patients received apy, continued surveillance with MRI at intervals
corticosteroids (variable dose and route of admin- of three to six months, or both seem reasonable
istration) before interferon beta-1a. During a two- in this setting.6
year period, multiple sclerosis was found to be
significantly less likely to develop in patients in Intravenous Immunoglobulin
the interferon beta-1a group than in patients in the A small pilot study suggested that intravenous
placebo group (34 percent vs. 45 percent), and immunoglobulin may have some benefit in pa-
significantly fewer new lesions on T2-weighted tients with resolved optic neuritis and substan-
MRI developed in patients in the interferon beta-1a tial residual visual deficits. However, subsequent
group. randomized trials in which the outcome measure
Preliminary results from the Betaferon/Beta- was either visual acuity or contrast sensitivity
seron in Newly Emerging Multiple Sclerosis for failed to demonstrate a significant benefit.39,40
Initial Treatment (BENEFIT) trial, involving 487
patients with a first clinical demyelinating event Pediatric Optic Neuritis
(80 patients with optic neuritis), suggest that Acute optic neuritis in children differs from the
250 μg of interferon beta-1b (Betaseron) subcu- typical adult form.18-20 Optic-disk swelling and
taneously every other day delays the development bilateral disease are more common in children,
of multiple sclerosis.15 Consistent with other as is severe loss of visual acuity (20/200 or worse
studies, multiple sclerosis was significantly less
in 84 percent of eyes in one series).19 Recovery of
likely to be diagnosed in the interferon group visual acuity is to 20/40 or better in 76 percent of
within two years of follow-up as compared with patients. As in adults, the condition is predictive
the placebo group (28 percent vs. 45 percent). of the subsequent risk of multiple sclerosis, al-
Patients in the interferon group also had signifi-
though estimates of risk vary among studies. In
cantly fewer lesions on brain MRI than did pa- one longitudinal study, multiple sclerosis devel-
tients in the placebo group. oped in 13 percent of children within 10 years
after the first episode of optic neuritis, and in 19
A r e a s of Uncer ta in t y percent within 20 years.18
Effects of corticosteroid treatment and other
High-Dose Oral Corticosteroids therapies on the recovery of visual function and
Treatment of optic neuritis with oral prednisone on the risk of multiple sclerosis in children have
at a dose of 1 mg per kilogram per day has been not been established by randomized trials, but

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 clinical pr actice

Table 2. Treatment Options for Acute Demyelinating Optic Neuritis in Patients at High Risk for Multiple Sclerosis.*

Treatment Standard Dosage Contraindications and Potential Side Effects

Short-term

Intravenous methylpred- 1 g daily for 3 days plus 1 mg/kg of body Contraindications: systemic infection, im-
nisolone weight of oral prednisone daily for 11 munodeficiency, severe hypertension
days followed by 4 days of tapering Potential side effects: sleep disturbances,
(day 1, 20 mg; days 2 and 4, 10 mg) mild mood changes, stomach upset,
weight gain, hyperglycemia, worsening
hypertension

Long-term

Interferon beta-1a (Avonex) 30 μg intramuscularly once weekly Contraindications: pregnancy, hypersensitivi-

Interferon beta-1a (Rebif) 22 μg subcutaneously once weekly ty to interferon beta or human albumin
Interferon beta-1b 250 μg subcutaneously every other day Potential side effects: influenza-like symp-
(Betaseron) toms (e.g., fever, chills, and myalgias,
which may be treated symptomatically),
depression, anemia, hepatic dysfunction,
inflammation at the injection site of sub-
cutaneous preparations
Monitoring: complete blood counts, liver
function tests

* Characteristic demyelinating lesions in patients at risk for multiple sclerosis (indicating high risk in first episodes of
acute optic neuritis) are 3 mm or larger in diameter, are ovoid, are located in periventricular areas of the white matter,
and radiate toward the ventricular spaces.12-15

on the basis of data in adults, treatment with of the development of multiple sclerosis. If there
intravenous methylprednisolone is generally rec- are two or more white-matter lesions that are
ommended if visual loss is unilateral and severe 3 mm or more in diameter, ovoid, and periven-
or is bilateral.20 Interferon therapy is considered tricular in location, which suggest a high risk of
in children with abnormal MRI scans of the multiple sclerosis, treatment to reduce this risk
brain, but data regarding the efficacy of therapy should be strongly considered. I recommend in-
to prevent multiple sclerosis are lacking in this travenous methylprednisolone (1 g per day for
population. 3 days) followed by oral prednisone (1 mg per
kilogram per day for 11 days, with subsequent
Guidel ine s tapering over a period of 4 days). This therapy is
based on data suggesting that it is likely to has-
Practice parameters published by the Quality ten recovery of visual function by two to three
Standards Subcommittee of the American Acad- weeks and may reduce the risk of multiple sclero-
emy of Neurology note that intravenous methyl- sis within two years after the first episode of
prednisolone may hasten recovery of visual func- optic neuritis. Treatment with interferon beta-1a
tion but that no evidence of long-term benefit or interferon beta-1b should be strongly consid-
exists.41 This practice guideline antedated the ered after methylprednisolone treatment (Table 2),
publication of the clinical trials of interferon. with the aim of further reducing or delaying de-
velopment of multiple sclerosis during the long
Sum m a r y a nd R ec om mendat ions term. Oral prednisone alone may increase the
risk for recurrent optic neuritis and should be
The patient described in the vignette has signs avoided.
and symptoms typical of acute monosymptom- Dr. Balcer reports having received research fees from Biogen,
atic demyelinating optic neuritis. Such patients Berlex, Centocor, and Serono. No other potential conflict of in-
terest relevant to this article was reported.
should undergo evaluation with gadolinium- I am indebted to Steven Galetta for helpful comments regard-
enhanced MRI of the brain to determine the risk ing the manuscript.

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 clinical pr actice

References
1. Beck RW, Cleary PA, Anderson MM Jr, 15. Kappos L, Polman C, Freedman MS, Contrast letter acuity as a visual compo-
et al. A randomized, controlled trial of cor- et al. Betaferon in newly emerging multi- nent for the Multiple Sclerosis Functional
ticosteroids in the treatment of acute optic ple sclerosis for initial treatment: clinical Composite. Neurology 2003;61:1367-73.
neuritis. N Engl J Med 1992;326:581-8. results. Presented at the 21st Congress of 30. Frisen L, Hoyt WF. Insidious atrophy
2. Beck RW, Cleary PA, Trobe JD, et al. the European Committee for the Treat- of retinal nerve fibers in multiple sclero-
The effect of corticosteroids for acute op- ment and Research in Multiple Sclerosis sis: funduscopic identification in patients
tic neuritis on the subsequent development (ECTRIMS), Thessaloniki, Greece, Septem- with and without visual complaints. Arch
of multiple sclerosis. N Engl J Med 1993; ber 28–October 1, 2005. (Accessed February Ophthalmol 1974;92:91-7.
329:1764-9. 24, 2006, at www.akm.ch/ECTRIMS2005.) 31. Rolak LA, Beck RW, Paty DW, Tourtel-
3. Optic Neuritis Study Group. The 5-year 16. Ischemic Optic Neuropathy Decom- lotte WW, Whitaker JN, Rudick RA. Cere-
risk of MS after optic neuritis: experience pression Trial Research Group. Optic nerve brospinal fluid in acute optic neuritis:
of the Optic Neuritis Treatment Trial. decompression surgery for nonarteritic an- experience of the Optic Neuritis Treat-
Neurology 1997;49:1404-13. terior ischemic optic neuropathy (NAION) ment Trial. Neurology 1996;46:368-72.
4. Beck RW, Trobe JD, Moke PS, et al. is not effective and may be harmful. JAMA 32. Sisto D, Trojano M, Vetrugno M, Tra-
High- and low-risk profiles for the devel- 1995;273:625-32. bucco T, Iliceto G, Sborgia C. Subclinical
opment of multiple sclerosis within 10 17. Newman NJ, Biousse V. Hereditary visual involvement in multiple sclerosis: a
years after optic neuritis: experience of optic neuropathies. Eye 2004;18:1144-60. study by MRI, VEPs, frequency-doubling
the Optic Neuritis Treatment Trial. Arch 18. Lucchinetti CF, Kiers L, O’Duffy A, et perimetry, standard perimetry, and con-
Ophthalmol 2003;121:944-9. al. Risk factors for developing multiple trast sensitivity. Invest Ophthalmol Vis
5. Arnold AC. Evolving management of sclerosis after childhood optic neuritis. Sci 2005;46:1264-8.
optic neuritis and multiple sclerosis. Am J Neurology 1997;49:1413-8. 33. Fraser CL, Klistorner A, Graham SL,
Ophthalmol 2005;139:1101-8. 19. Brady KM, Brar AS, Lee AG, Coats DK, Garrick R, Billson FA, Grigg JR. Multi-
6. Frohman EM, Frohman TC, Zee DS, Paysse EA, Steinkuller PG. Optic neuritis focal visual evoked potential analysis of
McColl R, Galetta S. The neuro-ophthal- in children: clinical features and visual inflammatory or demyelinating optic neu-
mology of multiple sclerosis. Lancet Neu- outcome. J AAPOS 1999;3:98-103. ritis. Ophthalmology 2006;113:315-23.
rol 2005;4:111-21. 20. Liu GT. Visual loss: optic neuropa- 34. Trip SA, Schlottmann PG, Jones SJ, et
7. Balcer LJ, Galetta SL. Optic neuritis. thies. In: Liu GT, Volpe NJ, Galetta SL, al. Retinal nerve fiber layer axonal loss
In: Rakel RE, Bope ET, eds. Conn’s cur- eds. Neuro-ophthalmology: diagnosis and and visual dysfunction in optic neuritis.
rent therapy. Philadelphia: W.B. Saunders, management. Philadelphia: W.B. Saunders, Ann Neurol 2005;58:383-91.
2004:187-90. 2001:103-87. 35. Fisher JB, Jacobs DA, Markowitz CE,
8. Foroozan R, Buono LM, Savino PJ, 21. Optic Neuritis Study Group. The clini- et al. Relation of visual function to retinal
Sergott RC. Acute demyelinating optic cal profile of acute optic neuritis: experi- nerve fiber layer thickness in multiple scle-
neuritis. Curr Opin Ophthalmol 2002;13: ence of the Optic Neuritis Treatment Trial. rosis. Ophthalmology 2006;113:324-32.
375-80. Arch Ophthalmol 1991;109:1673-8. 36. Wakakura M, Mashimo K, Oono S, et
9. Beck RW, Arrington J, Murtagh FR, 22. Beck RW, Cleary PA, Backlund JC. The al. Multicenter clinical trial for evaluating
Cleary PA, Kaufman DI. Brain magnetic course of visual recovery after optic neu- methylprednisolone pulse treatment of
resonance imaging in acute optic neuri- ritis: experience of the Optic Neuritis idiopathic optic neuritis in Japan. Jpn J
tis: experience of the Optic Neuritis Study Treatment Trial. Ophthalmology 1994;101: Ophthalmol 1999;43:133-8.
Group. Arch Neurol 1993;50:841-6. 1771-8. 37. CHAMPIONS Study Group. IM inter-
10. Brex PA, Miszkiel KA, O’Riordan JI, 23. The Optic Neuritis Study Group. Vi- feron β-1a delays definite multiple sclero-
et al. Assessing the risk of early multiple sual function 5 years after optic neuritis: sis 5 years after a first demyelinating
sclerosis in patients with clinically iso- experience of the Optic Neuritis Treatment event. Neurology 2006;66:678.
lated syndromes: the role of a follow-up Trial. Arch Ophthalmol 1997;115:1545-52. 38. Sellebjerg F, Nielsen HS, Frederiksen
MRI. J Neurol Neurosurg Psychiatry 2001; 24. Cole SR, Beck RW, Moke PS, Gal RL, JL, Olesen J. A randomized, controlled trial
70:390-3. Long DT. The National Eye Institute Vi- of oral high-dose methylprednisolone in
11. Beck RW, Gal RL, Bhatti MT, et al. Vi- sual Function Questionnaire: experience acute optic neuritis. Neurology 1999;52:
sual function more than 10 years after of the ONTT. Invest Ophthalmol Vis Sci 1479-84.
optic neuritis: experience of the Optic 2000;41:1017-21. 39. Noseworthy JH, O’Brien PC, Petterson
Neuritis Treatment Trial. Am J Ophthal- 25. Keltner JL, Johnson CA, Spurr JO, TM, et al. A randomized trial of intrave-
mol 2004;137:77-83. [Errata, Am J Oph- Beck RW. Baseline visual field profile of nous immunoglobulin in inflammatory
thalmol 2004;137:following 793; 2004;138: optic neuritis: the experience of the Optic demyelinating optic neuritis. Neurology
following 321.] Neuritis Treatment Trial. Arch Ophthal- 2001;56:1514-22.
12. Jacobs LD, Beck RW, Simon JH, et al. mol 1993;111:231-4. 40. Roed HG, Langkilde A, Sellebjberg F,
Intramuscular interferon beta-1a therapy 26. Idem. Comparison of central and pe- et al. A double-blind, randomized trial of
initiated during a first demyelinating ripheral visual field properties in the Op- IV immunoglobulin treatment in acute op-
event in multiple sclerosis. N Engl J Med tic Neuritis Treatment Trial. Am J Ophthal- tic neuritis. Neurology 2005;64:804-10.
2000;343:898-904. mol 1999;128:543-53. 41. Kaufman DI, Trobe JD, Eggenberger
13. CHAMPS Study Group. Interferon 27. Fang JP, Donahue SP, Lin RH. Global ER, Whitaker JN. Practice parameter: the
beta-1a for optic neuritis patients at high visual field involvement in acute unilateral role of corticosteroids in the management
risk for multiple sclerosis. Am J Ophthal- optic neuritis. Am J Ophthalmol 1999;128: of acute monosymptomatic optic neuritis:
mol 2001;132:463-71. 554-65. report of the Quality Standards Subcom-
14. Comi G, Filippi M, Barkhof F, et al. 28. Trobe JD, Beck RW, Moke PS, Cleary mittee of the American Academy of Neu-
Effect of early interferon treatment on PA. Contrast sensitivity and other vision rology. Neurology 2000;54:2039-44.
conversion to definite multiple sclerosis: tests in the Optic Neuritis Treatment Trial. Copyright © 2006 Massachusetts Medical Society.
a randomised study. Lancet 2001;357:1576- Am J Ophthalmol 1996;121:547-53.
82. 29. Balcer LJ, Baier ML, Cohen JA, et al.

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