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Demyelinating Optic Neuritis
Original article
contributed by:
All contributors:
Assigned editor:
Review:
Guy V. Jirawuthiworavong, M.D., M.A.
Aaron M. Miller, MD, MBA, FAAP, Dale Fajardo, Ed.D., M.B.A., Guy V.
Jirawuthiworavong, M.D., M.A. and WikiWorks Team
Guy Jirawuthiworavong
Assigned status Update Pending by Guy V. Jirawuthiworavong, M.D.,
M.A. on February 3, 2015.
Demyelinating optic neuritis in an adult is one of the most common reasons why a patient may seek
consultation with a neuro-ophthalmologist. This brief guide will help the general ophthalmologist to
understand:
1. optic neuritis is a clinical diagnosis, thus MRI of the orbit with gadolinium looking for optic nerve
enhancement, blood testing for inflammatory or infectious etiologies, and lumbar puncture are not
needed for the diagnosis,
2. typical (unilateral vision decrease, pain with eye movement) optic neuritis will recover with good
visual prognosis by 6-12 months,
3. the final amount of vision recovery is independent of treatment with or without IV steroids, (IV
STEROIDS DO NOT IMPROVE VISUAL OUTCOME, THE NATURAL HISTORY AND
PROGNOSIS OF TYPICAL OPTIC NEURITIS IS VERY FAVORABLE WITH OR WITHOUT IV
STEROID TREATMENT),
4. oral prednisone alone is CONTRAINDICATED because it has been shown to cause more
recurrences to the affected eye or new episodes in the contralateral eye compared to placebo or
IV steroids followed by oral prednisone,
5. MRI of the brain is a must after an initial episode of optic neuritis because the number of lesions
will stratify patients’ risk for developing clinically definite multiple sclerosis (CDMS) after a clinically
isolated syndrome (CIS), and
6. the ophthalmologist can play a vital role to decrease morbidity from multiple sclerosis (MS) by
understanding the role of early treatment with disease modifying drugs (DMD). This article will
focus on adults, 18 years and older who present with optic neuritis.
Disease Entity



Optic neuritis ICD 377.3
Retrobulbar neuritis (acute) ICD 377.32
Optic neuritis unspecified, ICD 377.30
Disease
Optic nerve inflammation that is accompanied with decreased vision, optic nerve dysfunction (decreased
peripheral vision, decreased color vision, decreased contrast/brightness sense, relative afferent papillary
defect (RAPD)) and tends to be associated with periorbital pain, especially with eye movement.
Prevalence roughly estimated to be 1-5/100,000 depending upon geography and ethnicity.
Etiology
Unknown cause, felt to be an autoimmune process
Risk Factors




3:2-female:male ratio
Young age (20-45 years old)
A prodromal flu like illness commonly accompanies the event but does not always occur
Multiple Sclerosis-up to 75% of patients with CDMS will have at least one episode of optic neuritis
in their lifetime. Autopsies of patients with CDMS show up to 90% optic nerve involvement.
General Pathology
Immune-mediated inflammatory demyelination of the optic nerve. The myelin undergoes destruction
causing axons to poorly conduct impulses. With recurrences, the damage to the retinal ganglion cell
becomes irreparable.
Pathophysiology
After myelin destruction occurs, the retinal ganglion cell axons starts to degenerate. Monocytes localize
along blood vessels, and macrophagaes follow to remove myelin. Astroctyes then proliferate with
deposition of glial tissue where axons may have been present before. These gliotic (sclerotic) areas can
be multiple in number througout the brain and spinal cord, hence the term mutliple sclerosis.
Diagnosis
Optic Neuritis is a clinical diagnosis that is made when a patient presents with

unilateral decreased visual acuity

pain with eye movement and/or periorbital discomfort

RAPD

visual field defect

optic nerve swelling (35% anterior disc edema, 65% retrobulbar)
Patients recruited in the Optic Neuritis Treatment Trial (ONTT) were selected based on decreased
unilateral vision loss for 8 days or less, but the presence of a RAPD or a visual field defect were not
required.
An enhancing optic nerve seen on MRI post-gadolinium is helpful but not required to make the diagnosis.
Less commonly, patients may present with absence of eye pain, absence of orbital discomfort, bilateral
vision loss, no light perception vision, severe disc swelling with hemorrhages of the optic disc or retinal
exudates. These are considered more atypical signs and symptoms of optic neuritis. 3% of patients in the
ONTT presented with no light perception vision.
History
A prodromal viral illness may occur. Patients often experience orbital pain and pain with eye movement
prior to visual changes. The pain can be excruciating or very mild like a foreign body sensation. The visual
change is often acute and typically worsens over a few days and nadirs around 2 weeks prior to
improvement.
Physical examination

Snellen visual acuity with best correction for distance and/or near vision

Color vision and/or Contrast measurement (Pelli-Robson or VisTech)

Swinging flashlight test for RAPD

Evaluation of extraocular movement

Confrontation visual fields


Amsler grid with best correction central visual field defects (be aware that this test may also be
abnormal in macular disease)
Biomicroscopy/direct ophthalmoscopy of the optic nerve and retina
SignsDecreased visual acuity

Decreased color vision (red desaturation) and/or decreased contrast/brightness sense

RAPD unless both eyes are affected or RAPD was present prior in contralateral eye

Ocular dysmetria of internuclear ophthalmoplegia

Any scotoma on Amsler grid and/or confrontation visual fields or formal visual field testing

Disc edema (only 35% noted in ONTT, thus lack of disc edema does not rule out acute optic
neuritis)

Retinal vascular sheathing, pars planitis (periphlebitis occurs in 5-10% of multiple sclerosis
patients)
Symptoms
acute vision loss that tends to worsen over days

eye discomfort or pain particularly with eye movement (mild to severe)

phosphenes (flashes of lights)

vision becomes blurry when body temperature rises during exercise or bathing in warm to hot
water (Uhthoff's phenomenon)

"washed out" color vision

dimmed vision (contrast on t.v. is turned down)

dark vision

loss of central vision or part of the peripheral/side vision

altered perception of motion (Pulfrich phenomenon)
Clinical diagnosis
Optic neuritis is diagnosed clinically by symptoms of acute unilateral decrease in vision, eye painespecially with movement and signs of a RAPD, decreased color vision/contrast/brightness sense and
documentation of a visual field defect. A MRI depicting enhancement of the optic nerve after administration
of gadolinium is helpful but not required to make the clinical diagnosis and neither is disc swelling required
to be present. Relative recovery of vision at 6 months from onset tends to be the natural progression of the
disease. However, 12% of patients may not recover 20/40 or better vision, and the ones that do recover,
have residual vision changes such as decreased contrast.
Diagnostic procedures
MRI is a must to help risk stratify patients for the development of MS after the acute initial onset of optic
neuritis. Multiple sclerosis plaques are seen as white matter lesions on MRI scans. MRI of the brain with
FLAIR sequences of axial, coronal and sagittal planes can help identify lesions >3mm in size, or large
(>6mm) ovoid lesions abutting the lateral ventricles. "Dawson's Fingers" (periventricular white matter
lesions on mid-sagittal FLAIR sequences that involve the corpus collosum) are highly suggestive of MS.
Not all high-signal abnormalities in white matter are diagnostic of MS, thus one must use caution when
considering these findings in the assessment for MS. The lesions can be present in healthy patients over
age 50 who have hypertension, atherosclerosis, as well as other diseases such as vasculitis.
Optical coherence tomography (OCT) of the nerve fiber layer (NFL) is helpful as an adjunctive
measurement of nerve function in patients with optic neuritis. OCT is a diagnostic technique introduced
into clinical practice in 1997 and widely utilized by retina specialists. It's use in glaucoma and neuroophthalmology is currently evolving and still at its formative stages. OCT uses the principal of reflection of
low coherence radiation from tissue to measure layers of the retina and nerve fiber layer at a resolution of
<10 microns with spectral-domain OCT. OCT can quantify the onset of optic atrophy and pallor that
ensues 6-8 weeks post onset of optic neuritis. Optic atrophy can be subtle on biomicroscopy, thus OCT is
useful for detection and quantification of the optic atrophy. OCT of the NFL also serves in patient
education and documentation.
A lumbar puncture is not required for the diagnosis of optic neuritis. However, presence of CSF levels of
oligoclonal bands and elevated IgG synthesis are data that is considered in the McDonald diagnostic
criteria for MS. A spinal tap can also help to rule out elevated intracranial pressure in cases of atypical
bilateral optic neuritis with bilateral anterior disc edema. The CSF can also be examined for infectious and
inflammatory conditions as well in atypical cases of optic neuritis.
Laboratory test
Typical optic neuritis (unilateral, pain with eye movment, no uveitis) does not require any blood testing.
Bilateral optic neuritis with poor visual recovery is atypical and a blood test for neuromyelitis optica
(Devic's disease) should be entertained. The test is the neuromyelitis optica (NMO) antibody which is
available commercially.
If vision loss has occurred in a young male with a significant family history of maternally-related males with
bilateral vision loss, genetic consulting and testing should be entertained for Leber's hereditary optic
neuropathy. Leber’s hereditary optic neuropathy patients are much less likely to recover vision and the
contralateral eye is often affected within weeks to months of the first eye.
Differential diagnosis
Differential Diagnosis for Retrobulbar Optic Neuritis (normal appearance of optic
nerve and vision loss)[edit source]

Of note, the conditions noted below tend to be painless in nature, whereas 92% of patients with
demyelinating optic neuritis present with some form of eye pain and/or eye pain with movement.
With a relative Afferent Pupillary Defect

Compressive lesion

Central serous chorioretinopathy (OCT of the macula can help to rule out macular etiology)

Central retinal artery occlusion

Posterior ischemic optic neuropathy

Infiltrative lesion

Toxic/metabolic (early without optic atrophy, tends to be more symmetric)
No relative Afferent Pupillary Defect

Visual field defects from brain infarct, tumor, lesion

Retinal degeneration such as retinitis pigmentosa

Macular disease (OCT of the macula helpful)
o
Age-related macular degeneration
o
Macular edema (post-cataract surgery, diabetic)
o
Central serous chorioretinopathy
o
Macular hole (traumatic, idiopathic)
o
Epiretinal membrane/surface wrinkling maculopathy
o
Documented apriori contralateral eye RAPD
Differential Diagnosis of Optic Neuritis (unilateral optic nerve edema, vision loss)

Anterior ischemic optic neuropathy (tends to be painless in nature)

Pending central retinal vein occlusion (painless)

Optic papillitis in patient with uveitis (Vogt-Koyanagi-Harada (VKH) syndrome, sarcoidosis)

Diabetic papillopathy (painless)

Compressive lesion along the anterior pathway of the optic nerve (up to and including optic
chiasm)

Disc drusen (pseudodisc edema, visual field defects common due to crowding of the disc,
painless)

Infectious optic neuritis (syphilis, lyme, herpes viradae (HSV, VZV); Bartonella-often with macular
star in neuroretinitis)

Vasculitis (SLE, granulomatous)

Malignant hypertension (tends to be bilateral)

Infiltrative-CNS leukemia, CNS lymphoma, metastatic lesion

Posterior scleritis (pain with eye movement, decreased vision, B-scan with thickened choroid and
fluid-"T-sign")

Mutiple evanescent white dot syndrome (MEWDS)-(painless, "wreath sign" on fluorescein
angiography)

Leber's hereditary optic neuropathy (painless, telangiectatic disc vessels)

Vascular lesion-(juxtapapillary hemangioblastoma, combined hamartoma of the retina and RPE)

Radiation induced optic neuropathy
Management
Optic Neuritis Treatment Trial (ONTT) Multi-centered, randomized, prospective, controlled clinical trial that
was designed to evaluate the efficacy and safety of oral prednisone vs. intravenous methylprednisolone
followed by oral prednisone as compared with oral placebo for the treatment of acute optic neuritis.
Patients were recruited from July, 1988 to June, 1991. 457 patients (85% Caucasian, range of 18-60 years
old) at 15 different medical centers with presentation of symptoms of decreased vision at 8 days or less
without any prior episodes of optic neuritis, not currently on any prednisone, and without any significant
systemic diseases were randomized to either: 1) oral placebo, 2) 250mg IV solumedrol q6hrs for 3 days
then 1mg/kg of prednisone for 11 days, or 3) 1mg/kg of PO prednisone alone for 14 days. Primary
outcome measures were contrast sensitivity and visual field and secondary measures were vision and
color. The patients were followed for a minimum of 6 months.
ONTT Outcomes
1. IV steroid treated patients recovered faster within the first 4-6 weeks post onset. However at 6
months to 10 years out, there was no statistical difference in final visual outcome between IVsteroid treated patients and placebo.
2. ORAL STEROIDS ALONE ARE CONTRAINDICATED FOR ACUTE OPTIC NEURITIS
BECAUSE OF HIGHER RATE OF RECURRENCES OF OPTIC NEURITIS.
Practically speaking, physicians may vary in the implementation of the ONTT. Some physicians give 1gm
IV bolus daily for 3 to 5 days as outpatient infusion. Furthermore, some physicians may or may not give
the 11 day oral prednisone taper that follows.
There still may exist among physicians the misconception that IV steroids improve visual outcome by 6
months out. This is not the case. It is given to hasten recovery the first 4-6 weeks after onset. Ultimate
visual outcome is the same with or without the administration of IV steroids in typical optic neuritis.
Medical therapy
-Side effects of IV steroids should be fully discussed, especially in diabetics.
-Oral steroids are contraindicated in patients who have acute optic neuritis especially in patients that carry
a diagnosis of MS
Medical follow up
Visual acuity, (color vision and/or contrast can elucidate subtle changes not seen on Snellen acuity
testing)
Visual field testing upon onset if possible (Humphrey visual field or Goldmann visual field) and repeat at
follow up visual fields at 3, 6 and 12 months.
OCT of the NFL at onset, at 6-8 week visit, and at 6 month follow up for quantitation of optic atrophy.
Complications
Visual prognosis is excellent with normal to near normal recovery. Patients may still complain of
decreased brightness sense, contrast deficit, and loss of steropsis. It is important to forewarn them at the
beginning that eventhough visual recovery is the norm, they still have the possibility of:

permanent visual loss either mild (20/30) to severe (20/200 or worse)

permanent scotomas that may limit driving

recurrences
IV steroids at high dosages for the treatment of optic neuritis according to the ONTT can cause insomnia,
mood changes, dyspepsia, weight gain, flushing, nausea, vomiting, and elevated blood pressure. Patients
should be advised to take a proton pump inhibitor such as omeprazole and may need to seek medical
attention for anxiety and insomnia. Diabetics may be at risk for episodes of hyperglycemia and also for
diabetic ketoacidosis. Co-management with the patient's primary physician, internist or endocrinologist is a
must.
Prognosi
94% recover 20/40 or better at 5 years out in the ONTT. 20/200 or worse visual outcome occurred in 3%
of patients at 5 years out in the ONTT.
Visual recovery tends to occur by 1 month after onset and the majority recover by 1-3 months time. At 6
months, patients tend to have similar visual outcomes no matter if they were treated with IV steroids or
placebo. Vision improvement can take up to one year. Prolonged pain with eye movement, lack of
recovery, recurrence within 2 months would alert the physician to re-evaluate for atypical causes of optic
neuritis such as sarcoidosis, syphilis or an idiopathic autoimmune optic neuritis that is steroid-responsive.
28% of patients developed recurrent optic neuritis which was associated with oral prednisone. As a result,
oral steroids is contraindicated in the management of acute optic neuritis.
Since optic neuritis is common among patients who have MS, (up to 75% have at least one episode of
optic neuritis in their life time), these patients are at risk for developing CDMS. The ONTT showed that
even without any lesions present on MRI, there still was a 16% chance of developing MS in 5 years and
22% in 10 years. Patients are counseled about the importance of getting a brain MRI as well as watchful
waiting of other peripheral or central neurological deficits in the future.
At 10 years, the overall risk of MS was 38% after an initial episode of optic neuritis. That risk is 56% if the
MRI had 1 or more lesions. The risk is lower if the patient is male, disc swelling is present, pain is absent,
vision is no light perception, severe optic disc swelling with hemorrhages are seen, or macular exudates
such as a retinal star pattern occur. In patients with CDMS, the median time to diagnosis was 3 years and
34% of the diagnoses were made in the first 2 years whereas 72% were made within 5 years.
In MS, clinically isolated syndromes (CIS) such as optic neuritis have been a focus for clinical trials. Is
there a role for disease modifying drugs (DMD) in the postponement of developing CDMS when patients
present initially with CIS optic neuritis and are at high risk for CDMS due to the presence of 2 or more
lesions on MRI? Three randomized prospective clinical trials have examined this question.



Controlled High-Risk Avonex Multiple Sclerosis Prevention Study (CHAMPS)
Early Treatment of Multple Sclerosis Study (ETOMS)
Betaseron in Newly Emerging Multple Sclerosis for Initial Treatment Trial (BENEFIT).
The DMD in these studies were as follows:



IM weekly interferon beta-1a (Avonex) in CHAMPS
SC weekly interferon beta-1a (Rebif) in ETOMS
SC every other day interferon beta-1b (Betaseron) in BENEFIT.
Patients were recruited and randomized to DMD or placebo. In CHAMPS, ETOMS, and BENEFIT, DMDs
were shown to reduce the probability of CIS converting to CDMS compared to placebo. MRI scans
showed less new lesions in DMD treated groups as compared to patients receiving placebo in CHAMPS
and ETOMS.
Thus, patients with signs and symptoms of acute optic neuritis (CIS) require prompt MRI brain imaging for
lesions (>3mm) to determine if they are at high risk for the development of CDMS. Early treatment with
interferon-beta can effectively reduce the risk of developing CDMS by up to 50% in patients with CIS.
Thus, the ophthalmologist plays a pivotal role on the front lines when a patient presents to their office with
acute optic neuritis.
Additional Resources
www.nanos-web.org
References
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