Ophthalmology – Optic Neuritis

Basics

Description

Optic neuritis (ON) is an inflammatory optic neuropathy characterized by acute or subacute visual dysfunction caused by inflammation and demyelination of the optic nerve.

The classic form is:

Typical demyelinating optic neuritis associated with multiple sclerosis (MS)

However, optic neuritis can also occur with:

• MOG antibody-associated disease (MOGAD)
• Aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD)
• Sarcoidosis
• Systemic autoimmune disease
• Infection
• Postinfectious inflammatory disease

Recognition of these distinct entities is important because their:

• Clinical phenotype
• Prognosis
• Risk of recurrence
• Long-term treatment

differ substantially.

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Typical Demyelinating Optic Neuritis

The classic presentation is:

• Young adult
• Usually female
• Unilateral painful visual loss
• Pain worsened by eye movement
• Dyschromatopsia
• RAPD
• Central or diffuse visual field defect
• Normal-appearing disc in many cases

Visual loss usually evolves over:

Hours to several days

and reaches its nadir within approximately:

1–2 weeks

Spontaneous improvement generally begins within:

2–3 weeks

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Papillitis vs Retrobulbar Optic Neuritis

Papillitis

Inflammation produces:

• Visible optic disc swelling

Retrobulbar Optic Neuritis

The optic disc initially appears:

• Normal

because inflammation is located posterior to the globe.

The classic phrase is:

“The patient sees nothing, and the doctor sees nothing.”

This refers to substantial visual dysfunction despite a normal fundus appearance.

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Epidemiology

Typical demyelinating optic neuritis most commonly affects:

• Young adults
• Approximately 20–50 years of age
• Women more often than men

It is one of the most common causes of:

Acute painful monocular visual loss in a young adult

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Association With Multiple Sclerosis

Optic neuritis may be:

• The first manifestation of MS
• A relapse in established MS
• An isolated clinically isolated syndrome

A substantial proportion of patients with typical ON ultimately develop MS, particularly when baseline brain MRI demonstrates characteristic demyelinating lesions.

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Risk of MS

The strongest predictor of subsequent MS after a typical optic neuritis attack is:

Baseline brain MRI

Risk is substantially higher when characteristic white-matter demyelinating lesions are present.

A normal MRI lowers, but does not eliminate, long-term MS risk.

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Pathophysiology

Typical optic neuritis involves:

Immune-mediated demyelination and axonal injury of the optic nerve

Mechanisms include:

• T-cell-mediated inflammation
• B-cell participation
• Blood–brain barrier disruption
• Myelin injury
• Secondary axonal degeneration

Recovery reflects:

• Resolution of inflammation
• Remyelination
• Neural adaptation

Some permanent retinal ganglion cell and axonal loss commonly remains even when visual acuity returns to normal.

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Etiologic Categories

Important causes include:

Demyelinating

• Multiple sclerosis
• MOGAD
• AQP4-NMOSD

Autoimmune / Inflammatory

• Sarcoidosis
• Systemic lupus erythematosus
• Sjögren syndrome
• Behçet disease
• Granulomatosis with polyangiitis
• IgG4-related disease

Infectious

• Syphilis
• Tuberculosis
• Lyme disease
• Viral infection
• Bartonella
• Other infections depending on exposure and geography

Other

• Postinfectious inflammation
• Postvaccination inflammatory disease
• Optic perineuritis

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History

Typical symptoms include:

• Blurred vision
• Loss of visual acuity
• Reduced color saturation
• Central blur or scotoma
• Pain with eye movement
• Reduced contrast sensitivity

Ask about:

• Previous neurologic symptoms
• Prior episodes of visual loss
• Weakness or sensory disturbance
• Ataxia
• Bladder dysfunction
• Lhermitte phenomenon
• Autoimmune disease
• Infection risk
• Medication or toxin exposure

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Pain With Eye Movement

Pain occurs in the majority of typical MS-associated cases.

It is usually:

• Periocular
• Mild to moderate
• Worse with eye movement

Absence of pain does not exclude ON, but a painless severe optic neuropathy should broaden the differential.

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Visual Acuity

Visual acuity may range from:

• Mildly reduced
• Moderately reduced
• Counting fingers
• Rarely profound loss in typical MS-associated ON

Very severe visual loss, particularly:

• NLP
• Bilateral profound loss

should increase suspicion for:

• AQP4-NMOSD
• MOGAD
• Ischemic optic neuropathy
• Infectious/infiltrative disease

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Color Vision

Dyschromatopsia is a hallmark.

Typical finding:

Color vision loss out of proportion to visual acuity

Patients may describe colors as:

• Washed out
• Less bright
• Less saturated

Red desaturation is common.

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Contrast Sensitivity

Contrast sensitivity is frequently impaired even when Snellen acuity is relatively preserved.

Residual contrast deficits may persist after apparent visual recovery.

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Relative Afferent Pupillary Defect

A RAPD is expected in unilateral or asymmetric optic neuritis.

Absence of RAPD in marked unilateral visual loss should raise concern for:

• Functional visual loss
• Media opacity
• Macular disease
• Symmetric bilateral optic neuropathy

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Visual Field Defects

Typical defects include:

• Central scotoma
• Cecocentral scotoma
• Diffuse depression
• Altitudinal defects
• Arcuate defects

No single visual field pattern is diagnostic.

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Optic Disc Appearance

In typical demyelinating ON:

• Most patients initially have a normal optic disc
• A minority have disc edema

Disc swelling is more common in:

• Children
• MOGAD

Marked disc edema with hemorrhages or macular exudates should prompt consideration of alternative diagnoses.

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Optic Atrophy

Following an attack, the optic nerve may develop:

• Temporal pallor
• Diffuse pallor
• RNFL thinning

usually becoming apparent over subsequent weeks.

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Uhthoff Phenomenon

Uhthoff phenomenon is transient worsening of previously impaired neurologic or visual function with increased body temperature.

Triggers include:

• Exercise
• Fever
• Hot shower
• Hot weather

It reflects impaired conduction in demyelinated axons and does not necessarily indicate recurrent inflammation.

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Pulfrich Phenomenon

Unequal visual conduction between the two eyes can cause moving objects to be perceived along an abnormal three-dimensional trajectory.

A swinging pendulum may appear to move:

Elliptically rather than in a flat plane

This is the Pulfrich phenomenon.

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Typical vs Atypical Optic Neuritis

Recognition of atypical features is critical.

Typical MS-associated ON usually demonstrates:

• Age approximately 20–50 years
• Unilateral disease
• Pain with eye movement
• Moderate visual loss
• Normal or mildly swollen disc
• Improvement beginning within several weeks

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Red Flags for Atypical Optic Neuritis

Features that should prompt broader evaluation include:

• Age <10 or >50 years
• Bilateral simultaneous disease
• Recurrent attacks
• Profound visual loss
• Lack of pain
• Marked optic disc swelling
• Disc hemorrhages
• Macular star
• Severe vitritis
• Retinal inflammation
• Progressive deterioration beyond 2 weeks
• No meaningful recovery
• Steroid dependence
• Chiasmal involvement
• Longitudinally extensive optic nerve enhancement

These findings raise concern for:

• MOGAD
• AQP4-NMOSD
• Sarcoidosis
• Infection
• Infiltrative disease
• Optic perineuritis

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MOG Antibody-Associated Optic Neuritis

MOGAD optic neuritis commonly demonstrates:

• Bilateral disease
• Recurrent attacks
• Severe optic disc edema
• Peripapillary hemorrhage
• Long-segment optic nerve enhancement
• Anterior optic nerve involvement
• Perineural enhancement

Visual loss may initially be severe, but recovery is often relatively good.

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AQP4-NMOSD Optic Neuritis

AQP4-associated ON commonly demonstrates:

• Severe visual loss
• Bilateral or sequential attacks
• Poorer visual recovery
• Posterior optic nerve involvement
• Chiasmal involvement
• Longitudinally extensive enhancement

It has a high risk of:

Permanent visual disability after recurrent attacks

Therefore early recognition is important.

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Pediatric Optic Neuritis

Children differ from typical adult MS-associated ON.

Features include:

• Bilateral involvement more common
• Optic disc edema more common
• Severe initial visual loss
• Often excellent acuity recovery

MOG-IgG-associated disease is particularly important in pediatric ON.

Children with ON require assessment for:

• MOGAD
• MS
• AQP4-NMOSD
• Postinfectious inflammation

depending on phenotype.

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Diagnosis

Typical optic neuritis remains primarily a:

Clinical diagnosis supported by MRI

However, modern evaluation increasingly aims to identify the underlying disease category.

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MRI

The preferred imaging study is:

MRI brain and orbits with and without contrast

using dedicated orbital sequences including:

• Fat-suppressed T1 post-gadolinium
• T2/STIR
• Thin orbital sections

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Orbital MRI Findings

Acute ON typically produces:

• Optic nerve enlargement
• T2 hyperintensity
• Gadolinium enhancement

MRI may also define:

• Anterior vs posterior involvement
• Length of involved nerve
• Chiasmal involvement
• Perineural enhancement

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MRI and Multiple Sclerosis

Brain MRI should assess for characteristic demyelinating lesions involving:

• Periventricular regions
• Juxtacortical/cortical regions
• Infratentorial structures
• Corpus callosum

MRI findings contribute to assessment under modern:

McDonald criteria for multiple sclerosis

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Spinal MRI

Spinal MRI is not required in every typical isolated case.

It becomes more useful when there are:

• Myelopathic symptoms
• Suspicion for NMOSD
• Suspicion for MOGAD
• Diagnostic uncertainty regarding MS

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OCT

OCT is useful for measuring:

• Peripapillary RNFL
• Macular ganglion cell–inner plexiform layer

After ON, OCT may demonstrate:

• RNFL thinning
• Ganglion cell loss

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Important OCT Timing Issue

During acute papillitis, RNFL may appear artificially thick because of edema.

The ganglion cell layer may therefore provide a more useful marker of early permanent neuronal injury.

Later, RNFL thinning becomes apparent.

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Visual Evoked Potentials

VEP may show:

Prolonged P100 latency

reflecting slowed conduction from demyelination.

VEP can support evidence of:

• Prior optic nerve demyelination
• Subclinical optic neuropathy

but is not required in every typical case.

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Laboratory Testing

Routine broad laboratory screening has low yield in a classic typical case.

Testing should be targeted toward:

• Atypical features
• Recurrent ON
• Bilateral disease
• Severe loss
• Poor recovery
• Systemic symptoms

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AQP4-IgG Testing

Serum AQP4-IgG, preferably using a cell-based assay, should be considered particularly in:

• Severe optic neuritis
• Bilateral disease
• Chiasmal involvement
• Recurrent disease
• Poor recovery
• Associated myelitis

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MOG-IgG Testing

Serum MOG-IgG, using a cell-based assay, should be considered in:

• Bilateral ON
• Recurrent ON
• Children
• Marked disc swelling
• Long-segment anterior optic nerve enhancement
• Steroid-responsive or steroid-dependent disease

Testing should be interpreted in the correct clinical context because low-positive results may be nonspecific.

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Infectious Testing

Depending on phenotype and risk factors, consider:

• Syphilis serology
• TB testing
• Lyme serology where epidemiologically appropriate
• Bartonella testing
• Other infection-specific studies

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Autoimmune Testing

Targeted testing may include:

• ACE / sarcoidosis evaluation
• ANA
• ANCA
• Sjögren antibodies

only when suggested by clinical findings.

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Lumbar Puncture

Lumbar puncture is not routinely required in a classic adult case with supportive MRI.

It may be useful when:

• MRI is equivocal
• MS diagnosis remains uncertain
• CNS infection is considered
• Inflammatory or infiltrative disease is suspected

CSF studies may include:

• Oligoclonal bands
• IgG index
• Cell count
• Protein
• Infectious testing

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Differential Diagnosis

Important mimics include:

• NAION
• Arteritic anterior ischemic optic neuropathy
• Compressive optic neuropathy
• Leber hereditary optic neuropathy
• Dominant optic atrophy
• Toxic/nutritional optic neuropathy
• Sarcoid optic neuropathy
• Syphilis
• Tuberculosis
• Neuroretinitis
• Optic perineuritis
• Retinal disease
• Functional visual disorder

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Optic Neuritis vs NAION

Typical Optic Neuritis

• Younger patient
• Pain with eye movement
• Central visual dysfunction
• Dyschromatopsia prominent
• Disc often normal
• Recovery usually good

NAION

• Usually older patient
• Painless
• Disc edema always present acutely
• Altitudinal defect common
• “Disc at risk”
• Recovery more limited

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Neuroretinitis

Neuroretinitis is characterized by:

• Optic disc edema
• Macular star

and is commonly associated with:

Bartonella henselae

A macular star is atypical for ordinary MS-associated ON.

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Compressive Optic Neuropathy

Consider compression when there is:

• Slowly progressive visual loss
• Little or no pain
• Proptosis
• Optic pallor
• Poor spontaneous recovery
• Atypical MRI findings

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Treatment Principles

Treatment depends on whether the patient has:

• Typical MS-associated optic neuritis
• MOGAD
• AQP4-NMOSD
• Another inflammatory/infectious optic neuropathy

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Typical Demyelinating Optic Neuritis

Most typical cases recover substantially even without treatment.

High-dose corticosteroids:

Accelerate visual recovery but do not materially improve long-term final visual acuity in typical MS-associated ON.

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High-Dose Corticosteroids

A traditional regimen is:

IV methylprednisolone 1 g/day for 3 days

Often used for:

• Significant visual impairment
• Bilateral disease
• Occupational or functional need for faster recovery
• Severe inflammation

Some clinicians use 3–5 days depending on disease context.

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High-Dose Oral Corticosteroids

Modern evidence indicates that bioequivalent high-dose oral corticosteroids can provide similar efficacy to high-dose IV therapy in selected typical ON patients.

Therefore, the important distinction is:

High-dose therapy vs inadequate low-dose oral prednisone, rather than IV route alone.

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Low-Dose Oral Prednisone

The older ONTT showed that:

Oral prednisone approximately 1 mg/kg/day alone should not be used for typical optic neuritis

because it was associated with an increased risk of recurrent ON.

This warning does not apply to appropriately dosed high-dose oral regimens.

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Oral Taper

A taper is generally:

• Not required after a short course for typical MS-associated ON

However, tapering may be important in:

• MOGAD
• Optic perineuritis
• Steroid-dependent inflammatory disease

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AQP4-NMOSD Treatment

AQP4-associated ON should be treated more aggressively because recovery may be poor.

Acute therapy generally includes:

• High-dose IV corticosteroids

If response is inadequate:

Early plasma exchange (PLEX)

should be considered.

Delay in escalation may reduce visual recovery.

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MOGAD Treatment

Acute MOG optic neuritis usually responds well to:

• High-dose corticosteroids

However:

• Relapse may occur during rapid steroid taper
• Longer tapering courses are sometimes used in selected patients

Recurrent disease may require long-term immunotherapy.

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Plasma Exchange

PLEX is particularly important for:

• Severe AQP4-NMOSD ON
• Severe steroid-refractory optic neuritis
• Selected MOGAD attacks with poor steroid response

It is not routinely required for uncomplicated typical MS-associated ON.

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Long-Term MS Therapy

A patient with optic neuritis and evidence suggesting MS should be evaluated by neurology for:

Disease-modifying therapy (DMT)

Modern MS treatment includes many options beyond older interferon and glatiramer therapies.

Selection depends on:

• MRI burden
• Relapse risk
• Diagnostic criteria
• Comorbidities
• Pregnancy plans
• Patient preference

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Clinically Isolated Syndrome

Patients with ON who do not yet fulfill MS criteria but have high-risk MRI findings may still be candidates for early neurologic treatment.

Neurology consultation is appropriate.

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Pregnancy

Management is individualized.

Important considerations include:

• MRI without gadolinium can generally be performed when necessary
• Gadolinium is usually avoided unless essential
• High-dose corticosteroids may be used for significant attacks when benefits outweigh risks

Neurology, ophthalmology, and obstetric teams should coordinate management.

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Follow-Up

Patients should be reassessed to ensure that the clinical course remains typical.

Monitor:

• Visual acuity
• Color vision
• RAPD
• Visual fields
• Optic nerve appearance
• OCT
• Neurologic symptoms

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Expected Course

In typical MS-associated ON:

• Vision worsens over days
• Nadir generally occurs within 1–2 weeks
• Recovery begins within approximately 2–3 weeks
• Improvement continues for months

Failure to improve should prompt reconsideration of the diagnosis.

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When to Re-Evaluate the Diagnosis

Urgently reconsider typical ON when:

• Vision continues worsening beyond 2 weeks
• No recovery begins within several weeks
• Repeated steroid dependence occurs
• Severe bilateral disease develops
• MRI pattern is atypical

Consider:

• AQP4-NMOSD
• MOGAD
• Compression
• Sarcoidosis
• Infection
• Ischemic optic neuropathy

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Prognosis

Typical demyelinating ON generally has an excellent visual acuity prognosis.

Most patients recover to:

20/40 or better

and many recover to:

20/20

However, even when acuity returns to normal, patients may have persistent deficits in:

• Color vision
• Contrast sensitivity
• Motion perception
• Low-contrast acuity

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Prognostic Factors

Poorer visual outcome is associated with:

• Profound initial visual loss
• AQP4-NMOSD
• Recurrent attacks
• Significant axonal loss
• Delayed treatment of severe atypical disease

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Recurrence

Recurrent optic neuritis may occur with:

• MS
• MOGAD
• AQP4-NMOSD
• Chronic relapsing inflammatory optic neuropathy

Repeated attacks increase the risk of:

• Optic atrophy
• Permanent RNFL loss
• Persistent visual disability

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Complications

Possible complications include:

• Optic atrophy
• RNFL thinning
• Ganglion cell loss
• Persistent dyschromatopsia
• Reduced contrast sensitivity
• Persistent visual field defect
• Recurrent optic neuritis
• Permanent visual loss

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Ophthalmology Pearls

• Typical optic neuritis = painful, subacute monocular visual loss in a young adult, usually with dyschromatopsia and RAPD.
• Pain with eye movement is highly characteristic but not mandatory.
• The optic disc is often normal initially because many cases are retrobulbar.
• Color vision and contrast sensitivity may be disproportionately impaired compared with Snellen acuity.
• Visual deterioration usually reaches its nadir within 1–2 weeks, followed by spontaneous improvement within several weeks.
• MRI of the brain and orbits with dedicated fat-suppressed sequences is the key imaging study.
• Baseline brain MRI is the most important predictor of future MS risk after typical ON.
• MOGAD should be considered with bilateral disease, marked disc edema, recurrent attacks, or anterior long-segment enhancement.
• AQP4-NMOSD should be considered with severe visual loss, poor recovery, chiasmal/posterior involvement, bilateral disease, or associated myelitis.
• Serum AQP4-IgG and MOG-IgG cell-based assays are central tests in atypical optic neuritis.
• High-dose corticosteroids speed recovery in typical ON but do not substantially improve long-term final visual acuity.
• Avoid low-dose oral prednisone alone (~1 mg/kg/day) for typical ON because of increased recurrence risk; bioequivalent high-dose oral therapy is a different regimen and may be effective.
• Severe steroid-refractory or AQP4-associated ON may require early plasma exchange.
• A normal-looking optic nerve does not exclude optic neuritis.
• Lack of recovery, profound bilateral loss, marked disc hemorrhage, macular star, or prolonged progression should prompt reconsideration of the diagnosis.