What are the treatment options for multiple sclerosis with acute painful optic neuritis, including the role of Plasma Exchange (PLEX)?

Treatment of Acute Painful Optic Neuritis in Multiple Sclerosis

First-Line Treatment: High-Dose Intravenous Methylprednisolone

Initiate intravenous methylprednisolone 1000 mg/day for 3 days immediately, followed by oral prednisone 1 mg/kg/day for 11 days with a 4-day taper (20 mg day 1,10 mg days 2-4). 1, 2, 3

This regimen is the gold standard based on the landmark Optic Neuritis Treatment Trial and is recommended by the American Academy of Neurology. 1, 3, 4 The treatment hastens visual recovery but does not alter the final degree of visual recovery from the attack. 4, 5

Critical timing consideration: Treatment must be initiated promptly—delays beyond 2 weeks are associated with significantly poorer visual outcomes. 1, 2, 6 Begin treatment immediately while diagnostic workup proceeds in parallel. 6

Why This Specific Regimen?

• The intravenous route followed by oral prednisone reduces the rate of progression to clinically definite multiple sclerosis at 2 years (7.5% vs 16.7% with placebo), though this benefit diminishes after 2 years. 3, 5
• Critical pitfall to avoid: Never use oral prednisone alone without prior IV methylprednisolone, as this may actually increase the risk of recurrent optic neuritis. 7
• Higher doses up to 30 mg/kg (not exceeding 1000 mg/day) may be considered in severe cases. 1, 2

Role of Plasma Exchange (PLEX)

PLEX should be considered as second-line therapy for severe cases not responding to intravenous steroids within 5-7 days or in patients with progressive vision loss despite steroid treatment. 8, 1, 2, 6

When to Use PLEX:

• Severe visual loss with no improvement after 3-5 days of IV methylprednisolone 1, 6
• Progressive worsening despite steroid therapy 6
• Neuromyelitis optica spectrum disorder (NMOSD)-associated optic neuritis not responding to steroids 2, 6
• Evidence supports PLEX particularly in refractory inflammatory optic neuropathies 8, 1

The evidence for PLEX in optic neuritis is moderate quality, but it represents an important salvage therapy when first-line treatment fails. 8, 1

Additional Second-Line Immunosuppressive Options

For refractory or relapsing cases, consider:

• Rituximab (RTX): Particularly effective in NMOSD-associated optic neuritis and refractory cases, with high-quality evidence supporting its use. 8, 1, 2, 6
• Azathioprine (AZA): May be used as a steroid-sparing maintenance agent, though less effective than rituximab in NMOSD. 8, 2
• Cyclophosphamide: Reserved for specific scenarios (see Special Populations below). 8, 2

Essential Diagnostic Workup

Perform MRI of brain and orbits with gadolinium contrast to: 8, 1, 2

• Confirm optic nerve enhancement and signal changes 8
• Assess for dissemination of demyelinating lesions in space and time (McDonald criteria) 8
• Stratify risk for progression to clinically definite MS 3, 7

Prognostic significance: Patients with ≥2 white matter lesions (≥3 mm diameter, at least 1 periventricular or ovoid) have 5.53 times higher risk of developing definite MS. 3, 7 These high-risk patients benefit most from IV methylprednisolone treatment. 3

Special Populations Requiring Modified Treatment

SLE-Associated Optic Neuritis:

Use combination therapy with pulse IV methylprednisolone PLUS IV cyclophosphamide. 8, 1, 2 Visual outcomes are significantly poorer in SLE-related optic neuritis—only 30% maintain visual acuity >20/25. 8, 2 Anticoagulation may be considered if antiphospholipid antibodies are present and patient doesn't respond to immunosuppression. 8, 2

NMOSD-Associated Optic Neuritis:

Initial treatment remains IV methylprednisolone 1000 mg/day for 3-5 days, but have a lower threshold for early PLEX. 2, 6 Long-term immunosuppression with rituximab is typically required to prevent relapses. 1, 2

Monitoring and Follow-Up

Short-term (every 4-6 weeks):

• Visual acuity, visual fields, funduscopy, and contrast sensitivity 1, 6
• Visual-evoked potentials to objectively assess optic nerve recovery and detect subclinical bilateral involvement 8, 1, 2, 6

Long-term surveillance:

• Repeat MRI at 3-6 months to assess for new demyelinating lesions 6
• Critical warning: Relapses occur in 50-60% of patients during corticosteroid dose reduction, necessitating maintenance immunosuppressive therapy in many cases. 8, 1, 2, 6
• Any new vision loss in either eye warrants immediate repeat MRI and consideration of repeat IV methylprednisolone 6

Important Caveats

• The standard MS disease-modifying therapies (interferon beta-1a) may be considered in high-risk patients (≥2 brain lesions) to reduce short-term risk of progression to clinically definite MS. 7
• Test for MOG-IgG antibodies after first recurrence, as standard MS treatments may worsen outcomes in MOG-antibody disease. 1
• Treatment decisions should account for severity of vision loss, degree of pain, and MRI findings—patients with significant vision loss, severe pain, and/or white matter lesions benefit most from treatment. 5