What are the causes of optic neuritis?

Causes of Optic Neuritis

Optic neuritis is most commonly associated with demyelinating disorders like multiple sclerosis, but can also be caused by neuromyelitis optica spectrum disorders, MOG antibody-associated disease, infectious conditions, autoimmune diseases, and ischemic or toxic neuropathies.

Demyelinating Causes

• Multiple Sclerosis (MS): The most common cause of typical optic neuritis in Western countries 1
• Neuromyelitis Optica Spectrum Disorders (NMOSD): Associated with anti-AQP4-IgG antibodies, often presenting with:
  • Posterior optic nerve involvement extending to the chiasm
  • More severe vision loss
  • Poorer visual outcomes 1, 2
• MOG Antibody-Associated Disease (MOGAD): Characterized by:
  • Often bilateral optic nerve involvement
  • Long optic nerve lesions
  • May have perioptic nerve sheath enhancement 1, 2

Inflammatory/Autoimmune Causes

• Systemic Lupus Erythematosus (SLE): Can cause inflammatory optic neuritis 1
• Sarcoidosis: Often presents with perioptic nerve sheath enhancement 1, 2
• Vasculitis: Including granulomatous diseases 1
• Chronic Relapsing Inflammatory Optic Neuritis (CRION): Steroid-dependent form of optic neuritis 2
• Susac Syndrome: Rare autoimmune microangiopathy 1

Infectious Causes

• Lyme Disease: Can cause optic neuritis, especially in endemic areas 3
• Viral infections: Including herpes viruses
• Bacterial infections: Including tuberculosis, syphilis
• Parasitic infections: Should be considered in patients with travel history to endemic areas 4, 5

Other Causes

• Ischemic Optic Neuropathy: Can be differentiated from inflammatory optic neuritis by lack of T2-hyperintense lesions in the optic nerve 1
• Leber's Hereditary Optic Neuropathy: Genetic mitochondrial disorder, typically does not show acute T2-hyperintense lesions 1
• Toxic Optic Neuropathies: Various toxins and medications can cause optic nerve damage 1
• Paraneoplastic Syndromes: Rare cause of optic neuritis 2
• Post-vaccination: Reported following various vaccinations 2

Distinguishing Features Between Typical and Atypical Optic Neuritis

Typical Optic Neuritis (MS-associated)

• Usually unilateral
• Associated with periocular pain, especially with eye movement
• Dyschromatopsia (color vision defects)
• Generally good visual recovery regardless of treatment 6, 7
• T2 hyperintensity on MRI with contrast enhancement 1

Atypical Optic Neuritis (Red Flags)

• Bilateral simultaneous involvement
• Severe vision loss
• Poor response to corticosteroids or steroid-dependency
• Posterior optic nerve/chiasm involvement
• Long optic nerve lesions
• Perioptic nerve sheath enhancement extending to orbit/cavernous sinus
• Lack of pain
• Poor visual recovery 1, 2, 7

Diagnostic Approach

• MRI of orbits and brain with contrast: Primary imaging study to visualize optic nerve enhancement and detect demyelinating lesions 1, 8
• Visual evoked potentials: Can detect bilateral optic nerve damage and show delayed conduction 8
• CSF analysis: For oligoclonal bands (MS) and to exclude infectious causes 8
• Serological testing: For AQP4-IgG and MOG-IgG antibodies, as well as infectious and autoimmune markers 2
• Anesthetic challenge test: Can help differentiate between peripheral/nociceptive pain and central/non-ocular origin 8

Treatment Considerations

• Corticosteroids: Intravenous methylprednisolone is first-line treatment for typical optic neuritis, with faster recovery and reduced risk of MS conversion 6
• Important caution: Oral prednisone alone is contraindicated due to increased risk of recurrence 5, 6
• For NMOSD/MOGAD: More aggressive immunosuppression may be needed 1
• For infectious causes: Appropriate antimicrobial therapy (e.g., doxycycline for Lyme disease) 3
• For autoimmune causes: Disease-specific immunosuppressive therapy 1

Early diagnosis and appropriate treatment are crucial for preserving vision and preventing recurrences, particularly in atypical forms of optic neuritis where the prognosis may be worse without targeted therapy.