What Causes Optic Neuritis
Optic neuritis is caused by inflammatory processes affecting the optic nerve, most commonly associated with demyelinating diseases (particularly multiple sclerosis), autoimmune disorders (including neuromyelitis optica spectrum disorders and MOG antibody disease), and less frequently by infectious or granulomatous conditions. 1, 2, 3
Primary Demyelinating Causes
Multiple sclerosis is the most common cause of typical optic neuritis in Western populations. 2, 4
- The inflammatory process involves activation of T-cells that cross the blood-brain barrier and cause hypersensitivity reactions to neuronal structures 2
- Even a single clinically silent T2 hyperintense brain lesion on MRI in patients with optic neuritis is highly associated with eventual MS diagnosis 5
- MS-associated optic neuritis typically presents unilaterally with relatively good visual recovery 3
Autoimmune and Antibody-Mediated Causes
Neuromyelitis optica spectrum disorders (NMOSD) represent a critical alternative diagnosis, characterized by anti-AQP4-IgG antibodies and typically more severe visual outcomes than MS-related optic neuritis. 6, 3
- NMOSD frequently presents with bilateral optic neuritis and more severe vision loss with poorer recovery compared to MS 6
- Red flags for NMOSD include posterior optic nerve involvement extending to the chiasm, simultaneous bilateral involvement, and long optic nerve lesions 1
MOG antibody-associated disease (MOGAD) is an increasingly recognized cause with distinct clinical features. 1, 4
- Anti-MOG-IgG disease is particularly suggested by long optic nerve lesions and bilateral simultaneous involvement 1
- Soft tissue enhancement extrinsic to the nerve, affecting the orbit, orbital apex, or cavernous sinus signifies anti-MOG-IgG disease rather than MS 1
- Visual recovery can be poorer and optic nerve atrophy more severe in MOG-seropositive individuals compared to typical MS-associated optic neuritis 3
Systemic lupus erythematosus can cause inflammatory optic neuritis with bilateral presentation and poor visual outcomes, with only 30% of patients maintaining visual acuity greater than 20/25. 6
Infectious Causes
Viral infections can trigger optic neuritis, particularly in specific populations. 6
- Measles (rubeola) can cause bilateral optic neuritis, particularly in unvaccinated individuals 6
- Epstein-Barr virus has been associated with optic neuritis 6
- Zika virus has been reported to cause bilateral optic neuritis 6
Granulomatous and Other Inflammatory Causes
Granulomatous diseases including sarcoidosis, tumors, and infections can cause optic neuritis with atypical features. 1
- Perioptic nerve sheath enhancement is recognized in typical optic neuritis, but soft tissue enhancement extrinsic to the nerve indicates non-MS etiology such as granulomatous disease, tumor, or infection 1
Key Diagnostic Distinctions
The imaging characteristics help differentiate causes: 1
- Typical acute optic nerve lesions show T2 hyperintensity, optic nerve swelling, and contrast enhancement, but these findings are not MS-specific and occur in other inflammatory conditions including NMOSD, ischemic, or infectious diseases 1
- A T2-hyperintense lesion in the nerve differentiates MS from ischemic and toxic optic neuropathies or Leber's hereditary optic neuropathy, which do not show acute T2-hyperintense lesions 1
Critical laboratory testing includes serum testing for AQP4-IgG and MOG-IgG antibodies in all cases of optic neuritis, particularly when bilateral or atypical features are present. 6