Is optic neuritis associated with Neuromyelitis Optica Spectrum Disorder (NMOSD), Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD), or Systemic Lupus Erythematosus (SLE)?

Optic Neuritis in NMOSD, MOGAD, and SLE

Yes, optic neuritis is a major clinical manifestation in all three conditions—NMOSD, MOGAD, and SLE—though with distinct characteristics and severity profiles that require immediate recognition for appropriate management. 1, 2, 3

NMOSD-Associated Optic Neuritis

Optic neuritis is one of the core clinical characteristics of NMOSD, typically presenting with severe visual deficit or blindness. 1

Key Clinical Features:

• Severe visual impairment or complete blindness is characteristic, often more severe than MS-related optic neuritis 2
• Bilateral simultaneous involvement is a red flag distinguishing NMOSD from MS 2
• Prominent papilledema, papillitis, or optic disc swelling during acute episodes 2
• Only 30% of patients maintain visual acuity >20/25, indicating poor visual outcomes 2

Diagnostic Imaging Characteristics:

• Longitudinally extensive optic nerve lesions extending over >50% of the optic nerve length or involving the optic chiasm 2
• Posterior optic nerve involvement extending to the chiasm is highly suggestive of AQP4-IgG-seropositive NMOSD 2
• Perioptic gadolinium enhancement (optic nerve sheath involvement) during acute episodes 2
• "Cloud-like" enhancement pattern on MRI, distinct from the nodular or ring enhancement seen in MS 2

Treatment Implications:

• Prompt plasmapheresis as adjunct to intravenous methylprednisolone (IVMP) is indicated, with shorter time-to-treatment associated with higher likelihood of recovery 4
• Long-term immunosuppression is mandatory with B-cell depleting therapies (rituximab, ocrelizumab, ofatumumab), anti-IL-6 receptor, or complement-inhibiting monoclonal antibodies 1

MOGAD-Associated Optic Neuritis

Optic neuritis is a major phenotype of MOGAD, frequently presenting with severe visual deficit or blindness during acute episodes, but with generally favorable long-term visual outcomes. 3

Key Clinical Features:

• Severe central visual deficit or complete blindness during acute episodes, with bilateral involvement being common 3
• Prominent optic disc swelling is the hallmark finding on fundoscopy 3
• Long-term visual outcomes after 5 years are generally as good as MS and much better than NMOSD 5
• Visual acuity recovers almost fully spontaneously or shortly after acute treatment in the majority of patients 5

Diagnostic Imaging Characteristics:

• Longitudinally extensive optic nerve lesions involving ≥4 of 5 segments (anterior intraorbital, posterior intraorbital, canalicular, intracranial, chiasmal) 6, 2
• Median optic nerve lesion length of 23.1 mm (compared to 9.9 mm in MS-related ON) 6
• Perioptic gadolinium enhancement (optic nerve sheath involvement) occurs frequently 3
• Involvement of >6/12 optic nerve segments may be associated with increased pre-test odds for MOG-IgG 6

Treatment Approach:

• IVMP is near-universal given phenotypic similarities with NMOSD, though natural history of untreated MOGAD-associated optic neuritis remains unclear 4
• 50-60% relapse rate during corticosteroid taper, necessitating maintenance immunosuppressive therapy 2
• Long-term immunosuppression warranted in patients with poor visual recovery or recurrent attacks 4

Important Caveat:

• A small fraction of patients with extensive optic nerve lesions involving the chiasma experience irreversible severe visual impairment despite appropriate acute treatment 5

SLE-Associated Optic Neuritis

Systemic lupus erythematosus can cause inflammatory optic neuritis, associated with poor visual outcomes. 2

Key Clinical Features:

• Only 30% maintain visual acuity >20/25, indicating poor prognosis 2
• May present bilaterally 2
• Treatment delay beyond 2 weeks is an unfavorable prognostic factor, particularly in SLE-related cases 2

Treatment Approach:

• SLE patients with major neuropsychiatric manifestations of inflammatory origin, including optic neuritis, may benefit from immunosuppressive therapy 2
• Earlier treatment correlates with better visual recovery 2

Diagnostic Consideration:

• NMOSD can coexist with SLE, and these should be considered independent diseases requiring separate therapeutic approaches 7
• Serum antibody testing for AQP4-IgG and MOG-IgG should be performed immediately in SLE patients presenting with optic neuritis, as these have significant therapeutic consequences 2

Critical Diagnostic Algorithm

When evaluating optic neuritis, immediately test for AQP4-IgG and MOG-IgG antibodies in parallel if costs permit, or test AQP4-IgG first if disease is stable and costs are a factor. 1

Red Flags Requiring Immediate Antibody Testing:

• Severe visual deficit or blindness 1
• Bilateral simultaneous optic neuritis 2
• Posterior involvement extending to the chiasm 1
• Longitudinally extensive optic nerve lesions 1
• Perioptic enhancement on MRI 2

Common Pitfall:

AQP4-IgG/MOG-IgG "double-positive" results are extremely rare and should prompt retesting for both antibodies using alternative methodologies 1