What is the appropriate diagnosis and treatment for a young to middle-aged adult, particularly a female, presenting with symptoms of optic neuritis, such as sudden vision loss, pain with eye movement, or blurred vision?

Optic Neuritis: Diagnosis and Treatment

Immediate Diagnostic Approach

Obtain urgent MRI of both orbits and brain with IV contrast as the primary diagnostic study, as this identifies abnormal optic nerve enhancement in 95% of cases and is critical for MS risk stratification—treatment delay beyond 2 weeks is an unfavorable prognostic factor. 1, 2

Clinical Confirmation

The diagnosis requires documentation of the classic triad:

• Subacute visual loss developing over hours to days 2
• Periocular pain worsening with eye movement 2
• Red-green color desaturation (dyschromatopsia) 2

Additional confirmatory findings include:

• Relative afferent pupillary defect (RAPD) in the affected eye in unilateral cases 3
• Optic disc edema present in approximately one-third of patients 3
• Central scotoma on visual field testing 2

Essential Imaging Characteristics

MRI findings that confirm optic neuritis include:

• T2 hyperintensity of the optic nerve 1, 2
• Optic nerve swelling 1, 2
• Gadolinium enhancement on T1-weighted post-contrast fat-suppressed sequences 1, 2
• Coronal fat-suppressed T2-weighted sequences are optimal for visualization 1, 2

Red Flags Requiring Urgent Antibody Testing

Immediately order serum AQP4-IgG and MOG-IgG antibody testing (using cell-based assays with full-length human MOG) if any of the following atypical features are present: 1, 4

• Bilateral simultaneous involvement 1, 2
• Severe vision loss with poor recovery after steroids or steroid dependence 1, 4
• Prominent optic disc edema 1, 4
• Posterior optic nerve involvement extending to chiasm 1, 2
• Long optic nerve lesions on MRI 1, 2
• Soft tissue enhancement extrinsic to the nerve 1
• Negative brain MRI in acute presentation 1

These features suggest neuromyelitis optica spectrum disorder (NMOSD) or MOG-antibody disease (MOGAD) rather than typical MS-related optic neuritis, which have dramatically different treatment requirements and prognoses. 1, 4, 5

Acute Treatment Protocol

Typical Optic Neuritis (MS-Related or Idiopathic)

Administer high-dose intravenous methylprednisolone as first-line treatment, which accelerates recovery and reduces the risk of MS conversion, though it does not improve final visual outcome. 6, 3

• IV methylprednisolone expedites recovery but does not change ultimate visual prognosis 3
• Never use oral prednisone alone—this is contraindicated as it increases the risk of recurrent episodes 6
• Visual acuity recovers in 95% of typical cases 3

Atypical Optic Neuritis (NMOSD/MOGAD)

For AQP4-IgG positive NMOSD or MOG-IgG positive MOGAD, initiate high-dose IV methylprednisolone immediately, and prepare for plasma exchange if inadequate response, as these conditions cause more severe vision loss with poorer recovery than typical optic neuritis. 7, 1, 5

• Pulse IV methylprednisolone combined with IV cyclophosphamide is recommended for NMOSD, particularly SLE-related optic neuritis 7
• Only 30% of SLE-related optic neuritis patients maintain visual acuity greater than 20/25 7, 1
• Plasma exchange should be used in severe cases not responding to steroids 7, 5
• Anticoagulation may be considered in antiphospholipid antibody-positive patients not responding to immunosuppression 7

MS Risk Stratification and Long-Term Management

Brain MRI Interpretation for MS Risk

Even one clinically silent T2 hyperintense brain lesion dramatically increases MS risk, with hazard ratios of 5.1 for 1-3 lesions and 11.3 for ≥10 lesions. 2

• Absence of brain lesions strongly predicts monophasic illness 2
• CSF oligoclonal bands combined with brain MRI lesions dramatically reduce the likelihood of monophasic disease 2

Additional Diagnostic Studies for High-Risk Patients

When bilateral optic neuritis occurs with negative brain MRI, obtain:

• MRI of complete spine with and without IV contrast to assess for longitudinally extensive transverse myelitis (LETM), which is 80% sensitive and 90% specific for NMOSD, MOGAD, or ADEM 1
• Lumbar puncture with CSF analysis: absence of CSF-restricted oligoclonal bands favors MOGAD over MS; neutrophilic pleocytosis or WBC >50/μL suggests MOGAD (70% sensitive, 80% specific) 1
• Visual evoked potentials (VEPs) to confirm optic nerve dysfunction with delayed conduction, providing objective evidence even when imaging is equivocal 2

Preventive Immunotherapy

For patients at high risk of MS conversion (based on brain MRI lesions), initiate disease-modifying therapy with interferon β-1a, interferon β-1b, or glatiramer acetate to reduce MS risk. 6, 3

Maintenance Therapy for Atypical Forms

NMOSD patients require long-term immunosuppression (commonly rituximab) to prevent devastating relapses, while MOGAD patients need maintenance therapy due to 50-60% relapse rates during corticosteroid taper. 7, 1

• Relapses are common (50-60%) during corticosteroid dose reduction in both NMOSD and MOGAD 7, 1
• Chronic immunosuppressive therapy is essential for preventing recurrence 7

Common Pitfalls to Avoid

• Do not use oral prednisone alone—this increases recurrence risk 6
• Do not delay treatment beyond 2 weeks—this is associated with worse neurological outcomes 7, 1
• Do not assume typical MS-related optic neuritis without checking for red flags—missing NMOSD or MOGAD leads to inadequate treatment and preventable severe disability 1, 4
• Do not skip brain MRI even in isolated optic neuritis—it is critical for MS risk stratification and guides preventive therapy decisions 2