In a 52‑year‑old man with bilateral optic neuritis due to myelin‑oligodendrocyte glycoprotein antibody‑associated disease who received three days of intravenous methylprednisolone 1 g daily followed by mycophenolate, and whose visual acuity has not improved after one month, what additional therapy can be given to accelerate visual recovery?

Additional Therapy for Persistent Vision Loss in MOGAD Optic Neuritis

For this patient with MOGAD-related bilateral optic neuritis showing no visual improvement one month after IV methylprednisolone, plasma exchange (PLEX) or IVIG should be initiated immediately, followed by consideration of rituximab for long-term relapse prevention. 1, 2

Immediate Second-Line Interventions

Plasma Exchange (PLEX)

• PLEX is the most strongly recommended rescue therapy for steroid-refractory MOG-associated optic neuritis, particularly when vision has not improved after initial corticosteroid treatment 3, 1
• Should be administered as 5-7 exchanges over 10-14 days, with each session removing approximately 1-1.5 plasma volumes 3
• Early initiation of PLEX (within 4-6 weeks of symptom onset) may prevent persisting visual loss and improve long-term outcomes 4
• PLEX is particularly effective in MOGAD when initiated promptly after steroid failure, as delays beyond this window significantly reduce efficacy 5, 4

Intravenous Immunoglobulin (IVIG)

• IVIG at 2 g/kg divided over 5 days (0.4 g/kg/day) is an alternative to PLEX, particularly useful in MOG-positive optic neuritis 3, 1
• Can be combined with repeat pulse methylprednisolone (1 g IV daily for 3-5 days) if not already attempted 3
• Note: If PLEX is planned after IVIG, allow adequate time between therapies as plasmapheresis will remove the administered immunoglobulin 3

Long-Term Immunosuppressive Therapy

Rituximab (First Choice)

• Rituximab is the most consistently effective immunomodulatory therapy for relapsing MOG-associated optic neuritis and should be strongly considered for this patient given the severity (bilateral involvement) and lack of response 1, 6, 4
• Typically dosed at 1000 mg IV on days 1 and 15, then repeated every 6 months based on CD19/CD20 B-cell monitoring 6, 4
• Shows superior efficacy compared to azathioprine in reducing relapse rates in MOG-associated disease 2, 4

Alternative Maintenance Immunosuppressants

• Mycophenolate mofetil (already initiated in this patient) can serve as a steroid-sparing maintenance agent, though it may be less effective than rituximab for preventing relapses 1, 6, 7
• Azathioprine is another option but appears less effective than rituximab based on comparative data 2, 6
• Monthly IVIG can be used for maintenance therapy in patients who cannot tolerate other immunosuppressants 6

Critical Pitfalls and Monitoring

Steroid Tapering Considerations

• Relapses occur in 50-60% of MOG-associated optic neuritis patients during rapid corticosteroid taper, which is a major cause of treatment failure 1, 2, 5
• MOG-associated optic neuritis is frequently associated with flare-ups if steroids are tapered too quickly, and this entity underlies many cases of "chronic relapsing inflammatory optic neuropathy" (CRION) 4
• Consider maintaining low-dose oral prednisone (5-10 mg daily) while establishing maintenance immunotherapy, then taper very slowly over 6-12 months 4

Avoid MS Disease-Modifying Therapies

• Do not use interferon-beta or natalizumab in MOG-positive patients, as these MS therapies can worsen disease activity and increase relapse rates 1, 4
• This is a critical distinction from MS-associated optic neuritis and represents a common treatment error 1

Essential Monitoring

• Ophthalmological evaluations every 4-6 weeks including visual acuity, visual fields, funduscopy, and optical coherence tomography (OCT) to assess for optic nerve atrophy 5, 7
• Visual evoked potentials to objectively assess optic nerve recovery and detect subclinical bilateral involvement 2, 5
• Repeat MRI brain and orbits with contrast at 3-6 months to assess for new demyelinating lesions 5
• Monitor for optic disc swelling resolution and development of optic atrophy on OCT (peripapillary RNFL and macular GCL thickness) 7

Prognostic Considerations

• Despite severe initial vision loss in MOG-associated optic neuritis, visual recovery is typically better than in AQP4-IgG-positive NMOSD, though delayed treatment significantly worsens prognosis 6, 4, 8
• The one-month timepoint without improvement in this patient is concerning and warrants aggressive escalation, as delays beyond 2 weeks from symptom onset are associated with poorer outcomes 2, 5
• Bilateral involvement at presentation increases the risk of relapsing disease and supports the need for long-term immunosuppression 9, 8