Article Highlights

• Bilateral optic neuritis, atypical demographics or optic disc swelling should prompt evaluation for NMO or MOGAD rather than MS.
• MS-related optic neuritis is typically unilateral with a normal disc, whereas MOGAD and NMO more often present with visible disc edema.
• MRI findings can distinguish etiologies, with MS showing multifocal white matter lesions, NMO demonstrating longitudinally extensive spinal cord involvement and MOGAD showing perineural enhancement.
• Antibody testing (AQP4 for NMO, MOG for MOGAD) is essential for accurate diagnosis and differentiation from MS.
• Correctly identifying NMO or MOGAD is critical, as these disorders require distinct management strategies and misdiagnosis can delay appropriate treatment.

In a new whiteboard video, Dr. Andrew Lee, neuro-ophthalmologist and chair of the Blanton Eye Institute at Houston Methodist, outlines how to identify optic neuritis and its lesser-known, clinically distinct mimics: neuromyelitis optica (NMO) spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

"Optic neuritis is inflammation of the optic nerve, and in young people, the most common cause is multiple sclerosis," Dr. Lee explains. "But every ophthalmologist needs to know about two important mimics of MS that are antibody-mediated: NMO and MOGAD."

These conditions can present differently from typical MS-related optic neuritis and require separate diagnostic and therapeutic approaches.

“These aren't just semantic differences. They have therapeutic implications, and missing the diagnosis can result in treatment delays or mismanagement.”

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Dr. Andrew Lee
Neuro-Ophthalmologist and chair of the Blanton Eye Institute at Houston Methodist

In the video, Dr. Lee shares three warning signs that suggest you may not be dealing with MS:

• Bilateral presentation – Optic neuritis caused by MS is usually unilateral. Bilateral inflammation should raise suspicion of NMO or MOGAD.
• Atypical demographics – MS is most common in young white females. If your patient is older, male, Black or Asian, consider testing for these antibody-mediated alternatives.
• Swollen optic disc – In classic retrobulbar neuritis from MS, the disc often appears normal. Visible swelling may point to MOGAD or NMO.

Radiographic features also offer important diagnostic clues, according to Dr. Lee. MS typically shows multifocal white matter lesions on MRI.

In contrast, NMO is associated with longitudinally extensive enhancement — spanning three or more vertebral segments in the spine — and often involves the optic nerve.

MOGAD, on the other hand, frequently shows perineural or nerve sheath enhancement on imaging, another atypical pattern for MS.

Dr. Lee emphasizes the importance of antibody testing for aquaporin-4 (AQP4) to diagnose NMO and myelin oligodendrocyte glycoprotein (MOG) to confirm MOGAD.

Click on the image above to watch the full video and see how Dr. Lee breaks down these important diagnostic distinctions to avoid common pitfalls in recognizing optic neuritis and its lookalikes.