Optic Neuritis – Symptoms, Diagnosis, MS, NMOSD, and MOGAD

Optic neuritis (ON) is an inflammatory optic neuropathy that leads to acute or subacute visual loss. It is a common manifestation in demyelinating central nervous system diseases and represents a key clinical syndrome in multiple sclerosis (MS), aquaporin-4–positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). Understanding the clinical features and diagnostic distinctions among these three entities is essential, as prognosis and management differ significantly.

Clinical Presentation

Typical symptoms of optic neuritis include decreased vision, color desaturation, pain with eye movements, and the presence of a relative afferent pupillary defect. Vision loss evolves over hours to days, most often reaching its nadir within the first week. Dyschromatopsia is a hallmark feature and is often disproportionate to the degree of visual acuity loss. Patients may also describe dimmer light perception in the affected eye.

Fundus examination may show a normal optic disc (“retrobulbar neuritis”) or mild optic disc swelling. Optical coherence tomography (OCT) often reveals peripapillary retinal nerve fiber layer (RNFL) thickening acutely, followed by progressive thinning over subsequent months.

Multiple Sclerosis–Associated Optic Neuritis

MS-associated optic neuritis is the most common subtype encountered in neurological practice. It typically presents with unilateral visual loss accompanied by pain on eye movements. Symptoms peak within several days, and progression beyond two weeks is atypical. Severe visual loss (no light perception) is rare.

MRI of the orbits usually demonstrates focal optic nerve enhancement that involves less than 50% of the nerve length, a distinction from NMOSD and MOGAD. Brain MRI is essential for MS risk stratification: the presence of demyelinating lesions significantly increases the likelihood of converting to MS after a first episode of optic neuritis.

Visual prognosis in MS-associated optic neuritis is generally excellent. Most patients recover to 20/40 or better visual acuity within 6–12 months. However, subtle visual complaints such as reduced contrast sensitivity, color desaturation, and motion perception difficulties may persist despite normal Snellen acuity.

AQP4-IgG NMOSD–Associated Optic Neuritis

Optic neuritis associated with NMOSD is typically more severe and may result in permanent visual disability if not treated promptly. AQP4-IgG NMOSD commonly presents with bilateral or sequential optic neuritis and often involves long segments of the optic nerve, including the chiasm. Vision at nadir is frequently 20/200 or worse.

MRI usually demonstrates longitudinally extensive optic nerve involvement (>50% of nerve length), posterior predominant lesions, and possible chiasmal extension. OCT reveals deeper RNFL loss than in MS, reflecting more severe injury.

Prompt initiation of high-dose corticosteroids is essential, and plasma exchange is frequently required. Long-term relapse prevention is mandatory due to the high risk of recurrence. FDA-approved therapies include eculizumab, ravulizumab, inebilizumab, and satralizumab.

MOGAD-Associated Optic Neuritis

MOGAD is a distinct antibody-mediated demyelinating disease that frequently presents with optic neuritis. Acute periocular pain occurs in approximately 90% of cases. In contrast to MS and NMOSD, optic disc swelling is very common in MOGAD (in more than 75% of cases), and peripapillary RNFL thickening can be pronounced.

Visual acuity at nadir may be markedly reduced, often down to counting fingers, but long-term prognosis is usually favorable, with good recovery in the majority of patients. MRI demonstrates longitudinally extensive optic nerve enhancement, often involving the anterior segments and frequently extending into the perineural sheath.

MOG-IgG titers must be interpreted carefully, as low titers (<1:40) may be nonspecific. Diagnosis relies on a compatible clinical phenotype, typical MRI features, and detection of MOG-IgG on a live cell–based assay.

Treatment Overview

Acute treatment of inflammatory optic neuritis generally involves high-dose intravenous methylprednisolone (1,000 mg/day for 3–5 days) or high-dose oral corticosteroids. MOGAD and NMOSD often require longer steroid tapers than MS. Plasma exchange is indicated for severe or steroid-refractory attacks, especially in NMOSD.

Long-term treatment differs significantly:

• MS-associated ON: no chronic therapy for ON itself, but disease-modifying therapy for MS when indicated.
• NMOSD: lifelong relapse-prevention therapy is required.
• MOGAD: approximately 50% of patients follow a monophasic course; prophylactic treatment (IVIg, rituximab, mycophenolate) is used for relapsing disease.

Other Causes of Optic Neuritis (Brief Differential Diagnosis)

Although inflammatory demyelinating disease accounts for most cases in neurological practice, other etiologies must be considered. These include sarcoidosis, granulomatosis with polyangiitis, autoimmune GFAP astrocytopathy, paraneoplastic optic neuropathies (e.g., CRMP-5), syphilis, Lyme disease, tuberculosis, viral infections (VZV, CMV), and fungal infection in immunocompromised patients. These entities typically have systemic manifestations or atypical imaging findings and require targeted evaluation.

Summary

Optic neuritis is a clinically and diagnostically important syndrome with distinct features in MS, NMOSD, and MOGAD. Accurate differentiation among these entities is crucial, as treatment strategies and long-term prognosis differ sharply. Modern neuroimmunology — including MRI, OCT, AQP4-IgG and MOG-IgG testing — enables precise diagnosis and timely therapy.

Key References

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