Optic Neuritis in Multiple Sclerosis, NMOSD and MOGAD: Symptoms, Diagnosis and Treatment

Optic neuritis is an inflammatory disorder of the optic nerve that typically presents with subacute visual loss, impaired color vision and often pain with eye movement. It may occur as an isolated episode, as the first manifestation of multiple sclerosis (MS), or in association with AQP4-IgG-positive NMOSD and MOGAD.

Distinguishing between these conditions is important from the first attack. They differ in clinical presentation, MRI and OCT findings, likelihood of visual recovery, relapse risk and the need for long-term preventive therapy.

Main Symptoms of Optic Neuritis

Typical inflammatory optic neuritis may present with:

• visual loss in one eye, less commonly bilateral involvement;
• progression over several days;
• pain behind the eye or pain with eye movement;
• reduced color saturation, especially for red;
• reduced brightness and contrast;
• visual field defects, often central or centrocecal scotoma;
• a relative afferent pupillary defect in unilateral or asymmetric disease.

The optic disc may appear normal in retrobulbar neuritis or may be swollen. Marked disc edema, hemorrhages, absence of pain, severe bilateral involvement, progression beyond two weeks, or poor visual recovery should prompt a broader differential diagnosis.

Optic Neuritis in Multiple Sclerosis

Optic neuritis is one of the most characteristic first manifestations of MS. Typical MS-associated optic neuritis is usually unilateral, painful with eye movement and associated with a generally favorable visual prognosis.

Even after standard visual acuity has recovered, some patients continue to experience reduced contrast sensitivity, mild color vision abnormalities, visual fatigue and Uhthoff phenomenon — transient worsening of vision with increased body temperature or physical exertion.

Brain MRI is important for estimating the probability of MS. The presence of typical demyelinating lesions substantially increases the likelihood that an episode of optic neuritis is part of multiple sclerosis.

In the 2024 McDonald criteria, the optic nerve is included as a fifth anatomical region that may contribute to dissemination in space. Objective optic nerve involvement may be demonstrated by orbital MRI, optical coherence tomography (OCT), or visual evoked potentials, provided that a more likely alternative diagnosis has been excluded.

Optic Neuritis in NMOSD

AQP4-IgG-positive NMOSD is an antibody-mediated disorder of the central nervous system in which optic neuritis often has a more severe course than in MS.

Features that are more typical include:

• severe visual loss;
• bilateral or rapidly sequential involvement;
• longitudinally extensive optic nerve lesions on MRI;
• involvement of the posterior optic nerve, optic chiasm or optic tracts;
• a higher risk of persistent visual disability after an attack.

When NMOSD is suspected, serum AQP4-IgG should be tested using a validated cell-based assay. In AQP4-IgG-positive NMOSD, long-term relapse-prevention therapy is usually indicated after the first clinical attack.

Optic Neuritis in MOGAD

MOGAD is a disease associated with antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG). In adults, optic neuritis is one of the most common clinical manifestations.

Typical features include:

• frequent pain with eye movement;
• marked optic disc edema;
• bilateral involvement relatively often;
• long segments of optic nerve involvement on MRI;
• possible perineural contrast enhancement;
• often severe visual loss during the acute attack with relatively good recovery after treatment.

The diagnosis of MOGAD is not based on a blood test alone. It requires a compatible clinical syndrome together with MOG-IgG detected by a validated cell-based assay. Low-positive results require particularly careful interpretation.

How Optic Neuritis Differs in MS, NMOSD and MOGAD

Diagnosis of Optic Neuritis

Neurological and Ophthalmological Examination

Assessment includes visual acuity, color vision, visual fields, pupillary responses, fundus examination and other signs of optic pathway involvement. The clinical pattern helps determine whether the episode is consistent with typical demyelinating optic neuritis or whether another cause should be considered.

MRI of the Brain and Orbits

Contrast-enhanced MRI of the orbits and brain is generally preferred, using a protocol that adequately visualizes the optic nerves. MRI can confirm inflammatory involvement, define the length and location of the lesion, and identify brain lesions suggestive of MS or other inflammatory CNS disorders.

A short unilateral optic nerve lesion is more typical of MS. Longitudinally extensive involvement, chiasmal disease, or marked bilateral abnormalities increase the likelihood of NMOSD or MOGAD, although no MRI feature is diagnostic on its own.

Optical Coherence Tomography — OCT

OCT measures the peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell layers. In the acute phase, marked swelling — especially in MOGAD — may increase RNFL thickness. Over subsequent months, OCT can demonstrate the degree of axonal and neuronal loss.

In the 2024 McDonald criteria, OCT findings may also be used as objective evidence of optic nerve involvement in the diagnosis of MS.

Visual Evoked Potentials

Visual evoked potentials can demonstrate delayed conduction along the visual pathway and are particularly useful when optic nerve involvement is uncertain or remote. Under the 2024 McDonald criteria, they may also serve as objective evidence of optic nerve involvement.

AQP4-IgG and MOG-IgG Testing

Testing for AQP4-IgG and MOG-IgG is especially important in severe, bilateral, recurrent or atypical optic neuritis, in longitudinally extensive optic nerve lesions, marked disc edema, or when the clinical picture is not typical for MS-associated optic neuritis.

Validated cell-based assays are preferred for both antibodies. Results should always be interpreted in the context of the clinical picture and MRI findings.

Cerebrospinal Fluid Examination

Lumbar puncture is not required in every case. It may be useful when MS is suspected, when the presentation is atypical, or when other inflammatory or infectious diseases need to be excluded. Oligoclonal bands and free kappa light chains in CSF may support the diagnosis of MS.

Treatment of Acute Optic Neuritis

High-Dose Corticosteroids

Clinically significant demyelinating optic neuritis is usually treated with high-dose corticosteroids. A commonly used regimen is intravenous methylprednisolone 1000 mg daily for 3–5 days. Equivalent high-dose oral regimens may be used in selected situations.

In typical MS-associated optic neuritis, corticosteroids mainly accelerate visual recovery. Low-dose oral prednisone as sole therapy for classic MS-associated optic neuritis is not recommended.

NMOSD: Early Treatment Escalation

Severe NMOSD attacks require treatment as early as possible. If recovery after high-dose corticosteroids is insufficient, plasma exchange (PLEX) should be introduced early; in very severe attacks, apheresis may be considered at an early stage of treatment.

MOGAD

MOGAD-associated optic neuritis usually responds well to corticosteroids, but symptoms may recur if treatment is tapered too quickly. The duration of subsequent oral corticosteroid treatment is therefore individualized. Plasma exchange or intravenous immunoglobulin may be used in severe or steroid-refractory attacks.

Is Long-Term Preventive Therapy Needed?

Multiple Sclerosis

If the evaluation confirms MS, disease-modifying therapy is selected according to disease activity, MRI findings, prognostic factors and individual patient characteristics.

AQP4-IgG-Positive NMOSD

NMOSD carries a high risk of recurrent attacks, and disability accumulates largely as a consequence of relapses. Therefore, long-term relapse-prevention therapy is usually started after the first attack in AQP4-IgG-positive NMOSD.

MOGAD

MOGAD may follow either a monophasic or relapsing course. After a first attack, the decision on long-term therapy is individualized. Recurrent attacks provide a stronger indication for preventive therapy; available options include intravenous immunoglobulin and other immunosuppressive approaches.

Other Causes of Optic Nerve Dysfunction

Not every episode of acute visual loss involving the optic nerve is demyelinating optic neuritis. The differential diagnosis includes ischemic optic neuropathies, sarcoidosis and other systemic inflammatory disorders, infections, compressive optic neuropathy, toxic and nutritional optic neuropathies, hereditary disorders, paraneoplastic syndromes and retinal disease.

Atypical age, absence of pain, progressive worsening over several weeks, marked hemorrhages or exudates on fundus examination, systemic symptoms, severe bilateral disease or failure to recover as expected should prompt a broader diagnostic evaluation.

When Urgent Medical Assessment Is Needed

New subacute visual loss in one or both eyes, especially when accompanied by pain with eye movement or impaired color vision, requires prompt assessment by an ophthalmologist and neurologist. Marked visual loss, bilateral involvement or rapid deterioration should not be evaluated electively.

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