Myelin Oligodendrocyte Glycoprotein (MOG) Optic Neuritis

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Article initiated by:

Andrew Go Lee, MD, Nita Bhat, MBBS, MS, Shruthi Harish Bindiganavile, MBBS, MS

All contributors:

Hannah Khan, MPH, Preston.Baker, Nagham Al-Zubidi, MD, Ayman Okla Suleiman, MD, Karl Golnik, MD, MEd, Shruthi Harish Bindiganavile, MBBS, MS

Assigned editor:

Ayman Okla Suleiman, MD

Review:

Assigned status Update Pending

 by Ayman Okla Suleiman, MD on April 14, 2025.

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Contributing Editors:	add

Myelin Oligodendrocyte Glycoprotein (MOG). © 2020 Neuro-ophthalmology Virtual Education Library: NOVEL

Disease Entity

Disease

Myelin Oligodendrocyte Glycoprotein (MOG) Optic Neuritis is an antibody mediated demyelinating disease of the central nervous system (CNS) that is a distinct entity from other demyelinating processes of the CNS such as Multiple Sclerosis (MS) or AQP4-Ab-associated neuromyelitis optica spectrum disorder (NMOSD). Typical optic neuritis (ON) presents with acute, unilateral, onset of variable visual acuity/visual field loss, retrobulbar pain (worse with eye movement), loss of color vison, a relative afferent pupillary defect (RAPD), and a normal fundus exam (retrobulbar ON). ON in MOG however is often “atypical” and may be markedly steroid responsive, bilateral rather than unilateral, and may be associated with optic disc edema rather than a retrobulbar ON. Although ON is the most common symptom in MOG-Ab seropositive disease it can present with acute disseminated encephalomyelitis, myelitis, or an NMOSD like presentation. Children less than 9 years old who are positive for MOG-Antibodies (Ab) more frequently present with acute disseminated encephalomyelitis (ADEM) that may be relapsing or recurrent and may present with ON later in life.

Etiology

MOG ON is an autoimmune condition where MOG-specific antibodies and T cells target myelin sheaths in the CNS. The genetic association for MOG ON is less defined, whereas patients with NMOSD are more likely to have associated HLA haplotypes, significantly more prevalent in pediatric patients compared to adult patients, signifying the genetic predisposition of the disease.

Risk Factors

MOG ON can present in all age groups, ethnicities and genders, whereas NMOSD presents typically in adults, with a strong female predominance and is more frequently seen in African and Asian ancestry.Additionally, disease relapse is more likely to occur in patients older than 45 years, potentially influenced by immunologic variations. One study found children with MOG ADEM had up to an 80% of eventually developing MOG ON in adulthood. Another study found that 50% of pregnant women with MOG-specific antibodies developed their first MOG ON episode during or shortly after pregnancy. There was no association between MOG ON and other autoimmune disorders and MOG ON is not typically associated with oligoclonal bands, a test specific for MS.

Pathophysiology

MOG ON is characterized by an autoimmune attack on the surface of myelin sheaths by MOG-specific antibodies; however, the pathophysiology is largely incompletely understood, and the precise mechanism of MOG-specific antibodies remains ill defined.Theoretically, MOG-specific antibodies are IGg1 and activate complement, as well as mediate antibody dependent cellular cytotoxicity, ultimately leading to optic nerve damage and extensive demyelination. MOG proteins are found on the surface of oligodendrocytes and have been known to bind to C1q, IgG antibodies, dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), c-type lectin receptor expressed on the surface of dendritic cells and macrophages, rubella virus, and nerve growth factor.

Diagnosis

Physical Examination

MOG presents with a variety of symptoms, including severity of acute vision loss, extraocular neurologic deficits and other demyelinating events, as well as epidemiologic factors and prognosis. Physical exam findings specific for MOG ON include variable vision loss, pain with ocular movement, and moderate to severe optic disc edema, which is a classic differentiating feature of MOG ON from other forms of ON and is seen in up to 80% of patients. Bilateral ocular involvement is common and perineural enhancement on MRI is an often present. Although overlapping clinical and radiographical features are noted in MOG ON and non-arteritic anterior ischemic neuropathy (NAION), patients with NAION typically experience painless acute vision loss, whereas patients MOG ON experience pain with ocular movement. Both MOG ON and NAION can present with optic disc edema and peripapillary hemorrhage, MOG ON is commonly seen in younger patients, whereas NAION is seen more in older patients, typically over 50 years, with obstructive sleep apnea and vascular risk factors.

Signs

The hallmark clinical signs of MOG ON include acute unilateral or bilateral recurrent episodes that are steroid responsive. The presence of autoantibodies against MOG in the serum explains the recurrence of attacks and has a positive predictive value on the presentation of subsequent attacks.

Patients with MOG ON can experience acute, rapidly progressive, severe vision loss which may or may not recover depending on the severity of the initial visual impairment and appropriate immunotherapy. Other common signs and symptoms of MOG ON include encephalopathy, myelitis, seizures, incontinence, and dysarthria.

Symptoms

Symptoms that are highly suggestive of MOG-Ab ON include bilateral and recurrent episodes of ON especially in the setting of steroid responsiveness and steroid dependence. A recent study demonstrated that children with MOG are most likely to present with ADEM, adults aged 20 to 45 are most likely to present with unilateral ON, and adults older than 45 are most likely to present with bilateral ON. Other neurologic deficits are seen in about 50% of cases but the presentation is highly variable from study to study (e.g., transverse myelitis, sensory nerve loss, incontinence, and ataxia).

Clinical Diagnosis

Definitive diagnosis of MOG ON is made in the appropriate clinical setting by seropositivity of MOG-Ab (cell-based assays are the current gold standard). One prospective cohort study of patients with ON showed that by testing all cases of ON with bilateral ON, recurrent ON, or optic disc swelling on fundoscopy for MOG antibody, all cases of MOG ON would be detected and only 50% of ON cases in the cohort would be tested overall. An absence of each of the atypical ON features that were considered to be higher risk for MOG had a negative predictive value of over 90%. MRI findings (e.g., OPN, lack of demyelinating white matter lesions for MS, longitudinally extensive enhancement) are also highly suggestive of MOG ON

Imaging

Longitudinally, extensive (involving >50% of the length of the optic nerve) enhancement and /or T2 weighted hyperintensities in the anterior visual pathways can be seen in MOG-Ab ON. Enhancing lesions are usually seen in the orbital and intracranial region of the optic nerve. Optic perineuritis (OPN) with enhancement the optic nerve sheath is a finding that is common in MOG ON as compared to MS related ON (parenchymal optic nerve enhancement). Spinal MRI findings include swelling of the spinal cord and contrast enhancement that can resemble the transverse myelitis of NMOSD. In contrast to the ovoid, periventricular, white matter lesions (including corpus callosum) seen in MS, non-specific white matter lesions or a normal brain MRI may be seen in MOG

Laboratory test

Cell based assays are still recommended for a serologic diagnosis of MOG-Ab. Positive MOG-IgG titers are strongly associated with clinical features of MOG-Ab disease, with a downward trend resulting in improved long-term prognosis. Very few patients with MOG ON have been found to have the CSF oligoclonal bands seen with MS.

Differential diagnosis

• MS
• NMOSD (caused by AQP4 IgG)
• Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION)
• Sarcoidosis
• Lyme Disease
• Granulomatosis with polyangiitis (Wegner granulomatosis)

Management

Treatment

The gold standard and most efficacious treatment for MOG ON acute attacks has been high dose intravenous (IV) corticosteroid therapy (ie. methylprednisolone, 1 gm per day for 5 days). In patients who are refractory to IV corticosteroid therapy, intravenous immunoglobulin (IVIG) or plasma exchange (PLEX) is considered. Studies indicate treatment of acute attacks with methylprednisolone improves recovery by 10-20% when compared to no treatment. Among IV corticosteroid treatment refractory patients, 40% demonstrated improvement with IVIG, though partial recovery was more common comparatively. The highest risk of relapsing disease occurs early; thus, prompt initiation of maintenance therapy (oral corticosteroids) is recommended to significantly reduce the risk, predominantly in patients with a history of recurrent attacks. One study found that 36% of patients who received maintenance therapy following their first attack had reduction in proportion of relapsing disease compared to patients who did not receive early maintenance therapy. In another study, 95% of patients receiving doses of at least 20 mg of prednisone for 6 months following a MOG ON attack had no recurrent episodes of ON at follow up of over a year. High dose and longer length of treatment was strongly associated with remittance, and patience who were given a tapered dose, or discontinued therapy earlier had relapse rates comparable to those with no treatment. Rituximab has been investigated as a maintenance therapy for MOG ON and MOGAD, and studies have demonstrated its efficacy with reduced relapse rates in both.While rituximab shows potential for reducing relapse frequency in MOGAD, further research is necessary to establish optimal doing and treatment protocols. Studies have indicated rituximab demonstrates a non-superiority efficacious profile to other maintenance immunotherapies, highlighting the importance of personalized treatment regimens.Randomized, controlled, treatment trials are limited for MOG ON, but observational open-label work suggests a role for high-dose steroids and plasma exchange in the treatment of acute attacks, and immunosuppressive therapy (e.g., steroids, oral immunosuppressants and rituximab) as maintenance treatment.

Prognosis

In one study, 25% of patients suffering an acute attack had permanent visual disability. In other studies, patients experienced complete or partial recovery in up to 90% of cases. Although MOG ON attacks have been show to permanently damage the neural retinal ganglion and peripheral nerve fiber layers of the retina, the majority of patients fully or partially regain vision. The majority of individuals in all studies have a recurrence within the first year of attack. Increased risk of permanent neurologic deficit with subsequent attacks is much worse than after the first attacks. Younger age at first attack is associated with increased risk of permanent vision loss. Persistent MOG-Ab titers have been associated with relapse compared with patients without persistent MOG-Ab.