The clinical picture of optic neuritis is classically associated with systemic demyelinating disease—primarily multiple sclerosis (MS). These patients typically experience dyschromatopsia, unilateral vision loss, and discomfort with eye movement. Over 20 years have passed since the monumental optic neuritis treatment trial (ONTT) was published.1 A greater understanding of systemic demyelinating disease has changed the way we address optic neuritis in a clinical setting.
In this article we’ll focus on two demyelinating conditions which are less frequently discussed in the context of optic neuritis—neuromyelitis optic spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD).
These less common conditions still require a timely and accurate diagnosis to optimize long-term systemic/visual outcomes and minimize long-term disability.
NMOSD and optic neuritis
Overview
NMOSD is an autoimmune disorder that results in astrocyte loss and demyelination of the optic nerves and spinal cord. Clinically, it may present with similar and overlapping findings most classically associated with multiple sclerosis, including retrobulbar optic neuritis and transverse myelitis (inflammation of the spinal cord). However, this condition is a distinct entity that requires different treatment, which may have a more severe, chronic, and relapsing course when compared to MS.
In the absence of treatment, 5 years after the first symptoms associated with the disease onset, 25% of NMOSD patients required gait assistance, more than 40% were legally blind in at least one eye, and mortality reached 10%.2 NMOSD accounts for approximately 1/3 of demyelinating disease in Asian and non-white populations, but only up to 2% in the United States and Europe.3
This condition is more common in females, and while it can affect individuals of any age, the median age of diagnosis is 40 (which is older than what is typically found in multiple sclerosis), with up to 20% of cases occurring in younger adults.3
Symptoms and diagnosis of NMOSD
In the exam room, a careful review of symptoms should include evaluation for limb weakness, numbness, bladder or bowel dysfunction, and sensory loss or pain below the level of the lesion.4
An automated visual field study will help to localize the lesion, as found in individuals with seemingly unilateral optic neuropathy. Contralateral field loss may suggest a junctional, or postchiasmal, lesion.
Patients may also report vomiting and hiccups which last longer than 48 hours as a result of a lesion in the dorsal medulla, called area postrema syndrome.5
Individuals presenting with these symptoms require an immediate MRI of the brain and cervical spinal cord (with and without contrast) and serum testing. This requires specifically evaluating for: infection, angiotensin converting enzyme (ACE), and myelin oligodendrocyte glycoprotein (MOG), which is most practically performed in an in-patient setting.6
Detection of IgG antibodies, which bind to water channel aquaportin-4 (AQP4-IgG), is considered pathogenic, and is detectable in more than 80% of patients with NMOSD.6,7
Treatment for NMOSD
In the setting of acute symptoms associated with NMOSD, systemic steroids are the most commonly employed treatment, with consideration of plasmapheresis immediately following steroid pulse, relapsing, or steroid-refractory cases.8 The goal of long-term management is to prevent relapses from occurring.
Remarkably, there are currently three FDA-approved monoclonal antibodies used for treatment of NMOSD and AQP4-IgG antibodies.
Access to these therapies remains a challenge, so individuals may be alternatively managed with more traditional immunosuppressive therapy.9
Long-term, patients with NMOSD tend to have a worse visual prognosis in comparison with other causes of optic neuritis associated with demyelinating disease. It has been shown that 70% of cases result in vision of 20/200 or worse, and typically face a relapsing course of the disease.10
Figure 1 illustrates a case of bilateral optic atrophy following an episode of optic neuritis of the right eye in a 66 year old white female with best corrected visual acuity of 20/40 in the right eye and 20/25 in the left eye.
Figure 1
MOGAD and optic neuritis
Overview
Myelin oligodendrocyte glycoprotein associated disease (MOGAD) is another important differential diagnosis of optic neuritis, which also shares features of NMOSD and MS. While MOGAD is an oligodendrocyte disease which results in demyelination (similar to MS), it can differ clinically.
MOGAD-associated optic neuritis can clinically differ from other demyelinating disorders in that optic disc edema is more common, and patients may exhibit additional ophthalmic findings including: neuroretinitis, acute macular neuroretinopathy, uveitis, and venous stasis retinopathy.11
Symptoms and diagnosis of MOGAD
Nonspecific signs and symptoms of systemic demyelination may be exhibited in patients with MOGAD, including: a history of seizures, weakness in limbs, loss of sensation in limbs, or loss of bladder and bowel control.12 Serological detection of MOG IgG antibodies (MOG-IgG) is diagnostic for MOGAD.13
Neuroimaging findings typically exhibit similar characteristics to NMOSD, including extended lesions affecting the optic nerve and spinal cord.12 MOGAD occurs equally in males and females and accounts for up to 50% of optic neuritis cases in children.12
Treatment for MOGAD
Acute exacerbations of MOGAD, including MOG optic neuritis (MOG–ON), are treated on an in-patient basis with high doses of intravenous corticosteroids. These patients tend to require extended periods of treatment with oral steroid therapy or immunosuppression.14
The long-term visual outcome of patients with MOG-ON is generally more favorable compared to those with NMOSD, with less than 6% of individuals having visual acuity of 20/200 or worse.15
Figure 2 demonstrates retinal nerve fiber layer (RNFL) analysis and ganglion cell complex (GCC) analysis exhibiting diffuse temporal RNFL loss in the right eye, and inferior temporal RNFL loss in the left eye, with significant generalized GCC loss in both eyes.
Figure 2
Conclusion
Diagnosis of optic neuritis in a clinical setting is commonly associated with an underlying autoimmune condition, including systemic demyelinating disease. While multiple sclerosis may be the most frequent and familiar demyelinating condition encountered, others, including NMOSD and MOGAD, must be carefully considered.
Co-management with primary care, neurology, and/or neuro-ophthalmology is vital. Coordinated referral for urgent specific radiologic evaluation, serologic evaluation, and possible lumbar puncture can optimize cellular-based treatments, and improve long-term visual outcomes for patients with demyelinating disease.
References
- Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 1992;326:581–88.
- Kitley J, Leite MI, Nakashima I, et al. Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain 2012;135:1834-49.
- Papp V, Magyari M, Aktas O, et al. Worldwide incidence and prevalence of neuromyelitis optica: a systematic review. Neurology 2021;96:59-77.
- Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 1999;53:1107-1114.
- Shosha E, Dubey D, Palace J, et al. Area postrema syndrome: frequency, criteria, and severity in AQP4-IgG-positive NMOSD. Neurology 2018;91:e1642-e1651.
- Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177-189.
- Lucchinetti CF, Guo Y, Popescu BF, et al. The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol 2014;24:83-97.
- Kleiter I, Gahlen A, Borisow N, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol 2016;79:206-216.
- Levy M, Fujihara K, Palace J. New therapies for neuromyelitis optica spectrum disorder. Lancet Neurol 2021;20:6-67.
- De Lott LB, Bennett JL, Costello F: The changing landscape of optic neuritis: a narrative review. J Neurol 2022; 269:111-124.
- Vosoughi AR, Ling J, Tam KT, et al. Ophthalmic manifestations of myelin oligodendrocyte glycoprotein-IgG-associated disorder other than optic neuritis: a systematic review. Br J Opthalmol 2021;105:1591-98.
- Maciej J, Silvia M, Mark WR, et al. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain 2017;140:3128-38
- Waters PJ, Komorowski L, Woodhall M, et. al.: A multicenter comparison of MOG-IgG cell-based assays. Neurology 2019; 92:e1250-e1255.
- Whittam DH, Karthikeayan V, Gibbons E, et. al.: Treatment of MOG antibody associated disorders: results of an international survey. J Neurol 2020; 267:3565-3577.
- Chen JJ, Flanagan EP, Jitprapaikulsan J, et al. Myelin Oligodendrocyte glycoprotein antibody-positive optic neuritis: clinical characteristics, radiologic clues, and outcome. Am J Ophthalmol. 2018;195:8–15.
