Idiopathic Optic Neuritis

Key points of this disease

• Optic neuritis is an inflammatory disease of the optic nerve caused by autoimmune mechanisms, with main symptoms of acute unilateral vision loss and eye movement pain.
• Peak age of onset is 15–45 years, more common in women. Annual incidence in Japan is 1.6 per 100,000 adults.
• Over 90% of idiopathic optic neuritis cases recover to visual acuity of 0.5 or better at 1 year after onset, and over 70% improve to 1.0 or better (ONTT).
• Anatomically classified into anterior optic neuritis (with optic disc swelling, about 50% in Japan) and retrobulbar optic neuritis.
• Risk of conversion to MS: 25% at 15 years without brain MRI demyelinating lesions, 78% with lesions.
• First-line treatment is steroid pulse therapy with methylprednisolone 1,000 mg/day for 3 days. Oral steroid monotherapy is contraindicated due to increased relapse rate.
• Anti-AQP4 antibody positivity accounts for about 10% of idiopathic cases and is steroid-resistant. Anti-MOG antibody positivity is steroid-responsive but prone to relapse. Antibody testing and treatment strategies based on disease type are important.

1. What is Idiopathic Optic Neuritis

Optic neuritis is a disease in which the optic nerve becomes inflamed for some reason, leading to decreased visual function. After excluding infectious and non-infectious (toxic, hereditary, compressive) optic neuropathies, the majority are idiopathic, thought to be caused by autoimmune mechanisms.

Peak age of onset is 15–45 years, more common in women, and presents as acute monocular optic neuropathy. Visual dysfunction progresses over several days to 2 weeks, then shows a tendency to recover within 5 weeks.

Anatomical Classification

• Anterior optic neuritis (optic disc inflammation): Accompanied by optic disc swelling. Seen in about 50% in Japan (higher than 35% in Western countries).
• Retrobulbar optic neuritis: The fundus appears normal in the acute phase. Optic disc pallor appears after 4–6 weeks.

Disease Type and Etiological Classification

Disease Type	Characteristics
Idiopathic (autoimmune mechanism)	Most common. Usually monophasic
Anti-AQP4 antibody positive (NMOSD-related)	About 10% of idiopathic cases. Steroid-resistant, female-to-male ratio 9:1
Anti-MOG antibody positive (MOGAD)	Bilateral, optic disc swelling, long segment lesions. Steroid-responsive but prone to relapse
MS-related	Up to 75% of MS patients experience ON at least once in their lifetime
CRION	Steroid-dependent, relapsing. Proposed by Kidd et al. in 20035)
Infectious	Syphilis, viruses, etc. Must be ruled out before steroids

At initial visit, measure anti-AQP4 antibody; if negative, treat as idiopathic.

Epidemiology

The annual incidence in Japan is 1.6 per 100,000 adults. Peak age is 15–45 years, with women accounting for about 70%. The global prevalence is estimated at 1–5 per 100,000 people.

The association with MS is very strong, with a cumulative probability of conversion to MS of 50% within 15 years after onset of idiopathic optic neuritis. If there are no demyelinating lesions on brain MRI at first onset, the conversion rate remains at 25%, but if there is one or more lesions, it reaches 78%.

In children, the peak age of onset is 9–10 years, and younger children tend to present with bilateral and severe visual impairment, especially those under 5 years old. The conversion rate to pediatric MS has been reported as approximately 30% by Adachi et al. and 16% by Mizota et al.

The annual incidence of MOGAD is estimated to be 1.6–4.8 per million people. ¹⁾

Q If I develop optic neuritis, will I get multiple sclerosis in the future?

A

Approximately 50% of idiopathic optic neuritis cases convert to MS within 15 years. However, if there are no demyelinating lesions on brain MRI at first onset, the conversion rate remains at 25%. After onset, risk assessment using brain MRI and follow-up in collaboration with a neurologist is important.

2. Main Symptoms and Clinical Findings

Swelling of the optic disc associated with optic neuritis

Wikimedia Commons. File:Optic_Neuritis.png. License: CC BY-SA.

Fundus photographs of a 34-year-old woman who developed decreased vision in the right eye (OD 2/60) followed by the left eye (OS 6/24) after a febrile illness, with central scotomas in both eyes and a relative afferent pupillary defect (RAPD) in the right eye. This corresponds to the “central scotoma” discussed in the section “2. Main Symptoms and Clinical Findings”.

Subjective Symptoms

It presents with an acute onset pattern, and the following symptoms are characteristic:

• Acute unilateral visual loss: Progresses over several days to about 2 weeks. Visual function is worst around 1 week after onset.
• Eye pain / pain on eye movement: Seen in about 50–60% of cases in Japan. May appear a few days before visual loss.
• Visual field defects: Central scotoma or centrocecal scotoma are common, but altitudinal hemianopia may also occur. Diffuse defects are also frequent.
• Color vision abnormality: Decreased saturation of red color is characteristic.
• Uhthoff phenomenon: Transient visual loss or blurring after an increase in body temperature (e.g., hot bath, exercise). Appears within minutes and resolves within 1 hour.
• Phosphenes: Perception of light flashes
• Pulfrich phenomenon: Altered depth perception of moving objects

Clinical Findings

• Relative afferent pupillary defect (RAPD): Most important finding. Positive when unilateral or asymmetric. In optic neuritis, it may be abnormal even with mild dysfunction. Check with a condensing lens and slit lamp before dilation.
• Degree of visual impairment: In ONTT, visual acuity ≥1.0 in 10%, 0.5–1.0 in 25%, 0.1–0.5 in 29%, and worse in 36%.
• Fundus findings: In anterior optic neuritis, optic disc hyperemia and swelling are seen, with hyperfluorescence on fluorescein angiography. In retrobulbar optic neuritis, the fundus is normal early, with pallor after 4–6 weeks.
• Internuclear ophthalmoplegia: Occurs in MS patients due to demyelination of the medial longitudinal fasciculus.
• Retinal vascular sheathing and peripheral uveitis: Seen in 5–10% of MS patients.

Findings Suggesting Atypical ON

If the following signs are present, suspect atypical optic neuritis and perform a detailed etiological workup.

• Age outside 15–45 years (under 18 or over 50)
• Simultaneous bilateral onset
• Progression of symptoms beyond 2 weeks after onset
• Steroid-dependent course
• Presence of systemic symptoms

Clinical features by disease type

Feature	MOG-ON	AQP4-ON	MS-ON	CRION
Sex ratio (M:F)	1:1	1:7–9	1:3	1:1.7–2.3
Bilateral involvement	31–84%	13–82%	Extremely rare	Present
Papilledema	45–92%	7–52%	11–14%	Mild
Eye pain	73–92%	28–50%	10–46%	Present
Worst visual acuity	Moderate to severe	Moderate to severe	Mild to moderate	Variable
Recovery	Good	May be poor	Good	Steroid-dependent

Source: Jeyakumar N, et al. Eye. 2024¹⁾

Pediatric-specific findings

In pediatric optic neuritis, typical papillitis with redness and swelling of the optic disc is more common than retrobulbar optic neuritis seen in adults. The inflammation extends along the entire length of the optic nerve, not just the disc. Bilateral involvement occurs in 50–75% of cases, and anterior optic neuritis type accounts for 50–75%.

Q What is Uhthoff's sign?

A

Uhthoff’s sign is a phenomenon of transient visual disturbance associated with an increase in body temperature. Patients notice decreased vision or blurred vision after bathing or exercise. It appears within minutes and resolves within one hour. It is known in optic neuritis associated with MS but has also been reported in other optic neuropathies and is not specific to MS.

Q How does anti-AQP4 antibody-positive optic neuritis differ from typical optic neuritis?

A

Anti-AQP4 antibody-positive optic neuritis is a refractory subtype accounting for about 10% of idiopathic optic neuritis. Compared to typical optic neuritis, visual acuity at onset is worse, response to steroid therapy is poor, and recurrence is more frequent. It also tends to become bilateral. Measurement of serum anti-AQP4 antibodies is essential for diagnosis.

3. Causes and risk factors

In idiopathic cases suspected to have an autoimmune mechanism, inflammatory cells such as microglia infiltrate the optic nerve and cause inflammation. Repeated inflammation leads to cumulative damage to nerve fibers and progression to optic atrophy.

A hypothesis has been proposed that viral infection triggers an autoimmune reaction, and viral antibodies against measles, varicella, influenza, etc., are detected in the cerebrospinal fluid of some patients. In children, an association with ADEM (acute disseminated encephalomyelitis) accompanied by fever and headache is known.

Risk Factors

• Sex: More common in women (male-to-female ratio approximately 1:2 to 1:3)
• Age: Most common between 20 and 45 years old
• Prodromal symptoms: May be preceded by an influenza-like illness
• MS patients: Up to 75% experience at least one episode of ON in their lifetime. Autopsy studies show optic nerve lesions in up to 90%.

Vaccination and infection have been reported as triggers for MOGAD onset, and mechanisms such as bystander activation leading to breakdown of immune tolerance are suspected. ¹⁾

There are reports of ON onset after COVID-19 infection or vaccination. The median time from vaccination to ON onset was 18 days, and 14 out of 55 cases were MOG-IgG positive. ¹¹⁾

When to See a Doctor

There is no established method to definitively prevent optic neuritis. If you suddenly have blurred vision in one eye or pain when moving your eye, see an ophthalmologist promptly. Especially if you have vision loss in both eyes or visual impairment that does not improve after two weeks, a thorough examination is necessary.

4. Diagnosis and Examination Methods

Optic neuritis is a clinical diagnosis. It is diagnosed based on a combination of acute unilateral vision loss, eye movement pain, positive RAPD, and visual field defects.

Basic Tests

• Visual acuity test: Evaluate corrected distance and near visual acuity
• Pupillary light reflex test (swinging flashlight test): Essential for detecting RAPD
• Visual field test: Use automated perimetry to detect central scotomas and nerve fiber layer defects
• Color vision and contrast sensitivity tests
• Critical flicker frequency (CFF): Decreased
• Fundus examination: Check for optic disc swelling

Imaging tests

• Orbital MRI: Coronal fat-suppressed STIR and contrast-enhanced T1-weighted images. Evaluate optic nerve enlargement, hyperintensity, and enhancement.
• Brain MRI FLAIR: Assess for demyelinating lesions in the brain. Essential for evaluating MS comorbidity and future risk of developing MS.

Typical ON and atypical ON differ in MRI findings as follows.

Feature	Typical ON (MS-related)	Atypical ON
Enhancement pattern	Short segment enhancement	Long segment enhancement (≥1/2)
Lesion location	Anterior (retrobulbar optic nerve)	Extends posteriorly (optic chiasm and tract)
Optic nerve sheath	No contrast enhancement	Contrast enhancement of optic nerve sheath and orbital fat

Comparison of imaging features of NMOSD-ON, MOG-ON, and MS-ON:

Feature	NMOSD-ON	MOG-ON	MS-ON
Affected pattern	Bilateral	Bilateral	Unilateral
Predilection site	Intracranial and optic chiasm	Retrobulbar (anterior)	Retrobulbar and intracanalicular
Lesion length	Long	Long	Short segment
Optic nerve sheath enhancement	Rare	Positive in 50%	Not reported

Source: Jeyakumar 2024¹⁾; Cacciaguerra & Flanagan⁴⁾

OCT (Optical Coherence Tomography)

Measures peripapillary retinal nerve fiber layer (pRNFL) thickness. In the acute phase, pRNFL thickening is observed (MOG-ON median 164 μm vs MS-ON 103 μm). In the chronic phase, pRNFL thinning occurs, and the number of relapses correlates with pRNFL reduction. Visual field mean deviation is significantly worse below a pRNFL threshold of 50 μm. ¹⁾

Visual Evoked Potentials (VEP)

P100 latency prolongation is observed. This finding reflects demyelination.

Antibody Testing

If the course is atypical, measure the following.

• Anti-AQP4 antibody: Covered by insurance in 2013. Early evaluation is important in cases of steroid resistance or recurrent relapses.
• Anti-MOG antibody (MOG-IgG): Serum testing by live cell-based assay is recommended. Fixed CBA has inferior sensitivity and specificity.
  • The 2023 international diagnostic criteria for MOGAD define a definite diagnosis as positive CBA plus core clinical phenotype plus exclusion of alternative diagnoses. In cases of low titer, at least one supportive clinical/MRI feature is required ²⁾.
  • Validation of these criteria: sensitivity 96.5%, specificity 98.9%, accuracy 98.5% ³⁾.

MS diagnosis by McDonald criteria

Evaluate the possibility that optic neuritis is the initial symptom of MS. Diagnosis is made by demonstrating dissemination in time and space of inflammatory demyelinating lesions in the central nervous system and excluding other diseases. Dissemination in space can be demonstrated if T2 hyperintense lesions are present in at least two of four areas: periventricular, cortical/juxtacortical, infratentorial, and spinal cord.

Differential diagnosis

Category	Main differential diagnoses	Key points for differentiation
Demyelinating	MS-related optic neuritis, NMO	Antibody testing, MRI
Immune-mediated	CRION, sarcoidosis, SLE	Steroid dependence, systemic findings
Infectious	Syphilis, herpes, tuberculosis	Must be ruled out before steroids
Hereditary	Leber hereditary optic neuropathy	Young male, bilateral, painless → genetic testing
Drug-induced	Ethambutol, linezolid	No enhancement on MRI
Vascular	Non-arteritic anterior ischemic optic neuropathy	Elderly, usually painless, partial pale disc edema
Pediatric	ADEM	Accompanied by fever, headache, altered consciousness

There have been reports of cases diagnosed with retrobulbar optic neuritis that were actually compressive optic neuropathy due to orbital lymphoma. If atypical features are present, steroids should not be administered casually, and a thorough examination should be performed. ⁹⁾

Examination in Children

Usually, FA (fluorescein angiography), CFF, and kinetic perimetry performed in adults are not suitable for children; diagnosis is made by fundus findings and head MRI.

Q What are the MRI points to distinguish typical from atypical optic neuritis?

A

In typical ON, contrast enhancement is seen only in a short segment of the optic nerve. In contrast, atypical ON shows findings such as long-segment contrast enhancement (more than half the length), posterior extension (to the optic chiasm and optic tract), and enhancement of the optic nerve sheath. These MRI findings are directly linked to the differential diagnosis of the underlying disease.

5. Standard Treatment

Natural Course and Treatment Goals

The visual prognosis of idiopathic optic neuritis is good. In more than 90% of optic neuritis cases, visual acuity improves with observation or systemic steroid administration. According to the long-term results of the ONTT, visual acuity at 1 year after onset is 0.5 or better in 93% and 1.0 or better in more than 70%.

Mild Cases / Observation

In idiopathic optic neuritis with relatively good corrected visual acuity, oral mecobalamin 1,500 μg/day (off-label use) may be used for observation.

Typical ON

First-line treatment: Steroid pulse therapy (methylprednisolone 1,000 mg/day IV drip infusion for 3 days). Off-label use.

After pulse: Start oral prednisolone at 0.5 mg/kg/day, then taper by 5–10 mg every 3–4 days.

If first pulse ineffective: Administer a second pulse after an interval of 4–5 days.

Effect: Shortens the recovery period, but there is no significant difference in final visual acuity at 1 year after onset.

Active indication: Bilateral onset, severe visual dysfunction, only functional eye, recurrent cases, MRI demyelinating plaques present, or patient strongly desires early improvement.

Anti-AQP4 antibody-positive ON

Acute phase: Steroid pulse therapy (first-line).

If ineffective: Repeat pulse after 3–4 days → if still ineffective → consider plasma exchange.

Plasma exchange: Simple plasma exchange > double filtration plasmapheresis > immunoadsorption (in order of efficacy). One course: 5–6 sessions.

Maintenance therapy: Prednisolone 5–10 mg/day + azathioprine 50–100 mg/day.

Note: Unlike idiopathic ON, prevention of recurrence with oral steroids is important.

Anti-MOG antibody-positive ON (MOGAD)

Acute phase: Steroid pulse therapy is highly effective. Complete recovery 50%, partial recovery 44%. ¹³⁾

Relapse tendency: Strong steroid dependence; 70% relapse during tapering of oral prednisolone (especially <10 mg/day or within 2 months after discontinuation). ¹⁴⁾

Maintenance therapy: IVIg (≥1 g/kg every 4 weeks significantly reduces relapse). ¹⁵⁾ Rituximab may be less effective than for AQP4-ON.

Timing of treatment initiation: Usually after the second attack (because >50% are monophasic).

CRION (Chronic Relapsing Inflammatory Optic Neuropathy)

Acute phase: Methylprednisolone IV 1 mg/kg × 3–5 days.

Intermediate phase: Oral prednisone 1 mg/kg, then taper to minimum effective dose.

Long-term maintenance: Azathioprine, methotrexate, cyclophosphamide, and mycophenolate mofetil are candidates. IVIG is also an option.

Note: Long-term continuation is necessary because stopping treatment leads to relapse.

Contraindications to Oral Steroid Monotherapy

Standard-dose (1 mg/kg/day) oral prednisolone monotherapy is not recommended because it was associated with a higher relapse rate compared to placebo or intravenous steroids in the ONTT.

Steroid Pulse Therapy in Children

Methylprednisolone 30 mg/kg/day for 3 days is administered. Visual prognosis is generally good.

Optic Neuritis Associated with ADEM

Aggressive steroid therapy is performed. If response to steroid pulse is poor, high-dose intravenous immunoglobulin or plasma exchange therapy are options.

Prevention of MS Relapse

In cases with MS, consider treatment for relapse prevention after visual improvement. In collaboration with a neurologist, consider disease-modifying drugs (interferon beta, glatiramer acetate, fingolimod, natalizumab, etc.).

Precautions and Side Effects in Treatment

• Steroid pulse therapy requires caution for hyperglycemia, peptic ulcers, and induction of infections.
• Standard-dose oral steroid monotherapy is not recommended due to increased relapse rate.
• Before systemic steroid administration, always rule out infections such as hepatitis B.
• Administering steroids without excluding infectious ON may worsen the condition.
• In CRION, abrupt discontinuation of immunosuppressive therapy can lead to relapse and permanent vision loss.

Q Does steroid treatment affect final visual recovery?

A

According to the ONTT results, steroid pulse therapy shortens recovery time but does not significantly affect final visual acuity one year after onset. In idiopathic optic neuritis, 93% of untreated patients recover to visual acuity of 0.5 or better. However, anti-AQP4 antibody-positive cases are steroid-resistant, requiring aggressive treatment including early plasma exchange.

Q How long should immunosuppressive therapy be continued?

A

Since CRION is a disease that relapses upon treatment discontinuation, long-term immunosuppressive therapy is often necessary even after symptom remission. After identifying the minimum effective dose of steroids, non-steroidal immunosuppressants are added, and the treatment regimen is individually designed.

6. Pathophysiology and Detailed Mechanisms

Pathology of Idiopathic (Autoimmune) Optic Neuritis

In idiopathic cases suspected to involve autoimmune mechanisms, inflammatory cells such as microglia infiltrate the optic nerve and cause inflammation.

1. Immune-mediated demyelination: The myelin sheath of the optic nerve is attacked by autoimmune mechanisms. Saltatory conduction becomes impossible, leading to impaired axonal impulse conduction.
2. Axonal degeneration: After demyelination, axons of retinal ganglion cells begin to degenerate.
3. Phagocytosis by macrophages: Macrophages remove residual myelin.
4. Gliosis: Astrocytes proliferate and form glial scars. The term “sclerosis” in multiple sclerosis originates from this process.

Repeated episodes of optic nerve inflammation cause cumulative damage to nerve fibers, leading to optic atrophy.

Mechanism of Anti-AQP4 Antibody-Positive Optic Neuritis

Anti-AQP4 antibodies bind to complement and attack astrocytes, the glial cells in the optic nerve, leading to disease onset. Astrocytes in the optic nerve and optic chiasm highly express AQP4, making them susceptible targets.

Mechanism of anti-MOG antibody-positive ON

MOG-IgG (mainly IgG1 subclass) targets MOG on the CNS myelin surface. Complement pathway activation and antibody-dependent cellular phagocytosis are involved in demyelination. However, complement activation is weaker compared to AQP4-IgG. In MOGAD, CD4-positive T cells and macrophages predominate, whereas in MS, CD8-positive T cells are predominant. ¹⁾⁴⁾

Although MOG is not expressed in the retina, MOG-ON causes damage to retinal ganglion cells. Glutamate toxicity and vulnerability of the blood-brain barrier at the optic nerve head have been proposed as mechanisms. ¹⁾

The mechanism by which IL-6 increases blood-brain barrier permeability and promotes plasmablast differentiation is also attracting attention.

Pathological positioning of CRION

CRION was originally proposed as a syndrome encompassing steroid-responsive and relapsing optic neuritis. ⁵⁾ Subsequent antibody testing in CRION cohorts revealed that up to 22% are AQP4-IgG positive and up to 25% are MOG-IgG positive. ⁶⁾⁷⁾⁸⁾ Therefore, CRION is considered a syndromic diagnosis encompassing heterogeneous etiologies including MOG antibody-associated optic neuritis and AQP4 antibody-associated optic neuritis.

Triggers of onset

The hypothesis that viral infection triggers autoimmune reactions has been proposed. There are reports of detection of varicella-zoster virus and herpes simplex virus DNA in the cerebrospinal fluid of some ON patients. In MOGAD, breakdown of immune tolerance due to vaccination or infection (bystander activation, molecular mimicry) is assumed. ¹⁾

7. Latest research and future perspectives

For patients: Please read

The following content is currently under research or in clinical trials and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

Novel biologics for AQP4-positive NMOSD

Biologics with Level 1 evidence have emerged for AQP4-positive NMOSD. ⁴⁾

• Eculizumab: C5 inhibitor. Phase 3 showed 94% reduction in relapse risk
• Ravulizumab: C5 inhibitor (improved version of eculizumab). Phase 3 showed 98.6% reduction in relapse risk
• Inebilizumab: CD19-targeted B-cell depleting agent. Reduces relapse risk by 77% in AQP4-positive NMOSD.
• Satralizumab: IL-6 receptor inhibitor. Reduces relapse risk by 74–79% in AQP4-positive NMOSD. Can be administered subcutaneously at home.

Both have established evidence for AQP4-positive NMOSD, but their indications for MOGAD are not yet established.

Clinical trials for MOGAD

Phase 3 RCTs of satralizumab (NCT05271409) and rozanolixizumab (NCT05063162) are ongoing. Off-label use of tocilizumab (IL-6 receptor antibody) has been reported to prevent relapse for up to 29 months. ¹⁾

COVID-19-associated optic neuritis

Cases of demyelinating optic neuritis following COVID-19 infection have been reported. Jossy et al. (2022) reported cases of optic neuritis during the recovery phase of infection, and all patients recovered vision with steroid pulse therapy. ¹⁰⁾

Reports of ON onset after COVID-19 vaccination have accumulated, with a median interval of 18 days from vaccination to ON onset. Among 55 cases, 14 were MOG-IgG positive, and none were AQP4-IgG positive. ¹¹⁾ Cases of MOG antibody-associated optic neuritis after SARS-CoV-2 infection have also been reported. ¹²⁾

Redefinition of the disease concept of CRION

With the widespread use of antibody testing for MOG-IgG and AQP4-IgG, some cases previously diagnosed as CRION are being reclassified as MOGAD or NMOSD. It is expected that the disease concept will be redefined based on antibody profiles in the future.

8. References

1. Jeyakumar N, Lerch M, Dale RC, Ramanathan S. MOG antibody-associated optic neuritis. Eye. 2024;38:2289-2301.
2. Banwell B, Bennett JL, Marignier R, et al. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. Lancet Neurol. 2023;22:268-82.
3. Varley JA, Champsas D, Prossor T, et al. Validation of the 2023 International Diagnostic Criteria for MOGAD in a Selected Cohort of Adults and Children. Neurology. 2024.
4. Cacciaguerra L, Flanagan EP. Updates in NMOSD and MOGAD Diagnosis and Treatment. Neurol Clin. 2024.
5. Kidd D, Burton B, Plant GT, Graham EM. Chronic relapsing inflammatory optic neuropathy (CRION). Brain. 2003;126:276-84.
6. Petzold A, Woodhall M, Khaleeli Z, et al. Aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in immune-mediated optic neuritis at long-term follow-up. J Neurol Neurosurg Psychiatry. 2019;90:1021-6.
7. Lee H-J, Kim B, Waters P, et al. Chronic relapsing inflammatory optic neuropathy (CRION): a manifestation of myelin oligodendrocyte glycoprotein antibodies. J Neuroinflammation. 2018;15:302.
8. Petzold A, Pittock S, Lennon V, et al. Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis. J Neurol Neurosurg Psychiatry. 2010;81:109-11.
9. McElhinney K, Rhatigan M, Tsvetanova Z, et al. Beware the retrobulbar optic neuritis diagnosis. Case Rep Ophthalmol. 2022;13:453-458.
10. Jossy A, Jacob N, Sarkar S, et al. COVID-19-associated optic neuritis - A case series and review of literature. Indian J Ophthalmol. 2022;70:310-6.
11. Bhatti MT, Gilbert AL, Watson G, et al. Shot in the dark. Surv Ophthalmol. 2023;68:821-829.
12. Bosello F, Marastoni D, Pizzini FB, et al. Atypical MOG antibody-associated optic neuritis and acute demyelinating polyneuropathy after SARS-CoV-2 infection. J Neuroimmunol. 2023;375:578011.
13. Jarius S, Ruprecht K, Kleiter I, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation. 2016;13:280.
14. Ramanathan S, Mohammad S, Tantsis E, et al. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry. 2018;89:127-37.
15. Chen JJ, Flanagan EP, Jitprapaikulsan J, et al. MOG antibody-positive optic neuritis: clinical characteristics, radiologic clues, and outcome. Am J Ophthalmol. 2018;195:8-15.