Optic Neuritis–How to assess for optic neuritis and ddx TESTING

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Authors: Sravanthi Vegunta, MD and Meagan Seay, DO
Date: 05/06/2021

Introduction:

Optic neuritis is inflammation of the optic nerves that can be caused by a variety of conditions including demyelination, vasculitis, infection, granulomatous disease, other autoimmune disorders, and paraneoplastic disorders. The most common cause of optic neuritis is typical optic neuritis that may be associated with multiple sclerosis or may be idiopathic.1

Presentation:

According to the optic neuritis treatment trial, 64% of patients have unilateral vision loss of >20/200, and 92% have associated pain with eye movements. The fundus examination is typically normal in patients as 2/3 have retroorbital optic nerve inflammation and only 1/3 have papillitis or optic nerve head swelling.2 Among those patients who present with edema, the severity is usually Grade 1-3 without associated hemorrhages or exudates. The presence of the latter findings should prompt evaluation for ischemic, infectious, or granulomatous inflammation optic neuritis or neuroretinitis.2,3,4 Myelin oligodendrocyte glycoprotein (MOG)-antibody associated optic neuritis is more likely to present with optic disc edema.5

Patients should be asked a neurological, rheumatological, and infectious disease review of systems to determine if there are any atypical features of their presentation. Associated findings of weakness, numbness or parasthesias may prompt evaluation and spinal imaging. Arthritis or shortness of breath, may prompt evaluation for sarcoidosis. Whereas fevers and/or multiple cranial neuropathies may prompt further evaluation for infection, inflammatory conditions, or leptomeningeal carcinomatosis.1,6

Differential:

  • Optic neuritis-clinically isolated syndrome
  • Optic neuritis associated with multiple sclerosis
  • MOG-Ab associated optic neuritis
  • Aquaporin-4 Ab (AQP4) – associated optic neuritis
  • Systemic lupus associated optic neuritis
  • Rheumatoid arthritis associated optic neuritis
  • Granulomatosis with polyangiitis associated optic neuritis
  • Neurosarcoidosis with optic neuritis
  • Infectious optic neuritis—syphilis, tuberculosis, herpes viruses,
  • Paraneoplastic optic neuritis
  • Optic perineuritis – inflammation of the optic nerve sheath
    • Syphilis
    • Tuberculosis
    • Sarcoidosis
    • Lymphoma
    • Crohns
    • Granulomatosis with polyangiitis
    • MOG-Ab
    • Optic nerve sheath meningioma
    • Giant Cell Arteritis
    • IgG4
  • Consider other causes of disc edema
    • NAION/AAION
    • Neuroretinitis – macular star may develop a couple weeks later
    • Leber’s hereditary optic neuropathy – usually minimal edema
    • Diabetic papillitis
    • Elevated intracranial pressure – more likely to be bilateral
    • Posterior uveitis
    • Glial fibrillary acidic protein Ab (GFAP-IgG)
    • Medications (PDE5 inhibitors, amiodarone)

Evaluation:

An ophthalmologic evaluation should include visual acuity, pupillary exam and careful testing for a relative afferent pupillary defect, color vision testing, red desaturation testing in each visual field, confrontation visual fields, and fundus examination to evaluate for vitreous cell, macular involvement, and severity of optic nerve edema. OCT RNFL, optic disc photos, and sometimes macular OCT can help to follow the level of swelling over time. If anomalous optic nerves are suspected OCT EDI can be used to evaluate for optic disc drusen or B-scan orbital ultrasound. Visual evoked potential can be used to help distinguish between a demyelinating process (slowed P100 time) versus an axonal injury (drop in amplitude).

Patients should have an MRI of the orbits and brain with contrast to evaluate for optic nerve enhancement and evidence of cerebral demyelination. MRI can help to evaluate for signs of atypical optic neuritis. Optic nerve lesions >3mm, bilateral optic nerve involvement, optic nerve sheath enhancement, and extension to the chiasm are characteristic of atypical optic neuritis.6 Patients with neuromyelitis optic spectrum disorder (NMOSD) can have periependymal, forniceal, and hypothalamic lesions.7 Infection, granulomatous disease, or leptomeningeal disease may present with meningeal enhancement. If there is concern for demyelinating disease, imaging of the spine with MRI is indicated to assess for further lesions. Consideration is given to performing a lumbar puncture based on the imaging findings and clinical picture. If there is good recovery of vision with a normal brain MRI, lumbar puncture may not be indicated. Likewise, if the MRI is characteristic of and fulfills criteria for MS (see McDonald diagnostic criteria below) and there are no other red flag signs or symptoms, a lumbar puncture may be deferred.8,9 A lumbar puncture may be indicated when imaging is suggestive of MS, though does not yet meet criteria, or if there are other concerning features of the clinical picture, such as infection. Serum labs should include AQP4-IgG antibody (evaluating for NMOSD) and likely MOG-IgG antibody. Additional labs for underlying rheumatologic, inflammatory, or infectious etiologies should be considered based on the clinical scenario.

NMOSD (see diagnostic criteria below) includes AQP4-IgG-seropositive patients who have had some clinical features of NMO such as transverse myelitis or bilateral/recurrent optic neuritis and who are at high risk for future inflammatory episodes. NMOSD also includes typical NMO plus cerebral, diencephalic, and brainstem lesions; coexisting autoimmune disorders; and opticospinal MS, an Asian phenotype of MS. Prior to the identification of MOG-IgG antibody, optic neuritis associated with MOG-Ab associated disease (MOGAD) was previously thought to be a subcategory of NMOSD.7 Additionally, nearly 17% of patients previously diagnosed with chronic relapsing inflammatory optic neuropathy, a steroid-dependent optic neuritis, have been found to have MOG-IgG positivity.10

Among all optic neuritis patients, 15% have MOG-IgG positivity, and 2% have AQP4-IgG positivity. During an episode of optic neuritis, most patients present with positive antibody titers. However, a minority of patients who have negative antibody testing may become positive when they are retested.6,14

Treatment:

The optic neuritis treatment trial showed us that patients with typical optic neuritis have the same recovery with or without treatment. Patients who received high dose IV steroids (total of 1g/day x 3 days followed by oral taper) experienced quicker recovery, however.2 More recently, bioequivalent mega dose oral prednisone (1250 mg/day x 3-5 days) has been used for optic neuritis/MS relapses. While it is common to treat typical optic neuritis with high dose steroids, one should discuss with the patient the risks of steroids, along with the evidence indicating that long-term outcomes are unchanged.

The importance of identifying atypical optic neuritis is the change in the approach to treatment. MOG-Ab associated optic neuritis is commonly very responsive to steroids with good recovery, though may have a higher risk of relapse.11 MOG-Ab patients with only one episode of optic neuritis with good recovery may be monitored without disease modifying treatment. MOG-Ab patients with additional lesions, incomplete recovery, or recurrent disease are more likely to need long-term immunosuppression.12 The presence of AQP4-Ab portends a worse prognosis and is often minimally responsive to steroids. Early consideration of plasma exchange should occur in a patient with optic neuritis with known AQP4-Ab or with high suspicion (see table 1 for characteristics of typical optic neuritis, AQP4-Ab, and MOG-Ab). All patients with AQP4-Ab should be treated long-term with immunosuppression, such as rituximab, azathioprine, or complement inhibitors. It is important to note that some MS DMTs worsen AQP4-Ab related disease.12-14

Other causes of optic neuritis such as infection or autoimmune diseases require treatment of the underlying disease itself.

Comparison of clinical features of optic neuritis1-17

Optic Neuritis Table 1

Multiple Sclerosis Diagnostic Criteria: McDonald Criteria

Optic Neuritis Table 2

NMOSD Diagnostic Criteria for AdultsMcDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul;50(1):121-7.

Wingerchuk, D. M. et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology vol. 85 177–189 (2015).

References:

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