How is optic neuritis in multiple sclerosis (MS) diagnosed?

Updated: Feb 21, 2019
  • Author: Fiona Costello, MD, FRCP; Chief Editor: Hampton Roy, Sr, MD  more...
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In cases characterized by a typical history and expected examination findings, optic neuritis can be reliably diagnosed based on clinical grounds. However, certain red flags should raise concern for a potential mimic and therefore prompt additional investigations (see Table 3). [14]

For example, young men who present with painless bilateral sequential or simultaneous optic nerve dysfunction should undergo testing for LHON. Middle-aged women who develop unilateral or bilateral optic neuritis should be evaluated for NMO because the management of optic neuritis in patients with NMO differs from that of patients with MS. Additional features that should increase the clinical suspicion for NMO include poor clinical recovery, lack of typical MRI findings for MS, cerebrospinal fluid (CSF) pleocytosis, and manifestations of transverse myelitis. Previously, NMO was diagnosed based on clinical parameters and spinal MRI, which tend to show extensive longitudinal lesions of three or more vertebral body segments. In recent years, the aquaporin 4 immunoglobulin G (IgG) antibody has been relied on to expand the clinical and neuroimaging spectrum of NMO. [20] The criteria for NMO spectrum disorders (NMOSD) devised by Wingerchuk and colleagues facilitate the diagnosis in patients who have not experienced clinical involvement of optic nerves or spinal cord. [20]

Some pediatric patients with recurrent optic neuritis harbor antibodies against myelin oligodendrocyte glycoprotein (anti-MOG antibodies). Anti-MOG antibodies can be found in patients with NMOSD features who are aquaporin 4–seronegative. These patients tend to be younger, present with positive oligoclonal bands in CSF, and develop brain MRI abnormalities during their disease course. A 2011 study reported that the mean time to the second attack was longer in the anti-MOG antibody–positive group. [21] Therefore, anti-MOG antibodies can serve as a diagnostic and potentially prognostic tool, and testing should be considered in aquaporin 4–seronegative patients with the NMO phenotype. [21] The distinction between optic neuritis associated with NMOSD versus MS is important because patients with the former often require long-term treatment with immunosuppressive drugs to obtain disease control.

Table 3. Differential Diagnoses of Optic Neuritis (Open Table in a new window)


Clinical Features

Investigations to Consider


Painless, altitudinal visual field defect is common, vision loss noted upon awakening, vascular risk factors, phosphodiesterase type 5 inhibitor use, nocturnal antihypertensive use, sleep apnea, physiological disc at risk, patients with NAION have optic disc edema acutely

Sleep study, 24-hour blood pressure monitoring, investigations for hypertension and diabetes

Compressive optic neuropathy (pituitary lesions, meningiomas, aneurysm)

Painless, progressive vision loss, color loss disproportionate to visual acuity deficit, nonglaucomatous optic disc cupping, temporal visual field cut, bilateral visual field involvement

Cranial and orbital MRI/MRA or CT/CTA

Infectious optic neuropathies (eg, tuberculosis, syphilis, Lyme disease, among others)

Associated uveitis, papillitis or retrobulbar optic neuropathy, macular star, infectious symptomatology

Serum/CSF culture/sensitivity; specific serological testing for syphilis, Lyme, Bartonella henselae, HIV, toxoplasmosis, viral hepatitis B and C; Epstein-Barr virus; histoplasmosis; tuberculin testing; chest imaging; serum sedimentation rate, C-reactive protein

Inflammatory/demyelinating optic neuropathies not associated with MS or an underlying systemic disorder: NMO, CRION, ADEM, anti-MOG–associated optic neuritis

Poor recovery, unilateral or bilateral optic neuritis, associated transverse myelitis, recurrent symptoms

Brain MRI, cervical spine MRI, anti-NMO antibody testing

Genetic optic neuropathies (LHON, autosomal-dominant optic neuropathy)

Bilateral vision loss, painless, poor recovery, family history

Genetics referral with specific mutation testing

Toxic/nutritional (tobacco-alcohol amblyopia and Cuban and Tanzanian epidemic optic neuropathies)

Bilateral optic nerve involvement, history of drug use (ethambutol, selenium, amiodarone), restricted nutritional intake, glue sniffing, methanol ingestion

Vitamin B-12 levels, toxic screen

Sarcoid optic neuropathy

Steroid responsive, poor recovery, systemic symptoms and signs

Chest imaging, serum ACE, Gallium scan, tissue diagnosis, bronchoalveolar lavage, soluble IL-2 receptor

Connective tissue/vasculitic optic neuropathy (lupus, Wegener granulomatosis, Sjögren syndrome, Behçet disease)

Steroid responsive, associated systemic symptoms and signs

Serum ESR, Sjögren specific antibodies, CRP, ANCA, ENA panel, ANA

Orbital inflammation/optic perineuritis

Orbital signs (proptosis)

MRI or CT orbital imaging, blood work including TSH ANCA, CRP, ESR, ACE

Uveitis/posterior scleritis

Severe pain, floaters, vitreous reaction

Fluorescein angiography, B-scan ultrasonography of orbits

Autoimmune optic neuropathy (Similar to CRION)

Steroid responsive

Skin biopsy for immunoglobulin deposition

Big blind spot syndromes

Blind spot on visual field testing, painless, photopsias, bilateral ocular involvement

Full-field/multifocal ERG, fluorescein angiography

Abbreviations: ACE = angiotensin converting enzyme; ADEM = acute disseminated encephalomyelitis; anti-DS DNA = anti-double-stranded DNA; anti-MOG = anti-myelin oligodendrocyte glycoprotein; ANA = anti-nuclear antigen; AON = autoimmune optic neuropathy; CRION = chronic relapsing inflammatory optic neuropathy; CSF = cerebrospinal fluid; ESR = erythrocyte sedimentation rate; FTA-ABS = fluorescent treponemal antibody absorption; HIV = human immunodeficiency virus; MRI = magnetic resonance imaging; NAION = nonarteritic anterior ischemic optic neuropathy; NMO-IgG = neuromyelitis optica immunoglobulin G; PCR = polymerase chain reaction; VDRL = Venereal Disease Research Laboratory

Table 3. Differential Diagnoses of Optic Neuritis (Modified From Table 2-1 in Costello F. Inflammatory optic neuropathies. Continuum (Minneap Minn). Aug 2014; 20 (4 Neuro-ophthalmology): 816-37.] [14]

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