Optic neuritis is an inflammation of the optic nerve(s) resulting in impaired visual function and often retroorbital pain worse with eye movements.

Optic papillitis

Retrobulbar neuritis

• Presentation with acute (days) or subacute (weeks) vision loss, often accompanied by retroorbital pain that worsens with eye movements. Visual field defects commonly are present; they can be either diffuse or discrete scotomas and are nonspecific. Fundus examination shows mild disc edema in approximately one third of affected eyes, which is typically less prominent than the disc swelling associated with papilledema (Fig. E1). In the majority of patients, the fundus appearance is normal.

• Marcus Gunn pupil (relative afferent pupillary defect [RAPD]): Consensual response is normal; however, when the flashlight is swung from the unaffected eye to the affected eye, the affected eye’s pupil paradoxically dilates in response to direct light.
• Decreased visual acuity.
• Unilateral (or bilateral with some diseases) visual field abnormalities-often a central scotoma (Fig. E2) or diffuse (in MS), or altitudinal (in NMOSD).
• Color desaturation; red is most often affected.
• Normal fundus examination in 66% of cases; disc edema is noted in 33% (more frequent and severe when associated with MOGAD, infectious, or granulomatous causes). Other abnormalities can include uveitis, periphlebitis, episcleritis, and retinitis. In neurosarcoidosis, the optic nerve head may exhibit a lumpy appearance suggestive of granulomatous infiltration, and there may be associated vitreitis (Fig. E3).
• May have movement or light induced phosphenes (flashes of light lasting 1 to 2 sec).
• Uhthoff phenomenon (benign exercise- or heat-induced deterioration of vision due to elevated core body temperature, lasting less than 24 h) is seen in some. Vision may also worsen in bright sunlight.
• Over time, the optic disc may atrophy and become pale.

An inflammatory response associated with infectious, paraneoplastic, or autoimmune disease (such as collagen vascular disease, granulomatous disease, MS, NMOSD, and MOGAD).

• Inflammatory: MS, NMOSD, MOGAD, sarcoidosis, granulomatosis with polyangiitis, lupus, Sjögren syndrome, acute disseminated encephalomyelitis, paraneoplastic (CRMP-5, CV-2), autoimmune optic neuropathy, autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy
• Infectious: Neurosyphilis, tuberculosis (TB), Lyme disease, HIV, cytomegalovirus, herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, West Nile virus, dengue fever, Bartonella henselae, Rickettsia spp., Toxocara spp., Q fever, histoplasmosis, toxoplasmosis, helminths, periorbital infections
• Ischemic: Anterior and posterior ischemic optic neuropathies, diabetic papillopathy, branch or central retinal artery or vein occlusion
• Drugs and toxins: Arsenic, methanol, ethambutol, cyclosporine, etc.
• Mitochondrial: Leber hereditary optic neuropathy, other mitochondrial

Thorough neurologic examination with dilated ophthalmoscopy

Acute optic neuritis is a clinical diagnosis based on presentation with classical features: Acute, painful, unilateral loss of vision associated with RAPD in a young person with no other apparent causes (such as trauma). In atypical cases, additional studies may be considered.

• CBC, antinuclear antibody (ANA), ACE, cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA), erythrocyte sedimentation rate (ESR)
• Consider HIV Ab, Lyme titer, rapid plasma reagin (RPR), Quantiferon TB gold, other autoimmune or infectious causes
• CSF studies: Can demonstrate pleocytosis, CSF-specific oligoclonal bands and IgG synthesis (more common with MS), GFAP-IgG (in autoimmune GFAP astrocytopathy)
• Bilateral or recurrent optic neuritis: Serum antiaquaporin-4 (AQP4) IgG (in NMOSD), serum and CSF MOG-IgG (in MOGAD), serum CRMP-5-IgG (in paraneoplastic disease)

• Contrast-enhanced MRI of the orbits (Fig. E4) with fat suppression and thin sections is highly sensitive in detecting acute or subacute optic neuritis, seen as enhancement of the optic nerve(s) (Fig. E5).
• Longitudinally extensive retrobulbar optic nerve involvement is common with NMOSD and MOGAD.
• Contrast-enhanced MRI of the brain should simultaneously be performed to assess for possible MS. Contrast-enhanced MRI of the cervical and thoracic spine should also be considered to assess for possible demyelinating disease.
• Visual evoked potentials: Tests the axonal transmission along the optic nerve. Prolonged P100 latency of the optic nerve(s) confirms the presence of optic neuropathy. Useful in confirming equivocal cases of optic neuritis.
• Optical coherence tomography (OCT): Can show peripapillary retinal nerve fiber layer (RNFL) thickening in acute optic neuritis, and peripapillary RNFL and macular thinning in chronic or recurrent optic neuritis. Useful to follow optic nerve atrophy objectively and longitudinally.

• Assure the patient that in most cases of typical optic neuritis, there is near-complete recovery of vision.

Treatment is with IV methylprednisolone (MP) 1000 mg daily for 3 days, followed by an oral prednisone taper (1 mg/kg/day) for 11 days. Plasma exchange can be considered in severe or refractory cases (such as in NMOSD). If an infectious cause is suspected, initiate appropriate antibiotic or antiviral treatment early.

Depends on the underlying cause. Consider starting disease-modifying treatment when there is increased risk of developing MS or other autoimmune disease. See topic “Multiple Sclerosis.”

Most often, vision is worst at the end of wk 1, followed by recovery over months. In the Optic Neuritis Treatment Trial (ONTT), 90% had 20/40 or better vision and 3% had 20/200 or worse vision at 1 yr. Of the initial group of patients with 20/200 or worse vision, only 5% remained in that group at 6 mo.

• To a neurologist for other neurologic signs and to assess the risk of developing MS. In the ONTT (Optic Neuritis Treatment Trial), the risk of developing MS after 15 yr was 72% with ≥1 lesion(s) on MRI, and 25% with a normal MRI.
• To an ophthalmologist for annual OCT testing, and when there are atypical features or a slowly progressing course. Refer urgently if other ocular pathology is present, if vision worsens or does not improve after several weeks, or if pain is severe.

Idiopathic Intracranial Hypertension (Related Key Topic)

Multiple Sclerosis (Related Key Topic)