Description

• Inflammation of the optic nerve (cranial nerve II)
• The most common form is acute demyelinating optic neuritis (ON), but other causes include infectious disease and systemic autoimmune disorders.
• Optic disc may be normal in appearance at onset (retrobulbar ON, 67%) or swollen (papillitis, 33%).
• Key features:
  • Abrupt visual loss (typically monocular)
  • Periorbital pain with eye movement (90%)
  • Pain in the distribution of the first division of the trigeminal nerve
  • Dyschromatopsia: color vision deficits
  • Relative afferent pupillary defect (RAPD)
• Usually unilateral in adults; bilateral disease more common in children
• Associated with multiple sclerosis (MS), presenting complaint (25% MS patients)
• In children, headaches are common.
• System(s) affected: nervous
• Synonym(s): papillitis, demyelinating optic neuropathy; retrobulbar ON

Epidemiology

Incidence

• 5/100,000 cases per year
• More common in whites than in other races
• Predominant age: 18 to 45 years; mean age of 30 years
• Predominant sex: female > male (3:1)

Etiology and Pathophysiology

• In both MS-associated and isolated monosymptomatic ON, the cause is presumed to be a demyelinating autoimmune reaction.
• Neuromyelitis optica (NMO) IgG autoantibody, which targets the water channel aquaporin-4
• Viral infections: measles, mumps, varicella-zoster, coxsackievirus, adenovirus, hepatitis A and B, HIV, herpes simplex virus, cytomegalovirus, SARS-CoV-2 (myelin oligodendrocyte glycoprotein [MOG] antibody-associated ON and myelitis in COVID-19) (1)
• Nonviral infections: syphilis, tuberculosis, meningococcus, cryptococcosis, cysticercosis, bacterial sinusitis, Group B Streptococcus, Bartonella, typhoid fever, Lyme disease, fungus
• Systemic inflammatory disease: sarcoidosis, systemic lupus erythematosus, vasculitis
• Local inflammatory disease: intraocular or contiguous with the orbit, sinus, or meninges
• Toxic: lead, methanol, arsenic, radiation
• Medications: ethambutol, chloroquine, isoniazid, chronic high-dose chloramphenicol, tumor necrosis factor α-antagonist, infliximab (Remicade), adalimumab (Humira), etanercept (Enbrel)

Genetics
Genetics: Some people have genetic mutations that increase their chance of ON (i.e., MS) and several immune-mediated inflammatory diseases (IMIDs).

Commonly Associated Conditions

• MS (common): ON is associated with an increased risk of MS.
• Other demyelinating diseases: Guillain-Barré syndrome, Devic NMO, multifocal demyelinating neuropathy, acute disseminated encephalomyelitis