Atypical Optic Neuritis

    • Optic nerve damage from inflammatory disorders other than multiple sclerosis (MS)
    • Common causes: idiopathic, sarcoidosis
    • Uncommon causes: neuromyelitis spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein (MOG) antibody-associated optic neuritis, cat scratch disease, syphilis, Lyme disease, other infectious and autoimmune meningitis, retinitis, uveitis, sinusitis, orbital inflammation, immune check point inhibitor-associated optic neuritis
    • Core clinical features
      • May affect one eye or both
      • Reduced visual acuity and/or nerve fiber bundle visual field defects
      • Afferent pupil defect in affected eye unless both eyes are equally affected
    • Possible accompanying clinical features
      • More pronounced optic disc elevation than in typical optic neuritis
      • Retinal hemorrhages, cotton wool spots, choroidal infiltrates, anterior chamber or vitreous cells, retinal infiltrates, serous detachment, exudates of macular star figure (“neuroretinitis”)
      • Elevated IGG4
      • Manifestations of systemic or neurologic infectious/inflammatory disorder other than MS
    • Possible imaging features
      • Enhancement and high T2/FLAIR signal affecting long segment of optic nerve, optic chiasm, spinal cord, meninges, hypothalamus, or area postrema (in NMOSD)
      • Enhancement of orbit soft tissues, paranasal sinuses, intracranial dura
      • No apparent lesions in periventricular or central cerebral white matter, as would be typical of MS
    • Papillitis
    • Typical optic neuritis
    • Non-arteritic ischemic optic neuropathy
    • Compressive optic neuropathy
    • Infiltrative (neoplastic) optic neuropathy
    • Leber hereditary optic neuropathy
    • Paraneoplastic optic neuropathy
    • Order NMO serum cell-based antibody assay (sensitivity 70%; specificity 100%) especially if
      • Optic neuritis is recurrent over short intervals
      • Vision does not recover within weeks
      • Patient displays severe nausea, vomiting, and intractable hiccups (“area postrema syndrome”)
      • MRI shows longitudinally-extensive enhancement in the optic nerve or spinal cord or enhancement in the aquaporin-rich diencephalic and brainstem regions
    • Order MOG antibody especially if
      • Optic neuritis is recurrent, bilateral, associated with optic disc edema, or is apparently corticosteroid-dependent
      • MRI shows longitudinally-extensive optic nerve and/or orbital soft tissue enhancement
    • Tip: cerebrospinal NMO and MOG antibody testing is not diagnostically helpful
    • Order appropriate imaging, blood and urine tests for systemic inflammatory disorders if you have excluded NMOSD and MOG-associated optic neuritis
    • Perform lumbar puncture as indicated
    • Treat according to diagnosis
      • NMOSD: high-dose corticosteroids, plasmapheresis acutely; rituximab or eculizumab prophylactically
      • MOG: high-dose corticosteroids acutely; mycophenolate or other immunomodulatory agents prophylactically
      • Cat scratch disease: oral doxycycline, corticosteroids
      • Sarcoidosis: prednisone or other immunomodulatory agents
      • Syphilis: high-dose penicillin
      • Other infections and non-infectious inflammatory disorders: as appropriate
    • Early immunomodulatory therapy, including plasmapheresis, is beneficial in NMOSD
    • Prophylactic immunomodulatory therapy with intravenous immunoglobulin is beneficial if there has been more than one attack of MOG-associated optic neuritis
    • Anticipate corticosteroid dependency in sarcoidal and idiopathic inflammatory optic neuritis, and avoid rapid dose-tapering which may provoke recurrences
    • Tip: idiopathic, chronic, recurrent, and often steroid-dependent optic neuritis, a common occurrence, was once called “autoimmune optic neuritis,”, but is now labeled “chronic relapsing inflammatory optic neuropathy” (CRION)
    • Tip: some patients with CRION may actually have MOG-associated optic neuritis
    • Trap: be aware that corticosteroid dependency is a feature of infiltrative (neoplastic) and compressive optic neuropathies
    • Long-term use of corticosteroids in doses equivalent to prednisone 10mg/day or more may lead to pneumonia, osteoporosis, systemic hypertension, diabetes, mania, aseptic necrosis of hips and shoulders, and cancer
    • Long-term use of corticosteroid-sparing immunomodulatory therapy predisposes to infection and cancer
    • Trap: failure to distinguish NMOSD from MS is dangerous because interferon may worsen the course of NMOSD
    • Tip: reports are appearing of optic neuritis associated with treatment of cancer with immune check point inhibitors (ipilimumab, nivolumab, pembrolizumab, abezolizumab); the vision loss typically occurs within 4 cycles of treatment but may occur later; it is variable in degree, subacute in onset, and painless; accompanying features include optic disc edema, nerve fiber bundle defects, and sometimes uveitis; orbit MRI may be normal, show enhancement of the retrobulbar optic nerve or its sheath, or high T2 signal; treatment is with corticosteroids, and improvement in vision is common
    • Tip: atypical optic neuritis is relatively uncommon; population-based studies in Olmsted County, Minnesota have shown the following relative prevalence of causes of optic neuritis: multiple sclerosis 57%, idiopathic 31%, MOG-associated 5%, NMOSD 3%

    Optic Nerve And Chiasm Disorders

    Drusen Optic Neuropathy Colobomatous Optic Neuropathy Optic Pit Neuropathy Morning Glory Optic Neuropathy Hypoplastic Optic Neuropathy Typical Optic Neuritis Atypical Optic Neuritis Papillitis (Neuroretinitis) Non-arteritic Ischemic Optic Neuropathy Arteritic Ischemic Optic Neuropathy Posterior Ischemic Optic Neuropathy Hypotensive Ischemic Optic Neuropathy Radiation-induced Optic Neuropathy Diabetic Papillopathy Hypertensive Optic Disc Edema Papilledema Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) Compressive Optic Neuropathy: Overview Optic Neuropathy of Graves Disease Optic Nerve Sheath Meningioma Sphenoid Meningioma Craniopharyngioma Pituitary Adenoma Pilocytic Astrocytoma (Optic Glioma) Carotid Aneurysm Suprasellar Germinoma Infiltrative (Neoplastic) Optic Neuropathy Paraneoplastic Optic Neuropathy Traumatic Optic Neuropathy Toxic Optic Neuropathy Nutritional Deficiency Optic Neuropathy Dominantly-Inherited Optic Neuropathy Leber Hereditary Optic Neuropathy Primary Open Angle Glaucoma