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Optic Neuritis
Olga M. Cerón, MD
Pablo I. Hernandez Itriago, MD, MS, FAAFP
image BASICS
DESCRIPTION
  • Inflammation of the optic nerve (cranial nerve II)
  • 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 is more common in children.
  • Presenting complaint in 25% of patients with multiple sclerosis (MS)
  • In children, headaches are common.
  • System(s) affected: nervous
  • Synonym(s): papillitis; demyelinating optic neuropathy; retrobulbar ON
EPIDEMIOLOGY
Incidence
  • 1 to 5/100,000 cases per year
  • More common in northern latitudes
  • More common in whites than in other races
  • Predominant age: 18 to 45 years; mean age 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.
  • Possible mechanisms of inflammation in immunemediated ON are the cross-reaction of viral epitopes and host epitopes and the persistence of a virus in CNS glial cells.
  • Neuromyelitis optica (NMO) IgG autoantibody, which targets the water channel aquaporin-4
  • Primarily idiopathic
  • MS
  • Viral infections: measles, mumps, varicella-zoster, coxsackievirus, adenovirus, hepatitis A and B, HIV, herpes simplex virus, cytomegalovirus
  • Nonviral infections: syphilis, tuberculosis, meningococcus, cryptococcosis, cysticercosis, bacterial sinusitis, streptococcus B, 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
  • Vascular lesions affecting the optic nerve
  • Posterior uveitis (i.e., birdshot retinochoroidopathy, toxoplasmosis, toxocariasis)
  • Tumors
  • Medications: ethambutol, chloroquine, isoniazid, chronic high-dose chloramphenicol, tumor necrosis factor &agr;-antagonist, infliximab (Remicade), adalimumab (Humira), etanercept (Enbrel)
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
image DIAGNOSIS
PHYSICAL EXAM
Complete general exam, full neurologic exam, and ophthalmologic exam looking for the following:
  • Decreased visual acuity and color perception
  • Central, cecocentral, arcuate, or altitudinal visual field deficits
  • Papillitis: swollen disc ± peripapillary flame-shape hemorrhage or often normal disc exam
  • Temporal disc pallor seen later at 4 to 6 weeks (1)[A]
  • RAPD (Marcus-Gunn pupil): The pupil of the affected eye dilates with a swinging light test unless disease is bilateral.
DIFFERENTIAL DIAGNOSIS
  • Demyelinating disease, especially MS
  • Infectious/systemic inflammatory disease
  • Neuroretinitis: virus, toxoplasmosis, Bartonella
  • Toxic or nutritional optic neuropathy
  • Acute papilledema (bilateral disc edema)
  • Compression:
    • Orbital tumor/abscess compressing the optic nerve
    • Intracranial tumor/abscess compressing the afferent visual pathway
    • Orbital pseudotumor
    • Carotid-ophthalmic artery aneurysm
  • Temporal arteritis or other vasculitides
  • Trauma or radiation
  • NMO (Devic disease)
  • Anterior ischemic optic neuropathy
  • Leber hereditary optic neuropathy
  • Kjer-type autosomal dominant optic atrophy
  • Severe systemic hypertension
  • Diabetic papillopathy
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • In typical presentations, ESR is standard, but other labs are unnecessary. Antinuclear antibodies (ANAs), angiotensin-converting enzyme level, fluorescent treponemal antibody absorption (FTA-ABS), and chest radiograph have been shown to have no value in typical cases (1)[A].
  • In atypical presentations, including absence of pain, a very swollen optic nerve, >30 days without recovery or retinal exudates, labs may be indicated to rule out underlying disorders:
    • CBC
    • ANA test
    • Rapid plasma reagin test
    • FTA-ABS test
  • MRI of brain and orbits: thin cuts (2 to 3 mm) gadolinium-enhanced and fat-suppression images to look for Dawson fingers of MS (periventricular white matter lesions oriented perpendicular to the ventricles) and also to look for enhancement of the optic nerve
  • CT scan of chest to rule out sarcoidosis if clinical suspicion is high.
  • Ocular coherence tomography (OCT) of the retinal nerve fiber layer (RNFL); a noninvasive imaging technique of the optic nerve. May serve as a diagnostic tool to quantify thickness of the nerve fiber layer objectively and, thus, monitor structural change (axonal loss) of the optic nerve in the course of the disease.
Follow-Up Tests & Special Considerations
  • Visual field test (Humphrey 30-2) to evaluate for visual field loss: diffuse and central visual loss more predominant in the affected eye at baseline (2)[A]
  • Low-contrast visual acuity (as a measure of disease progression)
  • A novel blood test called NMO-IgG checks for antibodies for NMO.
Diagnostic Procedures/Other
  • In atypical cases, including bilateral deficits, young age, or suspicion of infectious etiology, lumbar puncture (LP) with neurology consultation is indicated.
  • LP for suspected MS is a physician-dependent decision. Some studies indicate that it may not add value to MRI for MS detection (1)[A] but no consensus on the subject exists.
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image TREATMENT
Most persons with ON recover spontaneously.
MEDICATION
First Line
  • IV methylprednisolone has been shown to speed up the rate of visual recovery but without significant long-term benefit; consider for patients who require fast recovery (i.e., monocular patients or those whose occupation requires high-level visual acuity). For significant vision loss, parenteral corticosteroids may be considered on an individualized basis: Optic Neuritis Treatment Trial (ONTT):
    • Observation and corticosteroid treatment are both acceptable courses of action.
    • High-dose IV methylprednisolone (250 mg q6h for 3 days) followed by oral corticosteroids (1 mg/kg/day PO for 11 days, taper over 1 to 2 weeks) (3)[A]
  • Others use IV Solu-Medrol infusion (1 g in 250 mL D5 1/2 normal saline infused over 1 hour daily for 3 to 5 days):
    • No evidence of long-term benefit (1)[A],(4)[B]
    • May decrease recovery time (3)[A],(4)[B]
    • May decrease risk of MS at 2 years but not 5 years (3)[A]
  • Give antiulcer medications with steroids.
Second Line
  • Disease-modifying agents, such as interferon-&bgr;1a (IFN-&bgr;1a; Avonex, Rebif) and IFN-&bgr;1b (Betaseron), are used to prevent or delay the development of MS in people with ON who have ≥2 brain lesions evident on MRI.
    • These medications have been proposed for use in patients with one episode of ON (clinically isolated syndrome) at high risk of developing MS (1+ lesion on brain MRI).
  • The Controlled High Risk Avonex Multiple Sclerosis (CHAMPS) trial study has shown that IFN-&bgr;1a reduces the conversion to clinically definite MS in high-risk patients by ˜50% (5)[A].
  • Decisions should be made individually with neurology consultation.
Pediatric Considerations
  • No systematic study defining high-dose corticosteroids in children with ON have been conducted.
    • Consensus recommends: 3 to 5 days of IV methylprednisolone (4 to 30 mg/kg per day), followed by a 2 to 4 week taper of oral steroids (6)[C]
  • Optic disc swelling and bilateral disease are more common in children as is severe loss of visual acuity (20/200 or worse).
  • Consider infectious and postinfectious causes of optic nerve impairment.
ISSUES FOR REFERRAL
Referral to a neurologist and/or ophthalmologist
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Monthly follow-up to monitor visual changes and steroid side effects
PATIENT EDUCATION
  • Provide reassurance about recovery of vision.
  • If the disease is believed to be secondary to demyelinating disease, patient should be informed of the risk of developing MS.
  • For patient education materials favorably reviewed on this topic, contact:
    • National Eye Institute, Information Officer, Department of Health and Human Services, 9000 Rockville Pike, Bethesda, MD 20892, 301-496-5248
    • North American Neuro-Ophthalmology Society (NANOS), 5841 Cedar Lake Road, Suite 204, Minneapolis, MN 55416, 952-646-2037, fax: 952-545-6073, http://www.nanosweb.org/i4a/pages/index.cfm?pageid=3280
PROGNOSIS
  • Orbital pain usually resolves within 1 week.
  • Visual acuity
    • Rapid spontaneous improvement at 2 to 3 weeks and continues for several months (may be faster with IV corticosteroids)
    • Often returns to normal or near-normal levels (20/40 or better) within 1 year (90-95%), even after near blindness
  • Other visual disturbances (e.g., contrast sensitivity, stereopsis) often persist after acuity returns to normal.
  • Recurrence risk of 35% within 10 years: 14% affected eye, 12% contralateral, 9% bilateral; recurrence is higher in MS patients (48%).
  • ON is associated with an increased risk of developing MS; 35% risk at 7 years, 58% at 15 years (7)[A]:
    • Brain MRI helps to predict risk:
      • 0 lesions: 16%
      • 1 to 2 lesions: 37%
      • 3+ lesions: 51%
  • Poor prognostic factors:
    • Absence of pain
    • Low initial visual acuity
    • Involvement of intracanalicular optic nerve
  • Children with bilateral visual loss have a better prognosis than adults.
REFERENCES
1. Vedula SS, Brodney-Folse S, Gal RL, et al. Corticosteroids for treating optic neuritis. Cochrane Database Syst Rev. 2007;(1):CD001430.
2. Keltner JL, Johnson CA, Cello KE, et al. Visual field profile of optic neuritis: a final follow-up report from the optic neuritis treatment trial from baseline through 15 years. Arch Ophthalmol. 2010;128(3):330-337.
3. Simsek I, Erdem H, Pay S, et al. Optic neuritis occurring with anti-tumour necrosis factor alpha therapy. Ann Rheum Dis. 2007;66(9):1255-1258.
4. Gleicher NB, ed. Principles and Practice of Medical Therapy in Pregnancy. 3rd ed. Norwalk, CT: Appleton & Lange; 1998:1396-1399.
5. Galetta SL. The controlled high risk Avonex multiple sclerosis trial (CHAMPS Study). J Neuroophthalmol. 2001;21(4):292-295.
6. Bonhomme GR, Mitchell EB. Treatment of pediatric optic neuritis. Curr Treat Options Neurol. 2012;14(1):93-102.
7. Optic Neuritis Study Group. Visual function 15 years after optic neuritis: a final follow-up report from the Optic Neuritis Treatment Trial. Ophthalmology. 2008;115(6):1079.e5-1082.e5.
8. Kaufman DI, Trobe JD, Eggenberger ER, et al. Practice parameter: the role of corticosteroids in the management of acute monosymptomatic optic neuritis. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;54(11):2039-2044.
9. Arnold AC. Evolving management of optic neuritis and multiple sclerosis. Am J Ophthalmol. 2005;139(6):1101-1108.
10. Balcer LJ. Clinical practice. Optic neuritis. N Engl J Med. 2006;354(12):1273-1280.
See Also
&NA;
Multiple Sclerosis
Codes
&NA;
ICD10
  • H46.9 Unspecified optic neuritis
  • H46.00 Optic papillitis, unspecified eye
  • H46.10 Retrobulbar neuritis, unspecified eye
Clinical Pearls
&NA;
  • MRI is the procedure of choice for determining relative risk and possible therapy for MS prevention.
  • The ONTT showed that high-dose IV methylprednisolone followed by oral prednisone accelerated visual recovery but did not improve the 6-month or 1-year visual outcome compared with placebo, whereas treatment with oral prednisone alone did not improve the outcome and was associated with an increased rate of recurrence of ON (1,2,8)[A], (9)[B],(10)[C].