Optic Neuritis– Causes, Symptoms, Diagnosis, Treatment and Ongoing care

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 disordersOptic disc may be either normal in appearance at onset (retrobulbar ON, 67%) or swollen (papillitis, 33%)Key features: Abrupt visual lossPeriorbital pain especially with eye movement (90%)Dyschromatopsia: Color vision deficitsAfferent pupillary defectUsually unilateral in adults; bilateral disease more common in childrenPresenting complaint in 25% of multiple sclerosis (MS) patientsSystem(s) affected: NervousSynonym(s): Papillitis; Demyelinating optic neuropathy; Retrobulbar optic neuritisIn children, headache is common.

Epidemiology

Incidence

5 cases per 100,000 seen annuallyMore common in northern latitudesMore common in whites than in other racesPredominant age: Typically 18–45 years; mean age 30Predominant sex: Female > Male (3:1)

Pathophysiology

In both MS-associated and isolated monosymptomatic ON, the cause is presumed to be a demyelinating autoimmune reaction.Possible mechanisms of inflammation in immune-mediated optic neuritis are the cross-reaction of viral epitopes and host epitopes, and the persistence of a virus in central nervous system glial cellsNeuromyelitis optica (NMO) IgG autoantibody, which targets the water channel aquaporin-4

Etiology

Primarily idiopathicMSViral infections: Measles, mumps, varicella-zoster, coxsackievirus, adenovirus, hepatitis A and B, HIV, herpes simplex virus, cytomegalovirusNonviral infections: Syphilis, tuberculosis, meningococcus, cryptococcosis, cysticercosis, bacterial sinusitis, streptococcus B, Bartonella, Lyme disease, fungusSystemic inflammatory disease: Sarcoidosis, systemic lupus erythematosus, vasculitisLocal inflammatory disease: Intraocular or contiguous with the orbit, sinus, or meningesToxic: Lead, methanol, arsenic, radiationVascular lesions affecting the optic nervePosterior uveitisTumorsMedications: Ethambutol, chloroquine, isoniazid, chronic high-dose chloramphenicol, tumor necrosis factor a 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 neuromyelitis optica, multifocal demyelinating neuropathy, acute disseminated encephalomyelitis

Diagnosis

History

Decreased visual acuity, deteriorating in hours to days, usually reaching lowest level in 1 weekUsually unilateral but can also be bilateralBrow ache, globe tenderness, deep orbital pain exacerbated by eye movement (92%)Retro-orbital pain may precede visual loss.Desaturation of color vision (dull or faded colors), especially red tonesApparent dimness of light intensitiesImpairment of depth perception (80%); worse with moving objects (Pulfrich phenomenon)Transient increase in visual symptoms with increased body temperature and exercise (Uhthoff phenomenon)May present with a recent flulike viral syndromeDetailed history and review of systems, looking for a history of demyelinating, infectious, or systemic inflammatory disease

Physical Exam

Complete general exam, full neurologic exam, and ophthalmologic exam looking for the following:

Decreased visual acuity and color perceptionCentral, cecocentral, arcuate, or altitudinal visual field deficitsPapillitis: Swollen disc ± peripapillary flame-shape hemorrhage or often normal disc examTemporal disc pallor seen later at 4–6 weeks (1)Relative afferent pupillary defect (Marcus-Gunn pupil): The pupil of the affected eye dilates with swinging light test unless disease is bilateral.

Diagnostic Tests & Interpretation

Lab

Initial lab tests

In typical presentations, erythrocyte sedimentation rate 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).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: Complete blood countANA testRapid plasma reagin testFTA-ABS test

Follow-Up & 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 novel blood test called an NMO-IgG checks for antibodies for neuromyelitis optica.

Imaging

Initial approach

Magnetic resonance imaging (MRI) of brain and orbits: Thin cuts (2-3 mm) gadolinium enhanced and fat suppression images to look for Dawson fingers of MS (periventricular white matter lesions oriented perpendicular to the ventricles) and to also look for enhancement of the optic nerveComputed tomography scan of chest to rule out sarcoidosis if clinical suspicion is high

Diagnostic Procedures/Surgery

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), but there is no consensus on the subject.

Differential Diagnosis

Demyelinating disease, especially MSInfectious/systemic inflammatory diseaseNeuroretinitis: Virus, toxoplasmosis, BartonellaToxic or nutritional optic neuropathyAcute papilledema (bilateral disc edema)Compression: Orbital tumor/abscess compressing the optic nerveIntracranial tumor/abscess compressing the afferent visual pathwayOrbital pseudotumorCarotid–ophthalmic artery aneurysmTemporal arteritis or other vasculitidesTrauma or radiationNeuromyelitis optica (Devic disease)Anterior ischemic optic neuropathyLeber hereditary optic neuropathyKjer-type autosomal-dominant optic atrophySevere systemic hypertensionDiabetic papillopathy

Treatment

Most persons with optic neuritis recover spontaneously.

Medication

First Line

Intravenous 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 (ie, monocular patients or those whose occupation requires high-level visual acuity). For significant vision loss, parenteral corticosteroids may be considered on an individualized basis. Observation and corticosteroid treatment are both acceptable courses of action (3)[B].High-dose intravenous (IV) methylprednisone (250 mg q6h × 3 days) followed by oral corticosteroids (1 mg/kg/d p.o. × 11 days, taper over 1–2 weeks) (3)[B]Others use IV Solu-Medrol infusion (1 g in 250 mL D5 1/2 normal saline infused over 1 h daily for 3–5 days). No evidence of long-term benefit (14)May decrease recovery time (3,4)May decrease risk of MS at 2 but not 5 years (3)Give antiulcer medications with steroids.

Second Line

Disease-modifying agents such as interferon-ß-1a (IFN-ß-1a; Avonex, Rebif) and IFN-ß-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 1 episode of ON (clinically isolated syndrome) at high risk of developing MS (1+ lesion on brain MRI).The Controlled High Risk Avonex Multiple Sclerosis Trial study has shown that IFN-ß1–a reduces the conversion to clinically definite multiple sclerosis in high-risk patients by ~50%.Decisions should be made individually with neurology consultation.

Alert

Never use oral prednisone alone as primary treatment because this may increase the risk for recurrent ON and should be avoided (3).

Pediatric Considerations

No systematic study defining high-dose corticosteroids in childhood ON has been conducted. Walsh & Hoyt’s Clinical Neuro-ophthalmology recommends methylprednisolone 1–2 mg/kg × 3–5 days, followed by a longer taper. Farris and Pickard used doses of methylprednisolone ranging from 0.25–6.26 mg/kg, with half the patients receiving doses of 125 or 250 mg q6h × 5 days, followed by a taper.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.

Additional Treatment

General Measures

Referral to a neurologist and/or ophthalmologist

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; 301-496-5248North American Neuro-Ophthalmology Society (NANOS), 5841 Cedar Lake Road, Suite 204, Minneapolis, MN 55416; phone: 952-646-2037; fax: 952-545-6073; http://www.nanosweb.org

Prognosis

Orbital pain usually resolves within 1 week.Visual acuity: Rapid spontaneous improvement at 2–3 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 blindnessOther visual disturbances (eg, 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 increased risk of developing MS; 35% risk at 7 years, 58% at 15 years: Brain MRI helps to predict risk: 0 lesions: 16%1–2 lesions: 37%3+ lesions: 51% (5)Poor prognostic factors: Absence of painLow initial visual acuityInvolvement of intracanalicular optic nerveChildren with bilateral visual loss have a better prognosis than adults.

Complications

Permanent loss of vision (6)

References

1. Vedula SS, et al. Corticosteroids for treating optic neuritis. Cochrane Library. 2007;1:CD001430.

2. Keltner JL, Johnson CA, Cello KE, Dontchev M, Gal RL, Beck RW, Optic Neuritis Study Group 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;128:330–7.

3. Simsek I, Erdem H, Pay S, et al. Optic neuritis occurring with anti-tumour necrosis factor alpha therapy. Ann Rheum Dis. 2007;66:1255–8.

4. Gleicher N, et al. Principles and practice of medical therapy in pregnancy, 3rd ed. Norwalk, CT: Appleton and Lange; 1998:1396–9.

5. 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;54:2039–44.

6. Carter J. e-Medicine, Optic Neuritis August 8, 2009.

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;115:1079–1082.e5.

Additional Reading

Arnold AC. Evolving management of optic neuritis and multiple sclerosis. Am J Ophthalmol. 2005;139:1101–8.

Balcer LJ. Clinical practice. Optic neuritis. N Engl J Med. 2006;354:1273–80.

Galetta SL. The controlled high risk Avonex multiple sclerosis trial (CHAMPS Study). J Neuroophthalmol. 2001;21:292–5.

Rizzo JF, Andreoli CM, Rabinov JD. Use of magnetic resonance imaging to differentiate optic neuritis and nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 2002;109:1679–84.

See Also (Topic, Algorithm, Electronic Media Element)

Multiple Sclerosis

Codes

ICD9

377.30 Optic neuritis, unspecified377.31 Optic papillitis377.32 Retrobulbar neuritis (acute)377.33 Nutritional optic neuropathy377.34 Toxic optic neuropathy377.39 Other optic neuritis

Snomed

66760008 optic neuritis (disorder)73221001 optic papillitis (disorder)230507009 retrobulbar neuritis (disorder)82108004 nutritional optic neuropathy (disorder)26125006 toxic optic neuropathy (disorder)

Clinical Pearls

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.

Alert

Never use oral prednisone alone as primary treatment because this may increase the risk for recurrent ON and should be avoided (4).15-year Optic Neuritis Study Group results: After the initial period of recovery after an acute episode of ON, visual acuity remained stable in most patients.Overall, 72% of affected eyes had visual acuity of 20/20 or better, with 2/3 of patients having 20/20 or better vision in both eyes.In most patients, there was little change in vision between the 10- and 15-year follow-up examinations. 6 patients (2%) had visual acuity of 20/40 or worse in both eyes. Visual function was slightly better in patients without MS compared with those with MS (7).