• NANOS and AAO Quality of Care Secretariat, Hoskins Center for Quality Eye Care
    Comprehensive Ophthalmology, Neuro-Ophthalmology/Orbit
    Compendium Type: I

    I. Describe the approach to establishing the diagnosis

    A. Describe the etiology of this disease

    1. Inflammatory demyelination of the optic nerve, either idiopathic or related to multiple sclerosis (MS)

    B. Define the relevant aspects of epidemiology of the disease

    1. Typically age 20-50 years, but cases may occur outside this range
    2. Approximately 75% female (parallels MS epidemiology)

    C. List the pertinent elements of the history

    1. Acute visual loss (typically progresses over less than 7 days)
    2. Typically monocular
    3. Majority have peri-orbital pain initially, often increased with eye movement (resolves in week 1-2)
    4. May have history of demyelinating symptoms or known diagnosis of multiple sclerosis

    D. Describe pertinent clinical features

    1. Decreased visual acuity
    2. Decreased color vision (often out of proportion to acuity loss)
    3. Visual field defect (diffuse, altitudinal, cecocentral or other)
    4. Relative afferent pupillary defect (if unilateral or asymmetric)
    5. 2/3 normal disc appearance (retrobulbar), 1/3 disc edema (bulbar or papillitis); if present, disc edema is typically mild without hemorrhage or exudates

    E. Describe appropriate diagnostic/laboratory testing

    1. In typical case of optic neuritis with a known diagnosis of MS, no further testing may be required

    2. In monosymptomatic or clinically isolated syndrome cases (1st episode of demyelination), MRI provides prognostic information

    a. MRI T2 hyperintensities suggestive of demyelination stratifies to higher MS risk (approximate risk at 5, 10, and 15 years is 50%, 60%, and 70%, respectively)

    b. Normal MRI stratifies to low MS risk (Approximate risk at 5, 10, and 15 years is 15%, 20%, and 25%, respectively)

    1) Normal MRI with the following features define extremely low MS-risk cohort (no MS cases at 15 years): painless optic neuritis, no light perception vision at onset, severe disc edema or disc hemorrhage, or macular star figure exudate

    II. Define the risk factors

    A. Female and Caucasian predominance
    B. History of MS
    C. Age range 20-50 years

    III. List the differential diagnosis

    A. Anterior ischemic optic neuropathy
    B. Maculopathy with a normal appearing fundus
    C. Infiltrative optic neuropathy
    D. Compressive optic neuropathy
    E. Other inflammatory optic neuropathy (e.g., sarcoid)
    F. Infectious optic neuropathy (e.g., CMV, Lyme)
    G. Neuroretinitis (e.g., Bartonella henselae 'cat scratch disease')
    H. Hereditary (e.g., Leber hereditary optic neuropathy)
    I. Miscellaneous other optic neuropathies

    IV. Describe patient management in terms of treatment and follow-up

    A. Acute treatment options: high dose corticosteroids (e.g., intravenous methylprednisolone), or no treatment depending upon individual risk-benefit ratio

    1. Optic Neuritis Treatment Trial* protocol: methylprednisolone 250 mg iv q 6 hours x 3 days, then prednisone 1 mg/kg/day po qd x 11 days, then 20 mg po on day 15 and 10 mg on days 16 and 18 then discontinue prednisone; many centers now administer methylprednisolone 1000 mg iv q day x 3 days for outpatient convenience with or without corticosteroid taper

    B. Chronic treatment options: referral to a multiple sclerosis specialist for management and consideration of MS immunomodulatory therapy if abnormal MRI scan or other neurological abnormalities are suggested by examination or history

    C. Oral prednisone 1 mg/kg/day alone contraindicated due to increased risk of recurrent optic neuritis (and no more effective than placebo concerning visual function)

    * Results of the Optic Neuritis Treatment Trial: High dose IV methylprednisolone given to patientsfirst seen within 8 days of symptom onset with unilateral vision loss in an eye that had not had optic neuritis had quicker visual recovery but at one month, had no significant difference in VA, visual fields, color vision, or contrast sensitivity. Oral prednisone treatment alone did not improve visual outcomes and was associated with a higher rate of recurrence.

    V. List the complications of treatment, their prevention and management

    A. Complications of corticosteroids

    1. Mood alteration including rare psychosis
    2. Hyperglycemia
    3. Insomnia
    4. Gastrointestinal irritation
    5. Osteoporosis or avascular necrosis (rare with short steroid courses)
    6. Weight gain

    VI. Describe disease-related complications

    A. Persistent decreased visual acuity (only 5% of patients have visual acuity worse than 20/40 at 6 months)

    B. Persistent dyschromatopsia, decreased contrast sensitivity and impaired depth or motion perception

    C. Progression to MS

    VII. Describe appropriate patient instructions

    B. Obtain MRI of brain (consider orbital images) with and without gadolinium in appropriate cases

    1. If MRI reveals T2 hyperintensities consistent with MS

    a. Discuss potential relationship to MS, possible MS therapies, or refer to MS neurologist

    C. Monitor for atypical course or features

    1. Report new neurological symptoms
    2. Macular star figure emergence
    3. Failure to improve
    4. Treatment side effects

    Additional Resources

    1. Optic Neuritis Study Group. The clinical profile of optic neuritis. Experience of the Optic Neuritis Treatment Trial. Arch Ophthalmol. 1991;109:1673-78.

    2. Beck RW, Cleary PA, Trobe JD. The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis. The Optic Neuritis Study Group. N Engl J Med. 1993;329:1764-9.

    3. Beck RW, Arrington J, Murtagh FR. Brain magnetic resonance imaging in acute optic neuritis. Experience of the Optic Neuritis Study Group. Arch Neurol. 1993;50:841-6.

    4. Beck RW, Cleary PA, Backlund JC. The course of visual recovery after optic neuritis. Experience of the Optic Neuritis Treatment Trial. Ophthalmology. 1994;101:1771-8.

    5. Keltner JL, Johnson CA, Spurr JO. Visual field profile of optic neuritis. One-year follow-up in the Optic Neuritis Treatment Trial. Arch Ophthalmol. 1994;112:946-53.

    6. Beck RW, Trobe JD. What we have learned from the Optic Neuritis Treatment Trial. Ophthalmology. 1995;102:1504-8.

    7. Beck RW. The Optic Neuritis Treatment Trial: three-year follow-up results. Arch Ophthalmol. 1995;113:136-7.

    8. Beck RW. The Optic Neuritis Treatment Trial. Three-year follow-up results. Optic Neuritis Study Group. Arch Ophthalmol. 1995;113:136-7.

    9. Kline LB, Foroozan R. Optic Nerve Disorders 2nd ed. New York, NY: Oxford University Press; 2007:33-35, 55-73, 85.

    10. Optic Neuritis Study Group. The 5-year risk of multiple sclerosis after optic neuritis. Experience of the Optic Neuritis Treatment Trial. Neurology. 1997;49:1404-13.

    11. The Optic Neuritis Study Group. Visual function 5 years after optic neuritis: experience of the Optic Neuritis Treatment Trial. Arch Ophthalmol. 1997;115:1545-52.

    12. Warner JE, Lessell S, Rizzo JF III. Does optic disc appearance distinguish ischemic optic neuropathy from optic neuritis? Arch Ophthalmol. 1997;115:1408-10.

    13. Cleary PA, Beck RW, Bourque LB. Visual symptoms after optic neuritis. Results from the Optic Neuritis Treatment Trial. J Neuroophthalmol. 1997;17:18-23; quiz 24-28.

    14. Trobe JD, Beck RW, Moke PS. Contrast sensitivity and other vision tests in the optic neuritis treatment trial. Am J Ophthalmol. 1996;121:547-53.

    15. Sellebjerg F, Nielsen HS, Frederiksen JL. A randomized, controlled trial of oral high-dose methylprednisolone in acute optic neuritis. Neurology. 1999;52:1479-84.

    16. Cole SR, Beck RW, Moke PS. The National Eye Institute Visual Function Questionnaire: experience of the Optic Neuritis Treatment Trial. Optic Neuritis Study Group. Invest Ophthalmol Vis Sci. 2000;41:1017-21.

    17. Jacobs LD, Beck RW, Simon JH. Intramuscular interferon beta- 1a therapy initiated during first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med. 2000;343:898-904.

    18. Kaufman DI, Trobe JD, Eggenberger ER, Whitaker JN. American Academy of Neurology Practice Parameters: the role of corticosteroids in the management of acute monosymptomatic optic neuritis. Neurology, 2000; 54: 2039-44.

    19. CHAMPS Study Group. Interferon beta-1a for optic neuritis patients at high risk for multiple sclerosis. Am J Ophthalmol. 2001;132:463-71.

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

    21. Anonymous. Baseline MRI characteristics of patients at high risk for multiple sclerosis: results from the CHAMPS trial. Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study. Multiple Scler. 2002;8:330-8.

    22. Beck RW, Chandler DL, Cole SR. Interferon beta- 1a for early multiple sclerosis: CHAMPS trial subgroup analyses. Ann Neurol. 2002;51:481-90.

    23. American Academy of Ophthalmology, Focal Points: Multiple Sclerosis and Optic Neuritis, Module 12, 2003:6-7.

    24. Hickman SJ, Kapoor R, Jones SJ. Corticosteroids do not prevent optic nerve atrophy following neuritis. J Neurol Neurosurg Psychiatry. 2003;74:1139-41.

    25. Beck RW, Trobe JD, Moke PS. High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the Optic Neuritis Treatment Trial. Arch Ophthalmol. 2003;121: 944-9.

    26. Beck RW, Gal Mt, Bhatti MT. Visual function more than 10 years after optic neuritis: experience of the Optic Neuritis Treatment Trial. Am J Ophthalmol. 2004;137:77-83.

    27. The Optic Neuritis Study Group. Multiple sclerosis risk after optic neuritis: final Optic Neuritis Treatment Trial follow-up. Arch Neurol 2008;65:727-32.

    28. Optic Neuritis Study Group. Visual function 15 years after optic neuritis: a final follow-up report from the Optic Neuritis Treatment Trial. Ophthalmology 2008;115:1079-82 e5.

    29. 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;128:330-7.

    30. American Academy of Ophthalmology, Basic and Clinical Science Course. Section 5: Neuro-ophthalmology, 2012-13;144-6, 323-4.

    Prepared by: North American Neuro-Ophthalmology Society and the Hoskins Center for Quality Eye Care
    Approved by: Quality of Care Secretariat, July 3, 2012

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