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Ophthalmology / Neuro-ophthalmology

Optic Neuritis

Andrew G. Lee, MD This work was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY.
Article


Introduction

Optic neuritis refers to idiopathic or demyelinating optic neuropathy. A patient with optic neuritis typically is a young adult with acute, unilateral visual loss associated with eye movement pain. Childhood optic neuritis will not be reviewed in this tutorial.

A clinical examination of optic neuritis shows variable loss of visual acuity and/or visual field, dyschromatopsia, and an ipsilateral relative afferent pupillary defect. The optic nerve is typically normal in appearance (65%) (i.e., a retrobulbar optic neuropathy) or, less commonly, a swollen optic nerve is present (35%) (i.e., papillitis).

The Optic Neuritis Treatment Trial (ONTT) was a randomized, placebo-controlled clinical trial that provided evidence for the natural history, epidemiology, and treatment of optic neuritis. Optic neuritis has typical features1-10 (Table 1) and atypical features (Table 2).

Table 1. Features of Typical Optic Neuritis in Adults

  • Acute to subacute onset
  • Unilateral loss of visual acuity, contrast, color, or visual field
  • An ipsilateral relative afferent pupillary defect
  • Periocular pain (90%), especially with eye movement
  • Normal (65%) or swollen (35%) optic nerve head
  • A young adult patient (usually younger than 40 years of age), but optic neuritis may occur at any age
  • Eventual visual improvement in the majority of patients
  • Absence of anterior or posterior segment inflammation

Table 2. Features of Atypical Optic Neuritis in Adults

  • Bilateral simultaneous onset of optic neuritis in an adult patient
  • Painless visual loss
  • Unusual intraocular findings
    • Anterior uveitis*
    • Posterior uveitis*
    • Retinal exudates (e.g., macular "star figure")
    • Retinal infiltrates or retinal inflammation
    • Markedly swollen optic nerve
    • Marked retinal hemorrhages (e.g., 360º of peripapillary hemorrhages)
  • Lack of significant improvement or worsening of visual function after 30 days
  • Age older than 50 years
  • Diagnosis or evidence of systemic conditions other than multiple sclerosis that may cause an optic neuropathy
  • Extremely steroid-sensitive or steroid-dependent optic neuropathy
  • No light perception vision

*Anterior uveitis, pars planitis, and retinal periphlebitis may be seen in patients with optic neuritis associated with multiple sclerosis but should be considered to be unusual findings.

Evaluation

In the ONTT, all patients underwent magnetic resonance imaging and laboratory testing (e.g., syphilis serology, chest radiography, antinuclear antibody). A lumbar puncture was optional. A magnetic resonance image (MRI) of the brain showing demyelinating white matter lesions was the best prognostic indicator for the development of clinically definite multiple sclerosis. Laboratory testing in the ONTT did not reveal alternative etiologies for the optic neuropathy, and the lumbar puncture results were either normal or supported the clinical diagnosis of multiple sclerosis.

Based on these results, the ONTT recommended a brain MRI for all patients with optic neuritis but did not recommend any additional laboratory testing in patients with typical optic neuritis. However, patients with an atypical presentation (Table 2) should be evaluated for other causes of optic neuropathy.11

Treatment

The ONTT had three treatment groups — oral prednisone, intravenous (IV) methylprednisolone for 3 days followed by oral prednisone, and oral placebo. The final visual outcome was equivalent for the three treatment arms.1 IV steroids sped the rate of visual recovery, but oral steroids increased the rate of new attacks. Therefore, the ONTT recommended against the use of oral steroids in conventional doses for patients with optic neuritis. Another optic neuritis treatment trial from Japan showed results similar to the ONTT’s.12,13

Although conventional doses of oral steroids increased the rate of new attack in the ONTT, higher doses of oral steroids were not studied. Other clinical trials have shown that higher doses of oral methylprednisolone14 do not produce an increased rate of new attacks; however, the number of patients in these trials was relatively small.15,16

Interferon Therapy in Patients with Optic Neuritis

The Controlled High-Risk Subject Avonex Multiple Sclerosis Prevention Study (CHAMPS) was a randomized, double-blind, placebo-controlled, clinical trial of interferon (IFN) beta-1a (Avonex, Biogen Idec). All patients had an acute clinical demyelinating event (e.g., optic neuritis) and demyelinating white matter lesions on a brain MRI.

As in the ONTT protocol, all patients received IV methylprednisolone. All patients were then randomized to either treatment with IFN beta-1a or placebo.17 Patients in the IFN treatment arm of the study had a 44% reduction in the rate of clinically definite multiple sclerosis after 3 years, a relative reduction in the volume of brain lesions, fewer new or enlarging lesions, and fewer gadolinium-enhancing lesions on magnetic resonance.17

The Early Treatment Of Multiple Sclerosis (ETOMS) study was a randomized trial of interferon beta-1a (Rebif, Serano Inc. and Pfizer Inc.) 22 mg subcutaneously once weekly compared with placebo.

As in the CHAMPS study, patients had an acute demyelinating neurologic event (e.g., optic neuritis) and white matter lesions on a cranial MRI. There was a significant rate of reduction of clinically definite multiple sclerosis in the treatment group compared with placebo group.

Summary

Based on the studies that have been performed to date, the following guidelines may be useful to an ophthalmologist treating a patient with acute typical optic neuritis.17-19

  1. Patients with optic neuritis should undergo a cranial MRI to rule out demyelinating white matter lesions consistent with multiple sclerosis. An orbital fat suppressed post-gadolinium MRI may be a useful adjunctive study to the cranial magnetic resonance to differentiate non-demyelinating etiologies for an optic neuropathy (e.g., sarcoidosis, optic nerve sheath meningioma). In the ONTT, additional laboratory testing was not necessary for typical optic neuritis but laboratory testing should be considered for atypical cases.

  2. The presence of demyelinating white matter lesions on brain MRI is a powerful predictor of clinically defined multiple sclerosis (Slide 1). Patients with optic neuritis and white matter lesions on MRI should be offered neurologic consultation to discuss options for immunomodulatory therapies (e.g., interferon beta-1a).17,20
    3. Slide 1

  3. Treatment with IV steroids hastens recovery of optic neuritis but does not change final outcome that is excellent in optic neuritis regardless of therapy. Oral steroids in conventional doses are not recommended because of the increased rate of new attacks in the ONTT.

References

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