Current issues of ACP Journal Club are published in Annals of Internal Medicine


Optic neuritis posed a 40-year risk of 60% for multiple sclerosis

ACP J Club. 1995 July-Aug;123:21. doi:10.7326/ACPJC-1995-123-1-021

Source Citation

Rodriguez M, Siva A, Cross SA, O'Brien PC, Kurland LT. Optic neuritis: a population-based study in Olmsted County, Minnesota. Neurology. 1995 Feb;45:244-50.



To study the association between optic neuritis (ON) and the subsequent development of multiple sclerosis (MS).


Inception cohort followed for a mean of 13.2 years (range 0 to 51 y).


A county in Minnesota.


Patients living in Olmsted County, Minnesota, who developed ON between 1935 and 1991 were identified using the Mayo Clinic records system. The incidence group included 156 patients (69% women) who developed ON while living in the county, and the prevalence group included 128 patients with a documented history of ON who were living in the county on 1 December 1991. Inclusion criteria were diagnosis of idiopathic ON based on a relatively rapid onset of visual failure with no evidence for neurologic, infectious, metabolic, toxic, vascular, hereditary, or compressive cause; evidence of at least 2 of the following: ceco-central field defect, afferent pupillary defect, impairment of color vision, ocular pain on eye movement, or abnormal visual evoked potential; and diagnosis by a Mayo Clinic ophthalmologist.

Assessment of prognostic factors

Ophthalmologic data collected at onset and during follow-up, age, sex, and recurrent ON.

Main outcome measures

Type and date of neurologic symptoms or signs compatible with MS and whether these MS features were present before, concurrent with, or after ON.

Main results

Median age at onset of ON was 31 y. The age- and sex-adjusted prevalence rate of ON was 115.3/100 000 (95% CI 95.2 to 135.4/100 000). The overall average annual age-adjusted incidence rate of ON was 2.6/100 000 for men and 7.5/100 000 for women. For patients without a history of ON or concurrent neurologic symptoms during ON (n = 95), progression to MS was 39% at 10 years, 49% at 20 years, 54% at 30 years, and 60% at 40 years. Age at onset, sex, visual field defect, decreased visual acuity, impaired color vision, afferent pupillary defect, abnormal result of funduscopic examination, visual blurring, Uhthoff phenomenon, ocular pain, bilateral involvement, season or month of onset, and poor visual acuity at follow-up were not associated with development of MS. The presence of perivenous sheathing (P = 0.04) and recurrent ON (P < 0.001) were associated with development of MS. The 25-year survival after ON was 88.3% compared with 83.9% for the general U.S. population adjusted for age and sex (P = 0.1).


Optic neuritis was associated with the long-term development of multiple sclerosis.

Source of funding: National Institutes of Health.

For article reprint: Dr. M. Rodriguez, Departments of Neurology and Immunology, Mayo Clinic, Guggenheim Street, Rochester, MN 55905, USA. FAX 507-284-0161.


The patient presenting with isolated ON poses several problems for the clinician. The first among these is diagnostic; there are important differential considerations for an acute monocular or binocular visual disturbance, including drug-induced ON, syphilis, and sarcoidosis. Vascular disorders should be considered in older patients or those predisposed to small-vessel diseases (1).

The second issue is therapeutic. Treating the patient who has acute ON with intravenous methylprednisolone improves short-term (6-month) visual outcome, but this difference disappears with longer follow-up (2). Oral steroid treatment resulted in a higher incidence of subsequent ON than either intravenous therapy or placebo. Thus, oral steroids should not be used in patients with acute ON. Intravenous steroid treatment, however, reduced the rate of progression from ON to MS by about 50% during the next 2 years (3).

The third issue is prognostic. Previous analyses have yielded widely differing estimates of the risk for progression from symptomatic ON to some form of MS. These studies were not population-based and therefore may have had problems of ascertainment bias and incomplete follow-up. The study by Rodriguez and colleagues is the most thorough and accurate analysis to date. In contrast to previous analyses (4), this study indicates that the rate of progression to MS did not differ by sex, although it confirmed that ON was about twice as common in women as in men.

The other major unanswered questions raised by this study are the following: 1) Does ON predispose a patient to a particular subtype of MS (i.e., relapsing-remitting or chronic progressive) and 2) why does the prevalence and incidence of MS apparently increase over time? The first question has direct immunologic, diagnostic, and therapeutic relevance; the second may lead us to an understanding of cause and prevention.

Thomas P. Bleck, MD
University of VirginiaCharlottesville, Virginia, USA


1. Caplan L, Brust J, Feldman E, Goetz CG, Newman NJ. Neurology. In: Goldman L (editor-in-chief). MKSAP 1994-1995;10:569-75.

2. Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992;326:581-8.

3. Beck RW, Cleary PA, Trobe JD, et al. 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.

4. Rizzo JF 3d, Lessell S. Risk of developing multiple sclerosis after uncomplicated optic neuritis: a long-term prospective study. Neurology. 1988;38:185-90.