Sources: Optic Neuritis Study Group. The five-year risk of MS after optic neuritis. Neurology 1997;49:1404-1413; Optic Neuritis Study Group. Visual function 5 years after optic neuritis. Arch Ophthalmol 1997;115:1545-1552; Lucchinetti CF, et al. Risk factors for developing multiple sclerosis after childhood optic neuritis. Neurology 1997;49:1413-1418.
As an extension of the optic neuritis treatment trial (ONTT), 388 patients were followed to assess the five-year risk and prognostic factors for the development of clinically definite MS (CDMS). The five-year cumulative probability of CDMS was 30% and did not differ significantly between the treatment groups (IV solumedrol, 250 mg/q 6 hours for 3 days followed by 1 mg/kg/day oral regimen for 11 days; PO prednisone, 1 mg/kg/day for 14 days; or oral placebo for 14 days). The brain MRI performed on entry to the study was a strong predictor for the subsequent development of MS. The five-year risk of CDMS ranged from 16% in the 202 patients with no brain lesions on MRI to 51% in the 89 patients with three or more MRI lesions. Clinical features of the patients with no brain lesions associated with a low incidence of developing CDMS included lack of pain, the presence of optic disc swelling, mild visual loss, and lack of involvement of the fellow eye.
Long-term outcome of visual function for 397 patients was assessed including visual acuity, contrast sensitivity, visual field, and color vision. Most patients had normal or only slightly abnormal visual acuity at five years, with results that did not differ significantly by treatment group. A small group of 3% of patients had moderate (20/50 to 20/190) visual loss, and 3% had severe (20/200 or worse) visual loss. Optic neuritis in either eye recurred in 28% of the patients and was more frequent in patients who developed CDMS (P = 0.001) and in patients without MS who were in the PO prednisone treatment group (P = 0.004).
In a retrospective analysis of 94 pediatric cases (age < 16 years) of optic neuritis at the Mayo Clinic, long-term follow-up on 79 patients showed 13% had progressed to CDMS within 10 years, 19% by 20 years, and 22% by 30 years. The recurrence of optic neuritis in the same or other eye increased the risk of developing CDMS (P = 0.002), whereas the presence of infection two weeks before onset reduced the risk of developing MS (P = 0.06). The study of childhood optic neuritis supports a lower risk of progression to MS compared with adults.
COMMENTARY
The ONTT was designed to assess the efficacy of corticosteroids for optic neuritis, a large and important treatment issue in neurologic practice. There was no statistically significant difference in outcome for visual function between the three groups, although there was a subtle trend for minor benefit of IV steroids after five years. More significantly, data about the evolution of demyelinating disease revealed that patients treated with IV steroids or placebo, rather than PO prednisone, were less likely to develop recurrent optic neuritis in either eye or CDMS. While this result may seem counter-intuitive to some who might feel that low-dose PO prednisone is a benign intervention that should not produce a worse outcome than the placebo control, they should be reminded that the complex immunologic mechanisms that determine relapsing patterns of disease are not understood. Conceivably, low-dose prednisone at this critical point could unfavorably alter the homeostatic balance of the immune system by relative inhibition of regulatory suppressor lymphocytes, paradoxically contributing to immune activation of a subset population of undesirable cytotoxic lymphocytes (see d’Addmio F, et al. Immunity 1997;7:803-812).
As a guideline for clinical management, one interpretation of the above studies is that mild optic neuritis with slight reductions in visual acuity could be monitored without any treatment intervention. However, patients with severe visual loss, severe eye pain, or multiple lesions on brain MRI at time of presentation could have a better outcome with IV steroid therapy in reducing the likelihood of future disease activity.
A new national study is currently recruiting patients presenting with "monosymptomatic MS" (i.e., a first attack of optic neuritis, a brainstem event such as INO, or a spinal cord syndrome), but also having two or more lesions on brain MRI. The trial, organized by Larry Jacobs and Roy Beck, is taking this group of patients who are at high risk for future development of CDMS and, after standard treatment with IV solumedrol, randomizing patients into an interferon beta-1a (Avonex) group or placebo group. The primary and secondary outcomes measures should determine whether the therapy delays the onset of CDMS and progression of demyelination on brain MRI. If so, the trend in management would tilt toward early chronic therapy.
The New York Hospital-Cornell Medical Center is serving as the New York City treatment site in this controlled clinical trial for patient referral and enrollment (212/746-4504). The CHAMPS (Controlled trial of High risk subjects in A Multiple Sclerosis Prevention Study) referral center can provide interested persons with a site near you (800/324-2454). Patients must start the course of IV steroids within 14 days of initial symptoms and are then randomized at day 11 of the oral prednisone taper. ba
Clinical features of the patients with no brain lesions associated with a low incidence of developing CDMS included which of the following?
a. Presence of optic disc swelling
b. Lack of pain
c. Lack of involvement of the fellow eye
d. Mild visual loss
e. All of the above
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