Longitudinal Optic Neuritis Study (LONS)

Sponsor

National Eye Institute (NEI) (NIH)

Overall Status

Unknown status

CT.gov ID

NCT00000147

Collaborator

(none)

Locations

Study Details

Study Description

Brief Summary

To assess the beneficial and adverse effects of corticosteroid treatment for optic neuritis.

To determine the natural history of vision in patients who suffer optic neuritis.

To identify risk factors for the development of multiple sclerosis in patients with optic neuritis.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis Optic Neuritis	Drug: Methylprednisolone Drug: Prednisone	N/A

Detailed Description

Optic neuritis is an inflammatory disease of the optic nerve that typically affects young adults. Women are affected more often than men. It is second only to glaucoma as the most common acquired optic nerve disorder in persons younger than age 50.

In this disorder, closely linked to multiple sclerosis, prognosis for visual recovery is generally good. However, return of visual function is almost never complete. After resolution of optic neuritis, virtually all patients show some signs of optic nerve damage, and most are symptomatic. Even when a patient's acuity recovers to 20/20, abnormalities frequently remain in other measures such as contrast sensitivity, color vision, and visual field.

Prior to the Optic Neuritis Treatment Trial (ONTT), well-established guidelines for treating optic neuritis did not exist. Although corticosteroids had been used to treat this disease, studies to demonstrate their effectiveness had not been satisfactory. Some experts advocated treatment with oral prednisone while others recommended no treatment. Anecdotal reports suggested that high-dose intravenous corticosteroids might be effective.

The association between optic neuritis and multiple sclerosis is well established. Optic neuritis may be the first manifestation of multiple sclerosis, or it may occur later in its course. A strong case can be made for "isolated" optic neuritis being a forme fruste of multiple sclerosis, based on similarities between the two in such epidemiologic factors as gender, age, geographic distributions, cerebrospinal fluid changes, histocompatibility data, magnetic resonance imaging (MRI) changes, and family history. The magnitude of the risk of multiple sclerosis after optic neuritis is uncertain. Previous studies have reported very disparate results, with the risk being reported to be as low as 13 percent and as high as 88 percent. The importance of risk factors such as age, gender, and MRI changes in predicting which patients with optic neuritis are most likely to develop multiple sclerosis also is unclear.

The treatment phase of the study was called the Optic Neuritis Treatment Trial (ONTT), whereas the current long-term followup phase is called the Longitudinal Optic Neuritis Study (LONS). The study is being conducted at 15 clinical centers in the United States. Resource centers include a data coordinating center and a visual field reading center.

Patients were randomized to one of the three following treatment groups at 15 clinical centers:

Oral prednisone (1 mg/kg/day) for 14 days
Intravenous methylprednisolone (250 mg every 6 hours) for 3 days, followed by oral prednisone (1 mg/kg/day) for 11 days
Oral placebo for 14 days.

Each regimen was followed by a short oral taper. The oral prednisone and placebo groups were double masked, whereas the intravenous methylprednisolone group was single masked.

Baseline testing included blood tests to evaluate for syphilis and systemic lupus erythematosus, a chest x-ray to evaluate for sarcoidosis, and a brain MRI scan to evaluate for changes suggestive of multiple sclerosis.

The rate of visual recovery and the long-term visual outcome were both assessed by measures of visual acuity, contrast sensitivity, color vision, and visual field at baseline, at seven followup visits during the first 6 months, and then yearly. A standardized neurologic examination with an assessment of multiple sclerosis status was made at baseline, after 6 months, and then yearly.

Study Design

Study Type:

Interventional

Masking:

Single

Primary Purpose:

Treatment

Study Start Date :

Jul 1, 1988

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 46 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

The major eligibility criteria for enrollment into the ONTT included the following:

Age range of 18 to 46 years

Acute unilateral optic neuritis with visual symptoms for 8 days or less

A relative afferent pupillary defect and a visual field defect in the affected eye

No previous episodes of optic neuritis in the affected eye

No previous corticosteroid treatment for optic neuritis or multiple sclerosis

No systemic disease other than multiple sclerosis that might be the cause of the optic neuritis

Contacts and Locations

Locations

	Site	City	State	Country
1	University of Arkansas	Little Rock	Arkansas	United States
2	California Pacific Medical Center	San Francisco	California	United States
3	Georgetown University	Washington	District of Columbia	United States
4	University of Florida	Gainesville	Florida	United States
5	University of Illinois	Chicago	Illinois	United States
6	University of Iowa	Iowa City	Iowa	United States
7	Johns Hopkins University	Baltimore	Maryland	United States
8	University of Michigan	Ann Arbor	Michigan	United States
9	Michigan State University	East Lansing	Michigan	United States
10	New York University	New York	New York	United States
11	Duke University	Durham	North Carolina	United States
12	Devers Eye Institute	Portland	Oregon	United States
13	Wills Eye Hospital	Philadelphia	Pennsylvania	United States
14	Baylor College of Medicine	Houston	Texas	United States
15	Swedish Medical Center	Seattle	Washington	United States