The results of this study show that there is no difference in visual outcome in patients with acute ON, treated with high-dose MP (≥500 mg per day) given orally or intravenously. Interestingly, in analogy with the present study on ON, others have studied the effect on MS relapses following high-dose oral corticosteroids, showing no inferiority of oral administration compared to i.v. administration, regarding MS disability outcome [14,15,16]. Furthermore, the results of our study are supported by a recently published prospective study on bioequivalent doses of corticosteroids in the treatment of acute ON, showing that oral administration of corticosteroids is not inferior to i.v. administration in terms of visual acuity and visual evoked potentials at follow-up . It could be expected that the effects of oral and i.v. treatment would be similar as the bioavailability of oral MP has been reported to be as high as 82% of that given intravenously . Interestingly, we found no difference in visual outcome, even though the oral group did not receive bioequivalent doses. Replacing high-dose i.v. administration of corticosteroids with oral administration would be of benefit to both the patient and the health care system. Indeed, the tolerability has been reported to be similar for both oral and i.v. administration of corticosteroids [15, 16].
In previous studies of oral versus i.v. administration of corticosteroids for the treatment of ON, equally high doses have not been tested, i.e. low-dose oral corticosteroids have been compared to high-dose i.v. corticosteroids. This is the case in the ONTT, in which the patients treated with oral corticosteroids received much lower doses of corticosteroids than those receiving i.v. treatment . The rate of return of visual function was found to be higher following i.v. MP than with placebo, and the i.v. group exhibited slightly better visual field, contrast sensitivity, and color vision, but not better visual acuity, at 6 months. This was not found to be the case when oral administration of prednisone was compared to placebo. At 1 year, no difference was found between the groups, regardless of the route of administration .
In other studies, only a single route of administration of corticosteroids has been assessed, i.e. either i.v. or oral, and compared to the effect of a placebo. It has been reported that i.v. administration of corticosteroids increased the rate of recovery compared to placebo, but did not influence the final visual outcome [5,6,7], or the length of the lesion in the optic nerve . Interestingly, in a study by Sellebjerg et al., the rate of recovery of visual function was improved in patients receiving high-dose MP orally compared to those given the placebo , showing the beneficial effects of high-dose oral steroids in the treatment of ON, supporting the findings in the present study.
As disease-modifying therapy may alter the course of recovery in acute demyelinating events [19, 20], such cases were excluded from the present study. However, patients undergoing therapy prior to the incident of ON were not excluded. The number of patients undergoing disease-modifying therapy was higher in the group receiving i.v. MP. The contributing effect of these agents on the course of recovery in acute demyelinating events has rarely been evaluated , and an additional effect can therefore not be ruled out. Prospective studies evaluating the effect of corticosteroids without disease-modifying therapy in the acute phase might be difficult in patients with demyelinating acute ON, as the criteria for the diagnosis of MS have changed during the past decade, and treatment with disease-modifying agents is now initiated early.
The test methods chosen to measure visual function were visual acuity, visual field and color vision, as these together provide a comprehensive picture of visual function. Regarding the visual field, a strength of our study is that we measured visual field defects by counting the number of highly significantly depressed test points in the total deviation probability map. This is likely to provide a more sensitive measure of visual field defects than the MD, since the latter is the average value of all deviations from the age-corrected normal threshold values of all test points in the visual field. We included the MD in our analysis to enable comparison with previous studies using MD as a measure of the visual field.
One limitation of the present study is the small number of subjects, which makes it difficult to draw definitive statistically supported conclusions. As this was a retrospective study, the data available in the patient records were also limited. For example, there was no information on visual evoked potentials (VEP) or Optical Coherence Tomography (OCT), as these are not standard tools for evaluating recovery after optic neuritis in a clinical setting at the departments included in the current study. For future prospective studies, this information would be of interest to analyze. Furthermore, the test used for color vision measurement is a non-specific test that is not optimized for the detection of acquired color vision deficiencies. A more suitable test should be used in future trials evaluating acquired color vision deficiency.
Regardless of whether ON is treated or not, the visual function starts to recover within 1 month [3, 22]. As ON improves spontaneously, treatment with corticosteroids has been questioned. A Cochrane review found that there was no evidence of any beneficial effect of oral or i.v. corticosteroids compared to placebo regarding visual acuity, visual field or contrast sensitivity outcomes . However, even when visual acuity returns to normal, many patients have lasting symptoms of visual disability . Optimal treatment should include the rapid relief of symptoms, as well as the prevention of tissue damage. Previous studies have shown that treatment with corticosteroids in ON has an effect on the rate of recovery and that the short-term risk of development of MS is reduced . The effects of corticosteroid treatment have also been evaluated on brain MRI-derived quantities in MS, including gadolinium-enhancing lesions, showing a decrease in the number of lesions after treatment, also indicating the positive effect of corticosteroids [26, 27].