Optic Neuritis and Brain Lesions

Robert C. Sergott, MD: Rod, now you’ve got the patient. Let’s say they have optic neuritis and they’ve got brain lesions that look like MS [multiple sclerosis], and with their vision, they can see only the big E on the chart. What are you going to do next?

Rod Foroozan, MD: The next thing I’m going to do is look at the pattern. It’s important to point out also that we want to do the MRIs [magnetic resonance imaging tests] with contrast whenever possible. The pattern of contrast enhancement of the optic nerve is often important, and that will help distinguish some of the imitators from typical MS that we may talk about. Once I’ve made the decision that I think it’s inflammatory optic neuropathy, then I’m going to recommend treatment. We used to say, “Whether we treat or not really doesn’t make an impact as far as the visual outcome.” But now I think there is some accumulating evidence that suggests earlier treatment is more beneficial to saving the optic nerve. So that treatment for me is typically going to be intravenous [IV] corticosteroids.

Robert C. Sergott, MD: Intravenous corticosteroids have a very interesting history with optic neuritis. We were confronted with a number of patients who had terrible multiple sclerosis. We didn’t know what to do. We contacted a very good rheumatologist-immunologist in Philadelphia, Ralph DeHoratius, and he told us about using the steroids at these high doses for patients with lupus and kidney disease. And that’s how their high-dose IV steroids got started.

We kept using them, and eventually 1 of our fellows, Roy Beck, was fascinated by this and set up a clinical trial called the Optic Neuritis Treatment Trial, which enrolled over 400 patients with their initial episode of optic neuritis. Now when you look at clinical trial data, we always have to look about when the trial was done and what the technology was at that time.

At that time, MRI was not as powerful as it is now. The magnets weren’t as big. The magnet strength is measured in teslas—not the cars but the strength of the magnet. As Rod correctly pointed out, we do these scans now all the time with an enhancing agent called gadolinium. The initial scans on the patients in the Optic Neuritis Treatment Trial did not have gadolinium. If anything, that trial may have underestimated how many other lesions were present. Rod, what came out of that trial as far as guidelines for us now with optic neuritis leading to MS?

Rod Foroozan, MD: There were a handful of things that came out. One was that there was no difference in visual outcome when you looked at 6 months and subsequently, even out to 15 years, whether you got treatment or not. And there were actually 2 arms—either IV steroids or oral steroids, and that was it. One of the key things that came out of the trial was that if you got the oral only, and this was at a dose of around 1 mg/kg, then you had an increased incidence of optic neuritis in the same or fellow eye. To this day I don’t think that has been explained. But it is a strange thing that happened out of the study, an unexpected outcome.

The other thing was that there was a small protective effect within a 2-year window of developing clinical MS by the IV steroids. If you got IV steroids, your rate of clinical MS was less by 2 years. But after that, by year 3 and every other time point afterward out to 15 years, there was no protective difference with the IV steroids. We used to say, “We’re going to treat you with IV steroids because it will speed the onset of visual recovery,” but it’s not going to make a difference in the visual outcome.

Robert C. Sergott, MD: That’s right. I think there was a placebo oral arm as well but not a placebo IV. And the results have been somewhat controversial. It’s actually the first time that MRI was demonstrated, as I said earlier, to make the invisible visible in a controlled trial. While there’s a lot of debate still about what you do in terms of IV and oral, the Optic Neuritis Treatment Trial, which Rod just talked about, showed us the natural history of this disease. The trial was continued for 15 years, a really remarkable achievement by Roy and his team. And we were the leading recruiters for this trial. We enrolled 40 patients after 15 years, and remember this was before we had medication to treat MS; only 20 were well enough to come back for repeat examination. This shows you that multiple sclerosis must be treated. The FDA now will not allow trials with placebo. You must treat with a comparator agent.

So the Optic Neuritis Treatment Trial really showed that 15 years later, the majority of our patients were disabled. That’s getting back to what people read on the internet—that is still there. And we treat, as Rod said, with IV steroids and then quickly initiate 1 of the disease-modifying medications. If someone doesn’t want to take 1 of the disease-modifying medications, that’s a mandatory second opinion in our practice. All the trials have shown, as Rod was saying, that the sooner we treat, the better. We’re still looking for the first disease where it’s better to treat it later.