ACTH Neuroprotection in Acute Optic Neuritis

Robert C. Sergott, MD: Another big reason for patients to lose their jobs, not be able to work, is fatigue. This is a mitochondrial problem that they’re getting. As I mentioned earlier, we undertook a small study that looked at optic neuritis patients with an old medication called ACTH [adrenocorticotropic hormones], that has some properties in addition to steroids and often can be helpful for patients who are intolerant of steroids. And it’s not, is what we call mini immunosuppressive as steroids.

We looked at acute optic neuritis patients. It was a study of 24. They were treated with this rather than IV [intravenous] steroids, and the goal of the study was to see if they get a little better with their vision. Optical coherence tomography scans were done to see if there was any preservation of the retinal ganglia cells or the axons. That was our primary outcome. The medication failed there. It didn’t preserve those structures, but to our surprise—and we know it’s correct because we didn’t expect this at all—the opposite eye improved in low contrast. The patients told us this. These were eyes that nerve had optic neuritis, and this brings up this whole issue now of we can really do a good job, an excellent job of stopping attacks, but we have to start getting into the area of repair and neurodegeneration. Rod, what do you think about this? Would you ever start testing low contrast and cognitive function on your optic neuritis patients?

Rod Foroozan, MD: Low contrast is very simply done just by altering, as I said, with a computer chart. The thing is that when you’re measuring contrast sensitivity, you have to be careful because you have to have the ophthalmic background because there are many things that affect contrast sensitivity, anything from a cataract to even impaired astigmatism or a bad refraction. Let’s put all those things aside and say we can do it; that’s something that’s readily doable. I haven’t considered the cognitive part yet in my patients. As you said, they tend to be young. We think they tend to be doing well, but maybe that’s something we’ve been overlooking.

I’d really like to add, and I know you are a big advocate of structural measures in the retina and in the optic nerve, looking at patients with optic neuritis. This has also been a game changer. When I was in training, OCT, optical coherence tomography, was just becoming widely used in the clinic, and it had been used on a research basis for probably 10 years before that. But what it’s showing us now is basically in vivo, the structure of the ganglion cells, the structure of the retina, and what we know is not only patients with optic neuritis but patients with degenerative disease in general, and I think MS [multiple sclerosis] clearly falls into that category, showing decreased measures over time.

This tool has become instrumental not only in the clinic but in research studies even as a primary outcome for studies on optic neuritis in looking at changes over time in retinal thickness. In the study you’re talking about with ACTH, that was 1 of the concerns. One of the interesting findings was a change, maybe you could describe it for us, of the structural parameters we saw in the retina after treatment.

Robert C. Sergott, MD: We saw some increase there in ganglion cell thickness. And what was interesting is that it didn’t matter what the axons were doing. The axons disappeared no matter what. Is there something there that we use to get rid of these bad axons? Could something else come along to create repair? It’s a very complex issue but 1 that patients want and is completely where our field needs to go.

Getting back to the OCT, we found this to be extraordinarily important in finding NMO [neuromyelitis optica] versus MS. The central retinal artery with multicolor OCT—it’s a very special type of OCT—will show that that artery turns green, meaning it’s ischemic. This makes perfect sense because that’s what happens in the spinal cord. The reason why these patients don’t get better is because it proceeds to have central retinal artery occlusion. This is a vasculitis. So that’s key. We can also find rare diseases like Susac syndrome this way and a couple of other things that can resemble MS, even for the best neuro-ophthalmologists. We have to keep doing this.