Melanie Truong-Le, DO, OD, on the State of NMOSD and Optic Neuritis

Disease Spotlight | <b>Disease Spotlight: NMOSD</b>

The neuro-ophthalmologist from UT Southwestern Medical Center provided her opinion on the state of care for patients with NMOSD and associated optic neuritis technology.

Early detection of neuromyelitis optica spectrum disorder (NMOSD) is one of the key components for effective treatment of the disease, which has become more evident for providers since the identification of the aquaporin-4 antibody and NMOSD’s consequent deviation from association with multiple sclerosis (MS). Melanie Truong-Le, DO, OD, neuro-ophthalmologist, Peter O’Donnell Jr. Brain Institute, UT Southwestern Medical Center, highlighted the need to diagnose NMOSD and identify associated optic neuritis type early on in order to improve patient outcomes. 

In conversation with NeurologyLive, Truong-Le spoke on the latest advancements in the NMOSD field, as well antibody detection and the use of technology such as optical coherence tomography to observe nerve fiber layer and inform diagnosis. Although progress has been made within the field, questions still linger as to when providers can interrupt or discontinue therapy, Truong-Le said, and the high cost of infusion-based treatment has further limited access for patients.

Delving into discussion, Truong-Le provided unique perspective as an ophthalmologist, further commenting on the state of the pipeline and the overall state of care for patients with NMOSD. 

NeurologyLive: Can you speak about the latest advancements in clinical care or anything that has pushed the field forward over the last few years?

Melanie Truong-Le, DO, OD: This is a very interesting topic. Namely, because we now recognize this NMO spectrum disease to be related to a specific antibody. Prior to this, we thought it was part of this MS spectrum, and so with that knowledge from Dr. [Vanda A.] Lennon, MD, PhD, from Mayo Clinic, we realized that recognizing this condition early on is so important. That has driven our care in the neuro-ophthalmology side of things in a great way. What I mean by that is that it's so important to recognize the condition really early on. Very much like in neurology and stroke, we find that time is brain, and time is vision, as well. So, if we were able to see these patients early on, identify them, and treat them, the outcome is so much better. So that's how it's impacted our care and the way we diagnose our patients.

Now, some of the other findings we're also becoming more aware of is the pattern of enhancement on MRIs, [and] the ways in which we can detect these enhancements to allow us to diagnose the specific type of optic neuritis related to an NMO. What we understand now [is], not that there are specifically 2 types of optic neuritis, but specifically, there are divisions in optic neuritis. You have the typical optic neuritis that's related to MS, and then you have the atypical optic neuritis that we find with NMO spectrum disease. With that, the pattern of enhancement we see, and the involvement of the optic nerve, is different. In typical optic neuritis, we find that it's a small segment of optic nerve that's affected. In patients who have atypical optic neuritis, we find a larger segment of optic nerve involvement up to the chiasm, and in some instances, you're going to have bilateral involvement, which is highly significant, most patients will have decreased visual acuity 20 to 100 or worse. Sometimes they don't have the typical symptoms of optic neuritis as well; they may not have the pain that we typically associate with optic neuritis. We rely on these images to help gear towards that diagnosis now as opposed to before where we considered optic neuritis to be a clinical diagnosis. 

So, what are those patterns? On MRI we find that they tend to have T2 hyperintensities that may show, or enhancement patterns that may not be much longer and involving the chiasm, and they may also involve perineural tissue at the optic nerve sheaths. That speaks to the other aspect of NMO spectrum disorders in that we have found an association with another antibody, not just aquaporin-4 [AQP4] antibody but the MOG antibody that's also significantly related, although we still don't know the pathogenicity of that antibody in terms of the optic neuritis. That knowledge alone has helped us to diagnose our patients in the emergency room very acutely and say, “This I suspect to be atypical optic neuritis, and I need to…act on it really fast.” And that's because the outcomes for these patients are going to be dependent on how fast we treat these conditions.

What are the clinical applications of new technology involved with optic neuritis associated with NMOSD?

In NMO spectrum disorders and optic neuritis, in my clinical practice, some of the new technology—I wouldn't call it ‘new,’ although, if you compare that to 20 years ago, this is definitely new—but we do use other modes to monitor and continue to manage these patients, one of which is OCT.

OCT is optical coherence tomography, which is light rays in which we can detect or form cross sections of the retina, and this allows us to look at the nerve fiber layer. The nerve fiber layer is important because as part of the optic nerve, and in association with that is the ganglion cell layer. We find that the pattern of thinning in the NMO spectrum disorder [is] different from your typical MS, and that has helped us to monitor these patients using that as a new technology.

One of the other technological advances is in the detection of the antibodies themselves. Previously, we used ELISA [enzyme-linked immunosorbent assay] or the fluorescence sorting method to detect the antibodies, and we find that the sensitivity and specificity was not as high. So, with the use of cell-based assays, our detection rate for these antibodies is just so much more sensitive and specific, and that has helped us to diagnose fully these patients with more confidence. With that confidence, I think we are able to manage and treat them much more appropriately. Those two advances, I think, that I'm aware of in my practice, have given me more confidence in taking care of these patients, in terms of the optic neuritis aspect of it.

In your opinion, what is the state of the pipeline and R&D for NMOSD? Is there anything you’re watching closely?

What I would like to know, and [what] I'm looking at more actively, is some sort of evidence base to allow us to determine when to stop therapy. When should we interrupt therapy? Can we interrupt therapy? How long should we keep these patients on before we consider, “Well, sounds like you're therapeutic now, and I don't expect you to have another episode.” NMO spectrum disorders are very often recurrent, and they cause long lasting problems with these patients, for years. So, we still need that information, and I think that's most important to me in terms of clinical practice.

What would you say are obstacles that patients are still struggling to overcome or symptoms that are placing a large burden on patients?

The cost of vision loss, in general, is quite high in the United States as it is. Most of the studies are in the hundreds of billions of dollars for our patients and just overall global impact. It’s a high impact to our society, but in particular to optic neuritis, it's such a heterogeneous, mixed bag of conditions. For us to diagnose [patients] into NMO spectrum disorder, it is so helpful, so that we can tailor their treatment. The problem we have though, is the cost of the treatment is very high, and the access is difficult. A lot of the treatments are infusion based, and so you need to be in a large medical center to be able to receive these treatments. The access in terms of where patients are is difficult. 

Our knowledge about NMO and how the process affects the optic nerve is very helpful, and it's helping us to detect the condition well, but there are so many cases [where] because the vision loss is so severe, and those small percentages of patients that don't have antibody positive [NMOSD], that can’t be convinced that this is MOG associated, or that may have other autoimmune processes related with it as well—we don't have a good approach to treating them, and so there is a lot of uncertainty with these patients. That has made the burden of other health conditions difficult, like anxiety, depression, all those things impacting the patient.

I see a lot of burden on our patients because of this condition, and I also see the hope that we have in terms of understanding this process so much more now than we used to. Overall, if we can find a way in which we can diagnose it early and start the treatment early, I think the over the overcoming factor will be improved for the patient.

What is your opinion on the current state of care for patients with NMOSD?

I think the current state of care is pretty good. Where I am [at UT Southwestern, Dallas], we work to detect these patients really early on. We work together with a multidisciplinary team, and getting admission, getting plasma exchange, getting IV treatments early on is, I think, quite optimal. But as I said, access is key. So, the sooner we can get these patients here and recognize them, the better it would be. That’s the area I think we need to work on the most. 

Transcript edited for clarity.