Pupillary Light Reflex as a Pre-Treatment Biomarker For Repetitive Transcranial Magnetic Stimulation in Patients with MDD
In this video, Andrew F. Leuchter, MD, discusses his team’s study that examined pupillary light reflex (PLR) as a pre-treatment biomarker for repetitive Transcranial Magnetic Stimulation (rTMS) in patients with major depressive disorder (MDD). He talks about the outcomes associated with PLR and rTMS and how the study’s results may impact the treatment of patients with MDD.
Additional Resources:
- Citrenbaum C, Corlier J, Ngo D, et al. Pretreatment pupillary reactivity is associated with outcome of Repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder (MDD). J Affect Disord. 2023;339:412-417. doi:10.1016/j.jad.2023.07.008
- Citrenbaum C, Corlier J, Ngo D, et al. Pretreatment pupillary reactivity is associated with differential early response to 10 Hz and intermittent theta-burst repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD). Brain Stimul. 2023;16(6):1566-1571. doi:10.1016/j.brs.2023.10.006
TRANSCRIPTION:
Andrew Leuchter, MD: I am Dr Andrew Leuchter. I'm a distinguished professor of psychiatry at UCLA. I'm Director of the Neuromodulation Division and the TMS Clinical and Research Service in the Semel Institute of Neuroscience and Human Behavior at UCLA.
Consultant360: Can you tell us more about how your study came about?
Dr Leuchter: The TMS Clinical and Research Service at UCLA is a large treatment program where we're dedicated to helping patients recover from depression. We also, however, try to make every patient a research subject as we try to gather as much information about patients and how they're responding to treatment. And also study the changes in brain function that can occur during treatment as a way of potentially predicting who's going to do the best with TMS and also how we can adjust TMS stimulation to help each individual patient as much as possible.
We have run a series of studies over the years. We try to gather as much information as we can that will help us to elucidate how TMS works. We became interested in pupillometry a few years ago, that pupillometry is a very simple kind of measure. You shine a dim light into the eye and you see how it reacts to light, and it's a very interesting physiologic measure that tells you a lot about brain function. The eye is actually just a direct extension of the brain, so it's a very good window into understanding how the brain is reacting to treatment. What we found was very interesting. We looked at a series of patients before they came into TMS treatment, and we found that, in fact, how their eyes reacted to a very brief light stimulus told us a lot about how these patients were going to do during TMS treatment for their depression.
C360: Can you provide an overview of your study results, and were you surprised by what you found?
The very simple measure that we took here was taking a pupillometer, which is just a very small handheld device, shining it into the patients' eyes, right and left, and then looking to see how their eyes reacted to light even before we had treated them. I think the key and interesting finding here was that how the eye reacted to light told us a lot about how the patients are going to do in treatment in general. Specifically, the more briskly the eye constricted in response to a light stimulus was directly correlated with how well the patient was going to do during treatment. I think one surprising finding here was that even before we had started the treatment, the reactivity of the eye was a very good predictor of how well patients are going to do.
The second finding that we had from our study was that depending on which pupillary measure we looked at, we were able to say whether a patient was going to do well in treatment in general, but also what specific type of TMS might be of greatest benefit to them. So we looked at not just how much their eye reacted to light or how briskly their eye reacted to light. We also looked at the velocity of the pupillary constriction, and we found that if it was faster, that tended to predict response to one type of stimulation versus if it was a little bit slower, it tended to predict response to a different type of RTMS stimulation. I think the exciting thing about these results is that this very simple, easy to use measure, doing it before treatment can tell you a lot about how treatment should be delivered. So we're excited to get these results replicated, to have other investigators try to look at this and to tell us more about how reliable a measure this might be and whether it might someday be ready for use in clinical treatment.
C360: How do your results impact the clinical treatment of major depressive disorder in patients?
Our results suggest that depending on how your eye reacts to light, you may do better with one form of TMS stimulation, that is what's called theta burst, versus another type that is called rhythmic TMS or 10 hertz stimulation. Now, this is important because there are many different ways that one can deliver TMS. On average, they tend to be equally effective in large groups of patients. What our data suggests is that in subgroups of patients, one type of treatment or another might be more beneficial, and we hope that pupillometry is going to be a measure that will enable us to say, which type of treatment is going to be better for which particular patient. Now, obviously, this is just the first study of its kind. This is the first time that anybody has shown that pupillometry can tell us about TMS outcomes. This will need to be replicated hopefully in the hands of other researchers so that we can learn more about the potential usefulness and the impact of this on treatment.
C360: What is the next step in this area of research?
Dr Leuchter: One of the important principles of medical research is replication. We have very encouraging results in this initial study. We need to look at this in a larger number of patients. One would want to look at this in probably up to a couple of hundred patients to see if the same findings hold. Ideally, we'd also like to see other groups start to use pupillometry to see whether they get the same findings that we did, and then we'll be more confident that this is a robust measure that might be ready for prime time, that might be something we could use in clinical treatment.
C360: What is the overall take-home message from your study?
Dr Leuchter: The most important take home message here is number one, TMS is a very effective treatment for depression. If you take a look at the overall study, the great majority of patients benefited from TMS. What our study showed was that we were able to fine tune the TMS depending on how the eye and therefore the brain reacted to light. If we use these kinds of physiologic biomarkers to help guide TMS treatment, we might be able to make TMS treatment even more effective. Right now, we see that 60 to 65% of patients get better with TMS. We think that by using these kinds of physiologic biomarkers, we might be able to get the number of patients who benefit up to 75 or even 85% of patients just by carefully selecting the particular type of stimulation that is being offered to patients. So we're very excited to see these results out there, to have them go into the hands of other clinicians and researchers and see whether this finding holds up on replication.
Dr Leuchter: Thank you very much for the opportunity to talk with you today about these results. I think that it's important to get the message out there to patients that there are many effective treatments for depression, and TMS is one of the newer kinds of treatments and can be very effective for the treatment of depression. And we hope that research such as this will make it even more effective in the future.