Neuromodulator therapy for dry eye disease: an exciting new option
In part 3 of a 5-part video series, Marjan Farid, MD, of the University of California, Irvine; Karolinne Rocha, MD, PhD, of the Medical University of South Carolina; Nathan Lighthizer, OD, of the Northeastern State University Oklahoma College of Optometry; and Cory Lappin, OD, the Dry Center of Ohio, discuss a new treatment option for dry eye disease, TRYPTYR (acoltremon), which targets the basal tear production pathway.
Marjan Farid, MD:
Again, therapeutic-wise, we’ve had anti-inflammatories, now we have a couple of treatments that work upstream to try to improve the patient creating their own tears with neuromodulators. I kind of want to throw it maybe at Cory to talk about some of these new therapeutics. Where do they fit in? Are you using these early in the tear film?
Specifically, we have one neuromodulator that works through nasal stimulation of the trigeminal nerve, and now we have a new neuromodulator, which is acoltremon or TRYPTYR, that works with nerve stimulation on the ocular surface with the cold receptors. Tell us a little bit about where these fall into your therapeutics.
Cory Lappin, OD:
Yeah, these are really, really exciting because, like we talk about, dry eye being a vicious cycle and you can have inflammation, but a lot of times inflammation is actually a result of this tear film instability, it’s not necessarily the driver. Now, you can have autoimmune cases where you do have that primary inflammation, but oftentimes that inflammation is the result of tear film instability. Either you’re under-producing it or the tears you’re producing are of poor quality. If we can address that natural tear production, and I think it’s important that we discuss natural here because, as you even said at the very beginning, you can put artificial tears in all the time, but you’re not really … the key there is artificial. Because an artificial tear is not a real natural basal tear. The basal tears that we produce are compositionally different, I mean, and they’re so complex. There are over 1,500 different proteins, there are over 600 different lipid species. There’s up to 8 different mucins on the ocular surface. That’s a hard thing to replicate. I mean, we don’t even fully understand what’s in there.
But that natural tear is what we need to nourish and protect the ocular surface. All of our patients really no matter where they are in this dry eye cycle would benefit from increasing natural tear production. That’s where, again, you talked about we had this nasal mechanism, but for the first time we actually have a medication that directly targets, in a topical form, this basal tear production pathway. That’s what we have with TRYPTYR or acoltremon.
What it does, it’s really a cool way that it does this, is we have all these nerve receptors on the cornea, I always like to point out it’s the most densely innervated structure on the body. We have 7,000 nerve endings per square millimeter. That is crazy. It’s more than dental pulp. I like to say that because everyone talks about how bad root canal hurts. But you know what? The cornea is even more sensitive. Okay, dentists, we win in this one. I always like to bring that up, a win for the eye care providers here.
But the reason why we have so many nerve endings is because what they’re sensing. They can sense physical touch, they can sense noxious stimuli like when you’re cutting onions, but they can also sense temperature. Within that class there’s 2 types of receptors. Some of the receptors that sense temperature are extreme heat and extreme cold. When you go outside on a cold blustery day and your eyes start watering, that’s a reflex tear.
There’s also this subset of receptors called the TRPM8 receptors. These sense very small changes in temperature. The reason why they sense this is because they’re involved in our natural tear production. When we produce tears, eventually the tears will evaporate. If you’ve ever asked yourself, how does the body “know” how to produce more tears, this is what it does. When you get that natural evaporation of the tear film, you’re actually going to get a slight cooling of the surface. The same way that when we sweat, it’s supposed to evaporate and pull heat from our bodies, that’s what cools us down.
This cooling actually will trigger the body, basically these nerves to go back to the brain and say, “Hey, I got to produce more natural tears.” That’s where acoltremon or TRYPTYR comes in. It actually stimulates that TRPM8 receptor the same way and stimulates natural tear production. It’s a really cool, elegant way to use the body’s own natural tear pathway to produce these basal tears.
Marjan Farid, MD:
I totally agree. We’ve never really … it’s such a cool thought because this is what our body is naturally doing and we’re augmenting that process with acoltremon. We’re basically harnessing the body’s natural system, which I think is really cool.
The question is … and I love how you said there’s multiple proteins, thousands of proteins in the tear film, and a lot of those are growth factors. If you’re not only putting … An artificial tear does not have growth factors, it doesn’t have the mucins. Natural tear is going to have those growth factors. If you’re having erosions on the ocular surface and you’re looking at regrowing healthy epithelium, possibly even improving the nerves of the ocular surface, you have growth factors in your natural tears that can help do that. Augmenting those, I’m excited about it because it can really help potentially heal the ocular surface or let the body heal itself with its own natural mechanisms, so I love that.
