Podcast: Modern approaches for the optimal treatment of dry eye disease (Part 2)

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Bill B. Trattler, MD, Crystal Brimer, OD, Cynthia Matossian, MD, FACS, and Kelly K. Nichols, OD, MPH, PhD, discuss dry eye disease and the various approaches clinicians can take to treat the disease in the second part of the Viewpoints Podcast.

Editor’s note: This transcript has been edited for clarity.

Bill B. Trattler, MD: Thank you guys so much. That was just a great overview of all the different variety of ways we can diagnose patients with dry eye. And now we can get to the fun part, which is how we treat patient’s dry eye. Let's start with Dr. Nichols. You know, there's so many different ways you can treat patients. Let's talk about [if] your patient comes in. They only have had artificial tears. What's your kind of first line treatment for patients? If you want to separate evaporative versus aqueous-deficient, that's perfectly fine too.

Kelly K. Nichols, OD, MPH, PhD: I'm going to take a tiny little step back before that, though. I think it really depends on how they're coming to you, where they are in the dry eyes road. Because they make it to like a practice where, you know, a specialty practice and they've never seen anybody before. Like they think that they've they have dry, they've heard something on TV, they've gone to the market, you know, found something on their own. But then there's also people who have this long history. And so, they may look like they've not tried anything, but they've tried a lot, maybe not a lot for a long time, like they've never stayed on anything consistently. So, it really does depend on how they're coming to you, where you start. So if they're like a naive to everything [patient], they're usually not, because they've tried something on their own, like artificial tears, and so your next step should be a process so that you can follow a process with your patients depending on what type of dry eye they might have, whether you think it's aqueous-deficient or it's evaporative or some combination of both. And if it's one or the other, you're going to lean towards some different treatments, especially if you think there's a lot of inflammation there or not, or how bad their meibomian glands might look. So, what you don't want to do is like what I call a "kitchen sink it," all at one time where you're just throwing everything in at once. So, you should start with what you think is the most predominant factor of their dry eye, the finding of their dry eye, and go from there. But I don't know that there's a simple answer to that because they all come to you different, you know, from their history and what they've tried before. Finding out what they've failed is really important to success, I think, in a new setting.

Bill B. Trattler, MD: Now, those are great points. I totally appreciate exactly what you're saying because this is a difficult question. But for time reasons, we'll just try to make sure everyone gets some thoughts here. Dr. Brimer, when you see a patient, and I really want to set the stage as Dr. Nichols shared, there's not just one type of patient, but let's imagine a patient that is a contact lens wearer, they've used artificial tears and now they're coming to see you because they're having contact lens intolerance. What is your typical first line treatments for these types of patients?

Crystal Brimer, OD: I want to look at the underlying cause of what's creating the dryness. So, if it's a contact lens patient, I'm going to look at the material and I'll look at how they clean them, is it daily disposable, that sort of thing. But I'm just not the person that typically recommends tears much at all. And [it's] fine, if it's an occasional dry eye and its situational dry eye, I want them to use preservative-free tears. But most of the time and again, my perspective is different because they're coming to be more advanced. So, we've got to throw that out there. But most of the time they've gotten where they are because they've been using the tears chronically for years and it's progressed because they've pacified the emergent need by putting tears on it. So, they've made it through another day and another day, but meanwhile, things were getting worse. So, I tell patients, I'm not going to stop you on your tears. You can keep using them for now. But my goal is to figure out what's going on so that you don't need them anymore. And when you come back to me and you say, "Oh, I'm just using tears, you know, once or twice a week." Then we know we're where we need to be. So, I'm not going to change the tears. I am going to look at the material. I'm going to look at what their modality is, how they're cleaning them. But primarily, I'm going to take those contacts off and say, what else is going on here that we need to address more at the root cause?

Bill B. Trattler, MD: These are a beautiful way of approaching this type of patient. You're absolutely right. Well, let me ask Dr Matossian about artificial tears in general. What are your thoughts on artificial tears in general? Are there some challenges them or are you happy with them? And how often do you, you know, as Dr. Brimer suggests that she doesn't stop tears, but maybe tears aren't always the answer. I'm just curious of your thoughts on tears.

Cynthia Matossian, MD, FACS: You know, Bill, there are challenges with artificial tears. The first one is if we as eye care providers don't take the time to look at what's going on and instead just very rapidly or superficially say, "Oh, Mr. Jones or Mrs. Jones, just use some artificial tears." We are not doing the patient the service that they deserve. We need to dig and figure out the cause and appropriately treat. Just throwing tears just to kind of mollify the patient is not ideal. Secondly, if we don't specifically recommend a type of tear, we're also doing that patient a disservice. Have you recently checked the shelves in the grocery store or the drugstore, in the eye section? It's row after row after row of different types of artificial tears. So, somebody who is not an expert in the field, how are they to choose? They don't know. So, they go either A, the cheapest one, B, that's on sale, or thirdly, they buy something completely wrong, like an anti-allergy drop to get the red out because their eyes are red due to DED (dry eye disease), not from allergies, or they get an eye whitener. So, this then further exacerbates a dry eye condition. So, these are the challenges. We need to help our patients by digging deeper to specifically recommend certain types. And lastly, like Crystal said, preservative free artificial tears are the way to go. These are people who are already suffering. They're in your offices for a reason. And the preservatives in tears can make the situation worse.

Bill B. Trattler, MD: There's just such great points. I totally agree with you. So now that you've pointed all those issues out and ways of approaching artificial tears, I'm going to go back to Dr. Brimer and ask the next question, which is, okay, so they exhaust artificial tears, they've used them and they're not doing anything. So now you're ready to use an anti-inflammatory agent. I guess the question is, when do you make a decision? When decide, okay, now it's time to add an anti-inflammatory agent into the therapy for dry disease.

Crystal Brimer, OD: Two situations. So if a patient comes to me and it is very obvious they are on fire, their eye's red, their lid margins are thick and hyperemic, there's a lot of telangiectasia, there's just chronic inflammation, and especially if the patient's in a lot of pain, I know that a lot of the other things I'm about to ask them to do are going to involve delayed gratification. And so, if I go ahead and give them a steroid to kind of quench the fire at the moment, it's going to help them stay on course and stay on track to do what I'm asking them to do, because they're going to get some relief early on. Now, when I do that, honestly, I like to use a steroid ointment because I'm asking them to do other things. And that way it's only a once-a-day dosing and it kills two birds with one stone because it gives them that nighttime lubrication. And I'm not doing refills. I'm just trying to get them over this hump so they can feel a little relief while the other stuff is kicking in. And the other times that I'll do it is more when we're along the journey and there's a flare. So, I don't think that was really your question, but I threw it in there. And typically, I'm going to implement more in-office procedures than I am going to [use] a chronic drug. So, I use chronic anti-inflammatories, but I'm more likely to do a quick steroid to put out the fire, do in-office procedures to get to the root cause, and then if I need that ongoing anti-inflammatory, then I'll incorporate that.

Bill B. Trattler, MD: Okay, beautiful. And I totally agree. I mean, you made some great points on how we can use steroids so effectively for a dry eye patient in different scenarios. Maybe we just talk about, in general, just all the various anti-inflammatory technologies that we have available to us. I'm going to ask Dr Nichols because, you know, we have a few different options. We have cyclosporine, we have lifitegrast, we have obviously topical steroids, and Tyrvaya or varenicline, I hope I said that right. As everyone knows here, I'm not the best at pronouncing names. So, Dr. Nichols, maybe share kind of how these and anti-inflammatory treatments are similar or different and I guess an overview of those products’ product.

Kelly K. Nichols, OD, MPH, PhD: Great. And I will have a question for all the panelists too at the end, because if you don't have the ability or you haven't done in-office procedures, then your approach might be different relative to some of these other therapies that Bill just mentioned. So, you know, it is interesting, depending on where you are, I know if you have, I know what I would do if I had everything in my office versus if you only have yourself and your slit lamp. So having said that, you know, inflammation is one of the body's ways in which it can respond to insult or injury or irritation. And so, you're going to have inflammation with ocular surface conditions regardless. In some cases, it's not going to be obvious, and in others it's going to be much more obvious. And in some instances, there's going to be associated factors where they have inflammatory diseases that go along with what you're seeing on the ocular surface. So, your choices may be different depending on what else is going on. We have cyclosporine, [its] been around for the longest of all of these medications. It had like at least a 15-year head start on lifitegrast. So, we tried it, we used it. It was all that it was available. And originally when cyclosporine came out, I think a lot of doctors saved it for the worst dry patients because they really didn't know how it fit into the algorithm and what they should do. And then there were a number of doctors actually who tried it for a short period of time or patients, and then patients stopped for whatever reason, they didn't get the full effect or maybe they didn't realize they got some effect. And so, they quit. When we are seeing patients for clinical trials now, most of the time they've tried cyclosporine at some point in the past, but when they describe how they tried it, it can be like they just they say, "well, I did try it." Well, how long did you try it? "Well, I don't know." You know, you ask them if they refilled their prescription to find out if they really tried it. And most of the time they don't. And I would say that's even sort of true with lifitegrast, especially if the patient has symptoms of the negative side effects, you know, whether they have blurry vision, or with cyclosporine, if they have a lot of stinging. Now there are ways that you can coach a patient around those if you really do feel like having a chronic anti-inflammatory therapy works, and they do, they just do take some time to kick in based on their mechanism of action. They're all slightly different. Then of course, we talked about steroids just a moment ago, which give you that first initial burst acute help. And then there's, I'll just call it Tyrvaya as well, because Bill I'm with you, I'm the camp of can't pronounce any of the new names. There's a few that were just approved, that we'll talk about later, and I'm like, wait a minute, how do you say that? What do we to do? But yeah, so I don't know that I'd put that in the controlling inflammation category because it is sort of like an internal, self-regulated, artificial tear that your own body makes. So, I guess it can help calm any inflammation on the ocular surface because it's helping to sort of give some lubrication, perhaps, that might have been what was part of the problem, in terms of causing inflammation. But you do have to get to the root of it. And these can all help in their own ways, but they don't solve the problem in most cases.

Bill B. Trattler, MD: That is a great overview. That actually was lovely to hear because I think it really helps us kind of set the framework for everything. I think, you know, obviously the two main categories, cyclosporine and lifitegrast, we've had them both now a little while, and you know cyclosporine was first. I'm going to ask Dr. Matossian, maybe you should explain the mechanism of lifitegrast and give an overall view. Because I think even though it's newer and it's been around for a bit, I think it's always helpful to kind of review that.

Cynthia Matossian, MD, FACS: Well, I will try to make it as simple as I can, but it is complex. In essence, Xiidra or lifitegrast blocks LFA-1. So, what is LFA-1? LFA one is a surface protein found on the surface of T-cells. So, T-cells are just floating about regularly, looking to be invited to an inflammatory site. When the surface is stressed, there's something called ICAM-1s that are overexpressed. ICAM-1s invite or recruit T-cells. The way a T-cell docks onto the ICAM-1 is by its LFA-1. So, it's kind of how they come together. So lifitegrast blocks that ability of the LFA-1 to dock with the ICAM-1, and it's only through the docking that the T-cell is then activated and then it releases all the pro-inflammatory cytokines, and more recruitment of T-cells happens. So, by blocking it, not only inactive T-cells, but active T-cells as well, it kind of reduces that perpetual inflammatory cycle on the surface of the eye.

Bill B. Trattler, MD: That's a beautiful explanation. That was fantastic. I definitely could not have explained as concisely as you did, Dr Matossian, that was beautiful. We all realize, I think all of us, enjoy being able to use lifitegrast or Xiidra. And I'll ask Dr Brimer, you know, how do you decide? So, your patients come in, and you know, there's a cost to using medications, you obviously don't want to over medicate. How do you decide when to use lifitegrast versus cyclosporine, when you're going to add one or the other. What is the key [difference]? How do you decide between the two?

Crystal Brimer, OD: I feel like that's such a biased answer I'm going to give you. You know what I mean? In my clinic I have my favorite, I have my tear. I feel like absorption is important. You see all the newer molecules coming out with smaller size molecules and ways to protect it to get through the aqueous, so that it absorbs in the tissue better. But ultimately, I think a large factor is going to be patient tolerability. And I had a patient today, and I hardly ever do this, but I broke down and did it, I gave them samples of each because everything I've ever given, it was like, "No, no, no, no." And I said, "Listen, take five days with this. Take five days that call me back." Because I just don't expect a difference in how you feel. I just want to know what you can tolerate. So, at this point, I'm grateful to have options because none of these three, and even the ones to come are going to be perfect for every patient. And yes, we care about efficacy, and we want to get the most efficacy as quickly as we possibly can. But if they're not compliant, we're not going to get anything. And so, everybody is going to have a different response on what side effects they have, and what side effects they can tolerate. So, does it burn, does it give blurred vision? Is there a bad taste? And so that's one of the factors. One of the factors is cost. And I no longer can predict anything when it comes to that. But I do know that a couple of the companies have patient assist programs and I appreciate that, when they're able to come to the table and help my patients that can't afford it.

Bill B. Trattler, MD: Those are great comments and I agree. Any challenges? And I'll just briefly ask Dr. Nichols and then Dr. Matossian for this particular question, how do you decide between the two, because there are two good options. They both have really nice effects. But just curious, let’s go with Dr. Nichols, like how you kind of figure out which to use first

Kelly K. Nichols, OD, MPH, PhD: We're in a teaching institution, so we keep that in mind as well. I mean, you know, we allow for our students to select which [treatment] they're going to try on a patient so that they can experience that while they're in school. And so, I used to have a preference and now I just sort of like to see where it goes with overseeing patients. Because [in reference to] the cost issue, we have a clientele at the school which isn't necessarily well off. And so, the patient assistance programs are good. Medicaid reimbursement for some of them are really helpful for patients. And certainly, now there's generic, which can be helpful, with cyclosporine. So, I do think that there are some options to be thinking about that, that I would hate to say, you know, yeah, I think about cost, because you never know what a patient is willing to pay for and what they're not. But yet giving them good options is critical and allowing them to try and see what side effect profile they have is also important because they have to stay on it in order to see an effect.

Bill B. Trattler, MD: Right. Great. Great points. Dr. Matossian, your thoughts on the two options?

Cynthia Matossian, MD, FACS: You know, I wish I could say we were in control of what drug our patients received. Just because we are prescribing it does not mean that that is the medication the patient is ending up with. Unfortunately, many switch outs happen at the level of the pharmacy because of the insurance program that the patient has. Maybe because of the amount of co-pay difference. So, there are so many different factors that go into how a patient ends up with a particular drug that I can no longer predict, if I write for A, do they get B, do they actually get A, or is it switched out? So, I'm happy if they end up with an immunomodulator, when warranted.

Bill B. Trattler, MD: That's a great answer, and it’s so true. I find the same thing. I'll write one and then I hear from my tech, "oh, sorry. That one wasn't the first time on there are lists of drugs and you have to go to this one now, unless they had failed this one." You know, it’s kind of can be challenging times. But I guess the point is that we have these great options. Our patients do have options. If one doesn't work, they can switch to another, and vice versa.

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