. Today’s title is “Exploring the Management of Dry Eye.” I’m Cynthia Matossian from Matossian Eye Associates. I am exclusively focused on dry eye disease. I’m the founder and medical director of Matossian Eye, and we have offices in New Jersey and Pennsylvania. I am honored to be joined by my wonderful colleagues, who are esteemed in the area of dry eye disease. We have Dr Rahul Tonk, assistant professor of clinical ophthalmology and medical director at Bascom Palmer Eye Institute in Florida. We also have Milton Hom, an optometrist at Canyon City Eyecare in Azusa, California. And Dr Kelly Nichols, the dean at the School of Optometry at the University of Alabama at Birmingham. For today’s discussion, we are going to focus on dry eye disease, the various opportunities to diagnose, and the different treatment modalities that are available to us. Toward the end we’re going to talk a little about exciting new agents in the pipeline. Let’s get started. Is everybody ready?

 Good. Dry eye disease has so many names, right? Like dysfunctional tear syndrome, ocular surface disease, MGD [meibomian gland dysfunction]. Rahul, we’ll start with you. How do you define dry eye disease?

 To me, dry eye is a multifactorial disease that involves both symptoms and objective signs. At the root cause, many people would agree, as established by the Tear Film & Ocular Surface Society, that inflammation is at its core. There can be a variety of culprits at play, from lipid layer insufficiency and evaporative dry eye to aqueous deficiency, and there can be broad overlap with these subtypes. But there’s also a neurosensory component that we must recognize where we may not always be able to identify these portions and treat them in a purely scientific way, and we must give some thought toward the higher cortical aspects of neural sensation and pain. Broadly speaking, that was my sense of dry eye, and but there are many ways to define that.

 Milt, do you want to add anything to the wonderful description that Rahul gave?

 No, that sounds like a perfect description of what’s going on. I remember we were part of the Delphi panel a few years ago. It was the dysfunctional tear syndrome, and 1 of the things that we really struggled with was defining what dry eye was. We probably spent maybe half the discussion talking about what dry eye is. The problem is, as some of the clinicians brought up, “What happens if somebody has a wet eye? Is that considered to be a dry eye?” Things like that. Finally, we came up with dysfunctional tear syndrome. But what Rahul was saying, I perfectly agree with. That’s the updated definition of dry eye.

 That’s great. Kelly, in your position, you’re always with your students. What are the common symptoms of dry eye disease that you teach your students?

 Originally, we thought of dry eye symptoms as dry eye—just saying do you have dry eye?—but also discomfort, irritation, even itching can be a common symptom of dry eye. Now we focus on some of the visual symptoms that patients can have; blurry, distorted vision, vision that you need to blink to clear. Sometimes it might be a situation when they’re using computers or all the devices that we use; we’re hearing more of that. So you can’t just have it be the irritation type symptoms anymore when we listen to patients and try and understand their symptoms.

 I’m so glad you brought that up, Kelly. You’re right. As our understanding of dry eye disease is getting better, we are becoming more inclusive in what we are including in the definition. Don’t you agree?

Identifying Dry Eye Disease

 What are some of the causes? Kelly, I’ll start with you. That’s a big question.

 Yeah. Certainly there are many factors that are associated with dry eye. Age, gender, sometimes lifestyle things like mascara and makeup, arid environment. Especially coming out of winter, we have been seeing some of that with the forced heating and things that people experience. In the summertime it could be air-conditioning [AC]. But certainly a lot of patients are taking systemic medications like antidepressants, and that can impact the overall health of the eyes as well as in systemic conditions, and there are a number of those too that all play into the multifactorial condition that Rahul talked about earlier.

 And that list can go on, and 1 thing I want to add to that is a mask. With COVID-19, we’re all wearing masks, and that is contributing to and exacerbating dry eye disease. Milt, systemic diseases and autoimmune conditions make dry eye worse. Can you tell us a little about the impact of these situations on dry eye disease?

 Well, take a look. Diabetes, that’s 1. There’s a high correlation between diabetes and dry eye. In fact, studies are showing that the majority of the patients that have diabetes also have dry eyes. As eye doctors, if you’re in a general or a primary care practice, what happens is that you have to do diabetic retinopathy exams. As part of that, we also have to ask questions and look into the dry eye portion because the majority of those patients also have dry eyes. We have immune disorders; that’s very common. Going back to what Kelly was saying, I really liked when she was talking about the environment and everything like that. We’ve done work in that area, and we found that actually, if there’s a high temperature, that also exacerbates dry eye. That can be an environmental trigger. Another thing is pollen count. Rahul also was mentioning something about itch, or maybe Kelly was talking about itch. We’ve also found in our work that if you have a high pollen count, then you’re more likely to have a more severe dry eye. These environment factors and concerns are very important.

 You’re right. If you live in an arid area like what Kelly mentioned or if you’re on a long airplane flight—let’s say, to a Hawaiian eye meeting—that can contribute to or a trigger for dry eye disease for sure and create a flare. Any other environmental points that we did not mention? Rahul, did you want to add any points?

 This area is so critical. When we think about dry eye care, we frequently focus on what we can do as optometrists and ophthalmologists to prescribe or do in-office treatments, but the lion’s share comes down to environment, lifestyle, and self-care at home. The environment, we can’t hammer that down enough. My colleague at Bascom Palmer Eye Institute, Dr Anat Galor is involved in some very interesting research, where we’re looking at identifying sick building syndrome and air circulation within the AC vents. In South Florida we have a lot of mold, so we’re looking at allergens in the AC units. I have started to identify to patients to get homes’ air-quality tested and mold tested, to ask them about how old their home is, if they’ve got carpeting. There is a lot more that goes on. It stands to reason that we see a great deal of ocular surface disease and dry eye in countries like India, where I’ve spent a good amount of time, and in Egypt and in environments that there are a lot more dust. There’s a lot more allergic disease there. It doesn’t take too much research to identify there’s a link there between environmental symptoms and dry eye.

 There’s a huge link also between dry eye and also allergy. Everything you’re talking about with mold and dust and everything like that, there’s a huge crossover between those 2 comorbidities.

 Absolutely. If you look at a Venn diagram, dry eye and allergies, there’s a big overlap, as you said, Milt. A lot of times patients come to us saying, “My eyes are itching; therefore, I must have allergies.” Or they’re self-treating by going to their local drugstore and buying antihistamines and making their ocular surface situation even worse by drying it out further. Kelly, do you see patients like that who come to you?

 Definitely. As Milt mentioned, it can be hot and that’s an impact on the ocular surface, or all of that. Placement of the vents can be an important thing in terms of looking at the environment. I don’t know if I can really add any more to what these 2 have said.

 The other problem that we’re seeing is also profiling. Because if you take a look at a lot of the literature out there, it’s always the middle-aged female. That’s the 1 who has all the dry eyes. That’s the 1 who we have to look at for the dry eye problem. But how many of you have seen millennials with dry eye, with device use causing dry eye? People who are gamers. For people who are gamers, we’ll do a meibography and see that their meibomian glands are totally obliterated.

 That’s so true. They could be 29 years old and male. You’re right: We can’t have that postmenopausal woman as the model of dry eye disease anymore. It’s much broader than that.

 I’ve heard some of our colleagues say, “Suspect dry eye until proven otherwise, in everyone.”

 I love that. That is true. You really do have to suspect it until proven otherwise. I love that.

Common Causes of Dry Eye Disease

 Rahul, I’m going to come to you. What happens if we don’t address dry eye disease? What are the consequences of an unstable tear fill?

 This is an important question because we have so many patients that present to use for other reasons— blurry vision, cataracts in my practice, refractive surgery—who aren’t aware that they have dry eye. What they do get is the sense that they can’t read, maybe, or their vision comes and goes and it fluctuates. We are able to diagnose—just because we’re looking—with dry eye syndrome and then treat that. We find that in a lot of those cases, visual fluctuation levels out. They’re able to access more of that high-quality vision time, and we find in many cases that the patient may not need treatment or surgery. But in the patients that do need surgery we feel much more confident about how we’re treating those patients. For the measurements we need for lens calculations and good-quality refractions, we know we have got much better data and much better outcomes after we’ve optimized the ocular surface. On the other extreme, dealing with some more complex ocular surface disorders like ocular graft-vs-host disease and mucous membrane pemphigoid, a lot of these conditions—even in cases where they’re controlled, so to speak, and there’s no melting or ulceration—we can quickly see this punctate keratopathy that we all look at become more dense, grade 1 to 2 to 3, and then you have a confluent punctate keratopathy. That can become an ulcer, and especially in these highly inflamed eyes, an epithelial defect because of the lack of growth factors on the surface. It cannot repair, and then you have a melt, keratolysis, and a handful of other problems. Those extremes don’t tend to happen except in the most inflamed eyes, but I always have that in my mind for any patient with exposure keratopathy who’s got a little bit of dry spots. In the blink of an eye, the person sleeps the wrong way or has a bad day, and you see surface breakdown.

 That is a classic example of what Christophe Baudouin explained as his theory of the vicious circle of dry eye: It progresses, then it gets worse. That case is a perfect example.

Consequences of Untreated Dry Eye Disease

 Milt, how do you diagnose dry eye? When somebody is coming in, what is your process in the office to not clog up your clinic and not get behind? What do you do to keep the flow going yet not miss dry eye disease?

 There’s always that question: If you’re on a deserted island and you could only have 1 test, what test would that be for dry eye? My first choice test would absolutely be case history. Case history will really point you in the direction of dry eye. On virtually all our intake forms, every single patient is asked a very simple frequency questionnaire. In other words, “How often do you experience dry eye? None, sometimes, frequently, or always?” 

 correlates to severe dry eye. That’s the 1 test I would have or that I would want.

 That test is pretty easy to do. I’m going to go to you, Kelly. What tests do you do and have become your standard for the dry eye work-up? Then I’m going to go to you, Rahul.

 In our clinic, we have a specific dry eye clinic, but I like to think about the tests that you could do for dry eye screening, and what has been recommended in the Tear Film & Ocular Surface Society DEWS II report is that you do a symptom assessment, as Milt is saying, whether by interview or a survey like a DEQ-5 [5-item Dry Eye Questionnaire] or the OSDI [Ocular Surface Disease Index], cut points for those have been provided as screening tools. If they respond positively to having symptoms, you can do simple tests with your slit lamp. You can look for staining. You can also do a tear film break-up time fluorescein. It’s recommended that you do it noninvasive, but not everybody has a noninvasive way to measure tear film break-up time. If you have the opportunity to do osmolality, you could do that as well.

The presence of symptoms and any 1 of those 3 abnormal tests is a positive for screening for dry eye, meaning then you need to go further and try and sort through if it’s meibomian gland related or aqueous deficient. That’s simple enough, so you don’t need a whole lot of fancy equipment to make an initial diagnosis of dry eye and take care of your patient if you’re just starting out. I like to say that it’s ask, look, and then do something. So you just keep it really simple. I used to recommend all the fancy equipment, which is really great; it helps you really dive into what could be going on. But if you want to start, keeping it simple is, anybody can do it. We have a slit lamp at our disposal, which is very useful. If you don’t want to measure a Schirmer test to figure out if they have aqueous deficiency, then you can look with your slit lamp at tear meniscus height and make an assessment. Your slit lamp is your most valuable tool. I don’t know if I would want to take that with me to a desert island, but it is a valuable tool.

 You’re right. Kelly, I’m so glad you brought up the point that sometimes doctors are intimidated or overwhelmed, saying, “I don’t have any equipment; therefore, I can’t diagnose dry eye,” or “I don’t want to get into it because, oh my God, I have to spend so much money kind of getting all these different pieces of equipment.” The truth is, if you have a good way of asking questions and a slit lamp with maybe fluorescein—and we all have fluorescein, I use lissamine green too—that alone will get you so much of the time right on target about diagnosing dry eye disease. Rahul, do you want to add anything to the pearls that Milt and Kelly shared with us? Do you do anything differently?

 They’ve spoken very well. I want to underscore the point that Kelly made about the simplicity. There’s a drive toward making dry eye diagnosis and treatment more scientific, and that is very important to get patient buy-in. It’s very important to tailor the treatment. Our responsibility is to get into all the specifics and the science of it, but the patient shouldn’t see us sweating. We should be as simple on the surface as possible, and we should make dry eye diagnosis accessible to all. Because when we create the sense that dry eye can only be taken care of in a referral center or dry eye center of excellence, that’s a great disservice to our patients. There is too much dry eye out there, and we all need to be taking care of it to a degree.

I will make a couple of finer points. I love my fluorescein. I would say case history and just some fluorescein or lissamine staining on a slit lamp tells you so much: the staining patterns, diffuse, interpalpebral, and so on. Some assessment of tear volume, whether it’s a Schirmer, whether it’s looking at the tear height. Some assessment of the tear film quality, if you can, would be great. I like InflammaDry, which looks for the presence of matrix metalloproteinase. Others like tear osmolality. Getting back to that slit lamp, you can also assess the meibomian glands directly by just giving a push. That’s really important. We know about this entity of nonobvious MGD [meibomian gland dysfunction], and it’s very important for us to be pushing on the glands and expecting the lid margin for quality of the meibomian expressibility. I did some work that I presented at ASCRS [American Society of Cataract and Refractive Surgery] awhile back that I was able to, with almost 70% to 80% specificity in my case series, identify that there was gland atrophy based on decreased expressibility. I have found that even though I have infrared meibography, I’ve been using that more as a patient education tool rather than, “I must have this to take good care of my patients.”

 We did a paper. We said that meibomian gland expression is the test to dye for.

Evaluating Patients for Dry Eye Disease

I want to segue from what you said about patient education, because you’re right, the black and white pictures of the meibomian glands that we get on the LipiViews and LipiScans very clearly demonstrate to our patients if is there is dropout or not. It helps get the story across to them. Kelly, how do you educate your patients, especially those who come to see you who are asymptomatic and you’re making the diagnosis of dry eye? What resources do you use?

 I’m glad you brought that up because we’ve just finished a relatively large study where we were looking at the difference between symptomatic MGD [meibomian gland dysfunction] and asymptomatic MGD, and it is really prevalent, at least in the group we have. If you’re just relying on symptoms alone first, you’re going to probably miss quite a few of those patients. Having said that, sometimes I think it’s how you ask the question, and when we do research studies, we’ll give them the survey or something, but when they’re in the chair you can actually be having a conversation with them and maybe find out those visual symptoms they haven’t brought up as their chief complaint for the examination, for example. In our clinic, of course, it’s with students, and the students are the ones who are interfacing with the patients and learning how to have those conversations and learning how to educate the patients about the importance of the treatments and coming back for routine care; well, following up for dry eye care. So of course in your offices it would be staff members who do a lot of that work.

Milt, once you’ve made the diagnosis, and now you’re trying to educate the patient about treatment options, how do you start that conversation? Because often treatments are multipronged. We’re asking them to do stuff in the office, stuff at home, maybe purchase a pharmaceutical product. How do you have that conversation without scaring the patient?

 Well, I had to do a lecture with Doug Devries, OD, from Reno, Nevada, and he always says, “Everybody needs a Louie.” I go, “Who’s Louie?” “Well, Louie is the designated staff member in the practice who specializes in or does case management for dry eye.” As you said before, a lot of the device-oriented treatments, they require a lot of preprocedure and postprocedure work, and follow-up, and so on. If you have a designated member in your practice who specializes in that area, it is so helpful to educate the patient. Another thing, I don’t know if you guys have this problem, but a lot of times, I don’t really remember what I did in the past for the patient. A lot of times what happens is a patient will come in multiple times, and then I would say, “Oh, well, let’s try this treatment,” and then they’ll look at me and say, “Well, you already did that before. What’s going on? It didn’t work.” So what we do now is that we have a medication grid in our charts, and I have the dates down and what I did, just a very brief thing, 1 sheet that I can look at, so I can look up the treatments I’ve done in the past so I don’t embarrass myself and repeat the treatments I’ve already done that didn’t work.

Right. That’s really important, because sometimes you recommend a specific immunomodulator, and maybe they had a negative reaction to it, so you want to make sure you don’t rerecommend that particular product.

Educating Patients About Dry Eye Disease

 Rahul, based on what Milt said; those are really wonderful pearls, and Kelly, what you shared with us are great pearls too for how you’re helping your students become eye care providers. Rahul, in dry eye disease we have to keep layering treatments, I always say we layer treatments, we make this big sandwich, and we never know how thick that sandwich is going to be, how many layers of treatments we need.

 And patients laugh and they chuckle. How do you discuss sequential therapy with your patients? Because it’s never once and done, unlike cataract surgery.

 Right. I find that usually by the time patients get to any of the 4 of us, they’ve had some interaction with a previous doctor regarding their dry eye disease. The first thing we do of course is we unpack what they’ve done and what they’ve tried before. One of the things that frequently comes up is that people who have tried some amount of lid hygiene or some amount of over-the-counter tear products, they’ll say, “Oh, that didn’t work.” They’re looking for something by prescription or something procedural out of the gate. For me, right at the start of this we talked about environment, lifestyle, and self-care being the lion’s share of the work. I tell patients 1 of 3 things right up front. I tell them dry eye and ocular surface disease are a chronic condition. There’s no wonder drug that we’re going to pull off, although there are some things that are pretty fantastic, there’s no wonder drug we’re going to pull off that’s going to cure it and that you’ll have to take once or every 6 weeks and then you’re done. Then they know they’re in it for the long haul, they know about longitudinal care, and they know about the partnership, because things are going to go left and right. Some things are going to work better than others.

The second thing is, just as you mentioned, there’s this pyramid of care where we go higher and build on foundational treatments. So even if they have tried or think that they’ve tried lid hygiene, and environment modification, and so forth, I really blow that up and dive really deep into it, making sure they’re using good quality products that are targeted to their specific condition. How are they, for example, accomplishing lid hygiene? Do they need a hypochlorous acid-based cleanser? Do they need a detergent-based cleanser? Do they need something that targets, Demadex? Warm compresses: Are you using a washcloth that gets cold quickly? Are you using something that can maintain heat? There’s so much level of detail that we can get into just on that foundation. In terms of sequence, I very frequently go back to that foundation as a first step.

Then the third thing that I find is very helpful in these initial consults is targeting inflammation. We know inflammation is at the root cause of so much dry eye, and we know that patients in many cases respond to pulse courses of topical steroid, topical immunomodulators, and so forth. I find that controlling—especially if I find it from a matrix metalloproteinase being present or a high tear osmolarity—if I can find that inflammation and I can put them on a course of anti-inflammatory medication, that gives me a leg up that I’ve got patient buy-in on the next thing I’m going to do. We know that their disease is responding to things we’re doing. It’s not another path for sensory abnormality, and it helps build the pathway. That has been my approach, but I know there are many others out there. I’m curious to hear from the rest of the panel as well.

 I’m so glad you mentioned that just because somebody has tried it once and said it didn’t work, you really have to explore that. It could be that they tried something for a week or 2 weeks, expected a miracle, and stopped. You really have to delve into it and find out what it was that didn’t work, or what it was that made them perceive it was not helpful to them. It’s so true. Maybe they were using a cool washcloth instead of, let’s say, a heat-retaining mask that can stay hot for 7, 8, 9 minutes.

Layering Therapy for Dry Eye Disease

 To follow up on that, Rahul, because we were talking about adding layers of treatment, where do oral omega-3 fatty acids fit in with your treatment? And then Kelly and Milt, I’m going to open it up to both of you to comment on your views of incorporating omegas.

 I am an omega believer. I do very much believe in the importance of nutrition and antioxidants and a whole foods diet. It works for everything. But in particular with omega-3s, the first thing I have to admit to myself is that the data are a little interesting. We know that Penny Asbell, MD, put out the results of the DREAM study, which showed nonsuperiority, let’s say, of omega-3s against olive oil, which maybe wasn’t the best placebo there. Whereas others have studied this well and have some very nice data showing that indeed it is helpful. There is some movement, and I don’t want to say, there are others who might say, “I’m 100%, in every patient.” But for me I always prescribe with a grain of salt because I have to keep an eye on the data to a degree. I do believe in omega-3s, however, and I think there are a few brand names out there that have re-esterified omega-3 acids and those particular products that are built out to contain the therapeutic dose. It’s very important because oftentimes people will think they’re getting the appropriate amount of omega because they had salmon for dinner. And it just doesn’t get to that therapeutic dose. If they’re going to use it, I like the products that are on-label for that specific purpose.

 Great answer. Milt or Kelly, would you like to add to that? I do agree. I am a believer about omegas, and I do recommend them to my patients. Now there is a test you can do, the OmegaQuant test. It’s a finger prick test, one droplet of blood goes all the way to South Dakota and you get the result, and if it’s 8% or greater, it means the patient is within the therapeutic range of their omega-3 level. If they’re not, you have to bump up the dose or change brands to something that is more bioavailable and bioabsorbable. Kelly or Milt, any comments on omega fatty acids?

 I’ll say I too am a believer. Whether they help the eyes, they help your body too. If you’ve trying to overall reduce general inflammation, it can’t be bad to take them. Having that discussion about the data with the patients I think is important. But if they hear from you that you take them, I think they are influenced by that. In Penny’s study both groups did improve. It wasn’t like there was no improvement at all while on them. So although not Earth-shattering data, I still think they are suggestive, and it can’t hurt. There is a cost associated with taking omegas, and so if that’s a burden for the patient then they may opt not to.

 It’s a cost, but also having eye disease and the consequences of that, there’s a cost to that too. You always have to do that fine balancing act.

Omega-3 Fatty Acid Supplements for Dry Eye Disease

 When it comes to artificial tears, which so many of our patients use, they go to the drug store. They’re overwhelmed by the shelf with tens or dozens of bottles. Kelly, how do you guide your patients on how to select their tears? Do you sell them in your practice? Do you specify ones that have oil in them or ones that are preservative-free? How do you do it?

 We’re a teaching clinic, and so we can’t specifically recommend just one. We have to show the students the different brands, etc. It’s important for them to have exposure to as many of them as they can so they can make their own decisions once they are treating patients out in practice. Certainly, I tend to go for lipid-containing products because usually there is a lipid deficiency in most dry eye. But there are several good products. Those are usually the ones that are on the top shelf and not on the lower layers. Just the other day I was talking to somebody, not in the context of the clinic, but outside. She brought it up; she didn’t know I was an optometrist. She was asking, “Have you ever tried to buy eye drops at the grocery store? What do you pick? I get swayed by the price,” is what she told me. I think a very specific recommendation from a practitioner to a patient, whether you write it down or show them a picture or if you have a sample, give them a sample, so they know what to look for once they get to that massive section in the grocery store, and they don’t get swayed by whatever is on sale. If you can, tell them why those products are better, and that even though most artificial tears are similar, they do have inactive ingredients that have some action or activity to them that are helpful. I think the recommendation starts first. Then it’s how often they use it too because if they just use it once, a lot of patients use tears wrong. They use them once when their eyes are starting to feel bad, and they’re not using them several times a day. So they’re probably not getting the full benefit. But in my mind when somebody is not using them to the way they should be used, and they come to you saying that they’re not getting relief, that’s an artificial tear failure and time to move on to a different treatment. But I probably should let Milt comment on this too because he’s been so patient over there. Milt?

 I remember back in the old days. It was like all artificial tears are the same. It was saline in a dropper bottle. But since that time, artificial tears have changed so much. There is so much technology in artificial tears, it’s crazy. A lot of that technology comes from drugs. Drug development in general, topical drug development. There’s a lot of technology. There’s a question, should you use a generic artificial tear, or should you use a branded artificial tear? The branded artificial tears actually are the ones loaded with the technology. The generic artificial tears are more of the older technology, the older types of artificial tears. One of the big advancements is nano, nanomicellular technology. We’re seeing that in virtually all of the branded artificial tears and also in all of the drugs, the topical drugs we use.

Nano is fantastic because there are 3 different phases with the nanomicellular technology. We know that there’s the surface, which is the mucin layer, and the mucin layer has pores in it. It’s like a spider web. These pores are nano-sized, so in other words if you have nanomicellular technology, it’s more likely to penetrate the pore in the ocular surface. The mucus layer is also very hydrophilic; a lot of pathogens are hydrophobic, so what happens? The pathogen comes in, and the mucus layer bounces it right off. Nanomicellular technology, what that does is it makes the surface of the particle hydrophilic.

Finally, the third thing is the charges. We know that the mucin layer has multiple charges. It has positive charges; it has negative charges. What happens when this charged particle comes in or a pathogen comes in? It gets trapped by the mucus layer. Nano technology gives it a neutral charge, so the charges of the mucin layer do not effect it. It’s smaller because it’s nano-sized, and also it’s hydrophilic, so it’s not repelled by the mucin layer. Technology is one of the big things we’re seeing now in artificial tears.

Artificial Tears for Dry Eye Disease

 We’ve talked about treating with artificial tears branded, and we have to be very specific in the recommendation. I cannot agree with you more, Kelly and Milt, because otherwise the patient may end up with an antihistamine eye drop, making their eye condition worse or 1 that gets the red out instead of a true lubricating eye drop. Let’s move on to steroids. We’re fortunate that we now have an FDA-approved steroid for the treatment of intermittent dry eye flares. But we’ve been using steroids off-label for this entity for a long time. Rahul, Kelly, talk us about how you use steroids in the landscape of dry eye disease. Rahul, you first.

 Sure. There are probably 2 ways in which it fits into my practice. One is with initiation of, let’s say, a topical immunomodulator that might take a little more time to get started. We know that cyclosporine and Restasis may take a little while to get started. We have good data that a past course of Loteprednol or fluorometholone may help with initiation. I tend to carry that same principle through all my topical immunomodulators, including lifitegrast and higher-strength cyclosporine. It does help. If nothing else, it quiets the inflammation a great deal. It improves the tolerability of some of these topical immunomodulators. Sometimes patients will say that 1 burns or stings and is hard to get in. But if you’ve got an inflamed ocular surface, it’s that much more likely to bother. Initiation is 1.

The second way it’s used in my practice—dry eye is a condition we understand comes and goes. It has its peaks and valleys. The environment may change. Someone’s health status may change. Somebody’s ability to do self-care to keep up with that may change over time. As dry eye flares, it is nice to reach for something somebody can use responsibly, that a physician can feel comfortable using periodically to treat. Those are the 2 ways in which I use it. There’s a third case in some patients that are on long-term chronic steroids. With some sense, these are the most severe ocular surface patients who may benefit from that. That ocular GVHD [graft-vs-host disease] subset. In general I find them very useful.

 How about you, Kelly? In what ways do you use steroids for your patients with dry eye?

 Very similar to what Rahul just described. I really do like that there’s an FDA-approved steroid for dry eye for optometry on indication. It may not matter to some because many probably have been using steroids much as Rahul described for a long time. It’s nice to have something that’s on indication. I also like that we’re talking about flares because from the early years of seeing patients and studying dry eye, you’ve heard about this cyclical nature. What I probably neglected to do was talk to patients about when, more specifically, that happens. Some studies have shown that patients can have 4 to 6 flares per year. We’re missing most of them, especially if you don’t ask if your patients are having them or what those triggers are that cause them to happen. Then you might miss it altogether, and that could be emerging dry eye. It could be dry eye that hasn’t gotten so bad that they’re coming and complaining about it. That case history is reinforced. As Milt mentioned, it’s a critical part of the exam. You can’t go so fast through it that you don’t spend the time asking a patient about how often triggers create an episodic flare, which could be managed with a therapy that perhaps you wouldn’t have used before.

 It’s FDA approved with that very specific indication. Milt, what about the presurgical patient? If you’re comanaging and you need to tune up the surfaces, do you consider using a steroid under that scenario?

 Yes. Not only a steroid but anything that would clean up the ocular surface.

 Just not locked into that. The patient could also have lid disease. That’s another consideration when you’re getting prepared for a presurgical work-up. Rahul touched on this and also Kelly. The problem is that when we look at the complication of dry eye, our colleagues get really confused because it’s as if every week there’s a new dry eye treatment, a new device. There’s something else like that, and what I see is what Kelly was mentioning before. Most dry eye is actually MGD [meiobomian gland dysfunction]. There are 2 different camps. There’s 1 camp that’s called obstruction. Mechanical therapy. Opening the meibomian glands and also anti-inflammatory. When I do a treatment I like to pick things out of both camps, I do mechanical treatment and also anti-inflammatory, combining them because that will really increase your efficacy. Whatever you choose, that’s up to you. But you can get at the dry eye, MGD, at those 2 MOAs [mechanisms of action]— different ways of attacking it—not only for dry eye but for presurgical.

 Exactly. It’s almost like peanut butter and jelly. It’s a perfect combination. You need to do some in-office procedures while concomitantly addressing the inflammation. One is removing the impaction, and 1 is addressing the inflammation. I agree.

Corticosteroids for Dry Eye Disease

 Kelly, I’m going to come back to you. What types of in-office procedures do you offer? Then I’m going to open it up to you, Rahul and Milt.

 Cynthia, that’s your second sandwich reference. You’re making me hungry. There have been so many. As Milt mentioned, there have been so many new advances of things that we can have in practice. It can be really confusing because LipiFlow, TearCare, and iLux all are warning devices. They all function slightly different from one another. All have the same goal of clearing the meibomian glands. Also, as you mentioned, the sandwich of pairing that with manipulating the eye. There’s going to be some inflammation that, even in the short term, needs to be addressed. I like how you mentioned that, Cynthia. But then there are some other things, like cleaning up the eyelids, which may be more important in certain practices. We do that in our specialty dry eye clinic. We do not have IPL, or intensive pulse light, in our clinic. Maybe 1 of the other 2 could speak to that if you do, or radio frequency laser treatment. We’re more in the meibomian gland range with our treatments in clinic. I’ll turn it over to my fellow compatriots.

 I agree with you, Kelly. The ones you mentioned specifically address the viscosity and the impaction of the meibomian glands. There are, as you said, other options. Rahul, do you incorporate anything else?

 You referred to intense pulse light. That’s a really nice treatment, and there are good data to support it across different categories of patients with MGD [meiobomian gland dysfunction]. In particular, I like that for my ocular rosacea and facial rosacea patients. Optimizing that with IPL ahead of a thermal pulsation treatment actually gives me more longevity. In fact, I had a patient just the other day who underwent both on the same day. Pandemic related, he didn’t want to come and ago. Had IPL and LipiFlow—very savvy patient, and now she gets a little more extension in terms of her next appointment. I do believe in IPL. We don’t do radio frequency treatment, although that’s interesting technology. I’m keeping my eye on that.

Also, on the obstructive component of it, we’re talking a lot about how to heat and warm the meibum and then express it mechanically. There’s a lot of technology that’s come about in that regard. From a procedural standpoint, I am a growing believer in meibomian gland probing, which Steve Maskin is popularizing. He has excellent data that, to his credit, he has put out in some good journals. It’s a little traumatic. You do need some good anesthetic. You need to have some sense as to what you’re doing. The probe will find the meibomian gland. It tends not to move into the wrong area, and you can get started with shorter probes for those of you listening who are interested in that. Then move away to higher probes. For a patient with severe obstruction who has, to some extent, some working glands, I will do probing first and program a thermal pulsation shortly thereafter. But there are a variety of other treatments that we can do. Procedure-based office treatments. We now have treatments for conjunctivochalasis. Great cautery rate, frequency ablation in the office or excision with AMT [amniotic membrane transplant] in the operating room. We have punctal occlusion, punctal cautery. We have microblepharoexfoliation, which is quite important, particularly for 

 mites. I wanted to catch on the other side what Milton had mentioned about the comanagement and optimizing the ocular surface before cataract surgery. There’s this question, do we optimize that surface and then refer for cataract surgery, or do we send and then have the surgeon do that. Patients are much happier when all that has been worked on by the provider, who knows them best and optimizes that all and then they come, ready to go. Despite my best inclinations to get a surface optimized, when someone comes in hot for cataract surgery but has a poor surface, they’ll have to spend another few months optimizing that— the extent they’re dissatisfied. In a comanaged situation, we love when our optometrists take the bull by the horns on that.

 Excellent explanation. There are so many tools in our toolbox. Milt, what tools do you have in your toolbox?

 I’m not like Rahul. I don’t have a garage full of toys. We go with anti-inflammatory treatment, and then I do some basic mechanical therapy. If that doesn’t work, then we’ll add in manual expression behind the slit lamp. We have huge procedure of heating the lids and things like that. We go ahead and manually express the patient. As Rahul was talking about, a lot of times it’s 

 is a problem too. We’ll also do tea tree oil treatments in the practice and send them home with tea tree oil wipes.

 All these treatments are so complementary to one another because the 

 patient we have to consider tea tree oil. There are other pharmaceuticals in the pipeline; we’ll get to that shortly. As all of you said so astutely, a lot of it is combining, mixing, and matching and finding that right balance. I use IPL, and I also use a lot of other heating and expressing devices of the meibomian glands. Like you, Rahul, I have found that they work in perfect synchrony with one another. I might do a LipiFlow, and 6 months later I’ll do an IPL and that will help extend the efficacy of the LipiFlow. And microblepharoexfoliation to remove that biofilm to open the orifices of the glands so more of the lipid can come out and coat the ocular surface is also really important. That can be done as an in-office procedure, or there are at-home treatment options. NuLids has a device, an electric toothbrush that you hold like an instrument, and it has an oscillating head that cleans between the lashes. Do any of you have experience with that instrument? It works. They buy it, and the head changes after each treatment. They put a proprietary viscous artificial tear or 1 that Newsight provides, then they go back and forth 30 seconds on each eyelid. It’s an at-home version of the microblepharoexfoliation, but it’s a milder, kinder version.

 I was going to ask Cynthia if she’s had success using that.

 My patients really like it. These are patients who have blepharitis. They have a lot of debris and collarets at the base of the lashes. Often there’s 

 infestation. We’re using tea tree oil and this mechanical cleaning system.

 I was just going to add to that. That’s a clever idea, and I want to get into it. Anything that can put more power in patients’ hands is critical. From the ophthalmologist and optometrist perspective, we were talking about demystifying dry eye and not making it so difficult to diagnose and care for. The same is true from the patient perspective. We have incredible products. Thanks to impressive industry collaboration and initiatives, patients can take care of their dry eye and do self-care better than ever. They’re very savvy. We just have to trust them and point them in the right direction.

In-Office Procedures Used to Treat Dry Eye Disease

 Kelly, do you get any pushback? If so, how do you deal with it when you start saying to Mr Smith or Mrs Smith, “You need to do XYZ. And then we have to do this, and a few months later we have to add this.” Do they get the feeling you’re nickeling-and-diming them? How do you present it to the patient so they understand and don’t give you pushback? What are your pearls?

 In our setting, we have a different clientele from a regular private practice, being at a university teaching clinic. We have to be cognizant of all issues, choose treatments, and even worry whether patients are going to return for follow-up. Having said that, I have found over the years that—just like diagnoses—you have to go in a step-wise approach. If something isn’t working and they’re coming back to you, then you have to transition to something else. As you mentioned, you’re deciding, “OK we’re going to do this, and then we’re going to do that, and then after that we’re going to see how it works and maybe do something else.” You have to tell them why that series is going to be important for them to follow from the standpoint of maintaining their ability to keep coming back to you. So many times in dry eye clinical trials, when we’re recruiting patients from all over, patients are still seeking. If they don’t feel they’ve gotten what’s going to help them within, or at least a reason to keep them coming back for a while, they’re going to stop using whatever that is and end up in the dry eye clinical trial, or doing nothing, or going with another practitioner. Depending on your patient base, you have to decide how much you’re going to give them at 1 time and what tools you’re going to use to persuade them to keep going with it and to come back. Rahul mentioned earlier that a picture is worth a 1000 words. That can be a really useful patient education tool, as we’ve found.

 For many of these patients, the bottom line is symptoms. Whether or not we’re giving them symptom relief, what we do is a dry eye work-up or dry eye treatment. We want something like an OSDI [Ocular Surface Disease Index], and it will give us a basic score between 0 and 100. A lot of times, the patient will say it’s not working. I don’t like it, but if you look at the OSDI score, it could go up 5 points—or shall we say go down 5 points. We just say that, according to the symptoms questionnaire, you’re getting better, so why don’t you go on with that? Or we might switch to another treatment. It’s very nice to have that metric that you go on every single visit so that you can always compare and show the patient they’re actually getting better.

 Patients like numbers. They like to track these just like diabetics follow their hemoglobin A1C [glycated hemoglobin] with a hypertension monitor. I want to know what is my blood pressure today. Patients with dry eye want to know metrics too. You’re absolutely right, Milt.

Optimizing Adherence to Therapies for Dry Eye Disease

 We’re coming toward the end of our presentation. We have a lot in store for you. There are many wonderful and diverse, creative products in the pipeline to help our patients with dry eye disease. Milt, why don’t you get us started with some of the products in the pipeline?

 The first 1 is from Surface Ophthalmics. As a disclosure, I’m actually in the clinical study for this. It’s phase 2, and it’s interesting because what it’s being used is another steroid but not a steroid you’re familiar with. It’s a steroid that comes from dermatology. It’s betamethasone. If you take a look at all the steroids, according to dermatology, betamethasone is 1 of the most powerful steroids you can use. Now it’s being repurposed in a dry eye drug from Surface. What’s interesting about it is that it has a steroid-sparing agent. It’s called MPA, mycophenolic acid. The steroid sparing enhances the effect of the steroid or the effect of the betamethasone, so the betamethasone is coming in as a very low dose. That’s 1 of the phase 2 drugs in clinical studies. 

 That’s great that you’re participating in the clinical trials. Rahul, do you have any products that you’re excited about that are in the pipeline?

 First, it’s incredible that we have such a robust pipeline. This is an incredible time to be in dry eye and ocular surface because we have so much coming. Thank you to our industry partners who are involved in all of this. There are a few that I’ve got my eye on. One is reproxalap, which is entering phase 3 trials. It works against reactive aldehyde species. These are free species implicated in inflammation. What’s very interesting in their phase 3 trial is they’re doing a trial for an indication for dry eye and a trial for an indication for allergy or allergic conjunctivitis.

At the beginning of this talk, we talked about the interplay between the 2. Most of us prescribe for dry eye or allergy. There’s often overlap. I would love to have something on label to help to treat both. Another 1 I’m excited about is PaniDrop. We talked about these novel carriers, these nanocarriers, these nanomicelles that help deliver interesting immunomodulators to the surface. There are several in the pipeline. PaniDrop is just 1 of them—the active ingredient is dihydroorotate dehydrogenase. It’s a mouthful, but this molecule is well recognized in the oncology and rheumatology literature. It’s exciting to have access to it by this nanomicelle technology, by which it can be delivered to the ocular surface. They’re in phase 2b if I’m not mistaken. There are a few others I can talk about if we have time, but those 2 were really interesting.

 The 2 that I’m also very interested in, besides these, is 1 that’s a keratolytic agent targeting impacted meibum in the meibomian glands. Through this particular chemical product, it dissolves or melts or alters the viscosity by being a keratolytic agent and helping the meibum come out. It’s a chemical and a pharmacologically driven expression of the meibum, as opposed to heat and manual or automatic compression. So that sounds very interesting. One is the nasal spray that stimulates the trigeminal nerve. Through the activation of the lacrimal nerve, it creates a complete tear that has all 3 layers—the lipid, the aqueous, and the mucin—through 1 spray in each nostril to be used twice a day. There’s a lot of very interesting stuff coming down the pike, so be on the lookout. Our toolbox is going to become a huge tool trunk.

 Kelly, what are you finding exciting in the pipeline?

 There’s so much going on in the pipeline right now. You mentioned Oyster Point Pharma’s nasal spray, which is very exciting. But there are a few others that are far along in the FDA process that are worth mentioning. NOV03, which is Novaliq—they licensed it to B&L [Bausch & Lomb]—and it’s specifically for the meibomian glands. It’s a lipid stabilization to help prevent evaporation. It will be interesting to see how this goes through. It’s in its second phase 3 trial, so we should start to see some results relatively soon. Corneal staining and symptoms were their outcome measures that they’re looking at. HanAll Biopharma has a TNF [tumor necrosis factor] receptor fragment, which would bind to the receptor and hope that the release of inflammatory cytokines is reduced. They’ve gone through a phase 3 trial. Although they didn’t meet their outcomes, they’re still working to determine what their next steps are in their program. That’s a Korean company. Lastly, I’ll mention Visomitin SkQ1, another oxidative stress-type product that’s very similar to the 1 Rahul talked about a minute ago and is in a platform very similar. They’re looking at not only front-of-the-eye therapeutic targets with wound healing and inflammation but also some back-of-the-eye with the same compounds formulated slightly differently, and even an oral version of that same compound. So there are quite a few interesting things coming up.

 The pipeline, as we said, is incredibly robust to the point where we’re getting a little bit of a traffic jam, in a good way. Milt, what other products are exciting you?

 Novartis is working on lubricin. Lubricin is from David Sullivan of DEWS fame; that’s his drug. It’s in phase 2. We’re working with that 1. What they find is that lubricin is a naturally occurring glycoprotein, and what they found is that in dry eye, it’s actually reduced. By adding lubricin, it’s bringing the dry eye back to homeostasis. Lubricin is essentially a lubricant, so it reduces the friction that you see in the tear film. The other 1 we worked with is Silk Tech Biopharmaceuticals. This is a novel type of approach. It’s the silkworm cocoon. They call it the 

 silkworm cocoon. You know the silk that you wear? They actually use that. They extract the protein out of that. They found that it’s acting as an anti-inflammatory. What happens is that when you take a look at the inflammatory cascade and the whole immune system, 1 of the chief regulators of the inflammatory cells in the tear film in dry eye is called NF-κB. The silkworm glycoprotein helps regulate that NF-κB, and that affects the inflammatory cells that are in the tear film; therefore, it lowers the whole dry eye profile.

 Wow, fascinating pathways. Rahul, are there any other products exciting you in our pipeline?

 Yeah, I’ll mention 1 that’s interesting. It’s brought by Aerie Pharmaceuticals, and it’s targeting the TRPM8 receptor. What’s interesting is that this is a receptor that can boost tear production, which we mentioned that Oyster Point product coming forward. This space is ripe for innovation in terms of boosting natural tear production. We have a great deal of anti-inflammatories and immunomodulators. There are more coming, but it’s always interesting to see an increase in production. We’ll see how the phase 2b data come out, but it does have some ocular pain relief component to it. If we’re thinking about dry eye and ocular pain as being on a spectrum, that’s a very interesting element for us to look at. We have to be honest. So many of our patients are using over-the-counter products, Visine and Clear Eyes, because they feel good and they have some component of pain relief and that cooling sensation. If we can deliver something that we know is good for them and helps their tear film production, then that’s a win-win.

Eye Care Products in the Pipeline for Dry Eye Disease

 We’re coming to a close on this program. I want to go around 1 more time. I’ll start with you, Kelly. Any closing remarks that you wish to add? Is there a topic that we didn’t cover in adequate detail or another thought that you wish to add?

 Goodness. To wrap up, dry eye is very exciting. The pipeline is probably what is the most exciting, with Oyster Point’s product, the nasal spray. We’ll find out in October whether the FDA approves it. That’s probably the closest to getting approval. But there are several others in phase 3 and a number in phase 2. If you pay attention to this space, several are also in phase 1 and moving forward. That’s so exciting. For the longest time, we would have 1 or 2 that were in some development, and now there are 15 or so that are, and many could actually get approved. That’s very exciting. What we will need along with that are diagnostic tools to help us determine the most appropriate candidates to take these new therapeutics and then what the outcomes will be, to see if there’s success and how we can measure that best in practice. Because if we knew that a patient looked a certain way and we were able to detect that, and then we prescribed a certain medication for them and then they had an outcome that we could carefully watch, that’s going to result in the best care for our patients. Personalized dry eye care would be great to the point if we could do that. Let’s keep on our eyes on the pipeline but keep the diagnosis and treatment simple and in a sequential order, and explain it very well to your patients.

 I love that. Milt, we’ll go to you and then to Rahul to wrap up.

This is a very exciting time to be an eye doctor. I don’t think there’s any time in our history when we’ve had so many exciting new innovations and drug treatments. It’s crazy. It’s really wonderful. For dry eye, before we only had 1 drug, but now there are many drugs and a lot in the pipeline. Not only that, but we’re also looking at presbyopia, myopic progression, 

 mites. It’s a very exciting time to be an eye doctor, and I’m glad to be here for the ride.

 We want to thank our industry partners. Without them listening to what our needs are and without them understanding how these help treat our patients, we would not have this collaboration. Thank you so much for putting all those millions of dollars into R&D [research and development] to come up with such a robust pipeline. Rahul, what do you think? What are you excited about, and what are your closing comments?

 I just want to echo everything that’s been said. Our partners in the industry have done a great job. Also, they have provided opportunities for a number of investigator-initiated trials at academic centers. That has been a fantastic pathway and something that I’ve been privileged to take part in. It’s very nice on that end. On a clinical side, to ophthalmologists and optometrists who want to take it to the next level with their dry eye care, demystifying dry eye care is very important. As it gets more complicated, as we have more diagnostics, as we have more therapeutics, as we have procedural therapeutics as well as things that we prescribe, the basics are just the most important. At the end of the day, the principal thing that we need from our patients is buy in. We need patients to understand what’s happening on the ocular surface. So we need patient education tools. Milt mentioned a counselor. If you can do that, that’s great. If not, Kelly mentioned having a photograph or a meibography picture. I have a keratograph, so I print a report. Once the patient sees their tear break-up time on a video, they can understand what it means to be lipid deficient.

But low-tech tools are great if you have them. Just a fluorescein slit lamp photo can give you a sense of staining. Having patients buy in—understanding that it’s an ongoing partnership, that you’re going to go through the lumps and bumps together—is important. One other thing that I think is effective, at least I hope, is that I always tell a patient what’s coming next. As I close out my encounter and say, “We’re going to start here,” and then just as we know in our minds what’s next—the sandwich or the pyramid, whatever we want to call it. I put a note to myself in the chart to consider future therapeutics of a certain sort, and I tell the patient that much so we maintain their hope. Some of these patients have learned to deal with their dry eye disease or are bounced around among providers. To keep them optimistic about their care—not to mention that limbic optimism plays into their response to our treatment, so let’s be honest about that too—a partnership is so important. All the other comments across the panel were excellent. It’s been a fantastic opportunity to share this discussion with you all.

 Thank you very much to my wonderful panelists, Rahul, Kelly, and Milt. You guys have been terrific in sharing your wisdom with our audience. And I want to thank our audience for the time that you’ve spent with us. I hope you found 

Closing Remarks: Personalizing Dry Eye Care

Exploring the Management of Dry Eye

A panel of ophthalmologists and optometrists discuss the significance of addressing dry eye disease using various types of treatment strategies, including pharmacologic and non-pharmacologic options.

Exploring the Management of Dry Eye

EP 1: Identifying Dry Eye Disease

EP 2: Common Causes of Dry Eye Disease

EP 3: Consequences of Untreated Dry Eye Disease

EP 4: Evaluating Patients for Dry Eye Disease

EP 5: Educating Patients About Dry Eye Disease

EP 6: Layering Therapy for Dry Eye Disease

EP 7: Omega-3 Fatty Acid Supplements for Dry Eye Disease

EP 8: Artificial Tears for Dry Eye Disease

EP 9: Corticosteroids for Dry Eye Disease

EP 10: In-Office Procedures Used to Treat Dry Eye Disease

EP 11: Optimizing Adherence to Therapies for Dry Eye Disease

EP 12: Eye Care Products in the Pipeline for Dry Eye Disease

EP 13: Closing Remarks: Personalizing Dry Eye Care