Kelly K. Nichols, OD, MPH, PhD, FAAO

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 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.

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Types of in-office procedures currently being used by ophthalmologists and optometrists to aid in the treatment of dry eye disease.

In-Office Procedures Used to Treat 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.

Unique clinical trials and novel products of interest currently under investigation for the treatment of dry eye disease.

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 

A panel of ophthalmologists and optometrists conclude a discussion about dry eye disease by commenting on advances occurring in the field and future expectations for managing patients.

Closing Remarks: Personalizing Dry Eye Care

 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.

Strategies that can help eye care specialists work with patients to establish and stick to treatment plans for dry eye disease.

Kelly K. Nichols, OD, MPH, PhD, FAAO

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Eye Care Products in the Pipeline for Dry Eye Disease

Closing Remarks: Personalizing Dry Eye Care

Optimizing Adherence to Therapies for Dry Eye Disease

In-Office Procedures Used to Treat Dry Eye Disease