Brian Walker, RPh

 One of the [drugs] I’m really excited about coming down in the pipeline is OC-01 nasal spray from Oyster Point. That’s exciting to me because I used TrueTear to treat some of my patients with severe dry eye disease, which is nasal stimulation to the trigeminal nerve that causes release of tears that have the same composition as normal tears. This is a nasal spray that does the same thing, that causes neural stimulation of the trigeminal nerve to release tears. They’ve had excellent safety data that are already coming out, and they have a PDUFA [Prescription Drug User Fee Act] date at the end of October. That’s a treatment that I’m looking forward to utilizing for my patients with dry eye disease.



There are some additional formulations of cyclosporine that are in the works. Novaliq has one that’s very popular in Europe; they’re working on trials to bring to the United States. Finally, the new generation of treatments is always [found in] drug delivery, and I’m involved in some of the clinical trials for implanting punctal plugs that contain treatment for dry eye disease, such as steroids, cyclosporine, and others. There are a lot of exciting things that are coming down the pipeline. I’m really excited to have Eysuvis to use for patients, as well as adding to our armamentarium that we can help treat our patients with dry eye.



 That brings us to the end of our discussion. Before we close, I would just like to ask if you have any concluding remarks or any comments. We’ll start with Brian.



 Dry eye disease is nothing to play around with. We all have experienced that periodically, but you want to take the time to understand what the patient is going through and make the appropriate recommendations based on their timeline to help them feel better because outcomes do matter.



 Over-the-counter options definitely play a significant role in dry eye treatment. It’s an accessible first place to start when treating dry eyes, and it’s the mainstay of treatment to lubricate the eyes. We start with artificial tears, and based on the patient response, we make recommendations for a product that’s preserved or preservative-free, as well as ensuring that we make the appropriate recommendations for them to see a physician.



 I agree. Dry eye is an incredibly important condition that oftentimes gets overlooked for patients, but if you’ve ever experienced dry eye yourself, you know that this is something that significantly impacts how you feel in your daily life. It’s not something to overlook in our patients, especially now that we have so many more treatment options beyond artificial tears—with Eysuvis, with the other chronic therapies. Patients don’t have to suffer with being on just artificial tears and not really obtaining relief. There are short-term treatments. They can be on it for as little as 2 weeks with Eysuvis. If they’ve got underlying chronic conditions, there are treatments available and additional things that we can do, both pharmacologic and nonpharmacologic, in the office. I implore the pharmacy community to help us with that large population of patients with undiagnosed and underdiagnosed dry eye disease to help get our patients the treatment that they need.



 Thank you. This has really been an enriching discussion, and I thank you all for your time. To our viewing audience, we hope you found this 

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A panel of experts comment on new therapeutic agents being developed and discuss their final thoughts on dry eye disease.

New Therapeutic Agents and Final Thoughts on DED

I’ve utilized Eysuvis for a lot of different patient types that have had great results. There are those who are just experiencing a short-term flare of dry eye—whether it’s from screen overuse, allergies, air-conditioning or fans. There are all kinds of triggers, as was mentioned earlier, that could cause a short-term flare.

There are also patients, as we’ve discussed, who have chronic dry eye disease and need chronic treatments with chronic therapy, such as Cequa, Xiidra, or Restasis. Those patients usually have more staining on the cornea to begin with, so they have more findings at the slit lamp when we examine them. Though I know they need a chronic treatment, those patients usually need something to be able to calm the eye, to break that cycle and tolerate the chronic treatment, because otherwise, their eye is going to be too sensitive to do well with a chronic therapy. I’ve also used Eysuvis for those patients in conjunction with chronic treatment, and they’ve done very well.


It’s a first-line treatment for short-term relief of dry eye signs and symptoms, and it can be utilized either as a standalone, which I’ve had great results with—even in patients with glaucoma, which was great because I was able to use it without concern about increasing the intraocular pressure because they have studies that show little-to-no increase in intraocular pressure. I’ve also used it with chronic patients who needed it as induction therapy.


Eysuvis has the largest clinical development program in dry eye to date. There were over 2000 patients in STRIDE 1, STRIDE 2, and STRIDE 3, which were the hallmark studies that obtained FDA approval. They looked at conjunctival hyperemia as baseline and then inferior and nasal corneal staining, as well as ocular discomfort. They met all the end points. STRIDE 1 and STRIDE 3 had statistically significant improvement in conjunctival hyperemia in day 8 for all 3 trials. That’s why they were able to obtain FDA approval for this first-in-class drug.


The other thing that’s really important to note with the clinical trial data is the instillation site pain was similar between the vehicle and Eysuvis. It was very low, which is great because we know a lot of treatments that we have, especially for patients with dry eye disease who are suffering at the time of those drops, can be difficult to start with it. The IOP [intraocular pressure] increased, which is always good to ask about when we’re talking about a steroid, but there were only 3 of 1400 patients in the Eysuvis trial that demonstrated increased pressure in the eye. That’s extremely significant and very comforting for eye care professionals utilizing Eysuvis, that they can prescribe it and have a very low incidence of increased pressure or any adverse effects.

Lisa M. Nijm, MD, JD, educates on Eysuvis, an FDA-approved prescription therapeutic for dry eye disease.

Eysuvis for DED

 For a lot of people, though—and this is part of the reason that I think we have so many patients who are undiagnosed or underdiagnosed—it’s that they aren’t receiving actual medication treatment for the dry eye. We have so many more options now for treatment of dry eyes, especially one of my most recent ones that I’ve been so excited to use, Eysuvis, because it’s the first FDA-approved dry eye treatment for short-term treatment of dry eye signs and symptoms, and it’s just a 2-week course, 4 times a day. Those are options patients should be given the opportunity to have and to be able to utilize, rather than having them go through 2, 3, 4 artificial tears that are not going to solve the underlying problem because they’re not going to break that inflammatory cascade and will delay them getting care. That’s what happens when they come in.



 Dr Nijm, how would you help us frame a timeline to help guide the patient in seeing you? What do you recommend?



 It depends on what their symptoms are, how severe they are, and how long they’ve had them. If this is the first time they’re coming in, and they feel like there’s some dryness because they’ve been working on the computer more, as we all have recently, then yeah, it’s certainly reasonable. Pick up an artificial tear, and try it; aim for 2 to 4 times a day, and see how you do. If they’ve tried 1, 2, or 3 artificial tears, and they’re still having symptoms when it’s been more than a few weeks, then I would encourage them [to come in]. If it’s bothering them, I would encourage them to get seen because we have so many more options that we can utilize beyond artificial tears.

As a medical community, I think we have to start embracing what we have. Before, there were very limited options for treatment of dry eye disease, and I think that’s where artificial tears became our mainstay. Then we got Restasis, which was great, but that was it for the longest time. Those were the 2 things that we had. If those didn’t work for you, then you didn’t have more pharmacological treatments that were available. We’ve evolved so much with Xiidra, Eysuvis, and with what we understand about the pathophysiology of dry eye and the underlying inflammation that if patients have a lot of symptoms and have tried 1 or 2 artificial tears and aren’t getting relief, then they should be seen.

 Dr Nijm mentioned Restasis, which is cyclosporine. There’s also Cequa, which is cyclosporine, but it’s a higher concentration. That’s another one that’s more recently on the market which that has the same anti-inflammatory properties as Restasis. What I’ve seen with dry eye is that there’s a lot of mixing and matching because of the limited amount of prescription treatment options that are available. You have to figure out where your corticosteroids might come in. You have your softer steroids that can be used for that, and then you’ve got other things like antibiotics, and those will help to decrease the number of bacteria that break down that lipid layer of the tear film—not only topical antibiotics, but also oral antibiotics like doxycycline because it has shown anti-inflammatory effects.


There are others. We’ve talked about topical in terms of instilling drops, but Lacrisert is an ophthalmic insert that’s also used. It comes with a device that helps you insert Lacrisert inside your eye, and then it dissolves and offers continuous lubrication throughout the day. The other thing that’s opened a whole other world in terms of options for patients is sterile ophthalmic compounding. Things like methylpred preservative-free is something that would have to be compounded for a patient, as well as Serum Tears. Serum Tears is where a patient has to get their blood drawn and bring it to the compounding pharmacy. Based on the concentration that the provider has indicated on the prescription, it’s formulated in the end as an eye drop for the patient. I know a lot of patients have found relief using Serum Tears in addition to being on a couple of other things. It’s never just one thing that works, it feels like. There has to be a cocktail for the patient based on their case. It’s very case- and patient-specific.

The panel discusses the possible prescription treatments for dry eye disease.

Prescription Treatments for DED

 At what point would you recommend that patients go see a physician? What are some of the red flags they need to pay attention to? Brian?



 Eye pain and crusting of the eye. The other one that I thankfully don’t see much is new floaters, or like a spider web or curtain vision. Some people have that and say, “Oh, I think that my eyes are dry,” when in reality, their retina is becoming detached, and they need to be seen immediately. Those are things you would want to rule out first, and you are going to want to ask those questions like, “Have you been using this?” They say, “No, I’ve been using this,” or “I went from this to something else that’s maybe a little thicker, and I’m still not getting the relief that I want.” That’s when your dry eye disease is progressing to a point where you want to be seen by a doctor to possibly get a prescription medicine.



Since every case is different, how long should someone be on a particular eye drop? That’s hard to say. I wouldn’t say, “Well, try it for a week, and if it’s not working, then immediately go see a doctor,” but I would say give it a couple of weeks to try some over-the-counter products first—especially if you know it’s dry eye disease—as you wade through the myriad of choices. If someone is having problems, though, you don’t want to underestimate the patient’s lack of commitment to a single therapy. A lot of times, people are noncompliant—where they bought something and decided not to use it—or they keep it in their car and only use it periodically, and then they say, “I heard this commercial, and I want to try this. What do you think is for me?” I would say, if you’ve been doing what you should (eg, 2 to 4 drops a day of the over-the-counter tears or the TheraTears products), and you’re still having those problems or your symptoms are not improving—if they’re getting worse, or there are any other symptoms you’re getting—then you’re going to need a comprehensive eye examination by a doctor.



 I’m going to interject here about what happens from the physician side when patients come in and also make a plea to the pharmacy community to help us more on this angle. What often happens and what the data show is that patients have tried 3 or more artificial tears before they come in to seek medical care from a physician. The unfortunate thing is that they’ve been suffering throughout this time. I use artificial tears all the time; I’m a huge fan, especially of the preservative-free ones because I see so many patients with cornea issues who have dry eyes and have other comorbid conditions that are affected by preservatives. However, artificial tears are only a limited relief. They’re not medications. It’s merely to apply temporary additional moisture to the eye. For some mild forms, that can be great. They can use it 2 to 4 times a day and be fine; they won’t experience more problems.

A panel of pharmacists and doctors explain when a patient should seek professional help for dry eye disease.

When to Seek Professional Help for DED

 The good news is there are a lot of over-the-counter options available to patients for dry eye treatment. It can get very overwhelming. As you were listing all the ocular lubricants, I was thinking about when I talk to patients, one of the things I do—I keep one in my pocket—is show them. “If you’re getting a box that has a preservative, it comes as a bottle and is going to look something like this—maybe a different shape or size—and if it’s preservative-free, you’re going to get little ampules or packages that look like this.” This helps me talk it through with them. “This is preservative-free; it’s single use because you have to snap this off and use it as a single-use item,” kind of like what you were saying, Brian.


With the preserved products, I also try to get an idea of how long the patient is using it for, if it is for a mild case, because then I’m concerned about what it is preserved with. It’s most likely benzalkonium chloride, or BAK, and for short-term use, that won’t be an issue. If it is for chronic use, we know that BAK can be somewhat toxic to the surface of the eye because it does break down that corneal epithelium, and that will increase the permeability of the cornea. It changes that ocular surface and the epithelial cells, which becomes a concern to us. For long-term use, the good news is there are a lot of alternative preservatives on the market, like oxidizing agents, such as sodium perborate. You find that in things like GenTeal and TheraTears; chelating agents like EDTA [ethylenediaminetetraacetic acid]; oil-based products, like Soothe and Systane, which help to ensure that moisture is retained in the eye; and a lot of other oil-based products. Another thing I do is ask about surgeries because if someone has had a surgery like LASIK, for example, I try to avoid the oil-based products right away because there is a healing process they’re going through, so we try to wait. The preservative-free products are great for addressing patient allergies and any toxicity concerns we may have.



Gels and ointments are thicker; they offer more intensive lubrication than eye drops do, and there’s an extended contact time, so they stay longer in the eye. A counseling point that I always like to bring up with patients when we’re talking about solutions and gels and ointments is, sequence and timing. In what order are you going to put these drops in? Solutions go first. With a suspension, I always tell them this is milky. The medication settles at the bottom, so you have to shake it very well before you use it. Those go second, and gels and ointments go last. Then we talk about timing. When your solutions go first, you have to wait a minimum of 5 minutes. After your suspensions, wait a minimum of 10 minutes before instilling something else. After any gels and ointments, wait a minimum of 30 minutes. Counseling on blurry vision is another important point.



To get the best use out of the medication, [I talk about] gentle eyelid closure. Once you instill that drop, make sure you gently close your eyes. Then [there is] punctal occlusion for solutions and suspensions so the drop stays local in the eye because that will help to decrease any of those systemic and topical [adverse] effects we’re concerned about. It increases the bioavailability of the product and possibly decreases the frequency that the patient has to use drops because they’re getting the best use out of it locally in the eye. Getting that patient engaged and going through these points is an approach that pharmacists take and is crucial and critical when they’re having that one-on-one with a patient.

Monazzah Akbar Sarwar, PharmD, continues the conversation for over-the-counter treatment options for patients with dry eye disease.

Over-the-Counter Treatment Options for DED: Continued

 I think it’s tough sometimes for patients to look for over-the-counter treatments for dry eye disease. There is a whole aisle [of products], and it seems like there are new types of artificial tears all the time and all kinds of different ointments and gels and everything else. How do you guide patients when they ask about these different over-the-counter treatments?



 When researching this project, my eyes were opened to the myriad and the combinations of products. I don’t want to say, “the confusion,” because it’s also confusing for health care professionals to understand viscosities. The more petrolatum [that a product contains], the more likely that it’s going to be very thick and blur your vision. Where do you go to see which one is in which viscosity range? It is very confusing.

There is the water component of products, and there is an oil component. There are [also] emulsifiers that help mix those two things together because oil and water don’t really want to mix. [There are also] FDA rules on what [constitutes] an active ingredient versus an inactive ingredient. There is a lot of confusion because some active ingredients that are in one product in a specific concentration may be listed as the inactive ingredient in another product, just because it [appears at a lower concentration than] the threshold of what the FDA requires [for an active ingredient].

[I would recommend] artificial tear products first to someone who complains of mild eye dryness—maybe it’s a little seasonal, but it’s not necessarily an allergy or a slight environmental problem. Something that you could use 2 to 4 times a day [includes] Blink, Biotrue, Clear Eyes, Systane, TheraTears, Refresh, Rohto, or Soothe by Bausch + Lomb. Those are products that are going to be thinner or liquidy. They can be put in while a person is driving or wearing contacts. A lot of [their package labeling says] that [these products] haven’t been studied in people wearing contacts, but most manufacturers say that they have been proven to be safe for contact [lens] wearers.



Many manufacturers also have preservative-free options. Most come as single-dose or single-use vials. Many times, patients see the cost of those, and they only use 1 or 2 drops and then try to save it. [These people must be told that] these products are for single-use only and [should not be kept]. Ideally, preservative-free products should be used for people with moderate-to-severe dry eye, as well as those with glaucoma, [since] some preservatives can damage the corneal nerve.



An exception is the Optase dry eye drop. It’s a little expensive, but the manufacturing container doesn’t let air back in after the drop is released, so it can be kept for 3 months. There is also Nature’s Tears spray. I’m not a big fan of spraying any aerosol into the eye, but [this is an aerosol formulation to be sprayed] 8 inches or more away from your eye. It is just a cell culture-grade water that is pH balanced, so it’s not going to cause any stinging.



Then you have a thicker product for people who say, “Oh, I’ve tried the tears product, and I need something a little stronger.” You have GenTeal or Refresh that contains gels, and those really just have [ingredients] that are in higher concentrations than the regular tears products. It’s got a higher concentration of the thickener and lower concentration of water to make it more of a gel product. As you increase viscosity, however, you increase the possibility of blurriness or a little bit of vision loss at first by putting in those drops. Then you have ointments, which are more or less Vaseline or highly purified petrolatum products or mineral oil. Those will definitely cause blurry vision and are marketed [to apply] in the evening after a long day of computer use. They last a whole lot longer than a regular tears product would.



There are some exceptions. We’re talking about educating patients, as well as health care professionals, about over-the-counter eye drops. There are instances when, even within the same manufacturer, active ingredients are listed in the same exact quantity and concentration [for different products. For example,] Systane and TheraTears have identical products, and Systane Complete and Systane Balance have exactly the same active ingredients. The difference really is in the inactive ingredients that make it more pH balanced or [effective] slightly longer. You have to understand that the inactive ingredients play a really big role.



There are some products that are marketed specifically for people who are on a computer, such as Rohto Digi-Eye and Refresh Digital. Digi-Eye contains the decongestant tetrahydrozoline to get the red out in addition to the cellulose derivative hypromellose. Refresh Digital doesn’t contain a decongestant; it contains carboxymethylcellulose, liquid glycerin, and the emulsifier polysorbate 80. We all remember Visine as being the product that came out first to reduce redness. [That brand] has a dry eye-relief product that doesn’t have the decongestant like the older, original Visine. You have to grab the box, look at the active and inactive ingredients, and kind of help guide the patient because there is a lot of confusion about just the regular product name.

Brian Walker, RPh, elaborates on the over-the-counter treatment options for patients with dry eye disease.

Brian Walker, RPh

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