The Ophthalmic Project: Dry Eye Flares with Eric Donnenfeld, MD


Mark L. Dlugoss (00:05):

Hello, this is Mark Dlugoss, Senior Contributing Editor for Ophthalmology360. Welcome to the Ophthalmic Project sponsored by Ophthalmology360. In honor of July being Dry Eye Awareness Month, the Ophthalmic Project looks at a major problem associated with dry eye disease and it's called dry eye flares. Until recently there's been no real treatment for dry eye flares. Joining me now to discuss dry eye, dry eye flares and a new treatment to address these flares is Dr. Eric Donnenfeld. Dr. Donnenfeld is the founding partner of Ophthalmic Consultants of Long Island in New York and the Ophthalmic Consultants of Connecticut. He is also a clinical professor of ophthalmology at New York University. Dr. Donnenfeld, welcome to the Ophthalmic Project.


Eric D. Donnenfeld, MD (00:50):

Mark. It's a pleasure to be here. I always enjoy speaking with you.


Mark L. Dlugoss (00:53):

Thank you very much. Same here. Let's start off with a basic question, and I know most of our audience is probably going to understand this, but it sort of sets the groundwork for today's discussion. Basically, what is dry eye disease?


Eric D. Donnenfeld, MD (01:08):

Well, Mark, that's a very basic question and really sometimes difficult to answer, but it's widely perceived that dry eye disease is a chronic and symptomatic condition, but it doesn't have to be chronic. It can certainly be episodic. And it's a tear film dysfunction where the ocular surface tear film is abnormal, resulting in an inadequate supply of lubrication to the ocular surface. You know, Mark, it's the single most common reason why patients come into an eye doctor's office. Dry eye disease is really endemic and it's really thought that there are 30 to 40 million Americans who suffer from dry eye disease.


Mark L. Dlugoss (01:44):

There's a condition, obviously, that's an offshoot of that, and that's a dry eye flare. But what is a dry eye flare and what's the root cause of those flares?


Eric D. Donnenfeld, MD (01:54):

Well, you know, dry eye flares are something that I think every one of us have seen on a routine basis in our office, but we maybe haven't really thought through what this is. And that is that dry eye, in most patients, is actually episodic. And you can have a baseline dry eye, but you have periods of active exacerbation where the patients become more symptomatic. They become more dry, they become more irritated. And the average patient has four to six dry eye flares every year and these flares last for seven to fourteen days. And during these periods, the patients will feel significantly worse. They can be exacerbated by activities such as going out skiing on a dry day, or it can be exacerbated by certainly environmental changes as well. So, it's a very common condition. It affects the quality of life for many patients, and we're just starting to realize how important this is for most of us.


Mark L. Dlugoss (02:55):

You mentioned there was some environmental causes to triggering dry eye flares. Are there any other systematic or other environmental causes that would trigger the flares?


Eric D. Donnenfeld, MD (03:07):

Well, Mark, good question and certainly there are a variety of different patients will have different environmental flares. Things like the heat turning on in the fall for some patients, air conditioning in the summer, airplane travel is one that does it for me. Seasonal allergies can cause dry eye flares as well. And there's a big relationship between dry eye and allergies as we all know. Some patients will have flares with the use of contact lenses. We see them in surgery, very commonly in patients having LASIK or cataract surgery will cause a flare that can be significant. Finally, I think epidemic is the use of excessive digital devices can really cause dry eye flares on a routine basis.


Mark L. Dlugoss (03:53):

What's the percentage of dry eye patients who actually experienced the flares?


Eric D. Donnenfeld, MD (03:57):

You know, I would answer that question by saying every one of them, but the literature says 80 to 90% of patients have dry eye flares, but I don't think I've ever seen a patient who didn't experience some type of dry eye flares on a routine basis.


Mark L. Dlugoss (04:13):

Saying almost 80, 90% of them experienced dry eye flares, are there any particular types of dry eye patients who seem to be more susceptible to dry eye flares?


Eric D. Donnenfeld, MD (04:24):

Well, I think we see it everywhere, but it's very highly associated with patients with immunologic disease, such as rheumatoid disease, lupus, thyroid disease. It's also seen more commonly in the patients who have basic risk factors for dry eye, such as perimenopausal women, patients who had previous surgery. But dry eye flares have really affected all aspects of patient care, and we see it routinely almost every day. I know I experience dry eye flares on a routine basis when I do airplane travel for example, but everybody has their own trigger that releases dry eye flares. And the important concept about dry eye flares that we know about them is that they're almost always due to inflammation. Inflammation is the critical risk factor for patients having dry eye flares and controlling inflammation is the key aspect in controlling these dry eye flares in ameliorating patient's symptoms.


Mark L. Dlugoss (05:26):

Well, it's widely agreed that the majority of patients with a chronic dry eye experienced flares, as you said, the pathophysiology is not well understood. What do we know about the dry eye flares? And basically what I'm asking is what is the ophthalmic science telling us about dry eye flares?


Eric D. Donnenfeld, MD (05:43):

Well, what we know about dry eye flares is we know that they're inflammatory. We know that T lymphocytes are involved and they affect the adhesions of lymphocytes to the epithelial surface. We know that they can cause increase in inflammation. We can see elevation of tear osmolarity, metalloproteinases levels can be elevated in these patients. And there's been some wonderful research that's been done on dry eye flares recently, a wonderful article by Perez and Stern and Pflugfelder really looked at the science of dry eye flares and showed that there's an innate immune response in many of these patients that goes to lead to exacerbation of these patients' dry eye.


Mark L. Dlugoss (06:29):

Do you think we still need a lot of research to be conducted in this area? Is it still needed?


Eric D. Donnenfeld, MD (06:36):

You know, dry eye is the most common reason why patients come to our office and it's really, very simplistic to say this, but we just don't know a lot about dry eye. There's so much more that we're learning about it, there are new drugs that are being developed, but dry eye is one of the great unmet needs right now we have in eye care and I can't emphasize enough how important it is to continue research and to continue devoting time and effort to finding better understanding of dry and better treatments as well.


Mark L. Dlugoss (07:10):

I'm going to move things a little bit in terms of, from the eye care providers perspective. In treating patients suffering from dry eye flares, are there any targeted questions that eye care providers should ask their patients during their evaluation so that can help them develop a comprehensive treatment strategy?


Eric D. Donnenfeld, MD (07:28):

You know Mark, great question and I would take a step back from that and say that it's important to just ask your patients if they have dry eye to begin with. And we have a modified questionnaire, it's a modification of the speed questionnaire that we give to our patients when they walk into the office and we ask patients if they have certain baseline characteristics that we think put the patient at risk of having dry eye. Asking questions like, do the eyes feel irritated? Foreign body sensation? Do they feel dry? The simple questions like that. And now we've actually modified that questionnaire to ask them if they also have symptoms of dry eye flares and we ask them if their symptoms vary during certain periods of the year and whether there are any environmental or activities that predispose them to worsening of their ocular symptoms. I think it's a very fundamental question to ask your patients.


Eric D. Donnenfeld, MD (08:28):

So when you diagnose a patient with dry eye, I think it's really important to take a step beyond that and pursue the dry eye and find out how it affects the patient and whether it's chronic and a plateau, or whether it's episodic with large peaks and valleys of dry eye, which is really the hallmark of dry eye flares. As a matter of fact, Mark, you certainly know this, is that there are many patients, maybe 50% of patients, who are diagnosed with dry eye, who don't really have chronic dry eye. They really have episodic dry eye. They have flares and the flares occur four to six times a year, but for the rest of the year, they really don't have any signs or symptoms of dry eye. I think it's important to think about maybe treating these patients a little bit differently than we would treat a patient with a plateau of dry eye that may have just occasional flares during the course of the year.


Mark L. Dlugoss (09:25):

I don't know, you might've answered this question, but I'm going to throw it out anyway because dry eye flares being an inflammatory driven disorder, what should the eye care provider be evaluating and determining his or her treatment plan?


Eric D. Donnenfeld, MD (09:40):

Well, I think it's important that an eye care professional gets the history and dry eye flares may not be present when the patient walks into your office. So you want to know how the patient's level of dry eye symptomatology on that day compares to what it's like during other time periods when they may be worse. So when I evaluate a patient for dry eye, I do the fairly normal tests that most eye care professionals do. I look at the lid margins, I look at the tear film. I like staining the conjunctiva with lissamine green. I use Fluorescein to look at the cornea. I look at tear breakup time. I don't do Schirmer testing so often, and I like to use MMP-9 testing and tear osmolarity on patients who I'm convinced have dry eye to find out whether I think it's inflammatory or not. But you want to know from the patient, if their level of dry symptomatology varies during the course of the year and where they are in that cycle, when they walk into your office. Are they coming in at the period of time when they're least symptomatic or most symptomatic?


Eric D. Donnenfeld, MD (10:52):

Because my level of therapy is going to be predicated, not only by my physical findings, but actually more importantly by the patient's relating their symptomatology and how their symptoms vary during the course of the year. I might start off with a lower level of therapy for a patient who comes in, who says that they're experiencing their worst symptoms on that day as compared to a patient who comes in and says that they're actually fairly mild on that day, but they can get much worse. So my level of therapy is predicated not only on physical findings, but patient history.


Mark L. Dlugoss (11:34):

Prior to the recent FDA approval of a new drug to treat dry eye and dry eye flares, and we'll discuss that momentarily, what other therapies were available to eye care providers to manage dry eye flares?


Eric D. Donnenfeld, MD (11:49):

Well, foundational therapy for dry eye has few years been artificial tears, and I think tears treat the symptoms, but they don't treat the root cause of dry eye. And I think they're just, they just ameliorate the patient's symptoms. I think the real breakthrough in dry eye management was the development of cyclosporine, trade name, Restasis, which was FDA approved about 20 years ago, which really was the foundational therapy for managing dry eye. But, it actually treated the root cause of dry eye by treating the inflammatory disease, which is a T-cell mediated disease and cyclosporine, as you all know is a T-cell mediator. So that was kind of the first therapy and then we had other therapies developed. We have other cyclosporine products that are now available. We also have the use of Lifitegrast or Xiidra which is a wonderful T-cell modulator as well. And we have some new anti-inflammatory therapies that are being developed also. We've learned that treating the lid margin is important as well as treating the tear film. So there are a variety of therapies that are available, but for years we just used tears, more lubrication, maybe some ointments for patients who had dry eye flares and we use off-label corticosteroids occasionally as well. If the patient didn't respond well to just topical immunomodulation with cyclosporine or Lifitegrast.


Mark L. Dlugoss (13:19):

Well, as you know, earlier this year, the FDA approved Eysuvis from Kala Pharmaceuticals and it's the first drug to treat dry eye on a short-term basis, including dry eye flares. Can you outline some of the take-home points regarding this new drug?


Eric D. Donnenfeld, MD (13:36):

I think this is exciting and what I love about this product that I service from Kala is that it rapidly improves symptoms and patients who come in with flares don't want to have a long-term therapy that's going to take weeks to months to become asymptomatic. This drug works very quickly and what Eysuvis is, is it's a 0.25% loteprednol etabonate ophthalmic suspension and it's formulated with a nanotechnology. So the particles are approximately 300 nanometers in diameter and it's designed with a special delivery system called Ampplify that allows these very small nanotechnology loteprednol molecules to penetrate through the normal mucus that's on the tear film to get to the target tissue, which are the epithelial cells that are the root cause of dry eye. So that not only is it a FDA approved therapy for dry eye, it also really has dramatically changed the way the loteprednol is delivered by using this nanotechnology to get into the tissues. I've been a big fan of loteprednol for a long time.


Eric D. Donnenfeld, MD (14:56):

It's one of the safest drugs we use in ophthalmology as an anti-inflammatory. It's the only ester corticosteroid, which means that the body's innate esterases can take the molecule and inactivate it so that it doesn't have nearly the long-term complications of the amide corticosteroids. So there's much less cataract agenesis. There's much less pressure spikes making Eysuvis one of the safest drugs I've used. And the fact that it's FDA approved for the short-term treatment of dry eye makes me feel very comfortable with it. The official use of the drug is that it's approved for use for up to two weeks and it's meant to be used four times a day for that two week period of dry eye flares.


Mark L. Dlugoss (15:47):

Well, you outlined a very positive safety profile for Eysuvis. Are there any serious adverse results in patients using it?


Eric D. Donnenfeld, MD (15:58):

Well, in the FDA trials, it was very safe. And I want to point out that the FDA trials with Eysuvis are the largest FDA trials ever in the history of dry eye with over 2,800 patients participating in the trials and the level of safety was extraordinary. As a matter of fact, the incidents of a pressure elevation of greater than >10 millimeters of mercury from baseline and >21 millmeters of mercury was only 0.2% or one in about 333 patients had a pressure spike during the course of the study. Cataractogenesis was not a problem, and I think as long as eye care professionals use this drug, as it's meant to be used, and it's FDA approved at four times a day for two weeks, I think we can say the safety profile of this drug should be exceptional. And I think it will be a very useful treatment for a chronic disease that we really don't have a good treatment for right now and that is dry eye flares.


Mark L. Dlugoss (17:00):

How have you been using Eysuvis in your practice and what kind of results are you getting from the drug?


Eric D. Donnenfeld, MD (17:07):

Eysuvis is FDA indicated for dry eye, including flares, and I find it to be very helpful for that. And I use it all the time for dry eye flares. I find it to be exceptionally helpful for these patients and I kind of bifurcate my dry eye patients for patients who have chronic dry eye, I believe very strongly in starting on an immunomodulator first-line therapy for me has been lifitegrast. I also will occasionally use cyclosporine. And then when they flare up, I will add Eysuvis as a second line therapy and I view dry eye as having very many similarities to glaucoma. In glaucoma we have multiple therapies that we use to treat glaucoma and I think dry eye is the same way. And I think having multiple immunomodulators adds to the benefit of the therapy. I will also mention that one of the problems that I've seen and, and has been well-documented, is that many patients when they start a dry therapy like lifitegrast, or like cyclosporine, they experienced burning and irritation that makes the use of these medications difficult.


Eric D. Donnenfeld, MD (18:17):

And a lot of patients discontinue use of these immunomodulators before they really have a chance to be successful. A real pearl is I like to use Eysuvis in conjunction with cyclosporine or lifitegrast as initiation therapy for these medications. And what I do is I start the patient on Eysuvis four times a day, generally for two weeks, as FDA indicated, and then tapered down to twice a day for two weeks and then stop the medication. At the same time, I will start the immunomodulator, whether it be lifitegrast or cyclosporine, the way it's intended to be used. They're both BID drugs. I continue those medications twice a day and by the end of the month the patients are generally starting to feel much more comfortable and they just don't experience the burning, the irritation that are sometimes associated with initiation of these immunomodulators without the use of a potent and safe corticosteroid, like Eysuvis.


Eric D. Donnenfeld, MD (19:20):

So I use Eysuvis for flares. I use it on top of immunomodulators. I use it to initiate therapies with immunomodulators and the third indication that I found for using it, is for patients who have dry eye flares, but really don't have chronic dry eye. For a patient who has dry eye flares, maybe four or five times a year lasting for a week, I just don't think it makes sense to put a patient on a drop every single day for a year when they only have 20 or 30 days of dry eye flares. And for those patients, I use Eysuvis as primary therapy for those patients who have intermittent, but not chronic dry eye. And it's estimated that maybe there are 50% of the patients who have dry eye really just have dry eye flares.


Mark L. Dlugoss (20:15):

What are you hearing from your patients in terms of patient satisfaction? And could you provide a few case examples?


Eric D. Donnenfeld, MD (20:23):

I've been very happy with this. We have a large dry eye practice, and I think it dovetails into our cataract and refractive practice as well. And patients want rapid relief of symptoms, they want to use a drug that's been FDA approved. They feel comfortable with use of Eysuvis and we've had great success in these patients. And for patients who come in, who are having dry eye flares, I find it to be exceptional as an ophthalmic surgeon. I really like using Eysuvis for what I call rapid rehabilitation of the ocular surface for a patient who's coming in for cataract refractive surgery. These patients very commonly will present to me for possible surgical intervention and I very strongly believe as a good clinician, we should really optimize the ocular surface as quickly as possible before we consider surgery on these patients. The incidence of dry eye is very high in this patient population.


Eric D. Donnenfeld, MD (21:25):

And using Eysuvis has really been great in my hands for these patients who come in, who wants surgery and want it to be better quickly. So a good case study would be, I just saw a patient who came in for cataract surgery, actually had a significant cataract, but had significant SPK, dry eye signs and symptoms. The topography was irregular. And when I looked at the topography, I knew that I wasn't going to get a good IOL master and I wasn't going to get a good IOL prediction. So I started the patient on some non-preserved tears. I had the patient use Eysuvis four times a day, and I also started the patient on lifitegrast at the same time for chronic therapy. And I brought the patient back two weeks later. Two weeks later, the topography was normal. The SPK were gone and the patient was able to have a pristine IOL Master and went on to unremarkable cataract surgery with a great uncorrected visual acuity, because I was able to get the right IOL calculation because Eysuvis had rapidly rehabilitated the ocular surface.


Mark L. Dlugoss (22:35):

We've covered a lot of ground today on dry eye flares and dry eye disease in general. Is there any other final thoughts or advice you have for eye care professionals about proactively treating dry eye flares?


Eric D. Donnenfeld, MD (22:48):

Well I would just start by saying that dry eye flares are real, they're common. They affect patient quality of life. And as a good clinician, I think it's important to make the diagnosis. I really think that this is an area where ophthalmology and optometry need to work together to help manage these patients. And there's just an epidemic of dry eye that's going on now in the United States and it's due to a variety of different reasons. A lot of it is environmental, it's nutritional as well and treating dry eye and specifically dry eye flares, I believe is one of the most important things we can do as clinicians to improve the quality of life of our patients who come into our office whose needs have not been met by simple use of artificial tears. And I would finish by saying that I believe Eysuvis, which is a loteprednol etabonate ophthalmic suspension 0.25% has really been a breakthrough in the management of these patients. And I love the fact that it's FDA approved and gives me the ability to treat these patients and feel comfortable that I'm using a corticosteroid in managing a chronic condition that really needs my attention. So Mark, I really enjoy spending a little time with you. I always enjoy it. I hope that everyone found this to be useful.


Mark L. Dlugoss (24:10):

Well that concludes today's Ophthalmic Project video podcast. I want to thank Dr. Eric Donnenfeld for spending some time with me discussing dry eye, dry eye flares and the new therapy of Eysuvis. Again, thank you for listening and have a good day.