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Dry Eye
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Video: Navigating the Management and Treatment of Demodex Blepharitis

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Eric Donnenfeld, MD:

Well, hello everyone. I’m Eric Donnenfeld. I’m here on Long Island and I’m really delighted to be here with my very good friend, the amazing, incredible Preeya Gupta. Preeya, tell me a little bit about yourself.

Preeya Gupta, MD:

Of course. Eric, thanks so much for having me. Preeya Gupta, Triangle Eye Consultants, cornea, cataract, and refractive surgeon. And so this is always fun for me to spend time chatting with you really about anything in ophthalmology.

Eric Donnenfeld, MD:

Yeah. And we’re going to do some good chatting today because this is such an interesting subject and you know something? It’s one of those subjects that I just love talking about. We’re here with Ophthalmology 360. We’re going to be having a nice conversation about Demodex right now. And this is one of my favorite sayings, and it comes, I believe from Mark Twain who said, it’s not what we don’t know that gets us in trouble, it’s basically what we know for sure but are wrong about that gets us in trouble. And a perfect example of that is Demodex blepharitis. For decades, I thought that Demodex was a commensal organism. It’s a mite that lived in the lid. It didn’t bother anybody, but I was dead wrong and I’ve come to learn for a variety of different reasons that Demodex is actually a pretty serious problem, and it’s underdiagnosed, and the good news is we have a new treatment. So let’s start by asking you, Preeya, what is Demodex blepharitis?

Preeya Gupta, MD:

Well, Demodex is a parasite that it does live on all of our skin, but for a lot of patients who have ocular surface disease, but even just our average patients coming into our clinic as they get older tend to have increasing populations of Demodex on the ocular surface. And so it’s a little mite and it lives typically at the base of the lash. It actually will go inside the meibomian glands or the lash follicle area, and it kind of makes a home and leaves a little bit of wreckage behind it. It can create inflammation along the eyelid, excoriations from the mite, disrupting the epithelial barrier on the skin of the eyelid, and then also create a lot of inflammation and chemical reaction from their byproducts, which holy smokes. Let’s just pause for one second. Think about how much we know about Demodex today in 2024, and I’ve only been in practice maybe 13, 14 years at this point, but I never for a single minute thought that we would actually be really talking about Demodex blepharitis and having a way to treat it and being better diagnosticians to find it.

Eric Donnenfeld, MD:

Yeah. I couldn’t agree with you more. You know something? I never really looked for Demodex blepharitis because it was something I didn’t worry about. And if you don’t worry about it, you don’t look for it. But today I’m looking for it constantly, and it’s just so common. It’s estimated based on studies that there are about 25 million Americans with Demodex. I’m going to go out on a limb and say it’s a lot more common than that. We know that it’s found more commonly with age. We see it in men and in women. We know that it’s also very highly associated with dry eye, so that over 50% of people who have Demodex also have dry eye. And that makes sense.

There are two different Demodex organisms. One lives in the lash follicle and one lives in the meibomian gland, and both result in significant inflammation. And for me, Demodex is the missing link that I’ve been looking for decades now on the cause of dry eye, specifically meibomian gland disease. And I think Demodex plays a significant role in quality of the tear film because it really involves inflammation of the meibomian glands and we see it constantly. So let’s just talk a little bit about the diagnosis, and we’ll come back to that a little later on, but in the past, my partner, Hank Perry, diagnosed Demodex by plucking lashes and looking for Demodex on lashes. Is there a better way of making the diagnosis today? And do we need to do lash plucking on patients?

Preeya Gupta, MD:

Yeah. I used to have a toy microscope and would pluck lashes on very select patients, and it turns out you don’t have to do any of that to find Demodex. It actually is such a deterrent to think that you’d have to pluck a lash to make a diagnosis. I don’t think anybody really has time for that in clinic. And so the collarette, which is really just a compilation of the mites excrement and all their byproduct debris, that gets really stuck onto the base of the lash in a cylindrical sleeve.

So we call it cylindrical dandruff or collarette, but if you see that on your patient’s lash margin, eyelid margin, that is pathognomonic for Demodex blepharitis. And so the easiest way is to have the patient look down. I’ve always felt like I was a good clinician and learning more about Demodex blepharitis has made me realize that I was terrible at recognizing Demodex blepharitis. Like you said, Eric, if you’re not looking for it, you’re not going to see it. But it turns out that if you just having a patient look down into your slit lamp exam, you can’t help but see it. It’s everywhere.

Eric Donnenfeld, MD:

When you look for it, you’ll see it constantly. But what’s surprising to me is how many times it’s just fulminant. Every lash has a collarette behind it, there’s this crustiness to the lashes, the lashes are erythematous. And it’s felt that, as you mentioned, that the Demodex blepharitis collarettes are due to excrement. It’s also due to inflammatory debris. Sometimes the mites will actually cause inflammation at the lash border. So it’s really very pathognomonic. And in general, if you have two or less, we think that that’s not such a significant problem, but when you have the entire lash border filled these Demodex mites, it causes significant symptomatology. And these patients are very symptomatic. And I want to address another symptom that I think is really common. Now, Preeya, you and I have favorite symptoms, and we have that in common. It’s a mutual admiration society. When we think about dry eye, when we think about meibomian gland dysfunction, we talk about visual fluctuation.

Preeya Gupta, MD:

A hundred percent.

Eric Donnenfeld, MD:

And visual fluctuation is meibomian gland disease until proven otherwise. But there is another symptom that I’ve really been talking about for decades now that I thought was always related to allergy and that was itching. And when I hear the diagnosis of itching, I say, there’s nothing else other than allergy that causes itching. But again, I’ve been proven wrong. Tell me about itching and Demodex.

Preeya Gupta, MD:

Yeah. I share this sign with you for Demodex. It’s the one question that I ask anyone that I’m suspecting Demodex blepharitis. It’s the one question I always ask them. Do you feel the urge to just take your fingernail and itch your eyelid? And it’s a very specific Demodex symptom because the patients get irritation along their lash margin. And unlike allergy in which you want to get in there, rub the corner, rub the eyeball, these patients want to directly scrape their eyelid. And especially at night. We do know that the mites actually like to come out at night and are more active at night. And so patients that also will report, oh yeah, every evening, I feel like I want to rub or scrape my lash line, I’m looking for Demodex blepharitis until proven otherwise.

Eric Donnenfeld, MD:

So that’s exactly right. And the symptom that I’m looking for is itching. But when someone says, my eyes itch, I stop the patient right then and there and I say to them, do your eyes itch or do your eyelids itch? And that’s a very important differential that we should be asking all of our patients who come in with itching, whether it’s lid or whether it’s the eye itself. And when it’s a lid, it’s Demodex until proven otherwise. If it’s the eye, it’s probably going to be allergy as well. And it’s a very different type of itching. And you’re exactly right. And these patients, they’ll just be pressing on their lids. They’re very, very, very vocal about it. And many times, you look at the lids and you’ll see the demotic blepharitis and you’ll actually see erythema along the base of the lashes. And since we’re talking about the symptoms and signs of Demodex, tell us about erythema. Is erythema common in patients who have Demodex?

Preeya Gupta, MD:

Absolutely. I think erythema is essentially a sign that’s the most troublesome for patients. It would actually drive them into your clinic to seek eye care. Patients with Demodex blepharitis, as you mentioned, have that inflammatory reaction. So they will get that reddish hue. Some patients will even actually have frank swelling right around the base of the lash. And it is very common and it drives these patients crazy. It’s cosmetically unappealing to them, it’s uncomfortable, and it is something that will actually get patients in the door. So it’s something that we don’t want to miss.

Eric Donnenfeld, MD:

And what we’ve seen from some of the studies that have been done is that the erythema and irritation really has a profound psychological impact on these patients. These patients are troubled, they feel like they are cosmetically damaged, they feel like no one’s paid attention to them. And very commonly, these patients have seen half a dozen different eye doctors, both ophthalmologists and optometrists, and have never been diagnosed correctly, and it just leads these patients to feel like they’ve just been abandoned and they become depressed. This is not an insignificant problem for most patients. So the combination of itching and the combination of lid erythema are two of the signs and symptoms these patients have that really impact their quality of life. And you would think that this would not be as significant. But having treated patients now with some of the new therapies we’ll be talking about, these patients come back to me and they are extraordinarily grateful that number one, we’ve made a diagnosis.

Number two, we’ve taken the diagnosis seriously. And number three, we’ve actually made them better. And that’s the exciting part about Demodex blepharitis that we can talk about today is we actually have new therapy that actually is very successful in managing these patients. And that is lotilaner ophthalmic solution 0.25% from a company called Tarsus. The trade name is XDEMVY, and we’ve been extremely happy with this medication. But before you talk about your experience, maybe you could give us a little background on what was found in the FDA trials with lotilaner and the trials that allowed this drug to be approved.

Preeya Gupta, MD:

Yeah. It’s amazing. This is a trial, actually, there’s two trials and it contained over 800 patients. So that’s a lot of patients with Demodex blepharitis. On average, they had in that more severe grade three where there was over a hundred collarettes per lid, so these are not mild patients. The lotilaner 0.25% is dosed one drop twice a day for six weeks. And they found in their studies, when they looked at the number of patients that went from their grade on average of three to grade one, which is under 10 collarettes, 85% of the people that were treated with lotilaner went to that grade. And so that’s just a significant reduction in that load of collarettes on the eyelid, which to us, that’s the easiest clinical sign to see. They also went as far as they did pluck lashes, they actually counted the number of mites on the lashes, and all of those showed improvement as well.

So it really was demonstrated in these two large clinical trials to be robust at not only eradicating the mites, but one thing that I found really interesting is that it was well-tolerated. When we all think of traditional Demodex blepharitis therapies, this is like throw the kitchen sink, there’s tea tree oil, there’s compresses, there’s lid scrubs and things like that. But in the trial, patients didn’t do anything else. They just did the medication twice a day and it had an under 10% or less rate of burning and stinging, which is definitely unheard of in our prior generation of treatments.

Eric Donnenfeld, MD:

Let’s talk about lotilaner. What is lotilaner? It’s a neurotoxin that’s specific for Demodex. It has no effect on human beings. It doesn’t affect us in any way. And it obviously kills the Demodex that are there. We apply it for six weeks because we not only want to kill the Demodex, we want to kill the eggs that are being laid when they hatch so that you can actually get the first generation and the second generation as well. And we use it twice a day for six weeks based on the FDA trials. But what’s interesting is we know that Demodex is a commensal organism. It will come back very commonly. So one of the concerns with Demodex was that, well, what if you treat the patient for six weeks? Will it come back right away or do the results that you have from using lotilaner last for more than six weeks?

And there was just a paper that was presented on the long-term effects of using LOD for six weeks, and they followed these patients for one year. What they found was that at one year, these patients still had statistically significant reduced erythema, less itching, less irritation, and less dry eye symptoms, so that the patients who got lotilaner had a effect that went on for months after the therapy was stopped. Now, I do think we’ll have to retreat some of these patients, but the idea that the collarettes are gone and that the patients aren’t itching and the erythema is improved is very promising that this may be a good long-term solution for a lot of these patients. And that’s really a highlight of using this medication. Now, before we used lotilaner, we’re going backwards a little bit. We had other therapies and you mentioned tea tree oil, and that was probably the most common therapy that I used. But what were the problems with tea tree oil, Preeya?

Preeya Gupta, MD:

Yeah. It’s extremely toxic. It’s difficult to tolerate for patients. And if any of you have ever used a wipe with tea tree oil or gotten anything, it burns, it stings. Compliance is difficult. There’s also some studies that show that some of the active ingredients in tea tree oil are actually cytotoxic to cells within the meibomian gland. So it’s not a great long-term therapy. Of course, limited by compliance on its own. So I rarely see people that are taking high percentage tea tree oil on a regular basis. One treatment that I still do incorporate even in combination with lotilaner is microblepharoexfoliation. I think it’s really a win in the office. It’s very difficult for patients. They can’t just take a wipe and get rid of that cylindrical dandruff debris. And so to me, it prepares the lids, it debulks that inflammatory load, and then the lotilaner takes its effect, and so it’s a nice one-two combination, especially for those more severe collarette patients.

Eric Donnenfeld, MD:

I agree, and that’s exactly what I do. I like to use blepharoexfoliation. It removes the crust. It’s almost like having your teeth cleaned. It removes all the glycosaminoglycans, it removes all the nits that are there, and it allows the nodal to penetrate better and to be more effective more quickly. Now, there were a lot of other therapies that were there before. We talked a little bit about tea tree oil. There’s ivermectin, there are other medications as well. I basically have stopped using all these medications. For me, the risk reward ratio is so good for using lotilaner. It’s the most well-tolerated therapy that I’ve used and also the most effective. So that’s to me, a win-win for using this medication. So I basically just abandoned the other therapies and I’ve gone a hundred percent to using lotilaner, and I find myself using it more and more.

And what’s specifically interesting to me is how when you treat Demodex blepharitis, a lot of the ocular surplus problems the patient has, the dry eye, the blepharitis, the crust and the irritation, the erythema, all improve markedly. So Demodex is certainly not a commensal organism. It’s something that really has a profound effect on patients’ quality of vision, quality of tear film, and quality of life. And we have found that this has been one of the most remarkable adoptions that I’ve seen with a therapy that I never really even thought about a couple of years ago, and now I’m seeing that this is really changing the way I manage ocular surface disease. Preeya, any parting words for you on the use of lotilaner in the management of Demodex blepharitis? Is this a serious problem?

Preeya Gupta, MD:

It really is, and I have been just pleasantly surprised, just like you, at the spillover of its effects. And it really just highlights the fact that a lot of our patients with that more moderate to severe ocular surface disease, we know they have multifactorial disease, and I’ve been trying it in those patients, even if I see some collarettes. These are our patients that are really good at cleaning and you might not see them as well in clinic. And so it’s really become an anchor for patients that have those severe symptoms and it’s been great.

Eric Donnenfeld, MD:

And I’ll just close by saying that some of the most rewarding patients that I’ve seen in the last few months have been patients that I’ve been treating for Demodex blepharitis with lotilaner. These patients come in and they just gush on how appreciative they are that for the first time in their lives after having been either ignored or misdiagnosed for decades, they finally have a therapy that’s worked, it’s changed their outlook on life, and these patients are extraordinarily happy. And for me, that’s the most rewarding thing we do as ophthalmologists is to change patients’ lives. And something as simple and maybe something as mundane as Demodex blepharitis really is an important part of our management every day of ocular surface disease. Well, thank you for joining Preeya Gupta and me, Eric Donnenfeld in this recording of Ophthalmology 360. We hope you find this information educational and you enjoyed it as much as I enjoyed it. Thank you again, Preeya, for being with me. It’s always exceptional to have you in a conversation.

Preeya Gupta, MD:

Thanks for having me.

 

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