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ANDREA TOOLEY: Welcome to the Mayo Clinic Ophthalmology Podcast, brought to you by Mayo Clinic. I'm your host, Dr. Andrea Tooley.

ERICK BOTHUN: And I'm Dr. Erick Bothun. We're here to bring you the latest and greatest in ophthalmology, medicine, and more.

ANDREA TOOLEY: In today's episode, we are joined by cornea and surface disease expert Dr. Joanne Shen. Dr. Shen shares her insights for managing dry eye patients, including new and emerging treatments, and walks us through the management of severe surface disease in settings like graft-versus-host disease.

ERICK BOTHUN: Dr. Joanne Shen is a cornea and anterior segment specialist at the Mayo Clinic in Scottsdale, Arizona, where she also serves as department chair. We're going to be speaking about surface disease today, and she has meaningful leadership roles in that field.

She is the Director of the Dry Eye Clinic at the Mayo Clinic in Arizona. She's active nationally with the American Academy of Ophthalmology, Cornea and Anterior Segment Ophthalmic Technology Assessment subcommittee, the International Ocular Graft Versus Host Consensus group, and the Tear Film and Ocular Surface Society. Welcome, Dr. Shen.

JOANNE SHEN: Thank you. It's such an honor to be here with you today.

ANDREA TOOLEY: We are so happy to have you here today. You are a cornea anterior segment guru. Take us through how you've developed a niche in dry eye patients, anterior segment patients. How have you developed this specialty practice?

JOANNE SHEN: Certainly, when I came to Arizona, I knew I was going to the land of dry eye, but I didn't realize what was going to happen until I showed up. And so when you're at the Mayo Clinic and you're in the desert, then that means you're going to get all these seventh-opinion dry eyes.

So it became my niche, even though I probably wasn't really looking for that in particular. And my mentor is Bill Bourne, and still occasionally talk to him from time to time. But about 10 years ago, started working with him on trying to figure out what my niche was. And really, he said, we don't know stuff about GVHD. Our patients are living longer after transplant, so maybe you should start looking at your population and share what you know.

And we were getting lots of dry eye patients that didn't have any solutions. And there was a lot of really interesting things happening about that time in 2012. And fortunate to have some technology that we could acquire. So it sort of came to me because of a necessity. Either I got good at it, or I was going to have to find some other occupation. [LAUGHS]

ERICK BOTHUN: That's interesting that you say that, it came to me out of necessity. I think most ophthalmologists feel that any patient with dry eye comes to them out of necessity, and we'd really rather not see them. So it's phenomenal that you've appreciated that need and risen to the occasion and advanced the care and are now a thought leader in this field.

So it's exciting to share this time with you and just talk through lessons and tips that you have over basic management and then things that are new and cutting edge to help these complex patients. Share with us just a little bit-- because so many people do see patients with run-of-the-mill dryness, Meibomian gland dysfunction, chronic irritation with age, or-- and we'll talk about some of the more advanced diseases here in a minute that are associated with dryness.

But share some thoughts over-- when a patient comes in your exam room with dry eye symptomatology, what are the common questions you make sure you ask, and what are the things in the exam you make sure you do that you'd encourage the comprehensive ophthalmologists listening to do, too?

JOANNE SHEN: I think it's important to remember that I'm not seeing the typical dry eye patient. Rarely am I getting a-- oh, I've had it for three months. Usually, they've been battling it for a while. So maybe what I do is not going to be typical for the comprehensive person seen.

But if you've been seeing somebody for a while and not gotten anywhere, generally, I ask them-- I really delve into what their lifestyle is and what their occupation is, and when is the dryness the worst because if I find out that they have been bicycling without glasses in Arizona or any protective wear and they are having problems, I definitely need to address that. Or if they are waking up in the morning and their eyes feel the worst in the day, that's a question that maybe has not been asked before, but I think is this typical ceiling fan question.

We ask about ceiling fans. But we don't say, well-- so if they're not using a ceiling fan, but yet, they're waking up in the morning and their eyes feel terrible or pretty bad, then I am concerned. So I definitely feel like focusing on that aspect of the restorative nighttime-- that's the only time eyes get to rest and regenerate is nighttime.

So I think finding a little bit more about what-- are they a computer programmer, on the computer 12 hours a day? Are they in the right refractive prescription? Are they in their computer glasses? Those are basic questions that sometimes are missed by-- especially, in our late 40s-- a patient comes in late 40s and not wearing glasses at the computer. So they don't-- these are not rocket science questions.

In addition, every cornea external disease specialist would say a thorough exam. And it's hard when you're given five minutes to do your whole slit lamp exam. Are you going to take the time to flip the lids? Are you going to use some ingrain stain, which is very messy? Are you going to look for foreign bodies or just examine the ocular surface, instead of just diving right in to look at the cataract?

ANDREA TOOLEY: Yeah, I think those are all such good points. And I love that you're kind of coming back to the history as being so important because these patients are really unique. And at least I've found, in my oculoplastics practice, when I'm thinking about the lids and thinking about excess tearing-- that's what I see the most, and a lot of times, it's dryness-- It's not a one size fits all. They're all super different, and there's so many different causes.

Dr. Shen, one thing that I always feel like I'm behind the curve on is some of the workup and testing modalities we have for dry eye. Talk to me about-- do you do Schirmer testing or tear-film osmolarity or inflammatory markers in the tear film, like MMP type thing? I'm always hearing about this, but I haven't incorporated any of that in my practice. Do you recommend that? Like, what's your basic tearing or dry eye workup?

JOANNE SHEN: I think it's important to try to figure out-- for my practice, they're coming from far away. I try to get as much done. But that is virtually impossible in a comprehensive practice.

Generally, I feel like the tools that we have-- like, tear osmolarity really just sort of confirms what we already sort of know. If it's evaporative tearing, then they have reflux tearing as a response, then their tear osmolarity is going to be low. I do it to confirm what I've already suspected. Very rarely am I surprised.

An MMP-9 I think is helpful if you're trying to decide about doing oral doxycycline or topical azithromycin. The patient has a lot of maybe telangiectasias more of the ocular rosacea look. And you're trying to decide if you're going to add that to the plan, because we know that there are side effects in cost and difficulty getting topical azithromycin. There was a supply chain issue for a while. And trying to add that and explain to the patient why you're doing that-- it helps to have some data to show them.

And then I like to repeat it three months after I've done some treatment to see if we've had some at least qualitative differences because we can see-- sometimes MMP-9 testing is very, very positive. It just lights up. And sometimes it's very faint. And we do write that down because sometimes-- if we can get it to be a little more faint, sometimes that correlates with symptoms for the patient.

ANDREA TOOLEY: That's actually really helpful. Does MMP also-- sorry if these are really basic questions-- and a lot of this is just because I don't have the knowledge base. Is MMP also indicative of inflammatory disease? And does that help you decide if you want to use an anti-inflammatory like Restasis or Xiidra or any of these other newer agents? Or are there different testing that are more specific for those treatments?

JOANNE SHEN: No, and I don't think there's any data that says that, this is what you do, and this is what has been proven. So I want to just preface that-- whether or not a person decides to use MMP-9 in that way-- I do think that, yes, the underlying inflammatory etiology for these patients is something you want to look for for treatment modalities such as these topical lifitegrast and cyclosporine and whether or not you decide to incorporate.

ERICK BOTHUN: Talk to us a little bit about-- I mean, I think most of us are used to managing dry eye to a certain level of lubrication and lid scrubs and warm compresses or whatever people might have from their residency and their previous practice training. Share with us what your-- beyond the norm, what's your algorithm of, I'm going to try this next, as you go up the ladder for a dry eye patient that's already failed all that stuff and do they come in with their bag of all their lubricants, and they just want the next thing up the chain?

And I know there are some these newer treatments that are becoming available. But what's your-- besides education and looking at environmental things as you've talked about and heard their story-- but what do you pull out of your tool trick first, second and third? And what are your thoughts and why that way?

ANDREA TOOLEY: Yeah, tell us all your secrets. [LAUGHS]

JOANNE SHEN: I don't have any tricks. And honestly, if they pull in the whole bag, I'm like, OK, maybe we should just do a medication holiday. Let me just see what natural looks like. Obviously, at my stage, if I'm seeing them after months of what things have been going on, or years, sometimes the treatments that they've piled on have actually started to cause some toxicity to the ocular surface. And I can't figure out, are they just washing away tears?

We used to, in training say, OK, if they're not good, preservative-free tears every hour. And then if they're really not good, then preservative-free tears every 30 minutes. And then you just can escalate. And over the years-- I've been at Mayo in Arizona now for about 15 years. I really have just backed off on that because I feel like they're almost washing away their own natural tears. And we all know what's in those bottles is nothing biologic that we would naturally have occurring.

So unfortunately, I don't have-- if I did, I probably could have a robot do the dry eye clinic because then they could just give out the instructions. If a patient comes to me and he's in a wheelchair and he's with his wife and I can tell he's not going to be getting up to the shower very often-- someone like that-- you have to make it easy.

So, I may just say, you know with some OCuSOFT lid swipes or some things of that variety where it's commercially easy. You don't have to get a patient in the shower. It's kind of messy trying to baby shampoo in a wheelchair.

So realistic based on the patient. Most patients come to me-- their eyelids are already very clean, sometimes super clean. And some of these hypochlorous acid wipes are nice-- and sprays are nice to cut down on the dander, if patients can implement. So that's a nice added tool to our toolbox now.

ANDREA TOOLEY: I love the hypochlorous acid sprays. I tell everybody to use-- Avenova is my favorite thing ever. I think it's so great. I just have to add a little tidbit. It's, like, my new favorite thing.

JOANNE SHEN: Yeah. And I really like that I rarely see people react to it.

ANDREA TOOLEY: Yeah.

JOANNE SHEN: And I've looked at a lot of very allergenic patients, and the eyelid skin is very thin. So you have to be really careful not to overdo it. And people sometimes take scrubbing to the nth degree. Well, if a little is good, let me just go crazy. And then they start irritating the protective cuticle of the skin or whatever, that, Dr. Tooley, you know better. But honestly, it cannot take that much cleaning. So you got to be careful you're not scrubbing away vital epithelium.

ERICK BOTHUN: Talking about agents that you might choose, for Meibomian gland dysfunction that's meaningful, that you're going to use an oral agent, and doxycycline-- or in my-- I have a pediatric practice that I'll use clarithromycin. One of the things that I've found or seen variation on-- of how long people will treat to supplement or kind of reboot the surface health. How long to treat with some of those?

Some people give a course for two weeks, and other people do it for two months and taper. Thoughts on that, and when you choose a longer agent or shorter agent from a topical-- or from an oral antibiotic perspective?

JOANNE SHEN: When you're talking about shorter agent, what were you referring to?

ERICK BOTHUN: Well, shorter duration. So I just-- prescribing antibiotics for two months is something that-- a lot of ophthalmologists may hesitate to prescribe longer acting. And yet, at least in my population, when a child comes in with blepharitis of meaningful degree and surface disease and corneal changes, I'm on the understanding that I'll be tapering an oral medicine over many, many weeks, and oftentimes, it goes beyond two months.

But how common is that or uncommon and prescribing longer courses? And how would you encourage a comprehensive ophthalmologist that's going to prescribe doxy or clarithromycin? What's a typical regimen to try?

JOANNE SHEN: If a patient comes in and they're about average build, my standard dose is, like, 100 milligrams of doxycycline, and depending on which-- hyclate I liked, but monohydrate formula sometimes all that's available to a patient. I think I try either.

It really is a tolerability. I have some patients who could probably take it forever. They're the minority. Many patients are intolerant. They get a UTI or a yeast infection. They don't feel well. They have problems digesting. They love dairy, and they can't have it with this antibiotic. They're scared of side effects. They're scared of long-term antibiotics. So the myriad of excuses comes.

I just say let's try it for a month. And if we have any sort of indicator that things just feel calmer and less irritated, gritty, dry-- and my exam is consistent with that-- then I will have them finish a three-month. And then depending on how they did, if there was any tolerability issues, I generally will give them a three-month break. I feel like it stays in our system for a while, and then just reassess, do I need to pulse them later?

And otherwise, if they fail to taper off completely, they may be a candidate for a smaller dose, a smaller dose, or the same dose every other day. So we just play around with it depending on how the patient is doing.

ANDREA TOOLEY: I like that a lot. That's great advice and very customizable. I don't see this as much with patients that I put on doxycycline. But I don't know if you guys have ever taken doxycycline. I took it as a malaria prophylaxis a couple of years ago and had the most intense sun sensitivity. It was unbelievable.

And I don't see this as much with our patients. I think it's because it's a slightly lower dose. But I was on a beach. And I had to wrap my body-- my hands, especially-- my hands are so sensitive-- in cold washcloths to go outside because I felt like my skin was on fire. It was crazy.

And so I really commiserate with patients. I don't know if I would want to be on it long-term, but I think that's less of a side effect. But I just always think of that from when I had to take it. Everything changes when you're in the patient seat, you know?

One thing, Dr. Shen, I want to ask you about is IPL, laser options, LipiFlow-- these new tech options for dry eye that are super popular. I think some people were skeptical of things like LipiFlow. I've actually seen great data from IPL, and you are one of the first to publish on this. And so tell us about using IPL and other high-tech options for ocular rosacea, dry eye, lid disease, those kinds of things.

JOANNE SHEN: It's been exciting, just the developments and the attention towards dry eye. And intense pulsed light-- I was skeptical. And it really was out of a necessity-- born out of necessity. Patients had exhausted everything else. And had we given up on Meibomian glands, or were we going to try this?

And I have loyal patients who want it like it, come back for it. And it's not the most comfortable procedure. So I've done some limited pilot studies where I just did expression-only versus IPL with expression, and patients still like their IPL. And of course, it's very hard to mask because it is a very unique experience. You can't really fake it because they can actually feel the intense light hitting their skin.

So I think-- unfortunately, many of the studies in the literature are industry-funded because not a lot of people are spending the time doing IPL research. And the people who are doing it are sometimes in private practice, and they don't have time to publish their results on what their patients are experiencing.

I generally like to use IPL if patients are good responders to doxycycline but just become very intolerant. They're too sun-sensitive. They can't handle the GI side effects. Some other issue. And it has been nice. If they respond well to doxycycline and just can't tolerate it, they generally-- in my experience, of course-- have responded. We have not done a prospective study where we've sort of done a head-to-head doxycycline versus IPL.

LipiFlow and Eyelux and those other just massaging-only treatments aren't covered by insurance. I think they're very safe and can only help. There's very low risk, unlike IPL where if you don't do it properly and you accidentally subject IPL to the iris, internal eye, you can actually cause severe uveitis and damage and vision loss. So we want to avoid that.

But these other Meibomian gland, automated expression, or sort of semi-automated manual expressions I think are very helpful in just decompressing these glands that get backed up to keep them moving.

ERICK BOTHUN: So in a normal practice, a patient comes in and goes through the treatment algorithms or care and you find you're ready for that. Are those procedures being formed same day, or are they rescheduled? And at what frequency is a typical patient having those repeated?

For someone that-- my dry eye patients or my adult strabismus patients that really come in thinking they're double vision is because of strabismus-- and I send them back to say, we need more dry eye care. So just-- not being someone that manages those things, share with us how your practice manages those procedures and in what frequency.

JOANNE SHEN: Many of my patients are waiting three months to get in, so I try to have time to treat them at that first visit. If they're a candidate for LipiFlow or-- and that's what I have for thermal pulsation or intense pulse light-- then I actually will do it at that visit.

And then for intense pulse light, it's actually a series of monthly treatments. And it's a series of four, spread every four to six weeks. And generally, if they improve, then we'll finish the full-- if they improve 100%, then we're done after the first treatment. But that's rare.

Most of the time, patients will need three to four treatments to get to a plateaued effect. If they don't respond by the third treatment, we move on to other modalities because I don't know if we're going to achieve anything. And obviously, they have to have viable Meibomian glands.

So we do-- before I do any of these treatments, I'm doing a meibography, which is just flipping the lids and using infrared photography, which is now pretty widely available on multiple platforms, to look at the Meibomian glands and make sure there is something to save before we go on these expensive treatment and time-consuming--

For LipiFlow. I think it depends on their patients. So it can be anywhere from probably six to 12 months before we would do a repeat, assuming that they've got an effect after eight weeks. Usually, they'll be better after eight weeks of treatment, at eight weeks after their LipiFlow treatment.

ANDREA TOOLEY: That's really helpful to know. I think the other thing that comprehensivists, who are seeing these patients, might be deciding is when to invest in these platforms. LipiFlow, getting an intense pulsed light laser. These are really expensive investments in a practice. You're chair of the Department of Ophthalmology. So you understand the overhead and these investments.

Do you think with technology and where this is going and how we're treating these patients, that these are wise investments for practices? And how might a comprehensivist make that decision of when to incorporate some of these platforms into their practice?

JOANNE SHEN: That's a really good question. Some practices have made it so that the provider comes in and puts the actuators in for the LipiFlow and has a technician monitor and then remove them and then have the patient sit for a cornea check just to make sure the cornea is not abraded.

But it is-- I think you want to offer these services because you feel like it's going to make a difference in helping-- you're addressing what your patients are asking for. You're not just doing them to make money. I'm sure there's other ways to-- you could sell glasses and make money. You don't necessarily have to embrace this.

But if you do decide to do it, then you sort of own all of it. What are you going to do with the ones that don't respond, the ones that are angry that they spent hundreds to thousands of dollars on LipiFlow? You really have to have an idea of who are you going to partner with for these ones that don't respond and aren't getting better, looking for other ocular surface disease that may be also impacting the patients.

ERICK BOTHUN: On that note, I'd like to transition a little bit because part of your expertise has grown and matured in light of other ocular disease affecting your treatments. Share with us a little bit about graft versus host disease or other surface conditions that are rich in your practice that we could learn from.

And Mayo certainly has a unique tertiary, quaternary referral location with transplants being done at high levels. And so you see patients with complex graft-versus-host situations. And I just know that's an expertise of yours. So share with us how that practice is the same or different in managing their surface disease.

JOANNE SHEN: Back in training-- I alluded to it before. Back in probably 2000, many patients who got stem cell transplants for leukemia and lymphoma basically died if they got ocular GVHD. The mortality was quite high. We didn't have antifungals that were effective that we do now.

And so by the time I came out of fellowship and was in practice at Mayo, we started seeing people, fortunately, survive. They survived their transplant. They survived their cancer. And now their transplants were working really well, and their eyes were feeling terrible, and their quality of life was just miserable.

And I don't think, in training, we really had good experience because these patients were so sick. So we didn't-- they wouldn't live very many months. And so you never had to get good at this.

And I think what I've come to understand is-- and what we didn't back then-- is that I sort of treat these patients like once they're through their initial GVHD attack is there like Stevens Johnson's patients-- not as severe but quite scarred, quite aqueous-deficient. And our group showed that their, also, Meibomian glands were atrophied, and really much of the ocular surface was affected.

And I would get patients-- I was told, you just do steroids on them. You immune suppress them if they're symptomatic. It's an immune attack. But really, what I've come to realize is that they're just super dry. And so now, just like I would with a Sjogren's patient or a Stevens Johnson's patients, who's through the initial phase and now is three months out, is really working on rebuilding the ocular surface with-- the tear film was just missing.

And I got desperate to a point. I even tried running IPL on the series of patients, and ran a prospective trial where I actually was doing IPL on patients. And the one thing that-- IPL does not work for a GVHD. I just want make that quite clear.

But it was interesting because I saw these patients intensively for the six-month study. And I soon realized there was one eye that was worse than the other. And I really-- after hearing them complain about how bad their eyes were, despite this miracle IPL that had shown up, and they were so hoping that it would help-- I realized that they really just needed punctal occlusion.

So it's not very glamorous, but I am very aggressive about punctal occlusion for these patients. And I have seen a lot of patients do much better just with punctal occlusion. So if they come to me and they've been treated with a lot of topical steroids, generally, I'll try to say, let's just work on your tear film and tone back the steroids, which probably aren't helping with wound healing.

ANDREA TOOLEY: Those are all really good tips, and super challenging patients to treat. Is there a point where you have to flip to surgical options or anything different? I'm always thinking of this from an oculoplastics standpoint, or when do you need a tarsorrhaphy, or when do you just need to occlude these patients completely to let the surface heal versus just doing medical management?

JOANNE SHEN: I definitely am very aggressive with medical management. But I do-- if you call punctal cautery surgical, I implement that pretty quickly. I'll try plugs first. I use a three-month dissolvable because I don't want any silicone flange on the ocular surface, rubbing on the already irritated surface.

We do autologous serum tears. Moisture chambers are very important to protect the ocular surface. Unfortunately, they're not covered by insurance. And then without scleral lenses, I'm not sure how good of a cornea specialist I would be. I do a lot of combined scleral lenses and moisture chambers just to protect the ocular surface from the Arizona desert.

And my goal is to be aggressive so they don't show up with a neurotrophic ulcer because then that leads to a transplant. And once they've had a transplant, they don't have great feeling. They don't make good tears. And then that's a disaster ready to happen. And I-- knock on wood-- like to avoid doing tarsorrhaphy on them.

So if I can get them into a scleral lens, get their serum tears installed so they can have some tears to substitute what they don't have, I find that these patients are able to go back to work and have productive lives.

ANDREA TOOLEY: Yeah, we're so lucky, at Mayo, that we have the ability to get scleral lenses for our patients. I use them a lot, too, and I really love scleral lenses. They're such a good option for patients. I actually don't know what the landscape of scleral lens therapy looks like in private practice. How easy is it for comprehensivists to get those-- get them made, get them fitted for their patients?

JOANNE SHEN: I think 10 years ago, it was tough. Now we have-- I think the optometry community has definitely learned, in the last 10 years. And now the technology, between Pentacam imaging and working with these centers that make the scleral lenses-- they just have gotten so good at troubleshooting fits for--

And generally, these patients are fairly normal in their fit. You're not dealing with a very abnormal shaped cornea. The conjunctiva may be a little bit scarred, but most of what you're using on the scleral lens is-- that's sitting on the sclera is normal. So the community now has a lot more support that I think that most people know who's the regional specialist in their area.

ANDREA TOOLEY: Yeah that's so great. That's such a wonderful option. What do you think about Prokera or those other types of options? I don't use those in my practice.

JOANNE SHEN: I had difficulty having patients tolerate Prokera. I probably don't utilize amniotic membrane a whole lot because I just haven't had to. Some people like to use it just as early first-line. But for me it's like, OK, which eye's worse? I'm going to do one eye at a time. I can't do both. So generally, I like some of these other modalities first.

If they look like they're about to do an ulcer on me, then I will employ that. But I generally will use some of these bandage, soft contact lens and enabled disks that they have available that are easier to use, easier to store, and tolerant for the patients.

ERICK BOTHUN: Well, this has been wonderfully enlightening and sharing. I always like these podcasts that are very tangible. Like, whether it's a simple punctal plug discussion versus some of these new-- LipiFlow and what's new on the market and how to incorporate it in practices. Thank you for sharing, virtually, your expertise with us on a common condition that gets really tough. And we celebrate the expertise you have here at Mayo and the ability to share your voice on our podcast.

ANDREA TOOLEY: Agreed. Thank you so much. This was great. You can find all episodes of the Mayo Clinic Ophthalmology Podcast on our website.

ERICK BOTHUN: Thank you for listening, and we definitely look forward to sharing more.

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