Unraveling a Ball of Yarn

Laura M. Periman, MD, joins Gary N. Wörtz, MD, to discuss management approaches for dry eye and ocular surface disease. Dr. Periman says that treating dry eye is akin to unraveling a ball of yarn—treating symptoms while encountering a few "knots" along the way. She also shares details of her passion project, DryEyeMaster—an educational resource dedicated to providing treatment pearls, research, and other tools to help in the fight against dry eye.

Gary Wörtz, MD: Open, outspoken. It’s Ophthalmology off the Grid. An honest look at controversial topics in the field. I’m Gary Wörtz.

Dry eye is one of the most complex challenges today, for practitioners and patients alike. Many patients feel frustrated by a lack of relief, and their practitioners, by an inability to pinpoint the precise problem and solution. Fortunately, there are eye care providers who have dedicated so much of their focus to improving our understanding and treatment of ocular surface disease.

Today’s guest is one of the most dedicated warriors in the battle on dry eye disease. That’s right—it’s Dr. Laura Periman. In this episode, we talk about her passion project, DryEyeMaster, and how she likens treating dry eye to unraveling a ball of yarn. She also shares many invaluable tactics for effectively addressing the dry eye patient, both physically and psychologically. Here’s Laura.

Speaker 2: Ophthalmology off the Grid is an independent podcast supported with advertising by Alcon.

Gary: All right here we go. We're going to get started now. Welcome to another episode of Ophthalmology off the Grid. This is Dr. Gary Wörtz. I'm so excited to have Dr. Laura Periman with me today.

Laura has been a friend for years actually, since we first met in Miami at one of the ARC Conferences that Bill Trattler and others put on. If that's not on your radar, that's a great meeting, by the way. It's usually in Miami, usually in a really nice venue. That's how I got to meet Laura and some other folks. Since that time, Laura has been a dear friend and really a trusted resource for me whenever I get into the weeds with dry eye. Whenever I'm beyond my depth, I know that Laura will have the answer, typically. Usually she has a really cool way of explaining it that sticks in my brain.

As I was thinking about guests for Off the Grid, I knew at some point, I would have to con Laura into coming on the program. With that preamble, Laura, thank you so much for taking some time out of your evening tonight to share with us what's going on in your world and especially talking to us about your new program, DryEyeMaster.

Laura Periman, MD: Gary, thank you so much, for the invitation to be here. I am humbly delighted and thrilled. I feel the same way about you, brother. You're amazing.

Gary: Well, that's yet to be validated. Thank you anyways for that. Laura, I remember the lecture that you gave at ARC. This is like 3 or 4 years ago, I think maybe 3 years ago. I was so impressed with the basic science savvy that you presented at that conference about dry eye. But you did it in such a fun way that I remember a lot of Hall & Oates references and a lot of really cool rock-star analogies with dry eye. Anyways, we can talk about that more a little bit later.

I know that dry eye is really your passion. It's a passion that we share. I have gone away a little bit from that in my practice. I was very deeply involved with dry eye for a number of years. I understand where you're coming from. Give us a little bit of background on why you decided to start this program, DryEyeMaster.

Laura: Thank you for that. DryEyeMaster is my nerd outlet, if you will. It's where I'm trying to collect things that I've done over time, whether it's explaining things to patients about their cosmetics use, whether it's explaining high-level immunobiology, which I think is wicked cool, or a talk that I've done, or an article I've written. I just wanted a place where it's all together. It's purely for educational purposes. I don't have any financial interest in it. I just want a place where people can go and nerd out, or have a little fun, or if we're lucky, both.

Gary: Right. This is essentially a place where the resources that you have created, have place to live online. Because you're such a gracious person, it's really available for anyone to look at and utilize. Is that pretty fair?

Laura: That's the goal. That's the direction. It's very homespun. I'm just doing it myself, so don't judge too harshly. It's pretty basic.

Gary: No, not at all.

Laura: I have big goals for the thing. I would love for it to have educational videos, and a patient portal, and maybe even a blog section. Maybe if I'm lucky, I can have guests on there, like you. That would be cool.

Gary: You know, big things come from small beginnings. The website looks great. Let me just give you a plug real quick, dryeyemaster.com, for anyone who is looking for some great resources on dry eye from Laura. You can go there and check that out. It's very well done. It's very nicely organized. I think we can follow you on Twitter @dryeyemaster, is that correct?

Laura: That's correct.

Gary: People can tweet you questions. They can ask you stuff, and you're happy to respond to them.

Laura: I am happy, yes.

Gary: Laura, I want to get into the weeds a little bit on your practice because I want to make the most of this time that we have together. I know that because you have this passion and specialize in dry eye, I'm sure you are somewhat of a magnet for the problem patients, where people in your region ... I don't mean that as a negative.

Laura: It's all good. It's all good.

Gary: When someone specializes in something like dry eye, typically the other practitioners in our region, once they have become frustrated with someone, or can no longer feel like they're helping them, they all funnel to the person who is willing to be the backstop. I imagine, in the Seattle area, you are that backstop. Tell us a little bit about your practice and how you started specializing in dry eye.

Laura: Well, like most things in clinical practice, it grows somewhat organically. I found myself fresh out of maternity leave, working part-time, across the street from Microsoft. I saw all these young people with dry eye. I'm thinking, well gosh, why would that be? I'm used to seeing a post-menopausal female. That was my push back in the day, to dig into this a little bit further. As I dug into it, and read more, and started understanding more about the pathophysiology, I'm like, "I get this." My background is in molecular biology. I did research on Enbrel at Immunex before it went through FDA trials.

Gary: Really?

Laura: Yeah. I love cytokines and immunobiology and molecular biology. I'm a dork, Gary. I try to be presentable most of the time. I really, really enjoy what's going on in a pathophysiologic basis. I use that deep knowledge of 25-something years to support what I do clinically in looking at novel therapies and looking at ways of inspiring hope for that patient who might be at the end of their rope and has truly tried everything. In my mind, all that work, it's almost like this was the way it was supposed to be. I'm just following with it. I'm enjoying the heck out of my practice. I love my work so much. It's incredibly satisfying to me.

Gary: I have to stop you. There may be a past life here that I'm not familiar with. I want to know more about this research you did on Enbrel. Was this while you were in undergrad, or was this a job after college? Is this in the midst of med school?

Laura: You're spot on. I won a scholarship to study at the Primate Research Center in college. That's when I first started learning molecular biology. I'm like, "Wow, this is so interesting." I met my future husband, with 6 weeks to go, before we graduated from college. He was moving back to Seattle from Salem, Oregon, and headed to law school. I finished college early, and came up, and got a job doing molecular biology at Immunex, and worked there while he finished up law school. Then I got to go back to school.

Gary: You had a 3- or 4-year stint doing real research in molecular biology.

Laura: Yeah, yeah. I still use that knowledge and those tools today.

Gary: This is making so much more sense to me, Laura. I always wondered why you knew so much about molecular biology and cytokines when I had long forgotten all of that stuff. Here you are starting it off like it's second nature to you. OK, we can pick back up. I just needed to get into the weeds a little bit on this back story. I don't meet too many ophthalmologists who worked for 4 years doing research on Enbrel. Thank you for unpacking that.

Let's dive back into the average patient that you see that comes in, maybe they have tried a little bit of everything. Obviously, everyone tries tears. Maybe they've had plugs. Maybe they've tried Restasis. Maybe they've done warm compresses. The list goes on and on and on. When you see a patient, and they're frustrated, they feel like they've done everything, their ophthalmologist or optometrist is frustrated because they feel like they've done everything. How do you unpack that and get a patient on the right track?

Laura: That is a fantastic question. In my mind, my first priority to treat the disease, you have to put the mind at ease. You have to connect with that patient and instill in them a trust, "I've got you. You don't scare me. I'm not going to go anywhere. I'm going to keep trying until we get this thing addressed." Their anxiety level drops 20 decibels.

Gary: Right.

Laura: Sometimes I'll even move my chair and sit along beside them and talk to them about it. Just that connection of, I'm on your team, we can do this, is really the first thing that you need to address, where you're talking about that frustrated patient who's seen multiple other doctors. Just that human connection ...

Gary: Building up therapeutic alliance with the patient is step one, it sounds like.

Laura: Truly, I believe that very much. Form that connection, and just put the mind at ease to treat the disease. It's very important, words of comfort, right?

Gary: Yes.

Laura: We do that first. Then I unpack along the lines of the bio psychosocial modal, how much of this is molecular, and what can I do about part of the story. How much of this is impacting the entire nervous system, not only the sensation that someone's experiencing, but how the central nervous system is processing it? How is it affecting mood? How is it affecting coping mechanisms? Then, finally, there's the social part, productivity, connection with family. Some dry eye patients just need to close their eyes. They're not ready for bed. They miss out on family time. They miss out on all kinds of things because of their eyes. I'm drawn to that type of misery. I want so badly to help.

Gary: Right. Are there any particular questions that you have developed in your repertoire that really seem to get you answers that are more pertinent? What kind of questions do you typically ask to get to the meat of what you're trying to find?

Laura: Right. To get to the meat of what I'm trying to find, I like to rely on visuals. There's a wonderful vicious circle map in Christophe Baudouin's 2016 British Journal of Ophthalmology paper. I saw that, and it just ... my hair flew back. I was just like, "Whoa, this is what I've been trying to do all this time, and it's on one page. It's on an image. This is amazing."

I have it laminated in each room. It shows the risk factors on the outer wheel. It could be anything from autoimmune disease, to prior surgery, to medications. It's this big wheel of risk factors on the outside. All the arrows are pointing to the inside. That's where inflammation is driving OSD and MGD, almost everybody's a mixed mechanism.

Gary: Right.

Laura: When I show that to the patient, we're coming at this problem from one, two, three, four, five, six, seven different risk factors. All of it's driving the stuff in the middle. That's the work I got to do. They get it. They stop being so frustrated and antagonistic, and, "Well, that didn't work for me." There's some connection there when they see the big picture like that.

Gary: They see the battle that's being waged.

Laura: They see the battle, and they're like, "Oh OK, I'm going to fight these with you." It's a wonderful way of creating that team atmosphere between you and your patient. It doesn't always work. Obviously, there's some patients that are harder to connect with. That's my game plan. I find it time efficient and pretty effective. Then we unpack the risk factors that has been overlooked in the past. For example, the cosmetic stories, some you do that Vampires on the Vanity talk, which is just a quick distillation of a really interesting body of work, six articles I've cowritten with Leslie O'Dell and Amy Sullivan.

Gary: Right.

Laura: We've had an amazing time just unpacking this, just everyday chemical exposure aspect of dry eye disease. It's hugely underappreciated. We're having a lot of fun with that. We've based it as much on peer-reviewed literature on PubMed as we possibly can. It's surprising what you can find, if you're able to piece the story together. I guess, at the end of the day, that's how my brain works best. I can take that white paper, or microbiology, or whatever it is, and I see the clinical implications of it, and I can connect the dots and connect the story. That's what my brain does best.

Gary: Well, that's very unique. You have people commonly ... Steve Jobs is like this, or I don't know if you listen to Walter Isaacson, or read any of his stuff. He talks about the intersection of science and humanities, is really where some of the best work is done, by some of the most creative geniuses of our time, like Steve Jobs, like, for example, Benjamin Franklin. When you have someone who understands the human side of things, and the humanities, and you have someone who understands the science of it, and can be that bridge, beautiful things happen. I see that in what you do, and it is very, very special.

Laura: That's so kind, thank you.

Gary: Tell me a little bit. Do you use standard questionnaires? I know the SPEED questionnaire is something that a lot of folks use and love. What standardized questionnaires do you like?

Laura: I like having a standardized questionnaire because ... I use the SPEED, and the OSDI. The reasons why I always use them is, patients need a number to track over time. You forget how miserable you used to feel. If mother nature did not put a “forget pain” mechanism in your brain, there's no way a woman would ever give birth to more than one child. This is like, it's a protective mechanism.

You need that data to track progress over time. But, I find them to be just a quick thumbnail sketch of the situation. They're obviously subjective and prone to environmental changes. We saw a very interesting uptick in our SPEED scores in our clinical data during that massive forest fire season.

Gary: Interesting.

Laura: We had this period of forest fires out west, where in September, where the air quality was worse than Beijing. I remember flying to MillennialEYE in Nashville, where I got to see you and we played guitar together. You have a great singing voice, by the way. Oh man, I wish I had your skill.

Gary: Not really …

Laura: You do, it's beautiful. I wish I had your skill.

Gary: Thank you.

Laura: I was flying out to that meeting, and, oh my gosh, the entire West was on fire. It was cloudy. As soon as you crossed the river there, heading to Nashville, it's like, "Oh, the air is clear." It was very interesting. We saw an uptick in our MMP-9 testing and in our SPEED scores in forest fire season.

Gary: That is really interesting that you could track it and it would track that closely. That really validates the questionnaire in my mind.

Laura: Yeah, yeah. It's an interesting piece of the puzzle. It helps to just put things in perspective, not put blame where it's due, but just to put the normal ebbs and flows of chronic dry eye disease into perspective.

Gary: Got you. All right, I'm going to put you on the spot a little bit.

Laura: Oh, here we go.

Gary: Yeah. We always got to keep it real on Off the Grid here. In the last 5 years, let's say, maybe give or take, how would you rank the advancements or the innovations in dry eye? I'll give you some choices. Maybe you can say different situations, maybe these work differently. We'll say, generally, point-of-care testing would be one category. We'll say LipiFlow, and/or LipiScan, we can lump that together as an innovation. Obviously, we've had cyclosporine for a long time, so we can keep Restasis in the mix there, and then Lifitegrast. How would you rank those in terms of things you've seen? We can also put IPL in there. I know that you do a lot of IPL. As you're looking at maybe the newer generation of diagnostics and therapeutics, what are your go-to mechanisms and why?

Laura: Wow, that's a tough question. Really what I want to say is, we're just getting started. I envision a day where we will have this little point-of-care test where you can run a complete cytokine analysis profile for each patient, maybe even some other early biomarkers, looking for cancer proteins. The future is bright, indeed.

There is going to be a time where we can customize our treatment for each patient. We have the development of all these amazing tools. We need all of them. We need the immuno-modulators. We need the mechanical approach to MGD. We need the phototherapeutic approach to MGD, and LipiFlow and IPL, respectively. We need all these tools; no single one of them is going to crack the nut.

I'm going to put them in a pot, all together, rather than ranking them. I'm not trying to hedge. I'm happy to answer the question. I feel like it's not productive to say one's better than the other because we need every single one of those tools, and it depends on the individual.

Gary: That's actually a fantastic answer. It almost defines dry eye disease as a category, where things are never really cut and dry. It's like you said, most patients have a multi-modal mechanism. At this point anyways, it's typically, one thing is not the magic bullet. It's usually a part of the situation.

Laura: Correct. At any given time in a person's disease state and recovery, I view this as unraveling a ball of yarn. You unravel some little bits, and then you discover another knot. Then you address that knot at that time. It's a very dynamic process, in my mind, that there is no silver bullet. It's a very cluster-based approach to decision making. Sometimes I'm a little envious of our retina colleagues—“see hole, fix hole.”

Gary: Right.

Laura: That's not quite what we have in dry eye disease. As long as you're comfortable with multiplex analysis, and thinking, and decision making, it can actually be incredibly rewarding and engaging.

Gary: I actually found that to be true. I'm the “see cataract, remove cataract, repeat.”

Laura: Gary, you cut yourself short. You're a very creative, intelligent guy.

Gary: Well, in terms of what I am most productive doing, it's, if lens, then no more lens. But regardless of that, for a long time, for about 3 years, I worked in a different scenario and got to work with my dear friend Paul Karpecki, who is a genius.

Laura: He is a genius.

Gary: As smart as he is, he's actually nicer than he is smart.

Laura: I would agree with that. He's a sweetheart.

Gary: That's hard to even say, because he's so smart. He's so nice.

Laura: That's because he's Canadian.

Gary: Anyways, I was forced into this situation where there were a lot of really high acuity dry eye patients coming from ... we were that funnel. They were coming from all over the region. It so happened that, many times, I was the guy to care for them. It was interesting because, prior to that, my strategy for dry eye was just taking out their cataract. That's not really true, but, in some regards, it's a little bit true. My strategy for dry eye though, is basically, I would try some tears. I might try some warm compresses. But really, it was trying to just get them out of the clinic and minimize, and downplay.

I felt intimidated by it. It was a frustrating thing for me to recognize that it was going to take a lot of time, and handholding, and thinking, to address the patient's concerns. I just didn't feel that good at it. I didn't feel like I had a real systematic approach to it. It just didn't feel good to take care of dry eye patients. I just never left the encounter feeling like I had really helped them or given them something that was tangible that they could, I don't know, feel like they got their money's worth for seeing me.

It was really something that I avoided at all costs. I found myself in this situation, in a clinic, that was not going to be an acceptable answer. I decided just to dig in and really figure out some strategies. I'll share what I did, and then feel free to say, "Well that was not right,” or "I've found that to be true," but maybe you do some other things.

What I found was, that patients like to be put on a path. They wanted to know that there were some things to expect along the path or along the journey. We had a plan for them. Let's take for example, a patient who has pretty clear evaporative tear loss, meibomian gland deficiency, meibomian gland disease. I actually had a printout that had basically three categories, mild, moderate, severe. I said, there are basically three steps we can take. We want to put you on this path. We're going to try stage-one treatment, and that was pretty simple. Stage-one treatment, I think, was putting them on a lipid-based tear, doing some omega-3s, and doing some warm compresses.

Laura: Perfect.

Gary: We would see them back in 6 weeks or so to see if there had been any improvement. We actually sold a mask at the time, pretty much at cost, no financial interest. Bruder makes a fantastic warm compress mask that you can sell very easily in your clinic. It really was something that I could hand the patient, and say, "This is how you do a warm compress. Please get this and put it in the microwave." I'd walk them through that. The handout was great because I made it, it went through everything.

They'd come back in 6 to 8 weeks. Then, if they weren't better, a lot of times they weren't better at that time, I would add usually doxycycline, and I would add some Lotemax ointment to apply. Then I would say, "All right, let's see you back in another 6 to 8 weeks. If you're not better, we'll do ..." We didn't have LipiFlow, but we did a version of meibomian gland expression and heating of the glands.

What I found was, the patient wasn't necessarily irate or frustrated, if at 6 weeks they were not magically cured, because I set the expectation, pretty early on, that we are going to go through different phases of treatment, depending on how they responded. We're going to increase our level of sophistication with each step. It seemed like, I don't know if it was just setting the expectation, or having a systematic approach, but I found that it really put them at ease from the beginning and allowed us to be very logical in the way we approached taking care of that segment of patients.

Have you found something similar with maybe different segments of your dry eye patients?

Laura: Wow, thanks for sharing your story. I think you are intuitively good at this. To cut yourself a little bit of slack, you probably were in that clinic at a time before we had our advanced tools. We only have so much for so long. Now we have a lot more tools to offer patients.

Gary: That's true.

Laura: I love the idea of your stepladder approach. I love the idea of setting a safety net in mind for your patient. I think that's critical in putting the mind at ease. That's a key part of just being a doctor. I commend you for that. I think that's spot-on, that, "I've got you" alignment with the patient. "I'm on your side. We're going to keep at this until we get somewhere." I think it's brilliant. Good job.

Taking that idea of mild, moderate, severe construct that you trained with, and given that a lot of our tools have come online since then, I've expanded that idea of ... what you offered was thermal therapy, steroidal therapy, and nutritional therapy, then mechanical therapy, right?

Gary: Right, basically.

Laura: There's an incredible paper, actually, in the Ocular Surface Journal 2017, April issue, Christophe Baudouin's on that group, the lead author is Gerd Geerling, brilliant description of the six interrelated pathophysiological mechanisms of MGD. I read that list. I'm like, OK, that's awesome. I get it, but who's going to remember that?

In my crazy brain, I'm like, let's reorganize this. Let's call it The BEISTO. Let's call it the BEISTO of MGD, and that's an acronym. It stands for the bacterial component, the enzymatic compromise, the inflammatory component, the stasis of the meibum, the altered melting temperature of the meibum, and then finally, the obstruction.

That's my current construct for my stepladder approach. It creates a nice way to organize all of the wonderful tools we have, whether it's from Avenova, and hypochlorous acid, to the omegas and the thoughtful use of those, the immuno-modulators and steroids, the stasis component, the thermal component, and, finally, the obstruction. I use that to organize my approach. It basically becomes comical and fun for the patient.

Gary: Basically, you're taking a patient ... sorry to interrupt. It sounds like you're basically taking a patient and checking each box until you crack the puzzle.

Laura: Until I'm fully addressing the BEISTO, yes. I make sure I've got something on every one of those six levels for addressing the full BEIST.

Gary: That's fantastic.

Laura: That's just a fun way to organize it. I agree with you with that stepwise approach, and always letting them know that there's other things we have. There's more. There's more. Hang in there, we'll get there.

Gary: Let's talk about that, the other things, and the future, and innovations. You are a very innovative physician. What innovations are you working with, or are you excited about, or hopeful for in the future?

Laura: I am really excited about three things at the moment. I get excited about a lot of things. If it has anything to do with Daryl Hall & John Oates, or dry eye, I get excited.

Gary: Yeah, Hall & Oates shout-out.

Laura: Oh man, fourth row. I just bought my ticket yesterday. I'm so happy. I think it's my eighth concert. But anyway. Back to dry eye, my other passion. Now I've forgotten your question. This is what happens in old age, Gary. I'm ADHD.

Gary: That's OK. You said you had three innovations that you were currently excited about.

Laura: Oh yes, that I'm all excited about. With IPL, we've been tracking our data. We're finishing up a manuscript to submit, tracking our data, showing this incredible, impressive reduction in MMP-9 burden, with each treatment. A significant number of our patients convert to fully negative. What seems to be working extremely well is you use the IPL therapy for a five-out-of-six-prong approach for addressing the BEISTO. Then, follow it up with a LipiFlow. That one-two punch is awesome. We're finding that the omegas and the immuno-modulators as baseline support, helps to keep them there.

Of course, home measures like the Bruder mask, all those things are helpful. It seems to limit the amount of secondary medications people require, or additional pharmacy, which is increasing in cost all the time, higher copayments, pharmacy deductibles, side effects, etc., callbacks to your clinic for prior authorizations. There's lots of reasons to minimize a patient's secondary medication burdens. We're excited about that. I'm excited about a new canalicular plug technology that I'm involved in, in a young company, just to help them develop the idea and hopefully do some clinical trials.

Lastly, I'm really interested in advanced point-of-care testing. I would love to see a point-of-care test that can really customize a patient's treatment and track their response to treatment in an objective way. I think that would help to remove the frustration factor for a lot of my colleagues and create more of a linear decision-making process for dry eye disease, which is, as we understand it today, is completely non-linear.

I think that's one of the frustrations I hear from my colleagues. They feel like it just gets in the way of other things that they love to do, such as cataract surgery. I totally get that. I think it'll help to establish that swagger that you said that you wanted. It's like, "Oh, this is dry eye. I got you. This doesn't scare me. I understand this." All of these things will help to make you confident and give you some swagger and enhance your satisfaction with treating the disease state.

Gary: That's awesome.

Laura: There's lots coming on board.

Gary: That's fantastic. Well, Laura, I really appreciate your approach. I appreciate your friendship and your mentorship and all you've taught me through the years of just meetings and conversations. We'd love to continue to follow this. As innovations come along, and if there are things that you find worthy of sharing to a wider audience, please let us know. We'd love to have you back.

Laura: You're so kind. I thank you so much for all of your friendship as well and your support, and, I guess, really just have incredible respect and admiration for your creativity, and your innovation, and your drive, and your collegiality in creating a forum like this. I love your segments. I listen to pretty much all of them.

Gary: Well, this is just mutual admiration society here. There we go.

Gary: Dry eye disease can be an intimidating topic to sink one’s teeth into. I think it’s safe to say Laura is doing us all a service in her efforts to improve our education and management. For anyone facing challenges in their own practice regarding ocular surface disease, there are plenty of resources available, including Laura and DryEyeMaster. We owe it to our patients to do our best to glean some of her knowledge, and I thank Laura for allowing us to pick brain.

Once again, this has been Ophthalmology off the Grid with Dr. Gary Wörtz. Next time, Dr. Jai Parekh fills us in on his experiences as an ophthalmologist and industry member and what he’s learned about the physician-industry relationship in the process. Catch you then.

Speaker 2: Ophthalmology off the Grid is an independent podcast supported with advertising by Alcon.