The Evolution of MGD: Candid Conversation with Caroline Blackie

This podcast presents a discussion with Dr. Caroline Blackie, Senior Medical Director for Johnson & Johnson Vision, where she shares her thoughts on where we’ve been and where we are going to effectively address meibomian gland dysfunction.

Caroline Blackie: Well, thank you, Walt. It’s great to be here today. And in particular, it’s wonderful to have an opportunity to connect with you.

Dr. Walt Whitley: It’s been a while since we’ve connected as you just mentioned. And we know that you have a strong background in ocular surface disease. Can you tell us a little bit about what your role is in particular when it comes to that in Johnson & Johnson Vision?

Caroline Blackie: Oh, sure, Walt, and thank you for the question. So currently my role has fairly broad scope in that I’m essentially overseeing evidence generation for both the vision care business, as well as for surgical vision. And of course that includes our oculus surface portfolio.

Dr. Walt Whitley: Awesome. Awesome. So what we’re going to do is we’re going to talk about several different aspects of dry eye and one that is very near and dear to your heart and mine as well is MGD with meibomian gland dysfunction. So can you comment on the evolution of the treatment for MGD?

Caroline Blackie: This is one of my favorite topics, the evolution of the treatment for MGD. If we look back at the medical literature from going back to say the 1800s, there’s been an awareness and understanding that if you can evacuate stagnated contents from the glands, that those glands then have the opportunity to rehabilitate themselves. Primarily all of that literature was around the treatment of styes and hordeola. It wasn’t really until the mid to late 1970s, that there was a clarity around the impact of the meibomian gland function in terms of tear film stability.

And I think in a 1977 paper, essentially the very first dry eye cascade was published. A very, very simple, beautifully simple diagram, showing that when the gland function is not normal, that you have a compromised tear film breakup time. And when you can restore it back to normal, that you can improve the tear film stability by improving the tear film breakup time. And just a few years after that, there was another publication associating meibomian gland dysfunction with reduced contact lens comfort.

And so these are two key publications that sowed the seeds for what we were able to observe over the next 30 years, which is that the health of the ocular surface is dependent upon the health of the meibomian glands and meibomian gland function in particular. The problem was, and has been that the practice of manually expressing glands is uncomfortable for patients and actually uncomfortable for doctors. So while we had a medical literature that was growing in volume over time saying these glands are important and here’s how you can improve their function, at the clinical level, in terms of daily practice and patient care, we weren’t seeing this translate into an improved standard of care.

And you’ll remember yourself, Walt, from early optometry school days that we would talk about warm compresses with a wave of the hand and throw out conversations with patients about do warm compresses and things of that nature. But there was nothing really targeted or specific and no real kind of impassioned if you do this, this will work. So the kind of quality care that we like to deliver. And so if we go back to about 2005, 2006, when TearScience was founded, the goal at that time was to innovate a technology that would do the work for the doctor and the patient, and also not cause a lot of discomfort or safety concerns.

And so what was breakthrough about that innovation process was that that was achieved in that we now have this automated treatment in the form of the LipiFlow. And in parallel to that, we also had the evolution of a standardization of assessment of meibomian gland function. And that whole process was necessary in terms of being able to definitively demonstrate that you have a pre versus post gland function that you can compare versus relying on the symptom cascade, which is as you would well know from all of your years of clinical practice can be very frustrating.

So if we now fast forward to the present time, what we’ve seen is that as our knowledge around this disease state of the impact of meibomian gland dysfunction and the essential nature of meibomian gland function being so foundational to the health of the ocular surface, we now see that by automating and safely and easily being able to execute on the treatment of MGD in an in-office setting that’s efficacious and can be assessed using metrics that don’t all require the capturing and relying on symptomatology, we see that the field today is in a completely different situation.

So we have a number of different technologies that have been innovated and brought to market around, very specifically, the evacuation of meibomian gland contents. We also see a significant uptick and willingness of eye care professionals to perform expression of the meibomian glands. And for any of us who were practicing eye care 20 years ago, to imagine a day when you would be easily able to have a conversation with a colleague in a variety of settings about the importance of expressing meibomian glands, it’s almost incomprehensible. So it’s sort of ironic that it was the automation of this process and the efficacy of this treatment that have now brought us to the point where we’ve been able to go all the way back to where we started and we see [crosstalk 00:07:02] highly different landscape.

Dr. Walt Whitley: Yeah. And being involved with this, I mean, we were one of the early adopters that had one of the first LipiFlow units within the practice. And so it’s been exciting seeing the evolution of the treatment, but it comes back to what you were just mentioning earlier was structure with the… We know that we have to take a look at the glands, but also the function and having a way to quantify that, to see are we getting improvement over time? And so that’s one of the exciting things where we have these technologies that can help our patients. And so we know we have structure and function, but before we get to that, we have to look at the prevalence and have a better understanding of meibomian gland dysfunction. And where are we at within the prevalence? How do you feel environmental factors and patient behaviors contribute to MGD?

Caroline Blackie: Oh, gosh! Another wonderful question, Walt. Before we get right to the prevalence, if we think about one of the inciting factors for negatively impacting gland function, there’s been some beautiful work done on animal models showing the impact of desiccating stress or chronic unmanaged desiccating stress and how it accelerates the aging of the meibocytes within the glands themselves. So well, you’ll recall that these glands are holocrine glands, so basal cells of the glands become the oil. And with the accelerated aging of the meibocytes, the nature of the oil over time is changed when exposed to chronic desiccating stress. And so these glands can become stagnated. And so you have a vicious cycle of desiccating stress causing upregulation of gland function. But if it’s unchecked, of course, the system is not designed to stay in this hyper mode. And so ultimately, meibomian gland dysfunction results.

And so if you think about… Now going back to your question about the prevalence, and you think about our lifestyles and what we know about the exposure to computers, smartphones, digital displays, that we see, if you look at the medical literature, fairly high prevalence, or much higher prevalence of MGD in patients who spend more time to the tune of more than four hours a day versus less than four hours a day on some form of digital device. And if you think about that, and I think about that, of course, it’s horrifying because I don’t remember a day when I spent anywhere close to less than four hours on some kind of digital device.

Dr. Walt Whitley: The thing I’m staring at right now, but go ahead.

Caroline Blackie: I know. It’s terrible. What happens when you’re doing those tasks is you’re reducing both the quality and the quantity of your blink rate. And the blink is fundamental to the health and the function of these glands. So if we just think about lifestyle, there’s a problem. And so it’s concerning and we both have kids and we’re thinking about, how in the world do we manage this for little kids? And if you look at some of the recent work of people like Dr. Priya Gupta showing very high prevalence of meibomian gland atrophy among pediatric populations. We as medical professionals I think need to take it upon ourselves to really consider what we can do in terms of raising the standard of care so that we are assessing meibomian gland health in all of our patients and not waiting and practicing this highly reactive medicine until dry eye symptoms occur.

But if we consider other aspects like environmental exposures and makeup and all of those things, anything that disrupts the integrity of the homeostasis of the tear film is potentially going to have a negative impact and is likely to, or has the possibility of increasing exposure to this stress. And so any inciting inflammatory exercitation of the ocular surfaces is also going to have a potential negative effect.

Dr. Walt Whitley: I just had a patient earlier this morning that was complaining about dry eyes. I was asking about her makeup. She goes, “I haven’t worn makeup forever, which makeup should I use?” And we started having that conversation about all the different chemicals and need to know what’s good for the eye, what’s not so good, but there’s so many that have harmful chemicals that can exacerbate the dryness and make those meibomian glands worse. So if someone asked you, such as me asking you right now, what is that number? So what is the prevalence of MGD? What does that number that you would say? Is it 67%, 69%, 3%? Because we know those numbers can be all over the place.

Caroline Blackie: Right. So, great question, Walt. And if you think about why those numbers are all over the place, part of the reason is because we’ve had very poor boundaries laid down in terms of exactly what is required in terms of specific metrics that you would have at your fingertips in the exam lane to make the diagnosis of MGD. So other than the later stage diagnosis, which is sort of diagnosis itself, not terribly complicated. At what point do you draw the line and say, “This patient definitely has MGD?” And if you think to yourself about everything we read about in the literature, it’s not exquisitely clear in its earliest stages. And so that’s problematic. However, if we take a look at certain subpopulations, there’s a little more clarity around those numbers. So if I take dry eye disease as an example, there are some key studies that are pointed to that would give you some clarity on prevalence.

And [inaudible 00:13:29] published a study back in 2012 [inaudible 00:13:33] saying that 86% of patients with dry eye disease of known origin had MGD. There was a recent systematic review that was presented at ARVO in 2019 I believe, putting all studies and the published medical literature through a very rigid stringent filter over a number of years. So probably the last 15 years. And that came back with somewhere between 75 and 80% of all dry eye patients. So multiple studies, not one study, but a systematic review.

If we look at your Sjogren’s patients, there was a upwards of 90-plus percent all have MGD. If we look at glaucoma patients that are currently being treated with topical medications, those patients are in somewhere in the 80% category of MGD. If we look at pre-cataract patients, you’re looking at somewhere between 50 and 60% of those patients all have MGD. If we look at contact lens wearing patients, somewhere in the 60%, and [crosstalk 00:14:54] systematic review general clinical population is somewhere in the 40% ballpark.

Dr. Walt Whitley: You’ve brought up Sjogren’s, right? Normally we think of Sjogren’s, they don’t produce any tears. So we’re always thinking aqueous deficient, but I don’t know any of my Sjogren’s patients that don’t have MGD as well. And so that’s why you have to look at both all the time.

Caroline Blackie: You do. And if you think about your Sjogren’s patient, even if… And actually, I love the Sjogren’s patient because the Sjogren’s patients were the ones back in the 1950s, they are the reason that dry eye disease came to be known as a condition, was through the lens of the Sjogren’s patient. That’s when this term first came into being. And of course, it’s evolved tremendously over the last 70 years.

But if you think about the Sjogren’s patient and the fact that that… Let’s say it’s an exocrine gland issue, and that there is an insufficient quantity of lacrimal production and all of the inflammatory cascade that results in that, then of course, what you have is chronic exposure to desiccating stress, which is a perfect storm for resulting in meibomian gland disease. And so while that has not been tested or demonstrated in that, I mean, I don’t know how you would design a study to do that, but you can see why medically, understanding the pathophysiology, how it makes total sense. That would be almost impossible to find a Sjogren’s patient that doesn’t have some degree of negative impact on meibomian gland function.

Dr. Walt Whitley: In the end, when we’re looking at the prevalence and how it’s been increasing, the great thing is people have been lucky, right? We’ve talked about it’s only not obvious if you’re not looking, you’re not expressing the glands, you’re not taking a look at the meibography. And so the more that we look, the more we’re going to find that, and that’s one of the things that’s been fun to see all of our colleagues doing as eye care profession. So my next question for you, how does MGD impact the pre-surgical assessment of the patient and IOL selection?

Caroline Blackie: Sure. Well, if you think about the pre-surgical assessment and how much attention is paid to the measurements that allow the surgeon to determine what power of lens would be placed in the eye during the surgical process, many of those measurements or a significant number of them are actually measured off the tear film itself. So if we think about something as basic as keratometry, and we remember that keratometric readings are not actually measured off the cornea, they’re measured off the tear film which overlays the cornea, it becomes exquisitely clear that if that tear film is not as stable as it needs to be, that that will dramatically impact those measurements.

And there’ve been a number of studies over time, not directly focused on meibomian gland dysfunction, but rather on the impact of the stability of the tear film for these kinds of metrics that rely on the tear film or a measure of the tear film that you can imagine it makes total sense that we’re starting to see compelling data that indicates that the patient does have MGD, that you can be in a situation where you’re gathering very sub quality data in order to make your decisions.

Dr. Walt Whitley: Yeah. [crosstalk 00:18:26]. Go ahead.

Caroline Blackie: I was just going to say the other area that we do know quite a lot about now is just the patient experience and the post-surgical period. So there’s a number of studies showing that patients that have MGD pre-surgery experienced an exacerbation of their MGD post surgery. And this very significantly negatively impacts the experience of the patient in the post-surgical period, which if you don’t know about the MGD, even if you’ve elected not to treat it, which doesn’t make good medical sense, but even if you had done that, that can catch and does catch a lot of surgeons by surprise in the post-surgical period for good reason.

Dr. Walt Whitley: And we’ve had this discussion, you identify it before, it’s the patient’s issue. If you wait and you do surgery and the patient’s having issue, and it’s due to ocular surface disease, I mean, that’s the patient that keeps on giving and will be at your practice quite a bit because we’re not going to be able to meet their expectations. And so one of my partners, Liz Yu, I mean, she does the LipiScan on every single one of her cataract patients, that way she has an understanding of the ocular surface of the meibomian glands to see what she’s working with prior to making the IOL selection.

Caroline Blackie: And Walt, you’re reminding me that if you think about the ASCRS guidelines that were published in 2019 around the preclinical care for phaco and [inaudible 00:19:59] refractive surgery patients, and the importance of doing exactly what you’re describing with Dr. Yu, assessing the ocular surface in general, but calling out specifically the meibomian glands’ both function and structure. And as you were speaking, I was just remembering back in the early 90s, I don’t know, 1992 or something like that, there was a publication actually to do with GPC. So giant papillary conjunctivitis and contact lens wear. And in that article, the lead author whose last name I think was Martin, spoke about this old… I’m going to use this air quotes, “old ophthalmology axiom.” That an eye exam or an ophthalmological evaluation was not complete until the lids had been fully manipulated and evaluated.

And if you think about the ASCRS guidelines, they have this look, lift, push, pull component to their algorithm for these pre-surgical patients and how it’s something that we needed to be told to do. So it’s interesting how when you look back over time and you recognize our forefathers, while we do keep making progress, there are some areas where perhaps we should go back and read the old stuff and learn from the past. It’s about how to do it right and don’t skip steps.

Dr. Walt Whitley: Bringing up that algorithm from ASCRS is just looking at the noninvasive preop measurements and take a look at the topography. And that’s one of the things I learned from Liz. If you see the hot spots or cool spots, you got to figure out what’s going on with that cornea. If you have K measurements of one greater than the other, is that a flag on why are these corneas not symmetrical for these patients or any irregular patterns. And so trying to address that and taking that into consideration before you pursue further steps within the surgical procedure, or even before doing surgery. So does the pre-surgical treatment with LipiFlow enhance the patient experience and post-surgical outcomes? I know what my answer is, but I will let you go first.

Caroline Blackie: So I can say as simple, it appears the answer is yes. I could offer some data to support that. There are a couple of good studies I can mention. So Dr. Matossian recently published a study showing that… This was a retrospective study and a retrospective chart review, and she was able to show that for patients whom she had treated the MGD with LipiFlow Thermal Pulsation prior to surgery, she had significant changes to her measurements based on the fact that she had a more stable tear film. So you can imagine that more accurate measurements allow for more accurate results. And in terms of patient outcomes, that will translate into a variety of factors, not the least of which is quality of vision. So that’s really important.

Some other studies have shown the impact of improvement in patient’s symptoms in the post-surgical period. So I’ve mentioned previously that we know there is a flare up of the MGD in that post-surgical period, if you could pretreat the MGD effectively that you can avoid that and if you can avoid some of that, then you can avoid some of the inflammatory cascade on the MGD side, that would cause additional discomfort to the patient. So that would influence patient outcomes. And there are a number of other areas that we could talk about, but basically yes, it does.

Dr. Walt Whitley: And I’m going to say, yes, it does as well. And so that’s why for our practice, we are so aware, we’re always looking for dry eye. Everybody has dry eye until proven otherwise, especially at our cataract refractive surgery patients, because of these things that we talked about then with our referring doctors, we challenge them. Treat the ocular surface, look at the meibomian glands, treat that before the referral, that way we can have optimal calculations, get our patients optimal results. So LipiFlow technology, as I mentioned, I’ve a lot of experience with it. I mean, you were here when we first got it and helped train us and our team. So we know the technology treats the glands from the inside of the eye with vector and thermal pulsation. What advantage does this serve for patient outcomes?

Caroline Blackie: So let’s go back to the discussion we were having earlier about the evolution of treatment of MGD and how we’ve always known that evacuating gland contents will have positive results in terms of improving the gland function or allowing the glands the opportunity to rehabilitate, to improve their function. The problem is that it’s super uncomfortable when you experience it. And when you apply heat to the external surface, the heat source once removed is essentially rendered ineffective because the vasculature of the eyelid is such that it wicks the heat away almost instantaneously. And so what we learned in the innovative process of developing LipiFlow is that if you heat from the inside, the inner lid surface, that you get the heat right up to the location of the meibomian glands themselves, just based on the anatomy of the eyelid.

And if you can keep the heat there while you physically manipulate the glands directionally, so from the distant end of the gland to the orifice of the gland, that you can easily move the material out of the gland without causing so much discomfort to the patient. And so, because you’re not having to apply so much pressure and force to the eyelid in that process, so the heat is effective and it’s provided at the right time and it’s simultaneously applied along with the evacuation and directional evacuation pressure over those glands, that there’s significantly tremendous comfort to the eyelid tissue. Plus you can do all of the glands at the time, so you don’t have to target certain eyelid areas. And so I think all of these factors together probably explain why the LipiFlow is so effective at improving gland function and why it is often referred to as a preferred treatment of choice. So I’m not sure if that answers your question.

Dr. Walt Whitley: It does answer the question because once again, addressing the function and how those meibomian glands are working. But we do find many patients do show improvement in the symptoms, but it’s all about education as we know, setting proper expectation for the patients on what to expect. So long-term, I think the last data, the longest study I saw was Greiner. It was three years, patients were still having relief and improvement with their meibomian gland function. Is there longer data than that other than this three-year study?

Caroline Blackie: Not in a controlled study, Walt. Not in a controlled study. And if I were to think about just the way we live today, whether it would be reasonable to expect that, even if you could find a patient that never needed their meibomian gland disease treated more than once, I would say that would be not in alignment with the pathophysiology and our understanding of the condition.

Dr. Walt Whitley: Yeah. Well, typically my dry eye patients, I’m seeing them minimum twice a year, and if they need a repeat procedure, I’m still going to do that, but we all have that patient go, “Well, how long does this last?” And so that’s the paper that I do always reference. And actually I’m going to throw in [crosstalk 00:28:33]. Go ahead.

Caroline Blackie: Well, I can offer you just one thing. There is one study that was published in 2016, which was a large multicenter randomized control trial. And in that study, we found two things. One was that for… These were dry eye patients with MGD that were treated with LipiFlow and they were not permitted, or they would be exited from the study, which was fine, to receive additional prescription treatments for their dry eye during the study period. At the end of that study, it was a 12-month study, so they received one LipiFlow treatment, at the end of that study, 86% of patients were not eligible for re-treatment at the end of that study after a 12-month period. What we also learned in that study was that early intervention optimizes outcomes. So for those patients that had been diagnosed more recently versus your chronic dry eye sufferer, those patients tended to have better outcomes. So also very consistent with what you would expect from a chronic progressive disease.

Dr. Walt Whitley: Well, we are almost wrapping this up, but I could keep asking you questions all day long, but I’m going to ask you one more question here. What’s next for J&J in ocular surface disease?

Caroline Blackie: Thank you for that question, Walt. So at J&J we stand firmly in and on our credo. And so our main focus is always going to be increasing access to care for patients and increasing knowledge state around the disease state for doctors. And so, as you see us move forward, I would expect to see innovations that support access to care for patients. And then also increased understanding of the disease state for doctors. And we do have our next generation activator that will be launched later in 2021. So watch the space for that. But when you think about where we’re headed, that’s a good way to think about where our focus lies.

Dr. Walt Whitley: Well, awesome. Awesome. Hey, well, thank you so much, Caroline, for being here and sharing this with us, things that you’ve been working on, what J&J, Johnson & Johnson Vision has been up to. And thank you all the listeners to our Dry Eye Coach Podcast.

Caroline Blackie: Thank you, Walt. What a pleasure it is to have an opportunity to connect with you today, and to talk about one of my favorite subjects, meibomian gland disease, and maybe one day we’ll look back and feel really excited about the tremendous progress that we’ve all made as a profession in terms of raising the standard of care for all of our patients. I look forward to that.

Dr. Walt Whitley: Perfect. Well, thank you once again.

Caroline Blackie: Thank you, Walt. Have a great afternoon.

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