Podcast video (MP4 219775 KB)

FormalPara Key Summary Points

Patients with atopic dermatitis (AD) are at a higher risk for developing ocular surface disease (OSD) relative to the general population, and OSD may be exacerbated with the use of type 2 inflammation-inhibiting biologics.

An increased awareness is needed amongst dermatology providers on how OSD may present as well as appropriate care options for patients with AD.

It is important for dermatology providers to proactively build a partnership with an eye care specialist to enable prompt referral to eye care specialists when needed.

Digital Features

This article is published with digital features, including a podcast to facilitate understanding of the article. To view digital features for this article, go to: https://doi.org/https://doi.org/10.6084/m9.figshare.24874191.

Introduction

Lakshi Aldredge

Hi there, my name is Lakshi Aldredge and I’m a dermatology nurse practitioner at the Portland VA Medical Center. And joining me today for this podcast is Dr. Vivian Shi and Dr. Winston Chamberlain.

Vivian Shi

Hello everyone, my name is Vivian Shi. I’m a dermatologist practicing in Little Rock, Arkansas at the University of Arkansas for Medical Sciences. And I’m a big nerd in inflammatory skin conditions. Glad to be here.

Winston Chamberlain

Hi, I’m Win Chamberlain. I’m an ophthalmologist and a cornea subspecialist, and I run the cornea and refractive surgery division at the Oregon Health & Science University Casey Eye Institute. I also have a background in immunology and [am] very interested in topics related to crossover between systemic disease and ocular surface disease.

Lakshi Aldredge

Wonderful, thank you so much for joining me. In this podcast today we're going to be referring to the article, “Practical management of ocular surface disease in patients with atopic dermatitis, with a focus on conjunctivitis: a review,” published in the Journal of the American Academy of Dermatology, JAAD, in 2023 [1, 2].

The objectives of our podcast today [are], number one, to raise awareness of atopic dermatitisFootnote 1, or AD as we’ll refer to it, associated ocular surface diseases, or OSD. We really want to empower dermatology providers, which include dermatologists and advanced practice providers, to recognize and treat these diseases. We also want to highlight the importance of referral and partnership with eye specialists for optimal patient outcomes.

What Are OSD, and Why Do they Matter for Dermatology Providers?

Lakshi Aldredge

So before we get started, let’s focus on what is OSD. Why do we as dermatology providers need to know about this? So Dr. Shi, I’m going to ask you first, can you talk a little bit about ocular surface diseases, or OSD, as a comorbidity associated with AD?

Vivian Shi

Sure. So ocular surface disease or OSD will include the cornea, the conjunctiva, and our eyelid [1, 2, 4]. So individuals with AD or eczema, they do have increased risk of developing these OSD diseases, particularly atopic keratoconjunctivitis and vernal keratoconjunctivitis [5, 6]. So OSD associated with AD is really the two conditions occurring in the same patient [1, 2, 6].

Lakshi Aldredge

Thank you so much. And Dr. Chamberlain, can you expand on that and talk a little bit about the conditions specifically referred to as OSD? What does that term encompass specifically with eye diseases and diagnoses?

Winston Chamberlain

I think Vivian’s given a good introduction. We’re definitely thinking about the overlap between skin disease and the ocular surface. And the ocular surface is a complex micro-niche on the body where there’s interaction of skin, there’s a mucocutaneous junction, and then there’s mucous membranes on the conjunctiva [1, 2, 4]. There’s also the cornea, which is technically a mucous membrane [7], but the cornea itself is a unique organ. And of course, changes or deviations in that natural homeostasis have a huge impact on vision and on quality of life [8, 9].

Many of the patients that have atopic disease have probably subclinical disease on the eye surface already [1, 2, 6, 10], which has not been diagnosed because they’re not typically seeking out eye care. It may be mild, simple things like itchiness of eyes or allergic symptoms, and then some of them have more severe disease. There’s also an overlap of other known ocular diseases associated with atopic disease and we can discuss that in a little bit more detail, but just briefly to list a few of them, the incidences of glaucoma, of cataracts, of intraocular inflammation, and even of some mild retinal diseases are more common in patients with atopic disease [10]. And these are things that we’d like to make our dermatology colleagues aware of.

Lakshi Aldredge

Thank you for that. And Dr. Shi, can you talk a little bit about OSD that’s specifically associated with biologics, which is really how we, in dermatology, have come to know about the spectrum of ocular diseases?

Vivian Shi

This is a relatively new phenomenon. We knew that people with eczema or AD had some eye-related symptoms, but it’s not until the clinical trials in our novel biologics to treat AD through dupilumab, one of the first ones approved, that we really start to think about and study the association between AD and various ocular surface symptoms [11,12,13]. So OSD associated [with] biologics is really by definition development of ocular surface disease in conjunction with the treatment that can occur in a variety of timeframes [12]. It can occur as early as just 1 week of starting the biologics or as late as a year or more [12]. So which one goes first? Is it the atopic condition worsening or is it the biologic one?

So this cross-pollination podcast is really important for the community to help weed out these different timings of symptoms and associated factors, and what we can do as collaborators to help manage and recognize these conditions early.

Lakshi Aldredge

Dr. Chamberlain, this is an exciting time [of the] coming together of dermatology and ophthalmology that I think has never previously existed in this way. Can you talk about what you’re seeing as far as the connection between biologic use and the evidence supporting its connection with OSD? What are you seeing?

Winston Chamberlain

So this is actually, I would say, a reemerging topic in ophthalmology, the idea that there are many types of medications that have systemic impact; that have direct impact on the ocular surface [14, 15]. Specifically related to the biologics that target the immune deviation of AD, we’ve noticed an uptick in patients presenting to ophthalmology clinic or getting referred by dermatologists for symptoms related to the onset of these drugs as Vivian mentioned [14, 16]. And it’s interesting that the timing is so variable. As Vivian also mentioned, sometimes the onset of the symptoms can be quite early at the beginning of the treatment, but I would say on average many of these patients don’t start to experience symptoms for several months after using the medications, at least in my experience and what I’ve seen in the literature [12].

And I think that is probably telling us something that we don’t thoroughly understand about the mechanism of how the OSD is either starting or being aggravated. And I think it’s important to reiterate that many of these patients have a subclinical baseline disease and so it’s highly likely that the inflammation that we see on the surface is being probably aggravated by these medications [14]. There’s some biological hypotheses that may play into that, but before I just talk about those briefly, I want to state that from the ophthalmologist perspective, we have two critical goals when we approach these problems. One is that we know that these drugs are incredible drugs for the skin disease, that they’re life-changing, and we want to be able to keep the patients on these medications if possible [17], because most of them they walk in with incredibly red eyes and their eyes are uncomfortable, but they say, “This drug has changed my life,” and the way it’s affected their itchy skin and their eczema [is remarkable] and they don’t want to continue having those symptoms.

And so the thought of stopping the medication because their eyes are uncomfortable is a difficult decision for them. And we’ve had a few patients that have dropped out as a result of that. And so that’s the first goal. The second goal is that we know that there can be an overlap between some of these other atopic-defining eye illnesses and they could be confused or missed by a dermatologist who doesn’t have a luxury of looking in the microscope. And so one classic example would be that herpetic keratitis and herpetic keratoconjunctivitis can present like standard OSD and that’s something that’s potentially blinding and progressive and has to be treated and diagnosed by an ophthalmologist, and really is very difficult to detect without having the tools of a slit lamp and some staining protocols and the ability to see those changes in the eye [10, 18]. So our goal is also to keep the patients safe from other diseases that may present as a result of ocular surface immunological deviation that’s being driven by these medications.

In terms of what’s going on with the drugs, I think we have a sense that both the blocking of IL-4 and IL-13 pathways is probably changing the cytokine profiles on the ocular surface and is also changing the activities of cells that are active on the surface [19]. One of the cell types that’s been the source of a lot of discussion is goblet cells [19]. We feel that there is probably a deficiency of goblet cells on the surface of patients that have atopic disease [19]. This may not be true in patients that have other immune deviations such as asthma where these medications are also used, and that may be why we see OSD more frequently present in patients with atopic disease [14, 20].

The other thought is that the blocking of IL-4 pathways may be driving more of a type 1 response on the eye [21]. That type 1 response is driven by cytokines, such as interferon-gamma, and those are definitely known to drive ocular surface scarring, [activation] of cytotoxic T cells, and accumulation of cytotoxic T cells on the ocular surface [22, 23], which can [cause] the signs of inflammation and drive advanced ocular surface changes, such as scarring and neovascularization of the cornea [24].

Lakshi Aldredge

So onto that, one of the questions that the article poses, is there going to be a difference in the incidence of these OSDs with IL-13 targeting versus both IL-4 and IL-13 targeting biologics?

Winston Chamberlain

I think that we’re seeing based on what the literature’s reporting, that the incidence seems to be lower in the IL-13-specific targets. However, we’re still seeing conjunctivitis in those populations, although it does seem to be less than some of the initial reports with the Dupixent rates of conjunctivitis and OSD [12, 16].

OSD Presentation in Patients with Atopic Dermatitis and Steps Dermatology Providers Should Take for Appropriate Care

Lakshi Aldredge

So let’s switch gears just a little bit. Dr. Shi, can you talk a little bit about some of the challenges that dermatology providers face in actually recognizing OSD? What are some of the challenges that we’re facing in diagnosing these conditions in our AD patients?

Vivian Shi

So we’re dermatology providers, all we look at is the skin. Maybe we’ll look at the joint and actually that’s a good parallel I’ll come back to later. In med school I had 1 week [of ophthalmologic education]; [and] in PA and nursing school, I doubt it would be more than 2 weeks. And residency briefly mentioned, “Eye symptoms in rosacea, done, refer to eyecare specialists.” So the knowledge is one part of it. There’s also the fear of looking into the eye for many derm providers, myself included. I remember one of my most, no pun intended, eye-opening moments was in the OR with an ophthalmologist. And so the comfort level is another thing. And we don’t have diagnostic equipment in the derm office, definitely not a microscope. We have a dermatoscope and we have a pen light, that’s about it.

And so there’s also the time constraint in a derm visit. I think a lot of community appointments are 10, 15 min. We have a little bit longer buffer zone in the academic center, but still, we have this moderate-to-severe AD patient in front of us. We’re talking about labs, taking care of the skin, wet wraps, you name it. And then talking about what you expect from a biologic. I just think that we forget to ask about the eye and traditionally there’s not enough recognition. So I will give the parallel coming back to it. As dermatologists, we used to think about psoriasis just in the skin. And then when we start to think about collaboration with rheumatologists, now everybody who sees a psoriasis patient I think is asking about the joint. Do you have joint stiffness, joint swelling, joint redness? And so it’s becoming a second nature to link psoriasis in the skin to psoriasis of the joint [25].

And I think moving forward, we are going into this renaissance era where I think derm providers will be starting to link any eczematous conditions or inflammatory skin conditions, say, “Hey, do you got something going on in the eye? What are your symptoms?” So that’s one thing from the recognition of the provider’s part. But the patient recognition is also lacking. Patients are seeing a skin provider that’s like, “Why am I talking about my eye?” So if they don’t bring it up, we’re not asking, it’s not going to go anywhere.

So hopefully with the awareness in the clinical trials and the provider collaboration space increases, we’re going to be doing some work in patient awareness also.

Lakshi Aldredge

Who can make the diagnosis of OSD conditions? I think this is really important. We saw this in dermatology whether we could make the diagnosis, for example, of psoriatic arthritis, if that was in our wheelhouse. Can you talk a little bit about who can make the diagnosis of these conditions and what kind of sequelae can happen as a result of that diagnosis?

Winston Chamberlain

Dermatologists can start with this diagnosis because they have a number of simple tools and a lot of these are symptoms. And so asking and maybe even creating a simple questionnaire such as, “Is there a change in your eye comfort? Are you experiencing more discharge, more tearing, itchiness, or more light sensitivity? Are your eyes redder than they used to be?” So simple questions that basically are related to symptoms.

Those are initial assessments that can drive the decision, is there current ocular surface inflammation or periocular inflammation going on that merits a referral? I think the details are probably going to have to be [explored] by an ocular care provider—an optometrist or an ophthalmologist.

Lakshi Aldredge

Great. Dr. Shi, you’ve done a lot of research on these conditions in the dermatology sphere. How has this changed your practice as far as teaching your derm patients with AD about eye hygiene? What kind of tips are you telling them? And Dr. Chamberlain, I want you to add on to that after Dr. Shi shares what she is teaching our patients now.

Vivian Shi

Yes, so because there’s a high correlation, the one thing that myself and any dermatology provider should really recommend is good hand and eye hygiene [1, 2]. Minimizing airborne contact allergen exposure if possible [6]. And then staying hydrated [6]. Warm compresses for inflamed eyelids and to consider doing lubricating eye drops [1, 2, 26]. And just if you have a water-based humidifier, that’s also helpful too for your working and sleeping space [26]. So that’s just preventative care, knowing that people with atopy are more likely to have issues in the eye [1, 2, 10].

Lakshi Aldredge

Are there specific eye drops that we should use for these patients? Because I know some can actually exacerbate AD-related ocular symptoms.

Winston Chamberlain

Our preference as ophthalmologists is [to] use preservative-free tears [1, 2, 27]. The reason for that is mostly that there is a dose-dependent toxicity associated with the preservatives in preserved drops, and historically, many of the drops that have preservatives in them, some of these preservatives are things like benzalkonium chloride, which can actually aggravate OSD [1, 2, 18, 27]

The other medications that are safe for dermatologists to consider are the allergy-type drops that we think about. So mast-cell stabilizers and antihistamines that in drop form can actually provide quite a bit of relief with itching [1, 2, 28, 29]. Olopatadine is a great example. Ketotifen is another great example of medications that are very safe that could be started by the dermatologist without concerns of significant side effects [28].

We are not fans of patients starting other types of immunomodulators on the eye surface without the ophthalmologist weighing in. These medications would include ocular steroids because they have much more significant risk for driving the pressure in the eye, which can lead to glaucoma and also aggravating infections, which may be hard to diagnose without the benefit of a slit lamp bio-microscope [1, 2, 15]. And so when we get into those immunomodulating agents that can [suppress the local] immune response from [fighting] off infectious diseases, that it’s important for an ophthalmologist or an optometrist to [evaluate the patient] on whether they think there may be an active infection going on [1, 2].

Concluding Remarks on Remaining Unmet Needs

Lakshi Aldredge

Thank you so much. This has been really informative and so helpful. So to wrap up a little bit, I want each of you to think about some of the unmet needs. Where is the next step in the evolution of our understanding of OSD in AD patients? And what is their relevance for the everyday dermatology provider in clinic?

Vivian Shi

There’s a lot of questions to be answered. I think part of it is gaining more real-life data with the emergence of new immunomodulators, and we’re getting more combination use between a biologic and other immunomodulators, like a JAK inhibitor. Will that decrease the incidence of certain ocular diseases? We don’t know yet. Other than research study, I think the practice gap should evolve over time, like I mentioned about the parallel of psoriasis. This should become second nature over time to be included in the intake form, part of the history taking, and also this is dating me, but on your Rolodex, you should really have an ophthalmologist, an optometrist just like we have, say, a plastic surgeon or a rheumatologist or Mohs surgeon on the Rolodex. You don’t want to wait until the patient has emergent eye pain or vision loss and have to send [a] person to the ED. Having that long-lasting relationship is very important [1, 2].

It’s always less traumatic to do a skin biopsy [than an eye biopsy], and we do that every day. But I think there’s not enough tissue studies personally to link between the process that happens in the eye and in the skin. It’s not common. We actually don’t have much going on where we’re biopsying the skin and the conjunctiva in the same person and looking at that parallel at the same time. So hopefully more mechanistic studies and tissue-based studies will come out for us to have a better understanding.

Lakshi Aldredge

Dr. Chamberlain, your thoughts?

Winston Chamberlain

I agree that the mechanism is very interesting, and I think it’s complex because we know when you alter one component of the immune system that sometimes other components get secondarily altered as a response. And so really understanding what targets we can specifically hit to address a specific disease mechanism without driving some of these secondary effects is critical, both from a scientific standpoint but also from patient care. It’s probably unlikely that we’re going to find drugs that eliminate all of these secondary effects. So I agree with Vivian that the awareness of the problem from a real-world standpoint and from a practitioner’s perspective is: let’s be aware that eye problems do exist. For the most part, they’re actually manageable.

A large majority of our patients that are on these drugs are thriving; they’re doing well. A very small minority have to stop them because of significant problems, at least in my experience. And the reason is that we can actually treat these symptoms successfully and safely. They do require monitoring. They require the discipline of the patient and the provider, the commitment to continue follow-up to make sure that we’re not seeing secondary side effects from medications. I agree that communication between the dermatologist and the ophthalmologist or optometrist is really important.

Just going back to the very beginning of this conversation: being aware that atopic patients probably have baseline disease [14] and if patients are coming in with atopic disease, even if they’re not on biologics, some of the diseases that are associated with atopic disease in the eye would benefit from an early diagnosis if caught by an ophthalmologist [1, 2, 6]. So getting a routine eye exam would be really important in those general atopic patient populations as well.

Lakshi Aldredge

This is so helpful, and I know as a nurse practitioner, and I think I’m speaking for other APPs as well (NPs/NPAs); often we’re the ones seeing AD patients in our continuity clinics. And podcasts such as this, and the articles that are being written about this subject [1, 2], are so critical to us to gain this information because as Dr. Shi mentioned, we are just not getting a lot of this in our graduate curriculums or in our training programs.

Understanding, first of all, the correlation between atopic diseases and ocular symptoms and the diagnosis of OSD is so critical for us to know to ask those questions, to elicit that information. Great point that often patients come to see us, they’re not thinking about their eye symptoms, and so we need to be proactive in asking those questions. So with that, I really want to thank both of you for sharing your expertise with us and wishing all of you who are listening to our podcast, hoping that you’ll take away these great pearls in order to help improve your patient outcomes. Thank you.