A Clinician’s Guide to Dupilumab-related Ocular Surface Disease

J Clin Aesthet Dermatol. 2025;18(5):26–28.

by Sandi Assaf; Peter Lio, MD; and James Q. Del Rosso, DO

Ms. Assaf is with Sam Houston State University College of Osteopathic Medicine in Conroe, Texas. Dr. Lio is with Northwestern University Feinberg School of Medicine in Chicago, Illinois. Dr. Del Rosso is with Touro University Nevada in Henderson, Nevada; JDR Dermatology Research in Las Vegas, Nevada; and Advanced Dermatology and Cosmetic Surgery in Maitland, Florida.

FUNDING: No funding was provided for this article.

DISCLOSURES: Ms. Assaf declares no conflicts of interest. Dr. Lio reports being on the speaker’s bureau for AbbVie, Arcutis, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche-Posay/L’Oreal, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, Verrica; reports consulting/advisory boards for Alphyn Biologics (stock options), AbbVie, Almirall, Amyris, Arcutis, ASLAN, Bristol-Myers Squibb, Burt’s Bees, Castle Biosciences, Codex Labs (stock options), Concerto Biosci (stock options), Dermavant, Eli Lilly, Galderma, Janssen, LEO Pharma, Lipidor, L’Oreal, Merck, Micreos, MyOR Diagnostics, Regeneron/Sanofi Genzyme, Sibel Health, Skinfix, Suneco Technologies (stock options), Theraplex, UCB, Unilever, Verdant Scientific (stock options), Verrica, Yobee Care (stock options). In addition, Dr. Lio has a patent pending for a Theraplex product with royalties paid and is a Board member and Scientific Advisory Committee Member emeritus of the National Eczema Association. Dr. Del Rosso has served as a research investigator, consultant, and/or speaker for Allergan, Almirall, Amgen, Arcutis, Aslan, Bausch Health (Ortho Dermatologics), Beiersdorf, Botanix, Bristol Myers Squibb, Cassiopea, Cutera, Dermavant Sciences, Dr Reddy, Eli Lilly, Ferndale, Galderma, Johnson & Johnson, Journey, LEO Pharma, L’Oréal, Mayne Pharma, MoonLake, Nektar, Novan, Primus, Sebacia, Sol-gel, Sun Pharma, and Vyne.

ABSTRACT: Atopic dermatitis (AD) commonly presents in both children and adults with pruritic, eczematous lesions that can have a substantial impact on quality of life. Current biologics approved for AD include dupilumab, an IL-4 receptor alpha inhibitor, tralokinumab, an IL-13 inhibitor, lebrikizumab, an IL-13 inhibitor, and nemolizumab, an IL-31 receptor alpha inhibitor. Dupilumab, tralokinumab, and lebrikizumab are highly effective in addressing the inflammatory response and reducing pruritus in AD patients via the IL-13 pathway, but are also associated with conjunctivitis and ocular surface disorders (OSD) in some patients, especially compared to other biologics that do not inhibit the activity of IL-4 and/or IL-13. For practitioners, it is important to be aware that OSD is a relatively common side effect but rarely causes problems severe enough to lead to cessation of treatment. This brief report provides guidance on screening and managment of OSD in patients with AD receiving anti-IL-4 and/or IL-13 treatment.

Keywords: Atopic dermatitis, conjunctivitis, keratitis, eye pruritus, blepharitis, IL-13, tralokinumab, lebrikizumab, dupilumab

Introduction

Atopic dermatitis (AD) commonly presents in both children and adults with pruritic, eczematous lesions that can have a substantial impact on quality of life. More severe or widespread cases of AD have historically been particularly difficult to treat given the lack of targeted systemic treatment options in the past.¹ Topical therapies including corticosteroids and specific nonsteroidal agents remain as important first-line treatments for AD, but often fail as monotherapy to achieve sustained clinical improvement for patients with moderate-to-severe AD.² Fortunately, in recent years there has been an influx of new treatments for both adult and pediatric populations with AD, particularly with the emergence of biologics. 

Current biologics approved for AD include dupilumab, an IL-4 receptor alpha inhibitor,³ tralokinumab, an IL-13 inhibitor,⁴ lebrikizumab, an IL-13 inhibitor,⁵ and nemolizumab, an IL-31 receptor alpha inhibitor.⁶ Dupilumab, tralokinumab, and lebrikizumab are highly effectively in addressing the inflammatory response and reducing pruritus in AD patients via the IL-13 pathway, but are also associated with conjunctivitis and ocular surface disorders (OSD) in some patients, especially compared to other biologics that do not inhibit the activity of IL-4 and/or IL-13.^7–9  These OSDs include conjunctivitis, keratitis, eye pruritus, blepharitis, and dry eye. While the mechanism of how these biologics cause OSD has not been clear, a compelling hypothesis is that downregulation of IL-13 causes a significant decrease in goblet cells which help maintain normal secretions of the eye surface, thus predisposing the eye to OSD.¹⁰

However, it is important to note that patients with AD often have a compromised ocular surface epithelium at baseline due to the pathophysiology of the immune disease before being started on any medication,¹¹ and have a significantly higher rate of comorbid conjunctivitis and keratitis that correlates with severity.¹² Since patients with AD have a predisposition to ocular surface disease, it is possible that patients may develop conjunctivitis regardless of whether or not they are started on a biologic.

For practitioners, it is important to be aware that OSD is a relatively common side effect but rarely causes problems severe enough to lead to cessation of treatment. Generally, an ophthalmology referral is unnecessary before initiating a biologic unless the patient has active OSD or a significant history of OSD.¹³

There are some risk factors that increase a patient’s chance of having an OSD while on an IL-13-inhibiting biologic.^13–15 Asking a few brief screening questions may be useful in identifying those at higher risk. This screening may be used at clinician discretion prior to starting on a biologic such as dupilumab, tralokinumab, or lebrikizumab or even generally in AD patients who are predisposed to ocular surface disorders especially in cases of more severe AD (Figure 1).

Answering “yes” to any question in Figure 1 may help identify greater risk for developing OSD, though only the first question would warrant consideration of an ophthalmology referral prior to starting on a medication (Figure 2).

For cases of biologic-related OSD, preservative-free lubricant eye drops are usually recommended as initial treatment,¹³ and may be reasonable to suggest even prior to starting biologic therapy as a preventative measure to reduce the risk of OSD.¹⁶ In cases that do not adequately respond to lubricant eye drops, antihistamine eye drops, corticosteroid eye drops, and periocular application of tacrolimus are viable options.^13–15 For severe or treatment-resistant cases, which are fortunately rare, referral to ophthalmology is indicated.^13–15 However, this may vary from case to case and referral may be arranged earlier based on clinician discretion. 

Overall, the emergence of new biologic treatment options for moderate-to-severe AD has led to vast improvement in disease control and patient quality of life. Apparently due to both the pathophysiology of the disease and the mechanism of these biologics that inhibit IL-4 and/or IL-13 activity, ocular surface disorders may be seen in these patients. This brief review provides a screening approach for practitioners to assess initial risk at their discretion. Other systemic therapies, as well as emerging biologics with different mechanisms, may provide alternative options in severe cases of OSD.

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