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Atopic dermatitis (AD) is a chronic inflammatory skin disease for which new targeted therapies are currently available. Due to the increased rates of ocular surface disease (OSD) reported during treatment with these new targeted treatments, more insight into the occurrence and pathomechanism of OSD in moderate‐to‐severe AD patients is needed. Therefore, this review's first part highlights that most patients with moderate‐to‐severe AD already have characteristics of OSD before starting targeted treatment. Remarkably, not all AD patients with OSD report ocular symptoms. OSD in AD is associated with less conjunctival goblet cells (GC) compared to healthy controls. In addition, OSD severity in AD patients is associated with high AD activity, the presence of eyelid and/or facial eczema, and high levels of AD‐related severity biomarkers in tear fluid. The second part of this review highlights that pre‐existing ocular pathology (e.g. in combination with the use of ophthalmic medication or eyelid eczema) may be associated with the development of dupilumab‐associated ocular surface disease (DAOSD). During dupilumab treatment, DAOSD (which can be new‐onset OSD or worsening of pre‐existing OSD) is observed in approximately one‐third of the dupilumab‐treated AD patients. Anti‐inflammatory ophthalmic treatment improves DAOSD, and dose reduction of dupilumab may also be an effective treatment option. The pathomechanism of DAOSD is still not fully elucidated. In a prospective study low, but stable conjunctival GC numbers were observed in moderate‐to‐severe AD patients, before and during dupilumab treatment. However, the Mucin 5 AC (MUC5AC) expression of GCs decreased during dupilumab treatment, suggesting an impairment of the GC function by dupilumab treatment. In addition, higher dupilumab tear fluid levels were found in dupilumab‐treated AD patients with moderate‐to‐severe OSD compared to patients with no or mild OSD, whereas the dupilumab serum levels are similar. Clinicians should be aware of the frequent occurrence of OSD in moderate‐to‐severe AD patients, and a low‐threshold referral to an ophthalmologist is recommended. [ABSTRACT FROM AUTHOR]

Background: Dupilumab‐associated ocular surface disease (DAOSD) is frequently reported as side effect in atopic dermatitis (AD) patients. Therefore, the aim of this study was to investigate the frequency and severity of DAOSD, ophthalmic treatment response and to learn more about the effect of dupilumab on conjunctival goblet cells (GC). Methods: This prospective study included dupilumab‐treated AD patients between February 2020 and June 2022 from the University Medical Centre Utrecht. Patients were examined by an ophthalmologist and a dermatologist before start (baseline), and after 4 and 28 weeks of dupilumab treatment. Ophthalmological examination was assessed by the Utrecht Ophthalmic Inflammatory and Allergic disease (UTOPIA) score. DAOSD was defined as an increase in UTOPIA score of ≥3 points from baseline. To quantify conjunctival GCs and to investigate the percentage of Cytokeratin 19 (CK19)‐CD45‐Mucin 5 AC (MUC5AC)+ cells, conjunctival impression cytology samples were analysed. Results: Ocular surface disease (OSD) was present in 91.3% (n = 63/69) patients at baseline. DAOSD was observed in 28.9% (n = 20/69) patients, in whom GC numbers remained stable and the percentage of CK19‐CD45‐MUC5AC+ cells decreased at onset of DAOSD compared with baseline. After 28 weeks of dupilumab treatment, DAOSD was seen in 14.5% (n = 10/69) patients. Of the 85.5% (n = 59/69) patients without DAOSD or with controlled DAOSD at Week 28, 40.7% (n = 24/59) patients received anti‐inflammatory ophthalmic drugs. Conclusions: Ocular surface disease is common in moderate‐to‐severe AD patients before starting dupilumab. During treatment with dupilumab DAOSD severity improves with early ophthalmic treatment. The decrease in percentage of CK19‐CD45‐MUC5AC+ cells during dupilumab treatment suggests an impairment of the GC function due to dupilumab treatment. [ABSTRACT FROM AUTHOR]

Background: The patho‐mechanism of ocular surface disease (OSD) in dupilumab‐treated atopic dermatitis (AD) patients remains unclear. The aim of this study is to measure dupilumab levels in tear fluid and serum, and relate these findings to the severity of OSD during dupilumab treatment in AD patients. Methods: This prospective study included dupilumab‐treated moderate‐to‐severe AD patients who were seen by a dermatologist and an ophthalmologist before the start of dupilumab (baseline), and after 4 and 28 weeks of dupilumab treatment. Dupilumab levels in tear fluid and serum were measured by liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS). Additionally, a pilot study was conducted to measure dupilumab on conjunctival epithelial cells using flow cytometry and LC‐MS/MS. Results: At baseline, 89.6% (n = 43/48) of the patients had OSD, with 50.0% having moderate‐to‐severe OSD. After 28 weeks of dupilumab treatment, the median dupilumab tear fluid levels were 0.55 mg/L (IQR 0.35–1.31) and 0.29 mg/L (IQR 0.16–0.60) in patients with moderate‐to‐severe OSD and patients with no or mild OSD, respectively (p = 0.02). Dupilumab levels could be detected on conjunctival epithelial cells of 5 AD patients treated with dupilumab for 4 weeks. Conclusion: Patients with moderate‐to‐severe OSD had higher dupilumab tear fluid levels compared to patients with no or mild OSD, indicating that dupilumab reaches the ocular surface. Dupilumab was also detected in conjunctival cell suspensions and was found to directly bind CD45‐conjunctival epithelial cells. This suggests that AD‐induced changes of the conjunctival epithelium may play a role in the development of OSD as well as increased local drug availability. [ABSTRACT FROM AUTHOR]

Additionally, occurrence of both AD eyelid involvement and AD facial involvement in the past year was significantly higher in patients with moderate-to-severe OSD compared to patients with no or mild OSD ( I n i = 28 (90.3%) vs. I n i = 18 (46.2%), I p i = <.001 and I n i = 31 (100.0%) vs. I n i = 33 (84.6%), I p i = .030 respectively). Keywords: atopic dermatitis; goblet cell; ocular surface disease EN atopic dermatitis goblet cell ocular surface disease 801 805 5 06/01/22 20220601 NES 220601 Key Messages In a single-centre study, we assessed ocular surface disease prevalence in moderate-to-severe atopic dermatitis. Diagnosing OSD is important since it may be associated with chronic limbitis, possibly leading to irreversible limbal stem cell deficiency and subsequently to irreversible long-term visual loss.3 In our study, lower conjunctival GCD was found in patients with OSD, compared to patients without OSD. However, by comparing GCD of patients with OSD to GCD of healthy controls described in the literature, we can conclude that moderate-to-severe AD patients with OSD have lower GC counts. [Extracted from the article]