Dupilumab‐associated ocular surface disease in atopic dermatitis patients: Clinical characteristics, ophthalmic treatment response and conjunctival goblet cell analysis

Abstract

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.

Real‐world reported adverse events related to systemic immunomodulating therapy in patients with atopic dermatitis: Results from the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry

“…Ocular complaints including (blepharo-)conjunctivitis, dry eyes, eye pruritus, blurry vision, keratitis, meibomian gland dysfunction, limbus nodules and cicatricial ectropion can be covered under the umbrella term dupilumab-induced ocular surface disease (DIOSD). 1,[45][46][47] A systematic review that included 2883 AD patients on dupilumab reports that DIOSD occurred in 13% of patients. 46 Supporting these findings, we found that DIOSD was reported in 15% of patients.…”

“…[48][49][50] Since ocular diseases such as conjunctivitis are more common in AD patients, pre-existent ocular disease could predispose to higher rates of DIOSD. 47,51 As the risk of development of ocular comorbidities is disease severity-dependent, this is especially true for patients suffering from severe AD. 52 In our study, one patient with conjunctivitis and five patients with non-infectious conjunctivitis already experienced ocular complaints before treatment initiation, so these might be considered as dupilumab-exacerbated rather than dupilumab-induced.…”