DEAR EDITOR, Higher rates of conjunctivitis have been reported in patients with atopic dermatitis (AD) treated with dupilumab, an anti-interleukin (IL)-4Ro antibody inhibiting IL-4 and IL-13, vs. patients treated with placebo. 1 However, the exact pathomechanism has not been clarified. Given the necessity for optimal treatment and risk management, the aim of this study was to describe the histopathological characteristics of conjunctivitis during dupilumab treatment in patients with AD. Participants, selected from the BioDay registry, consisted of 74 patients with moderate-to-severe AD treated with dupilumab for at least 16 weeks. Of these, 23% developed ophthalmologist-confirmed conjunctivitis requiring anti-inflammatory treatment. We sequentially included six patients [three male; median age 39 years, interquartile range (IQR) 29–54] in whom a diagnostic conjunctival biopsy of the inferior fornix was performed before initiation of ocular anti-inflammatory treatment. Biopsies were fixed, paraffin-embedded and stained with haematoxylin and eosin for histological assessment, and additionally with CD3/CD4 [T helper (Th) cells] and Alcian blue [mucus-containing goblet cells (GCs)]. Conjunctival biopsies of two healthy controls were included. Biopsies were assessed by two independent experienced pathologists. This study did not fall under the scope of the Medical Research Involving Human Subjects Act, confirmed by the local Medical Research Ethics Committee (METC 18/537). The most prominent histopathological feature in conjunctival biopsies from patients with AD developing conjunctivitis during dupilumab treatment was a scarcity of intraepithelial GCs. Median GC density was 3Á3 cells mm À1 (IQR 1Á1–4Á9)(Fig. 1a, b) in patients with AD with conjunctivitis vs. 28Á3 and 36Á3 cells mm À1 in the two control samples. Five patients showed a multicellular immune-cell stromal infiltrate, consisting mainly of T cells (CD3+/CD4+) and eosinophils (Fig. 1c), partially migrating into the conjunctival epithelium. Conjunctival GCs are specialized mucus-secreting cells, vital for ocular surface function. 2 In healthy individuals lower forniceal GC counts vary between 8Á8 and 30 cells mm À1. 3 All patients included in our study had a decreased GC count (median 3Á3 cells mm À1) vs. controls (mean 32Á3 cells mm À1). Mice studies have demonstrated that ocular IL-13 expression normally stimulates GC proliferation and mucus secretion. 4 By blocking IL-13, dupilumab treatment may lead to GC hypoplasia, as IL-4Ro is expressed on conjunctival epithelium. This might result in decreased mucin production, subsequent tear film instability and mucosal epithelial barrier dysfunction, leading to conjunctival inflammation in a subpopulation of (predisposed) patients with AD. Clinically, the loss of GC-produced factors may result in dry eyes, as was reported by all patients, and subsequently irritative conjunctivitis. As in this study biopsies were performed after initiation of dupilumab, GC scarcity might already be present before dupilumab treatment, although patients did not experience ocular symptoms at start of treatment.(a)(b)(c)