Persistent Neutrophil Infiltration and Unique Ocular Surface Microbiome Typify Dupilumab-Associated Conjunctivitis in Patients with Atopic Dermatitis

Objective: To elucidate the pathogenesis of dupilumab (Dupixent (R))-associated ocular surface disease Subjects: Twenty patients with moderate-to-severe atopic dermatitis (AD) who received dupilumab and 10 age- and sex-matched healthy controls were enrolled in the study. Methods: The study cohort underwent a thorough slit-lamp and entire-body dermatologic examination. Conjunctival swabs and smears were collected at baseline, 4 and 16 weeks after treatment initiation, and during the conjunctivitis episode. To analyse the ocular surface microbiome, 16S ribosomal RNA sequencing was performed, smears were hematoxylin and eosin stained, and serum cytokines were measured by using a multiplex immunobead assay. Main Outcome Measures: Composition of ocular surface microbiome and cellular component as well as serum cytokine levels. Results: Six of the 20 patients with AD developed DAOSD after dupilumab initiation; these patients responded after a delay to treatment as quantified by Eczema Area and Severity Index and Investigator's Global Assessment score. Conjunctival smears showed massive neutrophilic infiltration and serum analysis revealed increased systemic levels of neutrophil-priming proinflammatory cytokines, in particular interleukin-1b and tumor necrosis factor a, in patients with DAOSD compared with those without it. The ocular surface microbiome of patients with DAOSD was characterized by a diverse and persistent microbial colonization, particularly by Acetobacter aceti. In contrast, microbial diversity decreased in patients with AD without DAOSD after the initiation of dupilumab treatment, especially the abundance of Staphylococcus aureus. In vitro experiments substantiated the potential role of the microbiome, showing increased growth of A. aceti and decreased growth of S. aureus in presence of dupilumab. Conclusions: Persistent neutrophilic infiltration and a unique microbial landscape on the ocular surface associated with elevated levels of systemic proinflammatory cytokines typify DAOSD. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology Science 2024;4:100340 (c) 2023 by the American Academy of Ophthalmology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

The objective of this study was to investigate the pathogenesis of ocular surface disease associated with the use of dupilumab in patients with atopic dermatitis. The study cohort included 20 patients with moderate-to-severe atopic dermatitis who received dupilumab treatment and 10 healthy controls. The ocular surface microbiome and serum cytokine levels were analyzed. The results showed that some patients developed ocular surface disease after dupilumab initiation, characterized by increased levels of proinflammatory cytokines and a unique microbial landscape on the ocular surface. These findings suggest a potential role of the microbiome in the development of ocular surface disease in patients receiving dupilumab treatment.