Ocular surface microbiome in dupilumab associated ocular surface disease
Objective: The aim of the study was to elucidate the pathogenesis of Dupilumab [Dupixent®] associated ocular surface disease.  Design: Prospective single-center cohort study. Subjects and Controls: Twenty patients with moderate to severe atopic dermatitis who received dupilumab and ten healthy controls were enrolled in the study.  Methods: The study cohort underwent a thorough slit lamp and whole-body dermatologic examination. Conjunctival swabs and smears and blood samples were collected at baseline, 4 and 16 weeks after treatment initiation, and during the conjunctivitis episode . 16S rRNA sequencing was performed to analyse the ocular surface microbiome, smears were stained histologically, and serum cytokines were measured. Main Outcome Measures: To investigate the role of the ocular surface microbiome and cellular components in the pathogenesis of dupilumab-associated ocular surface disease (DAOSD). Results: Six of the twenty AD patients developed DAOSD after treatment initiation and showed delayed response to treatment as measured by EASI and IGA. Smears of the conjunctiva showed massive neutrophil infiltration, and serum analysis revealed increased levels of IL -1ß and TNF-a in patients with DAOSD. Analysis of the ocular surface microbiome revealed diverse and persistent microbial colonisation, particularly Acetobacter aceti in patients with DAOSD. In contrast, AD patients without DAOSD showed a decrease in microbial diversity after the initiation of dupilumab, particularly a decrease in the abundance of Staphylococcus aureus. Conclusions: An increased neutrophilic infiltrate, associated with elevated levels of systemic pro-inflammatory cytokines (IL -1ß and TNF-a), and a unique microbial landscape on the ocular surface may be strongly associated to the pathogenesis of DAOSD.