Ocular Microbiome in Dupilumab‐Induced Ocular Surface Disease

Patients with moderate–severe atopic dermatitis (AD) receive a great benefit from the use of dupilumab, a human IgG4 monoclonal antibody inhibiting IL-4/IL-13 signaling. However, randomized controlled trials and real-world studies showed, in 30%–50% of cases, the development of dupilumab-induced ocular surface disease (DIOSD), characterized by blepharitis, conjunctivitis, dry eye disease (DED), limbal inflammation, evolving into scarring, ectropion, and keratitis. Higher risk of DIOSD has been associated with AD severity, history of eye disease, high serum IgE levels, and eosinophilia. Metabolic differences between AD patients with and without DIOSD have also been reported. Similarities between DIOSD and DED were suggested because of the decreased number of conjunctival goblet cells and secreted mucins in both [1]. Recently, a shift from a mixed Th2/Th17 toward a Th1/Th17 cytokine profile was shown in AD patients developing DIOSD with a decreased richness of the ocular microbiome. In our real-world cohort of 32 dupilumab-treated AD patients, 17 (53%) had no adverse effects, and 15 (47%) were affected by DIOSD. We conducted a pilot study in 13 dupilumab-treated AD patients, 5 without ocular symptoms (No-DIOSD) and 8 with ocular side effects (DIOSD), and in 6 healthy subjects (CT) applying full-length 16S rRNA gene amplicon sequencing (Oxford Nanopore Technologies, ONT).