Dupilumab-Associated Ocular Surface Disease: An In Vivo Confocal Microscopy Study

Dupilumab, trade name Dupixent (Regeneron & Sanofi, USA), is a monoclonal antibody that acts as an interleukin-4 (IL4) receptor antagonist, blocking the signaling of IL4 and IL13, and consequently the expression of Th2 cytokines which are primarily involved in allergic disorders. 

The experience about its use into clinical practice is therefore recent.

However, since its introduction, it became clear that Dupilumab is related to many ocular side effects, ranging from mild ocular surface disorders to severe inflammation requiring discontinuation of the therapy.

The purpose of this paper is to describe the alterations of ocular surface microstructure of these patients using noninvasive imaging, and the implications into clinical practice.

Eye Clinic, AOU Careggi, University of Florence, Florence, Italy

This is a monocentric observational study on 40 eyes of 20 patients affected by atopic dermatitis and treated with Dupilumab for at least 3 months (subcutaneous administration at 300 mg every 2 weeks). All patients underwent a complete clinical assessment, break up time test (BUT) and Schirmer test. In vivo images of the conjunctiva, cornea and meibomian glands have been acquired by confocal microscopy (Heidelberg Retina Tomograph II / Rostock Cornea Module - Heidelberg Engineering GmbH, Heidelberg, Germany). Meibomian glands, noninvasive break up time test and tear meniscus height have been investigated using OCULUS Keratograph (Oculus GmbH, Wetzlar, Germany).

The study included twenty patients with ages between 18 and 35 years. Three patients (15%) presented with symptoms and signs of meibomian glands dysfunction, conjunctival hyperemia, and superficial punctate keratopathy. 32 eyes (80%) had tear film instability: TBUT was < 10 sec. A Schirmer I test < 10 mm occurred in 24 eyes (60%), with a mean of 7 mm. At the in vivo confocal microscopy evaluation, the eyes of symptomatic patients showed a significantly higher density of conjunctival and anterior corneal stroma inflammatory infiltrates, but a decrease of the goblet cell population in the conjunctival epithelium. Meibography of both eyelids showed severely distorted anatomy. The mean was 6.1 sec for non- invasive keratograph TBUT.

The use of Dupilumab is raising, but a mild to severe conjunctivitis is a common side effect. The exact pathogenesis is still uncertain, but it seems clear that it’s a new entity. It has been previously reported the role of IL-13 on globet cell proliferation, differentiation, and expression of mucin and immunomodulatory genes. Our results confirm the primary involvement of the meibomian glands and globet cell population in the Dupilumab-induced conjunctivitis.