Dupilumab-Associated Blepharoconjunctivitis: Clinical and Morphological Aspects

Abstract

Purpose: To describe the clinical and morphologic changes in the ocular surface microstructure of patients affected with moderate-to-severe Atopic Dermatitis (AD) before and during Dupilumab treatment.

Methods: This is a monocentric observational study on thirty-three patients affected with AD before and during Dupilumab treatment. All patients underwent a slit-lamp examination: complete clinical assessment, Break Up Time test (BUT), Schirmer test, and corneal staining grading (Oxford scale) were performed. Meibomian Glands Dysfunction (MGD) evaluation (Meibography), Non-invasive Keratograph Break Up Time test (NIKBUT), Tear Meniscus Height (TMH), and ocular Redness Score (RS) have been investigated using an OCULUS Keratograph. In vivo images of the conjunctiva, cornea, and meibomian glands have been acquired by confocal microscopy.

Results: Sixty-six eyes were included in our study: twenty-two eyes of 11 naive patients with indication for treatment but not in therapy yet (Group 1) and forty-four eyes of 22 patients treated with Dupilumab for at least 4 months (subcutaneous administration of 300 mg every 2 weeks) (Group 2). Either patients treated with Dupilumab or naive patients with moderate-to-severe forms of AD had a tear film instability (TBUT and NIKBUT reduced), whereas the quantity of the tear film was overall normal (Schirmer test and TMH), without statistically significant differences between the two groups. When Meibography was performed with the Keratograph, the difference between Group 1 and Group 2 was statistically significant in terms of Meiboscore (p = 0.0043 and p = 0.0242, respectively), as well as the difference in terms of mean RS. These results paired well with the confocal microscopy results in which we found a decrease in the goblet cell population in the conjunctival epithelium in the treated group (5.2 cells/mm), along with inflammatory cells that were more concentrated around the adenoid lumina of the meibomian glands.

Conclusions: In recent years, the use of Dupilumab has been increasing, but mild-to-severe conjunctivitis is a common side effect. Our major results demonstrate a loss of meibomian glands at the Keratograph examination: we can assume a reduced meibum secretion and an evaporative dry eye with MGD. We suggest that the inflammation of the ocular surface may involve not only the cornea and the conjunctiva, but also the meibomian glands, and Dupilumab may play a role. However, the frequency of clear conjunctivitis is not as common as reported in the literature.

Keywords: Dupilumab; atopic dermatitis; cornea; meibomian glands.

Figure 1

Color images of the eye in a case of Dupilumab-related conjunctivitis in Group 2: four quadrants of bulbar vessels are strongly dilated.

Figure 2

Spine-plot graphical representation of percentage of eyes for each grade of Jenvis Meiboscore of the upper (left) and lower (right) eyelids. The association between color and meiboscore grading is summarized in the legend.

Figure 3

Keratograph 5M Meiboscan acquisition of the upper eyelid with grade 2 (Jenvis): we can observe a dropout of meibomian glands, which appears shorter than normal.

Figure 4

Box plot graphical representation of the Redness Score (RS) for each group.

Figure 5

In vivo images of bulbar conjunctiva of a naive patient (left) and treated patient (right). Note the presence of intraepithelial goblet cells (arrow) on the left, while they are absent in the image on the right.

Figure 6

In vivo images of bulbar conjunctiva of a treated patient: several cell infiltrates are present, probably a sign of an inflammatory process involving the conjunctiva.