July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Conjunctivitis due to Dupilumab Treatment in Atopic Dermatitis: Clinical features and impact on gut microbiome
Author Affiliations & Notes
  • Robert John Barry
    Academic Unit of Ophthalmology, Institute of Inflammation and Ageing University of Birmingham, Birmingham, United Kingdom
    Inflammatory Eye Disease Service, Birmingham & Midland Eye Centre, Birmingham, United Kingdom
  • Liying Low
    Academic Unit of Ophthalmology, Institute of Inflammation and Ageing University of Birmingham, Birmingham, United Kingdom
    Inflammatory Eye Disease Service, Birmingham & Midland Eye Centre, Birmingham, United Kingdom
  • Mohith Shamdas
    Inflammatory Eye Disease Service, Birmingham & Midland Eye Centre, Birmingham, United Kingdom
  • Kusy Suleiman
    Academic Unit of Ophthalmology, Institute of Inflammation and Ageing University of Birmingham, Birmingham, United Kingdom
  • Mariam Murad
    Academic Unit of Ophthalmology, Institute of Inflammation and Ageing University of Birmingham, Birmingham, United Kingdom
  • Kevin Molloy
    Department of Dermatology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
  • Shireen Velangi
    Department of Dermatology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
  • Philip Ian Murray
    Academic Unit of Ophthalmology, Institute of Inflammation and Ageing University of Birmingham, Birmingham, United Kingdom
    Inflammatory Eye Disease Service, Birmingham & Midland Eye Centre, Birmingham, United Kingdom
  • Graham R Wallace
    Academic Unit of Ophthalmology, Institute of Inflammation and Ageing University of Birmingham, Birmingham, United Kingdom
    Inflammatory Eye Disease Service, Birmingham & Midland Eye Centre, Birmingham, United Kingdom
  • Saaeha Rauz
    Academic Unit of Ophthalmology, Institute of Inflammation and Ageing University of Birmingham, Birmingham, United Kingdom
    Inflammatory Eye Disease Service, Birmingham & Midland Eye Centre, Birmingham, United Kingdom
  • Footnotes
    Commercial Relationships   Robert Barry, None; Liying Low, None; Mohith Shamdas, None; Kusy Suleiman, None; Mariam Murad, None; Kevin Molloy, None; Shireen Velangi, None; Philip Murray, None; Graham Wallace, None; Saaeha Rauz, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6712. doi:
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      Robert John Barry, Liying Low, Mohith Shamdas, Kusy Suleiman, Mariam Murad, Kevin Molloy, Shireen Velangi, Philip Ian Murray, Graham R Wallace, Saaeha Rauz; Conjunctivitis due to Dupilumab Treatment in Atopic Dermatitis: Clinical features and impact on gut microbiome. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6712.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Dupilumab is a humanised Ig4 monoclonal antibody directed against IL-4Rα which is used for treatment of severe atopic dermatitis (AD). Conjunctivitis has been reported as a side effect of treatment, although the mechanism for this is unknown. Immunosuppressive therapy influences the gut microbiome, and gut microbiota modulates medication efficacy and toxicity. Understanding of the immunotherapy-microbiome network in patients with AD is lacking. We wished to delineate the impact of Dupilumab therapy on the gut microbiota in patients with AD, and correlate this with ocular findings.

Methods : Pre- and post-Dupilumab ocular assessment was completed on 6 patients. Faecal samples were obtained from 4 patients. Each patient provided 2 samples collected at different time points: 3 patients before and after treatment, and 1 patient not yet treated with Dupilumab as disease control. Samples were placed in 80% ethanol prior to DNA extraction and 16Sv4 rRNA sequencing.

Results : 5/6 patients had undiagnosed conjunctivitis at baseline assessment, with deterioration in all patients following commencement of Dupilumab. Post-treatment clinical phenotype was variable, ranging from mild non-specific conjunctivitis to a severe psuedomembranous conjunctivitis.

There were no significant changes in the α-diversity during treatment. β-diversity analysis through principal coordinate profile using Bray-Curtis distance revealed alterations in the gut microbiome in response to Dupilumab. Linear Discriminant Analysis Effect Size detected significant increase in the relative abundance of Collinsella, and decrease in Bacteroidales, Anaerotruncus, Oscillospira genera (LDA score> 2.0, a=0.01) following treatment with Dupilumab.

Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis showed that different metabolic pathways were enriched post-Dupilumab, in particular, functional categories associated with transporters, ABC transporters, DNA repair and recombination proteins, ribosome, purine metabolism, peptidases, pyrimidine metabolism and transcription factors pathways (False Detection Rate <0.001).

Conclusions : There is a high prevalence of undiagnosed conjunctivitis in patients with AD, with deterioration following Dupilumab treatment. We have shown a previously unreported modulation of the taxonomy and predicted functional profile of the gut microbiome after Dupilumab therapy.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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