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Dupilumab-induced ocular surface disease (DIOSD) in patients with atopic dermatitis: clinical presentation, risk factors for development and outcomes of treatment with tacrolimus ointment
  1. Yoav Nahum1,2,
  2. Michael Mimouni3,4,
  3. Eitan Livny1,2,
  4. Irit Bahar1,2,
  5. Emmilia Hodak2,5,
  6. Yael Anne Leshem2,5
  1. 1 Ophthalmology, Rabin Medical Center, Petah Tikva, Israel
  2. 2 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  3. 3 Ophthalmology, Rambam Health Care Campus, Haifa, Israel
  4. 4 Technion Israel Institute of Technology Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
  5. 5 Dermatology, Rabin Medical Center, Petah Tikva, Israel
  1. Correspondence to Dr Yoav Nahum, Ophthalmology, Rabin Medical Center, Petah Tikva, Israel; yoav.nahum{at}


Aim To identify risk factors for the development of dupilumab-induced ocular surface disease (DIOSD) in adult patients with atopic dermatitis (AD) and describe outcomes of treatment.

Methods A retrospective institutional cohort study performed at the Rabin Medical Center, Petach Tikva, Israel. Adult patients with AD who received dupilumab from March 2018 to June 2019 were included. Demographics, AD severity scores, blood IgE levels, previous atopic keratoconjunctivitis (AKC), dermatological response to dupilumab, ophthalmological evaluation and treatment were noted. Univariate and multivariate analyses were used to identify risk factors for DIOSD.

Results Sixteen of 37 patients who were included in the study (43%) had new or exacerbated symptoms of ocular surface disease starting at 2 weeks following the first treatment. Three patients reported transient dry eye sensation which lasted 2 weeks; nine patients reported chronic dry eye sensation, and four patients (25%) had marked blepharoconjunctivitis. The presence of severe AD was the strongest predictor of DIOSD. Not a single patient with moderate AD had DIOSD. In multivariate analysis, prior AKC was a risk factor for DIOSD (R2=15.78, OR=23.28, p=0.005) while a family history of atopy was protective of DIOSD (R2=6.22, OR=0.13, p=0.05). All four patients with blepharoconjunctivitis had resolution of signs, and symptoms within days of starting periocular 0.03%–0.1% tacrolimus ointment.

Conclusions DIOSD is common in patients with AD receiving dupilumab. While most cases are mild, some patients can develop blepharoconjunctivitis which responds well to tacrolimus ointment. AD severity, and previous AKC are risk factors for DIOSD.

  • Ocular surface
  • Inflammation
  • Conjunctiva
  • Eye Lids

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  • Contributors YN, MM, EL, IB, EH and YAL: design and conduct of the study, collection, management, analysis and interpretation of the data. YN, MM, EL, IB, EH and YAL: statistics, preparation of the manuscript, management.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests EH and YAL were scientific advisors and speakers for Sanofi/Regeneron. Other authors declare no competing interests.

  • Patient consent for publication Obtained.

  • Ethics approval The study followed the tenets of the 1964 Declaration of Helsinki and was approved by the local ethics committee of Rabin Medical Center.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.