Immunopathological Features of Severe Chronic Atopic Keratoconjunctivitis and Effects of Topical Cyclosporine Treatment

Ocul Immunol Inflamm. 2019;27(7):1184-1193. doi: 10.1080/09273948.2018.1511811. Epub 2018 Sep 6.

Abstract

Purpose: To assess differential roles of inflammatory cells in pathophysiology of severe atopic keratoconjunctivitis (AKC) and evaluate immunomodulatory effects of topical cyclosporine A (CsA).

Methods: A total of 10 patients with severe, steroid-dependent/resistant chronic active AKC were treated using frequent topical CsA 0.05% as monotherapy for 2 months. Conjunctival biopsy specimens before and after treatment were examined using immunohistochemistry. A total of 10 healthy age-matched adults served as the control group.

Results: Baseline AKC samples revealed greater cluster of differentiation 4 (CD4), interferon gamma (IFNγ), human leukocyte antigen-D-related (HLA-DR) positive cell densities compared with healthy controls (P < 0.05), as well as interleukin (IL)-17 (P = 0.08). Topical CsA treatment induced a significant reduction in CD4 and IL-17 expressions (P < 0.05); post-treatment levels were same as normals (P > 0.05). Despite reduction after treatment (P = 0.06), HLA-DR expression remained higher than controls (P < 0.05).

Conclusions: AKC-related conjunctival inflammation appears to be mediated by delayed hypersensitivity. In this short-term trial, frequent topical CsA improved conjunctival inflammation.

Keywords: Atopic keratokonjunctivitis; immunopathology; topical cyclosporine.

MeSH terms

  • Administration, Topical
  • Adult
  • Biomarkers / metabolism
  • Biopsy
  • Chronic Disease
  • Conjunctiva / pathology*
  • Conjunctivitis, Allergic / diagnosis
  • Conjunctivitis, Allergic / drug therapy*
  • Conjunctivitis, Allergic / immunology
  • Cornea / pathology*
  • Cyclosporine / administration & dosage*
  • Female
  • Follow-Up Studies
  • HLA-DR Antigens / metabolism*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-33 / metabolism
  • Keratoconjunctivitis / diagnosis
  • Keratoconjunctivitis / drug therapy*
  • Keratoconjunctivitis / immunology
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Young Adult

Substances

  • Biomarkers
  • HLA-DR Antigens
  • Immunosuppressive Agents
  • Interleukin-17
  • Interleukin-33
  • Interferon-gamma
  • Cyclosporine