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

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

DECLARATION OF INTEREST

Dr. Michael Stern was an employee of Allergan Inc. at the time this study was conducted.

Additional information

Funding

This study was supported in part by William and Mary Greve Special Scholar Award from Research to Prevent Blindness, and a grant provided by Jerome L. Greene Sjögren’s Syndrome Center, Johns Hopkins University. The funding organizations had no role in the design or conduct of this research. Allergan, Inc. (Irvine, CA) provided the topical cyclosporine A treatment free of charge. The clinical part of the study was supported in part by a grant provided by Allergan Inc. to the Johns Hopkins University.