An immunohistochemical study of topical cyclosporine in vernal keratoconjunctivitis

PURPOSE: To determine the immunomodulating effects of topical cyclosporine on the immune cells in the conjunctival biopsy specimens obtained from patients with active vernal keratoconjunctivitis. METHODS: We studied six patients who had severe active vernal keratoconjunctivitis. Each patient was given topical cyclosporine 2% eyedrops four times daily. A 2 x 2-mm limbal conjunctival biopsy specimen was obtained from each patient before and three weeks after treatment. Using a panel of monoclonal and polyclonal antibodies and immunohistochemical techniques, we analyzed the conjunctival immune cells before and after cyclosporine treatment. RESULTS: Three weeks after topical cyclosporine treatment, there was marked clinical improvement and a statistically significant reduction in the number of epithelial and stromal class II MHC⁺ cells, UCHL₁⁺ T cells, and stromal IgA⁺ and IgG⁺ plasma cells. The mean number of cells before and after therapy, respectively, were: class II MHC⁺ (epithelium), 31.5 ± 13.1 and 8.3 ± 5.6 (P = .031); class II MHC⁺ (stroma), 77.0 ± 28.7 and 24.7 ± 17.5 (P = .031); UCHL₁⁺ T cells (epithelium), 24.5 ± 14.1 and 4.2 ± 2.9 (P = .031); UCHL₁⁺ T cells (stroma), 78.7 ± 31.1 and 44.5 ± 27.5 (P = .031); IgA⁺ plasma cells, 66.7 ± 32.1 and 22.2 ± 7.8 (P = .031); and IgG⁺ plasma cells, 37.3 ± 30.0 and 9.0 ± 6.4 (P = .031). There was a statistically insignificant decrease in the epithelial class II MHC⁺ dendritic Langerhans cells, epithelial and stromal KP₁⁺ macrophages, stromal OPD₄⁺ helper/inducer T cells, and stromal L26⁺ B cells. The numbers of IgE⁺ plasma cells and mast cells were unaltered. CONCLUSION: The clinical improvement in vernal keratoconjunctivitis after topical cyclosporine therapy may result from its immunomodulating effect on the components of cell-mediated and humoral immune responses. In contrast, the drug has no immunomodulatory effect on mast cells and IgE-mediated allergic response.