To compare conjunctival goblet cell numbers as well as epithelial turnover in patients with non-Sjö gren syndrome-associated keratoconjunctivitis sicca (NSS-KCS) and those with SS-KCS before and after 6 months of treatment with topical cyclosporine A (CsA) ophthalmic emulsion.Methods: Conjunctival biopsy specimens from 16 patients with NSS-KCS and 12 with SS-KCS were obtained at baseline and after 6 months' therapy with CsA or vehicle alone. Conjunctival biopsy specimens were also obtained from 11 normal subjects. Periodic acid-Schiff staining determined the number of goblet cells present. Immunofluorescence microscopy for Ki-67 localization was used to evaluate the number of actively cycling cells.Results: Periodic acid-Schiff staining showed fewer goblet cells at baseline in both dry eye populations when compared with normal subjects (PϽ.001). After 6 months of CsA treatment, conjunctival biopsy specimens of both NSS-KCS and SS-KCS groups revealed an increase in goblet cells compared with baseline (PϽ.05). More Ki-67positive cells were observed in NSS-KCS conjunctiva at baseline than in normal conjunctiva (PϽ.05) whereas numbers of these cells in SS-KCS conjunctiva were similar to normal at baseline. After 6 months of CsA treatment, conjunctival biopsy specimens of NSS-KCS revealed a decrease in Ki-67-labeled cells compared with baseline (PϽ.001). In contrast, no substantial change was observed for CsA treatment in patients with SS-KCS.Conclusions: Treatment of dry eye syndrome for 6 months with topical CsA resulted in an increase in goblet cell numbers in patients with NSS-KCS and SS-KCS and a decrease in epithelial turnover in those with NSS-KCS. Reducing ocular surface inflammation might have an effect on the proliferative activity of the epithelium.
To study the effect of topical cyclosporine on lymphocyte activation within the conjunctiva of patients with moderate to severe dry eye syndrome (Sjö gren and non-Sjö gren).Methods: Biopsy specimens were obtained at baseline and after 6 months of cyclosporine treatment from eyes of 32 patients with moderate to severe dry eye syndrome; 19 were cyclosporine treated (0.05% cyclosporine, n = 13; 0.1% cyclosporine, n = 6) and 13 were vehicle treated. Within this group there were 12 with Sjö gren syndrome and 20 with non-Sjö gren syndrome. Biopsy tissue was analyzed using immunohistochemical localization of binding of monoclonal antibodies to lymphocytic markers CD3, CD4, and CD8 as well as lymphocyte activation markers CD11a and HLA-DR.Results: In cyclosporine-treated eyes, biopsy results of conjunctivae showed decreases in the number of cells posi-tive for CD3, CD4, and CD8, while in vehicle-treated eyes, results showed increases in these markers, although these differences were not statistically significant. Following treatment with 0.05% cyclosporine, there was a significant decrease in the number of cells expressing the lymphocyte activation markers CD11a (PϽ.05) and HLA-DR (PϽ.05), indicating less activation of lymphocytes as compared with vehicle treatment. Within the Sjö gren patient subgroup, those treated with 0.05% cyclosporine also showed a significant decrease in the number of cells positive for CD11a (PϽ.001) as well as CD3 (PϽ.03), indicating a reduction in number of activated lymphocytes.
Conclusion:Treatment of dry eye syndrome with topical cyclosporine significantly reduced the numbers of activated lymphocytes within the conjunctiva.
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