Topical Cyclosporine in Thyroid Orbitopathy-Related Dry Eye: Clinical Findings, Conjunctival Epithelial Apoptosis, and MMP-9 Expression

Abstract

Objectives: To evaluate the effects of topical cyclosporine A (CsA) 0.05% (Restasis) on the signs and symptoms of dry eye, on apoptosis, and on MMP-9 expression in conjunctiva epithelial cells in thyroid orbitopathy (TO)-related dry eye patients.Methods: Prospective, clinical study. Twenty-four eyes of 12 consecutive TO patients with dry eye findings instilled CsA twice daily for 2 months. Ocular surface disease index, Schirmer tear test, tear breakup time (TBUT), conjunctival apoptosis index, and conjunctival MMP-9 expression were evaluated before and after 2 months treatment. Conjunctival biopsies were harvested from all eyes at baseline and after 2 months treatment. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) assay. MMP-9 expression was determined by immunohistochemistry.Results: After 2 months of topical CsA treatment, the mean OSDI score was significantly decreased from 58.08 ± 6.28 to 36.41 ± 11.75 (P = 0.001). At baseline, the mean Schirmer tear test score was 8.92 ± 5.52 mm. It was increased to 11.25 ± 4.71 mm after treatment (P > 0.05). The mean TBUT increased significantly from 3.92 ± 2.18 sec to 9.16 ± 3.34 sec (P = 0.001). The mean percentage of apoptosis index at baseline was 72.10 ± 35.82%. This was significantly decreased to 53.29 ± 34.46% after treatment (P = 0.008). The mean percentage of MMP-9 expression of the conjunctival epithelial cells was significantly decreased from 48.12 ± 28.58% to 26.66 ± 25.13% following treatment (P = 0.005).Conclusions: Topical CsA treatment appears to improve the signs and symptoms of dry eye and inhibits apoptosis and MMP-9 expression in conjunctival epithelial cells in TO-related dry eye patients after 2 months of treatment.