Effects of Sequential Artificial Tear and Cyclosporine Emulsion Therapy on Conjunctival Goblet Cell Density and Transforming Growth Factor-β2 Production

Abstract

To evaluate the effects of sequential treatment with artificial tears and cyclosporine emulsion on conjunctival goblet cell density and production of transforming growth factor (TGF)-beta2 in patients with dry eye disease. Patients with dry eye disease (N = 6) defined by an Ocular Surface Disease Index symptom score >or=25, Schirmer test 1 <10 mm, and corneal fluorescein and conjunctival lissamine green staining scores >or=3 were treated with artificial tears (Refresh Plus; Allergan, Irvine, CA) 4 times a day for 4 weeks, followed by 0.05% cyclosporine emulsion (Restasis; Allergan) twice a day for 12 weeks. Impression cytology was performed on the bulbar conjunctiva of both eyes at baseline, after artificial tear therapy, and after 6 and 12 weeks of cyclosporine therapy. Goblet cells were counted in 5 representative microscopic fields per membrane in those taken from the temporal and inferior bulbar conjunctiva of the worse eye, and membranes taken from the fellow eye were immunostained for TGF-beta2. There were no differences in mean goblet cell density between baseline and 4 weeks of artificial tears in the temporal and inferior bulbar specimens. After 6 weeks of cyclosporine emulsion, goblet cell density was significantly greater than baseline and artificial tears in the inferior bulbar conjunctiva (P < 0.01). After 12 weeks of cyclosporine emulsion, goblet cell density was significantly greater than baseline and artificial tears in both temporal and inferior bulbar sites (P < 0.01). The number of TGF-beta2-positive goblet cells was also noted to increase after 6 and 12 weeks of cyclosporine therapy (P < 0.001). Cyclosporine emulsion, but not artificial tears, increases goblet cell density and production of the immunoregulatory factor TGF-beta2 in the bulbar conjunctiva in patients with dry eye.