Effects of sequential artificial tear and cyclosporine emulsion therapy on conjunctival goblet cell density and transforming growth factor-beta2 production.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Pflugfelder
Stephen C
SC
Ocular Surface Center, Baylor College of Medicine, Houston, TX, USA. stevenp@bcm.tmc.edu
De Paiva
Cintia S
CS
Villarreal
Arturo L
AL
Stern
Michael E
ME
D000328:Adult; D000368:Aged; D002452:Cell Count; D002908:Chronic Disease; D003228:Conjunctiva / Q000187:drug effects* / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage*; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004655:Emulsions; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D020397:Goblet Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism; D009883:Ophthalmic Solutions / Q000008:administration & dosage*; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis*
D004655:Emulsions; D007166:Immunosuppressive Agents; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D009883:Ophthalmic Solutions; D053781:Transforming Growth Factor beta2; D016572:Cyclosporine