Topical cyclosporine in thyroid orbitopathy-related dry eye: clinical findings, conjunctival epithelial apoptosis, and MMP-9 expression.
OBJECTIVE
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.
Gürdal
Canan
C
Ankara Atatürk Training and Research Hospital, 2nd Ophthalmology Department, Ankara, Turkey. gurdalcm@yahoo.com
Genç
Ipek
I
Saraç
Ozge
O
Gönül
Ipek
I
Takmaz
Tamer
T
Can
Izzet
I
D000287:Administration, Topical; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D003228:Conjunctiva / Q000201:enzymology / Q000473:pathology*; D016572:Cyclosporine / Q000008:administration & dosage*; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology*; D005260:Female; D049970:Graves Ophthalmopathy / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D020287:In Situ Nick-End Labeling; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D016572:Cyclosporine; D020780:Matrix Metalloproteinase 9