[Flow cytometry in impression cytology during keratoconjunctivitis sicca: effects of topical cyclosporin A on HLA DR expression].
OBJECTIVE
Immune-based inflammation has been observed as a common mechanism of keratoconjunctivitis sicca (KCS). In KCS-affected eyes, up-regulated expression of HLA DR by conjunctival epithelial cells has been demonstrated in impression cytology (IC) specimens using a technique of flow cytometry. The purpose of this study was to monitor the effects of topical cyclosporin A on the expression of this marker over a 12-month period of treatment.


METHODS
Patients with moderate-to-severe KCS included in a large European multicenter clinical trial (Cyclosporin Dry Eye Study, Allergan, Irvine, CA) underwent collection of IC specimens at baseline, month 3, month 6, and month 12. They randomly received 0.05% or 0.1% cyclosporin A or vehicle. Patients randomized to receive vehicle received 0.1% cyclosporin A from month 6 onwards. Specimens were processed and analyzed in a masked manner by flow cytometry, using monoclonal antibodies directed to HLA DR.


RESULTS
We included 169 patients in this study. HLA DR expression, both in percentage of positive cells and level of expression, was highly significantly reduced after 0.05% and 0.1% cyclosporin A treatment at months 3, 6, and 12 compared with baseline values, whereas vehicle did not induce any change in HLA DR expression over time. The 0.05% and 0.1% cyclosporin emulsions were significantly more effective than the vehicle in reducing HLA DR at months 3 and 6 (0.05%) and at month 6 (0.1%).


CONCLUSIONS
Topical cyclosporin A strikingly reduced HLA DR, whereas the vehicle, used as a control tear substitute, had almost no effect. This study confirms that cyclosporin A may be effective in reducing conjunctival inflammation in moderate-to-severe KCS and is consistent with clinical results in this indication.
Galatoire
O
O
Service d'Ophtalmologie 3, Hôpital des Quinze-Vingts, 28, rue de Charenton, 75012 Paris.
Baudouin
C
C
Pisella
P J
PJ
Brignole
F
F
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004655:Emulsions; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007638:Keratoconjunctivitis Sicca / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles; D011446:Prospective Studies; D012859:Sjogren's Syndrome / Q000150:complications / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
D004655:Emulsions; D006684:HLA-DR Antigens; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles; D016572:Cyclosporine