Comparison of Efficacy of 0.05 % Cyclosporine Ophthalmic Emulsion and Artificial Tear

1. Comparison of Efficacy of 0.05% Cyclosporine Ophthalmic Emulsion and Artificial Tear in Meibomian Gland Dysfunction PinnitaPrabhasawat, MD., NattapornTesavibul, MD., WannareeMahawong, MD. Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Products in the study were supported by Allergan(Thailand), Ltd.

2. Diseases induce MGD via inflammatory pathway. • Anti-inflammatory agent might interrupt this vicious cycle. Purpose Infection Seborrhea Rosacea Medicamentosa Aging Androgen DHE Dry eye Infection Inflammation Inflammation • Meibomian glands secrete lipid to stabilize tear film. • Obstructive meibomian gland dystrophy (MGD) causes tear film instability Anti-inflammatory agent Inflammation Inflammation • To compare the efficacy of topical 0.05% cyclosporine with non-preservative • artificial tear in the treatment of meibomian gland dysfunction Methods • Prospective, double blind, randomized controlled trial • Department of ophthalmology,Siriraj hospital, Mahidol university,Bangkok, Thailand. 2007-2009 • Statistic Method : Intragroup: Paired t-test, Wilcoxon sign ranked test, Marginal homogeneity test • Intergroup: Independent t-test, Mann-Whitney U test, Chi-square test

3. Methods Inclusion criteria Exclusion criteria Meibomian gland dysfunction N = 40 pts, 40 eyes (Use right eye only) • Symptoms - irritation - photophobia - tearing • Signs - meibomian gland obstruction, inflammation - non-invasive tear break up time < 8 sec. • Age < 18 years old • Severe ocular surface abnormalities • Topical CSA < 1 year • Oral cyclosporine, anticholinergic within 2 months • Immunocompromise patients • Eye infection • Allergicto eye drop • Pregnancy or lactation • Contact lens wearer Masking Randomized Study (19 pts) Control (20 pts) Tear (0.5%CMC) bid 0.05%CSA bid Tear as needed Tear as needed Stop med due to burning 1 case Examine every 1 M Schirmer I test Schirmer I test 3 M 0 M 1 M 2 M

4. OSDI score • Lid inflammation • Meibomian gland secretion and expressibility • Conjunctival injection • Corneal staining • Non-invasive (tear scope) and fluorescein tear break up time Examinations Severity grading

5. Baseline : no significant among both groups No significant among both groups

6. Fluorescein tear break up time (2 m) Non-invasive tear break up time(Tear scopeR) # # # # # #       Fluorescein tear break-up time (sec.) Non-invasive tear break up time (sec.) CSA : Significant TBUT from baseline : Significant > Control P < 0.01 P < 0.01 p < 0.01 intragroup #p < 0.05 intergroup

7. Ocular Surface Disease Index (OSDI) Symptoms improve from baseline at 2, 3 M in both groups P < 0.01   + + OSDI score No different among both groups  , + p < 0.01 intragroup

8. Corneal staining Corneal Rose Bengal stain score Corneal Fluoresceinestain score Schirmer I test No significant from baseline No significant among groups Tear volume by SchirmerI test (mm)

9. Lid margin inflammation CSA : Significant improvement from baseline Conjunctival injection P < 0.05   + + Number of patients No different among both groups and from base line Bulbar injection + CSA : Significant improvement from baseline P < 0.05 +  + Tarsal injection  , + p < 0.05 intragroup Baseline Month 1 Month 2 Month 3

10. Meibomian gland No different among both groups. No improvement in both groups Secretion # CSA : Significantly improvement from baseline Expressibility P < 0.05 Baseline Month 1 Month 2 Month 3 p < 0.05 intragroup # p < 0.05 intergroup

11. Discussion • Cyclosporine (CSA) : T-cell modulator, decrease inflammatory cytokine eg. Interleukin-6¹ • Topical CSA in dry eye can improve²´³ - OSDI - Tear film stability, increase TBUT - Schirmer score - Goblet cell • Topical CSA in MGD can improve⁴ - Lid margin inflammation - Tarsal conjunctival injection - Fluorescein staining References Turner K, et al. Interleukin-6 levels in the conjunctival epithelium of patients with dry eye disease treated with cyclosporine ophthalmic emulsion. Cornea 2000;19:492-6. Sall K, et al. Two Multicenter, Randomizied Studies of the Efficacy and Safety of Cyclosporine Ophthalmic Emulsion in Moderate to Severe Dry Eye Disease. Ophthalmology 2000;107:631-9. Kunert KS, et al. Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. Arch Ophthalmol 2000;118:1489-96. Perry HD, et al. Efficacy of Commercially Available Topical Cycolsporine A 0.05% in the Treatment of Meibomian Gland Dysfunction. Cornea 2006;25:171-5.

12. Tear break up time • OSDI score • Lid margin inflammation • Tarsal conjunctival injection • MGD expressibility • CSA : significantly improve Conclusion from this study Topical 0.05%CSA could improve tear film stability in MGD patients with or without aqueous tear deficiency. • Control: significantly improve • OSDI score From baseline • Topical 0.05% CSA twice daily demonstrated superior effects over a non-preservative artificial tear in the treatment of meibomian gland dysfunction with tear film instability by increasing TBUT and improving MG function during the treatment