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

2. Change of lipid composition
Diseases induce MGD via inflammatory pathway.
Anti-inflammatory agent might interrupt this vicious cycle.
Infection
MGD
Obstruction
Tear film instability
Change of lipid composition
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
Purpose
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
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. Meibomian gland dysfunction
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
Allergic to eye drop
Pregnancy or lactation
Contact lens wearer
Masking
Randomized
Study (19 pts)
Control (20 pts)
0.05%CSA bid
Tear (0.5%CMC) bid
Tear as needed
Tear as needed
Stop med due to burning
1 case
Examine every 1 M
Schirmer I test
Schirmer I test
0 M
1 M
2 M
3 M

4. < 1/3-total occlusion
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
score 1 2 3 4
Lid inflammation No
Mild
Moderate
Severe -
Conjunctival injection
Meibomian gland secretion
Clear fluid
Cloudy fluid
Cloudy particulate
Toothpaste-like
No secretion
Meibomian gland expressibility
Excellent
>2/3
1/3-2/3 express
< 1/3-total occlusion
Corneal staining
Fluorescein
( 0-15 )
Rose Bengal

5. Baseline : no significant among both groups
Signs & Symptoms
CSA ( N=19 )
Control ( N=20 )
Female: Male
16:3
15:5
Lid inflammation
- no inflammation
- mild inflammation
- moderate inflammation 5 10 4 3 14
Meibomian gland secretion
- clear fluid
- cloudy fluid
- cloudy particulate fluid
- inspissated, toothpaste-like
- no secretion 8 2 1 9
Expressibility of meibomian gland
- 2/3 expressibility
- 1/3-2/3 expressibility
- <1/3-total occlude 12 13
Bulbar conjunctival injection
- no injection
- mild injection
- moderate injection 16 15
Tarsal conjunctival injection
- severe injection 6
Corneal fluoresceine stain score
1.74
2.75
Corneal Rose Bengal stain score
0.21
1.0
Non-invasive tear break-up time (TBUT) (sec.)
2.23
2.24
Fluoresceine tear break-up time (sec.)
2.32
2.05
Schirmer’s I test (mm.)
19.26
19.20
OSDI score
42.65
37.25
No significant among both groups

6. Non-invasive tear break up time (Tear scopeR)
Fluorescein tear break up time
(2 m)  #  #  #  #  #  #
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) P < 0.01
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 Rose Bengal stain score Corneal Fluoresceine stain score
Corneal staining
Corneal Rose Bengal stain score
Corneal Fluoresceine stain score
Schirmer I test
No significant from baseline
No significant among groups
Schirmer I test (mm)
Tear volume by

9. Conjunctival injection
Lid margin inflammation
CSA : Significant improvement from baseline
P < 0.05  +  +
Number of patients
Conjunctival injection
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 Secretion Expressibility P < 0.05 Baseline Month 1
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:
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. Conclusion from this study
Topical 0.05%CSA could improve tear film stability in MGD patients with or without aqueous tear deficiency.
From baseline
CSA : significantly improve
Control: significantly improve
Tear break up time
OSDI score
Lid margin inflammation
Tarsal conjunctival injection
MGD expressibility
OSDI score
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