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.

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.

2007-2009

SeborrheaRosacea

Medicamentosa Aging

AndrogenDHE

Dry eyeInfection

MGD

Obstruction

Tear film instability

Change of lipid

composition

Inflammation

Inflammation

Inflam

mationInflammation

Infection

• Diseases induce MGD via inflammatory pathway. • Anti-inflammatory agent might interrupt this vicious

cycle.

• Meibomian glands secrete lipid to stabilize tear film.

• Obstructive meibomian gland dystrophy (MGD) causes tear film instability

Statistic Method : Intragroup: Paired t-test, Wilcoxon sign ranked test, Marginal homogeneity test Intergroup: Independent t-test, Mann-Whitney U test, Chi-square test

Anti-inflammatory agent

MethodsMeibomian gland dysfunction

N = 40 pts, 40 eyes (Use right eye only)

Control (20 pts)Study (19 pts)

Tear as neededTear as needed

0.05%CSA bid Tear (0.5%CMC) bid

MaskingRandomized

0 M 1 M 3 M2 M

Schirmer I test Schirmer I test

Inclusion criteria

• Symptoms- irritation- photophobia- tearing

• Signs- meibomian gland obstruction, inflammation- non-invasive tear break up time < 8 sec.

Exclusion criteria

• 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 wearerStop med due to burning

1 case

Examine every 1 M

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

time

score 0 1 2 3 4

• Lid inflammation

No Mild Moderate Severe -

• Conjunctival injection

No Mild Moderate Severe -

• 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( 0-15 )

Severity grading

Signs & Symptoms CSA ( N=19 ) Control ( N=20 )

• Female: Male 16:3 15:5

• Lid inflammation - no inflammation - mild inflammation - moderate inflammation

5104

3143

• Meibomian gland secretion - clear fluid - cloudy fluid - cloudy particulate fluid - inspissated, toothpaste-like - no secretion

38521

19811

• Expressibility of meibomian gland - 2/3 expressibility - 1/3-2/3 expressibility - <1/3-total occlude

4123

3134

• Bulbar conjunctival injection - no injection - mild injection - moderate injection

1621

1550

• Tarsal conjunctival injection - no injection - mild injection - moderate injection - severe injection

01540

11360

• 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

Baseline : no significant among both groups

No significant among both groups

Baseline Month 1 Month 2 Month 30

0.5

1

1.5

2

2.5

3

3.5

4

CSA Control

Baseline Month 1 Month 2 Month 30

0.5

1

1.5

2

2.5

3

3.5

4

4.5

CSA Control

Non

-inva

sive

tear

bre

ak u

p tim

e (s

ec.)

P < 0.01 P < 0.01

Non-invasive tear break up time(Tear scopeR)

Fluorescein tear break up time(2 m)

#

#

Fluo

resc

ein

tear

bre

ak-u

p tim

e (s

ec.)

#

#

#

#

CSA : Significant TBUTfrom baseline

: Significant > Control p < 0.01 intragroup# p < 0.05 intergroup

Baseline Month 1 Month 2 Month 30

5

10

15

20

25

30

35

40

45

CSAControl

OSD

I sco

reOcular Surface Disease Index (OSDI)

Symptoms improve from baseline at 2, 3 M in both groups

P < 0.01 +

+

No different among both groups , + p < 0.01 intragroup

Corneal staining

Baseline Month 1 Month 2 Month 30

0.5

1

1.5

2

2.5

3

CSA Control

Cor

neal

Flu

ores

cein

e st

ain

scor

e

Baseline Month 1 Month 2 Month 30

0.2

0.4

0.6

0.8

1

1.2

CSA Control

Cor

neal

Ros

e B

enga

l sta

in s

core

Baseline Month 317

18

19

20

21

22

23

CSA

Control

Schirmer I test

Tear

vol

ume

bySc

hirm

er I

test

(mm

)

No significant from baseline

No significant among groups

CSA Control CSA Control CSA Control CSA Control02468

10121416

no inject

mild inject

mod.inject

severe inject

Conjunctival injection

CSA Control CSA Control CSA Control CSA Control05

1015

20

no inject

mild inject

mod.inject

Baseline Month 2 Month 3

Bul

bar

inje

ctio

nTa

rsal

in

ject

ion

Month 1

No different among both groups and from base line

CSA : Significant improvement from baselineP < 0.05

+

+

+

CSA Control CSA Control CSA Control CSA Control0

5

10

15no inflam

mild inflam

mod.inflam

severe inflam

Lid margin inflammation CSA : Significant improvement from baseline

+ +

P < 0.05

Num

ber o

f pat

ient

s

, + p < 0.05 intragroup

CSA Control CSA Control CSA Control CSA Control02468

10121416

well express

2/3 express

1/3-2/3 express

<1/3-total occlude

CSA Control CSA Control CSA Control CSA Control02468

101214

clear fluid

cloudy fluid

cloudy particulate fluid

toothpaste-like

no secretion

No different among both groups. No improvement in both groups

CSA : Significantly improvement from baseline

Meibomian glandS

ecre

tion

Exp

ress

ibili

ty

Baseline Month 1 Month 2 Month 3

P < 0.05

#

p < 0.05 intragroup# p < 0.05 intergroup

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

1. 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.

2. 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.

3. 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.

4. 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.

• Tear break up time• OSDI score• Lid margin inflammation• Tarsal conjunctival injection• MGD expressibility

Conclusion from this study

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

Topical 0.05%CSA could improve tear film stability in MGD patients with or without aqueous tear deficiency.

• OSDI score

Control: significantly improveCSA : significantly improve