Evaluation of Systane® Evaluation of Systane® versus Placebo in Corneal versus Placebo in Corneal

Epithelial Healing Following Epithelial Healing Following Photorefractive Keratectomy Photorefractive Keratectomy

(PRK)(PRK)Lt Col Charles D. Reilly Lt Col Charles D. Reilly

Major Vasudha A. PandayMajor Vasudha A. PandayWilford Hall Medical CenterWilford Hall Medical Center

Lackland Air Force BaseLackland Air Force BaseSan Antonio, TXSan Antonio, TX

Financial disclosure: Study medication gifted by Alcon

BackgroundBackground

Post-surgical dry eye is a common Post-surgical dry eye is a common problem facing all refractive problem facing all refractive surgeons/patientssurgeons/patients

Pre-existing dry eye can be exacerbated Pre-existing dry eye can be exacerbated following refractive surgeryfollowing refractive surgery

Variety of artificial tears often included Variety of artificial tears often included in in post-refractive surgery care post-refractive surgery care

Clinical evidence of artificial tear safety Clinical evidence of artificial tear safety neededneeded

PurposePurpose

To evaluate the amount of time needed to To evaluate the amount of time needed to achieve epithelial closure after PRK in achieve epithelial closure after PRK in patients using Systanepatients using Systane®® compared to compared to placebo (B&L Sensitive Eyes)placebo (B&L Sensitive Eyes)

Subjective patient comfort and dry eye Subjective patient comfort and dry eye symptoms in each eye also evaluated over symptoms in each eye also evaluated over 6 month study period6 month study period

Why Systane?Why Systane?

Unique advanced formulation Unique advanced formulation Polyethylene glycolPolyethylene glycol Propylene glycolPropylene glycol HP-guar (a gelling agent)HP-guar (a gelling agent) Borate ionsBorate ions

On contact with ocular surface, pH induced On contact with ocular surface, pH induced reaction strengthens bonds between borate reaction strengthens bonds between borate and HP-guar creating long-lasting polymer and HP-guar creating long-lasting polymer gel matrix gel matrix Serves as protective shield and retains Serves as protective shield and retains

lubricating demulcents on surfacelubricating demulcents on surface

Why Systane?Why Systane?

Adds volume to tear film; also promotes Adds volume to tear film; also promotes restructuring of tear filmrestructuring of tear film

Enhances stability of tear film and Enhances stability of tear film and significantly increases TFBUT relative to significantly increases TFBUT relative to other artificial tears on market other artificial tears on market 11

Higher lubricity (ability of fluid to reduce Higher lubricity (ability of fluid to reduce friction between two moving surfaces)friction between two moving surfaces) Decreases damage caused by friction between Decreases damage caused by friction between

lid and ocular surface during each blinklid and ocular surface during each blink

1Christensen MT et al. Evaluation of the effect on TFBUT extension by artificial tears in dry eye patients. Presented at 23rd biennial Cornea Research Conference: Boston, MA; 2003.

MethodsMethods

Inclusion criteria:Inclusion criteria: > 21 years of age> 21 years of age Typical candidates for Typical candidates for

bilateral PRK bilateral PRK Pre-operative Pre-operative

anisometropia < 2.00 anisometropia < 2.00 D D

Willing to abstain Willing to abstain from using from using medications known to medications known to cause dryness for at cause dryness for at least 2 weeks prior to least 2 weeks prior to PRK and through PRK and through duration of studyduration of study

Exclusion criteriaExclusion criteria Intraocular surgery Intraocular surgery

or active rosacea or active rosacea within 3 months prior within 3 months prior to studyto study

Previous ocular laser Previous ocular laser surgerysurgery

Evidence of active Evidence of active intraocular intraocular inflammation or inflammation or diseasedisease

Use of Restasis® Use of Restasis® within 30 days prior within 30 days prior to studyto study

MethodsMethods

68 patients,68 patients, IRB approved, IRB approved, randomized, randomized, double blinddouble blind study study

Alcohol-assisted epithelial removal, Alcohol-assisted epithelial removal, standard 8.5mm defectstandard 8.5mm defect

Post-operative administration of Systane Post-operative administration of Systane in one eye and placebo in the other:in one eye and placebo in the other: Right and left eyes randomized Right and left eyes randomized Day of surgery, study drops were used up to Day of surgery, study drops were used up to

every 30 minutes as needed; subsequently every 30 minutes as needed; subsequently used 2 times/day, 1-2 drops/doseused 2 times/day, 1-2 drops/dose

Patients required to document how much and Patients required to document how much and how often ‘rescue drops’ were usedhow often ‘rescue drops’ were used

MethodsMethods

Daily follow up for first 5 days (until closure of Daily follow up for first 5 days (until closure of epithelial defect)epithelial defect) Vertical and horizontal measurements of epithelial Vertical and horizontal measurements of epithelial

defect takendefect taken Subsequent visits on days 7, 14, 30, 60, 90 Subsequent visits on days 7, 14, 30, 60, 90

and 180and 180 On each visit patients asked:On each visit patients asked:

Rate pain on scale from 0-10 with 0 being no pain, Rate pain on scale from 0-10 with 0 being no pain, and 10 being excruciating painand 10 being excruciating pain

Comfort and relief of dry eye symptoms in each eyeComfort and relief of dry eye symptoms in each eye Compliance with drops, issues with contact lensCompliance with drops, issues with contact lens

Mean Epithelial DefectMean Epithelial Defect

TimeTimePlacebo (n-68)Placebo (n-68) Systane (n-68)Systane (n-68)

P – P – ValueValue11Mean Defect Mean Defect

AreaArea22 ( (++ SD) SD) RangeRange22 Mean Defect Mean Defect AreaArea22 ( (++ SD) SD) RangeRange22

Day 1Day 1 39.9 (9)39.9 (9) 16.00 – 16.00 – 64.0064.00 40.1 (10)40.1 (10) 13.00 – 72.0013.00 – 72.00 0.80.8

Day 2Day 2 11.7 (6.7)11.7 (6.7) 0.00 – 25.000.00 – 25.00 11.1 (6.1)11.1 (6.1) 0.00 – 25.000.00 – 25.00 0.20.2

Day 3Day 3 0.6 (2.3)0.6 (2.3) 0.00 – 18.000.00 – 18.00 0.4 (2.2)0.4 (2.2) 0.00 – 18.000.00 – 18.00 0.10.1

Day 4Day 4 0.059 (0.4)0.059 (0.4) 0.00 – 4.000.00 – 4.00 0.04 (0.4)0.04 (0.4) 0.00 – 3.000.00 – 3.00 0.30.3

1 p-values of paired t-test for between treatment comparison using paired data2 Mean epithelial defect size calculated from the recorded vertical and horizontal dimensions of the defect at each observation and presented as square mm.

Day 1 Day 2Day 3

Day 4

0.0

10.0

20.0

30.0

40.0

50.0

Placebo

Systane

Mean Epithelial DefectMean Epithelial Defect

Post Operative Time

Mea

n S

ize*

(mm

2 )

* Mean epithelial defect size calculated from recorded vertical and horizontal dimensions of the defect at each observation and presented as square mm.

4 Weeks 12 Weeks 24 Weeks

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Placebo

Systane

Post Operative DiscomfortPost Operative Discomfort

Post Operative Time

Co

mfo

rt S

core

(0-

4)(L

ow

er i

s B

ette

r)

Post Operative Dry Eye Post Operative Dry Eye SymptomsSymptoms

4 Weeks12 Weeks

24 Weeks

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Placebo

Systane

Time Post Operative

Dry

Eye

Sym

pto

ms

(0-4

)(L

ow

er i

s B

ette

r)

ConclusionsConclusions No adverse impact of Systane on post-No adverse impact of Systane on post-

PRK epithelial healing when compared to PRK epithelial healing when compared to placeboplacebo Demonstrates safety of SystaneDemonstrates safety of Systane

No increase in post-operative ocular No increase in post-operative ocular discomfort associated with Systane discomfort associated with Systane compared to placebocompared to placebo

Very low level of post-operative dry eye Very low level of post-operative dry eye symptoms with Systanesymptoms with Systane