Evaluation of Systane® versus Placebo in Corneal Epithelial Healing Following Photorefractive Keratectomy (PRK) Lt Col Charles D. Reilly Major Vasudha A. Panday Wilford Hall Medical Center Lackland Air Force Base San Antonio, TX Financial disclosure: Study medication gifted by Alcon

Background Post-surgical dry eye is a common problem facing all refractive surgeons/patients Post-surgical dry eye is a common problem facing all refractive surgeons/patients Pre-existing dry eye can be exacerbated following refractive surgery Pre-existing dry eye can be exacerbated following refractive surgery Variety of artificial tears often included in post- refractive surgery care Variety of artificial tears often included in post- refractive surgery care Clinical evidence of artificial tear safety needed Clinical evidence of artificial tear safety needed

Purpose To evaluate the amount of time needed to achieve epithelial closure after PRK in patients using Systane ® compared to placebo (B&L Sensitive Eyes) To evaluate the amount of time needed to achieve epithelial closure after PRK in patients using Systane ® compared to placebo (B&L Sensitive Eyes) Subjective patient comfort and dry eye symptoms in each eye also evaluated over 6 month study period Subjective patient comfort and dry eye symptoms in each eye also evaluated over 6 month study period

Why Systane? Unique advanced formulation Unique advanced formulation Polyethylene glycol Polyethylene glycol Propylene glycol Propylene glycol HP-guar (a gelling agent) HP-guar (a gelling agent) Borate ions Borate ions On contact with ocular surface, pH induced reaction strengthens bonds between borate and HP-guar creating long-lasting polymer gel matrix On contact with ocular surface, pH induced reaction strengthens bonds between borate and HP-guar creating long-lasting polymer gel matrix Serves as protective shield and retains lubricating demulcents on surface Serves as protective shield and retains lubricating demulcents on surface

Why Systane? Adds volume to tear film; also promotes restructuring of tear film Adds volume to tear film; also promotes restructuring of tear film Enhances stability of tear film and significantly increases TFBUT relative to other artificial tears on market 1 Enhances stability of tear film and significantly increases TFBUT relative to other artificial tears on market 1 Higher lubricity (ability of fluid to reduce friction between two moving surfaces) Higher lubricity (ability of fluid to reduce friction between two moving surfaces) Decreases damage caused by friction between lid and ocular surface during each blink Decreases damage caused by friction between lid and ocular surface during each blink 1 Christensen MT et al. Evaluation of the effect on TFBUT extension by artificial tears in dry eye patients. Presented at 23 rd biennial Cornea Research Conference: Boston, MA; 2003.

Methods Inclusion criteria: Inclusion criteria: > 21 years of age > 21 years of age Typical candidates for bilateral PRK Typical candidates for bilateral PRK Pre-operative anisometropia < 2.00 D Pre-operative anisometropia < 2.00 D Willing to abstain from using medications known to cause dryness for at least 2 weeks prior to PRK and through duration of study Willing to abstain from using medications known to cause dryness for at least 2 weeks prior to PRK and through duration of study Exclusion criteria Intraocular surgery or active rosacea within 3 months prior to study Previous ocular laser surgery Evidence of active intraocular inflammation or disease Use of Restasis® within 30 days prior to study

Methods 68 patients, IRB approved, randomized, double blind study 68 patients, IRB approved, randomized, double blind study Alcohol-assisted epithelial removal, standard 8.5mm defect Alcohol-assisted epithelial removal, standard 8.5mm defect Post-operative administration of Systane in one eye and placebo in the other: Post-operative administration of Systane 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 every 30 minutes as needed; subsequently used 2 times/day, 1-2 drops/dose Day of surgery, study drops were used up to every 30 minutes as needed; subsequently used 2 times/day, 1-2 drops/dose Patients required to document how much and how often ‘rescue drops’ were used Patients required to document how much and how often ‘rescue drops’ were used

Methods Daily follow up for first 5 days (until closure of epithelial defect) Daily follow up for first 5 days (until closure of epithelial defect) Vertical and horizontal measurements of epithelial defect taken Vertical and horizontal measurements of epithelial defect taken Subsequent visits on days 7, 14, 30, 60, 90 and 180 Subsequent visits on days 7, 14, 30, 60, 90 and 180 On each visit patients asked: On each visit patients asked: Rate pain on scale from 0-10 with 0 being no pain, and 10 being excruciating pain Rate pain on scale from 0-10 with 0 being no pain, and 10 being excruciating pain Comfort and relief of dry eye symptoms in each eye Comfort and relief of dry eye symptoms in each eye Compliance with drops, issues with contact lens Compliance with drops, issues with contact lens

Mean Epithelial Defect Time Placebo (n-68) Systane (n-68) P – Value 1 Mean Defect Area 2 (+ SD) Range 2 Mean Defect Area 2 (+ SD) Range 2 Day (9) – (10) – Day (6.7) 0.00 – (6.1) 0.00 – Day (2.3) 0.00 – (2.2) 0.00 – Day (0.4) 0.00 – (0.4) 0.00 – p-values of paired t-test for between treatment comparison using paired data 2 Mean epithelial defect size calculated from the recorded vertical and horizontal dimensions of the defect at each observation and presented as square mm.

Mean Epithelial Defect Post Operative Time Mean Size* (mm 2 ) * Mean epithelial defect size calculated from recorded vertical and horizontal dimensions of the defect at each observation and presented as square mm.

Post Operative Discomfort Post Operative Time Comfort Score (0-4) (Lower is Better)

Post Operative Dry Eye Symptoms Time Post Operative Dry Eye Symptoms (0-4) (Lower is Better)

Conclusions No adverse impact of Systane on post-PRK epithelial healing when compared to placebo No adverse impact of Systane on post-PRK epithelial healing when compared to placebo Demonstrates safety of Systane Demonstrates safety of Systane No increase in post-operative ocular discomfort associated with Systane compared to placebo No increase in post-operative ocular discomfort associated with Systane compared to placebo Very low level of post-operative dry eye symptoms with Systane Very low level of post-operative dry eye symptoms with Systane