1. Safety, Efficacy, and Acceptability of Optive™ Sensitive for Dry-Eye Treatment After LASIK Surgery
Peter A SimmonsA
Cindy Carlisle-WilcoxA
Perry S BinderB
ADr. Simmons and Ms. Carlisle-Wilcox are employees of Allergan, Inc.
BDr. Binder has served as a consultant for Allergan, Inc., and AMO, Inc.
ASCRS 2009

2. Background
As many as 50% of LASIK surgery patients may suffer from post-LASIK dry eye
Dry eye symptoms decrease patient satisfaction with the outcome of LASIK surgery
A dry ocular surface affects UCVA, BCVA and refractive errors
Artificial tears for dry eye symptoms are an integral part of post-LASIK standard of care
Initial use of non-preserved unit-dose artificial tears is recommended, followed by transition to a multi-dose tear, typically at 1-8 weeks post-op
Recommended dosing frequency with tears typically decreases during the post-op period
ASCRS 2009

3. Purpose
Refresh Plus® is a standard non-preserved tear used in post-LASIK care
Optive Sensitive is a new non-preserved tear, containing additional beneficial ingredients
Research questions:
Is Optive Sensitive safe and effective for use in post-LASIK patients?
How does the performance of Optive Sensitive compare with Refresh Plus?
ASCRS 2009

4. Methods Multi-center, double-masked, parallel-group prospective trial.
Subjects were myopic LASIK patients without pre-existing dry eye
All procedures were performed using wavefront-guided surgery with the VISX S4 excimer laser and iris registration. Eyes with >0.3 µm HOA RMS prior to surgery were excluded.
Flaps were created with the IntraLase femtosecond laser in 93% of the eyes and in 7% of the eyes with a mechanical microkeratome.
Following uncomplicated bilateral surgergy, subjects were randomized to use either non-preserved OPTIVE™ Sensitive or Refresh Plus® (both Allergan) in both eyes.
Standard postoperative antibiotics and steroids were used as per the investigator site and were discontinued by postoperative day 7.
Subjects were followed for 90 days post-op
Artificial tear dosing was:
Day 1 every hour while awake,
Days 2-14 every 2 hours while awake,
Days 14-90, surgeon option to decrease dosing in steps down to 1-2 per day.
Neither the surgeon nor the patient knew which tear they were using.
ASCRS 2009

5. Study variables
Corneal topography primarily on the Humphrey Atlas or Oculus Pentacam
Wavefront aberrometry (VISX Wavescan)
BCVA, UCVA, manifest refraction
Dry eye variables: Schirmer test (w/ anesthesia), corneal staining (unpreserved fluorescein), conjunctival staining (lissamine green), and tear break-up time
Subjective variables: Ocular Surface Disease Index© (OSDI) (primary variable), Subjective Evaluation of Symptoms of Dryness (SESoD), Dryness Comfort Level Visual Analog Scale (Dryness VAS), patient acceptability questionnaire
Safety variables: biomicroscopy, adverse events
ASCRS 2009

6. Ocular Surface Disease Index (OSDI)
The OSDI, which was the primary variable in this study, is a 12-item patient-reported outcomes questionnaire designed to provide a quick assessment of dry eye symptoms, related visual functions and environmental triggers
OSDI questions are scored on a 0 to 4 frequency scale (0 = None of the time, 1 = Some of the time, 2 = Half of the time, 3 = Most of the time, 4 = All of the time, and N/A)
OSDI scores are calculated using this formula:
OSDI = Sum of Scores for All Questions Answered x Total Number of Questions Answered x 4
Scores range from 0 to 100 (0 = no disability, 100 = complete disability)
ASCRS 2009

7. Patient Demographics OPTIVE™ Sensitive Refresh Plus®
Number of patients
114 randomized, 111 complete
114 randomized, 109 complete
Average Age
34.5 years
33.8 years
Gender
52 male, 62 female
63 male, 51 female
Ethnicity
85.1% Caucasian
78.1% Caucasian
Pre-op Spherical Equivalent
-4.196
-4.068
Post-op Spherical Equivalent
-0.263
-0.057
Pre-op UCVA
20/261
20/244
Post-op UCVA
20/19
20/18
ASCRS 2009

8. Similar OSDI Scores in Patients Treated with OPTIVE™ Sensitive or Refresh Plus®
Optive Sensitive (N = 114)
Refresh Plus (N = 114)
Primary endpoint of non-inferiority was met at day 90
OSDI Scores
Screeninga c
Days After LASIK
The between-group difference in the OSDI scores at day 2 was likely due to the relatively higher viscosity of OPTIVE ™ Sensitive combined with a QH dose
a1-36 days prior to surgery.
ASCRS 2009

9. Corneal Staining Scores
Significantly Lower Corneal Fluorescein Staining with OPTIVE™ Sensitive at Day 14
Refresh Plus
Optive Sensitive
P = 0.039
Corneal Staining Scores
Number of patients included in this analysis at each study visit was as follow:
Screening: N = 113 for Optive Sensitive and N = 113 for Refresh Plus.
Day 2: N = 112 for Optive Sensitive and N = 112 for Refresh Plus.
Day 14: N = 110 for Optive Sensitive and N = 110 for Refresh Plus.
Day 30: N = 110 for Optive Sensitive and N = 110 for Refresh Plus.
Day 60: N = 109 for Optive Sensitive and N = 106 for Refresh Plus.
Day 90: N = 111 for Optive Sensitive and N = 109 for Refresh Plus.
Screeninga
Days after LASIK
a 1-36 days prior to surgery.
ASCRS 2009

10. Tear Dosing Assignment and Use
More OPTIVE ™ Sensitive subjects were assigned to 1-2 drops per day dosing earlier in the study
OPTIVE™ Sensitive subjects reported less drop usage than Refresh Plus® subjects
ASCRS 2009

11. CONCLUSIONS
In this group of patients without prior dry-eye history, LASIK-induced dry eye symptoms and findings peak by day 14 and decreased to baseline by month 3 following surgery with the IntraLase femtosecond laser and VISX wavefront-guided excimer laser ablation
OPTIVE™ Sensitive was safe and effective for the management of dry eye signs and symptoms following LASIK surgery
OPTIVE™ Sensitive demonstrated incremental benefits over standard tear management, including significantly less corneal staining at Day 14
Both treatment groups demonstrated a return to baseline in dry eye signs and symptoms by day 90
Overall, patients in the OPTIVE™ Sensitive group showed a faster trend in the reduction of dose and higher subjective agreement at day 90 that, “I no longer need to use artificial tears”
The differential staining at 2 weeks post-LASIK suggests artificial tear formula influences status of (at least) corneal epithelium and supports continued unit-dose use during this “vulnerable” period
Additional analysis of wavefront aberrometry and topography results is ongoing
ASCRS 2009

12. Clinical Investigators
The following served as surgeons and clinical investigators on this study. The authors wish to thank them for their participation.
Perry S. Binder, MD David A. Kinsler, MD
Thomas E. Clinch, MD Colman R. Kraff, MD
Elizabeth A. Davis, MD Robert K. Maloney, MD
Steven J. Dell, MD William Trattler, MD
Richard Grutzmacher, MD J. Trevor Woodhams, MD
ASCRS 2009