Transcript Safety, Efficacy, and Acceptability of Optive™ Sensitive

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
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
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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 postLASIK patients?
– How does the performance of Optive Sensitive
compare with Refresh Plus?
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Methods
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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:
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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.
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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
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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:
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OSDI = Sum of Scores for All Questions Answered x 100
Total Number of Questions Answered x 4
• Scores range from 0 to 100
(0 = no disability, 100 = complete disability)
ASCRS 2009
Patient Demographics
OPTIVE™ Sensitive
Refresh Plus®
114 randomized, 111
complete
114 randomized, 109
complete
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
Number of patients
Average Age
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Similar OSDI Scores in Patients Treated
with OPTIVE™ Sensitive or Refresh Plus®
30
Optive Sensitive (N = 114)
OSDI Scores
25
Refresh Plus (N = 114)
20
Primary endpoint of noninferiority was met at day 90
15
10
5
0
Screeninga
c
2
14
30
60
90
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
Significantly Lower Corneal Fluorescein Staining
with OPTIVE™ Sensitive at Day 14
Corneal Staining Scores
2.0
Refresh Plus
Optive Sensitive
1.8
1.6
1.4
P = 0.039
1.2
1.0
0.8
0.6
0.4
0.2
0.0
Screeninga
2
14
30
Days after LASIK
a 1-36
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days prior to surgery.
60
90
Tear Dosing Assignment and Use
OPTIVE™ Sensitive subjects
reported less drop usage than
Refresh Plus® subjects
10
40
Drops per Day
Subjects Assigned to 1-2
drops per day
More OPTIVE ™ Sensitive subjects
were assigned to 1-2 drops per day
dosing earlier in the study
30
20
10
0
Day 14
Day 30
Day 60
Study Visit
Optive Sensitive
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Refresh Plus
8
6
4
2
0
Screening
Day 30
Day 90
Study Visit
Optive Sensitive
Refresh Plus
CONCLUSIONS
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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
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
Thomas E. Clinch, MD
Elizabeth A. Davis, MD
Steven J. Dell, MD
Richard Grutzmacher, MD
ASCRS 2009
David A. Kinsler, MD
Colman R. Kraff, MD
Robert K. Maloney, MD
William Trattler, MD
J. Trevor Woodhams, MD