Comparison of Topography Guided LASIK With WaveLight® EX500 to SMILE With Zeiss VisuMax
Phase: NA
Conditions: Myopia, Astigmatism
Sponsor: Alcon, a Novartis Company

Page 1 of 81
a Novartis company
Clinical Trial Protocol
Comparison of Topography Guided LASIK with WaveLight EX500 to 
SMILE with Zeiss VisuMax
Protocol Number: 
Sponsor Name & Address:
Project Name / Number:
Test Article(s) / Product(s):
Investigator Agreement:
RFL605-P001 / NCT02987660
Alcon Research, Ltd. and its affiliates (“Alcon”)
6201 South Freeway
Fort Worth, Texas 76134-2099
A02827
WaveLight EX500 for Topography Guided LASIK
I have read the clinical study described herein, recognize 
its confidentiality, and agree to conduct the described 
trial in compliance with Good Clinical Practice (GCP), 
ISO 14155, the ethical principles within the Declaration 
of Helsinki, this protocol, and all applicable regulatory 
requirements. Additionally, I will comply with all 
procedures for data recording and reporting, will permit 
monitoring, auditing, and inspection of my research 
center, and will retain all records until notified by the 
Sponsor.
Principal Investigator:
Signature
Date
Name and Investigator Number:
Address:
Telephone:
Release Date:
<Refer to e-signature date>
Property of Alcon Laboratories
Confidential
May not be used, divulged, published, or otherwise disclosed without the consent of Alcon 
Laboratories
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TDOC-0052425
Protocol - Clinical
19-Mar-2017

Pa ge 2 of 8 1
1
P R O T O C O L  S Y N O P SI S
Fi na ncial Discl os ure 
f or U S F D A 
S u b missi o n Re q uire d?
Ye s
X
N o
Te st Article(s) / 
Pr o d uct(s):
Wa veli g ht ® E X 5 0 0 f or To p o gra p h y G ui de d L A SI K
O bjecti ve(s):
T he pri mar y  o bjecti ve of t he st u d y is t o de m o nstrate t hat 
To p o gra p h y G ui de d Laser i n sit u K erat o mile usis (L A S I K) is 
s u peri or t o S mall Incisi o n L e ntic ule E xtracti o n ( S MI L E) i n t he 
perce nta ge of e y es wit h ma nifest r efracti o n c yli n der ≤ 0. 5 D at 
3 m o nt hs.
T he sec o n dar y o bjecti ves of t he st u d y are:

To  de m o nstrate t hat To p o gra p h y  G ui de d L A SI K is
s u peri or t o S MI L E i n mea n ma nifest refracti o n c yli n der at
3 m o nt hs.

To  de m o nstrate t hat To p o gra p h y  G ui de d L A SI K is
s u peri or t o S MI L E i n mea n u nc orrecte d vis ual ac uit y
( UC V A) at 3 m o nt hs.
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Pa ge 3 of 8 1
T he safet y o bjecti ves of t he st u d y  are:

To  e val uate t he a d verse e ve nts ( A Es) ass ociate d wit h 
To p o gra p h y G ui de d L A SI K a n d S MI L E.

To  e val uate p ost -s ur gery B C V A after To p o gra p h y  G ui de d 
L A S I K a n d S MI L E.

To  e val uate mes o pic u nc orrecte d c o ntrast se nsiti vit y after 
To p o gra p h y G ui de d L A SI K a n d S MI L E.

To  e val uate q ualit y of visi o n a n d visi o n relate d q ualit y  of 
life after To p o gra p h y G ui de d L A SI K a n d S MI L E.
Cli nical St u d y  Desi g n: T his is a pr os pecti ve, parallel gr o u p, m ulti -ce nter, gr o u p ra n d o mize d 
( 1: 1 rati o), a n d o bser ver mas ke d st u d y .
N o. of S u bjects:
P ote ntial s u bjects will be scree ne d , a n d a p pr o xi matel y 4 5 0 s u bjects 
( 2 2 5 s u bjects per treat me nt gr o u p) will be e nr olle d at a p pr o xi matel y  
8 st u d y  sites i n or der t o all o w a p pr o xi matel y 4 0 0 s u bjects ( 2 0 0 
s u bjects per treat me nt gr o u p) t o be treate d wit h bilateral laser 
refracti ve s ur gery ( b ot h e yes o n sa me da y), eit her To p o gra p h y 
G ui de d L A SI K or S MI L E. T his s h o ul d res ult i n at least 3 7 0
e val ua ble s u bjects ( 1 8 5 per treat me nt gr o u p ).
Re gi o n(s):
E M E A , Asia , L A C A R
Cli nical St u d y  
D urati o n:
S u bjects are re q uire d t o atte n d a t otal of 7 visits o ver a peri o d of u p 
t o 1 5 m o nt hs as f oll o ws: Pre -S ur ger y  V isit ( Da y - 4 5 t o Da y -1), 
S ur ger y  Visit ( Da y 0), a n d 5 P ost -S ur ger y f oll o w- u p Visits ( o n 
D a y 1, Wee k 1 [ Da y  5 t o Da y 9], M o nt h 1 [Da y  2 1 t o Da y 3 5], 
M o nt h
3 [ Da y  7 0 t o Da y 9 8] a n d M o nt h 1 2 [ Da y  3 3 0 t o Da y 3 7 5], 
res pecti vely ).
Cli nical St u d y  
P o p ulati o n:
S u bjects 1 8 ye ars or ol der [ s u bjects i n Si n ga p ore m ust be 2 1 ye ars of 
a ge or ol der a n d s u bjects i n K orea m ust be u p o n c o m pleti o n of 1 9 
ye ars of a ge or ol der d ue t o l ocal re g ulati o ns] wit h m y o pia re q uiri n g 
o ptical i nfi nit y  a dj uste d ma nifest refractio n s p herical correcti o n of -
0. 5 t o -8. 0 D a n d asti g matis m c orrecti o n of - 0. 7 5 t o - 5. 0 D ma nifest 
refracti o n c yli n der wit h at least 0. 7 5 D of c or neal asti g matis m .
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

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Treatments:
Test Article:
Wavelight EX500 for Topography Guided 
LASIK
Administration:
The EX500 laser is used to ablate the corneal 
stroma which results in the refractive error 
correction. Prior to ablation, the corneal flap 
may be created with a femtosecond laser or 
microkeratome blade at the surgeon’s 
discretion. Treatment planning will be based 
on topography.
General Description: Wavelight EX500 is a stationary 
scanning-spot excimer laser system used to 
perform the LASIK procedure. Ablation of the 
corneal tissue with the WaveLight EX500 
results in the refractive error correction.
Duration of 
Treatment:
The treatment is intended to last the subject’s
lifetime.
Control Article:
Zeiss VisuMax for SMILE
Administration:
The VisuMax Laser keratome is used to create 
a lenticule in the corneal stroma and a channel 
for the removal of the lenticule. Removal of 
the lenticule results in the refractive error 
correction.
General Description: Zeiss VisuMax Laser keratome, a 
femtosecond laser, generates a beam of ultra-
short laser pulses used to perform the SMILE 
procedure, for refractive error correction.
Duration of 
Treatment :
The treatment is intended to last the subject’s 
lifetime.
Inclusion & Exclusion 
Criteria:
Inclusion criteria: Ocular criteria must be met in both eyes.
1. Subjects 18 years of age or older at the time of informed consent
[subjects in Singapore must be 21 years of age or older and 
subjects in Korea must be upon completion of 19 years of age or 
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Pa ge 5 of 8 1
ol der d ue t o l ocal re g ulati o ns] .
2.
A ble t o c o m pre he n d a n d si g n a n i nf or me d c o nse nt f or m (I C F).
3.
Wi lli n g a n d a ble t o c o m plete all p ost -s ur gery visits.
4.
M y o pia re q uiri n g (a) refracti ve err or correcti o n of -0. 5 t o -8. 0 D 
o ptical i nfi nit y  a dj uste d ma nifest refracti o n s p here wit h ( b) 
asti g matis m c orrecti o n of -0. 7 5 t o -5. 0 D ma nifest refracti o n 
c yli n der a n d (c) at least 0. 7 5 D of c or neal asti g matis m.
5.
I nte n de d treat me nt is tar gete d f or e m metr o pia.
6.
Pre -s urger y  B C V A of 0 l o garit h m of t he mi ni m u m a n gle of 
res ol uti o n (l o g M A R) ( 2 0/ 20) or better.
7.
S p herical e q ui vale nt differe nce of ≤0. 5 D bet wee n t he o ptical 
i nfi nit y a dj uste d ma nifest a n d o ptical i nfi nit y  a dj uste d 
c ycl o ple gic refracti o n o utc o mes.
8.
S p herical e q ui vale nt differe nce of ≤0. 5 D bet wee n refracti ve 
err or c orrecti o ns f or a mi ni m u m of 1 2 m o nt hs pri or t o s ur ger y
verifie d b y c o nsec uti ve o ptical i nfi nit y  a dj uste d refracti o ns 
a n d/ or me dical rec or ds or prescri pti o n hist or y .
9.
F or c o ntact le ns wearers - S p herical e q ui vale nt differe nce of 
≤0. 5 D bet wee n o utc o mes fr o m c o nsec uti ve o ptical i nfi nit y  
a dj uste d ma nifest refracti o n o utc o mes perf or me d at least 7 da y s 
a part after t he c o ntact le ns w ear has bee n st o p pe d f or t he 
a p pr o priate peri o d of ti me as f oll o ws:

S oft (e xte n de d a n d dail y wear) = 3 d a y s

Ri gi d Gas Per mea ble (R G P ) or Toric = 2 wee ks

Har d p ol y m et h yl  met hacr ylate (P M M A) = 3 wee ks
E xcl usi o n Criteria: Oc ular criteria m ust n ot be met i n ei t her e ye.
1.
Pre g na nc y  or lactati o n, c urre nt or pla n ne d, d uri n g t he c o urse of 
t he st u d y.
2.
Ma nifest refracti o n asti g matis m t hat is m ore t ha n 1. 0 0 D t ha n t he 
t o p ol yzer asti g matis m assesse d b y C o nt o ura s oft ware.
3.
Mi xe d asti g matis m refracti ve err or .
4.
De ge nerati o ns of str uct ure of t he c or nea i ncl u di n g dia g n ose d 
kerat oc o n us, f or me fr uste keratac o n us or pell uci d mar gi nal 
de ge nerati o n.
5.
Dr y  e ye as i de ntifie d b y t he s h ort q uesti o n naire f or dr y e ye 
s yn dr o me (S Q D E S ).
6.
A calc ulate d resi d ual str o mal be d t hic k ness t hat is less t ha n 
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Page 6 of 81
250 µm.
7. History or evidence of active or inactive corneal or other anterior 
segment disease (e.g, herpes simplex keratitis, recurrent erosion 
syndrome).
8. Diagnosed advanced glaucoma.
9. Uncontrolled diabetes.
10. Nystagmus or any other condition that would prevent a steady 
gaze during the treatment.
11. Previous intraocular or corneal surgery.
12. Weakened immune system, including diagnosed collagen 
vascular, autoimmune or immunodeficiency disease.
13. Systemic medications that may affect corneal healing including, 
but not limited to steroids, antimetabolites, immune response 
modifying drugs, etc.
14. Presence or history of any condition or finding that makes the 
subject unsuitable as a candidate for refractive surgery or study 
participation or may confound the outcome of the study, in the 
opinion of the Investigator.
15. Any subject currently participating in another investigational 
drug or device study that may confound the results of this 
investigation.
16. A known sensitivity to medications used during the study.
Effectiveness 
Endpoints and 
Assessments
Endpoints
Assessments
Primary 
Percentage of eyes with manifest 
refraction cylinder ≤ 0.5 D at 
3 months
Manifest refraction
Secondary
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Mean manifest refraction cylinder 
at 3 months
Manifest refraction
Mean UCVA at 3 months
Photopic distance UCVA
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Pa ge 9 of 8 1
Safet y  E n d p oi nts a n d 
Assess me nts
E n d p oi nts
Assess me nts
Mea n i ntra oc ular press ure (I O P)
at Scree ni n g, 1 m o nt h, 3 m o nt hs, 
a n d 1 2 m o nt hs
T o n o metr y
Fre q ue nc y  of treat me nt-e mer ge nt 
a d verse e ve nts 
D oc u me nt a d verse e ve nts
Fre q ue nc y  of de vice deficie ncies
at da y of s ur ger y
D oc u me nt de vice deficie ncies

U nc orrecte d c o ntr ast se nsiti vit y:
Mea n mes o pic u nc orrecte d 
c o ntrast se nsiti vit y at eac h 
c o ntrast le vel at Scree ni n g, 1 
m o nt h, 3 m o nt hs, a n d 1 2 m o nt hs .
Mes o pic u nc orrecte d c o ntrast 
se nsiti vit y

B C V A:
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Pa ge 1 0 of 8 1
Mea n B C V A at Scree ni n g, 1 
wee k, 1 m o nt h, 3 m o nt hs, a n d 1 2 
m o nt hs
P h ot o pic d ista nce B C VA
Perce nta ge of e y es wit h 
p ost -s urger y  B C VA m ore t ha n 
t w o li nes better t hat is t w o li nes 
better , o ne li ne better , less t ha n 
o ne li ne better a n d greater t ha n 
o ne li ne w orse, o ne li ne w orse, 
t w o li nes w orse, m ore t ha n t w o 
li nes w orse t ha n pre-s urger y
B C V A at Scree ni n g, 1 wee k, 1 
m o nt h, 3 m o nt hs, a n d 1 2 m o nt hs .
P h ot o pic d ista nce B C VA

Q u alit y of visi o n a n d q u alit y of life (f or  b ot h R S V P a n d 
S Q D E S):
Fre q ue nc y  of dr y e ye s yn dr o me at 
Scree ni n g, 1 m o nt h, 3 m o nt hs, 
a n d 1 2 m o nt hs.
S h ort q uesti o n naire f or dr y  e ye 
s yn dr o me ( S Q D E S)
Mea n o verall a n d s u bscale visi o n 
relate d q ualit y of life sc ore at 
Scree ni n g, 1 m o nt h, 3 m o nt hs, 
a n d 1 2 m o nt hs
Refracti ve Stat us a n d V isi o n 
Pr ofile ( R S V P) q uesti o n naire
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

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Planned Analysis
The main analyses for effectiveness and safety will be conducted 
when the last subject completes the 3 months post-surgery 
follow-up visit. Subjects will be followed-up for an additional 9 
months (Day 330 to Day 375) for safety 
 
assessments.
The primary endpoint is the percentage of eyes with manifest 
refraction cylinder less than or equal to 0.5 D at 3 months. The 
following superiority hypothesis for the primary effectiveness 
objective will be tested at the 5% significance level (α= 0.05) 
(two-sided):
H0: pL= pS vs H1: pL ≠pS
where pL and ps refer to the percentage of eyes with manifest 
refraction cylinder within (≤) 0.5 D in the Topography Guided 
LASIK arm and SMILE arm, respectively.
It will be analyzed using the chi-square test, accounting for the 
correlation between eyes within subjects. 
The secondary effectiveness hypotheses will be relevant only if the 
primary effectiveness null hypothesis is rejected at the 5% 
significance level (two-sided). If the aforementioned null 
hypothesis is rejected, then the familywise Type I error rate for the 
secondary effectiveness endpoints will be controlled at the 5% 
significance level by using the Hochberg testing procedure. 
The superiority hypothesis for the first secondary effectiveness 
objective will be tested (two-sided):
H0: µL = µS vs H1: µL ≠µS
where µL and µs denote the mean manifest refraction cylinder in 
the Topography Guided LASIK arm and SMILE arm, respectively. 
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The superiority hypothesis for the second secondary effectiveness 
objective will be tested (two-sided):
H0: µL = µS vs H1: µL ≠µS
where µL and µS denotes the mean UCVA in the Topography 
Guided LASIK arm and SMILE arm, respectively. 
The secondary effectiveness endpoints will be analyzed using the 
statistic of Donner, which accounts for the intraclass correlation 
between eyes within subjects.
 
. Descriptive statistics will be 
presented for 
 safety endpoints. 
Sample Size
Justification
Based on the assumed rates of 90% vs 80% of eyes with manifest 
refraction cylinder less than or equal to 0.5 D at 3 months for 
Topography Guided LASIK and SMILE, respectively, and a 
correlation between eyes within subject of 0.39, a sample size of 
185 subjects (treated bilaterally) per treatment group will provide 
90% power to reject the hypothesis for the primary effectiveness 
objective (based on the two sided 5% significance level). In total, 
740 eyes from approximately 370 subjects are required for this 
study.
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Page 13 of 81
2
TABLE OF CONTENTS
Table of Contents
Comparison of Topography Guided LASIK with WaveLight EX500 to SMILE with Zeiss 
VisuMax..................................................................................................................1
1
PROTOCOL SYNOPSIS .......................................................................................2
2
TABLE OF CONTENTS......................................................................................13
Table of Contents.....................................................................................................................13
List of Tables............................................................................................................................15
List of Figures..........................................................................................................................15
3
ABBREVIATIONS ..............................................................................................17
4
GLOSSARY OF TERMS.....................................................................................19
5
AMENDMENTS..................................................................................................21
5.1
Amendment 1 ...................................................................................................21
6
SCHEDULE OF VISITS......................................................................................33
7
INTRODUCTION................................................................................................35
7.1
Background ......................................................................................................35
7.2
Clinical Study Design.......................................................................................36
8
CLINICAL STUDY OBJECTIVES.....................................................................37
8.1
Primary Objective.............................................................................................37
8.2
Secondary Objectives.......................................................................................38
38
8.4
Safety Objectives..............................................................................................38
8.5
Study Endpoints ...............................................................................................38
8.5.1
Effectiveness Endpoints ...............................................................................38
8.5.2
Safety Endpoints...........................................................................................40
9
INVESTIGATIONAL PLAN ...............................................................................41
9.1
Outline of Clinical Study..................................................................................41
9.2
Rationale for Study Design ..............................................................................42
9.2.1
Procedures Per Study Visit ...........................................................................42
9.3
Risk Benefit Assessment ..................................................................................43
9.3.1
Potential Risks..............................................................................................43
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9.3.2
Potential Benefits .........................................................................................45
9.3.3
Risk Benefit Assessment ..............................................................................45
10
SUBJECT POPULATION....................................................................................46
10.1
Inclusion Criteria..............................................................................................46
10.2
Exclusion Criteria.............................................................................................47
11
TREATMENT ......................................................................................................48
11.1
Investigational Products ...................................................................................49
11.2
Usage................................................................................................................52
11.3
Accountability Procedures ...............................................................................52
12
CLINICAL STUDY PROCEDURES ..................................................................53
12.1
Clinical Study Assessments..............................................................................53
12.1.1
Pre-Surgery screening Visit (Day -45 to Day -1) .........................................53
12.1.2
Surgery Visit (Day 0)....................................................................................56
12.1.3
Post-Surgery follow-up Visits (Day 1, Week 1, Months 1, 3 and 12) ..........57
12.2
Unscheduled Visits...........................................................................................59
12.3
Missed Visits ....................................................................................................60
12.4
Discontinued Subjects......................................................................................60
12.5
Clinical Study Termination...............................................................................60
13
DEVICE DEFICIENCIES AND ADVERSE EVENTS.......................................61
13.1
General Information .........................................................................................61
13.2
Monitoring for Adverse Events ........................................................................63
13.3
Procedures for Recording and Reporting .........................................................63
13.4
Return product analysis....................................................................................66
13.5
Unmasking of the Study Information...............................................................66
13.6
Follow-Up of Subjects with Adverse Events ...................................................66
13.7
Pregnancy in the Clinical Study.......................................................................67
14
DATA REVIEW AND HANDLING....................................................................67
14.1
Completion of Source Documents and Case Report Forms.............................67
14.2
Data Review and Clarifications........................................................................68
15
ANALYSIS PLAN ...............................................................................................69
15.1
Subject Evaluability .........................................................................................69
15.2
Analysis Data Sets............................................................................................69
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15.3
Demographics and Baseline Characteristics ....................................................70
15.4
Effectiveness Analyses .....................................................................................70
15.4.1
Primary Effectiveness...................................................................................70
15.4.1.1
Statistical Hypotheses...............................................................................70
15.4.1.2
Analysis Methods .....................................................................................70
15.4.2
Secondary Effectiveness...............................................................................70
15.4.2.1
Statistical Hypotheses...............................................................................71
15.4.2.2
Analysis Methods .....................................................................................71
71
71
71
15.5
Handling of Missing Data ................................................................................72
15.6
Multiplicity.......................................................................................................72
15.7
Safety Analysis.................................................................................................72
15.8
Interim Analyses...............................................................................................74
15.9
Sample Size Justification..................................................................................74
16
ADMINISTRATIVE PROCEDURES .................................................................75
16.1
Regulatory and Ethical Compliance.................................................................75
16.2
Informed Consent Procedures ..........................................................................75
16.3
Responsibilities of the Investigator and IRB/IEC ............................................75
16.4
Sponsor and Monitoring Responsibilities ........................................................76
16.5
Regulatory Documentation and Records Retention.........................................77
16.6
Confidentiality and Publication of the Clinical Study......................................77
17
REFERENCES.....................................................................................................79
18
APPENDICES......................................................................................................81
List of Tables
Table 6–1
Schedule of Assessments .................................................................................33
Table 11–1
Treatments........................................................................................................49
Table 12–1
Minimum time to stop wearing contact lens before Pre-Surgery Visit............54
List of Figures
Figure 7–1
Study Design....................................................................................................37
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Figure 11–1
Wavelight EX500 Laser System......................................................................50
Figure 11–2
VisuMax...........................................................................................................51
Figure 13-1
Categorization of All Adverse Events..............................................................61
Figure 13–2
Categorization of All Serious Adverse Events.................................................62
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3
ABBREVIATIONS
Abbreviation
Definition
ADE
Adverse device effect 
AE
Adverse event
BCVA
Best corrective visual acuity
CFR
Code of Federal Regulations 
CJD
Creutzfeldt-Jacob Disease
CRO
Clinical research organization
CSM
Clinical site manager
CTM
Clinical trial management
DBL
Database lock
eCRF
Electronic case report form 
EDC
Electronic data capture 
ETDRS
Early Treatment Diabetic Retinopathy Study
FDA
US Food and Drug Administration
FWHM
Full width at half maximum
GCP
Good Clinical Practice
HIV
Human immunodeficiency virus
ICF
Informed consent form
ICH
International Conference on Harmonization
IEC
Independent ethics committee
IOP
Intraocular pressure
IRB
Institutional review board
ITT
Intent to treat
LASIK
Laser in situ keratomileusis
LCSM
Lead clinical site manager 
LogMAR
Logarithm of the minimum angle of resolution
MedDRA
Medical dictionary for regulatory activities
MOP
Manual of procedures 
MRSE
Manifest refraction spherical equivalent 
PMMA
Polymethyl methacrylate
PRK
Photorefractive keratectomy
PRO
Patient-reported outcomes
RGP
Rigid gas permeable
RSVP
Refractive Status and Vision Profile
PT
Preferred term
SADE
Serious adverse device effect 
SAE
Serious adverse event
SAP
Statistical analysis plan
SD
Standard deviation
SMILE
Small incision lenticule extraction
SOC
System organ class
SOPs
Standard operating procedures 
SQDES
Short questionnaire for dry eye syndrome 
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TEAE
Treatment emergent adverse events
UCVA
Uncorrected visual acuity
UNSV
Unscheduled visit 
US
United states
VA
Visual acuity
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Pa ge 1 9 of 8 1
4
G L O S S A R Y O F  TE R M S
A d verse E ve nt ( A E)
A n y  u nt o war d me dical occ urre nce, u ni nte n de d disease or i nj ur y, or 
u nt o war d cli nical si g ns (i ncl u di n g a b n or mal la b orat or y  fi n di n gs) i n 
s u bjects, users or ot her pers o ns, w het her or n ot relate d t o t he 
i n vesti gati o nal me dical de vice (test article). N ote: F or s u bjects, t his 
defi niti o n i ncl u des eve nts rel ate d t o t he test article, t he c o ntr ol 
article, or t he pr oce d ur es i nv olve d. F or users or ot her pers o ns, t his 
defi niti o n is r estricte d t o eve nts rel ate d t o t he test article.
A d verse De vice 
Ef fect ( A D E)
A d verse e v e nt relate d t o t he use of a n i n vesti gati o nal me dical de vice 
(test article) or c o ntr ol article. N ote: T his defi niti o n i ncl u des a dverse 
eve nts res ulti n g fro m i ns ufficie nt or i n a de q u ate i nstr ucti o ns f or use, 
de pl oy me nt, i m pl a nt ati o n, i nst all ati o n, or o per ati o n; a ny 
m alf u ncti o n; a n d use err or or i nte nti o n al mis use of t he test article or 
c o ntrol article.
De vice Deficie nc y
I na de q uac y of a me dical de vice wit h res pect t o its i de ntit y, q ualit y, 
d ura bilit y, relia bilit y, safet y, or perf or ma nce. N ote: T his de fi niti o n 
i ncl u des m alf u ncti o ns, use errors, a n d i n a de q u ate l a beli n g.
Malf u ncti o n
Fail ure of a me dical de vice t o meet its perf or ma nce s pecificati o ns or 
ot her wise perf or m as i nte n de d. Perf or ma nce s pecificati o ns i ncl u de 
all clai ms ma de i n t he la beli n g of t he de vice. T he i nte n de d 
perf or ma nce of t he de vice refers t o t he i nte n de d use f or w hic h t he 
de vice is la bele d or mar kete d.
Pr o d uct C o m plai nt
A n y  oral, electr o nic, or writte n c o m m u nicati o n t hat alle ges 
deficie ncies relate d t o t he i de ntit y  (la beli n g), q ualit y, d ura bilit y, 
relia bilit y, safety,  effecti ve ness, or perf or ma nce of a mar kete d 
pr o d uct, i ncl u di n g fail ure of t he pr o d uct, la beli n g or pac ka gi n g t o 
meet s pecificati o ns, w het her or n ot t he pr o d uct is relate d t o or 
ca use d t he alle ge d deficie nc y. A c o m plai nt m a y  alle ge t hat a n 
a d verse e ve nt or me dical de vice malf u ncti o n has occ urre d.
N o n -seri o us A d verse 
E ve nt
A d verse e ve nt t hat d oes n ot meet t he criteria f or a seri o us a d verse 
e ve nt.
Seri o us A d verse 
E ve nt ( S A E)
A d verse e ve nt t hat le d t o a n y  of t he f oll o wi n g: 

Deat h.

A seri o us deteri orati o n i n t he healt h of t he s u bject t hat eit her 
res ulte d i n:
a)
a life -t hreate ni n g ill ness or i nj ur y. 
N ote: Life -t hre ate ni n g me a ns t h at t he i n divi d u al w as at 
i m me di ate risk of de at h fro m t he eve nt as it occ urr e d, ie, it 
d oes n ot i ncl u de a n eve nt w hic h hy p ot hetic ally mi g ht h ave 
c a use d de at h h a d it occ urre d i n a m ore severe f or m.
b)
a n y p ote ntiall y si g ht-t hreate ni n g e ve nt or per ma ne nt 
i m pair me nt t o a b o d y str uct ure or a b o d y f u ncti o n.
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Pa ge 2 0 of 8 1
c)
i n-pat ie nt h os pitalizati o n or pr ol o n ge d h os pitalizati o n.  
N ote: Pl a n ne d h os pit aliz ati o n f or a pr e-existi n g c o n diti o n, 
wit h o ut seri o us deteri or ati o n i n he alt h, is n ot c o nsi der e d a 
seri o us a dverse eve nt. I n ge ner al, h os pit aliz ati o n si g nifies 
t h at t he i n divi d u al re m ai ne d at t he h os pit al or e mer ge ncy 
w ar d f or o bserv ati o n a n d/ or tr e at me nt ( us u ally i nv olvi n g a n 
over ni g ht st ay) t h at w o ul d n ot h ave bee n a p pr o pri ate i n t he 
p hysici a n's office or a n o ut - p atie nt setti n g. C o m plic ati o ns 
t h at occ ur d uri n g h os pit aliz ati o n are adverse eve nts. If a 
c o m plic ati o n prol o n gs h os pit aliz ati o n or f ulfills a ny ot her 
seri o us criteri a, t he eve nt is seri o us. Whe n i n d o u bt as t o 
w het her “ h os pit aliz ati o n ” occ urr e d, t he eve nt s h o ul d be 
c o nsi dere d seri o us.
d)
a me dical or s ur gical i nter ve nti o n t o pre ve nt a) or b
e)
a n y i n direct har m as a c o nse q ue nce of i nc orrect dia g n ostic 
test res ults w he n use d wit hi n ma n ufact urer’s i nstr ucti o ns f or 
use.

Fetal distress, fetal deat h, or a c o n ge nital a b n or malit y  or birt h 
defect.
Refer t o Secti o n 1 3 f or a d diti o n al S A Es.
Seri o us A d verse 
De vice Ef fect 
( S A D E)
A d verse de vice ef fect t hat has res ulte d i n a n y of t he c o nse q ue nces 
c haracteristic of a seri o us a d verse e ve nt.
Seri o us P u blic Healt h 
T hreat
A n y  e ve nt ty pe w hic h res ults i n i m mi ne nt ris k of deat h, seri o us 
deteri orati o n i n state of healt h, or seri o us ill ness t hat re q uires pr o m pt 
re me dial acti o n. T his w o ul d i ncl u de: E ve nts t hat are of si g nifica nt 
a n d u ne x pecte d nat ure s uc h t hat t he y  bec o me alar mi n g as a p ote ntial 
p u blic healt h hazar d, e. g., h u ma n i m m u n o deficie nc y  vir us ( HIV) or 
Cre utzfel dt-Jac o b Disease ( CJ D).
Use Err or
Act or o missi o n of a n act t hat res ults i n a dif fere nt me dical de vice 
res p o nse t ha n i nte n de d b y ma n ufact urer or e x pecte d b y user. 
N ote: T his defi niti o n i ncl u des sli ps, l a pses, a n d mist akes. A n 
u nex pecte d p hysi ol o gic al r es p o nse of t he s u bject d oes n ot i n itself 
c o nstit ute a use error.
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Page 21 of 81
5
AMENDMENTS
Modification of the protocol is prohibited without prior written agreement in the form of a 
protocol amendment. All amendments will be created by the Sponsor and must be approved 
by the IRB/IEC prior to implementation except when required to mitigate immediate safety 
risks or when the changes involve only logistical or administrative revisions.
5.1
Amendment 1
Purpose of Amendment: To implement clarifications and revisions learned during the 
planning of the study.
Rationale:  Ensures proper documentation for processes and procedures that will be executed 
during the study.
Current Study Status:  This study is recruiting with 2 patients enrolled at one site in France at 
this point in time.
Case Report Form Revision Required:
Yes
X No
Informed Consent Modifications Required:
X Yes
No
Changes made to the Informed Consent are only applicable to Dr. Sanchez site in Mexico.
Applicable Investigators:
X All
Selected (list below)
Itemized Changes:
Sections
Revisions
Rationale 
Protocol 
synopsis,
Section 
7.2
Section 
10
Inclusion/
Exclusion 
Text updated from:
Subjects 18 years or older
with myopia requiring
manifest refraction 
spherical correction of -0.5 
to -8.0 D and astigmatism 
correction of -0.75 to -5.0 
D manifest refraction 
cylinder with at least 0.75
Text updated to:
Subjects 18 years or older
[subjects in Singapore must 
be 21 years of age or older 
and subjects in Korea must be 
upon completion of 19 years 
of age or older due to local 
regulations] with myopia 
To be consistent 
with legal adult 
age for other 
participating 
countries such as 
Singapore and 
Korea.
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Sections
Revisions
Rationale 
criteria
D of corneal astigmatism.
requiring optical infinity 
adjusted manifest refraction 
spherical correction of -0.5 to 
-8.0 D and astigmatism 
correction of -0.75 to -5.0 D 
manifest refraction cylinder 
with at least 0.75 D of corneal
astigmatism.
Protocol 
synopsis
Table 
11.1 and 
section 
11.2
Section 
12.1.2
Text updated from:
Microkeratome laser.
Text updated to:
Microkeratome blade.
For accuracy; 
microkeratome is 
not a laser.
Protocol 
synopsis
Section 
7.2
Section 
10
Text updated from:
Myopia requiring (a) 
refractive error correction 
of -0.5 to -8.0 D manifest 
refraction sphere with (b) 
astigmatism correction of -
0.75 to -5.0 D manifest 
refraction cylinder and (c) 
at least 0.75 D of corneal
astigmatism.
Text updated to:
Myopia requiring (a) 
refractive error correction of -
0.5 to -8.0 D optical infinity 
adjusted manifest refraction 
sphere with (b) astigmatism 
correction of -0.75 to -5.0 D 
manifest refraction cylinder 
and (c) at least 0.75 D of 
corneal astigmatism.
To emphasize that 
the inclusion 
criterion is based 
on the optical 
infinity adjusted 
manifest 
refraction.
Protocol 
synopsis, 
Section 
10.1
Text updated from:
Spherical equivalent 
difference of ≤ 0.5 D 
between the manifest and 
cycloplegic refraction 
outcomes.
Text updated to:
Spherical equivalent 
difference of ≤ 0.5 D between 
the optical infinity adjusted 
manifest and optical infinity 
adjusted cycloplegic 
refraction outcomes.
To emphasize that 
the inclusion 
criterion is based 
on the optical 
infinity adjusted 
refraction.
Protocol 
synopsis, 
Section 
Text updated from:
Spherical equivalent 
difference of ≤0.5 D 
Text updated to:
Spherical equivalent 
difference of ≤0.5 D between 
To emphasize that 
the inclusion 
criterion is based 
on the optical 
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Sections
Revisions
Rationale 
10.1
between refractive error 
corrections for a minimum 
of 12 months prior to 
surgery verified by 
consecutive refractions 
and/or medical records or 
prescription history.
refractive error corrections for 
a minimum of 12 months 
prior to surgery verified by 
consecutive optical infinity 
adjusted refractions and/or 
medical records or 
prescription history.
infinity adjusted 
manifest 
refraction.
Protocol 
synopsis, 
Section 
10.1
Text updated from:
For contact lens wearers -
Spherical equivalent 
difference of ≤0.5 D 
between outcomes from 
consecutive manifest 
refraction outcomes 
performed at least 7 days 
apart after the contact lens 
wear has been stopped for 
the appropriate period of 
time as follows.
Text updated to:
For contact lens wearers -
Spherical equivalent 
difference of ≤0.5 D between 
outcomes from consecutive 
optical infinity adjusted 
manifest refraction outcomes 
performed at least 7 days 
apart after the contact lens 
wear has been stopped for the 
appropriate period of time as 
follows.
To emphasize that 
the inclusion 
criterion is based 
on the optical 
infinity adjusted 
refraction.
Protocol 
synopsis, 
Section 
10.2
Text updated from:
Manifest refraction 
astigmatism that is more 
than 1.00 D than the 
topolyzer astigmatism
assessed by Topolyzer 
Vario.
Text updated to:
Manifest refraction 
astigmatism that is more than 
1.00 D than the topolyzer 
astigmatism assessed by
Contoura software.
The data from the 
Topolyzer Vario is 
used to derive the 
data provided by 
the Contoura 
Software, but data 
from the Contoura 
software is more 
relevant to this 
criterion.
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Sections
Revisions
Rationale 
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Sections
Revisions
Rationale 
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Sections
Revisions
Rationale 
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Pa ge 2 7 of 8 1
Secti o ns
Re visi o ns
R ati o n ale 
Pr ot oc ol 
s yn o psis, 
Secti o n 
8. 5. 2
Te xt u p date d fr o m:
Mea n i ntra oc ular press ure 
(I O P).
Te xt u p date d t o::
Mea n i ntra oc ular press ure 
(I O P) at Scree ni n g, 1 m o nt h, 
3 m o nt hs, a n d 1 2 m o nt hs .
To  s pecif y t he 
rele va nt ti me 
p oi nts .
Pr ot oc ol 
s yn o psis, 
Secti o n 
8. 5. 2
Bel o w te xt was delete d:

Fre q ue nc y of slit la m p fi n di n gs

Fre q ue nc y  of dilate d f u n d us fi n di n gs
Delete d as n o 
descri pti ve 
statistics will be 
perf or me d f or 
eit her assess me nt, 
o nl y  listi n gs
pr o vi de d .
Pr ot oc ol 
s yn o psis, 
Secti o n 
8. 5. 2
Te xt u p date d fr o m:
Fre q ue nc y  of a d verse 
e ve nts.
Te xt u p date d t o:
Fre q ue nc y  of treat me nt-
e mer ge nt a d verse e ve nts.
To  clarif y t hat t he 
a nal ys is will be 
ar o u n d A Es w hic h 
occ ur after 
s urger y .
Pr ot oc ol 
s yn o psis, 
Secti o n 
8. 5. 2
Te xt u p date d fr o m:
Mea n mes o pic u nc orrecte d 
c o ntrast se nsiti vit y at eac h 
c o ntrast le vel at eac h st u d y 
visit.
Te xt u p date d t o :
Mea n mes o pic u nc orrecte d 
c o ntrast se nsiti vit y at eac h 
c o ntrast le vel at Scree ni n g, 1 
m o nt h, 3 m o nt hs, a n d 1 2 
m o nt hs .
To  s pecif y t he 
rele va nt ti me 
p oi nts .
Pr ot oc ol 
s yn o psis, 
Secti o n 
8. 5. 2
Te xt u p date d fr o m:
Mea n B C V A at eac h st u d y 
visit .
Te xt u p date d t o :
Mea n B C V A at Scree ni n g, 1 
wee k, 1 m o nt h, 3 m o nt hs, 
a n d 1 2 m o nt hs.
To  s pecif y t he 
rele va nt ti me 
p oi nts .
Pr ot oc ol 
s yn o psis, 
Secti o n 
8. 5. 2
Te xt u p date d fr o m:
Perce nta ge of e y es wit h 
p ost -s urger y  B C VA t hat is 
t w o li nes better , o ne li ne
better , o ne li ne w orse, t w o 
li nes w orse t ha n pre-s urger y
Te xt u p date d t o :
Perce nta ge of e y es wit h 
p ost -s urger y  B C VA m ore 
t ha n t w o li nes better t hat is 
t w o li nes better, o ne li ne 
better , less t ha n o ne li ne 
To  s pecif y t he 
rele va nt ti me 
p oi nts a n d a d de d 
m ore cate g ories 
f or c o m plete ness.
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Page 28 of 81
Sections
Revisions
Rationale 
BCVA at each study visit.
better and greater than one 
line worse, one line worse, 
two lines worse, more than 
two lines worse than pre 
surgery BCVA at Screening, 
1 week, 1 month, 3 months, 
and 12 months.
Protocol 
synopsis, 
Section 
8.5.2
Text updated from:
Frequency of dry eye 
syndrome at each study visit.
Text updated to:
Frequency of dry eye 
syndrome at Screening, 1 
month, 3 months, and 12 
months.
To specify the 
relevant time 
points.
Protocol 
synopsis,
Section 
8.5.2
Text updated from:
Mean overall and subscale 
vision related quality of life 
score at each study visit.
Text updated to:
Mean overall and subscale 
vision related quality of life 
score at Screening, 1 month, 
3 months, and 12 months.
To specify the 
relevant time 
points.
Protocol 
synopsis, 
Section 
15.4.1.1
Text updated from:
H0: pL≤ pS
H1: pL > pS
Text updated to:
H0: pL= pS
H1: pL ≠ pS
To be consistent 
with the 
objectives of the 
study.
Protocol 
synopsis, 
Section 
15.4.2.1
Text updated from:
H0: µL ≥ µS
H1: µL < µS
where µL and µs denote the 
mean UCVA in the 
Topography Guided LASIK 
arm and SMILE arm, 
respectively.
Text updated to:
H0: µL = µS
H1: µL ≠ µS
where µL and µs denote the 
mean manifest refraction 
cylinder in the Topography 
Guided LASIK arm and 
SMILE arm, respectively.
To be consistent 
with the study 
objectives.
Protocol 
synopsis, 
Section 
15.4.2.1
Text updated from:
H0: µL ≥ µS
H1: µL < µS
Text updated to:
H0: µL = µS
H1: µL ≠ µS
To be consistent 
with the study 
objectives.
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Sections
Revisions
Rationale 
where µL and µs denote the 
mean manifest refraction 
cylinder in the Topography 
Guided LASIK arm and 
SMILE arm, respectively.
where µL and µs denote the 
mean UCVA in the 
Topography Guided LASIK 
arm and SMILE arm, 
respectively.
Section 
7.2
Text updated from:
Subjects are randomized 1:1 
by investigational site on day 
of Pre-Surgery Visit to 
undergo bilateral surgery 
with either Topography 
Guided LASIK or SMILE 
scheduled on Day 0.
Text updated to:
Subjects are randomized 1:1 
by investigational site 
during the Pre-Surgery 
period to undergo bilateral 
surgery with either 
Topography Guided LASIK 
or SMILE scheduled on Day 
0.
To clarify
randomization 
may be over a 
period versus on a 
single day.
Section 
12.1.1
Text updated from:
Measure manifest refraction.
Text updated to:
Measure manifest refraction
at 4 meters and adjust for 
optical infinity.
To emphasize that 
the manifest 
refraction at 4 
meters needs to be 
converted to 
optical infinity.
Section 
12.1.1
Text updated from:
Perform pupillometry under 
mesopic conditions using an 
infrared pupilometer or any 
other instrument.
Text updated to:
Perform pupillometry under 
mesopic conditions using an 
infrared pupilometer.
For consistency of 
measurement.
Section 
12.1.1
Text updated from:
Perform cycloplegic 
refraction using a phoropter 
or trial lenses.
Text updated to:
Perform cycloplegic 
refraction using a phoropter 
and adjust for optical 
infinity.
Trial frame 
refraction could 
be unreliable.
Section 
12.1.1
Below text was added:
NOTE: A contact lens wearer is defined as someone who 
has worn contact lenses within 3 months prior to the Pre-
Surgery Visit.
To clarify the 
definition of a 
contact lens 
wearer.
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Sections
Revisions
Rationale 
Section 
12.1.1
Below text was deleted:
A subject reschedules surgery and this rescheduling result in 
the pre-surgery/ screening assessments falling outside of the 
45 day screening window (Day-45 to Day -1). The subject 
must not be re-randomized and must not be assigned a new 
subject number.
Not applicable.
Section 
12.1.2
Below text was added:
Record the surgeon who performed the surgery. No more 
than two surgeons per site should perform a type of surgery.
To minimize 
variability in 
outcomes from 
having too many 
surgeons 
performing a 
procedure.
Section 
12.1.2
Text updated from:
NOTE: Although the surgery 
is planned to be bilateral, in 
the case where the 
Investigator decides to not 
perform the surgery on the 
second eye on the same day 
the first eye is treated, the 
Investigator may treat the 
second eye at a later date 
while the subject is still in 
the study. In this case, AEs 
will also be collected for this 
eye.
Text updated to:
NOTE: Although the 
surgery is planned to be 
bilateral, in the case where 
the Investigator decides to 
not perform the surgery on 
the second eye on the same 
day the first eye is treated, 
the Investigator may treat 
the second eye at a later date 
while the subject is still in 
the study. In this case, 
effectiveness and safety 
assessments will be 
conducted as per 
post-surgery follow up visits 
if the fellow eye is treated 
with the study treatment. If 
the fellow eye is not treated 
at all or treated with a non-
study treatment, AEs will 
only be collected for this 
eye. Refer to the MOP Table 
4-1 for further details.
To 
comprehensively 
outline data to be 
collected if both 
eyes do not have 
surgery on the 
same day or a 
non-study 
treatment is 
performed.
Section 
12.1.3
Text updated from:
Measure manifest refraction
Text updated to:
Measure manifest refraction
To emphasize that 
the manifest 
refraction at 4 
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Sections
Revisions
Rationale 
at the Week 1, Month 1, 3 
and 12 visits.
at 4 meters and adjust for 
optical infinity at the 
Week 1, Month 1, 3 and 12 
visits.
meters needs to be 
converted to 
optical infinity.
Section 
13.3
Text updated from:
The completed form will be 
then faxed or emailed to the 
Study Sponsor at 
 
according to the 
timelines outlined above; 
however, the reported 
information must be entered 
into the EDC system once it 
becomes operational.
Text updated to:
The completed form will be 
then emailed to the Study 
Sponsor at 
according to the 
timelines outlined above; 
however, the reported 
information must be entered 
into the EDC system once it 
becomes operational.
The safety fax 
number is no 
longer 
operational.
Section 
15.6
Text updated from:
The next largest p-value 
(p[1]) will then be checked to 
see if it is less than the 
critical value (α=0.025).
Text updated to:
The next largest p-value 
(p[1]) will then be checked 
to see if it is less than the 
critical value (α/2=0.025).
To clarify the 
alpha value for the 
next largest p-
value (i.e. p[1] < 
α/2).
Section 
15.7
Text updated from:
Ocular and non-ocular 
treatment emergent AEs will 
be summarized separately by 
SOC and PT.
Text updated to:
Ocular treatment emergent 
AEs will be summarized 
separately by SOC and PT.
Non-ocular 
treatment 
emergent AEs will 
not be 
summarized.
Section 
15.7
Text updated from:
Although the surgery is 
planned to be bilateral, in the 
case where the Investigator 
decides to not perform the 
surgery on the second eye, 
AEs will be collected for this 
eye.
Text updated to:
Although the surgery is 
planned to be bilateral, the 
investigator may decide to 
not perform the surgery on 
the second eye on the same 
day as the first eye. In the 
following scenarios, if 
during the 12-month post-
surgery study period: 
To 
comprehensively 
outline data to be 
collected if both 
eyes do not have 
surgery on the 
same day or a 
non-study 
treatment is 
performed.
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Pa ge 3 2 of 8 1
Secti o ns
Re visi o ns
R ati o n ale 

n o s ur ger y  is 
perf or me d o n t he 
sec o n d e ye

s ur ger y is perf or me d 
o n t he sec o n d e y e 
usi n g a n o n -st u d y 
s ur ger y o nl y A Es 
will be c ollecte d f or 
t he sec o n d e ye
Secti o n 
1 5. 7
Te xt u p date d fr o m:
Ot her safet y e val uati o ns 
i ncl u de slit la m p fi n di n gs
I O P, dilate d f u n d us fi n di n gs 
a n d P R O Q uesti o n naires 
( R S V P, S Q D E S).
Te xt u p date d t o:
Ot her safet y e val uati o ns 
i ncl u de slit la m p fi n di n gs, 
I O P, s ur gical pr o ble ms, 
dilate d f u n d us fi n di n gs a n d 
P R O Q uesti o n naires ( R S V P , 
S Q D E S) .
To  ta ke care of a n 
o missi o n (s urgical 
pr o ble ms) .
Secti o n 
1 5. 7
Bel o w te xt was delete d:
All ot her i nf or mati o n c ollecte d (e. g., se verit y or relati o ns hi p 
t o st u d y treat me nt) will be s u m marize d a n d liste d as 
a p pr o priate. S u m mar y ta bles will als o be prese nte d f or t he 
s u bset of A Es s us pec te d t o be treat me nt relate d.
T he a nal ys is f or 
a d verse e ve nts has 
bee n re vise d t o 
ma ke it m ore 
c o ncise (e. g. 
re m o val of 
a nal ys is f or 
se verity or 
relati o ns hi p t o 
st u d y treat me nt).
Secti o n 
1 5. 7
Bel o w te xt was a d de d:
F or S Q D E S, a s u bject is defi ne d as h avi n g dry eye 
sy n dro me if t her e w as occ urre nce of b ot h dry ness a n d 
irrit ati o n of t he eyes eit her c o nst a ntly or ofte n (t h at is, 
severe sy m pt o ms) or a re p ort of a previ o us cli nic al 
di a g n osis of dry eye sy n dr o me.
To  o utli ne h o w 
dr y  e ye is defi ne d
fr o m t he S Q D E S.
Secti o n 
1 5. 7
Bel o w te xt was a d de d:
I nf or m ati o n fro m t he n o m o gr a m, if o ne is use d, a n d s ur gic al 
rep ort will als o be pr ovi de d .
To  s pecif y t hat
data fr o m 
n o m o gra m use 
will be pr o vi de d .
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Page 33 of 81
6
SCHEDULE OF VISITS
Table 6–1
Schedule of Assessments
Level
Pre-surgery
Surgeryh
Post-Surgery
UNSVj
Procedure
Subject/Eye
Screening
(Day -45 to 
Day -1)
Day 0a
Day 1
Week 1
(Day 5 to Day 
9)
Month 1
(Day 21 to 
Day 35)
Month 3
(Day 70 to Day 
98)
Month 12k
(Day 330 to Day 
375)
N/A
Informed consentb
S
X
Demographics
S
X
Medical/ocular 
history/concomitant 
medications
S/E
X
X
X
X
X
X
X
X
Inclusion/exclusion 
criteria
S/E
X
X
Pregnancy testc, f
S
X
RSVP questionnairef
S
X
X
X
X
SQDESf
S
X
X
X
X
Photopic Distance 
UCVAe, f
E
X
X
X
X
X
X
X
Mesopic Uncorrected 
contrast sensitivityf
E
X
X
X
X
Manifest refractionf
E
X
X
X
X
X
X
Photopic Distance 
BCVAe, f
E
X
X
X
X
X
Pupillometryf
E
X
Keratometryd, f
E
X
Topographyd, f
E
X
X
X
X
Pachymetry f
E
X
Axial lengthf
E
X
Slit lamp examinationf
E
X
X
X
X
X
X
X
X
IOPf
E
X
X
X
X
X
Cycloplegic refraction
E
X
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Level
Pre-surgery
Surgeryh
Post-Surgery
UNSVj
Procedure
Subject/Eye
Screening
(Day -45 to 
Day -1)
Day 0a
Day 1
Week 1
(Day 5 to Day 
9)
Month 1
(Day 21 to 
Day 35)
Month 3
(Day 70 to Day 
98)
Month 12k
(Day 330 to Day 
375)
N/A
Dilated fundus 
examination
E
X
X
X
Randomizationg
S
X
LASIK or SMILE
E
X
Adverse eventsi
S/E
X
X
X
X
X
X
X
X
Device deficiencies
NA
X
Problems during surgeryl
S/E
X
Other procedures during 
surgery
S/E
X
a. Relevant measurements from the Pre Surgery Visit should be repeated prior to surgery if needed to provide accurate Baseline measurements pre-surgery. This includes the 
second optical infinity adjusted manifest refraction to demonstrate refractive stability in contact lens wearers as outlined in Inclusion Criteria 9.
b. All subjects must consent to bilateral treatment; both eyes are to be treated on the day of surgery.
c. Women of child-bearing potential only.
d. Keratometry and corneal topography must be done prior to IOP and pachymetry.
e. Distance UCVA and BCVA will be measured at each visit using an ETDRS chart at 3 meters (10 feet) or 4 meters (13 feet). For subjects who cannot read English letters, a 
numerical, Tumbling E or a Landolt C logMAR chart can be used.
f. These tests must be done prior to the instillation of dilating or cylcoplegic agents.
 
g. Randomization must be completed following all screening procedures and confirmation of subject eligibility during the Pre-Surgery visit.
h. Surgery must occur within 45 calendar days from the Pre Surgery Visit. Pre Surgery Visit and Surgery Visit cannot occur on the same day.
i. AEs should be collected from time of consent.
j. At an unscheduled visit, safety assessments and other assessments needed as per investigator’s discretion may be performed.
k. If a subject discontinues early, these procedures should be performed before exiting the subject. Month 12 (Final Visit) procedures should be performed at the last available visit, 
if at all possible.
l. Includes intraoperative complications.
RSVP=Refractive Status and Vision Profile, SQDES=short questionnaire for dry eye syndrome, UCVA=uncorrected visual acuity, BCVA=best corrective visual acuity,
IOP=intraocular pressure, LASIK=Laser in situ keratomileusis, SMILE=Small incision lenticule extraction, ETDRS=Early Treatment Diabetic Retinopathy Study, 
LogMAR=Logarithm of the Minimum Angle of Resolution, UNSV= unscheduled visit.
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7
INTRODUCTION
7.1
Background
Laser in situ keratomileusis (LASIK), a refractive surgery procedure, has been in use for over 
20 years for the correction of refractive error. The refractive error correction is achieved by 
the ablation of the required amount of corneal stromal tissue by an excimer laser. The 
WaveLight® EX500 excimer laser system is the most recent Alcon excimer laser (Sugar 
2002).
Treatment planning for LASIK is done with the refractive error correction data and with or 
without other patient specific pre-surgical data. The use of patient specific pre-surgical data 
offers customization of LASIK. For example, with Topography Guided LASIK, corneal 
height data is used to plan the LASIK surgery. Topography Guided LASIK has been available 
outside the US since 2003 and had been used primarily for the treatment of irregular or 
diseased corneas that either had never been treated or had been previously treated 
(Knorz 2000, Kymionis 2004, Holland 2013). More recently, Topography Guided LASIK is 
being used as a primary treatment for regular corneas. A study by Stulting et. al showed that 
Topography Guided LASIK as a primary treatment for myopia with or without astigmatism 
was safe and effective in subjects who had regular corneas (Stulting 2016).
Small incision lenticular extraction (SMILE) is the newest refractive surgery procedure that 
is being used for the correction of myopia with or without astigmatism. The Zeiss VisuMax 
laser keratome ophthalmic surgical laser, a femtosecond laser, is the only marketed laser for 
the SMILE procedure. The VisuMax creates a lenticule of corneal tissue and a small (<4mm) 
channel through which the lenticule is removed. The removal of the lenticule results in 
correction of the refractive error. Refractive error correction data but not corneal height data 
is used in the treatment planning of SMILE. Data in the literature for SMILE is showing 
good outcomes for safety and effectiveness (Ivarsen 2014, Moshirfar 2015).
Fundamental difference between the EX500 and VisuMax are that the EX500 provides 
centration and cyclotorsion control, and the VisuMax does not. Centration and cyclotorsion 
control allow for better correction of astigmatism. Additionally, use of the topography data 
for treatment planning of Topography Guided data should allow for better correction of 
astigmatism compared to SMILE for which topography data is not used for treatment 
planning. 
Myopia with astigmatism is a common refractive error (MarketScope 2015), and this study is 
designed to determine if the Topography Guided LASIK with the EX500 is superior to
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SMILE with the VisuMax for the correction of astigmatism in subjects with myopia and
astigmatism.
7.2
Clinical Study Design
This is a prospective, parallel group, multi-center, randomized, observer masked study
comparing topography guided LASIK vs. SMILE, both of which are commercially available 
in the countries where the study is being conducted.
Potential subjects are screened and up to 450 subjects (225 subjects per treatment group) are
enrolled at approximately 8 study sites in order to achieve about 185 evaluable subjects per 
treatment group. In total, 740 eyes from approximately 370 subjects are required for this 
study.
Subjects (18 years or older [subjects in Singapore must be 21 years of age or older and 
subjects in Korea must be upon completion of 19 years of age or older due to local 
regulations]) with myopia requiring refractive error correction of -0.5 to -8.0 D optical 
infinity adjusted manifest refraction sphere and astigmatism correction of -0.75 to -5.0 D 
manifest refraction cylinder and at least 0.75 D of corneal astigmatism in both eyes, and 
fulfilling all other eligibility criteria, are enrolled into the study and undergo pre-surgery
screening. Among other exclusion criteria, subjects are excluded if they have a history or 
evidence of active or inactive corneal disease, and systemic disease and medications that may 
confound wound healing. 
Qualifying subjects are required to attend a total of 7 visits over a period of up to 15 months
(See Section 9.1).
Subjects are randomized 1:1 by investigational site during the Pre-Surgery period to undergo 
bilateral surgery with either Topography Guided LASIK or SMILE scheduled on Day 0. 
The main analyses for effectiveness and safety are conducted when the last subject completes 
the 3 months Post-Surgery follow-up Visit. Subjects are followed-up for an additional 9 
months (Day 330 to Day 375) for safety and 
 assessments. Final data 
analyses are conducted at study completion.
An overview of the study design is presented in Figure 7–1. 
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Figure 7–1
Study Design
Site personnel performing the manifest refraction subjective assessment and all uncorrected 
visual acuity (UCVA) testing after randomization are to remain masked with regard to 
treatment assignment until after the final database lock (DBL). Alcon and other site personnel
[e.g., nurses and technicians involved with the surgery, site personnel entering data in the 
electronic case report forms (eCRF), site personnel administering other study related 
procedures, e.g. Refractive Status and Vision Profile (RSVP) and short questionnaire for dry 
eye syndrome (SQDES) questionnaires] must not reveal the treatment assignment to masked 
site personnel at any time during the study. Refer to Section 13.5 for unmasking of study 
information.
8
CLINICAL STUDY OBJECTIVES
8.1
Primary Objective
The primary objective of the study is to demonstrate that Topography Guided LASIK is 
superior to SMILE in the percentage of eyes with manifest refraction cylinder ≤ 0.5 D at 
3 months.
Subjects with 
myopia and 
astigmatism
Pre Surgery
Screening
Topography 
Guided 
LASIK
SMILE
Randomization
Bilateral Surgery
12 months 
Follow-up with 
3 months 
analysis for the 
primary and 
secondary 
objectives
-45 Day to -1 Day
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Pa ge 3 8 of 8 1
8. 2
Sec o n d ar y O bjecti ves
T he sec o n dar y  o bjecti ves of t he st u d y are:

To  de m o nstrate t hat To p o gra p h y  G ui de d L A SI K is s u peri or t o S MI L E i n mea n 
ma nifest refracti o n c y li n der at 3 m o nt hs.

To  de m o nstrate t hat To p o gra p h y  G ui de d L A SI K is s u peri or t o S MI L E i n mea n U C V A
at 3 m o nt hs .
8. 4
S afet y O bjecti ves
T he safet y o bjecti ves of t he st u d y  are:

To  e val uate t he a d verse e ve nts ( A Es) ass ociate d wit h To p o gra p h y G ui de d L A SI K a n d 
S MI L E .

To  e val uate p ost -s ur gery B C V A after To p o gra p h y  G ui de d L A SI K a n d S MI L E.

To  e val uate mes o pic u nc orrecte d c o ntrast se nsiti vit y after To p o gra p h y G ui de d L A SI K 
a n d S MI L E .

To  e val uate q ualit y of visi o n a n d visi o n relate d q ualit y  of life after To p o gra p h y  
G ui de d L A SI K a n d S MI L E .
8. 5
St u d y E n d p oi nts
8. 5. 1
Effecti ve ness E n d p oi nts
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
T he pri mar y  effecti ve ness e n d p oi nt is t he perce nta ge of e y es wit h ma nifest refracti o n 
c yli n der ≤0. 5 D at 3 m o nt hs .

Pa ge 3 9 of 8 1
S ec o n dar y effecti ve ness en d p oi nt s are as f oll o ws:

Mea n ma nifest refracti o n c y li n der at 3 m o nt hs.

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
Mea n U C V A at 3 m o nt hs .

Pa ge 4 0 of 8 1
8. 5. 2
S afet y E n d p oi nts
T he sec o n dar y  safety e n d p oi nts are as f oll o ws: 

Fre q ue nc y  of treat me nt-e mer ge nt A E s.

Mea n i ntra oc ular press ure ( I O P) at Scree ni n g, 1 m o nt h, 3 m o nt hs, a n d 1 2 m o nt hs .

Fre q ue nc y  of de vice deficie ncies

B C V A:
o
Mea n B C V A at Scree ni n g, 1 wee k, 1 m o nt h, 3 m o nt hs, a n d 1 2 m o nt hs.
o
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
Perce nt a ge of e y es wit h p ost -s urger y  B C V A m ore t ha n t w o li nes better, t w o 
li nes better, o ne li ne better , less t ha n o ne li ne better a n d greater t ha n o ne li ne 

Pa ge 4 1 of 8 1
w orse, o ne li ne w orse, t w o li nes w orse , m ore t ha n t w o li nes w orse t ha n 
pre -s urger y B C V A at Scree ni n g, 1 wee k, 1 m o nt h, 3 m o nt hs, a n d 1 2 m o nt hs .

U nc orrecte d c o ntrast se nsiti vit y :
o
Mea n mes o pic u nc orrecte d c o ntrast se nsiti vit y at eac h c o ntrast le vel at 
Scree ni n g, 1 m o nt h, 3 m o nt hs, a n d 1 2 m o nt hs.

Q ualit y  of visi o n a n d q ualit y of life (f or b ot h R S V P a n d S Q D E S):
o
R S V P: Mea n o verall a n d s u bscale visi o n relate d q ualit y  of life sc ore at 
Scree ni n g, 1 m o nt h, 3 m o nt hs, a n d 1 2 m o nt hs .
o
S Q D E S: Fre q ue nc y  of dr y e ye s yn dr o me at Scree ni n g, 1 m o nt h, 3 m o nt hs, 
a n d 1 2 m o nt hs.
9
I N V E S TI G ATI O N A L  P L A N
9. 1
O utli ne of Cli nic al St u d y
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
I n t his pr os pecti ve, parallel gr o u p, m ulti-ce nter, gr o u p ra n d o mize d, o bser ver mas ke d st u d y, 
s u bjects re q uiri n g refracti ve c orrecti o n of m y o pia a n d asti g matis m will be scree ne d. If t he 
pr ot oc ol i nc l usi o n a n d e xcl usi o n criteria are met, s u bjects will be i n vite d t o partici pate. A n 
i nstit uti o nal re vie w b oar d (I RB ) or i n de pe n de nt et hics co m mitt ee ( IE C) a p pr o ve d I nf or me d 
C o nse nt D oc u me nt will be si g ne d pri or t o i nitiati o n of a n y st u d y relate d pr oce d ures. 
T he i nte n de d treat me nt is bilateral (i.e. s ur ger y i n b ot h e yes) To p o gra p h y  G ui de d LA SI K or 
S MI L E . It is pla n ne d t hat eac h s u bject will ha ve s ur ger y o n b ot h e yes o n t he sa me da y. 
S u bjects partici pati n g i n t his st u d y  will atte n d a t otal of 7 visits f or b ot h e yes as f oll o ws : 
Pre - S urger y V isit ( Da y - 4 5 t o Da y -1), S ur ger y  Visit ( Da y 0), a n d 5 P ost - Sur ger y f oll o w- u p 
V isits ( o n Da y 1, Wee k 1, M o nt h 1, M o nt h 3, a n d M o nt h 1 2 , res pecti vely ). Eac h s u bject is 
e x pecte d t o c o m plete t he st u d y i n a p pr o xi matel y 1 2 m o nt hs ( Da y 3 3 0 t o Da y  37 5 ) after t he 
S ur ger y V isit ( Da y 0). T he t otal e x pecte d d urati o n of eac h s u bject’s partici pati o n is u p t o 1 5 
m o nt hs ( Pre -s ur gery t o M o nt h 1 2 p ost -s urger y ). Refer t o Fi g ure 7 – 1 St u d y Desi g n f or a st u dy 
o utli ne dia gra m.
Re -treat me nt pr oce d ures are n ot all o we d f or a ny e nr olle d st u d y e ye. U nsc he d ule d visits ma y  
occ ur as nee de d. 

Page 42 of 81
9.2
Rationale for Study Design
This study is designed to test the differences in astigmatism treatment between Topography 
Guided LASIK and SMILE. The difference in astigmatism treatment between the two 
refractive surgeries is hypothesized to be related to the differences in the lasers and treatment 
planning. With Topography Guided LASIK, the cyclotorsion control and the centration 
features of the EX500 laser and the use of topography data for treatment planning should 
enhance the accuracy of astigmatism treatment. In contrast, with SMILE, the VisuMax Laser 
keratome does not have cyclotorsion control or centration nor is topography data used for 
treatment planning. The study population includes subjects with myopia and astigmatism 
because this is a prevalent refractive error (Market Scope 2015) and is an approved indication
for both lasers. (refer to Procedure’s and Operator’s or User’s manual).
9.2.1
Procedures Per Study Visit
The clinical study procedures to be conducted at each study visit are listed in Table 6–1 and 
detailed in Section 12. Further details on the actual assessments are provided in full in the 
Manual of Procedures (MOP) for this study. A brief summary of the procedures performed 
by visit is provided here.
NOTE: All assessments performed at the eye level as listed in Table 6–1 will be done 
monocularly.
At the Pre-Surgery Visit (Day -45 to Day -1) the subject will sign the informed consent form
(ICF). Standard procedures will be performed to determine subject eligibility. The subject 
will be evaluated against all entry criteria. The subject status (e.g, continuing or screen 
failure) will be documented and the subject’s data will be entered into electronic data capture 
(EDC) at the time of consent to assign subject number. For continuing subjects:
1. The subject will be randomized to Topography Guided LASIK or SMILE in the EDC
system.
2. The subject will be provided with pre-surgery information and medications in accordance 
with investigational site’s standard of care.
3. The Investigator will consider any unresolved complications or events in either eye prior 
to surgery.
4. The Surgery Visit (Day 0) will be scheduled to occur within 45 calendar days of the 
Pre-Surgery Visit (Screening).
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a.
Incl usi o n/ e xcl usi o n criteria will be re vie we d pri or t o s ur ger y  t o e ns ure s u bjects 
are still eli gi ble f or t he st u d y (see Secti o n 1 0. 1 a n d 1 0. 2 ). S u bjects faili n g t o pass 
e ntr y criteria will n ot be re-scree ne d. If a s u bject is e xcl u de d p ost-ra n d o mizati o n 
a n d pri or t o t he laser t o uc hi n g t he e y e ( defi ne d as o nce fla p creati o n is i nitiate d 
f or L A SI K a n d o nce laser t o uc hes t he e ye f or S MI L E ), t he s u bject s h o ul d be 
disc o nti n ue d fr o m partici pati o n i n t he st u d y . 
b.
T he s ur ger y will be perf or me d o n b ot h e yes. T he s u bject will be pre pare d f or 
s urger y  i n acc or da nce wit h site s pecific o perati n g pr oce d ures.
5.
After s ur ger y , t he oc ular a n d/ or n o n- oc ular c o nc o mita nt me dicati o n will be a d mi nistere d 
as per I n vesti gat or ’s sta n dar d pr oce d ures.
6.
T he s u bject will ret ur n t o t he i n vesti gati ve site t o c o m plete p ost- s ur ger y f oll o w- u p 
assess me nts. At all P ost - S urger y  f oll o w- u p Visits ( Da y 1, Wee k 1, M o nt h 1, M o nt h 3, 
M o nt h 1 2), effecti ve ness a n d safet y assess me nts will be perf or me d. N o sec o n dar y  
s ur gical i nter ve nti o n or re-treat me nt pr oce d ures are all o we d i n t his st u d y.
N O T E S : 

A Es will be rec or de d at eac h visit a n d re p orte d fr o m t he ti me of i nf or me d c o nse nt 
f or all s u bjects i n t he st u d y.

P atie nt-re p orte d o utc o mes ( P R Os) will be meas ure d i n t he st u d y t o assess t he 
i nci de nce of sy m pt o ms a n d/ or p ost -s ur gery c ha n ge i n s ym pt o ms fr o m pre -s urger y
stat us via s u bjecti ve rati n gs. T hese will c o nsist of t he R S V P q uesti o n naire ( Vitale 
2 0 0 0), a vali date d i nstr u me nt f or t he meas ure me nt of visi o n relate d q ualit y of life, 
a n d S Q D E S f or t he dia g n osis of dr y e ye ( G ulati 2 0 0 6).
9. 3
Ris k  Be nefit Assess me nt
9. 3. 1
P ote nti al Ris ks
L A SI K a n d S MI L E
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
T he ris ks of L A SI K are well k n o w n, h o we ver, t he ris ks of S MI L E are still bei n g i n vesti gate d 
beca use it is a ne wer pr oce d ure ( Se k u n d o 2 0 1 1 , S ol o m o n 2 0 0 9).
S o me ris ks are si milar f or L A SI K a n d S MI L E . First, t he laser c o ul d malf u ncti o n a n d t he 
pr oce d ure w o ul d nee d t o be st o p pe d bef ore c o m pleti o n. If t his ha p pe ns, a sec o n d s ur gical 
pr oce d ure ma y  be nee de d. Sec o n d, LA SI K a n d S MI L E ma y  n ot f ull y c orrect, or ma y 
o verc orrect t he refracti ve err or , lea vi n g t he s u bject wit h s o me resi d ual refracti ve err or . 

Pa ge 4 4 of 8 1
U n derc orrecti o n or o verc orrecti o n ma y  be treata ble b y perf or mi n g a sec o n d refracti ve 
s urger y. A d diti o nall y , dece ntrati o n of t he treat me nt as a res ult of off -ce nter place me nt of t he 
laser ma y occ ur, w hic h c o ul d affect t he o utc o me a n d c o nse q ue ntly t he s u bject’s visi o n. 
L A SI K
L A S I K i n v ol ves t he creati o n of a c or neal fla p, a n d t he f oll o wi n g c o m plicati o ns ma y 
i nfre q ue ntly occ ur: dece ntere d or disl ocate d fla p, de bris u n der t he fla p, fla p tears, c o m pletely 
dissecte d fla p (free fla p), a n d fla p t hat’s t o o t hi n ( S h ortt 2 0 1 3). T hese c o m plicati o ns are 
ma na ge d d uri n g t he s ur ger y w hic h ma y i ncl u de s witc hi n g t o a n ot her s ur gi cal pr oce d ure s uc h 
as p h ot orefracti ve keratect o m y  ( P R K).
Seri o us c o m plicati o ns lea di n g t o si g nifica nt p er ma ne nt vis ual l oss s uc h as i nfecti o ns a n d 
c or neal ectasia occ ur rarel y  wit h L A SI K; h o we ver, c o m plicati o ns s uc h as c hr o nic dr y e ye, 
star b ursts, glare, hal os a n d re d uce d c o ntrast se nsiti vit y occ ur m ore fre q ue ntl y ( S u gar 2 0 0 2). 
S o me of t hese c o m plicati o ns, s uc h as c or neal ectasia a n d dr y e yes, ma y be mi ni mize d b y 
selecti n g s uita ble s u bjects f or L A SI K. To mi ni mize t he ris k of c or neal ectasia, s u bjects wit h 
s us pici o us pre-s urger y  t o p o gra p hies a n d t hi n c or neas s h o ul d n ot be treate d wit h LA SI K . To 
mi ni mize t he r is k of c hr o nic dr y e ye, e xisti n g dr y e ye s h o ul d be treate d pri or t o t he L A S I K. It 
is m ore c halle n gi n g t o mi ni mize t he vis ual s ym pt o ms ris ks s uc h as glare, hal os, star b ursts ,
a n d re d uce d c o ntrast se nsiti vit y beca use t hese c o m plicati o ns are i n here nt t o h o w r efracti ve 
s urger y  w or ks. S u bject e d ucati o n of t he p ossi bilit y  of ha vi n g t hese t ypes of c o m plicati o n s is 
ke y.
T he ris ks of To p o gra p h y  G ui de d L A SI K are n ot k n o w n t o be dif fere nt t ha n t he ris ks of ot her 
met h o ds of L A SI K.
S MI L E
I varse n et al (I varse n 2 0 1 4) perf or me d a st u d y t o e val uate t he safet y of S MI L E. A t otal of 
1 5 7 4 e yes were treate d wit h S MI L E a n d f oll o we d f or 3 m o nt hs. I n t his st u d y, t he p re-s urger y
c o m plicati o ns re p orte d i n at least o ne e ye were as f oll o ws:

A brasi o n at t he i ncisi o n

Le ntic ule e xtract i o n diffic ulties

Mi n or tear at t he i ncisi o n

S ucti o n l oss

Ce ntral a brasi o n 

Ca p perf orati o n 

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
Maj or tear

Pa ge 4 5 of 8 1

I m p ossi ble le ntic ule e xtracti o n 
T he p ost -s ur gery c o m plicati o ns re p orte d i n at least o ne e y e were as f oll o ws:

Haze

Dr y  s urface

E pit helial isla n ds at i nci si o n

Fi ber i n t he i nterface

I nfiltrates/ keratitis

M o n oc ular g h ost i ma ges

I nterface i nfla m mati o n 
I n ge neral, t hese c o m plicati o ns ma y be mi ni mize d b y  s ufficie nt pr oficie nc y i n perf or mi n g t he 
S MI L E pr oce d ure , a n d laser setti n g o pti mizati o n .
9. 3. 2
P ote nti al Be nefit s
L A SI K a n d S MI L E
A k e y  be nefit of L A S I K a n d S MI L E is t he c orrecti o n of t he s u bject’s refracti ve err or 
res ulti n g i n t he eli mi nati o n or re d ucti o n of t he nee d f or glasses or c o ntact le nses. S u bject s 
w h o ha ve s pe nt m ost of t heir li ves de pe n de nt o n glasses rea ll y e nj oy re d uci n g or eli mi nati n g 
t his de pe n de nce. C o ntact le ns wearers w h o ha ve L A SIK or S MI L E be nefit fr o m t he 
c o n ve nie nce of n ot ha vi n g t o mai ntai n a c o ntact le ns re gi me n. O ne st u d y s h o we d t hat c o ntact 
le ns wearers w h o ha d L A SIK were ver y  satisfie d after t he s ur ger y ( Price 2 0 1 6).
9. 3. 3
Ris k  Be nefit Assess me nt
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
O verall, t he be nefits of L A SI K a n d S MI L E o ut wei g h t he ris ks. Se veral strate gies are 
e m pl o ye d t o mi ni mize t he ris ks ass ociate d wit h eit her s ur ger y. Stri n ge nt i ncl usi o n/e xcl usi o n 
criteria are utilize d d uri n g t he s u bject scree ni n g pr ocess t o ass ure t hat p ote ntial s u bjects are 
acce pta ble ca n di dates. P ost - S urger y f oll o w- u p Visits are sc he d ule d at re g ular i nter vals t o 
m o nit or i m pr o ve me nt i n visi o n, as well as t o m o nit or s u bject safet y.  S u bject s are gi ve n 
detaile d p ost -s urger y i nstr ucti o ns t o mi ni mize disc o mf ort a n d p ost-s urger y c o m plicati o ns a n d 
are i nstr ucte d t o call t heir d oct or i m me diatel y if a n y pr o ble ms occ ur. I n a d diti o n, e xte nsi ve 
tec h nical trai ni n g of s ur ge o ns a n d cli nical staff i n t he pr o per use of s ur gical e q ui p me nt a n d 
tec h ni q ues use d wit h t hese pr oce d ures is e m pl o ye d t o re d uce t he ris ks of user err or. 

Page 46 of 81
10
SUBJECT POPULATION
Subjects ≥ 18 years of age [subjects in Singapore must be 21 years of age or older and 
subjects in Korea must be upon completion of 19 years of age or older due to local 
regulations] with myopia requiring refractive error correction of -0.5 to -8.0 D optical infinity 
adjusted manifest sphere and astigmatism correction of -0.75 to -5.0 D manifest refraction 
cylinder and at least 0.75 D of corneal astigmatism in both eyes, and fulfilling all other 
eligibility criteria in Section 10.1 and Section 10.2, will be enrolled into the study.
Within a 45 calendar day window prior to surgery, subjects will be screened and randomized 
in a 1:1 manner to receive EX500 for Topography Guided LASIK or VisuMax for SMILE.
All ocular related inclusion and exclusion criteria apply to both eyes. It is estimated that 
approximately 6 months will be required to complete enrollment for this study.
NOTE: No one site will randomize more than 25% of the total subject cohort and enrolment 
will be competitive in order to complete enrolment on time.
10.1
Inclusion Criteria
Below is a list of inclusion criteria. Ocular criteria must be met in both eyes.
1. Subjects 18 years of age or older at the time of informed consent [subjects in Singapore 
must be 21 years of age or older and subjects in Korea must be upon completion of 19 
years of age or older due to local regulations]
2. Able to comprehend and sign an informed consent form (ICF).
3. Willing and able to complete all post-surgery visits.
4. Myopia requiring (a) refractive error correction of -0.5 to -8.0 D optical infinity adjusted 
manifest refraction sphere with (b) astigmatism correction of -0.75 to -5.0 D manifest 
refraction cylinder and (c) at least 0.75 D of corneal astigmatism.
5. Intended treatment is targeted for emmetropia.
6. Pre-surgery BCVA of 0 logarithm of the minimum angle of resolution (logMAR) (20/20) 
or better.
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Pa ge 4 7 of 8 1
7.
S p herical e q ui vale nt differe nce of ≤0. 5 D bet wee n t he o ptical i nfi nit y  a dj uste d ma nifest 
a n d o ptical i nfi nit y  a dj uste d c ycl o ple gic refracti o n o utc o mes.
8.
S p herical e q ui vale nt differe nce of ≤0. 5 D bet wee n refracti ve err or c orrecti o ns f or a 
mi ni m u m of 1 2 m o nt hs pri or t o s ur ger y verifie d b y c o nsec uti ve o ptical i nfi nit y  a dj uste d 
refracti o ns a n d/ or me dical rec or ds or prescri pti o n hist or y.
9.
F or c o ntact le ns wearers - S p herical e q ui vale nt differe nce of ≤0. 5 D bet wee n o utc o mes 
fr o m c o nsec uti ve o ptical i nfi nit y  a dj uste d ma nifest refracti o n o utc o mes perf or me d at least 
7 da y s a part after t he c o ntact le ns wear has bee n st o p pe d f or t he a p pr o priate peri o d of 
ti me as f oll o ws:

S oft (e xte n de d a n d dail y  wear) = 3 da y s 

Ri gi d Gas Per mea ble ( R G P ) or T oric = 2 wee ks

Har d p ol y m et h yl  met hacr ylate ( P M M A) = 3 wee ks
1 0. 2
E xcl usi o n Criteri a
Bel o w is a list of e xcl usi o n criteria. Oc ular criteria m ust n ot be met i n eit her e ye.
1.
Pre g na nc y  or lactati o n, c urre nt or pla n ne d, d uri n g t he c o urse of t he st u d y.
2.
Ma nifest refracti o n asti g matis m t hat is m ore t ha n 1. 0 0 D t ha n t he t o p ol y zer asti g matis m
assesse d b y C o nt o ura s oft ware.
3.
Mi xe d asti g matis m refracti ve err or .
4.
De ge nerati o ns of str uct ure of t he c or nea i ncl u di n g dia g n ose d kerat oc o n us, f or me fr uste 
keratac o n us or pell uci d mar gi nal de ge nerati o n.
5.
Dr y  e ye as i de ntifie d b y t he S Q D E S .
6.
A calc ulate d resi d ual str o mal be d t hic k ness t hat is less t ha n 2 5 0 µ m.
7.
Hist or y  or e vi de nce of acti ve or i nacti ve c or neal or ot her a nteri or se g me nt disease (e .g, 
her pes si m ple x keratitis, rec urre nt er osi o n s y n dr o me).
8.
Dia g n ose d a d va nce d gla uc o ma.
9.
U nc o ntr olle d dia betes.
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Page 48 of 81
10. Nystagmus or any other condition that would prevent a steady gaze during the treatment.
11. Previous intraocular or corneal surgery.
12. Weakened immune system, including diagnosed collagen vascular, autoimmune or 
immunodeficiency disease.
13. Systemic medications that may affect corneal healing including, but not limited to
steroids, antimetabolites, immune response modifying drugs, etc.
14. Presence or history of any condition or finding that makes the subject unsuitable as a 
candidate for refractive surgery or study participation or may confound the outcome of 
the study, in the opinion of the Investigator.
15. Any subject currently participating in another investigational drug or device study that 
may confound the results of this investigation.
16. A known sensitivity to medications used during the study.
11
TREATMENT
The treatment in this study involves the use of either the EX500 for Topography Guided 
LASIK or the VisuMax for SMILE as described in Table 11–1.
For the purposes of this study, treatment will be considered to have begun once the flap 
creation is initiated for LASIK and once the laser touches the eye for SMILE.
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Table 11–1
Treatments
Test Article: Wavelight 
EX500 for Topography 
Guided LASIK
Control Article: Zeiss 
VisuMax for SMILE
Administration
The EX500 laser is used to 
ablate the corneal stroma 
which results in the refractive 
error correction. Prior to 
ablation, the corneal flap may 
be created with a 
femtosecond laser or 
microkeratome blade at the 
surgeon’s discretion. 
Treatment planning will be 
based on topography.
The VisuMax Laser keratome
is used to create a lenticule in 
the corneal stroma and a 
channel for the removal of 
the lenticule. Removal of the 
lenticule results in the 
refractive error correction.
Duration of treatment
The treatment is intended to 
last the subject’s lifetime.
The treatment is intended to 
last the subject’s lifetime.
The Investigator will be responsible for ensuring that the EX500 and VisuMax Laser Systems 
are used in accordance with their indications and procedural guidance provided in their 
respective Operator’s (or User’s) and Procedure’s Manuals by a licensed ophthalmologist 
with LASIK and/or SMILE surgery experience. A summary of the necessary training and 
experience needed to use the investigational device must be recorded at the site.
11.1
Investigational Products
Test Article: Wavelight EX500 Laser System for Topography Guided LASIK
EX500 is a stationary scanning-spot excimer laser system used in refractive surgery for the 
treatment of myopia, myopia with astigmatism, hyperopia, hyperopia with astigmatism and 
mixed astigmatism. The system consists of technologically refined features, including a 
compact excimer laser with leading edge high pulse frequency, a galvanometer scanner for 
positioning the laser spot and a fast eye tracker for determining eye position and laser-beam 
direction. The Gaussian shaped beam profile of the individual pulses and an ablation 
diameter of approximately 0.95 mm (0.68 mm Full Width at Half Maximum [FWHM]) 
assure the desired contour and minimize surface irregularities during ablation. 
The small spot of the EX500 requires the use of only minimal pulse energy. The result is a 
compact excimer laser beam source with minimal gas volume and minimal gas consumption. 
As the excimer laser is operated at a high repetition frequency, short treatment times are 
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Page 50 of 81
assured. The integrated eyetracker offers automatic centering of the ablation and tracking of 
even rapid eye movements.
Treatments by the EX500 may be planned at an auxillary laptop and the information is 
transferred by a network or may be planned at the EX500 itself. 
Figure 11–1
Wavelight EX500 Laser System 
The product is manufactured by WaveLight GmbH and manufactured for Alcon Laboratories, 
Inc. The product is a CE Marked device approved for use and commercially available in the 
countries with participating Investigators as well as other countries across the globe.
More information on the laser and accessories, auxiliary parts, and consumables can be found 
in the EX500 User Manual.
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Page 51 of 81
Control Article: VisuMax Laser keratome for SMILE
Figure 11–2
VisuMax
The VisuMax laser keratome generates a beam of ultra-short laser pulses which are guided to 
the aperture in the treatment objective by an optical system (including controllable laser 
beam deflectors). The optical system focuses the laser beam into the corneal tissue. At its 
focal point, each ultra-short laser pulse causes an optical breakdown, creating plasma with a 
diameter of only a few microns. Continuous movement of the laser beam by the optical 
system creates incision surfaces within the cornea. All desired incisions are created in one 
work sequence. 
For the laser treatment, a contact glass (part of the treatment pack) adheres both to the 
subject's eye and to the laser aperture by vacuum applied to the laser aperture and the contact 
glass. 
The laser keratome’s integrated viewing optics allows the surgeon the immediate examination 
and preparation of the eye as well as the observation of the ongoing operation through the 
surgical microscope. An integrated video camera records the sequence of treatment.
An integrated computer with special software enables easy control of the laser keratome and 
saves the treatment data; other computers control and monitor the internal sequences. 
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Page 52 of 81
The product is manufactured by Carl Zeiss Meditec AG, Jena. The product is a CE Marked 
device approved for use and commercially available in the countries with participating 
Investigators as well as other countries across the globe.
More information on the laser and accessories, auxiliary parts, and consumables can be found 
in the VisuMax User Manual.
11.2
Usage
The EX500 is used with the LASIK procedure for the correction of refractive errors. The 
LASIK procedure involves the creation of corneal flap, with a femtosecond laser or 
microkeratome blade that is hinged and pulled back to expose the corneal stroma. Then, the 
EX500 is used to ablate the necessary amount of corneal stroma to correct the refractive 
error. 
LASIK may be customized by using subject specific diagnostic data. With Topography 
Guided LASIK, corneal topography data from each subject is used to customize the LASIK 
treatment. 
The VisuMax is used with the SMILE procedure for the correction of refractive errors. The 
SMILE procedure involves the creation of a refractive lenticule and small incision of less 
than 4 mm all in one step. The lenticule is removed through the incision which results in 
changing the shape of the cornea thereby achieving the desired refractive correction. 
Any significant discrepancy and/or deficiency when using the lasers must be recorded in the 
source documents and reported to the Sponsor, with an explanation (for details Refer to 
Section 13).
11.3
Accountability Procedures
Throughout the study, the Investigator will be responsible for accounting of the use of the 
investigational devices and all ancillary supplies and will ensure that the study products are 
not used in any unauthorized manner.
Upon receipt of any clinical supplies and ancillary supplies, the Investigator will conduct an 
inventory audit, complete and sign the Receipt of Clinical Supplies form as directed by the 
Sponsor. A copy must be retained in the Investigator’s clinical trial records.
The Investigator/staff must not use any ancillary supply that is damaged (such as broken, or 
seal is broken, etc). Damaged and/or deficient supplies should be brought to the attention of 
the Sponsor as soon as discovered. Refer to Section 13 Device Deficiencies and Adverse 
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Page 53 of 81
Events for more instructions on reporting. Please follow instructions from your Clinical Site 
Manager (CSM) to ensure return, destruction and or replacement as needed.
During laser use, a daily temperature, humidity and pressure log will be maintained and
appropriate investigational devices room environmental conditions will be documented and 
will be made available for inspection.
12
CLINICAL STUDY PROCEDURES
12.1
Clinical Study Assessments
The following section outlines the assessments to be performed in this clinical study.
The study assessments are listed by study visit in Table 6–1 and full details of the 
assessments for this study are described in the RFL605-P001 MOP. 
All assessments must be documented in source documentation and eCRFs (if applicable).
12.1.1
Pre-Surgery screening Visit (Day -45 to Day -1)
Below is a list of study procedures to be undertaken at Pre-Surgery Visit (Screening). The 
procedures must be performed in the order presented below unless otherwise stated. All 
ocular assessments must be done monocularly.
For applicable assessments, both eyes must qualify for the study, therefore the screening 
assessments will be performed in both eyes.
Upon signing the informed consent, subjects are considered enrolled. The subject is assigned 
a single subject identifier at the Pre-Surgery Visit. The subject identifier consists of a 
combination of a 4 digit investigator number and a 5 digit subject number. The number is 
automatically generated sequentially by the EDC system. As an example: “4584.00001” (The 
investigator number and subject number are separated by a “.” character).
This number is used throughout the clinical study. Within 45 business days of surgery, 
subjects will be screened and randomized based on 1:1 allocation to receive EX500 for 
Topography Guided LASIK or VisuMax for SMILE.
1. Upon identification of a possible study participant, carry out the informed consent 
process. Refer to Section 16.2 Informed Consent Procedures.
NOTE: Subjects must formally consent to participate in the study prior to undergoing any 
study specific testing. Upon signing informed consent, subjects are considered enrolled in 
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Pa ge 5 4 of 8 1
t he st u d y.
2.
Perf or m a uri ne pre g na nc y test if t he s u bject is a w o ma n of c hil d beari n g p ote ntial.
3.
D oc u me nt de m o gra p hics, oc ular a n d n o n - oc ular me dical hist or y, oc ular a n d n o n-oc ular 
c o nc o mitant me dicati o ns.
4.
A d mi nister t he R S V P Q uesti o n naire (a 5 2-ite m q uesti o n naire) t o assess q ualit y of visi o n 
a n d visi o n relate d q ualit y of life .
5.
A d mi nister t he S Q D E S t o e val uate dr y  e ye s ym pt o m a n d se verit y .
N O T E: I nvesti gat ors a n d site staf f m ust re vie w b ot h q uesti o n naire s res ults pri or t o 
s u bjects lea vi n g t he office t o e ns ure c o m plete ness.
6.
C o n d uct t he f oll o wi n g pr oce d ures i n a n or der t hat is feasi ble f or y o ur site :
N O T E S : 

Eac h s u bject m ust be refracte d b y a n o p ht hal m ol o gist, o pt o me trist, or a s kille d 
tec h nicia n. F or f urt her details, refer t o M O P.

To  e ns ure t he sta bility of refracti o n, eli gi ble s u bjects w h o c urre ntl y wear c o ntact 
le nses m ust disc o nti n ue t heir use f or t he a p pr o priate a m o u nt of ti me bef ore 
u n der g oi n g refracti ve laser s ur ger y i n t he st u d y as i n d icate d i n Ta ble 1 2 – 1.
N O T E : A c o ntact le ns wearer is defi ne d as s o me o ne w h o has w or n c o ntact le nses 
wit hi n 3 m o nt hs pri or t o t he Pre -S ur ger y  Visit.
Ta ble 1 2 – 1
Mi ni m u m ti me t o st o p we ari n g c o nt act le ns bef or e P re -S ur ger y 
V isit
Ty pe of C o n t act Lens
M i nim u m Ti me t o St o p W e ar i n g C o nt act Le ns
bef ore P r e- Sur ger y Vi sit
Har d ( P M M A) lenses
3 wee ks
R G P le nses
2 wee ks
S oft (extended and daily wear)
3 da ys

Perf or m li g hti n g m eas ure me nts f or V A a n d c o ntrast se nsiti vit y testi n g.

M eas ure d ista nce U C VA i n p h ot o pic c o n diti o ns usi n g a n Earl y T reat me nt 
Dia betic Reti n o pat h y St u d y ( E T D R S) c hart at 3 meters ( 1 0 feet) or 4 meters ( 1 3 
feet) rec or de d i n l o g M A R. F or s u bjects w h o ca n n ot rea d E n glis h letters, a 
n u merical, T u m bli n g E or a La n d olt C l o g M A R c hart ca n be use d. 

M eas ure u nc orrecte d c o ntrast se nsiti vit y  i n mes o pic c o n diti o ns usi n g a Ve ctor 
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Pa ge 5 5 of 8 1
Vi si on C hart, rec or de d i n l o g C S. 

Meas ure
ma nifest ref racti o n at 4 meters a n d a dj ust f or o ptical i nfi nit y .

Meas ure
dista nce B C VA i n p h ot o pic c o n diti o ns usi n g Earl y T reat me nt E T D R S
c hart at 3 meters ( 1 0 feet) or 4 meters ( 1 3 feet) rec or de d i n l o g M A R. F or s u bjects 
w h o ca n n ot rea d E n glis h letters, a n u merical, T u m bli n g E or a La n d olt C l o g M A R 
c hart ca n be use d. 
7.
C o n d uct t he f oll o wi n g pr oce d ures i n a n or der t hat is feasi ble f or y o ur site:

Perf or m kerat o metr y  usi n g a To p ol y zer Va ri o. 

P erf or m t o p o gra p h y usi n g a To p ol y zer Va ri o. V erif y t hat t he c or neal asti g matis m 
is re g ular ( b o w-tie s ha pe). 

Perf or m p u pill o metr y  u n der mes o pic c o n diti o ns usi n g a n i nfrare d p u pil o meter. 
T he sa me i nstr u me nt s h o ul d be use d t hr o u g h o ut t he st u d y.

Perf or m a xial le n gt h meas ure me nt usi n g a n o ptical bi o met er or a n y ot her
i nstr u me nt. T he sa me i nstr u me nt s h o ul d be use d t hr o u g h o ut t he st u d y.  

Perf or m pac h y m etr y usi n g a n ultras o nic c o ntact pac h ymeter de vice or a n y  ot her 
i nstr u me nt. T he sa me i nstr u me nt s h o ul d be use d t hr o u g h o ut t he st u dy.  
8.
Perf or m slit la m p e xa mi nati o n. 
9.
Meas ure
I O P usi n g a G ol d ma n n t o n o meter or a n y ot her i nstr u me n t. T he sa me i nstr u me nt 
will be use d t hr o u g h o ut t he st u d y . 
1 0. Perf or m c ycl o ple gic refracti o n usi n g a p h or o pter a n d a dj ust f or o ptical i nfi nit y . T h e sa me 
e q ui p me nt s h o ul d be use d t hr o u g h o ut t he st u d y. 
1 1. Perf or m dilate d f u n d us e xa mi nati o n.
1 2. Rec or d a n y A Es . Refer t o Secti o n 1 3 f or f urt her details.
N O T E: S A Es m ust be e ntere d i nt o E D C wit hi n 2 4 h o urs of t he I n vesti gat or ’s k n o wle d ge. 
1 3. E val uate s u bject a gai nst all e ntr y  criteria. D oc u me nt t he s u bject stat us. 
1 4. Ra n d o mize t he s u bject a n d sc he d ule t he S ur ger y V isit t o occ ur wit hi n 4 5 da ys of t he P re-
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Pa ge 5 6 of 8 1
S ur ger y  Visit ( Scree ni n g). 
N O T E: T he s u bject s h o ul d be disc o nti n ue d fr o m partici pati o n i n t h e st u d y if:

A n y  c o m plicati o n occ urre d pri or t o a n y laser c o mi n g i n c o ntact wit h t he e ye.
1 2. 1. 2
S ur ger y Vi sit ( D a y 0)
Pri or t o s urger y, t he I n vesti gat or m ust e ns ure t hat t he treat me nt pla n ni n g has bee n c o m plete d 
a n d t hat t he s u bject is still q ualifie d.
If a s ubject is e xcl u de d p ost -ra n d o mizati o n a n d pri or t o t he S ur ger y  Visit (i.e. t he laser d oes 
n ot c o me i n c o ntact w it h t he e ye), t he s u bject m ust be disc o nti n ue d fr o m partici pati o n i n t he 
st u d y. Refer t o Secti o n 1 2. 4 f or f urt her details.
D uri n g t he da y  of s ur ger y, t he I n vesti gat or m ust rec or d i nf or mati o n re gar di n g t he s ur ger y a n d 
relate d c o n diti o ns a n d als o details re gar di n g me dicati o n use d d uri n g t he s ur ger y, a n y 
pr o ble ms or c o m plicati o ns or ot her pr oce d ures t hat occ ur d uri n g t he s ur ger y .
Bel o w is a list o f pr oce d ures t o be u n derta ke n at S ur ger y Visit. Pr oce d ures m ust be 
perf or me d i n t he or der prese nte d bel o w u nless ot her wise state d . All oc ular assess me nts will
be d o ne m o n oc ularl y.
Acti vities i n v ol vi n g m ulti ple dele gate d staff me m bers ma y  be perf or me d i n parallel if t his 
ali g ns wit h t he st u d y s pecifie d se q ue nce .
Pr e p ar ati o n f or s ur ger y :
1.
Pri or t o s ur ger y, re vie w i ncl usi o n/e xcl usi o n criteria a n d e ns ure s u bject has bee n pr o perly 
c o nse nte d f or partici pati o n i n t he st u d y. Refer t o Secti o ns 1 0. 1 a n d 1 0. 2. Als o, d oc u me nt 
a n y c ha n ges t o oc ular a n d n o n-oc ular c o nc o mita nt me dicati o ns .
2.
Perf or m slit la m p e xa mi nati o n pri or t o s ur ger y .
3.
Pre pare s u bject/e y es f or s urger y  i n acc or da nce wit h site s pecific o perati n g pr oce d ures.
4.
E ns ure t he i n vesti gati o nal de vice t o w hic h t he s u bject is ra n d o mize d is utilize d f or t he 
s urger y.
Pr oce d ures rel ate d t o l aser s ur geries :
Laser s ys te ms a n d s ur geries s h o ul d be perf or me d acc or di n g t o t he O perat or ’s ( or User’s) a n d 
P r oce d ure’s m a n ual s. Refer t o t he ma n uals f or s pecific i nstr ucti o ns f or de vice set u p a n d 
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Pa ge 5 7 of 8 1
mai nte na nce t o e ns ure pr o per f u ncti o n pri or t o treat me nt.
1.
E ns ure t he Laser S ys te m is cali brate d per ma n ufact urer ’s i nstr ucti o ns pri or t o t he 
pr oce d ure.
2.
E ns ure t hat treat me nt para meters are precisely tra nsfer re d fr o m t he files t o t he laser 
s yste m.
N O T E : Tr eat me nt tar get is e m metr o pia f or all e yes.
3.
P erf or m s ur gery u n der t o pical a nest hesia as per t he n or mal r o uti ne of t he s ur ge o n.
N O T E : Alt h o u g h t he s ur ger y is pla n ne d t o be bilateral, i n t he case w here t he I n ves ti gat or 
deci des t o n ot perf or m t he s ur ger y o n t he sec o n d e ye o n t he sa me da y t he first e ye is 
treate d, t he I n vesti gat or ma y treat t he sec o n d e ye at a later date w hile t he s u bject is still i n 
t he st u d y. In t his case, eff ecti ve ness a n d safet y assess me nt s will be c o n d ucte d as per 
p ost -s urger y  f oll o w u p visits if t he fell o w e ye is treate d wit h t he st u d y treat me nt. If t he 
fell o w e ye is n ot treate d at all or treate d wit h a n o n -st u d y treat me nt, A Es will o nl y  be 
c ollecte d f or t his e ye. Refer t o t he M O P Ta ble 4 -1 f o r f urt her details. 
4.
Rec or d a n y A Es a n d de vice deficie ncies. Refer t o Secti o n 1 3 f or f urt her details.
N O T E: S A Es m ust be e ntere d i nt o E D C wit hi n 2 4 h o urs of t he I n vesti gat or ’s k n o wle d ge. 
O T H E R N O T E S:

Rec or d t he met h o d of fla p creati o n f or t he To p o gra p h y  g ui de d L A SI K s ur ger y 
(micr o kerat o me bla de or fe mt osec o n d laser) i n s o urce d oc u me nt.

Rec or d o perati n g r o o m te m perat ure a n d e n vir o n me ntal c o n diti o ns c o ntr ol i n s o urce 
d oc u me nt .

Rec or d a ll s ur gical me dicati o ns use d d uri ng t he pr oce d ure i n so urce d oc u me nt .

Rec or d s ur gical pr o ble ms or c o m plicati o ns t hat occ ur d uri n g s ur ger y i n s o urce d oc u me nt.

Rec or d a n y ot her pr oce d ures d uri n g s ur ger y i n s o urce d oc u me nt.

Rec or d t he s ur ge o n w h o perf or me d t he s ur ger y . N o m ore t ha n t w o s ur ge o ns per site 
s h o ul d perf or m a t y pe of s ur ger y.
1 2. 1. 3
P ost - Sur ger y f oll o w -u p V isits ( D a y 1 , We e k 1, M o nt hs 1, 3 
a n d 1 2 )
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
Bel o w is a list of st u d y pr oce d ures t o be u n derta ke n at t he P ost - Sur ger y f oll o w- u p Visits 
( Da y 1, Wee k 1 [ D a y  5 t o Da y 9], M o nt hs 1 [Da y  2 1 t o Da y 3 5], 3 [Da y  7 0 t o Da y 9 8] a n d 1 2 

Pa ge 5 8 of 8 1
[Da y  3 3 0 t o Da y 3 7 5]). Pr oce d ures m ust be perf or me d i n t he or der prese nte d bel o w u nless 
ot her wise state d. All oc ular assess me nts m ust be d o ne m o n oc ularl y .
1.
Rec or d a n y c ha n ges t o s u bjects’ oc ular a n d n o n-oc ular me dical hist or y  or c o nc o mitant
me dicati o ns at all visits.
2.
A d mi nister t he R S V P  Q uesti o n naire at t he M o nt h 1, 3 , a n d 1 2 visits .
3.
A d mi nister t he S Q D E S Q uesti o n naire at t he M o nt h 1, 3, a n d 1 2 visits .
N O T E: I nvesti gat ors a n d site staf f m ust re vie w b ot h q uesti o n naire s res ults pri or t o 
s u bjects lea vi n g t he office t o e ns ure c o m plete ness.
4.
C o n d uct t he f oll o wi n g pr oce d ures i n a n or der t hat is feasi ble f or y o ur site :

Perf or m l i g hti n g m eas ure me nts f or V A a n d c o ntrast se nsiti vit y testi n g at all visits.

Meas ure dista nce U C VA i n p h ot o pic c o n diti o ns at all visits.

M eas ure u nc orrecte d c o ntrast se nsiti vit y  i n mes o pic c o n diti o ns at t he M o nt h 1, 3,
a n d 1 2 visits .

Meas ure
ma nifest refracti o n at 4 meters a n d a dj ust f or o ptical i nfi nit y  at t he 
We e k 1, M o nt h 1, 3 , a n d 1 2 visits .

Meas ure dista nce B C VA i n p h ot o pic c o n diti o ns at t he Wee k 1, M o nt h 1, 3, a n d 1 2 
visits .
5.
C o n d uct t he f oll o wi n g pr oce d ures i n a n or der t hat is feasi ble f or y o ur site :

Perf or m t o p o gra p h y at t he M o nt h 1, 3, a n d 1 2 visits .
6.
Perf or m slit la m p e xa mi nati o n at all visits.
7.
Meas ure
I O P at t he M o nt h 1, 3, a n d 1 2 visits.
8.
P erf or m d ilate d f u n d us e xa mi nati o n at M o nt h 1 2.
9.
Rec or d a n y A Es at all visits . Refer t o Secti o n 1 3 f or f urt her details.
N O T E: S A Es m ust be e ntere d i nt o E D C wit hi n 2 4 h o urs of t he I n vesti gat or ’s k n o wle d ge. 
N O T E: Sec o n dar y  S ur gical Inter ve nti o n: Retreat me nts will n ot be all o we d i n t his st u d y.
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7

Pa ge 5 9 of 8 1
1 2. 2
U nsc he d ule d Vi sits
If a s u bject is e xa mi ne d m ore t ha n o nce d uri n g a n y of t he sc he d ule d f oll o w-u p peri o ds, or 
bet wee n sc he d ule d f oll o w- u p peri o ds, a n u nsc he d ule d visit ( U N S V) f or m s h o ul d be 
c o m plete d re p orti n g a n y st u d y para meters or a ny rele va nt data c olle cte d at t his visit. 
A n U N S V  is defi ne d as o ne t hat meets all of t he f oll o wi n g:

E xa mi nati o n t hat is n ot sta n dar d of care a n d n ot re q uire d b y  t he pr ot oc ol

E xa mi nati o n c o n d ucte d b y t he st u d y staff

Ne w fi n di n g, c o nti n uati o n of a n e xisti n g fi n di n g, or a c ha n ge t o a pre vi o us fi n di n g is
n ote d
A n U N S V  ma y or ma y n ot res ult i n t he ca pt ure of a n A E . Li ke wise, a n A E ma y  be ca pt ure d 
wit h o ut t he re p ort of a n U N S V  (e.g, A E i de ntifie d s u bse q ue nt t o st u d y  e ye e xa mi nati o n b y 
n o n- st u d y pers o n nel).
T he assess me nts ca pt ure d a t t he U N S V are dictate d b y t he I n vesti gat or per his/ her me dical 
j u d g me nt. T he f oll o wi n g assess me nts/ d oc u me ntati o n are rec o m me n de d.

C ha n ges t o s u bjects’  oc ular a n d n o n-oc ular me dical hist or y  or c o nc o mita nt 
me dicati o ns 

Slit la m p e xa mi nati o n

Ma nifest refracti o n

Dista nce U C V A

F u n d us e xa mi nati o n

I O P

A Es
N O T E
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
: Assess me nts/ d oc u me ntati o n are n ot li mite d t o t he a b o ve list.
If t he s u bject is disc o nti n ue d at t he U N S V , t he n all early e xit pr oce d ures m ust be perf or me d 
(refer t o Ta ble 6 – 1). 
F or safet y p ur p oses, if a n U N S V is re q uire d after t he fi nal st u d y visit ( M o nt h 1 2), t he n t he 
visit will be d oc u me nte d i n t he s o urce d oc u me nts.

Pa ge 6 0 of 8 1
1 2. 3
Misse d Vi sits
If a s u bject misses a sc he d ule d visit, t he s u bject s h o ul d be resc he d ule d wit hi n all o we d 
wi n d o w f or t he sa me visit. D ilige nce s h o ul d be s h o w n i n tr yi n g t o sc he d ule t he s u bject f or all 
visits, a n d all atte m pts t o c o ntact t he s u bject d oc u me nte d i n t he s u bject’s c hart. I n 
d oc u me ntati o n, i ncl u de dates, ti mes, met h o d of c o ntact, etc. If atte m pts t o c o ntact t he s u bject 
are u ns uccessf ul, t he date t he s u bject is c o nsi dere d l ost t o f oll o w- u p m ust be d oc u me nte d . If 
a s u bject is u na ble t o ret ur n f or t he fi nal st u d y  visit, t he E xit e C R F wit h t he a p pr o priate 
reas o n f or disc o nti n uati o n i n dicati n g t he s u bject is l ost t o f oll o w- u p will be c o m plete d.
1 2. 4
Disc o nti n ue d S u bjects
Disc o nti n ue d s u bjects are t h ose w h o wit h dra w , or are wit h dra w n fr o m t he st u d y after si g ni n g 
t he IC F a n d pri or t o c o m pleti n g all st u d y visits. S u bjects si g ni n g c o nse nt, b ut wit h dra w or are 
wit h dra w n pri or t o ra n d o mizati o n will be c o nsi dere d disc o nti n ue d d ue t o scree n fail ure, a n d 
t he faile d e ntr y criteri o n m ust d oc u me nte d i n s o urce d oc u me nt a n d E D C (refer t o 
Secti o n 1 0).
S u bjects ma y  disc o nti n ue st u d y partici pati o n at a n y ti me a n d f or a n y reas o n. S u bjects w h o 
c o m plete t he laser treat me nt i n eit her e y e will n ot be disc o nti n ue d b y t he I n vesti gat or.
S u bject n u m bers fr o m disc o nti n ue d s u bjects will n ot be reiss ue d. Disc o nti n ue d s u bjects will 
n ot be re place d.
It is t he I n vesti gat or’s res p o nsi bilit y t o select o nl y t h ose s u bjects w h o are li kel y t o be b ot h 
willi n g a n d a ble t o c o m plete t he re q uire d f oll o w -u p f or partici pati o n i n t his st u d y.
1 2. 5
Cli nic al St u d y Te r mi n ati o n
T he S p o ns or reser ves t he ri g ht t o cl ose t he i n vesti gati o nal site or ter mi nate t he st u d y  i n its
e ntiret y at a n y ti me, f or reas o na ble ca use. T he I n vesti gat or als o ma y  ter mi nate t he st u d y at
his/ her site f or reas o na ble ca use. Reas o ns f or t he cl os ure of a n i n vesti gati o nal site or
ter mi nati o n of a st u d y ma y i ncl u de:

T he I n vesti gat or fails t o c o m pl y  wit h t he pr ot oc ol or G o o d Cli nical Practice (G C P )
g ui deli nes .

Safet y  c o ncer ns.

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
I na de q uate recr uit me nt of s u bjects b y t he I n vesti gat or.

Page 61 of 81
If the clinical study is prematurely terminated or suspended, the Sponsor will inform the
Investigator and the regulatory authorities (where applicable) of the termination/suspension
and the reason for the termination/suspension. The Investigator must promptly notify the
IRB/IEC of the termination or suspension and of the reasons. If the Sponsor terminates the 
study for safety reasons, it will immediately notify the Investigator(s), and provide written 
instructions for study termination and applicable subject follow-up.
13
DEVICE DEFICIENCIES AND ADVERSE EVENTS
13.1
General Information
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users, or other persons, 
whether or not related to the investigational medical device (test article). Refer to the 
Section 4 Glossary of Terms for categories of AEs and SAEs.
Figure 13-1
Categorization of All Adverse Events
Alcon - Business Use Only 
 
Effective Date:  
Document:  
Version:  
Status:  
Printed By: 
Print Date:  
Effective
2.0; Most-Recent; Effective; CURRENT
TDOC-0052425
Protocol - Clinical
19-Mar-2017

Pa ge 6 2 of 8 1
Fi g ur e 1 3 – 2
C ate g oriz ati o n of All Seri o us A d verse E ve nts
S pecific E ve nts Rele v a nt t o t his Pr ot oc ol
I n a d diti o n t o re p orti n g all A Es (seri o us a n d n o n-seri o us) meeti n g t he defi niti o ns, t he 
I n vesti gat or m ust re p ort a n y occ urre nce of t he f oll o wi n g oc ular e ve nts as a seri o us a d verse 
e ve nt (S A E ):

Dif f use la mellar keratitis m o derate or w orse .

C or neal i nfiltrate or ulcer .

A n y  persiste nt c or neal e pit helial defect at o ne m o nt h or later .

M o derate or se vere (as defi ne d i n Secti o n 1 3. 3 ) cor neal e de ma at 1 m o nt h or later (f or 
L A S I K, s pecif y fla p or be d).

Melti n g of t he fla p ( L A SI K o nl y ).

Decrease i n B C V A of greater t ha n or e q ual t o 2 li nes ( ≥1 0 letters E T D R S).

Reti nal detac h me nt .

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
Oc ular perf o rati o n.
A n y  ot her p ote ntiall y si g ht-t hreate ni n g e ve nt ma y als o be c o nsi dere d seri o us base d o n t he 
j u d g me nt of t he I n vesti gat or a n d s h o ul d be re p orte d a p pr o priately. 

Pa ge 6 3 of 8 1
Device Deficie ncies 
A de vice deficie nc y  ma y or ma y n ot be ass ociate d wit h s u bject har m (ie, a d verse de vice 
eff ect [ A D E ] or seri o us a d verse de vice effect [S A D E ]); h o we ver, n ot all A D Es or S A D Es are 
d ue t o a de vice deficie nc y. T he I n vesti gat or m ust deter mi ne t he a p plica ble cate g or y f or t he 
i de ntifie d or s us pect de vice deficie nc y a n d re p ort a n y s u bject har m se paratel y. E xa m ples of 
de vice deficie ncies i ncl u de t he f oll o wi n g:

I nc orrect laser o ut p ut e ner g y

Fail ure t o meet pr o d uct s pecificati o ns (e. g, i nc orrect laser asse m bl y )

U na ble t o cali brate laser

S us pect dis p osa ble pr o d uct c o nta mi nati o n or defect ( s u bject i nterface)

C o m p uter s oft ware iss ue or s y ste m err or messa ge

Fail ure of e y e trac ker

Fail ure of laser firi n g
1 3. 2
M o nit ori n g f or A d verse E ve nts
At eac h visit, after t he s u bject has ha d t he o p p ort u nit y t o s p o nta ne o usly me nti o n a n y 
pr o ble ms, t he I n vesti gat or s h o ul d i n q uire a b o ut A Es b y  as ki n g t he sta n dar d q uesti o ns:

“ Ha ve y o u ha d a n y healt h pr o ble ms si nce y o ur last st u d y  visit?”

“ Ha ve t here bee n a n y c ha n ges i n t he me dici nes y o u ta ke si nce y o ur last st u d y  visit?”
C ha n ges i n a n y pr ot oc ol -s pecific para meters a n d/ or q uesti o n naires e val uate d d uri n g t he st u d y 
are t o be re vie we d b y t he I n vesti gat or . A n y u nt o war d ( u nfa v ora ble a n d u ni nte n de d) c ha n ge i n 
a pr ot oc ol -s pecific para meter or q uesti o n naire res p o nse t hat is cli nicall y rele va nt, i n t he 
o pi ni o n of t he I n vesti gat or , is t o be re p orte d as a n A E. T hese cli nicall y rele va nt c ha n ges will 
be re p orte d re gar dless of ca usalit y.
1 3. 3
Pr oce d ures f or Rec or di n g a n d Re p orti n g
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
A Es are c ollecte d fr o m t he ti me of i nf or me d c o nse nt. A n y pre -e xisti n g me dical c o n diti o ns or 
si g ns/s ym pt o ms prese nt i n a s u bject pri or t o t he start of t he st u d y  (i.e., bef ore t he I C F is 
si g ne d) are n ot c o nsi dere d A Es i n t he st u d y  a n d s h o ul d be rec or de d i n the Me dical Hist or y  
secti o n of t he e C R F. 
I n a d diti o n, c or neal e de ma a n d s u perficial p u nctate keratitis are e xa m ples of earl y 
p ost -o perati ve fi n di n gs t hat are t y picall y o bser ve d f oll o wi n g oc ular refracti ve s urger y. T hese 

Pa ge 6 4 of 8 1
are n ot c o nsi dere d A Es if t he y  ca n be reas o na bl y e x pecte d t o res ol ve wit hi n a wee k a n d n ot 
res ult i n a n y u nt o war d l o n g ter m vis ual o utc o me i m pact.
F or eac h rec or de d e ve nt, t he A D Es a n d S A Es d oc u me ntati o n m ust i ncl u de: date of 
occ urre nce, se verit y, treat me nt (if a p plica ble), o utc o me, a n d assess me nts of t he seri o us ness 
a n d ca usalit y. In a d diti o n, t he I n vesti gat or m ust d oc u me nt all de vice deficie ncies re p orte d or 
o bser ve d wit h t he Wa veli g ht E X 5 0 0 Laser s ys te m a n d t he Vi s u Ma x Laser kerat o me s ys te m 
o n t he De vice Deficie nc y e C R F. T he site m ust s ub mit all a vaila ble i nf or mati o n o n A D Es, 
S A Es, a n d de vice deficie ncies t o t he St u d y  S p o ns or i m me diatel y as f oll o ws:

All S A Es m ust be re p orte d i m me diatel y  ( wit hi n 2 4 h o urs) of t he I n vesti gat or ’s or 
site’s a ware ness. 

A D Es t hat d o n ot meet seri o us ness criteri a a n d de vice deficie ncies m ust be re p orte d 
wit hi n 1 0 cale n dar da y s of t he I n vesti gat or ’s or site’s a ware ness. 

A pri nte d c o p y of t he c o m plete d Seri o us A dverse Eve nt a n d A dverse Device Ef fect
a n d/ or Device Deficie ncy e C R F m ust be i ncl u de d wit h pr o d uct ret ur ns (refer t o 
Secti o n 1 1 . 3Acc o u nta bilit y  Pr oce d ures ).

A d diti o nal rele va nt i nf or mati o n after i nitial re p orti n g m ust be e ntere d i nt o t he e C R F 
as s o o n as t he data bec o me a vaila ble.

D oc u me nt a n y c ha n ges t o c o nc o mita nt me dicati o ns o n t he a p pr o priate e C R Fs.

D oc u me nt all rele va nt i nf or mati o n fr o m Disc har ge S u m mar y , A ut o ps y  Re p ort, 
Certificate of Deat h etc., if a p plica ble, i n narrati ve secti o n of t he A d verse De vice 
Ef fect (f or relate d A Es) a n d Seri o us A d verse E ve nt e C R F .
N O T E : I n t he case of t he E D C s yste m bec o m i n g n o n - o perati o nal, t he site m ust c o m plete t he 
a p pr o priate pa per Seri o us A dverse Eve nt a n d A dverse Device Effect a n d/ or Device 
Deficie ncy F or m. T he c o m plete d f or m will be t he n e maile d t o t he St u d y S p o ns or at 
acc or di n g t o t he ti meli nes o utli ne d a b o ve; h o we ver, t he 
re p orte d i nf or mati o n m ust be e ntere d i nt o t he E D C s yste m o nce it bec o mes o perati o nal.
A n y  AEs a n d de vice defi cie ncies f or de vices ot her t ha n t he test a n d c o ntr ol de vices (i.e.
To p ol y zer Va ri o, P u pill o meter a n d A nal yz er I or II) will be c o nsi dere d a n d pr ocesse d as 
s p o nta ne o us (f oll o wi n g t he p ost- mar ket vi gila nce pr oce d ures) a n d s h o ul d be c o m m u nicate d 
t o t he de vice’s/ pr o d uct’s ma n ufact urer as per l ocal re q uire me nts.
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
St u d y S p o ns or  re prese nt ati ves m a y be c o nt acte d f or  a n y prot oc ol r el ate d q uesti o n a n d 
t heir c o nt act i nf or m ati o n is pro vi de d i n t he M O P
t h at acc o m p a nies t his prot oc ol.

Page 65 of 81
Further, depending upon the nature of the AE or device deficiency being reported, the Study 
Sponsor may request copies of applicable portions of the subject’s medical records. The 
Investigator must also report all AEs and device deficiencies that could have led to a SADE 
according to the requirements of regulatory authorities or IRB/IEC.
Intensity and Causality Assessments
Where appropriate, the Investigator must assess the intensity (severity) of the AE based on 
medical judgment with consideration of any subjective symptom(s), as defined below:
Intensity (Severity)
Mild
An AE is mild if the subject is aware of but can easily tolerate the sign or 
symptom.
Moderate
An AE is moderate if the sign or symptom results in discomfort significant 
enough to cause interference with the subject’s usual activities.
Severe
An AE is severe if the sign or symptom is incapacitating and results in the 
subject’s inability to work or engage in their usual activities.
For every AE in the study, the Investigator must assess the causality (Related or Not Related 
to the medical device or study procedure). An assessment of causality will also be performed 
by Study Sponsor utilizing the same definitions, as shown below:
Causality
Related
An AE classified as related may be either definitely related or possibly related 
where a direct cause and effect relationship with the medical device or study 
procedure has not been demonstrated, but there is a reasonable possibility that 
the AE was caused by the medical device or study procedure.
Not Related
An AE classified as not related may either be definitely unrelated or simply 
unlikely to be related (i.e, there are other more likely causes for the AE).
The Study Sponsor will assess the AEs and may upgrade the Investigator’s assessment of 
seriousness and/ or causality. The Study Sponsor will notify the Investigator of any AE that is 
upgraded from non-serious to serious or from unrelated to related.
Alcon - Business Use Only 
 
Effective Date:  
Document:  
Version:  
Status:  
Printed By: 
Print Date:  
Effective
2.0; Most-Recent; Effective; CURRENT
TDOC-0052425
Protocol - Clinical
19-Mar-2017

Page 66 of 81
13.4
Return product analysis
Study Sponsor representatives and their contact information are provided in the MOP that 
accompanies this protocol.
Alcon products associated with device deficiencies and/or product-related AEs should be 
returned as specified in the MOP and must include the Complaint number which will be 
provided by the study Sponsor after the case is entered in the Study Sponsor’s Global Product 
Complaint Management System (GPCMS).
13.5
Unmasking of the Study Information
Site personnel performing the manifest refraction subjective assessment and all UCVA testing
after randomization are to remain masked with regard to treatment assignment until after the 
final DBL. Alcon and other site personnel (nurses and technicians involved with the surgery, 
site personnel entering data in eCRF, site personnel administering other study related 
procedures, e.g. RSVP and SQDES questionnaires) must not reveal the treatment assignment 
to masked site personnel at any time during the study.
13.6
Follow-Up of Subjects with Adverse Events
The Investigator is responsible for adequate and safe medical care of subjects during the 
study and for ensuring that appropriate medical care and relevant follow-up procedures are 
maintained after the study. 
The Investigator should provide the Study Sponsor with any new safety information (which 
includes new AEs and changes to previously reported AEs) that may affect the safety 
evaluation of the device. For AEs that are unresolved/ ongoing at time of subject exit from 
study, any additional information received at follow-up should be documented in the eCRFs 
up to study completion (i.e, DBL). 
All complaints received after this time period will be considered and processed as 
spontaneous (following the post-market vigilance procedures) and should be communicated 
to the medical device’s manufacturer as per local requirements.
The Investigator should also report complaints on non-Alcon products directly to the 
manufacturer as per the manufacturer’s instructions or local regulatory requirements.
Alcon - Business Use Only 
 
Effective Date:  
Document:  
Version:  
Status:  
Printed By: 
Print Date:  
Effective
2.0; Most-Recent; Effective; CURRENT
TDOC-0052425
Protocol - Clinical
19-Mar-2017

Pa ge 6 7 of 8 1
1 3. 7
Pre g n a nc y i n t he Cli nic al St u d y
If a w o ma n bec o mes pre g na nt d uri n g t he st u d y  t his s h o ul d be n ote d wit hi n t he s o urce 
d oc u me ntati o n a n d S p o ns or n oti fie d. Pre g na nc y is n ot re p orta ble as a n A E; h o we ver , 
c o m plicati o ns ma y be re p orta ble a n d will be deci de d o n a case-b y -case basis .A n Alc o n f or m 
will be utilize d t o ca pt ure all pre g na nc y  relate d i nf or mati o n u ntil birt h of t he c hil d.
1 4
D A T A  R E VI E W A N D H A N D LI N G
1 4. 1
C o m pleti o n of S o ur ce D oc u me nts a n d C ase Re p ort F or ms
T he nat ure a n d l ocati o n of all s o urce d oc u me nts m ust be i de ntifie d t o e ns ure t hat ori gi nal 
data re q uire d t o c o m plete t he e C R Fs e xist a n d are accessi ble f or verificati o n b y  t he m o nit or. 
If electr o nic s o urce rec or ds are mai ntai ne d, t hese rec or ds will be re vie we d f or 2 1 C o de of 
Fe deral Re g ulati o ns (C F R ) Part 1 1  c o m plia nce a n d t he met h o d of verificati o n will be 
deter mi ne d i n a d va nce of starti n g t he st u d y . Data re p orte d o n t he e C R Fs m ust be deri ve d 
fr o m s o urce d oc u me ntati o n a n d be c o nsiste nt wit h s o urce d oc u me ntati o n, a n d a n y  
discre pa ncies m ust be e x plai ne d i n writi n g. At a mi ni m u m, s o urce d oc u me ntati o n m ust 
i ncl u de t he f oll o wi n g i nf or mati o n f or eac h s u bject:

S u bject i de ntificati o n ( na me, se x)

D oc u me ntati o n of s u bject eli gi bilit y

Date of i nf or me d c o nse nt, a n d a c o p y of t he si g ne d I CF

Dates of visits

D oc u me ntati o n t hat pr ot oc ol- s pecific pr oce d ures were perf or me d

Res ults of st u d y  assess me nts, as re q uire d b y t he pr ot oc ol

D oc u me ntati o n of A Es a n d ot her safet y para meters (as a p plica ble)

Rec or ds re gar di n g me dical hist ories a n d t he use of c o nc o mita nt t hera pies pri or t o a n d 
d uri n g t he st u d y

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
Date of st u d y c o m pleti o n a n d reas o n f or earl y disc o nti n uati o n (if a p plica ble)
It is re q uire d t hat t he a ut h or of eac h e ntr y i n t he s o urce d oc u me nts be i de ntifia ble (e g, i nitials 
or si g nat ure a n d date). A n y  c ha n ge or c orrecti o n t o data re p orte d i n t he s o urce, or o n a e C R F, 
m ust be date d, i nitiale d, a n d e x plai ne d if necessar y . C ha n ges m ust n ot o bsc ure t he ori gi nal 
e ntr y (ie, a n a u dit trail m ust be mai ntai ne d). Direct access t o s o urce d oc u me ntati o n ( me dical 
rec or ds) m ust be all o we d f or t he p ur p ose of verif yi n g t hat t he data rec or de d o n t he e C R F are 
c o nsiste nt wit h t he ori gi nal s o urce data.

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EDC is designated for data collection and should be completed by designated individuals 
only. Required examinations must be recorded on the eCRFs. All data reported must have 
corresponding entries in the source documents. The Investigator will review the reported data 
and certify that the eCRFs are accurate and complete as indicated by signature. Subject 
identifiers must not be recorded on the eCRFs beyond subject number, demographics 
information, and/or other study identifiers.
Deviations from this protocol, regulatory requirements, and GCP must be recorded in the 
study records. An explanation of the deviation should be included, as applicable. In addition, 
corrective and preventive action should be identified, implemented, and documented within 
the study records.
14.2
Data Review and Clarifications
Upon completion of the eCRFs, the data will be reviewed by Alcon study personnel for 
accuracy and completeness. If corrections and/ or any additions to the data are deemed 
necessary, queries will be generated by Alcon data management or the site management 
(study monitor) team and forwarded to the investigative site. Staff at each site are expected to 
respond to data queries in a timely manner and ensure that the corrections and changes made 
to the data in the EDC system are reflected in the subjects’ source documentation. In addition, 
prior to study start (first subject first visit) a plan for data validation will be completed by 
Alcon Clinical Data Management and agreed upon by members of the Clinical Trial 
Management (CTM) team.
Concomitant medications entered into the database will be coded using the current version of 
the WHO (World Health Organization) Drug Reference List. Medical history and AEs will be 
coded using the current version of the medical dictionary for regulatory activities (MedDRA) 
terminology.
Upon completion of the study and once the database is declared complete and accurate, the 
database will be locked and data will be available for data analysis. Any changes to the 
database after lock will be implemented upon agreement between Alcon’s and PLSS’s CTM
and biostatistics department, and will be completed following Alcon’s procedures for changes 
to a database after DBL.
NOTE: Missing data can have a detrimental effect on the integrity and soundness of a clinical 
study. All efforts should be made by the clinical investigative site to prevent missing study 
visits and procedures during the study.
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15
ANALYSIS PLAN
The main focus of the analyses is the eye (individual-level) rather than subject (group-level). 
However some data (e.g. demographics, non-ocular AEs) will only be available at the subject 
level.
At each study visit, quantitative variables will be presented based on descriptive statistics (the 
number of non-missing observations, mean, median, standard deviation [SD], minimum and 
maximum values) for the observed values and change from pre-surgery (if applicable). 
Qualitative variables will be presented by frequency tables. 
The baseline value is the last available, non-missing, value collected prior to surgery (i.e.
prior to the laser being in contact with the eye). 
Further technical details and discussion of the following statistical considerations will be 
provided in the statistical analysis plan (SAP), which will be finalized before DBL.
15.1
Subject Evaluability
All subjects who satisfy the inclusion and exclusion criteria, and who sign the informed 
consent form, will be considered enrolled in the study.
15.2
Analysis Data Sets
The following analysis sets will be defined for this study: intention to treat (ITT) and safety 
analysis set. Assignment of study eyes to the appropriate analysis set(s) will be determined 
prior to DBL.
The ITT analysis set will contain all study eyes for which study treatment has begun for the 
set of subjects that are randomized. For the purposes of this study, the treatment will be 
considered to have begun once the flap creation is initiated for LASIK and once laser touches 
the eye for SMILE.
All eyes in the ITT analysis set will be assigned to the treatment to which they are 
randomized. 
The safety analysis set will contain all study eyes for which study treatment has begun; all 
eyes in the safety analysis set will be assigned to the treatment actually received.
In general, the ITT analysis set will be used to display subject disposition, demographics and 
baseline characteristics, medical history and the analysis of the effectiveness endpoints. The 
safety analysis set will be used for the analysis of the safety endpoints.
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15.3
Demographics and Baseline Characteristics
Demographic and baseline characteristics will be summarized by treatment group and 
overall.
Relevant medical history (ocular and non-ocular) and current medical conditions will be 
tabulated by system organ class (SOC) and preferred term (PT) of the MedDRA dictionary. 
Other relevant baseline information will be listed and summarized as appropriate with 
descriptive statistics.
15.4
Effectiveness Analyses
All effectiveness endpoints are defined at the eye (as opposed to subject) level. As the 
measurements from the paired eyes of the same subject will have a tendency to be positively 
correlated, the main analyses will adjust for this correlation (i.e. intracluster correlation).
15.4.1
Primary Effectiveness
The primary effectiveness endpoint is stated in Section 8.5.1.
15.4.1.1
Statistical Hypotheses
The following superiority hypothesis for the primary effectiveness objective will be tested at 
the two-sided 5% significance level (α=0.05):
H0: pL= pS
H1: pL ≠pS
where pL and ps refer to the percentage of eyes with manifest refraction cylinder within (≤) 
0.5 D in the Topography Guided LASIK arm and SMILE arm, respectively. 
15.4.1.2
Analysis Methods
The primary effectiveness analysis will be analyzed using the chi-square test quoted in Fleiss 
et al (Fleiss 2003) at the two-sided 5% significance level (α=0.05). This statistic takes into 
account the intracluster correlation/ agreement between eyes within subject.
15.4.2
Secondary Effectiveness
The secondary effectiveness endpoints are stated in Section 8.5.1.
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15.4.2.1
Statistical Hypotheses
The following superiority hypothesis for the first secondary effectiveness objective will be 
tested (two-sided):
H0: µL = µS
H1: µL ≠µS
where µL and µs denote the mean manifest refraction cylinder in the Topography Guided 
LASIK arm and SMILE arm, respectively. 
The following superiority hypothesis for the second secondary effectiveness objective will be 
tested (two-sided):
H0: µL = µS
H1: µL ≠µS
where µL and µS denotes the mean UCVA in the Topography Guided LASIK arm and SMILE
arm, respectively. 
15.4.2.2
Analysis Methods
The secondary effectiveness analysis will be analyzed using the statistic of Donner, et al 
(Donner 1981), which accounts for the intraclass correlation between eyes within subjects, at
the two-sided 5% significance level (α=0.05).
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15.5
Handling of Missing Data
The primary analysis of the effectiveness endpoints will be based on observed data (i.e. no 
imputation will be performed). The influence of missing data is expected to be minimal.
15.6
Multiplicity
In order to control the type 1 error at the 5% significance level (α=0.05) over the family of 
primary and secondary hypotheses, the secondary effectiveness hypotheses will be relevant 
only if the primary effectiveness null hypothesis is rejected at the 5% significance level 
(two-sided).
If the null hypothesis of the primary effectiveness endpoint is rejected, then the secondary 
effectiveness endpoints will be tested using the Hochberg testing procedure (Hochberg 1988).
The Hochberg procedure is a step-up method for multiple testing controlling for the type I 
error rate. 
First, the p-values obtained from the analysis of the secondary effectiveness endpoints will be 
ranked from smallest (1) to largest (2). Second, if the largest p-value (p[2]) associated with 
the two secondary effectiveness endpoints is less than the critical value (α=0.05), then the 
two secondary effectiveness null hypotheses will be rejected and testing will stop. If the 
aforementioned p-value is greater than or equal to the critical value (α=0.05), then the 
associated secondary effectiveness null hypothesis will fail to be rejected. The next largest 
p-value (p[1]) will then be checked to see if it is less than the critical value (α/2=0.025).
15.7
Safety Analysis
No inferential testing will be performed on these parameters.
The eye-level safety analyses will be performed using the safety analysis set. For safety 
parameters collected on the subject-level (e.g. PRO questionnaires, non-ocular AEs), the 
population of interest will be the set of subjects with at least one eye for which treatment has 
begun (i.e. at least one eye in the safety analysis set).
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Pa ge 7 3 of 8 1
A d verse E ve nts
A Es will be assesse d t hr o u g h o ut t he st u d y  peri o d ( fr o m pre -s ur gery Da y  - 4 5 u p t o
p ost -s urger y  f oll o w-u p f or M o nt h 1 2 ). F or m ore details, refer t o Secti o n 1 3. 1 .
A Es will be dee me d treat me nt e mer ge nt if t he o nset date is o n or after t he date of s ur ger y. 
A n y  A Es rec or de d pri or t o t he start of s ur gery will be liste d se paratel y fr o m t he treat me nt 
e mer ge nt A Es . O nly treat me nt e mer ge nt a d verse e ve nts ( T E A Es) will be s u m marize d. Oc ular 
treat me nt e mer ge nt a d verse e ve nts will be s u m marize d se paratel y b y S O C a n d P T.
B ot h s u bject a n d e ve nt c o u nts will be prese nte d f or A Es. S u bject c o u nts refer t o t he n u m ber 
of s u bjects wit h t he res pecti ve A E of i nterest. S u bjects w h o e x per ie nce m ulti ple A Es f or a P T  
will be c o u nte d o nce, si milarl y f or s u bjects wit h m ulti ple A Es per S O C, f or s u bject c o u nts. 
E ve nt c o u nts refer t o t he n u m ber of occ urre nces of t he res pecti ve A E of i nterest, re gar dless of 
w het her a s u bject alrea d y ha d t his e ve nt . 
All i nf or mati o n o btai ne d o n A Es (i ncl u di n g t h ose w hic h are c ollecte d pre-s ur gery as well as 
T E A Es) will be dis p l a ye d b y treat me nt a n d s u bject.
Alt h o u g h t he s ur ger y is pla n ne d t o be bilateral, t he i n vesti gat or ma y deci de t o n ot perf or m 
t he s ur gery o n t he sec o n d e ye o n t he sa me da y as t he first e ye. I n t he f oll o wi n g sce nari os, if 
d uri n g t he 1 2 -m o nt h p ost -s ur gery st u d y peri o d:

n o s ur ger y  is perf or me d o n t he sec o n d e ye

s urger y  is perf or me d o n t he sec o n d e ye usi n g a n o n -st u d y s ur ger y
T he n o nl y  AEs will be c o llecte d f or t he sec o n d e ye.
T hese A Es (i ncl u di n g t h ose w hic h are c ollecte d pre-s urger y  as well as t h ose after t he pla n ne d 
s urger y ) will be liste d se paratel y.
De vice Deficie ncies
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  M o s t - R e c e n t ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 2 4 2 5
P r o t o c o l  -  C l i n i c a l
1 9- Mar- 2 0 1 7
De vice deficie nc y  will be e val uate d at da y of s ur ger y ( Da y 0). F or m ore detai ls, refer t o 
Secti o n 1 3. 1.
T he n u m ber a n d perce nta ge of all de vice deficie ncies will be ta b ulate d b y treat me nt. A listi n g 
of all de vice deficie ncies will als o be pr o vi de d.

Page 74 of 81
Other Safety Assessments
Other safety evaluations include slit lamp findings IOP, surgical problems, dilated fundus 
findings and PRO Questionnaires (RSVP, SQDES). For details refer to Section 12.1.
The mean overall and eight subscale vision related quality scores will be derived from the 
RSVP questionnaire.
For SQDES, a subject is defined as having dry eye syndrome if there was occurrence of both 
dryness and irritation of the eyes either constantly or often (that is, severe symptoms) or a 
report of a previous clinical diagnosis of dry eye syndrome.
Information from the nomogram, if one is used, and surgical report will also be provided.
15.8
Interim Analyses
There is no formal interim analysis planned. The main analysis will occur after the 3 months 
post-surgery follow-up. Subjects will be followed up for an additional 9 months post-surgery 
(i.e. in total 12 months [Day 330 to Day 375] after surgery) for safety 
 
.
15.9
Sample Size Justification
The sample size calculation is based on conservative estimates of the interim results from a 
pilot study comparing Topography Guided LASIK to SMILE (single center investigator 
initiated trial) (data not published).
Based on the assumed rates of 90% vs 80% of eyes with manifest refraction cylinder less 
than or equal to 0.5 D at 3 months for Topography Guided LASIK and SMILE, respectively, 
and an intracluster correlation coefficient (i.e. correlation between eyes within subject) of 
0.39, a sample size of 185 subjects (treated bilaterally) per treatment group will provide 90% 
power to reject the hypothesis for the primary effectiveness objective (based on the two-sided 
5% significance level). In total, 740 eyes from approximately 370 subjects are required for 
this study. 
To ensure the required sample size is achieved, approximately 225 subjects (contributing 2 
eyes each) will be enrolled per treatment arm. This will take into account drop-outs prior to 
surgery. It is expected that 400 subjects (200 subjects per treatment arm) will receive bilateral 
treatment. Of these subjects, it is expected that a further 7% may drop out during the 
3 months post-surgery.
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16
ADMINISTRATIVE PROCEDURES
16.1
Regulatory and Ethical Compliance
This clinical study will be conducted in accordance with the principles of the Declaration of 
Helsinki, and in compliance with ISO 14155:2011 Clinical investigation of medical devices 
for human subjects, GCP, the Code of Federal Regulations (CFR), and laws and regulations 
of foreign countries, whichever affords greater protection to subjects. The study will also be 
conducted in accordance with the Sponsor’s Standard Operating Procedures (SOPs) and all 
other applicable regulations. The Investigator and all clinical study staff will conduct the 
clinical study in compliance with this protocol. The Investigator must ensure that all 
personnel involved in the conduct of the clinical study are qualified to perform their assigned 
duties through relevant education, training, and experience.
16.2
Informed Consent Procedures
Voluntary informed consent must be obtained from every subject prior to the initiation of any 
screening or other clinical study-related procedures. The Investigator must have a defined 
process for obtaining consent. Specifically, the Investigator, or designee, will explain the 
clinical study to each potential subject and the subject must indicate voluntary consent by 
signing and dating the approved ICF. The subject must be provided an opportunity to ask 
questions of the Investigator, and if required by local regulation, other qualified personnel. 
The Investigator must provide the subject with a copy of the consent form written in a 
language the subject understands. The consent document must meet all applicable local laws 
and will provide subjects with information regarding the purpose, procedures, requirements, 
and restrictions of the clinical study, along with any known risks and potential benefits 
associated with the investigational product, the available compensation, and the established 
provisions for maintaining confidentiality of personal, protected health information. Subjects 
will be told about the voluntary nature of participation in the clinical study and will be 
provided with contact information for the appropriate individuals should questions or 
concerns arise during the clinical study. The subject also will be told that their records may be 
accessed by appropriate authorities and Sponsor-designated personnel. The Investigator must 
keep the original, signed copy of the consent and must provide a duplicate copy to each 
subject.
16.3
Responsibilities of the Investigator and IRB/IEC
Before clinical study initiation, this protocol, the ICF (and assent form, if applicable), any 
other written information provided to subject, and any advertisements planned for subject 
recruitment must be approved by an IRB / Independent Ethics Committee (IEC). A master list 
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of IRBs/IECs for this clinical study can be found in the Trial Master File. The Investigator 
must provide documentation of IRB/IEC approval to the Sponsor. The approval must be 
dated and must identify the applicable protocol, amendments (if any), ICF, assent form (if 
any), all applicable recruiting materials, written information for subjects, and subject 
compensation programs. The IRB/IEC must be provided with a copy of the Directions for 
Use, any periodic safety updates, and all other information as required by local regulation 
and/or the IRB/IEC. At the end of the clinical study or in the case of early termination, the 
Investigator will notify the IRB/IEC of the clinical study’s final status. Finally, the 
Investigator will report to the IRB/IEC on the progress of the clinical study at intervals 
stipulated by the IRB/IEC.
16.4
Sponsor and Monitoring Responsibilities
The Sponsor will designate a monitor to conduct the appropriate site visits at the appropriate 
intervals. The clinical investigation will be monitored to ensure that the rights and wellbeing 
of the subjects are protected; the reported data are accurate, complete, and verifiable from the 
source documents; the equipment used to assess variables in the clinical investigation is 
maintained and calibrated per manufacturer instructions and Sponsor requirements; and the 
study is conducted in compliance with the current approved protocol (and amendment[s], if 
applicable), with current GCP, and with applicable regulatory requirements. All investigative 
sites will have a site initiation. Monitoring will be conducted periodically while the clinical 
study is ongoing. Monitoring methods may include site visits, telephone, written, and fax 
correspondence. The assigned CSM will contact each site at appropriate intervals. The Lead 
Clinical Site Manager (LCSM) will determine the frequency of site visits. Close-out visits 
will take place after the last visit of the last subject. Enrollment will be tracked and reported 
at regular intervals. Details regarding enrollment (eg, number of subjects pre-screened, 
screened, reasons for screen failures, etc.) may be requested of the investigative site and must 
be provided within a reasonable time period. The Sponsor will be responsible for 
implementing and maintaining quality assurance and quality control systems to ensure the 
study is conducted and data are generated, documented and reported in compliance with the 
protocol, GCP and applicable regulatory requirements.
The Sponsor will secure agreement from all involved parties to ensure direct access to all 
study related sites, source data and documents, and reports for the purpose of monitoring and 
auditing by the Sponsor, and inspection by domestic and foreign regulatory authorities. 
Quality control will be applied to each stage of data handling to ensure that all data are 
reliable and have been processed correctly. Agreements made by the Sponsor with the 
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Investigator/Institution and any other parties involved in the clinical study will be provided in 
writing as part of the protocol or as a separate agreement.
16.5
Regulatory Documentation and Records Retention
The Investigator is accountable for the integrity, retention, and security of all study related 
data. The Investigator must maintain accurate, complete, and current records relating to the 
clinical study. The Investigator must maintain the required records during the investigation 
and for a period of time specified by local law or per the Clinical Study Agreement, 
whichever is longer. If the Investigator retires, relocates, of for any other reason withdraws 
from responsibility of keeping the study records, the Sponsor must be notified and suitable 
arrangements made for retention of study records and source documents needed to comply 
with national and international regulations.
16.6
Confidentiality and Publication of the Clinical Study
Any information other than that which is disclosed upon registration should not be discussed 
with persons outside the study. The protocol, study data, and information related to the study 
or to Alcon’s products or research programs that is provided by Alcon (Confidential 
Information) is to be kept confidential, and not disclosed directly or indirectly to any third 
party other than those involved in the study who have a need to know. All data and 
discoveries arising out of the study, patentable or non-patentable, shall be the sole property of 
Alcon, Inc. Alcon reserves the right of prior review of any publication or presentation of 
information related to the study. Alcon may use these data now and in the future for 
presentation or publication at Alcon’s discretion or for submission to government regulatory 
agencies.
The existence of this clinical study is confidential and should not be discussed with persons 
outside of the study. You shall hold confidential, and not disclose directly or indirectly to any 
third party other than those persons involved in the study who have a need to know, the 
protocol, the data arising out of the study, and any other information related to the study or to
Alcon’s products or a research program that is provided by Alcon to you (the “Confidential
Information”). All such persons must be instructed not to further disseminate this information 
to others. You shall not use the Confidential Information for any purpose other than the study. 
The foregoing obligations of confidence and non-use assumed by you shall not apply to: (a) 
information which at the time of disclosure is in the public domain; (b) information which 
thereafter lawfully becomes part of the public domain other than through disclosure by or 
through you; (c) information which, as evidenced by your written records, was known by you 
prior to Alcon’s disclosure; (d) information which is lawfully disclosed to you by a third 
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party not under any obligation of confidence to Alcon; or (e) information which is required to 
be disclosed by law or government regulatory agency, provided reasonable advance notice of 
such disclosure is given to Alcon. In signing this protocol, you agree to the release of the data 
from this study and acknowledge the above confidentiality and publication policy. The 
provisions of this Statement shall survive the completion of the study.
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17
REFERENCES
Donner A, Birkett N, Buck C. Randomization by cluster. Sample size requirements and 
analysis. Am J Epidemiol, 1981;114: 906-14
Eydelman MB, Drum B, Holladay J, Hilmantel G, Kezirian G, Durrie D et al. Standardized 
analyses of correction of astigmatism by laser systems that reshape the cornea. J Refract Surg 
2006;22:81-95
Fleiss JL, Levin B, Paik MC. Statistical methods for rates and proportions. 3rd ed. New York: 
John Wiley and Sons, Inc.; 2003
Gulati A, Sullivan R, Buring JE, Sullivan DA, Dana R, Schaumberg DA. Validation and 
Repeatability of a Short Questionnaire for Dry Eye Syndrome. American journal of 
ophthalmology 2006; 142(1):125-131
Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika 
1988;75(4):800-802
Holland S, Lin DTC, and Tan JCH. Topography-guided laser refractive surgery. Curr Opin 
Ophthalmol 2013; 24:302–309
Ivarsen A, Asp S, and Hjortdal J. Safety and complications of more than 1500 small-incision 
lenticule extraction procedures. Ophthalmology. 2014;121(4):822-8
Knorz MC, Jendritza B. Topographically-guided Laser In Situ Keratomileusis to Treat 
Corneal Irregularities. Ophthalmology 2000; 107:1138–1143
Kymionis GD, Panagopoulou SI, Aslanides IM, Plainis S, Astyrakakis N, and Pallikaris IG. 
Topographically Supported Customized Ablation for the Management of Decentered Laser In 
Situ Keratomileusis. American Journal of Ophthalmology 2004; 137(5):806-811
MarketScope. Report on the Global Refractive Surgery Market, 2015.
Moshirfar M, McCaughey MV, Reinstein DZ, Shah R, Santiago-Caban L, Fenzl CR. Small-
incision lenticule extraction. J Cataract Refract Surg 2015; 41:652–665
Price MO, Price DA, Bucci FA, Durrie DS, Bond WI, Price FW. Three-year longitudinal 
survey comparing visual satisfaction with LASIK and contact lenses. Ophthalmology 
2016;1-8
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Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery using the small 
incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic 
astigmatism: results of a 6 month prospective study. Br J Ophthalmol 2011;95:335-339
Shortt AJ, Allan BDS, Evans JR. Laser-assisted in-situ keratomileusis (LASIK) versus 
photorefractive keratectomy (PRK) for myopia (Review). The Cochrane Library 2013;1 
Single center investigator initiated trial by Dr. Kanellopoulos (data not published).
Solomon KD, Fernández de Castro LE, Sandoval HP, Biber JM, Groat B, Neff KD et al. 
LASIK World Literature Review, Quality of Life and Patient Satisfaction. Ophthalmology 
2009;116:691–701
Stulting RD, Fant BS, the T-CAT Study Group. Results of topography-guided laser in situ 
keratomileusis custom ablation treatment with a refractive excimer laser. J Cataract Refract 
Surg 2016; 42:11–18
Sugar A, Rapuano CJ, Culbertson WW, Huang D, Varley GA, Agapitos PJ, et al. Laser In Situ 
Academy of Ophthalmology. Ophthalmology. 2002;109(1):175-87
Vitale S, Schein OD, Meinert CL, Steinberg EP. The Refractive Status and Vision Profile, A 
Questionnaire to Measure Vision-related Quality of Life in Persons with Refractive Error. 
Ophthalmology 2000;107:8
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18
APPENDICES
Not Applicable
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TDOC-0052425
Protocol - Clinical
19-Mar-2017