Pivotal Trial of WaveLight® EX500 Excimer Laser System for the Correction of Myopia With and Without Astigmatism Using InnovEyes™ in Conjunction With InnovEyes™ Sightmap
Phase: NA
Conditions: Myopia
Sponsor: Alcon Research

 
 
 
 
 
Pivotal Trial of WaveLight® EX500 Excimer Laser System for the 
Correction of Myopia with and without Astigmatism Using 
InnovEyes™ in Conjunction with InnovEyes™ sightmap 
 
STUDY ID 
RFP911-C001 
 
 
PROTOCOL 
 
 
NCT04219891 

Document ID: 
V-CLN-0000116 
Status: Approved, Version: 3.0 
Approved Date: 09 Jun 2021 
Page 1 of 79 
 
Alcon – Business Use Only 
 
Device Protocol for RFP911-C001 
Title: Pivotal Trial of WaveLight® EX500 Excimer Laser System for the 
Correction of Myopia with and without Astigmatism Using InnovEyes™ in 
Conjunction with InnovEyes™ sightmap 
 
Protocol Number: 
RFP911-C001 
Development Stage of 
Project: 
Development 
Sponsor Name and 
Address: 
Alcon Research, LLC and its affiliates (“Alcon”) 
6201 South Freeway 
Fort Worth, Texas 76134-2099 
Test Product: 
WaveLight® EX500 excimer laser system using InnovEyes™ 
in conjunction with InnovEyes™ sightmap 
 
 
 
Property of Alcon 
Confidential 
May not be used, divulged, published, or otherwise disclosed without the consent of Alcon 

Document ID: 
V-CLN-0000116 
Status: Approved, Version: 3.0 
Approved Date: 09 Jun 2021 
Page 2 of 79 
 
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Investigator Agreement: 
• 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), the ethical 
principles contained within the Declaration of Helsinki, this protocol, all applicable 
regulatory authority regulations, and conditions of approval imposed by the reviewing 
IRB or regulatory authority. 
• I will supervise all testing of the device involving human subjects and ensure that the 
requirements relating to obtaining informed consent and IRB review and approval are 
met in accordance with applicable local and governmental regulations. 
• I have read and understand the appropriate use of the investigational product(s) as 
described in the protocol, current Investigator’s Brochure, product information, or other 
sources provided by the Sponsor. 
• I understand the potential risks and side effects of the investigational product(s). 
• I agree to maintain adequate and accurate records in accordance with government 
regulations and to make those records available for inspection. 
• I agree to comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements of the Sponsor and government 
agencies. 
• I agree to ensure that all associates, colleagues, and employees assisting in the conduct of 
the study are informed of their obligations in meeting the above commitments. 
Have you ever been disqualified as an Investigator by any Regulatory Authority? 
 No        Yes 
Have you ever been involved in a study or other research that was terminated? 
 No        Yes 
If yes, please explain here: 
 
 
Principal Investigator: 
 
Signature 
 
 
 
 
 
Date 
Name and Professional 
Position: 
 
Address: 
 

Document ID: 
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Table of Contents 
Device Protocol for RFP911-C001 ............................................................................................ 1 
Table of Contents ....................................................................................................................... 3 
List of Tables .............................................................................................................................. 6 
List of Figures ............................................................................................................................ 6 
1 
GLOSSARY OF TERMS .................................................................................................... 7 
2 
LIST OF ACRONYMS AND ABBREVIATIONS ........................................................... 10 
3 
PROTOCOL SUMMARY ................................................................................................. 12 
4 
PROTOCOL AMENDMENTS ......................................................................................... 20 
 
 
5 
INTRODUCTION ............................................................................................................. 31 
5.1 
Rationale and Background ................................................................................ 31 
5.2 
Purpose of the Study .......................................................................................... 32 
5.3 
Risks and Benefits ............................................................................................. 33 
6 
STUDY OBJECTIVES...................................................................................................... 33 
6.1 
Primary Objective(s) ......................................................................................... 33 
6.1.1 
Primary Endpoints ............................................................................. 33 
 
 
 
 
6.3 
Safety Objective(s) ............................................................................................ 35 
6.3.1 
Primary Safety Endpoints .................................................................. 35 
 
 
6.4 
Refractive Stability ............................................................................................ 36 
7 
INVESTIGATIONAL PLAN ............................................................................................ 37 
7.1 
Study Design ..................................................................................................... 37 
7.2 
Rationale for Study Design ............................................................................... 38 
7.2.1 
Purpose and Timing of Interim Analyses and Resulting Design 
Adaptations ........................................................................................ 39 
7.3 
Rationale for Duration of Treatment/Follow-Up ............................................... 39 
7.4 
Data Monitoring Committee.............................................................................. 39 
8 
STUDY POPULATION .................................................................................................... 39 
8.1 
Inclusion Criteria ............................................................................................... 40 

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8.2 
Exclusion Criteria .............................................................................................. 41 
8.3 
Rescreening of Subjects .................................................................................... 42 
9 
TREATMENTS ADMINISTERED................................................................................... 42 
9.1 
Investigational Product(s) .................................................................................. 43 
9.2 
Other Medical Device or Medication Specified for Use During the Study ...... 48 
9.3 
Treatment Assignment/Randomization ............................................................. 48 
9.4 
Treatment Masking ............................................................................................ 49 
9.5 
Accountability Procedures ................................................................................. 49 
9.6 
Changes to Concomitant Medications, Treatments/Procedures ........................ 49 
10 STUDY PROCEDURES AND ASSESSMENTS ............................................................. 51 
10.1 Informed Consent and Screening ...................................................................... 51 
10.2 Description of Study Procedures and Assessments ........................................... 52 
10.2.1 
Adverse Event Collection .................................................................. 52 
 
 
 
10.2.3 
Best Corrected Distance Visual Acuity ............................................. 53 
10.2.4 
Concomitant Medication ................................................................... 53 
10.2.5 
Cycloplegic Refraction ...................................................................... 53 
10.2.6 
Demographics .................................................................................... 54 
10.2.7 
Device Deficiencies ........................................................................... 54 
10.2.8 
Dilated Fundus Examination ............................................................. 54 
10.2.9 
InnovEyes LASIK Planning .............................................................. 54 
10.2.10 InnovEyes LASIK ............................................................................. 55 
10.2.11 InnovEyes Sightmap Assessments .................................................... 55 
10.2.11.1 Aberrometry ....................................................................... 55 
10.2.11.2 Biometry ............................................................................ 55 
10.2.11.3 Keratometry ....................................................................... 56 
10.2.11.4 Pachymetry (Corneal Thickness) ....................................... 56 
10.2.11.5 Topography ........................................................................ 56 
10.2.11.6 Wavefront Refraction ......................................................... 56 
10.2.12 Intraocular Pressure ........................................................................... 56 
10.2.13 Manifest Refraction / Subjective Refraction ..................................... 57 
10.2.14 Medical History ................................................................................. 57 
10.2.15 Mesopic Pupil Size ............................................................................ 57 
 
10.2.17 Slit Lamp Examination ...................................................................... 58 

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10.2.18 Uncorrected Distance Visual Acuity .................................................. 58 
10.2.19 Uncorrected Near Visual Acuity ........................................................ 58 
10.2.20 Urine Pregnancy Test ......................................................................... 59 
10.3 Unscheduled Visits ............................................................................................ 59 
10.4 Discontinued Subjects ....................................................................................... 59 
10.4.1 
Screen Failures .................................................................................. 59 
10.4.2 
Incomplete Treatments ...................................................................... 60 
10.4.3 
Discontinuations ................................................................................ 60 
10.5 Clinical Study Termination ................................................................................ 61 
10.5.1 
Follow-up of Subjects after Study Participation has Ended .............. 61 
11 ADVERSE EVENTS AND DEVICE DEFICIENCIES ................................................... 61 
11.1 General Information .......................................................................................... 61 
11.2 Monitoring for Adverse Events ......................................................................... 65 
11.3 Procedures for Recording and Reporting .......................................................... 65 
11.4 Return Product Analysis .................................................................................... 67 
11.5 Unmasking of the Study Treatment ................................................................... 68 
11.6 Follow-Up of Subjects with Adverse Events ..................................................... 68 
11.7 Pregnancy in the Clinical Study ........................................................................ 68 
12 ANALYSIS PLAN ............................................................................................................ 68 
12.1 Subject Evaluability........................................................................................... 69 
12.2 Analysis Sets ..................................................................................................... 69 
12.2.1 
Safety Analysis Set ............................................................................ 69 
12.2.2 
Full Analysis Set ................................................................................ 69 
12.2.3 
Consistent Cohort Analysis Set ......................................................... 69 
12.3 Demographic and Baseline Characteristics ....................................................... 69 
12.4 Refractive Stability ............................................................................................ 69 
12.5 Effectiveness Analyses ...................................................................................... 70 
12.5.1 
Analysis of Primary Effectiveness Endpoints ................................... 70 
12.5.1.1 
Statistical Hypotheses ........................................................ 71 
12.5.1.2 
Analysis Methods .............................................................. 71 
 
 
12.6 Handling of Missing Data ................................................................................. 71 
12.7 Safety Analyses ................................................................................................. 72 
12.7.1 
Analysis of Primary Safety Endpoints .............................................. 72 
12.7.1.1 
Statistical Hypotheses ........................................................ 72 

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12.7.1.2 
Analysis Methods .............................................................. 72 
 
 
12.8 Interim Analyses and Reporting ........................................................................ 73 
12.9 Sample Size Justification ................................................................................... 73 
13 DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS ............................... 73 
13.1 Subject Confidentiality ...................................................................................... 73 
13.2 Completion of Source Documents and Case Report Forms .............................. 74 
13.3 Data Review and Clarifications ......................................................................... 75 
13.4 Sponsor and Monitoring Responsibilities ......................................................... 75 
13.5 Regulatory Documentation and Records Retention .......................................... 76 
13.6 Quality Assurance and Quality Control ............................................................. 76 
14 ETHICS ............................................................................................................................. 77 
15 REFERENCES .................................................................................................................. 78 
15.1 References Applicable for All Clinical Studies ................................................. 78 
15.1.1 
US References Applicable for Clinical Studies ................................. 78 
15.2 References for This Clinical Study .................................................................... 79 
 
List of Tables 
Table 2–1 
List of Acronyms and Abbreviations Used in This Protocol ........................... 10 
Table 3–1 
Schedule of Study Procedures and Assessments ............................................. 17 
Table 9–1 
Test Product – WaveLight EX500 Excimer Laser System .............................. 43 
Table 9–2 
Test Product - InnovEyes Software .................................................................. 45 
Table 9–3 
Test Product – InnovEyes sightmap ................................................................. 46 
 
 
 
List of Figures 
Figure 11–1 
Categorization of All Adverse Events .............................................................. 62 
Figure 11–2 
Categorization of All Serious Adverse Events ................................................. 62 
 

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1 GLOSSARY OF TERMS 
Names of Test Product(s) 
In this document, test product(s) will be referred to as: 
• Wavelight EX500 for the WaveLight EX500 excimer 
laser system 
• InnovEyes or InnovEyes LASIK for the laser treatment  
• InnovEyes sightmap for the diagnostic device 
Name of Control Product(s) N/A 
Adverse Device Effect 
(ADE) 
Adverse event related to the use of an investigational 
medical device (test product) or control product. Note: This 
definition includes adverse events resulting from insufficient 
or inadequate instructions for use, deployment, 
implantation, installation, or operation; any malfunction; 
and use error or intentional misuse of the test product or 
control product. 
Adverse Event (AE) 
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 product). Note: For subjects, this definition includes 
events related to the test product, the control product, or the 
procedures involved. For users or other persons, this 
definition is restricted to events related to the test product. 
Requirements for reporting Adverse Events in the study can 
be found in Section 11. 
Anticipated Serious 
Adverse Device Effect 
(ASADE) 
Serious adverse device effect, which by its nature, 
incidence, severity, or outcome has been identified in the 
risk management file. 
Device Deficiency 
 
Inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance. Note: 
This definition includes malfunctions, use errors, and 
inadequate labeling. 
Requirements for reporting Device Deficiencies in the study 
can be found in Section 11. 

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Enrolled Subject 
 
Any subject who signs an informed consent form for 
participation in the study. 
Interventional Clinical Trial 
 
A research trial that prospectively assigns, whether 
randomly or not, human participants or groups of humans to 
one or more health-related interventions to evaluate the 
effects on health outcomes, and/or a research trial in which 
diagnostic or monitoring procedures beyond standard of care 
are conducted and generate outcomes for use in analysis of 
data.  
Investigational Product 
Is defined as a preventative (vaccine), a therapeutic (drug or 
biologic), device, diagnostic, or palliative used as a test or 
control product in a clinical trial, including a product with a 
marketing authorization when used or assembled 
(formulated or packaged) in a way different from the 
authorized form, or when used for an unauthorized 
indication, or when used to gain further information about 
the authorized form. 
Malfunction 
Failure of a medical device to perform in accordance with its 
intended purpose when used in accordance with the 
instructions for use or clinical investigation plan. 
Non-Serious Adverse Event Adverse event that does not meet the criteria for a serious 
adverse event. 
Serious Adverse Device 
Effect (SADE)  
Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
Serious Adverse Event 
(SAE) 
Adverse event that led to any of the following: 
• Death. 
• A serious deterioration in the health of the subject that 
either resulted in: 
a. a life-threatening illness or injury. 
Note: Life-threatening means that the individual was 
at immediate risk of death from the event as it 
occurred, ie, it does not include an event which 
hypothetically might have caused death had it 
occurred in a more severe form. 

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b. any potentially sight-threatening event or permanent 
impairment to a body structure or a body function. 
c. in-patient hospitalization or prolonged 
hospitalization. 
Note: Planned hospitalization for a pre-existing 
condition, without serious deterioration in health, is 
not considered a serious adverse event. In general, 
hospitalization signifies that the individual remained 
at the hospital or emergency ward for observation 
and/or treatment (usually involving an overnight 
stay) that would not have been appropriate in the 
physician's office or an out-patient setting. 
Complications that occur during hospitalization are 
adverse events. If a complication prolongs 
hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether 
“hospitalization” occurred, the event should be 
considered serious. 
d. a medical or surgical intervention to prevent a) or b).  
e. any indirect harm as a consequence of incorrect 
diagnostic test results when used within 
manufacturer’s instructions for use. 
• Fetal distress, fetal death, or a congenital abnormality or 
birth defect. 
Refer to Section 11 for additional SAEs. 
Unanticipated Serious 
Adverse Device Effect 
(USADE)  
Serious adverse device effect which by its nature, incidence, 
severity or outcome has not been identified in the risk 
management file. 
Use Error 
Act or omission of an act that results in a different medical 
device response than intended by manufacturer or expected 
by user. Note: This definition includes slips, lapses, and 
mistakes. An unexpected physiological response of the 
subject does not in itself constitute a use error. 
 
 
 

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2 LIST OF ACRONYMS AND ABBREVIATIONS 
Table 2–1 
List of Acronyms and Abbreviations Used in This Protocol 
Abbreviation 
Definition 
ADE 
Adverse device effect 
AE 
Adverse event 
ANSI 
American National Standards Institute 
ASADE 
Anticipated serious adverse device effect 
BCDVA 
Best corrected distance visual acuity 
°C 
Degrees Celsius 
CC 
Consistent cohort 
cd/m2 
Candela per square meter 
CFR 
Code of Federal Regulations 
cm 
Centimeter 
 
 
 
 
CTS 
M&S Technologies’ Clinical Trial Suite 
CYL 
Cylinder 
D 
Diopter 
eCRF  
Electronic Case Report Form 
EDC 
Electronic Data Capture 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
EX 
Excimer 
°F 
Degrees Fahrenheit 
FAS 
Full analysis set 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
GmbH 
Gesellschaft mit beschränkter Haftung - company with limited liability 
hPa 
hectopascal 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference for Harmonization of Technical Requirements 
for Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IOP 
Intraocular Pressure 
IP 
Investigational product 
IRB 
Institutional review board 
ISO 
International Organization for Standardization 
Kg 
Kilogram 
LASIK 
Laser-assisted in situ keratomileusis   
Lb 
Pound 
LED 
Light emitting diode 
logMAR 
Logarithm of the minimum angle of resolution 
m 
Meter 

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Abbreviation 
Definition 
mm 
Millimeter 
mmHg 
Millimeter of mercury 
MOP 
Manual of Procedures 
MRC 
Manifest Refraction Cylinder 
MRSE 
Manifest Refraction Spherical Equivalent 
N 
Number 
N/A 
Not applicable 
 
 
 
 
 
 
 
 
 
 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SAF 
Safety analysis set 
SOP 
Standard Operating Procedure 
SPH 
Sphere 
µm 
Micrometer 
UCDVA 
Uncorrected distance visual acuity 
UCNVA 
Uncorrected near visual acuity 
US 
United States 
USADE 
Unanticipated serious adverse device effect 
USB 
Universal Serial Bus 
USV 
Unscheduled Visit 
VA 
Visual Acuity 
 
 
 
 

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3 PROTOCOL SUMMARY 
Investigational 
Product Type 
Device 
Study Type 
Interventional 
Investigational 
Products 
Test Product: WaveLight® EX500 excimer laser system using 
InnovEyes in conjunction with InnovEyes sightmap 
Purpose and 
Rationale   
Current treatment planning for LASIK treatment, such as wavefront 
optimized, wavefront guided, and topography guided is based on 
simplified formulas and a standardized eye model and does not 
consider the multiple lens structure of the eye. InnovEyes takes the 
multi-lens nature of the eye into consideration. The purpose of this 
study is to evaluate the safety and effectiveness of the WaveLight 
EX500 excimer laser system for the correction of myopia with and 
without astigmatism using InnovEyes in conjunction with 
InnovEyes sightmap. 
Objective(s)  
To evaluate the safety and effectiveness of the WaveLight EX500 
excimer laser system for the correction of myopia with and without 
astigmatism using InnovEyes in conjunction with InnovEyes 
sightmap. 
Details and additional information on objectives are provided in 
Section 6. 
Endpoint(s)  
 
Co-Primary Effectiveness 
Endpoint 
Target  
Percentage of eyes with UCDVA of 20/40 or better (in 
eyes with preoperative BCDVA of 20/20 or better) at 
refractive stability  
≥ 85% 
Percentage of eyes with MRSE within 0.50 D at 
refractive stability  
≥ 50% 
Percentage of eyes with MRSE within 1.00 D at 
refractive stability  
≥ 75% 
Percentage of eyes that achieve refractive stability  
≥ 95% 
 

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Co-Primary Safety 
Endpoint 
Target at 
refractive stability 
Percentage of eyes with BCDVA worse than 20/40 
(for eyes with BCDVA of 20/20 or better pre-op)  
≤ 1% 
Percentage of eyes that lose 2 lines or more of 
BCDVA  
≤5% 
Percentage of eyes that have an increase of 
manifest refractive astigmatism of greater than 
2.00 D of absolute cylinder as compared to the 
preoperative refraction 
≤ 5% 
Percentage of eyes with a serious, non-flap related, 
ocular adverse event at the postoperative visits 
≤ 1% 
Assessment(s)  
Effectiveness 
• Mesopic pupil size 
• Keratometry with InnovEyes sightmap 
• Topography with InnovEyes sightmap 
• Biometry with InnovEyes sightmap 
• Uncorrected photopic distance visual acuity (UCDVA) 
• Manifest refraction 
• Cycloplegic refraction 
Safety 
 
 
• Slit lamp examination 
• Dilated fundus examination 
• Best corrected photopic distance visual acuity (BCDVA) 
• Aberrometry with InnovEyes sightmap 
• Pachymetry with InnovEyes sightmap 
 
 
 
• Intraocular Pressure (IOP) 

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Study Design 
This is a prospective, single-arm, multi-center, interventional study 
with planned bilateral treatment. 
Qualified subjects will receive bilateral InnovEyes treatment and be 
followed for 1 year. Subjects will be asked to attend a total of 
9 visits (screening, surgery, day 1, 1 week, 1 month, 3 month, 
6 month, 9 month, and 1 year). Total expected duration of subject 
participation is approximately 1 year. 
Subject Population   Subjects who desire to have LASIK will be consented and screened 
for meeting the inclusion and exclusion criteria. Subject enrollment 
will be monitored to ensure inclusion of required numbers of 
subjects in each one diopter interval based on the ranges of 
spherical and cylindrical refractive error (bin). 
Key Inclusion 
Criteria 
(See Section 8.1 for 
a complete list of 
inclusion criteria) 
Subjects must meet all inclusion criteria as listed in Section 8.1   
Key Inclusion Criteria include: 
• Myopia up to and including -11.00 D with or without 
astigmatism up to -4.50 D, with  spherical equivalent no more 
than -12.00 D as shown from InnovEyes sightmap Measured 
refraction 
• Best corrected photopic distance visual acuity of 20/20 or better 
(≤ 0.04 logMAR) 
• Uncorrected photopic distance visual acuity of 20/40 or worse 
(≥ 0.34 logMAR) 
• Stable refraction (within ± 0.50 D) as determined by MRSE for 
a minimum of 12 months prior to surgery 
Key Exclusion 
Criteria 
(See Section 8.2 for 
a complete list of 
exclusion criteria) 
Subjects must not meet exclusion criteria as listed in Section 8.2   
Key Exclusion Criteria include: 
• History or evidence of active or inactive corneal disease or 
retinal vascular disease, keratoconus or glaucoma (or suspect) 
• Previous intraocular or corneal surgery 
• Intent to have monovision treatment 
Data Analysis and 
Sample Size 
Justification 
The safety analysis set (SAF) will contain all eyes that undergo 
surgery or attempted surgery (defined as eye drops given for flap 
treatment); the SAF will be the primary analysis set for the safety 

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analyses. The full analysis set (FAS) will contain all eyes that 
successfully undergo surgery; the FAS will be the primary analysis 
set for the effectiveness analyses. The consistent cohort (CC) will 
contain all eyes in the FAS that have manifest refraction data at all 
post-operative visits. The CC will be the primary analysis set for the 
refractive stability analyses. 
Refractive stability is said to have been achieved at the latter of two 
postoperative manifest refractions performed at least 3 months apart 
(or at 3 months after surgery when compared with the 1-month 
visit) if all the requirements for stability listed in the endpoints 
section of the synopsis have been met. Stability will be confirmed 
by an adequate subgroup (at least 80% of the cohort) at the next 
scheduled visit interval. 
The number and percentage of eyes meeting each of the primary 
effectiveness endpoints will be calculated. The effectiveness criteria 
will be considered to have been met if the percentage meets or 
exceeds the target rate at the time of refractive stability for all 
primary effectiveness endpoints. 
The number and percentage of eyes experiencing each of the 
primary safety endpoints will also be calculated. The safety criteria 
will be considered to have been met if the percentage is less than 
the target rate at the time of refractive stability for all of the primary 
safety endpoints. 
An analysis will be performed once refractive stability is achieved; 
a final analysis will be performed once the one-year follow-up is 
complete. 

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Up to 374 eyes will be treated in this study. With 374 eyes treated, 
any ocular serious adverse event type that occurs in at least 1% of 
the population undergoing the procedure will be observed in this 
study at least one time, with approximately 95% probability. This is 
in accordance with ANSI Z80.11-2012(R2017). 
Key Words 
• LASIK 
• Ray Tracing 
• Myopia 
• Astigmatism 
Associated 
Materials 
• WaveLight® EX500 Laser System 
• WaveLight® FS200 Laser System 
• Patient Interface for WaveLight FS200 Laser System 
• WaveCard 

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Table 3–1 
Schedule of Study Procedures and Assessments 
Screening1 
Surgery 
Postoperative  
Other 
 
Visit 0  
Visit 00 / 
Visit 00A2 
Visit 1 / 
Visit 1A 
Visit 2 / 
Visit 2A 
Visit 3 / 
Visit 3A 
Visit 4 / 
Visit 4A 
Visit 5 / 
Visit 5A 
Visit 6 / 
Visit 6A 
Visit 7 / 
Visit 7A 
Early 
Exit  
USV3 
Procedure/ Assessment 
Day -30 to  
-1  
Day 0  
Day 1 
Day 5   
to 9 
Day 21 
to 35 
Day 70 
to 98 
Day 147 
to 182 
Day 245 
to 301 
Day 330 
to 420 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X4 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Pregnancy Test5* 
X 
 
 
 
 
 
 
 
 
 
 
Cycloplegic Refraction 
X 
 
 
 
 
 
X 
 
 
 
 
Mesopic pupil size 
X 
 
 
 
X 
X 
X 
X 
X 
X 
 
InnovEyes sightmap 
Aberrometry 
X6 
 
 
 
X 
X 
X 
X 
X 
X 
 
Biometry  
X6 
 
 
 
X 
X 
X 
X 
X 
X 
 
Keratometry  
X6 
 
 
 
X 
X 
X 
X 
X 
X 
 
Pachymetry (Corneal 
Thickness)  
X6 
 
 
 
X 
X 
X 
X 
X 
X 
 
Topography* 
X6 
 
 
 
X 
X 
X 
X 
X 
X 
 
Wavefront Refraction 
X6 
 
 
 
X 
X 
X 
X 
X 
X 
 
UCDVA 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Manifest/Subjective Refraction7  
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 

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Screening1 
Surgery 
Postoperative  
Other 
 
Visit 0  
Visit 00 / 
Visit 00A2 
Visit 1 / 
Visit 1A 
Visit 2 / 
Visit 2A 
Visit 3 / 
Visit 3A 
Visit 4 / 
Visit 4A 
Visit 5 / 
Visit 5A 
Visit 6 / 
Visit 6A 
Visit 7 / 
Visit 7A 
Early 
Exit  
USV3 
Procedure/ Assessment 
Day -30 to  
-1  
Day 0  
Day 1 
Day 5   
to 9 
Day 21 
to 35 
Day 70 
to 98 
Day 147 
to 182 
Day 245 
to 301 
Day 330 
to 420 
 
 
BCDVA 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
UCNVA 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IOP 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Slit Lamp Examination  
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dilated Fundus Examination  
X 
 
 
 
 
 
X 
 
 
X 
X 
InnovEyes LASIK Planning 
X 
 
 
 
 
 
 
 
 
 
 
InnovEyes LASIK 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Device Deficiencies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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1 Screening should cover evaluation of both eyes with intent for bilateral treatment on the same surgery day 
2 ‘A’ denotes visit for 2nd eye treated 
3 Unscheduled visit - other study assessments may be performed per the Investigator’s discretion  
4 Confirm inclusion/exclusion criteria as needed  
5 Required only for women of child-bearing age, not postmenopausal or surgically sterile 
6 Measured twice, once with cycloplegia and once for treatment planning 
7 Subjective Refraction to assess for inclusion stability at Screening (Visit 0) should be performed on the site’s chart; subjective refraction for VA testing will be 
refraction on Sponsor provided electronic chart 
 
 
 
 
 
 
* Data collected in source only 

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4 PROTOCOL AMENDMENTS 
Modification of the protocol is prohibited without prior written agreement in the form of a 
protocol amendment. All amendments must be created by the Study Sponsor and must be 
approved by the IRB/IEC and global and regional Health Authorities, as applicable, prior to 
implementation except when required to mitigate immediate safety risks or when the changes 
involve only logistical or administrative revisions.  
Amendments may necessitate that the informed consent and other study-related material be 
revised. If the consent form is revised, all subjects currently enrolled in the study must sign 
the approved, revised informed consent (re-consent), as required by the IRB/IEC. 

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Itemized Changes: 

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5 INTRODUCTION 
5.1 Rationale and Background 
The goal of refractive surgery is to provide the patient with his or her best possible visual 
performance. Accurate methods of calculation are required to achieve satisfactory surgical 
outcomes. In order to improve the clinical outcome from LASIK treatment, a new treatment 
option named “InnovEyes” has been developed. Current treatment planning for LASIK 
procedures, such as wavefront optimized, wavefront guided and topography guided is based 
on simplified formulas and a standardized eye model and does not consider the multiple lens 
structure of the eye. The InnovEyes software for the WaveLight EX500 uses a new, 
computer-based method to calculate ablation profiles based on a ray tracing algorithm and 
also takes the multi-lens nature of the eye into consideration. For the InnovEyes procedure, 
the model data of the eye are replaced by measured diagnostic data of the individual patient 
from the subject’s eye such as topography, aberrometry, wavefront, and eye length. By 
combining these data, a patient-specific ablation profile is then generated from the calculated 
individual eye model based on an iterative “Ray Tracing” calculation. By considering all 
optical elements of the eye, such as the back and front surfaces of the cornea and the 
crystalline lens, as well as the corresponding distances in the eye model, ray tracing offers 
currently the highest possible accuracy to improve the refractive predictability of corneal 
laser surgery (Simon 2011). 
An initial clinical trial in which the ray tracing algorithm was used was conducted by 
WaveLight GmbH in 2009-2010. The purpose of the study was to assess the efficacy, safety, 
and predictability of an individualized laser-assisted in situ keratomileusis (LASIK) ablation 
profile based on an optical ray tracing algorithm to treat moderate to high myopic 
astigmatism (Schumacher 2012). For this initial Ray tracing (now called InnovEyes) 
treatment, calculation was performed with a Mathlab program installed on a separate 
computer and treatment was implemented by the WaveLight Concerto or Allegretto laser. In 
addition, in this initial clinical trial, the diagnostic data were collected from three different 
WaveLight diagnostic devices. This trial provided evidence of the safety, efficacy, and 
predictability of laser-assisted in situ keratomileusis outcomes using an optical ray tracing 
algorithm to treat moderate to high myopic astigmatism and shows that good results are 
sustained through 1 year (Cummings 2013).   

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Since the past study using the InnovEyes software and ray tracing algorithm was completed, 
a new diagnostic device named “InnovEyes™ sightmap” has been developed. Historically 
needed data for LASIK treatment has been gathered from different diagnostic devices, but for 
improved usability and a defined common coordinate system, the InnovEyes sightmap 
combines the necessary measurements for InnovEyes treatment within one device.   
The InnovEyes sightmap is designed to perform measurements (Scheimpflug Camera 
principle, Hartmann-Shack principle, and interferometry) which includes the cornea, pupil, 
anterior chamber, lens, and length of the eye. Furthermore, it provides the axial dimensions of 
the eye. It is also indicated to analyze the optical aberrations of the eye by using wavefront 
technology. 
In detail, the InnovEyes sightmap provides data to evaluate the: 
• Corneal shape including corneal thickness, anterior, and posterior corneal surface 
• Anterior chamber angle, depth, and volume 
• White-to-white distance 
• Pupil diameter 
• Conditions of the lens (eg, opaque crystalline lens) 
• Location of cataracts (eg, nuclear, sub-capsular, and/or cortical) 
• Axial length 
• Optical aberrations of the eye 
This device has been developed for ophthalmic diagnosis and for use in hospitals, in eye 
doctor medical practices and at optometrists/opticians. The examination data get stored 
electronically and can be exported and used in combination with the WaveLight GmbH laser 
systems (ie, EX500) to perform InnovEyes treatment for qualified subjects. 
5.2 Purpose of the Study 
The purpose of this clinical study is to determine the safety and effectiveness of the 
WaveLight EX500 excimer laser system for the correction of myopia with and without 
astigmatism using InnovEyes in conjunction with InnovEyes sightmap. 
At the end of the study, a clinical study report will be prepared in accordance with applicable 
regulatory requirements and standards. 

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Results of the study may be used for publication if they are of scientific interest and for 
marketing after approval or clearance for marketing. 
5.3 Risks and Benefits 
As with any refractive surgical procedure or diagnostic device, there are potentials risks with 
the use of the InnovEyes sightmap and InnovEyes treatment. However, there are no 
additional warnings or precautions associated with these outside of the risks identified for the 
use of other similar diagnostic devices or other LASIK procedures performed on the EX500. 
There may also be unknown risks to use of the InnovEyes sightmap and InnovEyes treatment. 
Any risk to subjects in this clinical study will be minimized by compliance with the eligibility 
criteria and study procedures, clinical oversight, and monitoring. 
The medical benefit of the InnovEyes sightmap is in its collection of diagnostic data and data 
of the optical properties of the whole eye in order to facilitate treatment planning for 
refractive surgery. The diagnostic data may be used to screen out patients that are not eligible 
for surgery or for planning treatment with the intent of improving outcomes with InnovEyes 
LASIK.  
The medical benefit of the InnovEyes software is in the accuracy of determining an 
individual eye’s ablation profile.  
More information on summary of the literature, description of the investigational device, 
guidance for the Investigator, as well as known and potential risks and benefits can be found 
in the Investigator’s Brochure (IB) [IB-0171] Investigator Brochure for InnovEyes and 
InnovEyes sightmap and the InnovEyes sightmap user manual. 
6 STUDY OBJECTIVES 
6.1 Primary Objective(s) 
The primary objective of this study is to evaluate the effectiveness of the WaveLight EX500 
excimer laser system for the correction of myopia with and without astigmatism using 
InnovEyes in conjunction with InnovEyes sightmap.  
6.1.1 
Primary Endpoints 
• Percentage of eyes with UCDVA of 20/40 or better (in eyes with preoperative BCDVA 
of 20/20 or better) at refractive stability (Target ≥ 85%) 
• Percentage of eyes with MRSE within 0.50 D at refractive stability (Target ≥ 50%) 

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• Percentage of eyes with MRSE within 1.00 D at refractive stability (Target ≥ 75%) 
• Percentage of eyes that achieve refractive stability (Target ≥ 95%) 
Note: Refractive stability is defined in Section 6.4 and Section 12.4 

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6.3 Safety Objective(s) 
The primary safety objective of this study is to evaluate the safety of the WaveLight EX500 
excimer laser system for the correction of myopia with and without astigmatism using 
InnovEyes in conjunction with InnovEyes sightmap. 
6.3.1 
Primary Safety Endpoints 
• Percentage of eyes that lose 2 lines or more of BCDVA (Target at refractive stability ≤ 5%) 
• Percentage of eyes with BCDVA worse than 20/40 (for eyes with BCDVA of 20/20 or 
better pre-op) (Target at refractive stability ≤ 1%) 
• Percentage of eyes that have an increase of manifest refractive astigmatism of greater 
than 2.00 D of absolute cylinder as compared to the preoperative refraction (Target at 
refractive stability ≤ 5%) 
• Percentage of eyes with a serious, non-flap related, ocular adverse event at the 
postoperative visits (Target per event type at refractive stability ≤ 1%) 

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6.4 Refractive Stability 
Stability analyses will be performed on eyes that have every follow-up exam from 1-month 
up to the stability time point (the Consistent Cohort), as well as on the eyes that have 2 
consecutive exams, but not necessarily every follow-up exam. The following stability 
analyses will be performed for the time intervals between all consecutive pairs of scheduled 
postoperative refractions: 
• Percentage of eyes that achieve: 
o a change of less than or equal to 1.00 D of MRSE between two refractions 
performed at 1 month and 3 months, and between subsequent refractions 
performed at least 3 months apart; 

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o a change of less than or equal to 0.50 D of MRSE between two refractions 
performed at 1 month and 3 months, and between subsequent refractions 
performed at least 3 months apart; 
• Mean overall change and change per month in MRSE between consecutive scheduled 
visits as determined by a paired analysis; 
• Mean ± SD MRSE for the preoperative and each postoperative visit; 
• Assessment of cylinder stability for correction of spherocylindrical refractive errors 
Refractive stability is achieved at the latter of two postoperative manifest refractions 
performed at least 3 months apart or at 3 months after surgery when compared with the 1-
month interval, when all of the following recommended criteria are met: 
• At least 95% of the treated eyes have a change ≤ 1.00 D of MRSE between the 2 
refractions; 
• The mean rate of change in MRSE, as determined by a paired analysis, is ≤ 0.5 D per 
year (0.04 D/month) over the same time period; 
• The mean rate of change of MRSE decreases monotonically over time, with a 
projected asymptote of zero or a rate of change attributable to normal aging; 
• The 95% confidence interval for the mean rate of change in MRSE includes zero or a 
rate of change attributable to normal aging; and  
• Stability is confirmed at least 3 months after the stability time point by a statistically 
adequate subgroup (at least 80% of the cohort). 
7 INVESTIGATIONAL PLAN 
7.1 Study Design 
This is a prospective, single-arm, multi-center, interventional study with planned bilateral 
InnovEyes LASIK treatment for subjects requiring refractive correction of myopia with or 
without astigmatism. All treated eyes will be targeted for emmetropia. The postoperative state 
of each treated eye will be compared to the preoperative state of the same eye.  
Subjects will be evaluated initially for suitability as candidates for bilateral LASIK. Potential 
subjects willing to participate will be consented and screened. Approximately 187 qualified 
subjects (up to 374 eyes) will receive bilateral InnovEyes LASIK and be followed for 1 year. 
Total duration of subject participation is approximately 1 year and includes 9 study visits 
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12 months. Subjects will be enrolled with intent to treat at least 20 eyes in each spherical 
diopter and each cylindrical diopter range (with only 10 eyes in the highest cylinder bin). 
Approximately 10 US study sites will participate in this clinical study. It is estimated that 
enrollment and follow-up of all subjects will take approximately 22 months. Additional 
information on the study population can be found in Section 8. 
Assessments will be obtained at baseline and at appropriate times after InnovEyes LASIK to 
evaluate the safety and effectiveness of the treatment. 
 
 
 
 
  
The main analyses for effectiveness and safety will be conducted when refractive stability for 
the cohort has been determined and 80% of the eyes in the cohort have completed the next 
scheduled visit after refractive stability (Refractive Stability is defined in Section 6.4 and 
12.4). The Sponsor may file a Pre-Market Approval application once this analysis is 
complete. Subjects are followed for at least 12 months (Day 330 to Day 420) for safety and 
supportive effectiveness assessments. Final data analyses will be conducted at study 
completion. 
7.2 Rationale for Study Design  
The prospective, single group study design, objectives, planned visits and assessments, and 
planned analysis at refractive stability are based on recommendations by ANSI Z80.11-
2012(R2017) (American National Standard for Ophthalmics – Laser Systems for Corneal 
Reshaping, approved August 9, 2012 and Reaffirmed December 11, 2017) and ISO 
14155:2011.  
The study population includes subjects with myopia, with or without astigmatism, based on 
this being a prevalent refractive error for LASIK treatments today and the intended 
population for InnovEyes LASIK. 
Bilateral treatments of subjects will be implemented in this study based on past clinical study 
results that provide initial safety, effectiveness, and stability data (Schumacher 2012; 
Cummings 2013). 

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7.2.1 
Purpose and Timing of Interim Analyses and Resulting Design 
Adaptations 
Analysis will occur for review of refractive stability as specified by ANSI Z80.11-
2012(R2017), which includes 1 additional visit beyond stability completed by at least 80% of 
the cohort.   
No changes to study design, after the initiation of the study, are planned. 
7.3 Rationale for Duration of Treatment/Follow-Up 
One year follow-up (Day 330 to 420) of subjects will be implemented in this study based on past 
clinical study results using the ray tracing algorithm that provided initial safety, effectiveness, 
and stability data through one year follow-up. (Schumacher 2012; Cummings 2013). 
7.4 Data Monitoring Committee 
Not applicable.  
8 STUDY POPULATION 
The study population consists of subjects who desire to have and qualify for LASIK 
treatment, are 18 years of age or older, and have myopia up to -11.00 D with or without 
astigmatism up to -4.50 D. This study is aimed to enroll (consent) approximately 374 subjects 
at up to 10 sites in the United States with a target of up to 374 eyes treated. Because about 
50% screening failure rate and up to 10% lost to follow-up rate is expected, these numbers 
will allow for treatment and follow-up of at least 300 eyes and account for overlap or over-
enrollment in certain ranges to achieve the required number of 20 eyes per diopter over the 
intended refractive range. Allocation of study bins will be closely monitored through the use 
of listings generated from the InnovEyes sightmap Measured refraction entered in EDC.  
Investigative sites will be trained on the importance of timely entry of data in EDC to ensure 
enrollment bin allocation is up to date.  When enrollment in a refractive bin is complete, sites 
will be instructed to refrain from enrolling eyes in that bin.  Site-specific targets may vary 
based upon individual site capabilities, but each site is expected to treat a minimum of 20 
eyes and no more than 92 eyes per site.   
Enrollment will be monitored to aim for 20 or more eyes treated and followed to refractive 
stability in each diopter interval based on the ranges of spherical and cylindrical refractive 
error (bin). Therefore at least 220 eyes will be treated for the sphere range (20 eyes/diopter 
interval of 0 to -11.00) and at least 110 eyes will be treated for the cylinder range (20 eyes for 
0 to ≤ -0.50 and > -0.50 to ≤ -1.00 cylinder and 20 eyes/diopter for intervals from > -1.00 to   

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-4.00 and 10 eyes in > -4.00 to -4.50). For a diagram showing the study bins, refer to the 
Manual of Procedures (MOP). All bin assignments are made based on the InnovEyes 
sightmap Measured refraction entered in EDC. Estimated time needed to recruit subjects for 
the study is approximately 10 months; however, unanticipated circumstances may shorten or 
lengthen this time and would not require amendment of this protocol.  
8.1 Inclusion Criteria 
Written informed consent must be obtained before any study specific assessment is 
performed. Upon signing informed consent, the subject is considered enrolled in the study. 
Subjects eligible for inclusion in this study must fulfill all of the following criteria: 
1. 
Subject must be able to understand and sign an IRB/IEC approved Informed 
Consent form 
2. 
Willing and able to attend all scheduled study visits as required per protocol 
3. 
Minimum of 18 years of age, or age of adulthood as determined by local 
regulations 
4. 
Myopia up to -11.00 D with or without astigmatism up to -4.50 D, with spherical 
equivalent no more than -12.00 D as shown from InnovEyes sightmap Measured 
refraction  
5. 
Best corrected photopic distance visual acuity of 20/20 or better (≤ 0.04 logMAR) 
6. 
Uncorrected photopic distance visual acuity of 20/40 or worse (≥ 0.34 logMAR) 
7. 
Less than 0.75 D MRSE difference between cycloplegic and subjective manifest 
refractions       
8. 
Less than 0.75 D MRSE difference between InnovEyes sightmap Measured 
refraction and subjective manifest refractions  
9. 
Stable refraction (within ± 0.50 D) as determined by MRSE for a minimum of 12 
months prior to surgery, verified by consecutive subjective refractions and/or 
medical records or prescription history 
10. 
Demonstrated stable refraction for contact lens wearers: within ± 0.5 D MRSE on 
two consecutive exam dates under the following conditions 

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a. Lenses are not worn for at least 3 weeks (rigid or toric contact lenses) or 1 
week (soft contact lenses) prior to the first refraction used to establish 
stability and through the day of surgery 
b. the two subjective refractions are performed at least 7 days apart 
8.2 Exclusion Criteria 
Subjects fulfilling any of the following criteria are not eligible for participation in this study. 
1. 
Women of childbearing potential, defined as all women who are physiologically 
capable of becoming pregnant and who are not postmenopausal for at least 1 year or 
are less than 6 weeks since sterilization, are excluded from participation if any of 
the following apply: 
a. they are currently pregnant, 
b. have a positive urine pregnancy test result at Screening, 
c. intend to become pregnant during the study period, 
d. are breast-feeding 
Note: Subjects who become pregnant during the study will not be discontinued; 
however, data will be excluded from the effectiveness analyses because pregnancy 
can alter refraction and visual acuity results. 
2. 
Acute or chronic disease or illness that would increase the operative risk or 
confound the outcomes of the study 
3. 
Systemic medications that may confound the outcome of the study or increase the 
risk to the subject, including, but not limited to steroids, antimetabolites, 
isotretinoin, or amiodarone hydrochloride 
4. 
Ocular condition (other than high myopia) that may predispose the subject to future 
complications, for example: 
• history or evidence of active or inactive corneal disease (eg, herpes simplex 
keratitis, herpes zoster keratitis, recurrent corneal erosion syndrome, corneal 
dystrophy, etc) 
• evidence of retinal vascular disease 
• keratoconus or keratoconus suspect 
• glaucoma or glaucoma suspect by exam findings and/or family history 
5. 
Previous intraocular or corneal surgery 

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6. 
Predicted residual stromal bed thickness < 250 μm 
7. 
Intended to have monovision treatment 
8. 
Participation in other clinical trials during the course of the study that may 
confound study results 
9. 
Other condition or assessment that causes subject to not be an acceptable candidate 
for treatment or study participation as clinically assessed and documented by the 
Investigator 
8.3 Rescreening of Subjects 
Rescreening of subjects is allowed for the conditions listed below: 
Rescheduling of surgery: If a subject reschedules surgery or surgery is rescheduled due to 
other reasons, and this rescheduling results in preoperative/screening assessments (Visit 0) 
falling outside of the -30 to -1 day window, assessments should be repeated and 
inclusion/exclusion criteria re-verified to ensure the subject still qualifies to proceed with 
study surgery. 
Criteria not met: Rescreening of subjects who did not meet inclusion/exclusion criteria is 
allowed one time per subject. Rescreening is allowed only if criteria previously not met could 
reasonably have changed since the prior screening. Criteria that could change and rescreening 
would be allowed include: Inclusion 3, 6, or if changes in refractive stability or receipt of 
additional past records can show stability for criteria 7 – 10. 
NOTE: IF a subject is rescreened, THEN use the same subject number. Update the screening 
data in EDC with date and results of the rescreening. Keep the original consent date captured 
in EDC. Document the rescreening, and keep results from both screening visits in the 
subject’s chart. 
9 TREATMENTS ADMINISTERED 
In this study, the WaveLight EX500 excimer laser will be used to perform InnovEyes LASIK 
treatment using preoperative data from the InnovEyes sightmap. Subjects who qualify for 
inclusion into the study will undergo treatment in both eyes. All treated eyes will be targeted 
for emmetropia. 
An outline of key LASIK treatment steps after confirming subject qualification, including 
obtaining data from the InnovEyes sightmap, include: 

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• Prepare subject for treatment using standard of care methods for LASIK treatment 
• Create corneal flap using the WaveLight FS200 using standard of care methods for 
LASIK treatment 
• Perform InnovEyes LASIK using the WaveLight EX500 
o Target should be emmetropia  
o Treatment must be performed by trained and delegated Investigator (no 
more than 2 Investigators per site allowed) 
• Use standard of care methods for post-LASIK treatment 
• Follow subject according to Table 3–1 
Note: Additional procedure information is listed in the MOP and User Manuals. 
Note: Retreatment of the eye is not allowed in the study. 
9.1 Investigational Product(s) 
Test Product(s): 
• WaveLight EX500 excimer laser system  
• InnovEyes Software  
• InnovEyes sightmap  
[See Table 9–1 to Table 9–3 for details on each 
product] 
Control Product(s) (If applicable): Not applicable 
 
Table 9–1 
Test Product – WaveLight EX500 Excimer Laser System 
Test Product 
WaveLight EX500 excimer laser system  
Manufacturer 
WaveLight GmbH 
Am Wolfsmantel 5  
91058 Erlangen, Germany 
Indication for Use 
and Intended 
Purpose in the 
Current Study 
The WaveLight EX500 is an FDA approved stationary scanning-spot 
excimer laser system used in refractive surgery for the treatment of 
myopia, myopic astigmatism, hyperopia, hyperopic astigmatism, and 
mixed astigmatism, including customized refractive surgery based on 
data delivered by WaveLight’s diagnostic devices. 

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For this clinical study, the WaveLight EX500 software will be 
upgraded to include the ray tracing treatment (InnovEyes). This 
treatment option on the EX500 can only be activated by use of the 
WaveCard supplied by the Sponsor and will be used for treatment of 
myopia, with or without astigmatism. 
Product 
Description and 
Parameters 
Available for this 
Study 
For treatments, at least the following components of the system have 
to be operated: 
• Laser Console - containing operating elements, laser head, optical 
transmission system, energy, and system controls; 
o Eyetracker, scanner motors, gas supply, plume evacuator, 
headup display, video system, N2 generator focusing and 
fixation lights, system software and ablation profiles with 
scanning spot patterns, operating microscope with 
illumination, LED slit illumination system, and test systems 
• Patient Bed - with moving motors and bed control 
• System Notebook (WaveNet Planning System) – containing 
software for programming treatment parameters 
Formulation 
N/A 
Usage 
In this study, the WaveLight EX500 excimer laser will be used to 
perform InnovEyes LASIK treatment. 
Prior to usage for the laser portion of the treatment, a corneal flap 
must be created. For this study, the WaveLight FS200 femtosecond 
laser unit will be utilized to create the flap. 
The WaveLight EX500 laser system is intended for use solely by the 
physicians trained in the use of this laser system and its accessories. 
During its operation, it does not come into contact with the eye, and 
treatment usually lasts 1.3 seconds per diopter. 
The WaveLight EX500 can be used in combination with a class B 
network (WaveNet) as a data exchange medium for importing 
treatment data from the WaveLight GmbH diagnostic devices, such as 
InnovEyes sightmap in this study, see Table 9–3. 
Operating 
Conditions 
Temperature: + 64°F (+ 18°C) to + 86°F (+ 30°C) above dew point 
Humidity: 20% to 70% at + 77°F (+ 25°C), not condensing 

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Air pressure (recommended): 800 hPa to 1060 hPa (Barometric) 
Supply 
Each selected investigational site must have an EX500. 
 
Table 9–2 
Test Product - InnovEyes Software 
Test Product 
InnovEyes software for WaveLight EX500 excimer laser system 
Manufacturer 
WaveLight GmbH 
Am Wolfsmantel 5 
91058 Erlangen, Germany 
Indication for Use 
and Intended 
Purpose in the 
Current Study 
InnovEyes is the tradename of a software which uses the ray tracing 
algorithm and is intended for the treatment of myopia, with and 
without astigmatism. It uses ocular data from the InnovEyes sightmap 
to calculate a subject specific ablation profile for refractive correction 
using the EX500. 
Treatment ranges for Ray Tracing: 
• Myopia -11.00 to 0.00 D 
• Myopic Astigmatism -4.50 to 0.00 D 
• Optical zones Between 6.0 and 7.0 mm 
Product 
Description and 
Parameters 
Available for this 
Study 
InnovEyes software is loaded onto the WaveLight EX500 excimer 
laser to perform customized InnovEyes treatments, and can be 
activated only by use of a specific Platinum WaveCard in 
combination with a data set transferred from the InnovEyes sightmap. 
The Workflow and graphical user interface for the InnovEyes 
planning and treatment shall be similar to existing workflows and 
graphical user interfaces. 
Formulation 
N/A 
Usage 
InnovEyes software will display as an InnovEyes treatment option on 
the EX500 for selection by the user. A Sponsor supplied Wavecard is 
required to activate this treatment option. InnovEyes treatment is 
permitted only with a complete set of valid diagnostic data from the 
InnovEyes sightmap. 
InnovEyes software is intended for use solely by the physicians 
trained in the use of the EX500 laser system and its accessories. 

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Operating 
Conditions 
N/A 
Supply 
WaveLight/Alcon representatives will install the InnovEyes software 
onto the site’s EX500 laser. 
 
Table 9–3 
Test Product – InnovEyes sightmap 
Test Product 
InnovEyes sightmap 
Manufacturer 
WaveLight GmbH 
Am Wolfsmantel 5  
91058 Erlangen, Germany 
Indication for Use 
and Intended 
Purpose in the 
Current Study 
The InnovEyes™ sightmap is a non-contact ophthalmic diagnostic 
device designed to capture images of the anterior segment of the 
eye, which includes the cornea, pupil, anterior chamber, and lens of 
the eye. Furthermore, it provides the axial dimensions of the eye. It 
is also indicated to analyze the optical aberrations of the eye by 
using wavefront technology. 
This device has been developed for ophthalmic diagnosis and for 
use in hospitals, in eye doctor medical practices including use by 
optometrists/opticians. The examination data get stored 
electronically and can be exported and used in combination with the 
WaveLight GmbH laser systems in the field of refractive surgery. 
Data transfer can be done via a network interface or via USB stick. 
Product Description 
and Parameters 
Available for this 
Study 
The InnovEyes sightmap is a non-contact ophthalmic diagnostic 
device. 
The InnovEyes sightmap contains the following components: 
• InnovEyes sightmap detector head mounted on a cross table 
(adjustable platform) 
• Head Rest 
• Panel Personal Computer 
• Electronics unit including power supply 
• Set of connecting cables 
• Test Object 
• Black Cloth 

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• Dust protection cap 
The following components are optional: 
• Operator chair 
• Patient chair 
• Lift Table Diagnostic System 
Formulation 
N/A 
Usage 
The InnovEyes sightmap will be used to collect subject ocular data 
to be used in InnovEyes LASIK treatment on the EX500. 
In this study, the InnovEyes sightmap will provides data to evaluate 
the following areas in planning InnovEyes LASIK: 
• Corneal shape including corneal thickness, anterior, and 
posterior corneal surface 
• Anterior chamber angle, depth, and volume 
• White-to-white distance 
• Pupil diameter 
• Conditions of the lens (eg, opaque crystalline lens) 
• Location of cataracts (eg, nuclear, sub-capsular, and/or 
cortical) 
• Axial length 
• Optical aberrations of the eye 
The InnovEyes sightmap should only be used by specially trained 
physicians, medical staff, and optometrists who are well versed in 
its diagnostics abilities and possible dangers. It should only be 
operated according to the operating instructions as listed in the user 
manual. 
Operating 
Conditions 
Temperature (recommended) + 10°C (+ 50°F) to + 40°C (+ 104°F) 
Humidity (recommended) 30% to 75% at + 25°C (+ 77°F) 
Air pressure (Barometric) 700 hPa to 1060 hPa 
Supply 
The InnovEyes sightmap will be delivered in appropriate packaging 
to cover and protect the 16 kg (35.7 lb) device that measures 
approximately 275 x 320 to 400 x 500 to 535 mm (10.8 x 12.6 to 
15.7 x 19.7 to 20.0 in). WaveLight/Alcon representatives will install 
the device at the clinical site prior to study startup. 
 

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The Investigator will be responsible for ensuring that the products are used in accordance 
with their respective indications and procedural guidance provided in the appropriate User 
and Procedure Manuals. The EX500 and the InnovEyes sightmap operating conditions fall 
within routine ambient conditions for a medical/ophthalmic office; therefore, a daily log will 
not be required to document environmental conditions. Clinical sites should ensure 
conditions are met as they do in standard clinical practice. IF conditions occur outside of the 
accepted ranges, THEN do not operate the device and contact the study Sponsor.   
More information on the test product can be found in the Investigator’s Brochure (IB) 
[IB-0171] Investigator Brochure for InnovEyes and InnovEyes sightmap and in the 
InnovEyes sightmap user manual. Information on the WaveLight EX500 can be found in the 
EX500 User Manual and Quick User Manual EX500 InnovEyes.   
9.2 Other Medical Device or Medication Specified for Use During the 
Study 
During the clinical study, additional medical devices and/or medications that are required in 
conjunction with the treatment include the following: 
• WaveLight FS200:  The FDA approved FS200 will be used for creation of the corneal 
flap according to MOP and associated user manuals, and is to be performed by a 
qualified ophthalmic surgeon. 
• Patient Interface: The patient interface designed for use with the FS200 will be used 
according to the approved user guide.  
• WaveCard: The clinical study treatment, InnovEyes, can be executed only by using a 
specific WaveCard that has not been available in the U.S. to date. This WaveCard is 
serial-number-specific for a particular laser and a defined number of treatments. This 
WaveCard will be provided to the site upon installation of the InnovEyes Software and 
will be labeled “CAUTION--Investigational device. Limited by Federal (or United 
States) law to investigational use.” 
• Medications given for InnovEyes LASIK will be per the Investigator’s standard of 
care for LASIK. 
9.3 Treatment Assignment/Randomization 
After signing the ICF, a subject must be entered into the EDC system and will be assigned a 
subject number upon entry. This subject number will be used to identify the subject through 
the clinical study.  Subjects that qualify based on inclusion and exclusion criteria should be 

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treated as schedules allow surgery to be performed. This is a single group study as 
recommended by ANSI Z80.11 2012(R2017) and all subjects will be planned for bilateral 
InnovEyes LASIK with a target of emmetropia; therefore, no randomization will be used. 
9.4 Treatment Masking 
The clinical study design is a single-arm treatment and therefore all members associated with 
the study (at the site and the Study Sponsor) are unmasked to the assigned treatment. 
9.5 Accountability Procedures 
Upon receipt of the InnovEyes sightmap and InnovEyes software installation on the EX500, 
the Investigator or delegate must complete study-specific confirmation of receipt procedures 
as described in the MOP, and retain any required documentation in the Investigator’s clinical 
study records. Throughout the study, the Investigator or delegate must maintain records of IP 
use for each subject (eg, dispensation log and WaveCard use documentation). These records 
must be made available to the study monitor for the purposes of verifying the accounting of 
IP use. Any discrepancies and/or deficiencies between the observed disposition and the 
written account must be recorded along with an explanation. All IPs sent to the Investigator 
must be accounted for by Study Sponsor personnel, and in no case be used in an unauthorized 
manner. 
Return investigational products associated with a device deficiency to the Study Sponsor, as 
appropriate. Refer to Section 11 of this protocol for additional information on the reporting of 
device deficiencies and to the MOP for information on return of study products associated 
with these events. 
The Investigator is responsible for proper disposition/return of all unused IP (such as 
sightmap device and removal or inactivation of software) at the conclusion of the study, 
according to the instructions provided in the MOP. 
9.6 Changes to Concomitant Medications, Treatments/Procedures 
After the subject is enrolled into the study, the Investigator must instruct the subject to notify 
the study site about: 
• Any new medications,  
• Alterations in dose or dose schedules for current medications,  
• Any medical procedure or hospitalization that occurred or is planned, 
• Any non-drug therapies (including physical therapy and blood transfusions).  

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The Investigator must document this information in the subject’s case history source 
documents. 
Preoperative and Postoperative medications should be given as per site standard of care, 
documented in the subjects chart, confirmed as used by subject, and be listed as required in 
the EDC for each subject.  

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10 STUDY PROCEDURES AND ASSESSMENTS 
Study specific assessments will be obtained, including baseline prior to InnovEyes LASIK 
and postoperatively at the study visits outlined below (where A denotes the visit for the 2nd 
eye treated): 
• Screening - Visit 0 [-30 to -1 day prior to treatment] 
• Visit 00 / Visit 00A [Day 0 – surgery] 
• Visit 1 / Visit 1A [Day 1] 
• Visit 2 / Visit 2A [Day 5 to 9] 
• Visit 3 / Visit 3A [Day 21 to 35] 
• Visit 4 / Visit 4A [Day 70 to 98] 
• Visit 5 / Visit 5A [Day 147 to 182] 
• Visit 6 / Visit 6A [Day 245 to 301] 
• Visit 7 / Visit 7A [Day 330 to 420] 
In addition to the scheduled visits listed above, the following visits may apply as needed: 
• Early Exit [completed when a treated subject reports they wish to discontinue 
study participation, if subject is willing] 
• Unscheduled Visit [completed when a treated subject reports for additional 
follow-up] 
Clinical assessments to be obtained at study visits are outlined in Table 3–1 and are defined in 
the sections below.  
10.1 Informed Consent and Screening 
Visit 0 / Screening 
The Investigator or delegate must explain the purpose and nature of the study, and have the 
subject read, sign, and date the IRB/IEC-approved informed consent document. The subject 
must sign the ICF before any study-specific procedures or assessments can be performed, 
including study-specific screening procedures. Additionally, have the individual obtaining 
consent from the subject and a witness, if applicable, sign and date the informed consent 
document.  

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The Investigator or delegate must provide a copy of the signed document to the subject and 
place the original signed document in the subject’s chart, or provide documentation as 
required by local regulations. 
IF a patient has reported for routine LASIK screening, THEN data obtained from the routine 
evaluation can be used for screening data as long as protocol requirements for timeframe 
(within 30 days of surgery) and required details have been met. [Examples of this data 
include, but are not limited to IOP, Subjective Manifest Refraction for stability, and 
Cycloplegic refraction]. 
IF a screening phone script is used, THEN the subject should be pre-screened via phone and 
if interested in participating and a potential candidate for treatment, should be scheduled for 
an in-person visit as schedules allow, and consented prior to any study-specific testing. 
10.2 Description of Study Procedures and Assessments 
Detailed descriptions of assessments and procedures are provided in the MOP. The 
Investigator is responsible for ensuring that all procedures and assessments are delegated to 
appropriately qualified site personnel. 
10.2.1 Adverse Event Collection 
All Study Visits 
Assess and record any adverse events that are observed or reported, including those 
associated with changes in concomitant medication dosing since the previous visit. 
Note: AEs and device deficiencies must be recorded for all enrolled subjects from the time of 
signature of informed consent until their exit from the study, regardless of subject enrollment 
status (screen failure or received treatment). 

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10.2.3 Best Corrected Distance Visual Acuity 
Visit 0, Visit 2/2A – 7/7A, Early Exit 
Perform best corrected visual acuity testing with the Sponsor provided electronic visual 
acuity system for both eyes prior to any assessment requiring administration of eye drops to 
dilate the eyes, or any assessment requiring contact with the eye. The system for this study is 
M&S Technologies’ Clinical Trial Suite (CTS). The CTS is comprised of a 13-inch laptop 
computer and a control tablet. Background luminance is standardized and automatically 
calibrates to study specifications (approximately 85 cd/m2 for photopic lighting conditions). 
VA optotypes are calibrated for both distance-to-subject and pixels-per-inch. The testing 
distance for this assessment is 4m. Visual acuity must be obtained by study personnel who 
have successfully completed required training to conduct the assessment. 
10.2.4 Concomitant Medication 
All Study Visits 
Collect all medications used by the subject within the past 30 days or ongoing at time of 
screening. Include herbal therapies, vitamins, and all over-the-counter as well as prescription 
medications. Throughout the subject’s participation, obtain information on any changes in 
concomitant medications. Follow the MOP and Case Report Form Completion Guidelines for 
additional information on documentation and EDC entry for routine LASIK medications and 
take home and non-routine medications. 
10.2.5 Cycloplegic Refraction 
Visit 0, Visit 5/5A 
Perform the cycloplegic refraction after instilling cycloplegic drops using your standard of 
care method.  

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10.2.6 Demographics 
Visit 0 
Obtain demographic information including age, race, ethnicity, and sex. 
10.2.7 Device Deficiencies 
All Study Visits 
Assess and record any device deficiencies that are reported or observed.  Requirements for 
reporting device deficiencies in the study can be found in Section 11.   
Note: AEs and device deficiencies must be recorded for all enrolled subjects from the time of 
signature of informed consent, regardless of subject enrollment status (screen failure or 
received treatment). 
10.2.8 Dilated Fundus Examination 
Visit 0, Visit 5/5A, Early Exit, USV 
Dilated fundus examination includes ophthalmoscopic assessments of the vitreous, retina, 
macula, choroid, and optic nerve of both eyes. 
10.2.9 InnovEyes LASIK Planning 
Visit 0 
Treatment planning using the InnovEyes planning software can be completed on the WaveNet 
Planning Station or EX500 using the exported data from the InnovEyes sightmap. The 
InnovEyes treatment will be based on the InnovEyes sightmap Measured refraction. Ensure 
sphere is between 0 and -11.00 D and cylinder is between 0 and -4.50 D, with a spherical 
equivalent of no more than -12.00 D (Inclusion Criteria 4). Additional details are listed in the 
MOP.

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10.2.10 InnovEyes LASIK 
Visit 00 / Visit 00A 
Using the FS200 to create corneal flap, then use the EX500 laser to perform the InnovEyes 
LASIK based on the subject data from InnovEyes sightmap. Treatment must be performed by 
a qualified surgeon (no more than 2 per site). Additional details are listed in Section 9 and in 
the MOP. 
10.2.11 InnovEyes Sightmap Assessments 
Perform InnovEyes sightmap measurements according to the user manual and additional 
details listed in the MOP.  Measurements for treatment are obtained on undilated eyes, but a 
cycloplegic assessment will be obtained at screening also for evaluation purposes. 
Note: InnovEyes sightmap may only be used by specially trained physicians, medical staff 
and optometrists who are well versed in its diagnostic abilities and possible dangers and who 
possess the necessary skills to use it in conformity with the operating instructions contained 
in the User Manual.   
10.2.11.1 Aberrometry 
Visit 0, Visit 3/3A – 7/7A, Early Exit 
Measure wavefront aberrometry using the InnovEyes sightmap according to the user manual 
and MOP instructions. The magnitude of the following aberrations will be collected in the 
database: astigmatism, coma, sphere/focus, spherical aberration, tilt, trefoil, and root mean 
square height (RMSh).    
10.2.11.2 Biometry 
Visit 0, Visit 3/3A – 7/7A, Early Exit 
Measure Axial Length and Anterior Chamber Depth using the InnovEyes sightmap according 
to the user manual and MOP instructions. 
Note: Anterior Chamber Depth is collected as Biometry data, but instructions are under 
Tomography in the InnovEyes sightmap user manual. 

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10.2.11.3 Keratometry 
Visit 0, Visit 3/3A – 7/7A, Early Exit 
Measure Keratometry (K1 and K2 with axis) using the InnovEyes sightmap according to the 
user manual and MOP instructions. 
Note: Keratometry is collected separately, but instructions are under Tomography in the 
InnovEyes sightmap user manual. 
10.2.11.4 Pachymetry (Corneal Thickness) 
Visit 0, Visit 3/3A – 7/7A, Early Exit 
Measure central corneal thickness using the InnovEyes sightmap according to the user 
manual and MOP instructions. Ensure that at least a 250 µm residual stromal bed will remain 
with the planned InnovEyes LASIK (Exclusion Criteria 6). 
Note: Pachymetry is collected separately, but instructions are under Tomography in the 
InnovEyes sightmap user manual. 
10.2.11.5 Topography 
Visit 0, Visit 3/3A – 7/7A, Early Exit 
Measure corneal topography using the InnovEyes sightmap according to the user manual and 
MOP instructions. 
Note: The results from the topography will not be recorded in EDC. 
10.2.11.6 Wavefront Refraction 
Visit 0, Visit 3/3A – 7/7A, Early Exit 
Measure wavefront refraction using the InnovEyes sightmap according to the user manual 
and MOP instructions.  
10.2.12 Intraocular Pressure 
Visit 0, Visit 3/3A – 7/7A, Early Exit, USV 
Intraocular pressure must be measured in both eyes using a Goldmann tonometer or any other 
instrument. The same instrument should be used throughout the study. 

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10.2.13 Manifest Refraction / Subjective Refraction 
Visit 0, Visit 2/2A – 7/7A, Early Exit 
Perform manifest refraction under photopic lighting conditions and measure vertex distance 
using a phoropter.  
Note: The chart used for subjective Manifest Refractions can depend on use of the data:  
• For Inclusion stability at Screening (Visit 0) – performed on site chart  
• For VA testing - performed on Sponsor provided electronic chart  
• See MOP for more details.  
Note: Refraction for Inclusion Criteria 4 for myopic and astigmatic range must come from 
the InnovEyes sightmap Measured refraction. 
10.2.14 Medical History 
Visit 0 / Screening 
Collect subject medical history information. Throughout the subject’s participation, update if 
a condition ends. Follow Case Report Form Completion Guidelines for additional 
information. 
10.2.15 Mesopic Pupil Size 
Visit 0, Visit 3/3A – 7/7A, Early Exit 
Measure mesopic pupil size using an infrared-based pupilometer. 

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10.2.17 Slit Lamp Examination  
Visit 0, Visit 1/1A – 7/7A, Early Exit, USV 
Slit Lamp Exam of the cornea, iris/anterior chamber and lens must be performed in both eyes 
before instillation of any diagnostic eye drops. Follow the MOP for specific areas of detailed 
assessment according to required grading scales for Corneal Haze, Diffuse Lamellar 
Keratitis, and Epithelium Ingrowth. 
10.2.18 Uncorrected Distance Visual Acuity 
Visit 0, Visit 1/1A – 7/7A, Early Exit, USV 
Perform uncorrected visual acuity testing with the Sponsor provided electronic visual acuity 
system for both eyes prior to any assessment requiring administration of eye drops to dilate 
the eyes, or any assessment requiring contact with the eye. The system for this study is M&S 
Technologies’ Clinical Trial Suite (CTS). The CTS is comprised of a 13-inch laptop computer 
and a control tablet. Background luminance is standardized and automatically calibrates to 
study specifications (approximately 85 cd/m2 for photopic lighting conditions). VA optotypes 
are calibrated for both distance-to-subject and pixels-per-inch. The testing distance for this 
assessment is 4m. Visual acuity must be obtained by study personnel who have successfully 
completed required training to conduct the assessment.  
10.2.19 Uncorrected Near Visual Acuity 
Visit 0, Visit 5/5A 
Perform uncorrected near visual acuity testing with the Sponsor provided electronic visual 
acuity system for both eyes prior to any assessment requiring administration of eye drops to 

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dilate the eyes, or any assessment requiring contact with the eye. The system for this study is 
M&S Technologies’ CTS. The CTS is comprised of a 13-inch laptop computer and a control 
tablet. Background luminance is standardized and automatically calibrates to study 
specifications (approximately 85 cd/m2 for photopic lighting conditions). The testing distance 
for this assessment is 40 cm. Visual acuity must be obtained by study personnel who have 
successfully completed required training to conduct the assessment. 
10.2.20 Urine Pregnancy Test 
Visit 0 
Collect a urine pregnancy test on female subjects of childbearing potential that are not post-
menopausal or surgically sterile. 
Note: The results from the urine pregnancy test will not be recorded in EDC. 
10.3 Unscheduled Visits 
After InnovEyes LASIK is performed, IF a subject visit occurs between any regularly 
scheduled visits, THEN this visit must be documented as an Unscheduled Visit. During all 
unscheduled visits, the Investigator must conduct the USV procedures according to Table 3–
1. 
The Investigator may perform additional procedures for proper diagnosis and treatment of the 
subject as needed. The Investigator must document this information in the subject’s chart. 
IF during an Unscheduled Visit the subject is discontinuing from the study, THEN the 
Investigator must conduct Early Exit procedures and discontinue the subject as per 
Section 10.4. 
10.4 Discontinued Subjects 
10.4.1 Screen Failures 
Subjects who were excluded from the study after signing the informed consent and prior to 
surgical procedures beginning (prior to eye drops given for flap creation), are considered a 
screen failure. The Investigator must document the reason for screen failure in the subject’s 
chart. 
Subject numbers must not be re-used. 

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10.4.2 Incomplete Treatments 
IF a subject’s surgical treatment is started but discontinued due to complications or other 
reasons, THEN every effort must be made to keep the subject in the study and to continue 
with the study required visits. For these subjects, appropriate follow-up assessments as per 
standard of care (including a minimum of slit lamp examination, UCDVA, manifest 
refraction, and BCDVA) should be conducted and collected. IF the subject is not willing to 
complete all required follow-up visits, THEN document in the chart and exit the subject 
according to Section 10.4.3. See Section 11.6 for additional instructions for any adverse 
events.   
Note: IF drops are given for surgical treatment, but no laser procedure started and the surgery 
needs to be rescheduled, THEN ensure to reschedule InnovEyes Treatment within protocol 
window or following instructions in Section 8.3. 
Note: Please inform the Sponsor as soon as possible when an incomplete treatment occurs in 
order to discuss and confirm proper reporting and follow-up. 
10.4.3 Discontinuations 
Discontinued subjects are individuals who voluntarily withdraw or are withdrawn from the 
study by the Investigator after the surgical procedure (eye drops given for flap creation), has 
begun.  
Subjects may discontinue from study or study treatment at any time for any reason. Subjects 
may also be discontinued from study or study treatment at any time if, in the opinion of the 
Investigator, continued treatment poses a risk to their health. 
For subjects choosing to discontinue from the study after treatment, the Investigator must 
complete all Early Exit procedures according to Table 3–1 if the subject is willing and able, 
and if in the opinion of the Investigator it is safe for the subject to do so. 
The Investigator must document the reason for study or treatment discontinuation in the 
subject’s chart. 
To ensure the safety of all subjects who discontinue early, Investigators must assess each 
subject and, if necessary, advise them of any therapies and/or medical procedures that may be 
needed to maintain their health. 
Subject numbers of discontinued subjects must not be re-used. 

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10.5 Clinical Study Termination 
The Study Sponsor reserves the right to close the investigational site or terminate the study in 
its entirety at any time. 
If the clinical study is prematurely terminated or suspended by the Study Sponsor:  
• The Study Sponsor must: 
o Immediately notify the Investigator(s) and subsequently provide 
instructions for study termination. 
o Inform the Investigator and the regulatory authorities of the 
termination/suspension and the reason(s) for the termination/suspension.  
• The Investigator must: 
o Promptly notify the IRB/IEC of the termination or suspension and of the 
reasons.  
o Provide subjects with recommendations for post-study treatment options 
as needed. 
The Investigator may terminate the site’s participation in the study for reasonable cause. 
10.5.1 Follow-up of Subjects after Study Participation has Ended 
Following this study, the subject will return to their eye care professional for their routine eye 
care. In cases where a subject has a continuing adverse event at the time of study completion, 
see Section 11.6. 
11 ADVERSE EVENTS AND DEVICE DEFICIENCIES 
11.1 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 product). Refer to the 
Glossary of Terms and figures below for categories of AEs and SAEs. 

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Figure 11–1 
Categorization of All Adverse Events 
 
Figure 11–2 
Categorization of All Serious Adverse Events 
All SAEs
Device /
procedure 
related?
SAE
SADE
Anticipated?
Unanticipated 
SADE
No
Yes
No
Anticipated 
SADE
Yes
 
 
Specific Events Relevant to this Protocol  
In addition to reporting all AEs (serious and non-serious) meeting the definitions, the 
Investigator must report any occurrence of the following as an ocular SAE: 
• Diffuse lamellar keratitis (Grade 3 or above) 
• Corneal infiltrate or ulcer 
• Any persistent corneal epithelial defect at one month or later 
• Corneal edema at 1 month or later (specify flap or bed) 
• Epithelium in the interface with loss of 2 lines (10 letters) or more BCDVA 
ALL AEs
Device/
procedure-
related?
NO
AE
NO
SAE
ADE
YES
Meet 
seriousness 
criteria?
YES

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• Miscreated flap (lost, incomplete, too thin)  
• Melting of the flap 
• IOP with increase of > 10 mmHg above baseline on two consecutive examinations or 
an IOP greater than 30 mmHg on two consecutive examinations 
• Haze beyond 6 months with loss of 2 lines or greater (≥ 10 letters ETDRS) of BCDVA 
• Decrease in BCDVA of greater than or equal to 2 lines (≥ 10 letters ETDRS) not due to 
irregular astigmatism as shown by rigid contact lens refraction at 3 months or later 
• Retinal detachment 
• Retinal vascular accidents 
• Ocular penetration 
• Any other vision-threatening event 
The Investigator must also report the following ocular AEs: 
• Diffuse lamellar keratitis (Grade 2 or less) 
• Corneal edema between one week and 1 month after the procedure 
• Peripheral corneal epithelial defect at 1 month or later (location of the defect to be 
identified as on, off, or across the flap) 
• Epithelium in the interface  
• Foreign body sensation at 1 month or later 
• Pain at 1 month or later 
• Ghost/double images in the operative eye 
• Flap is not of the size and shape as initially intended or microkeratome stopped in mid-
cut or resultant flap is misaligned  
AEs that occur in association with a device that is used in conjunction with the FS200 laser 
system will be reported separately from those occurring with the EX500 laser or sightmap.   
This list is consistent with the categories provided in ANSI Z80.11 2012(R2017). Any other 
potentially sight-threatening event may also be considered serious based on the judgment of 
the Investigator and should be reported appropriately as delineated in Section 11.3. 

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Device Deficiencies  
A device deficiency may or may not be associated with subject harm (ie, ADE or SADE); 
however, not all ADEs or SADEs are due to a device deficiency. The Investigator should 
determine the applicable category for the identified or suspect device deficiency and report 
any patient harm separately. Examples of device deficiencies include the following: 
• Calibration issue: Error in or Unable to calibrate laser or diagnostic device 
• Computer software issue or system error message 
• Defective component  
• Detachment of device or device component  
• Device breakage (eg, headrest, chin rest, and joystick) 
• Device emits odor (eg, gas leak, and smoke) 
• Failure of laser firing 
• Failure to meet product specifications (eg, incorrect laser assembly) 
• Failure to transmit record  
• Foreign material present in device  
• Image display error  
• Incorrect laser output energy 
• Incorrect measurement  
• Instructions difficult to understand/follow  
• Lack of effectiveness  
• Mechanical issues (e.g., failure to focus, align, track, position, or unintended system 
motion) 
• No display or display failure  
• Poor quality image  
• Power issue: Equipment will not power on; power loss; or intermittent connection 
• Suspect product contamination (patient interface) 
• Unable to capture image  
• Other events that may meet the definition of device deficiency 

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11.2 Monitoring for Adverse Events 
At each visit, after the subject has had the opportunity to spontaneously mention any 
problems, the Investigator should inquire about AEs by asking the standard questions shown 
below and report as applicable: 
• “Have you had any health problems since your last study visit?” 
• “Have there been any changes in the medicines you take since your last study visit?” 
In addition, changes in any protocol-specific parameters 
evaluated 
during the study are to be reviewed by the Investigator. Any untoward (unfavorable and 
unintended) change in a protocol-specific parameter 
 that is 
clinically relevant, in the opinion of the Investigator, is to be reported as an AE. These 
clinically relevant changes will be reported regardless of causality.  
11.3 Procedures for Recording and Reporting 
AEs are collected from the time of informed consent.  Any pre-existing medical conditions or 
signs/symptoms present in a subject prior to the start of the study (ie, before informed consent 
is signed) are not considered AEs in the study and should be recorded in the Medical History 
section of the eCRF. 
In addition, dry eye, superficial punctate keratitis, and optical visual disturbances (eg, glare, 
halo, and starburst) are examples of early post-operative findings that are typically observed 
following kerato-refractive surgery. These are not considered AEs if they can be reasonably 
expected to resolve within 6 months and not result in any untoward long term visual outcome 
impact. However, based on the Investigator’s medical judgment, signs and symptoms of dry 
eye and ocular visual disturbances prior to 6 months, or persisting beyond 6 months post 
kerato-refractive surgery, may be considered an AE. 
For each recorded event, the ADEs and SAEs documentation must include: date of 
occurrence, severity, treatment (if applicable), outcome, and assessments of the seriousness 
and causality. In addition, the Investigator must document all device deficiencies reported or 
observed with test and control products on the Device Deficiency eCRF. The site must submit 
all available information on ADEs, SAEs, and device deficiencies to the Study Sponsor 
immediately as follows: 
• ADEs or SAEs are documented on the Serious Adverse Event and Adverse Device 
Effect eCRF within 24 hours of the Investigator’s or site’s awareness.  

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• Device deficiencies are documented on the Device Deficiency eCRF within 24 hours 
of the Investigator’s or site’s awareness.  
• A printed copy of the completed Serious Adverse Event and Adverse Device Effect 
and/or Device Deficiency eCRF must be included with product returns.  
• Additional relevant information after initial reporting must be entered into the eCRF as 
soon as the data become available.   
• Document any changes to concomitant medications on the appropriate eCRFs. 
• Document all relevant information from Discharge Summary, Autopsy Report, 
Certificate of Death, etc, if applicable, in narrative section of the Serious Adverse 
Event and Adverse Device Effect eCRF. 
Note: Should the EDC system become non-operational, the site must complete the 
appropriate paper Serious Adverse Event and Adverse Device Effect and/or Device 
Deficiency Form. The completed form is emailed to the Study Sponsor at 
MSUS.Safety@Alcon.com according to the timelines outlined above; however, the 
reported information must be entered into the EDC system once it becomes 
operational. 
Any AEs and device deficiencies for non-study marketed devices/products (eg, FS200, 
Custom Paks, etc.) will be considered and processed as spontaneous (following the post-
market vigilance procedures) and should be communicated to the device’s/product’s 
manufacturer as per local requirements. 
Study Sponsor representatives may be contacted for any protocol related question and their 
contact information is provided in the Manual of Procedures that accompanies this protocol. 
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: 

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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 (ie, 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 AEs that is 
upgraded from non-serious to serious or from unrelated to related. 
Furthermore, the Study Sponsor shall promptly conduct an evaluation of any unanticipated 
adverse device effect, including anticipated adverse events that occur in unanticipated 
severity or frequency. The results of this evaluation will be reported to the FDA, the IRB, and 
participating Investigators within 10 working days upon receiving notification of the effect. 
11.4 Return Product Analysis 
Study Sponsor representatives and their contact information are provided in the MOP that 
accompanies this protocol.  

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Alcon products associated with device deficiencies and/or product related AEs should be 
returned and must include the Complaint # which will be provided by Study Sponsor after the 
case is entered in the Study Sponsor’s Global Product Complaint Management System.  
11.5 Unmasking of the Study Treatment  
Not applicable; this study is open-label. 
11.6 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 (ie, database lock).  
Any additional data received up to 6 months after subject discontinuation or exit must be 
documented and available upon the Study Sponsor’s request. 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. 
11.7 Pregnancy in the Clinical Study 
Pregnancy is not reportable as an AE; however, complications may be reportable and will be 
decided on a case–by-case basis. An Alcon form will be utilized to capture all pregnancy-
related information until birth of the child. 
12 ANALYSIS PLAN 
This information will also be contained within a separate biostatistical analysis plan which 
will be prepared and finalized prior to database lock.  
Counts and percentages will be presented as categorical variables. N, mean, standard 
deviation, median, minimum, and maximum will be presented for continuous variables. 

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12.1 Subject Evaluability 
Final subject evaluability must be determined prior to locking the database, based upon the 
Deviations and Evaluability Plan. 
12.2 Analysis Sets 
All eligible subjects will be screened to determine if they meet all inclusion and no exclusion 
criteria. Subjects who provide informed consent will be considered enrolled in the study. 
12.2.1 Safety Analysis Set 
The safety analysis set (SAF) will contain all eyes that undergo surgery or attempted surgery 
(defined as eye drops given for flap treatment); the SAF will be the primary analysis set for 
the safety analyses.  
12.2.2 Full Analysis Set 
The full analysis set (FAS) will contain all eyes that successfully undergo surgery; the FAS 
will be the primary analysis set for the effectiveness analyses. 
12.2.3 Consistent Cohort Analysis Set 
The consistent cohort (CC) will contain all eyes in the FAS that have manifest refraction data 
at all post-operative visits from one month up to and including the visit where refractive 
stability is established. The CC will be the primary analysis set for the refractive stability 
analyses. 
12.3 Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized for each subject. Appropriate 
summary statistics will be presented for each characteristic. These summaries will be based 
on the FAS. 
12.4 Refractive Stability 
Stability analyses will be performed on eyes that have every follow-up exam from 1-month 
up to the stability time point (the CC), as well as on the eyes that have 2 consecutive exams, 
but not necessarily every follow-up exam. The following stability analyses will be performed 
for the time intervals between all consecutive pairs of scheduled postoperative refractions: 
• Percentage of eyes that achieve: 

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o a change of less than or equal to 1.00 D of MRSE between two refractions 
performed at 1 month and 3 months, and between subsequent refractions 
performed at least 3 months apart; 
o a change of less than or equal to 0.50 D of MRSE between two refractions 
performed at 1 month and 3 months, and between subsequent refractions 
performed at least 3 months apart; 
• Mean overall change and change per month in MRSE between consecutive scheduled 
visits as determined by a paired analysis; 
• Mean ± SD MRSE for the preoperative and each postoperative visit; 
• Assessment of cylinder stability for correction of spherocylindrical refractive errors 
Refractive stability is achieved at the latter of two postoperative manifest refractions 
performed at least 3 months apart or at 3 months after surgery when compared with the 1-
month interval, when all of the following recommended criteria are met: 
• At least 95% of the treated eyes have a change ≤ 1.00 D of MRSE between the 2 
refractions; 
• The mean rate of change in MRSE, as determined by a paired analysis, is ≤ 0.5 D per 
year (0.04 D/month) over the same time period; 
• The mean rate of change of MRSE decreases monotonically over time, with a 
projected asymptote of zero or a rate of change attributable to normal aging; 
• The 95% confidence interval for the mean rate of change in MRSE includes zero or a 
rate of change attributable to normal aging; and  
• Stability is confirmed at least 3 months after the stability time point by a statistically 
adequate subgroup (at least 80% of the cohort). 
The primary safety and effectiveness endpoints for the study can only be evaluated once 
refractive stability has been established within the CC, as well as on the eyes that had 2 
consecutive exams, but not necessarily every follow-up exam.  
12.5 Effectiveness Analyses 
12.5.1 Analysis of Primary Effectiveness Endpoints 
In order to establish effectiveness of the WaveLight EX500 excimer laser system for the 
correction of myopia with and without astigmatism using InnovEyes in conjunction with 
InnovEyes sightmap, the following four co-primary endpoints are defined: 

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• Percentage of eyes with UCDVA of 20/40 (in eyes with preoperative BCDVA of 20/20 
or better) or better at refractive stability (Target: ≥ 85%) 
• Percentage of eyes with MRSE within 0.50 D at refractive stability (Target: ≥ 50%) 
• Percentage of eyes with MRSE within 1.00 D at refractive stability (Target: ≥ 75%) 
• Percentage of eyes that achieve refractive stability (Target: ≥ 95%) 
12.5.1.1 
Statistical Hypotheses 
No hypothesis testing of the primary effectiveness endpoints is planned. 
12.5.1.2 
Analysis Methods 
The FAS will be used for this analysis. The number and percentage of eyes meeting each of 
the primary effectiveness endpoints will be calculated. The effectiveness criteria will be 
considered to have been met if the percentage meets or exceeds the target rate at the time of 
refractive stability for all primary effectiveness endpoints. These analyses will be performed 
for the whole FAS 
. An analysis will be 
performed once refractive stability is achieved; a final summary of these endpoints will be 
performed once the one year follow-up is complete. 
12.6 Handling of Missing Data 
No imputation of missing data is planned. 

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12.7 Safety Analyses 
All adverse events occurring from the time a subject signs informed consent to study exit will 
be accounted for in the reporting. Safety analyses will be conducted using the SAF through 
descriptive summaries (counts and percentages) and listings. In addition, separate subject 
listings will be provided for AEs that occur in subjects: 
• after signing informed consent but prior to exposure to IP (InnovEyes sightmap) 
• exposed to IP (InnovEyes sightmap) but do not proceed to InnovEyes treatment (and 
thus are not included in the SAF) 
12.7.1 Analysis of Primary Safety Endpoints 
In order to establish safety of the WaveLight EX500 excimer laser system for the correction 
of myopia with and without astigmatism using InnovEyes in conjunction with InnovEyes 
sightmap, the following four co-primary endpoints are defined:  
• Percentage of eyes that lose 2 lines or more of BCDVA (Target at refractive stability  
≤ 5%) 
• Percentage of eyes with BCDVA worse than 20/40 (for eyes with BCDVA of 20/20 or 
better pre-op) (Target at refractive stability ≤ 1%) 
• Percentage of eyes that have an increase of manifest refractive astigmatism of greater 
than 2.00 D of absolute cylinder as compared to the preoperative refraction (Target at 
refractive stability ≤ 5%) 
• Percentage of eyes with a serious, non-flap related, ocular adverse event at the 
postoperative visits (Target per event type at refractive stability: ≤ 1%) 
12.7.1.1 
Statistical Hypotheses 
No hypothesis testing of the primary safety endpoints is planned. 
12.7.1.2 
Analysis Methods 
The SAF will be used for this analysis.  The number and percentage of eyes experiencing 
each of the primary safety endpoints will also be calculated. The safety criteria will be 
considered to have been met if the percentage is less than the target rate at the time of 
refractive stability for all of the primary safety endpoints.   

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12.8 Interim Analyses and Reporting 
An analysis will be performed once refractive stability is achieved; a final analysis will be 
performed once the one year follow-up is complete. 
12.9 Sample Size Justification 
Up to 374 eyes will be treated in this study. With 374 eyes treated, any ocular serious adverse 
event type that occurs in at least 1% of the population undergoing the procedure will be 
observed in this study at least one time, with approximately 95% probability. This is in 
accordance with ANSI Z80.11-2012(R2017). 
13 DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS 
13.1 Subject Confidentiality 
The Investigator must ensure that the subject’s anonymity is maintained throughout the 
course of the study. In particular, the Investigator must keep an enrollment log with 
confidential identifying information that corresponds to the subject numbers and initials of 
each study participant. At the end of the clinical study, the Study Sponsor will collect a copy 
of the enrollment log without any identifying subject information. All documents submitted 
to the Study Sponsor will identify the subjects exclusively by number and demographic 
information. No other personally identifying information will be transmitted to the Study 
Sponsor. 
The Study Sponsor may release anonymized study data to external researchers for purposes 
of future research directly related to the study objectives, or future research that is beyond the 

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scope of the current study objectives. The Informed Consent Form explains this to study 
subjects. Anonymization means that all identifiable information will be removed from the 
dataset and all links to the subjects in the study will be removed. Anonymization of the data 
will maintain confidentiality of the subjects who participate in the study so that they cannot 
be identified by external researchers. The anonymized data set will contain records from all 
of the subjects in the current study, but the anonymization process might change the data set 
in some ways, so external researchers will be informed that they might not be able to 
duplicate some of the results from this study. 
13.2 Completion of Source Documents and Case Report Forms 
The nature and location of all source documents will be identified to ensure that original data 
required to complete the CRFs exist and are accessible for verification by the site monitor, 
and all discrepancies shall be appropriately documented via the query resolution process. Site 
monitors are appointed by the Study Sponsor and are independent of study site staff. 
If electronic records are maintained, the method of verification must be determined in 
advance of starting the study.  
At a minimum, source documents include the following information for each subject: 
• Subject identification (name, sex, race/ethnicity) 
• Documentation of subject eligibility 
• Date of informed consent 
• Dates of visits 
• Documentation that protocol specific procedures were performed 
• Results of study parameters, as required by the protocol 
• IP accountability records 
• Documentation of AEs and other safety parameters (if applicable) 
• Records regarding medical histories and the use of concomitant therapies prior to and 
during the study 
• Date of study completion and reason for early discontinuation, if applicable 
It is required that the author of an entry in the source documents be identifiable. Direct access 
to source documentation (medical records) must be allowed for the purpose of verifying that 
the data recorded on the CRF are consistent with the original source data. 

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Only designated individuals at the site will complete the CRFs. The CRFs must be completed 
at regular intervals following the clinical study visit schedule. It is expected that all data 
reported have corresponding entries in the source documents. The Principal Investigator is 
responsible for reviewing and certifying that the CRFs are accurate and complete. The only 
subject identifiers recorded on the CRFs will be subject number, and subject demographic 
information.  
The Sponsor reserves the right to collect anonymized raw data from the InnovEyes sightmap 
or InnovEyes software at any point of the study and at the end of the study in order to use for 
further review of the treatment results and for future development of the procedure.   
13.3 Data Review and Clarifications 
A review of CRF data to the subject’s source data will be completed by the site monitor to 
ensure completeness and accuracy. After the CRFs have been completed, additional data 
clarifications and/or additions may be needed as a result of the data cleaning process. Data 
clarifications are documented and are part of each subject’s CRF. 
13.4 Sponsor and Monitoring Responsibilities 
The Study Sponsor will designate a monitor to conduct the appropriate site visits at the 
appropriate intervals according to the study monitoring plan. The clinical investigation will 
be monitored to ensure that the rights and well-being of the subjects are protected, the 
reported data are accurate, complete, and verifiable from the source documents, and the study 
is conducted in compliance with the current approved protocol (and amendments[s], if 
applicable), with current GCP, and with applicable regulatory requirements. 
The site may not screen subjects or perform the informed consent process on any subject until 
it receives a notification from an appropriate Study Sponsor representative that the site may 
commence conducting study activities. Monitoring will be conducted periodically while the 
clinical study is ongoing. Monitoring methods may include site visits, telephone, written, and 

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email correspondence. Close-out visits will take place after the last visit of the last subject at 
the site. 
A Coordinating Investigator may be identified by the Study Sponsor to review and endorse 
the final study report. In cases where a Coordinating Investigator is engaged, the Study 
Sponsor will select the Coordinating Investigator based upon their experience, qualifications, 
active study participation, and their willingness and availability to take on this role. 
Additionally, Alcon may have an expert Sponsor Representative present during screening (eg, 
for the collection of InnovEyes sightmap measurements) or surgery to offer training to the 
Investigator on proper operation of the device and/ or to make technical observations during 
the study visit.  
• The Sponsor Representative must be supervised by the Investigator or designee to 
ensure the Sponsor Representative’s presence or activities do not bias the outcome of 
the study, affect the quality of the research data, and/or compromise the rights and 
welfare of the subject. The Sponsor Representative will not intervene with the standard 
of care provided to study subjects or make safety-related decisions or assessments. The 
activities of Sponsor Representatives will be described in the Informed Consent. 
13.5 Regulatory Documentation and Records Retention 
The Investigator is required to maintain up-to-date, complete regulatory documentation as 
indicated by the Study Sponsor and the Investigator’s files will be reviewed as part of the 
ongoing study monitoring. Financial information is to be kept separately.  
Additionally, the Investigator must keep study records and source documents consistent with 
the terms of the clinical study agreement with the Study Sponsor. If the Investigator retires, 
relocates, or for any other reason withdraws from responsibility of keeping the study records, 
then the Study Sponsor must be notified and suitable arrangements made for retention of 
study records and source documents needed to comply with national and international 
regulations. 
13.6 Quality Assurance and Quality Control 
The Study 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 Study 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 Study Sponsor 

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with the 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. 
14 ETHICS 
This clinical study must be conducted in accordance with the ethical principles contained 
within:  
• The Declaration of Helsinki, and in compliance with the ICH E6 GCP Consolidated 
Guideline, ISO 14155:2011, and the applicable US FDA 21 CFR Regulations.  
• SOPs of the Study Sponsor and contract research organizations participating in the 
conduct of the clinical study and all other applicable regulations.  
• Notifications and timelines for reporting protocol deviations should be based upon 
applicable Ethics Committee requirements 
The Investigator must ensure that all personnel involved in the conduct of the study are 
qualified to perform their assigned responsibilities through relevant education, training, and 
experience. The Investigator and all clinical study staff must conduct the clinical study in 
compliance with the protocol. Deviations from this protocol, regulatory requirements, and/or 
GCP must be recorded and reported to the Sponsor prior to database lock. If needed, 
corrective and preventive action should be identified, implemented, and documented within 
the study records. Use of waivers to deviate from the clinical protocol is prohibited. 
Before clinical study initiation, this protocol, the informed consent form, any other written 
information given to subjects, and any advertisements planned for subject recruitment must 
be approved by an IRB/IEC. The Investigator must provide documentation of the IRB/IEC 
approval to the Study Sponsor. The approval must be dated and must identify the applicable 
protocol, amendments (if any), informed consent form, assent form (if any), all applicable 
recruiting materials, written information for subject, and subject compensation programs. The 
IRB/IEC must be provided with a copy of the InnovEyes sightmap investigator brochure, any 
periodic safety updates, and all other information as required by local regulation and/or the 
IRB/IEC. At the end of the study, the Investigator must notify the IRB/IEC about the study’s 
completion. The IRB/IEC also must be notified if the study is terminated prematurely. 
Finally, the Investigator must report to the IRB/IEC on the progress of the study at intervals 
stipulated by the IRB/IEC. 
Voluntary informed consent must be obtained in writing from every subject and the process 
shall be documented before any procedure specific to the clinical investigation is applied to 

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the subject. The Investigator must have a defined process for obtaining consent. Specifically, 
the Investigator, or their delegate, must explain the clinical study to each potential subject and 
the subject must indicate voluntary consent by signing and dating the approved informed 
consent form. 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 provide subjects 
with information regarding the purpose, procedures, requirements, and restrictions of the 
study, along with any known risks and potential benefits associated with the IP and the study, 
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 study and must be provided with contact information for the appropriate 
individuals should questions or concerns arise during the study. The subject also must 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 (file in 
subject’s medical records) and must provide a duplicate copy to each subject according to 
local regulations.  
The Study Sponsor assures that the key design elements of this protocol will be registered on 
www.clinicaltrials.gov as required by current regulations and, if applicable, other public 
databases as required by local country regulations. In addition, results of this study will be 
made publicly available on www.clinicaltrials.gov regardless of outcome as required by 
current regulations and, if applicable, in other public databases as required by local country 
regulations.  
15 REFERENCES 
15.1 References Applicable for All Clinical Studies 
• ISO 14155:2011 Clinical investigation of medical devices for human subjects - Good 
clinical practice 
15.1.1 US References Applicable for Clinical Studies 
• 21 CFR Part 11 - Electronic Records; Electronic Signatures 
• 21 CFR Part 50 - Protection of Human Subjects 
• 21 CFR Part 56 - Institutional Review Boards 
• 21 CFR Part 812 - Investigational Device Exemptions 

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• 21 CFR Part 54 - Financial Disclosure by Clinical Investigators 
• The California Bill of Rights 
15.2 References for This Clinical Study 
• ANSI Z80.11-2012 (R2017) American National Standard for Ophthalmics – Laser 
Systems for Corneal Reshaping 
• Cummings AB, Kelly GE. Optical ray tracing-guided myopic laser in situ 
kertomileusis: 1-year clinical outcomes. Clinical Ophthalmol 2013;7:1181-1191. 
• 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. 
• Simon D, Schumacher S, Mrochen M. Ray Tracing: the Future of Refractive Surgery. 
Cataract & Refractive Surgery Today. August 2011(55-56). 
• Schumacher S, Seiler T, Cummings A, Maus M, Mrochen M. Optical ray tracing-
guided laser in situ keratomileusis for moderate to high myopic astigmatism. J 
Cataract Refract Surg. 2012;38(1):28–34. 

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