Comparison of Cumulative Dissipated Energy (CDE) and Balanced Salt Solution (BSS) Fluid Used With the Centurion® With the 45° Degree Balanced Ultrasound (U/S) Tip vs the Centurion® With Mini Flared Kelman U/S Tip vs the Infiniti® With Mini Flared Kelman U/S Tip on Hard Lenses
Phase: NA
Conditions: Cataracts
Sponsor: Alcon Research

Page 1 of 75
a Novartis company
Clinical Trial Protocol
Short Title
Comparison of Centurion® Vision System with Balanced Tip and Infiniti®
Vision System with the MFK tip during cataract extraction surgery of 
Hard Lenses.
Long Title
Comparison of Cumulative Dissipated Energy (CDE) and BSS Fluid used 
with the Centurion® with the 45° Balanced U/S tip vs the Centurion® with 
Mini Flared Kelman U/S tip vs the Infiniti® with Mini Flared Kelman U/S 
tip on Hard Lenses
Protocol Number: 
Version Number
Sponsor Name & Address:
Project Name / Number:
Test Article(s) / Product(s):
Release Date:
CTU424-P001 / NCT02502526
02
Alcon Research, Ltd. and its affiliates (“Alcon”) 
6201 South Freeway
Fort Worth, Texas  76134-2099
Centurion® Hard Lenses Study (
Centurion® Vision System – version 2.04
45° Balanced Tip*
*Used with INTREPID® Ultra Sleeve
Refer to electronic signature date
Principal Investigator: 
________________________________________________
Signature
     Date
Principal Investigator Name:
_________________________________________________
Principal Investigator Address:
_________________________________________________
_________________________________________________
Property of Alcon Laboratories
Confidential
May not be used, divulged, published, or otherwise disclosed without the consent of Alcon 
Laboratories
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1
PROTOCOL SYNOPSIS
Financial Disclosure 
for US FDA 
Submission Required?
Yes
X No
Test Article(s) / 
Product(s):
Centurion® Vision System – version 2.04
45° Balanced Tip*
*Used with INTREPID® Ultra Sleeve
Objective(s):
Primary objective is to demonstrate that the Centurion® Vision 
System used with the 45° Balanced Tip will result in less 
Cumulative Dissipated Energy (CDE) than the Infiniti® Vision 
System used with the 45° Mini-Flared Kelman (MFK) tip during 
cataract extraction surgery via phacoemulsification of cataract 
grades NII- NIV (LOCSII).
The Secondary objectives for this study are as follows;
1. Demonstrate that the Centurion® Vision System used with the 
45° Balanced Tip will result in less CDE than the Centurion® 
Vision System used with the 45° MFK tip during cataract
extraction surgery via phacoemulsification of cataract grades 
NII-NIV (LOCSII).
2. Demonstrate that the Centurion® Vision System used with the 
45° Balanced Tip will result in less BSS Fluid Used than the 
Infiniti® Vision System used with the 45° MFK tip during 
cataract extraction surgery via phacoemulsification of cataract 
grades NII-NIV (LOCSII).
3. Demonstrate that the Centurion® Vision System used with the 
45° MFK tip will result in less BSS Fluid Used than the Infiniti® 
Vision System used with the 45° MFK tip during cataract 
extraction surgery via phacoemulsification of cataract grades 
NII-NIV (LOCSII).
4. Demonstrate that the Centurion® Vision System used with the 
45° MFK tip will result in less CDE than the Infiniti® Vision 
System used with the 45° MFK tip during cataract extraction 
surgery via phacoemulsification of cataract grades NII- NIV 
(LOCSII).
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Clinical Trial Design: Prospective, parallel, randomized, patient-masked, 3-arm, multi-
center clinical study following subjects with surgery done with:
• Centurion® Vision System, 45°Balanced Tip1
• Centurion® Vision System, 45°Mini Flared Kelman Tip1
• Infiniti® Vision System, 45°Mini Flared Kelman Tip2
1Used with INTREPID® Ultra Infusion Sleeve
2 Used with Ultra infusion Sleeve
Phaco-emulsification of a harder lens requires more CDE and more 
BSS fluid. For this study, the softest lenses (LOCSII Opacities N0 
and NI) will be excluded, leaving all lenses with LOCSII Opacities 
NII-NIV.
For each group, cataract surgery will be performed on subjects who 
will be randomized with an equal number having their surgery 
performed with each configuration.
Clear Cornea Incision: 2.2mm-2.4mm
No. of Subjects:
Approximately 177 subjects (59 per group) randomized with an 
expectation to have at least 159 completed subjects (53 per group) 
for evaluability.
Region(s):
Approximately 5 investigational sites across the USA, LACAN, 
Asia-Pacific and EMEA
Clinical Trial 
Duration:
a) Total expected duration of clinical investigation: approximately 
12 months
b) Expected duration of each subject participation: up to 5 months
c) Planned follow-up duration for each subject: up to 3 months 
postoperative
d) Estimated subject recruitment period (time needed to select the 
number of patients): approximately 6 months
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Clinical Trial 
Population:
Adult subjects of 21 years of age and above requiring cataract 
extraction followed by IOL implantation. Nuclear Opalescence II to 
IV using LOCS II.
Treatments:
Test Article:
Centurion® Vision System - version 2.04
45°Balanced Tip1
1Used with INTREPID® Ultra Infusion Sleeve
Administration:
Surgical instrumentation
General Description: Centurion® Vision System (v2.04) will be 
used with the 45° Balanced Tip (coupled with 
the INTREPID® Ultra Infusion sleeve) for 
phaco-emulsification procedure.
Duration of 
Treatment:
One time routine surgical procedure followed 
by 3 months (+/- 14 days) of postoperative 
follow-up.
Control Article:
Centurion® Vision System (version 2.04) with 
45° Mini Flared Kelman u/s Tip1 (with 
INTREPID® Ultra infusion sleeve)
Infiniti® Vision System (version 3.01) with 
45° Mini Flared Kelman u/s Tip2
1Used with INTREPID® Ultra Infusion Sleeve
2Used with Ultra infusion Sleeve
Administration:
Surgical instrumentation
General Description: Centurion® Vision System (version 2.04) will 
be used with the 45° Mini Flared u/s Tip 
coupled with INTREPID® Ultra infusion 
sleeve) for phaco-emulsification procedure.
Infiniti® Vision System (version 3.01) will be 
used with 45° Mini Flared Kelman u/s Tip 
(coupled with Ultra Infusion Sleeve) for 
phaco-emulsification procedure.
Duration of 
Treatment:
One time routine surgical procedure followed 
by 3 months (+/- 14 days) of postoperative 
follow-up.
Inclusion & Exclusion 
Criteria:
Detailed information on inclusion and exclusion criteria can 
be found in Section 10:Subject Population
Assessments:
Primary 
Variable
-
Cumulative Dissipated Energy (CDE)
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Secondary 
Variables
-
CDE (depending on the objective)
-
Balanced Salt Solution (BSS) fluid used
Safety 
Variables
-
Adverse Events (including SSIs)
-
Slit-lamp examination
-
Anterior chamber cells
-
Anterior chamber flare
-
Corneal oedema
-
Endothelial cell count
-
Dilated fundus examination
-
BCDVA 
-
IOP
-
Problems during surgery
-
IOL placement 
-
Device deficiencies
 
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Statistical Analysis:
-
Safety Data Set- Safety analyses will be conducted using the safety analysis set 
on a treatment- emergent basis. The Safety data set will include all subjects/ eyes 
exposed to any study procedures evaluated in this study.
-
Intent-to-Treat (ITT) Data Set – will include all subjects who are randomized in 
the study and receive treatment. The ITT set will be the primary analysis set for 
efficacy.
-
Per Protocol Set (PPS) - The PP set is a subset of ITT which excludes those who 
meet the critical deviation criteria as specified in the Deviations and Evaluability 
Plan. Supportive analyses of the primary and secondary endpoints will be 
conducted using the PP set if the number of subjects excluded from PP exceeds 
5% of the ITT.
Safety summaries will be reported by treatment. For safety variables, all variables will be 
summarized descriptively by treatment group. No inferential testing will be performed for 
safety. If more than 5% of subjects are excluded due to deviations, the PPS will become 
the primary analysis set, and will be compared to the ITT to check for robustness of the 
results.
A sequential (closed) testing procedure will be used to control type I error rate due to 
multiplicity for primary and secondary endpoints at one- sided 0.05 significant level.
Primary:
The primary hypothesis is to demonstrate that the Centurion® Vision System used with 
the 45° Balanced Tip will result in less Cumulative Dissipated Energy (CDE) than the 
Infiniti® Vision System used with the 45° Mini Flared tip during cataract extraction 
surgery via phacoemulsification:
Ho: µcenturion_Bal CDE ≥ µlnfiniti_MFK CDE
HA: µcenturion_Bal CDE < µlnfiniti_MFK CDE
µcenturion_Bal CDE and µlnfiniti_MFK CDE are the true mean values of the primary performance 
endpoint, CDE under Centurion with the Balanced Tip, and Infiniti with the Mini Flared 
Kelman (MFK) tip, respectively.
The difference of CDE between two groups will be examined by using an analysis of
covariance model (ANCOVA) adjusting for site and baseline opacity grade. Display of 
ANCOVA results in summary tables will contain difference between LS means, a one-
sided p- value < 0.05 will conclude superiority of Centurion® over Infiniti® group.
Secondary:
The difference between two groups will be examined by using ANCOVA adjusting for site 
and baseline opacity grade. Display of ANCOVA results in summary tables will contain 
difference between LS Means, a one-sided p- value <0.05 will conclude superiority.
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Safety:
Demographics and baseline characteristics will be summarized overall and by treatment 
arm. Other exploratory and safety variables will be summarized descriptively. Continuous 
measurements will be presented using n, mean, standard deviation, minimum, maximum 
and confidence intervals at each visit. Categorical measurements will be tabulated with 
the number and percent in each category at each visit.
Sample Size Justification:
Based on previous studies, a sample size of 53 in each group will have 80% power to 
detect a difference in means of -7.4 (the difference between a Group 1 mean, µ1, of 38.5 
and a Group 2 mean, µ2, of 45.9) assuming that the common standard deviation is 15.2 
using a two group t-test with a 0.05 one-sided significance level. Assuming a 10% dropout 
rate, approximately 59 subjects per group (177 in total) will be randomized.
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2
TABLE OF CONTENTS
Table of Contents
Comparison of Cumulative Dissipated Energy (CDE) and BSS Fluid used with the 
Centurion® with the 45° Balanced U/S tip vs the Centurion® with Mini Flared 
Kelman U/S tip vs the Infiniti® with Mini Flared Kelman U/S tip on Hard Lenses . 1
1
PROTOCOL SYNOPSIS........................................................................................... 2
2
TABLE OF CONTENTS........................................................................................... 9
Table of Contents .......................................................................................................................... 9
Table of Tables............................................................................................................................ 13
Table of Figures .......................................................................................................................... 13
3
ABBREVIATIONS.................................................................................................. 14
4
GLOSSARY OF TERMS ........................................................................................ 16
5
AMENDMENTS ..................................................................................................... 18
5.1
Amendment 1 ...................................................................................................... 18
6
SCHEDULE OF VISITS......................................................................................... 19
7
INTRODUCTION................................................................................................... 20
7.1
Background.......................................................................................................... 20
7.2
Clinical Trial Design............................................................................................ 21
8
CLINICAL TRIAL OBJECTIVES.......................................................................... 23
8.1
Primary Objective................................................................................................ 23
8.2
Secondary Objectives .......................................................................................... 23
23
8.4
Study Endpoints................................................................................................... 24
8.4.1
Effectiveness Endpoints .................................................................................. 24
8.4.2
Safety Endpoints.............................................................................................. 26
9
INVESTIGATIONAL PLAN .................................................................................. 27
9.1
Outline of Clinical Trial....................................................................................... 27
9.2
Study Design ....................................................................................................... 28
9.3
Rationale for Study Design ................................................................................. 28
9.4
Procedures Per Study Visit .................................................................................. 29
9.5
Risk Benefit Assessment ..................................................................................... 29
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10
SUBJECT POPULATION....................................................................................... 30
10.1
Inclusion Criteria................................................................................................. 30
10.2
Exclusion Criteria................................................................................................ 30
11
TREATMENT.......................................................................................................... 32
11.1
Investigational Products ...................................................................................... 32
11.2
Usage ................................................................................................................... 35
11.3
Accountability Procedures................................................................................... 35
12
CLINICAL TRIAL PROCEDURES ....................................................................... 36
12.1
Clinical Trial Assessments................................................................................... 36
12.1.1
Pre-operative visit (Visit 0; Day -60 to Day 0)................................................ 36
12.1.1.1
Pre-Screen.................................................................................................... 36
12.1.1.2
Informed Consent ........................................................................................ 36
12.1.1.3
Subject Number Assignment ....................................................................... 36
12.1.1.4
Demographics, Medical History and Concomitant Medications................. 37
12.1.1.5
Inclusion/Exclusion Criteria ........................................................................ 37
12.1.1.6
Selection of Study Eye................................................................................. 37
12.1.1.7
Visual Acuity (UCDVA and BCDVA) Testing ............................................ 37
12.1.1.8
Intraocular pressure (IOP) ........................................................................... 38
12.1.1.9
Specular Microscopy ................................................................................... 38
38
12.1.1.11
Slit-lamp Examination................................................................................. 38
12.1.1.12
Crystalline Lens Assessment ....................................................................... 38
12.1.1.13
Inflammatory Signs...................................................................................... 38
12.1.1.14
Dilated Fundus Examination ....................................................................... 39
12.1.1.15
Randomization............................................................................................. 39
12.1.1.16
Adverse Events ............................................................................................ 39
12.1.2
Operative Visit (Visit 00 – Day 0, Unilateral)................................................. 39
12.1.2.1
Medical History ........................................................................................... 39
12.1.2.2
Ocular and Non-ocular Concomitant Medication........................................ 39
12.1.2.3
Inclusion/ Exclusion Criteria ....................................................................... 39
12.1.2.4
Surgery......................................................................................................... 39
12.1.2.4.1
Problems During Surgery......................................................................... 40
12.1.2.4.2
Other Procedures at Surgery..................................................................... 40
12.1.2.4.3
Lens Information...................................................................................... 40
12.1.2.4.4
Successful Placement of IOL in Capsular Bag......................................... 40
12.1.2.5
Programmable Phacoemulsification Settings .............................................. 41
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12.1.2.6
Phacoemulsification Metrics........................................................................ 41
12.1.2.6.1
Cumulative Dissipated Energy (CDE) ..................................................... 41
12.1.2.6.2
BSS Fluid Use .......................................................................................... 41
41
41
12.1.2.7
Adverse Events ............................................................................................ 41
12.1.2.8
Device Deficiencies ..................................................................................... 41
12.1.3
1-Day Postoperative Visit (Visit 1 – Day 1, Unilateral).................................. 41
12.1.3.1
Ocular and Non-ocular Concomitant Medication........................................ 41
12.1.3.2
Intraocular Pressure (IOP) ........................................................................... 42
42
12.1.3.4
Slit-lamp Examination................................................................................. 42
12.1.3.5
Inflammatory Signs...................................................................................... 42
12.1.3.6
Adverse Events ............................................................................................ 42
12.1.4
1-Week Postoperative Visit (Visit 2 – 7 +/- 2 Days, Unilateral) ..................... 42
12.1.4.1
Ocular and Non-ocular Concomitant Medication........................................ 42
12.1.4.2
Visual Acuity (UCDVA and BCDVA) Testing ............................................ 42
12.1.4.3
Intraocular Pressure (IOP) ........................................................................... 43
43
12.1.4.5
Slit-lamp Examination................................................................................. 43
12.1.4.6
Inflammatory Signs...................................................................................... 43
12.1.4.7
Adverse Events ............................................................................................ 43
12.1.5
3-Month Postoperative Visit (Visit 3 – 90 +/- 14 Days, Unilateral)................ 43
12.1.5.1
Ocular and Non-ocular Concomitant Medication........................................ 43
12.1.5.2
Visual Acuity (UCDVA and BCDVA) Testing ............................................ 44
12.1.5.3
Intraocular Pressure (IOP) ........................................................................... 44
12.1.5.4
Specular Microscopy ................................................................................... 44
12.1.5.5
Slit-lamp Examination................................................................................. 44
12.1.5.6
Inflammatory Signs...................................................................................... 44
12.1.5.7
Dilated Fundus Examination ....................................................................... 45
12.1.5.8
Adverse Events ............................................................................................ 45
12.1.6
Additional 6-Month Safety Follow-up Visit................................................ 45
12.2
Discontinued Subjects ......................................................................................... 45
12.3
Clinical Trial Termination ................................................................................... 46
12.4
Unscheduled Visit................................................................................................ 46
12.5
Missed Visit......................................................................................................... 47
12.6
Early Exit Visit .................................................................................................... 47
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13
DEVICE DEFICIENCIES AND ADVERSE EVENTS.......................................... 48
13.1
General Information ............................................................................................ 48
13.2
Monitoring of Adverse Events............................................................................. 52
13.3
Procedures for Recording and Reporting ............................................................ 52
13.4
Unmasking of the Trial Information.................................................................... 54
13.5
Follow-Up of Safety Information........................................................................ 55
13.6
Pregnancy in the Clinical Trial............................................................................ 55
14
DATA REVIEW AND HANDLING ....................................................................... 56
14.1
Completion of Source Documents and Case Report Forms................................ 56
14.2
Data Review and Clarifications........................................................................... 57
15
ANALYSIS PLAN .................................................................................................. 58
15.1
Subject Evaluability............................................................................................. 58
15.2
Analysis Data Sets............................................................................................... 58
15.2.1
Safety analysis set............................................................................................ 58
15.2.2
Intention-to-Treat (ITT) Analysis Set.............................................................. 58
15.2.3
Per-Protocol (PP) Analysis Set........................................................................ 58
15.3
Demographics and Baseline Characteristics ....................................................... 58
15.4
Performance Analyses ......................................................................................... 59
15.4.1
Primary Performance....................................................................................... 59
15.4.1.1
Statistical Hypotheses.................................................................................. 59
15.4.1.2
Analysis Methods ........................................................................................ 59
15.4.2
Secondary Performance................................................................................... 59
15.4.2.1
Statistical Hypotheses.................................................................................. 59
15.4.2.2
Analysis Methods ........................................................................................ 60
60
15.4.3.1
Analysis Methods ........................................................................................ 61
15.5
Handling of Missing Data ................................................................................... 61
15.6
Multiplicity.......................................................................................................... 61
15.7
Safety Analysis .................................................................................................... 61
15.8
Interim Analyses.................................................................................................. 62
15.9
Adaptive Study Design........................................................................................ 62
15.10
Sample Size Justification..................................................................................... 62
16
ADMINISTRATIVE PROCEDURES..................................................................... 64
16.1
Regulatory and Ethical Compliance.................................................................... 64
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16.2
Informed Consent Procedures ............................................................................. 64
16.3
Responsibilities of the Investigator and IRB/IEC ............................................... 64
16.4
Sponsor and Monitoring Responsibilities ........................................................... 65
16.5
Regulatory Documentation and Records Retention ............................................ 66
16.6
Publication of the Clinical Trial .......................................................................... 66
17
REFERENCES ........................................................................................................ 68
18
APPENDICES ......................................................................................................... 69
Table of Tables
Table 9–1
Visit Schedule ..................................................................................................... 27
Table 9–2–1
Study Visit Plan................................................................................................... 28
Table of Figures
Figure 7–1
Study Design....................................................................................................22
Figure 11–1
Test Article Diagram........................................................................................33
Figure 11–2
Control Article Diagrams.................................................................................34
Figure 13–1
Categorization of All Adverse Events..............................................................48
Figure 13-2
Categorization of All Serious Adverse Events.................................................49
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3
ABBREVIATIONS
Abbreviation
Definition
ADE
Adverse Device Effect
AE
Adverse event
ASADE
Anticipated Serious Adverse Effect
Asp
Aspiration
BCDVA
Best Corrected Distance Visual Acuity
BSS
Balanced Salt Solution
CDE
Cumulative Dissipated Energy
CRF
Case report form
CV
Coefficient of Variance
CVS
Centurion® Vision System
CS
Clinically significant
DD
Device Deficiency
EC
Ethics Committee
ECD
Endothelial Cell Density
EMEA
Europe, Middle-east and Africa
ESCRS
European Society of Cataract and Refractive Surgeons
ETDRS
Early Treatment Diabetic Retinopathy Study
FDA
US Food and Drug Administration
GCP
Good Clinical Practice
HIPAA
Health Insurance Portability and Accountability Act
IB
Investigator brochure
IEC
Independent ethics committee
ICD
Informed Consent Documentation
ICH
International Conference on Harmonization
ITT
Intent-to-Treat
IRB
Institutional review board
IRT
Interactive randomization technology
IOL
Intraocular lens
IOP
Itnraocular Pressure
ISO
International Organization for Standardization
ITT
Intent-to-Treat
IVS
Infiniti® Vision System
JCRS
Journal of Cataract and Refractive Surgery
LACAN
Latin America and Canada
LASIK
Laser-Assisted in situ Keratomileusis
LOCSII
Lens opacities classification system II
LogMAR
Logarithm of the Minimum Angle of Resolution
LRI
Limbal Relaxing Incision
MOP
Manual of Procedure
MedDRA®
Medical Dictionary for Regulatory Activities
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Abbreviation
Definition
MFK tip
Mini-Flared Kelman tip
NSAID
Non-steroidal anti-inflammatory drug
NCS
Not clinically significant
PI
Principal Investigator
PPS
Per-Protocol Set
PP
Per protocol
POD
Post-Operative Day
POW
Post-Operative Week
SAE
Serious adverse event
SADE
Serious Adverse Device Effect
SAS®
SAS statistical software, SAS Institute Inc., Cary, NC
SSI
Secondary Surgical Intervention
TDOC
Technical document (Alcon numbering system for internal documents)
u/s
Ultra-sound
µ
Mean
UCDVA
Uncorrected Distance Visual Acuity
USA
United States of America
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4
GLOSSARY OF TERMS
Adverse Device 
Effect (ADE)
Adverse event related to the use of an investigational medical device 
or comparator, if applicable. 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 
investigational medical device or comparator, if applicable.
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. Note: For subjects, this definition 
includes events related to the investigational medical device, the 
comparator, or the procedures involved. For users or other persons, 
this definition is restricted to events related to investigational medical 
devices.
Anticipated 
Serious Adverse 
Device Effect 
(ASADE)
Serious adverse device effect which by its nature, incidence, severity, 
or outcome has been identified in the risk analysis.
Assessment
A procedure used to generate data required by the study.
Device Deficiency
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety, or performance. Note: This definition 
includes malfunctions, misuse or use errors, and inadequate labeling.
Performance 
(Clinical)
Behavior of a medical device or response of the subject to that 
medical device in relation to its intended use, when correctly applied 
to appropriate subjects.
Malfunction
Failure of an investigational medical device to perform in accordance 
with its intended purpose when used in accordance with the 
instructions for use or clinical investigation plan.
Nonserious 
Adverse Event
Adverse event that does not meet the criteria for a serious adverse 
event.
Period
A minor subdivision of the study timeline; divides phases into smaller 
functional segments such as screening, baseline, operative, 
postoperative, etc.
Randomization 
Number
A unique identifier assigned to each randomized subject, 
corresponding to a specific treatment arm assignment.
Serious Adverse 
Device Effect 
(SADE)
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event.
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Seri o us A d verse 
E ve nt ( S A E)
A d verse e ve nt t hat le d t o a n y  of t he f oll o wi n g: 

Deat h.

A seri o us deteri orati o n i n healt h t hat eit her res ulte d i n:
a)
a life-t hreate ni n g ill ness or i nj ur y.
N ote: Life -t hre ate ni n g me a ns t h at t he i n divi d u al w as at 
i m me di ate risk of de at h fro m t he eve nt as it occ urr e d, ie, it 
d oes n ot i ncl u de a n eve nt w hic h hy p ot hetic ally mi g ht h ave 
c a use d de at h h a d it occ urre d i n a m ore severe f or m.
b)
per ma ne nt i m pair me nt t o a b o d y  str uct ure or a b o d y f u ncti o n.
c)
i n-patie nt h os pitalizati o n or pr ol o n ge d h os pitalizati o n.
N ote: Pl a n ne d h os pit aliz ati o n f or a pr e-existi n g c o n diti o n, or 
a pr oce d ur e re q uire d by t he cli nic al i nvesti g ati o n pl a n, 
wit h o ut se ri o us deteri or ati o n i n he alt h, is n ot c o nsi dere d a 
seri o us a dverse eve nt. I n ge ner al, h os pit aliz ati o n si g nifies 
t h at t he i n divi d u al re m ai ne d at t he h os pit al or e mer ge ncy 
w ar d f or o bserv ati o n a n d/ or tr e at me nt ( us u ally i nv olvi n g a n 
over ni g ht st ay) t h at w o ul d n ot h ave bee n a p pr o pri ate i n t he 
p hysici a n's office or a n o ut -p atie nt setti n g. C o m plic ati o ns t h at 
occ ur d uri n g h os pit aliz ati o n ar e A Es. If a c o m plic ati o n 
pr ol o n gs h os pit aliz ati o n or f ulfills a ny ot her seri o us criteri a, 
t he eve nt is seri o us. W he n i n d o u bt as t o w het her 
“ h os pit aliz ati o n ” occ urr e d, t he eve nt s h o ul d be c o nsi dere d 
seri o us.
d)
a me dical or s ur gical i nter ve nti o n t o pre ve nt a) or b).
e)
a n y i n direct har m as a c o nse q ue nce of i nc orrect dia g n ostic 
test res ults w he n use d wit hi n ma n ufact urer's i nstr ucti o ns for 
use.

Fetal distress, fetal deat h, or a c o n ge nital a b n or malit y  or birt h 
defect.
S u bject N u m ber
A n u m ber assi g ne d t o eac h s u bject w h o e nr olls i n t he st u d y . W he n 
c o m bi ne d wit h t he site n u m ber, a u ni q ue i de ntifier is create d f or eac h 
s u bject i n t he st u d y.
U na ntici pate d 
Seri o us A d verse 
De vice Ef fect 
( U S A D E)
Seri o us a d verse de vice effect w hic h b y its nat ure, i nci de nce, se verit y 
or o utc o me has n ot bee n i de ntifie d i n t he ris k a nal y sis.
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6

Page 18 of 75
5
AMENDMENTS
Modification of the protocol is prohibited without prior written agreement in the form of a 
protocol amendment. All amendments will be created by the Sponsor and must be approved 
by the IRB/IEC prior to implementation except when required to mitigate immediate safety 
risks or when the changes involve only logistical or administrative revisions.
5.1
Amendment 1
This protocol has been amended to include an additional 6-Month Safety Follow-up Visit for 
subjects meeting a specified criteria for a decrease in endothelial cell density (ECD) 
following cataract surgery. Subjects who have completed the 3 month visit with an ECD 
count of less than 1500 cells/mm2 and/or a decrease in ECD of 20% or more (in comparison 
to the screening visit value), must return 3 months later for a 6 month safety follow up 
visit. Subject data from the additional safety assessments at this visit will be captured in the 
electronic database, accordingly. For subjects who meet the criteria for the 6 month visit, an 
adverse event will be reported for the decrease in ECD.
In addition, the protocol now requires the application and use of VisCoat® during the surgical 
procedure.  
A diagram for Control article 2 was added. 
Table 9-2-1 was titled Study Visit Plan.
Numbering for some tables and formatting of the document has changed to comply with the 
new document management system template. 
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Page 19 of 75
6
SCHEDULE OF VISITS
Activity
Visit 0      
(-60 to 0 d)
Unilateral 
examination
Visit 00    
(0 d)
Unilateral 
examination
Visit 1 
(1 d)
Unilateral 
examination
Visit 2     
(7 +/- 2 d)
Unilateral 
examination
Visit 3    
(90 +/- 14d)
Unilateral 
examination
6-Month 
Safety 
Follow-
up 
Visit**
Informed Consent
X
Demographics
X
Medical History
X
X
Concomitant Medications
X
X
X
X
X
Inclusion/Exclusion
X
X
Surgery
X
Problems During Surgery
X
Other Procedures at Surgery
X
Lens Information
X
IOL Placement
X
Programmable
Phacoemulsification Settings
X
Phacoemulsification Metrics
(Including CDE, BSS Fluid Use, 
X
Visual Acuity (UCDVA & 
BCDVA)
X
X
X
X2
Intraocular Pressure
X
X
X
X
Specular Microscopy
X
X
X
 
Slit-Lamp Examination
X
X
X
X
X
Crystalline Lens Assessment
X
Anterior chamber cells and 
flare
X
X
X
X
Dilated Fundus Examination
X
X
Randomization*
X
Adverse Events (Including 
Secondary Surgical Intervention)
X
X
X
X
X
X
Device Deficiencies
X
Complete Exit Form1
X
X
1 If a subject exits early, the Visit 3 procedures should be performed at the last available visit, if at all possible
2 Only BCDVA Visual Acuity to be completed at 6-Month Safety Follow-up visit 
*Randomization should be completed within 2 working days prior to the date of surgery
**6-Month Safety Follow-up Visit (if required). See section 12.1.6 Additional 6-month 
Safety Follow-up Visit
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7
INTRODUCTION
7.1
Background
Cataract surgery is a commonly performed procedure with over 5.0 million cases performed 
annually worldwide. Modern cataract surgery utilizes small incision and phacoemulsification 
surgical techniques to emulsify and aspirate the cataractous lens for implantation of a 
foldable intraocular lens (IOL).
The Centurion® Vision System [510(k) Number: CVS K121555, US-FDA approved in 
December 2012] is a new phaco-emulsifier aspirator manufactured by Alcon. The system 
incorporates Active Fluidics™control system that maintains a stable surgical IOP despite 
variations in aspiration flow rate. A more stable surgical IOP allows the surgeon to experience
less movement of ocular structures, as well as the option to lower the IOP setting. This 
coupled with the higher resistive aspiration tubing coupled with lower compliant aspiration 
tubing and Active Fluidics™minimize occlusion break surge. The system is capable of 
creating significantly higher vacuum levels which creates higher tip holding forces. Previous 
studies have indicated that higher vacuum correlates to a lower Cumulative Dissipative 
Energy (CDE), which is a measure of the amount of energy dissipated at the incision. The 
metric also correlates to how much energy is required to perform the surgery. This study will 
be assessing the CDE as well as measuring the total BBS fluid used during the surgical 
procedure.
INTREPID® Balanced Ultrasound (u/s) Tip
The INTREPID® Balanced u/s tip [510(K) Number K911808] minimizes energy along the 
shaft area that interfaces with the incision while maximizing energy at the cutting edge. Since 
the u/s tip creates up to 190 microns of tip movement at 100% amplitude as compared to 130 
micron of movement of the Mini Flared Kelman (MFK) tip, the amplitude is normally 
lowered to 60% amplitude to achieve equivalent cutting. The Balanced tip cuts in a superior 
fashion to the Mini Flared Kelman tip. Coupled with the INTREPID® Ultra Infusion sleeve, 
less energy is dissipated in the incision.
A previous Alcon-sponsored study (Clinicaltrials.gov identifier: NCT01848288) showed 
lower Cumulative Dissipated Energy (CDE), Aspiration Time and Aspiration Fluid Used for 
the Centurion® (K121555) with the Balanced tip vs the Infiniti® with a Mini Flared Kelman 
tip. 
This study is designed to determine if Centurion® Vision System enhancements translate to a 
more efficient cataract procedure as defined by CDE and BSS fluid use.
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B ot h t he Ce nt uri o n ® ( K 1 2 1 5 5 5) a n d I nfi niti® ( K 11 2 4 2 5, K 1 2 0 9 1 2) V isi o n S yste ms a n d t he 
I NT R E PI D ® Bala nce d T i ps a n d t he M F K Ti ps are U S F D A cleare d a n d C E mar ke d, a n d will 
be use d as per t he la bel i n dicati o ns. N o ne w ris ks are i ntr o d uce d wit h t he use of t he eit her t h e 
Ce nt uri o n ® or t he I nfi niti ® . As wit h a n y  ty p e of cataract s ur ger y wit h i ntra oc ular le ns 
i m pla ntati o n, t here is a p ossi bilit y of c o m plicati o ns d ue t o a nest hesia, dr u g reacti o ns, a n d 
s urgi cal pr o ble ms. P ote ntial ris ks /s ur gical c o m plicati o ns ass ociate d s pe cificall y t o t he 
p hac oe m ulsificati o n cataract pr oce d ure i ncl u de t he f oll o wi n g:

ca ps ular i nj ur y

t her mal b ur ns

vitre o us l oss

persiste nt c or neal e de ma
A s u m mar y of k n o w n a n d p ote ntial ris ks a n d be nefits t o h u ma ns, as i de ntifie d i n t he literat ure 
or t hr o u g h pr ecli nical testi n g a n d/ or pri or cli nical e val uati o ns, f or eac h i n vesti gati o nal 
pr o d uct ca n be f o u n d i n t he Directi o ns f or Use a n d O perat or ’s Ma n ual f or t he Ce nt uri o n®
Vi s o n S yste m a n d t he I nfi niti ® Vi si o n S yste m.
7. 2
Cli nic al Tr i al Desi g n
Pr os pecti ve, parallel, ra n d o mize d, patie nt-mas ke d, 3 -ar m, m ulti -ce nter cli nical st u d y 
f oll o wi n g s u bjects wit h s ur ger y d o ne wit h:

Ce nt uri o n ® Vi si o n S yste m, 4 5° Bala nce d Ti p1

Ce nt uri o n ® Vi si o n S yste m, 4 5° Mi ni Flare d Kel ma n Ti p 1

Infi niti ® Vi si o n S yste m, 4 5° Mi ni Flare d Kel ma n Ti p2
1Use d wit h I N T R E PI D ® Ultra I nf usi o n Slee ve
2Use d wit h Ultra i nf usi o n Slee ve
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
P hac o -e m ulsificati o n of a har der le ns re q uires m ore C D E a n d m ore B S S fl ui d f or t his st u d y, 
t he s oftest le nses ( L O C SII O pacities N O a n d N 1) will be e xcl u de d, lea vi n g all le nses wit h 
L O C SII O pacities NII -NI V .
T he clear c or nea i ncisi o n will be bet wee n 2. 2 m m a n d 2. 4 m m.
A ra n d o mizati o n list will be ge nerate d by S p o ns or pers o n nel w h o is n ot i n v ol ve d i n t he 
da y -t o-da y  c o n d uct of t he st u d y, a n d w h o d oes n ot ha ve c o ntact wit h t he st u d y s u bjects, t he 
site, or t he Alc o n e m pl o yees w h o d o ha ve site c o ntact.

Page 22 of 75
Randomized treatment assignment will be provided via Interactive Randomization 
Technology (IRT).
This is a subject-masked study and not observer-masked. Subjects will be masked to the 
treatment for the study eye. The surgeon (Investigator) is not masked to treatment as this is an 
impossibility with the medical devices studied here. Site personnel not participating in 
surgery and not requiring knowledge of randomization will be masked to the extent possible. 
Investigative sites will take all precautions necessary to ensure the subjects remain masked 
for the duration of the trial. It is encouraged that the Investigator take the opportunity to 
remind the subject that he/she will be masked for the duration of the trial.
Post-operatively (day 0), the subject will be required to attend follow-up visits at day 1, day 7 
(+/- 2 days) and month 3 (+/- 14 days).
Figure 7–1
Study Design
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8
CLINICAL TRIAL OBJECTIVES
8.1
Primary Objective
Primary objective is to demonstrate that the Centurion® Vision System used with the 45° 
Balanced Tip will result in less Cumulative Dissipated Energy (CDE) than the Infiniti®
Vision System used with the 45° MFK tip during cataract extraction surgery via 
phacoemulsification of cataract grades NII- NIV (LOCSII).
8.2
Secondary Objectives
1. Demonstrate that the Centurion® Vision System used with the 45° Balanced Tip will 
result in less CDE than the Centurion® Vision System used with the 45° MFK tip 
during cataract extraction surgery via phacoemulsification of cataract grades NII- NIV 
(LOCSII).
2. Demonstrate that the Centurion® Vision System used with the 45° Balanced Tip will 
result in less BSS Fluid Used than the Infiniti® Vision System used with the 45° MFK 
tip during cataract extraction surgery via phacoemulsification of cataract grades NII-
NIV (LOCSII).
3. Demonstrate that the Centurion® Vision System used with the 45° MFK tip will result
in less BSS Fluid Used than the Infiniti® Vision System used with the 45° MFK tip 
during cataract extraction surgery via phacoemulsification of cataract grades NII- NIV 
(LOCSII).
4. Demonstrate that the Centurion® Vision System used with the 45° MFK tip will result 
in less CDE than the Infiniti® Vision System used with the 45° MFK tip during 
cataract extraction surgery via phacoemulsification of cataract grades NII- NIV 
(LOCSII).
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Page 24 of 75
8.4
Study Endpoints
8.4.1
Effectiveness Endpoints
Cumulative Dissipated Energy (CDE) - CDE is a metric displayed on the system user 
interface of both the Centurion® and Infiniti® systems. CDE represents the energy dissipated 
of the u/s tip and infusion sleeve at the ‘incision point’ defined as 5.6mm behind the cutting 
edge. It reflects the total of CDE (ie, CDE longitudinal + CDE torsional).
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CDE = CDElong + CDETor = (Longitudinal Time x Average Longitudinal Power) + (Torsional 
Time x 0.4 x Average Torsional Amplitude)
CDE will be used as both a primary or secondary endpoint, depending on the objective.
BSS Fluid Used - BSS Fluid will be measured by weighing the BSS bag after priming. The 
BSS bag will then be re-inserted and the system will then require a re-prime. A clamp will be 
temporarily used on the administration tubing to prevent fluid from being pulled from the 
bag. The BSS bag will be weighed after the case.
BSS fluid used corresponds to the total fluid through the anterior chamber.
 is a function of
, Aspiration Flow Rate, and Pump 
modulation. The Pump modulation varies as tissue is occluded and unclouded against the tip.
Incision Leakage is a function of surgical IOP, incision size, incision construction, and how 
the phaco hand-piece and 2nd instrument is used.
A reduction in BSS Fluid Used implies less induced trauma to tissues. BSS Fluid Used will 
be used as 
 a secondary 
 endpoint
.
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Pa ge 2 6 of 7 5
8. 4. 2
S afet y E n d p oi nts

B C D V A - Best c orrecti o n usi n g t he 1 0 0 % c o ntrast E T D R S c harts at 3 meters 
( M o n oc ular)

I ntra oc ular Press ure (I O P)

Pr o ble ms d uri n g s ur ger y

Ot her pr oce d ures at s ur ger y

I OL place me nt

Slit -la m p e xa mi nati o n

Dilate d f u n d us e xa mi nati o n

A d verse E ve nts (i ncl u di n g S SI s)

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
De vice deficie ncies

Pa ge 2 7 of 7 5
9
I N V E S TI G ATI O N A L  P L A N
9. 1
O utli ne of Cli nic al Tr i al
T he p ur p ose of t his st u d y is t o e val uate t he Ce nt uri o n ® Vi si o n S yste m d uri n g cataract 
e xtracti o n s urger y  f oll o we d b y p osteri or c ha m ber I O L  i m pla ntati o n i n a d ult patie nts ( ≥ 2 1 
ye ars of a ge ) wit h n uclear o palesce nce gra di n g of NII – NI V ( usi n g L O C SII gra di n g scale).
F or t his st u d y , t he s oftest le nses ( L O C SII O pacities N 0 a n d NI) will be e xcl u de d, lea vi n g all 
le nses wit h L O C SII O pacities NII-NI V.  
F or eac h gr o u p, cataract s ur ger y  will be perf or me d o n eli gi ble s u bjects ra n d o mize d wit h a n 
e q ual n u m ber i n t he f oll o wi n g t hree ar ms, ha vi n g t heir s ur ger y perf or me d wit h eac h 
c o nfi g urati o n.

Ar m 1: Ce nt uri o n ® Vi si o n S yste m, 4 5° Balance d Ti p 1

Ar m 2: Ce nt uri o n ® Vi si o n S yste m, 4 5° Mi ni Flare d Kel ma n Ti p 1

Ar m 3: I nfi niti ® Vi si o n S yste m, 4 5° Mi ni Flare d Kel ma n Ti p 2
1Use d wit h I N T R E PI D ® Ultra I nf usi o n Slee ve
2Use d wit h Ultra i nf usi o n Slee ve
A p pr o xi matel y  1 7 7 s u bjects ( 5 9 i n eac h gr o u p) will u n der g o u nilateral cataract s ur ger y i n t he 
st u d y t o reac h a mi ni m u m of 1 5 9 e val ua ble s u bjects ( 5 3 i n eac h gr o u p) at t he c o ncl usi o n of 
t he 3- m o nt h p ost o perati ve visit. S u bjects will be e nr olle d se q ue ntially i n c o nse nt date a n d 
ti me or der. T he e x pecte d d urati o n of s u bject partici pati o n is a p pr o xi matel y fi ve m o nt hs. T he 
st u d y i ncl u des 5 visits as o utli ne d bel o w.
Ta ble 9 – 1
Vi sit Sc he d ule
E x a mi n ati o n
Visit
Ti m e f or Pr oc e d ur e
Pr e -o p er ati v e ( Scr e e ni n g)
Visit 0 
- 6 0 t o 0 d a ys fr o m st u d y e y e s ur g er y
O p er ati v e ( D a y of S ur g er y)
Visit 0 0
D a y 0
1- D a y p ost o p er ati v e f oll o w-u p
Visit 1
D a y 1
1- W e e k p ost o p er ati v e
f oll o w-u p
Visit 2
D a y 7 (+/ - 2 d a ys )
3- m o nt hs p ost o p er ati v e f oll o w-u p
Visit 3
D a y 9 0 (+/ - 1 4 d a ys )
N O T E:
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
Missi n g data ca n ha ve a detri me ntal effect o n t he i nte grit y a n d s o u n d ness of a cli nical 
trial. All eff orts s h o ul d be ma de b y t he cli nical i n vesti gati ve site t o pre ve nt missi n g st u d y 
visit a n d pr oce d ures d uri n g t he trial.

Page 28 of 75
Adverse events (including SSIs) and any DDs will be assessed and reported at all scheduled 
and unscheduled visits for each subject beginning at the time of informed consent.
NOTE: At the time of study close, unresolved AEs/SAEs related to the device will be 
followed to conclusion, or for six months following close, whichever comes first. The 
Sponsor will be updated accordingly. A 6-Month Safety Follow-up Visit will be conducted (if 
required). See section 12.1.6 Additional 6-Month Safety Follow-up Visit.
External Evaluation Group
External Reading Center to be used to measure the Endothelial Cell Density (ECD), 
Coefficient of Variance (ΔCV), morphology and hexagonality preoperatively and 
postoperatively at month 3 using Konan microscope. This will help us to determine the 
degree of cell loss following cataract extraction surgery.
9.2
Study Design
Detailed in Section 9.1 of this protocol. The schematic representation of the study visit plan is 
given in the below table.
Table 9-2-1
Study Visit Plan
9.3
Rationale for Study Design
The Centurion® Vision System incorporates Active Fluidics™control system that maintains a 
stable surgical IOP despite variations in aspiration flow rate. A more stable surgical IOP 
allows the surgeon to experience less movement of ocular structures, as well as safely lower 
the surgical IOP. This coupled with the higher resistive aspiration tubing coupled with lower 
compliant aspiration tubing and Active Fluidics™minimize occlusion break surge. The 
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Pa ge 2 9 of 7 5
s yste m is ca pa ble of creati n g si g nifica ntly hi g her vac u u m le vels ( ~ 2 0 % hi g her t ha n t he 
I nfi niti® Vi si o n s yste m) w hic h creates hi g her ti p h ol di n g f orces.
Pre vi o us Alc o n -s p o ns ore d st u d y ( M- 1 3-0 0 6, Data o n File) ha ve als o s h o w n t hat t he 
Ce nt uri o n ® wit h t he 4 5° Bala nce d u/s ti p use d si g nifica ntl y  less C D E t ha n t he Infi niti ® wit h 
t he 4 5° M F K ti p. At 1 0 0 % a m plit u de, t he Bala nce d ti p creates 1 9 0 µ m str o ke vs 1 3 0 µ m 
str o ke f or t he M F K ti p. T he Ce nt uri o n a m plit u de is n or mall y set at 6 0 % ma x a n d t he Infi n iti 
at ~ 9 0 % ma x. C D E is t heref ore re d uce d b y 3 3 % .
T his st u d y  has bee n desi g ne d t o o btai n a better u n dersta n di n g of h o w b ot h t he Ce nt uri o n®
a n d t he Bala nce d Ti p affect C D E a n d B S S fl ui d use d, as well as assess t he c orrelati o n t o 
Δ C C T  a n d Δ E C D.
9. 4
Pr oce d ures Pe r St u d y Visit
Refer t o S ecti o n 1 2 ( Cli nical Trial Pr oce d ures) f or i nf or mati o n o n st u d y-s pecific assess me nts 
a n d pr oce d ures.
9. 5
Ris k  Be nefit Assess me nt
B ot h t he Ce nt uri o n ® ( K 1 2 1 5 5 5) a n d I nfi niti® ( K 11 2 4 2 5, K 1 2 0 9 1 2) V isi o n S yste ms a n d t he 
I NT R E PI D ® Bala nce d T i ps a n d t he M F K Ti ps are U S F D A cleare d a n d C E mar ke d, a n d will 
be use d as per t he la bel i n dicati o ns. N o ne w ris ks are i ntr o d uce d wit h t he use of t he eit her t he 
C V S or t he I V S. As wit h a n y  ty p e of i ntra oc ular s ur ger y, t here is a p ossi bilit y of 
c o m plicati o ns d ue t o a nest hesia, dr u g reacti o ns, a n d s ur gi cal pr o ble ms. P ote ntial ris ks / 
s urgi cal c o m plicati o ns ass ociate d s pecificall y t o t he p hac oe m ulsificati o n cataract pr oce d ure 
i ncl u de t he f oll o wi n g:

ca ps ular i nj ur y;

t her mal b ur ns;

vitre o us l oss; a n d

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
persiste nt c o r neal e de ma.
A d diti o nal s u bject disc o mf orts ma y  i ncl u de p u pil dilati o n a n d t he use of n u m bi n g e ye dr o ps. 
T here is a n a d diti o nal s u bject b ur de n of o ne n o n -sta n dar d p ost o perati ve visit ( Visit 3).

Page 30 of 75
10
SUBJECT POPULATION
The study population will include approximately 177 (59 per group) subjects screened and 
randomized, with an expectation to have at least 159 evaluable subjects (53 per group). The 
study will be conducted globally at approximately 5 sites with about 35 subjects enrolled per 
site.
To participate in this clinical trial, subjects must be of 21 years of age and above requiring 
cataract extraction followed by IOL implantation. Subjects should have a Nuclear 
Opalescence grading of NII to NIV (using LOCS II grading scale) to be eligible for this 
study.
10.1
Inclusion Criteria
1. Adult patients 21 years of age or older of either gender or any race.
2. Willing and able to consent for participation.
3. Willing and able to attend postoperative examinations per protocol schedule.
4. Patients must have a cataract in at least one eye with a Nuclear Opalescence of II-IV 
(via LOCS II) followed by posterior chamber IOL implantation
10.2
Exclusion Criteria
1. Subjects whose postoperative best corrected visual potential is expected to be worse 
than 20/60 Snellen (0.5 effects logMAR) at the final study visit.
2. Planned multiple procedures, including Laser Phaco, LASIK, LRI's etc during surgery 
or the course of this study. 
3. Clinically significant corneal endothelial dystrophy (eg, Fuch's dystrophy, ECD 
< 1500 cells/mm2)
4. Patients who have severe conditions of acute or chronic diseases or illnesses that, per 
Investigator's clinical judgment, would increase the operative risk or confound the 
result of this investigation.
5. Small pupil size that will require mechanical dilation using iris hooks, Malyugin ring 
or similar devices effects.
6. Weaken /Broken zonules
7. Subjects who were enrolled in the study may not be re-enrolled for the second eye.
8. Untreated or uncontrolled Glaucoma
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9. Previous intraocular or corneal surgery of any kind, including any type of surgery for 
either refractive or therapeutic purposes.
10. A poorly dilating pupil or other pupil defect that prevents the iris from retracting 
peripherally to at least 5 mm dilation.
11. Current or previous usage of an alpha-1-selective adrenoceptor blocking agent or an 
antagonist of alpha 1A adrenoceptor (eg, Flomax® (tamsulosin hydrochloride), 
Hyntrin® (terazosin hydrochloride), or Cardura® (doxazosin mesylate).
12. Diagnosed with severe retinal disorders (eg, macular degeneration, proliferative
diabetic retinopathy).
13. History of corneal disease (eg, herpes simplex, herpes zoster, etc).
14. History of retinal detachment.
15. Known zonular instability or zonular dehiscence (eg, Marfan’s syndrome, 
pseudoexfoliation syndrome, etc).
16. Any patient currently participating in another drug or device study
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11
TREATMENT
Upon signing informed consent, subjects will be considered enrolled in the study and a 
subject ID number will be assigned by entering the subject into the EDC system. The 
qualified subjects will be randomized in a 1:1:1 manner to receive treatment with Centurion®
Vision System/ 45°Balanced Tip1 or Centurion® Vision System/ 45°Mini Flared Tip1 or 
Infiniti® Vision System/ 45°Mini Flared Tip2. 
Throughout the clinical trial, the Investigator will be responsible for the accounting of all 
investigational products and will ensure that the clinical trial products are not used in any 
unauthorized manner.
1Used with INTREPID® Ultra Infusion Sleeve
2Used with Ultra infusion Sleeve
11.1
Investigational Products
The Centurion® Vision System and Infiniti® Vision System, including accessories approved 
by Alcon (ie, tips, sleeves and packs, etc), constitute complete surgical systems. These 
systems are intended for use by licensed ophthalmic surgeons and their surgical teams. The 
Vision System devices utilized in this postmarket trial are CE Marked and 510k cleared. 
Approved labeling will be applied and devices provided in standard manufacturer’s 
packaging (where applicable).
Test Article: Centurion® Vision System (v2.04) will be used with the 45° Balanced Tip 
(coupled with the INTREPID® Ultra Infusion sleeve).
The Centurion® Vision System is a phacoemulsification aspiration platform indicated for 
emulsification, separation, and aspiration of cataracts, residual cortical material and lens 
epithelial cells; vitreous aspiration and cutting associated with anterior vitrectomy; bipolar 
coagulation; and intraocular lens injection. The system employs similar functionality and 
technologies of its predecessor, the Infiniti® Vision System. In addition to the existing 
functions for irrigation/aspiration, phacoemulsification, vitreous aspiration cutting, and 
bipolar coagulation, the CVS also introduces new modalities for active irrigation, automated 
IOL injection, and advanced surgical display for viewing of biometry data and surgical 
operating parameters.
Standard, sterile, single-use pack of supplies and accessories necessary to perform one 
cataract removal procedure each will be locally procured by the investigational sites (Alcon 
will reimburse the costs). 
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See Figure 11-1 and Figure 11-2 for product and accessory diagrams.
Figure 11–1
Test Article Diagram
Control Articles: 
1. Centurion® Vision System (v2.04) used with the 45° Mini Flared Kelman u/s Tip 
(coupled with INTREPID® Ultra Infusion Sleeve)
2. Infiniti® Vision System (version 3.01) used with 45° Mini Flared u/s Tip (coupled with 
Ultra Infusion Sleeve) for phaco-emulsification procedure.
The Infiniti® Vision System is a phacoemulsification aspiration platform indicated for 
emulsification, separation, and aspiration of cataracts, residual cortical material and lens 
epithelial cells; vitreous aspiration and cutting associated with anterior vitrectomy; and 
bipolar coagulation. Standard, sterile, single-use packs of supplies and accessories necessary 
to perform one lens removal procedure each will be procured by the investigational sites 
(Sponsor will reimburse the costs). Protocol defined accessories will include the Mini-Flared 
tip and Ultra infusion sleeve. These products represent the standard of care for the Infiniti®
Vision System.
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Figure 11–2
Control Article Diagrams
Control Article 1
Control Article 2
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11.2
Usage
The approved surgical products employed in this study will be utilized in accordance with 
approved indication(s). Refer to the system operator manuals and consumable surgical pack 
DFUs for in-depth instructions.
11.3
Accountability Procedures
The Investigator or the designee will order/ procure the clinical supplies (surgery packs, BSS 
Bags and other surgery-related ancillary supplies) and Alcon will reimburse the costs on an 
actual basis (if available, copies of the invoices and/ or order forms should be filed in the 
Investigator’s clinical trial records for the Clinical Site Manager or any other Sponsor-
personnel to review during the monitoring visits). 
Upon receipt of study products, the Investigator or designee will conduct an inventory. Alcon 
will provide the site with accountability logs  which will can be used to capture information 
on the subject ID, pack lot/ batch number, expiry date, date of dispensation, name of 
dispenser and will also have a column for ‘sticking’ the labels from the surgery packs. The 
Clinical Site Manager will train the site on appropriately completing this log. 
The Investigator or the designee should follow the manufacturer’s instruction on the storage-
specifications of the supplies.
During the study, the site must maintain records (either in the Alcon provided log or site-
specific logs) of study article dispensation and collection for each subject. The accountability 
log or any similar record must be made available to the study monitor for the purposes of 
verifying the accounting of clinical supplies.
Any discrepancies and/or deficiencies between the observed disposition and the written 
account must be recorded in the source notes along with a detailed explanation.
At the conclusion of the study, the Clinical Site Manager will perform a final reconciliation 
of the accountability records. The Investigator will be responsible for the collection of all 
unused supplies unless otherwise instructed by the Sponsor.
Throughout the study, the Investigator will be responsible for the accounting of all study 
products and will ensure that the study products are not used in any unauthorized manner.
NOTE: Over-labeling is not required as the site staff are all unmasked for this study.
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12
CLINICAL TRIAL PROCEDURES
12.1
Clinical Trial Assessments
The following section describes in general the assessments to be performed in this clinical 
trial. Assessments are thoroughly described in the Manual of Procedures (hereto MOP). Refer 
to section 6 SCHEDULE OF VISITS for an overview of assessments by visit.
NOTE: All ocular assessments are to be performed on the study eye only. Refer to section 10 
SUBJECT POPULATION for information on study eye selection.
12.1.1
Pre-operative visit (Visit 0; Day -60 to Day 0)
Conduct pre-screening, screening and assign patient screening number as follows:
12.1.1.1
Pre-Screen
Where permitted by national and local laws and regulations, pre-screen all potential cataract 
patients via chart review. Additionally prescreen patients spontaneously presenting for 
cataract evaluation and/or annual examinations. In both cases, prescreen inclusion/exclusion 
criteria based upon routine testing conducted for all cataract patients.
NOTE: Prior to undertaking study specific testing, informed consent is required.
12.1.1.2
Informed Consent
Refer to Section 16.2: Informed Consent Procedures for specifics regarding informed consent 
process. For patients that pass pre-screening, explain the nature of the study. If the patient is 
willing to participate, appropriately consent the potential study subject and have him/her sign 
and date the Institutional Review Board (IRB) or Ethics Committee (EC) approved Informed 
Consent Document (ICD). If the patient is unable to comprehend and sign the ICD, 
he/she is not eligible for the study. Assign the potential subject a screening number (refer to 
Section 12.1.1.3 below) prior to any study specific testing.
NOTE: The subject’s medical record must indicate participation in this study and desire to 
continue participation in the study.
12.1.1.3
Subject Number Assignment
Once the patient has been formally consented, the relevant patient information should be 
entered in the EDC system (Medidata® Rave) and the system will assign the subject number 
sequentially starting with 
 etc.
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12.1.1.4
Demographics, Medical History and Concomitant 
Medications
Document demographics, ocular and non-ocular medical history, ocular and non-ocular 
concomitant medications and pregnancy status (where applicable). Refer to MOP for further 
instruction.
Ensure pregnancy status is documented for all women of child-bearing potential. Compare 
with Inclusion/Exclusion criteria (refer to Section 10: Subject Population). Identify potential
safety issues for subject if enrolled in the study.
Record all concomitant medications for ocular and non-ocular conditions used by the subject 
at the time of the examination. No study specific medications are required for this study. The 
medications used during the trial are those that the Investigator deems necessary for cataract 
surgery procedures and treatment.
NOTE: Routine preoperative and intra-operative medications do not require capture.
12.1.1.5
Inclusion/Exclusion Criteria
Refer to the list of Inclusion/Exclusion criteria in Section 10: Subject Population. Ensure the 
subject meets all requirements for participation and eligibility; ie meets all the inclusion and 
none of the exclusion criteria.
12.1.1.6
Selection of Study Eye
The study eye should be the eye with the worse cataract as indicated by LOCS II assessment. 
Where cataract grade is the same in both eyes, the right eye should be chosen as the study 
eye. Record the assigned study eye in the medical notes.
12.1.1.7
Visual Acuity (UCDVA and BCDVA) Testing
Perform Uncorrected Distance Visual Acuity (UCDVA) testing and Best Corrected Distance 
Visual Acuity (BCDVA) testing with study specified equipment. Refer to MOP for further 
instruction.
Ensure UCDVA and BCDVA testing precedes IOP measurement, the administration of eye 
drops to dilate or anesthetize the eyes, or any examination requiring contact with the eye.
NOTE: Lighting conditions must be measured and recorded prior to VA testing.
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12.1.1.8
Intraocular pressure (IOP)
Measure IOP using Goldmann or other applanation method. For each subject, the same 
instrument type should be used for all measurements in the study.
12.1.1.9
Specular Microscopy
Utilize a commercially available specular microscope (Konan microscope) to photograph the 
corneal endothelial cells as per the instructions provided by the Reading Center. Detailed 
information on transmission of the images to the reading Center for analysis is provided in 
the MOP.
NOTE: If the subject has been dismissed prior to assessment of image quality (not 
recommended) and images are of poor quality, the subject will be asked to return and the 
assessment will be repeated.
12.1.1.11
Slit-lamp Examination
Examine the anterior segment of the eye, including the eyelid, sclera, conjunctiva, cornea, 
iris, and natural crystalline lens. Record all preoperative baseline clinical observations and 
the clinical significance of each observation. Give consideration to Inclusion/Exclusion 
criteria (refer to Section 10: Subject Population).
NOTE: Certain pathologies may become apparent after cataract extraction and IOL 
implantation. In these instances, the preoperative pathology status should be updated.
12.1.1.12
Crystalline Lens Assessment
Assess cataract grade using LOCS II classifications (Chylack 1989). Refer to MOP (LOCS II 
Instructions for Grading) for detailed grading instructions.
12.1.1.13
Inflammatory Signs
Grade inflammatory signs including cells and flares, and corneal edema. Refer to MOP 
(Inflammatory Signs Grading) for details including grading scale.
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12.1.1.14
Dilated Fundus Examination
Perform a dilated fundus examination (indirect and direct ophthalmoscopy). Record diameter 
of dilated pupil. Record all preoperative baseline clinical observations with consideration 
given to the inclusion and exclusion criteria (Refer to Section 10. Subject Population) and 
note clinical significance.
NOTE: Certain pathologies may become apparent after cataract extraction and IOL 
implantation. In these instances, the preoperative pathology status should be updated.
12.1.1.15
Randomization
Randomization should be undertaken within 2 business days of the operative visit. Ensure 
that all inclusion/exclusion criteria have been met and that all preoperative (Visit 0) 
assessments have been performed. Utilize the IRT system to randomize subject’s study eye to 
the test or to the control group.
12.1.1.16
Adverse Events
Record AEs as described in Section 13: Device Deficiencies and Adverse Events.
12.1.2
Operative Visit (Visit 00 – Day 0, Unilateral)
12.1.2.1
Medical History
Update subject’s ocular and non-ocular medical history.
12.1.2.2
Ocular and Non-ocular Concomitant Medication
Record changes in ocular and non-ocular concomitant medications.
NOTE: Routine preoperative and intra-operative medications do not require capture.
12.1.2.3
Inclusion/ Exclusion Criteria
Refer to the list of Inclusion/Exclusion criteria in Section 10: Subject Population. Ensure the 
subject still meets all requirements for participation and eligibility.
12.1.2.4
Surgery
NOTE: Prior to performing study surgeries, surgeons should have a minimum experience of 
100 cases with the Infiniti® Vision System and 100 cases with the Centurion® Vision System.
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Confirm subject meets all inclusion/exclusion criteria (refer to Section 10: Subject 
Population), and has been randomized (refer to Section 12.1.1.17. Randomization) prior to 
proceeding with surgery.
Care should be taken to protect endothelium with the Ophthalmic Viscosurgical Device, 
VisCoat®. As the nuclear disassembly is performed, reapplication of the VisCoat® should be 
done throughout the procedure in order to protect the endothelium. The surgeon should create 
a working space each time before re-engaging the ultrasound.
NOTE: Prepare subject for surgery per site specific standard operating procedures. Manually 
create a 5.0 to 5.5 mm capsulorhexis and proceed with phacoemulsification as specified by 
randomization.
Femtosecond laser use at any point in the surgery (eg, incision, capsulotomy, lens 
fragmentation, etc) is prohibited. Additionally pre-chop nucleofracture technique is 
prohibited. The IOL implantation needs to be managed either with Alcon Monarch® IOL 
injector (or the INTREPID® AutoSert® IOL injector) and the same cartridge D (2.2-2.4 mm).
12.1.2.4.1
Problems During Surgery
Indicate what problems, if any, occurred during surgery.
12.1.2.4.2
Other Procedures at Surgery
Indicate other procedures, if any that occurred at the time of surgery. Other procedures 
include those performed outside of routine cataract surgery.
NOTE: Other planned procedures at the time of surgery are exclusionary (Refer to 
Section 10: Subject Population).
12.1.2.4.3
Lens Information
Document details of the IOL implanted including IOL model and brand in the medical notes.
12.1.2.4.4
Successful Placement of IOL in Capsular Bag
Indicate in the medical notes if IOL placement in the capsular bag was successful.
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12.1.2.5
Programmable Phacoemulsification Settings
Document whether preferred pre-programmed phacoemulsification machine settings were 
altered prior to or during the surgical procedure. If settings were altered, indicate the 
setting(s) modified.
12.1.2.6
Phacoemulsification Metrics
12.1.2.6.1
Cumulative Dissipated Energy (CDE)
At the conclusion of the surgery, record CDE as reported on the Vision System interface.
12.1.2.6.2
BSS Fluid Use
Weigh the empty drain bag in preparation for the total BSS consumption calculation. Refer to 
the MOP for calculation details.
NOTE: It is preferable to use the same BSS Bags (BSS or BSS Plus) for all the case.
12.1.2.7
Adverse Events
Record all AEs including SSIs. Use the AE form as described in Section 13: Device 
Deficiencies and Adverse Events.
12.1.2.8
Device Deficiencies
Record device deficiencies if observed. Use the Device Deficiency Form as described in 
Section 13: Device Deficiencies and Adverse Events.
12.1.3
1-Day Postoperative Visit (Visit 1 – Day 1, Unilateral)
12.1.3.1
Ocular and Non-ocular Concomitant Medication
Record changes in ocular and non-ocular concomitant medications.
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12.1.3.2
Intraocular Pressure (IOP)
Measure IOP using Goldmann or other applanation method. For each subject, the same 
instrument type should be used for all measurements in the study.
12.1.3.4
Slit-lamp Examination
Examine the anterior segment of the eye, including the eyelid, sclera, conjunctiva, cornea, 
iris, and natural crystalline lens. Record all new clinical observations and note the clinical 
significance of each observation.
NOTE: Certain pathologies may become apparent after cataract extraction and IOL 
implantation. In these instances, the preoperative pathology status should be updated.
12.1.3.5
Inflammatory Signs
Grade inflammatory signs including cells and flares, and corneal edema. Refer to MOP 
(Inflammatory Signs Grading) for details including grading scale.
12.1.3.6
Adverse Events
Record all AEs including SSIs. Use the AE form as described in Section 13: Device 
Deficiencies and Adverse Events.
12.1.4
1-Week Postoperative Visit (Visit 2 – 7 +/- 2 Days, Unilateral)
12.1.4.1
Ocular and Non-ocular Concomitant Medication
Record changes in ocular and non-ocular concomitant medications.
12.1.4.2
Visual Acuity (UCDVA and BCDVA) Testing
Perform Uncorrected Distance Visual Acuity (UCDVA) testing and Best Corrected Distance 
Visual Acuity (BCDVA) testing with study specified equipment. Refer to MOP for further 
instruction.
Ensure UCDVA and BCDVA testing precedes IOP measurement, the administration of eye 
drops to dilate or anesthetize the eyes, or any examination requiring contact with the eye.
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NOTE: Lighting conditions must be measured and recorded prior to VA testing.
12.1.4.3
Intraocular Pressure (IOP)
Measure IOP using Goldmann or other applanation method. For each subject, the same 
instrument type should be used for all measurements in the study.
12.1.4.5
Slit-lamp Examination
Examine the anterior segment of the eye, including the eyelid, sclera, conjunctiva, cornea, 
iris, and natural crystalline lens. Record all new clinical observations and note the clinical 
significance of each observation.
NOTE: Certain pathologies may become apparent after cataract extraction and IOL 
implantation. In these instances, the preoperative pathology status should be updated.
12.1.4.6
Inflammatory Signs
Grade inflammatory signs including cells and flares, and corneal edema. Refer to MOP 
(Inflammatory Signs Grading) for details including grading scale.
12.1.4.7
Adverse Events
Record all AEs including SSIs. Use the AE form as described in Section 13: Device 
Deficiencies and Adverse Events.
12.1.5
3-Month Postoperative Visit (Visit 3 – 90 +/- 14 Days, 
Unilateral)
12.1.5.1
Ocular and Non-ocular Concomitant Medication
Record changes in ocular and non-ocular concomitant medications.
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12.1.5.2
Visual Acuity (UCDVA and BCDVA) Testing
Perform Uncorrected Distance Visual Acuity (UCDVA) testing and Best Corrected Distance 
Visual Acuity (BCDVA) testing with study specified equipment. Refer to MOP for further 
instruction.
Ensure UCDVA and BCDVA testing precedes IOP measurement, the administration of eye 
drops to dilate or anesthetize the eyes, or any examination requiring contact with the eye.
NOTE: Lighting conditions must be measured and recorded prior to VA testing.
12.1.5.3
Intraocular Pressure (IOP)
Measure IOP using Goldmann or other applanation method. For each subject, the same 
instrument type should be used for all measurements in the study.
12.1.5.4
Specular Microscopy
Utilize a commercially available specular microscope (Konan microscope) to photograph the 
corneal endothelial cells as per the instructions provided by the Reading Center; the images 
will then be transferred to the Reading Center for analysis.
NOTE: If the subject has been dismissed prior to assessment of image quality (not 
recommended) and images are of poor quality, the subject will be asked to return and the 
assessment repeated.
12.1.5.5
Slit-lamp Examination
Examine the anterior segment of the eye, including the eyelid, sclera, conjunctiva, cornea, 
iris, and natural crystalline lens. Record all new clinical observations and note the clinical 
significance of each observation.
NOTE: Certain pathologies may become apparent after cataract extraction and IOL 
implantation. In these instances, the preoperative pathology status should be updated.
12.1.5.6
Inflammatory Signs
Grade inflammatory signs including cells and flares, and corneal edema. Refer to MOP 
(Inflammatory Signs Grading) for details including grading scale.
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12.1.5.7
Dilated Fundus Examination
Perform a dilated fundus examination (indirect and direct ophthalmoscopy). Record diameter 
of dilated pupil. Record all preoperative baseline clinical observations with consideration 
given to the inclusion and exclusion criteria (Refer to Section 10: Subject Population) and 
note clinical significance.
NOTE: Certain pathologies may become apparent after cataract extraction and IOL 
implantation. In these instances, the preoperative pathology status should be updated.
12.1.5.8
Adverse Events
Record all AEs including SSIs. Use the AE form as described in Section 13: Device 
Deficiencies and Adverse Events.
12.1.6
Additional 6-Month Safety Follow-up Visit
Subjects who have completed the 3 month visit with an ECD count of less than 1500 
cells/mm2 and/or a decrease in ECD of 20% or more (in comparison to the screening visit 
value) at their 3 month visit, must return 3 months later for a 6 month safety follow-up visit.
The following safety assessments are to be performed at the 6-Month Safety Follow-up visit:
-
A repeat ECD assessment
-
Visual Acuity - BCDVA
-
Slit lamp examination - corneal edema
-
-
Any other assessment performed as standard of care at the site
Subject data from the additional safety assessments will be captured in the electronic 
database, accordingly.
12.2
Discontinued Subjects
Discontinued subjects withdraw, or are withdrawn, from the study after 1) signing consent, 
2) meeting the inclusion and exclusion criteria, and 3) having been randomized. Subjects 
signing consent, but withdrawing prior to randomization shall be considered a screen failure, 
and the failed entry criterion documented (eg, inclusion criterion 2, exclusion criterion 4). 
Refer to Section 10 SUBJECT POPULATION. Subjects randomized, but withdrawing prior to 
surgery shall be considered discontinued, and the reason for discontinuation documented (eg, 
discontinued due to withdrawal by subject).
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TDOC-0050176
Protocol - Clinical
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Pa ge 4 6 of 7 5
S u bjects ma y  disc o nti n ue st u d y partici pati o n at a n y ti me a n d f or a n y reas o n. S u bjects ma y be 
disc o nti n ue d fr o m t he st u d y  at a n y ti me if i n t he o pi ni o n of t he PI or desi g nate d, qualifie d 
me dical pers o n nel, c o nti n ue d partici pati o n p oses a healt h ris k. S u bject n u m bers fr o m 
disc o nti n ue d s u bjects will n ot be reiss ue d. Disc o nti n ue d s u bjects will n ot be re place d.
1 2. 3
Cli nic al Tr i al Te r mi n ati o n
T he st u d y  ca n be ter mi nate d at a n y ti me b y t he S p o ns or . If t he st u d y is ter mi nate d, t he 
I n vesti gat or a n d a ny re g ulat or y a ut h orities will be i nf or me d wit hi n 5 da ys of t he decisi o n. 
T he I n vesti gat or will be res p o nsi ble f or i nf or mi n g t he s u bjects a n d t heir I nstit uti o nal Re vie w 
B oar d (I R B) of t he earl y termi nati o n of t he trial. T he S p o ns or will be res p o nsi ble f or 
pr o vi di n g pr oce d ures t o e ns ure pr otecti o n of t he s u bject i nterests.
1 2. 4
U nsc he d ule d Vi sit
After si g ni n g I C F , if a s u bject re q uires a st u d y e ye visit t hat is n ot s pecifie d i n t he pr ot oc ol, 
t he visit is c o nsi dere d a n U nsc he d ule d Visit ( U N S V). F or t he 6- M o nt h Safet y  F oll o w-u p Visit 
please refer t o Secti o n 1 2. 1. 6 .
St u d y  e ye oc ular e xa mi nati o ns c o n d ucte d b y n o n -st u d y pers o n nel are n ot c o nsi dere d a n 
U N S V . Als o, Pre -pla n ne d, r o uti ne p ost o perati ve visits (e g, 1- m o nt h p ost o perati ve visit) are 
n ot c o nsi dere d u nsc he d ule d visits u nless a n A E (seri o us or n o n -seri o us) is re p orte d a n d st u dy 
pers o n nel are i n v ol ve d i n t he c o n d uct of t he visit.
N O T E: A n y A E (seri o us or n o n -seri o us) arisi n g fr o m a pre-pla n ne d, r o uti ne p os t o perati ve 
visit m ust be ca pt ure d a n d re p orte d as i n acc or da nce wit h Secti o n 1 3: De vice Deficie ncies 
a n d A d verse E ve nts re gar dless of st u d y  pers o n nel i n v ol ve me nt.
D uri n g a n u nsc he d ule d visit, it is rec o m me n de d t hat t he f oll o wi n g i nf or mati o n be c ollecte d:

C o nc o mita nt me dicati o ns

V is ual ac uit y ( U C D VA, B C D V A)

Slit -la m p e xa m

C o nj u ncti val e de ma gra di n g

Wo u n d lea ka ge

F u n d us e xa m

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
I O P

Pa ge 4 7 of 7 5

A d verse e ve nts a n d de vice deficie ncies
Acti vities u n derta ke n d uri n g a n U N S V  s h o ul d be c ollecte d in acc or da nce wit h t his pr ot oc ol 
a n d t he M O P. Data c ollecte d will be e ntere d i nt o E D C.
If t he s u bject is disc o nti n ue d at t he u nsc he d ule d visit, all Earl y E xit pr oce d ures s h o ul d be 
perf or me d. Refer t o S ecti o n 6 S C H E D U L E O F VI SI T S . If a n U N S V is re q uire d after t he fi nal 
st u d y visit f or safet y p ur p oses, t he data will n ot be ca pt ure d i n E D C. Refer t o Secti o n 1 3. 5 
F oll o w -U p of S afety I nf or m ati o n .
1 2. 5
Misse d Vi sit
If a s u bject u na v oi da bly misses a sc he d ule d e xa m, he/s he s h o ul d be resc he d ule d wit hi n t he 
sa me e xa m peri o d. T he I n vesti gati o nal site s h o ul d s h o w dili ge nce i n tr yi n g t o sc he d ule t he 
s u bject f or all e xa ms. If a s u bject is u na ble t o ret ur n f or t he fi nal st u dy visit, t he E xit F or m 
s h o ul d be c o m plete d wit h t he a p pr o priate reas o n f or disc o nti n uati o n i n dicate d.
1 2. 6
E arl y E xit Vi sit
If a s u bject e xits fr om t he st u d y  early (ie, d oes n ot c o m plete t he sc he d ule d or pla n ne d st u d y 
visits) c o m plete t he earl y e xit f or m i ncl u di n g t he f oll o wi n g rec o m me n de d acti vities:

U C D V A a n d B C D V A

I O P

S pec ular micr osc o p y

Slit -la m p e xa mi nati o n

I nfla m mat or y si g ns

Dilate d f u n d us e xa m

N ote A Es (i ncl u di n g S SIs)

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
N ote c ha n ges t o s y ste mic a n d oc ular c o nc o mita nt me dicati o ns

Page 48 of 75
13
DEVICE DEFICIENCIES AND ADVERSE EVENTS
13.1
General Information
An adverse event (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 product (test or control article). For 
subjects, this definition includes events related to the test article, the control article, or the 
procedures involved. For users or other persons, this definition is restricted to events related 
to the test article.
Figure 13–1
Categorization of All Adverse Events
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Status:  
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TDOC-0050176
Protocol - Clinical
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Pa ge 4 9 of 7 5
Fi g ur e 1 3- 2
C ate g oriz ati o n of All Seri o us A d verse E ve nts
Seri o us A dverse Eve nts
A seri o us a d verse e ve nt is a n A E t hat le d t o a n y of t he f oll o wi n g: 

Deat h.

A seri o us deteri orati o n i n t he healt h of t he s u bject t hat eit her res ulte d i n:
a.
a life -t hreate ni n g ill ness or i nj ur y. 
N ote: Life -t hre ate ni n g me a ns t h at t he i n divi d u al w as at i m me di ate risk of 
de at h fr o m t he eve nt as it occ urr e d, ie, it d oes n ot i ncl u de a n eve nt w hic h 
hy p ot hetic ally mi g ht h ave c a use d de at h h a d it occ urr e d i n a m ore severe f or m.
b.
a n y p ote ntiall y si g ht-t hreate ni n g e ve nt or per ma ne nt i m pair me nt t o a b o d y  
str uct ure or a b o dy f u ncti o n. 
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6

Pa ge 5 0 of 7 5
c.
i n-patie nt h os pitalizati o n or pr ol o n ge d h os pitalizati o n. 
N ote: Pl a n ne d h os pit aliz ati o n f or a pr e-existi n g c o n diti o n, wit h o ut seri o us 
deteri or ati o n i n he alt h, is n ot c o nsi der e d a S A E. I n ge ner al, h os pit aliz ati o n 
si g nifies t h at t he i n divi d u al re m ai ne d at t he h os pit al or e merge ncy w ar d f or 
o bserv ati o n a n d/ or tr e at me nt ( us u ally i nv olvi n g a n over ni g ht st ay) t h at w o ul d 
n ot h ave bee n a p pr o pri ate i n t he p hysici a n's office or a n o ut - p atie nt setti n g. 
C o m plic ati o ns t h at occ ur d uri n g h os pit aliz ati o n ar e A Es. If a c o m plic ati o n 
pr ol o n gs h os pit aliz ati o n or f ulfills a ny ot her seri o us criteri a, t he eve nt is 
seri o us. Whe n i n d o u bt as t o w het her “ h os pit aliz ati o n ” occ urre d, t he eve nt 
s h o ul d be c o nsi dere d s eri o us.
d.
a me dical or s ur gical i nter ve nti o n t o pre ve nt a) or b)
e.
a n y i n direct har m as a c o nse q ue nce of i nc orrect dia g n ostic test res ults w he n 
use d wit hi n ma n ufact urer ’s i nstr ucti o ns f or use.  

Fetal distress, fetal deat h, or a c o n ge nital a b n or malit y  or birt h defect.
S pecific E ve nts Rele v a nt t o t his Pr ot oc ol
I n a d diti o n t o re p orti n g all A Es (seri o us a n d n o n -seri o us) meeti n g t he defi niti o ns, t he 
I n vesti gat or m ust re p ort a n y occ urre nce of t he f oll o wi n g as a n S A E:

Ca ps ule i nj ur y

T her mal b ur ns of t he e y e

Vi tre o us l oss
A c h a n g e i n c or n e al e n d ot h eli al c ell c o u nt f oll o wi n g p h a c o e m ulsifi c ati o n a n d p ost eri or 
c h a m b er IO L  i m pl a nt ati o n i n s u bj e cts wit h a m or e a d v a n c e d c at ar a ct (i e, Gra des NII -NI V 
via L O C SII sc ori n g) is a n e ve nt of s pecial i nterest. A c h a n g e i n c or n e al e n d ot h eli al c ell 
c o u nt h as b e e n d efi n e d as a n E C D c o u nt of less t ha n 1 5 0 0 cells/ m m2
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
a n d/ or a decrease i n 
E C D of 2 0 % or m ore at t he s u bjects 3 m o nt h visit. T o f urt her c haracterize c ha n ges i n E C D 
fr o m baseli ne, a n A E m ust be re p orte d f or a n y s u bject w h o e x perie nces a c ha n ge as defi ne d 
a b o ve. A d verse e ve nts f or c or neal e n d ot helial cell l oss ma y  be c o nsi dere d seri o us base d o n 
t he j u d g me nt of t he i n vesti gat or.
A n y  ot her p ote ntiall y si g ht-t hreate ni n g e ve nt ma y als o be c o nsi dere d seri o us base d o n t he 
j u d g me nt of t he I n vesti gat or a n d s h o ul d be re p orte d a p pr o priately as deli neate d i n 
Secti o n 1 3. 2. I n a d diti o n, p ost o perati ve hi g h I O P  or c or neal e de ma ( gra de 3) prese nte d 

Pa ge 5 1 of 7 5
persiste ntl y  fr o m 1 da y t o 1 m o nt h p ost o perati ve s h o ul d be c o nsi dere d as a seri o us a d verse 
e ve nt.
A n a d verse de vice effect ( A D E) is a n A E relate d t o t he use of a n i n vesti gati o nal pr o d uct (test 
or c o ntr ol article). T his defi niti o n i ncl u des A Es res ulti n g fr o m i ns uf ficie nt or i na de q uate 
i nstr ucti o ns f or use, de pl o yme nt, i m pla ntati o n, i nstallati o n, or o perat i o n; a n y malf u ncti o n; 
a n d use err or or i nte nti o nal mis use of t he test article or c o ntr ol article. 
Seri o us A dverse Device Ef fect 
A seri o us a d verse de vice effect ( S A D E) is a n A D E t hat has res ulte d i n a n y  of t he 
c o nse q ue nces c haracteristic of a S A E.
A ntici p ate d Seri o us A dverse Device Effect
A n a ntici pate d seri o us a d verse de vice ef fect ( A S A D E) is a S A D E w hic h by its nat ure, 
i nci de nce, se verit y, or o utc o me has bee n i de ntifie d i n t he ris k a nalys is re p ort.
U n a ntici p ate d Seri o us A dverse Device Ef fect
A n u na ntici p ate d seri o us a d verse de vice effect ( U S A D E) is a S A D E w hic h b y its nat ure, 
i nci de nce, se verity or o utc o me has n ot bee n i de ntifie d i n t he ris k a nal ys is re p ort.
Device Deficie ncies
A de vice deficie nc y  is a n i na de q uac y of a me dical de vice wit h res pect t o its i de ntit y, q ualit y, 
d ura bilit y, relia bilit y, safet y, or perf or ma nce. T his defi niti o n i ncl u des malf u ncti o ns, use 
err ors, a n d i na de q uate la beli n g. Malf u ncti o n is defi ne d as a fail ure of a me dical de vice t o 
perf or m i n acc or da nce wit h its i nte n de d p ur p ose w he n use d i n acc or da nce wit h t he 
i nstr ucti o ns f or use or cli nical i n vesti gati o n pla n. Use err or is defi ne d as a n act or o missi o n of 
a n act t hat res ults i n a differe nt me dical de vice res p o nse t ha n i nte n de d by ma n ufact urer or 
e x pecte d b y user; t his i ncl u des sli ps, la pses, a n d mista kes. A n u ne x pecte d p h y si ol o gical 
res p o nse of t he s u bject d oes n ot i n itself c o nstit ute a use err or.
A de vice deficie nc y  ma y or ma y n ot be ass ociate d wit h patie nt har m (ie, A D E or S A D E); 
h o we ver , n ot all A D Es or S A D Es are d ue t o a de vice deficie nc y. T he I n vesti gat or s h o ul d 
deter mi ne t he a p plica ble cate g or y  f or t he i de ntifie d or s us pect de vice deficie nc y a n d re p ort 
a n y patie nt har m se paratel y. E xa m ples of de vice deficie ncies i ncl u de t he f oll o wi n g:

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
As pirati o n/Irri gati o n f u ncti o nalit y  fail ure

Pa ge 5 2 of 7 5

Fail ure of press ure se ns or

I m pr o per use of visc oelastic

F o ots witc h n o n -f u ncti o ni n g

U nseale d de vice pac ka gi n g

S us pect pr o d uct c o nta mi nati o n 

Lac k of ef ficac y
1 3. 2
M o nit ori n g of A d verse E ve nts
At eac h visit, after t he s u bject has ha d t he o p p ort u nit y  t o s p o nta ne o usly me nti o n a n y 
pr o ble ms, t he I n vesti gat or s h o ul d i n q uire a b o ut A Es b y  as ki n g t he sta n dar d q uesti o ns:

“ Ha ve y o u ha d a n y healt h pr o ble ms si nce y o ur last trial visit?”

“ Ha ve t here bee n a n y c ha n ges i n t he me dici nes y o u ta ke si nce y o ur last trial vis it?”
A Es s h o ul d be re p orte d f or a n y cli nicall y rele va nt c ha n ge, i n t he o pi ni o n of t he I n vesti gat or , 
i n c o nc o mita nt me dicati o n(s) t hat is t he res ult of a n u nt o war d ( u nfa v ora ble a n d u ni nte n de d) 
c ha n ge i n a s u bject's me dica l healt h.
C ha n ges i n a n y pr ot oc ol -s pecific oc ular or s ys te mic para meter e val uate d d uri n g t he trial are 
t o be re vie we d by t he I n vesti gat or. I n a d diti o n, t he s u bject’s res p o nses t o a n y q uesti o n naire 
utilize d d uri n g t he trial are t o be re vie we d b y t he I n vesti gat or. A n y u nt o war d ( u nfa v ora ble 
a n d u ni nte n de d) c ha n ge i n a pr ot oc ol -s pecific para meter or q uesti o n naire res p o nse t hat is 
cli nicall y rele va nt, i n t he o pi ni o n of t he In vesti gat or , is t o be re p orte d as a n A E. T hese 
cli nicall y rele va nt c ha n ges will be re p orte d re gar dless of ca usalit y.
1 3. 3
Pr oce d ur es f or Rec or di n g a n d Re p orti n g
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
All A Es m ust be d oc u me nte d o n t he A E e C R F b y  t he site a n d are m o nit ore d o n a r o uti ne 
basis b y  t he trial S p o ns or.
A Es are c ollecte d fr o m t he ti me of i nf or me d c o nse nt. A n y pre -e xisti n g me dical c o n diti o ns or 
s ym pt o ms prese nt i n a s u bject are n ot c o nsi dere d A Es i n t he trial.
A q ue o us cells a n d flare, c or neal e de ma, raise d I O P  a n d s u perficial p u nctate keratitis are 
e xa m ples of earl y p ost o perati ve fi n di n gs t hat are t y picall y o bser ve d f oll o wi n g oc ular s ur ger y . 
T hese are n ot c o nsi dere d A Es if t he y  ca n be reas o na bl y e x pecte d t o res ol ve wit hi n a wee k 
a n d n ot res ult i n a n y u nt o war d l o n g ter m vis ual o utc o me i m pact.

Pa ge 5 3 of 7 5
T he I n vesti gat or m ust pr o m ptl y  d oc u me nt all A D Es a n d S A Es wit h details i ncl u di n g t he date 
of occ urre nce, se verit y, treat me nt (if a p plica ble), o utc o me, a n d assess me nts of t he seri o us ness 
a n d ca usalit y. In a d diti o n, t he I n vesti gat or m ust pr o m ptl y  d oc u me nt all de vice deficie ncies o n 
t he Device Deficie ncy e C R F. T he site m ust s u b mit all a vaila ble i nf or mati o n o n A D Es, S A Es, 
a n d de vice d eficie ncies t o t he trial S p o ns or i m me diatel y  as f oll o ws:

A D Es or S A Es are d oc u me nte d o n t he A dverse Device Effect a n d Seri o us A dverse 
Eve nt e C R F wit hi n 2 4 h o urs of t he I n vesti gat or ’s or site’s a ware ness. 

De vice deficie ncies are d oc u me nte d o n t he Device De ficie ncy e C R F wit hi n 2 4 h o urs 
of t he I n vesti gat or ’s or site’s a ware ness. Please i ncl u de a pri nte d c o p y of t he 
c o m plete d De vice Deficie nc y e C R F wit h pr o d uct ret ur ns. 

A d diti o nal rele va nt i nf or mati o n after i nitial re p orti n g is t o be e ntere d i nt o t he e C R F as 
s o o n as t he data bec o me a vaila ble. 

D oc u me nt a n y c ha n ges t o c o nc o mita nt me dicati o ns o n t he a p pr o priate e C R Fs.

All rele va nt d oc u me ntati o n s uc h as Disc har ge S u m mar y , A ut o psy Re p ort, Certificate 
of Deat h , etc, s h o ul d be fa xe d t o t he trial S p o ns or at 
.
N ote: S h o ul d t he E D C syste m bec o me n o n- o per ati o n al, t he site m ust c o m plete t he 
a p pr o pri ate p a per A dverse Device Effect a n d Seri o us A dverse Eve nt F or m or Device 
Deficie ncy F or m. T he c o m plete d f or m is f axe d t o t he tri al S p o ns or at 
 wit hin 
2 4 h o urs of t he I nvesti g at or ’s or site’s a w are ness; h o wever, t he re p orte d i nf or m ati o n m ust be 
e ntere d i nt o t he E D C syste m o nce it bec o mes o per ati o n al.
S p o ns or  re prese nt ati ves a n d t heir c o nt act i nf or m ati o n are pro vi de d i n t he M O P t h at 
acc o m p a nies t his pr ot oc ol.
F urt her , de pe n di n g u p o n t he nat ure of t he A E or de vice deficie nc y  bei n g re p orte d, t he trial 
S p o ns or ma y  re q uest c o pies of a p plica ble p orti o ns of t he s u bject’s me dical rec or ds. T he 
I n vesti gat or m ust als o re p ort all A Es a n d de vice deficie ncies t hat c o ul d ha ve le d t o a S A D E 
acc or di n g t o t he re q uire me nts of re g ulat or y  a ut h orities or IR B/I E C.
I nte nsit y a n d C a us alit y Assess me nts
F or e ver y  AE i n t he trial, t he I n vesti gat or m ust assess t he ca usalit y ( Relate d or N ot Relate d t o 
t he me dical de vice or test proce d ure). A n assess me nt of ca usalit y will als o be perf or me d b y a 
trial S p o ns or p h ysicia n utilizi n g t he sa me defi niti o ns, as s h o w n bel o w:
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
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Related
Not 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 test procedure has not been demonstrated, but there is a 
reasonable possibility that the AE or device deficiency was caused by 
the medical device or test procedure.
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).
Where appropriate, the Investigator must assess the intensity (severity) of the AE as mild, 
moderate, or severe, based on medical judgment with consideration of any subjective 
symptom(s), as defined below: 
Intensity (Severity)
Mild
Moderate
Severe
An AE is mild if the subject is aware of but can easily tolerate the sign 
or symptom.
An AE is moderate if the sign or symptom results in discomfort 
significant enough to cause interference with the subject’s usual 
activities.
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.
13.4
Unmasking of the Trial Information
Subjects will be masked to the treatment for the study eye. The surgeon (Investigator) is not 
masked to the treatment. Site personnel not participating in surgery and not requiring 
knowledge of randomization will be masked to the extent possible (see section 7.2 Clinical 
trial design). 
Masked information on the identity of the assigned medical device should not be disclosed 
during the trial. If the treatment code needs to be broken in the interest of subject safety, the 
Investigator is encouraged to contact an appropriate trial Sponsor representative prior to 
unmasking the information if there is sufficient time. Dependent upon the individual 
circumstances (ie, medical emergency), the code may be broken prior to contact with the trial 
Sponsor. The trial Sponsor must be informed of all cases in which the code was broken and 
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of the circumstances involved. Additionally, the trial Sponsor may be required to unmask the 
information in order to fulfill expedited regulatory reporting requirements.
13.5
Follow-Up of Safety Information
The Investigator is responsible for adequate and safe medical care of subjects during the trial 
and for ensuring that appropriate medical care and relevant follow-up procedures are 
maintained after the trial. The Investigator should provide the trial 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. Any additional data from these follow-up 
procedures must be documented and available upon the trial Sponsor’s request.
Subjects with an ECD count of less than 1500 cells/mm2 and/or a decrease in ECD of 20% or 
more (in comparison to the screening visit value) at their 3 month visit, must return for a
safety follow-up visit approximately 6 months following the date of surgery. (Refer to 
Section 12.1.6). Subject data from the additional safety assessments at this visit will be 
captured in the electronic database, accordingly. 
13.6
Pregnancy in the Clinical Trial
Women of childbearing potential or women who are pregnant at the time of trial entry are not 
excluded from participation. Pregnancy should be included in the Medical History section of 
the eCRF when a pregnant woman enters the trial. If a woman becomes pregnant during the 
trial, this information should be documented. Pregnancy is not reportable as an AE; however, 
complications may be reportable and will be decided on a case-by-case basis. An Alcon 
prepared form will be utilized to capture all pregnancy-related information until birth of the 
child.
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1 4
D A T A  R E VI E W A N D H A N D LI N G
1 4. 1
C o m pleti o n of S o ur ce D oc u me nts a n d C ase Re p ort F or ms
T he nat ure a n d l ocati o n of all s o urce d oc u me nts will be i de ntifie d t o e ns ure t hat ori gi nal data 
re q uire d t o c o m plete t he e C R Fs e xist a n d are accessi ble f or verificati o n b y t he m o nit or. If 
electr o nic s o u rce rec or ds are mai ntai ne d, t hese rec or ds will be re vie we d f or 2 1 C F R Part 11 
c o m plia nce a n d t he met h o d of verificati o n will be deter mi ne d i n a d va nce of starti n g t he 
st u d y. Data re p orte d o n t he e C R Fs s hall be deri ve d fr o m s o urce d oc u me nt a n d be c o nsiste nt 
wit h s o urce d oc u me nt, a n d a n y  discre pa ncies s hall be e x plai ne d i n writi n g. At a mi ni m u m, 
s o urce d oc u me ntati o n s h o ul d i ncl u de t he f oll o wi n g i nf or mati o n f or eac h s u bject:

S u bject i de ntificati o n ( na me, se x)

D oc u me ntati o n of s u bject eli gi bilit y

Date of i nf or me d c o nse nt, a n d c o p y of si g ne d i nf or me d c o nse nt f or m

Dates of visits

D oc u me ntati o n t hat pr ot oc ol- s pecific pr oce d ures were perf or me d

Res ults of st u d y  testi n g, as re q uire d by t he pr ot oc ol

D oc u me ntati o n of A Es a n d ot her safet y para meters (as a p plica ble)

Rec or ds re gar di n g me dical hist ories a n d t he use of c o nc o mita nt t hera pies pri or t o a n d 
d uri n g t he st u d y

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
Date of st u d y c o m pleti o n a n d reas o n f or earl y disc o nti n uati o n (if a p plica ble)
It is re q uire d t hat t he a ut h or of eac h e ntr y i n t he s o urce d oc u me nts be i de ntifia ble (e g, i nitials 
or si g nat ure a n d date). A n y  c ha n ge or c orrecti o n t o data re p orte d i n t he s o urce, or o n an
e C R F, s hall be date d, i nitiale d, a n d e x plai ne d if necessar y. C ha n ges s hall n ot o bsc ure t he 
ori gi nal e ntr y  (ie, a n a u dit trail s hall be mai ntai ne d). Direct access t o s o urce d oc u me ntati o n 
( me dical rec or ds) m ust be all o we d f or t he p ur p ose of verif yi n g t hat t he data rec or de d o n t he 
e C R F are c o nsiste nt wit h t he ori gi nal s o urce data. 
E D C will be desi g nate d f or data c ollecti o n a n d s h o ul d be c o m plete d b y  desi g nate d 
i n di vi d uals o nl y. Re q uire d e xa mi nati o ns m ust be rec or de d o n t he e C R Fs. All data re p orte d 
will ha ve c orres p o n di n g e ntries i n t he s o urce d oc u me nts. T he I n vesti gat or will re vie w t he 
re p orte d data a n d certif y t hat t he e C R Fs are acc urate a n d c o m plete as i n dicate d b y si g nat ure. 
N o s u bject i de ntifiers s h o ul d be rec or de d o n t he e C R Fs be y o n d s u bject n u m ber , 
de m o gra p hics i nf or mati o n, a n d/ or ot her st u d y i de ntifiers.

Page 57 of 75
Deviations from this protocol, regulatory requirements and Good Clinical Practice (GCP) 
must be recorded in the study records. An explanation of the deviation should be included, as 
applicable. In addition, corrective and preventive action should be identified, implemented, 
and documented within the study records.
14.2
Data Review and Clarifications
Upon completion of the eCRFs, the data will be reviewed by Alcon study personnel for 
accuracy and completeness. If corrections and/or any additions to the data are deemed 
necessary, queries will be generated by Alcon data management or the site management 
(study monitor) team and forwarded to the investigative site. Staff at each site is expected to 
respond to data queries in a timely manner and ensure that the corrections and changes made 
to the data in the EDC system are reflected in the subjects’ source documentation. In addition, 
prior to study start (first subject first visit) a plan for data validation will be completed by 
Alcon Clinical Data Management and agreed upon by members of the Clinical Trial 
Management (CTM) team.
Concomitant medications entered into the database will be coded using the current version of 
the WHO Drug Reference List. Medical history and adverse events will be coded using the 
medical dictionary for regulatory activities (MedDRA) terminology.
Upon completion of the study and once the database is declared completed and accurate, the 
database will be locked and data will be available for data analysis. Any changes to the 
database after lock will be implemented upon agreement between Alcon’s clinical trial 
management and biostatistics department, and will be completed following Alcon’s 
procedures for changes to a database after database lock.
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15
ANALYSIS PLAN
15.1
Subject Evaluability
The final subject evaluability will be determined prior to locking the database.
15.2
Analysis Data Sets
Three analysis sets will be defined: Safety, Intention-to-Treat (ITT) and Per-Protocol (PP).
15.2.1
Safety analysis set
Safety analyses will be conducted using the safety analysis set on a treatment-emergent basis. 
The Safety data set will include all subjects/eyes exposed to any study procedures evaluated 
in this study. 
Safety data is to be collected for each subject beginning at the time of informed consent. 
Should any AEs occur prior to any study procedures these AEs will be presented separately 
from those treatment-emergent AEs considered in the safety analysis.
15.2.2
Intention-to-Treat (ITT) Analysis Set
The ITT set will include all subjects will include all subjects who are randomized in the study 
and receive treatment. The ITT set will be the primary analysis set for efficacy.
15.2.3
Per-Protocol (PP) Analysis Set
The PP set is a subset of ITT which excludes those who meet the critical deviation criteria as 
specified in the Deviations and Evaluability Plan. Supportive analysis of the primary and 
secondary endpoints will be conducted using the PP set if the number of subjects excluded 
from PP exceeds 5% of the ITT.
15.3
Demographics and Baseline Characteristics
Demographic information (age, sex, ethnicity, and race) and baseline characteristics will be 
summarized overall and by procedure group, on both Safety and ITT datasets.
Baseline Characteristics descriptive statistics for the crystalline lens assessment LOCS II 
scores, ECD and 
 will be presented by procedure group and overall. 
A listing showing the baseline crystalline lens assessment LOCS II scores will be provided.
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15.4
Performance Analyses
15.4.1
Primary Performance
The primary endpoint is Cumulative Dissipated Energy (CDE).
15.4.1.1
Statistical Hypotheses
The null and alternative hypotheses for the primary analysis are:
Ho: µcenturion_Bal CDE ≥ µlnfiniti_MFK CDE
HA: µcenturion_Bal CDE < µlnfiniti_MFK CDE
µcenturion_Bal CDE and µlnfiniti_MFK CDE are the true mean values of the primary endpoint, CDE 
under Centurion® with the Balanced Tip, and Infiniti® with the Mini Flared Kelman (MFK) 
tip, respectively.
15.4.1.2
Analysis Methods
The difference of CDE between two groups will be examined by using ANCOVA adjusting 
for site and baseline opacity grade. Display of ANCOVA results in summary tables will 
contain difference between LS means, a one- sided p- value < 0.05 will conclude superiority 
of Centurion® over Infiniti® group.
15.4.2
Secondary Performance
The secondary endpoints are CDE and BSS fluid used.
15.4.2.1
Statistical Hypotheses
The null and alternative hypotheses for the secondary analyses are:
Secondary hypotheses 1
Ho: µcenturion_Bal CDE ≥ µcenturion _MFK CDE
HA: µcenturion_Bal CDE < µcenturion _MFK CDE
Where µcenturion_Bal CDE and µcenturion_MFK CDE are the true mean values of the secondary 
endpoint, CDE under Centurion® with the Balanced Tip, and Centurion® with the Mini Flared 
Kelman (MFK) tip, respectively.
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Secondary hypotheses 2
Ho: µcenturion_Bal BSS ≥ µlnfiniti _MFK BSS
HA: µcenturion_Bal BSS < µlnfiniti _MFK BSS
Where µcenturion_Bal BSS and µlnfiniti _MFK BSS are the true mean values of the secondary endpoint, 
BSS under Centurion® with the Balanced Tip, and Infiniti® with the Mini Flared Kelman 
(MFK) tip, respectively.
Secondary hypotheses 3
Ho: µcenturion_MFK BSS ≥ µlnfiniti _MFK BSS
HA: µcenturion_MFK BSS < µlnfiniti _MFK BSS
Where µcenturion_MFK BSS and µlnfiniti _MFK BSS are the true mean values of the secondary 
endpoint, BSS under Centurion® with the Mini Flared Kelman (MFK) Tip, and Infiniti® with 
the Mini Flared Kelman tip, respectively.
Secondary hypotheses 4
Ho: µcenturion_MFK CDE ≥ µlnfiniti _MFK CDE
HA: µcenturion_MFK CDE < µlnfiniti _MFK CDE
Where µcenturion_MFK CDE and µlnfiniti _MFK CDE are the true mean values of the secondary 
endpoint, CDE under Centurion® with the Mini Flared Kelman (MFK) Tip, and Infiniti® with 
the Mini Flared Kelman tip, respectively.
15.4.2.2
Analysis Methods
The difference between two groups will be examined by using ANCOVA adjusting for site 
and baseline opacity grade. Display of ANCOVA results in summary tables will contain 
difference between LS Means, a one-sided p-value < 0.05 will conclude superiority.
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Pa ge 6 1 of 7 5
1 5. 4. 3. 1
A n al ysis Met h o ds
Descri pti ve statistics will be dis pla ye d f or t he s u p p orti ve e n d p oi nts. T he varia bles will be 
s u m marize d b y pr oce d ure gr o u p, wit h n, mea n, me dia n, sta n dar d de viati on [ S D], mi ni m u m 
a n d ma xi m u m f or c o nti n u o us varia bles, a n d c o u nts a n d perce nta ges f or cate g orical varia bles.
1 5. 5
H a n dli n g of Missi n g D at a
N o i m p utati o n tec h ni q ue will be perf or me d f or missi n g val ues.
1 5. 6  
M ulti plicit y
A se q ue ntial (cl ose d) testi n g pr oce d ure will be use d t o c o ntr ol t y pe I err or rate d ue t o 
m ulti plicit y  f or pri mar y a n d sec o n dar y e n d p oi nts at o ne-si de d 0. 0 5 si g nifica nce le vel.
1 5. 7
S afet y A n al ysis
T he safet y e n d p oi nts are:

A d verse E ve nts (i ncl u di n g S SI s)

Slit -la m p e xa mi nati o n

A nteri or c ha m ber cells

A nteri or c ha m ber flare

C or neal e de ma

A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
E n d ot helial cell c o u nt

Pa ge 6 2 of 7 5

Dilate d f u n d us e xa mi nati o n

B C D V A

I O P

Pr o ble ms d uri n g s ur ger y

I OL place me nt

De vice deficie ncies
A nal y sis of t he safet y e n d p oi nts will i ncl u de descri pti ve statistics f or eac h para meter b y 
pr oce d ure gr o u p. De scri pti ve statistics ge nerate d f or safety para meters will be base d u p o n t he 
t ype of para meter (ie, w het her t he data are cate g orical or c o nti n u o us) bei n g a nal yz e d. F or 
cate g orical para meters, t he statistics use d t o s u m marize t he data descri pti vel y  will i nclu de 
sa m ple size, n u m ber i n t he cate g or y a n d perce nt i n t he cate g or y. F or c o nti n u o us para meters, 
sa m ple size, mea n, me dia n, sta n dar d de viati o n, mi ni m u m a n d ma xi m u m will be prese nte d.
Listi n gs descri bi n g details of a d verse e ve nts will be pr o vi de d. Listi n gs d escri bi n g details of 
a d verse e ve nts re p orte d pri or t o t he s ur ger y will be prese nte d se paratel y fr o m t he safet y 
a nal ys is.
A Es will be c o de d b y Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A). C o u nts a n d 
perce nta ges of s pecific A Es will be prese nte d b y S y ste m Or ga n Class ( S O C) a n d Preferre d 
Te r m ( P T). Relate d ness a n d se verity will be prese nte d f or eac h A E e ntr y . A Es will be 
classifie d as oc ular a n d n o n- oc ular , treat me nt-e mer ge nt a n d n o n -treat me nt-e mer ge nt. All A Es 
a n d D Ds will be liste d.
1 5. 8
I nteri m A n al yse s
N ot a p plica ble.
1 5. 9
A d a pti ve St u d y Desi g n
N ot a p plica ble.
1 5. 1 0
S a m ple Size J ustific ati o n
A lc o n - B usi ness Use O nl y  
 
Effecti ve D ate:  
D oc u me nt:  
Versi o n:  
St at us:  E f f e c t i v e
Pri nte d B y:  
Pri nt Date:  
2 . 0 ;  E f f e c t i v e ;  C U R R E N T
T D O C - 0 0 5 0 1 7 6
P r o t o c o l  -  C l i n i c a l
1 8-J ul- 2 0 1 6
Base d o n pre vi o us st u dies, a sa m ple size of 5 3 i n eac h gr o u p will ha ve 8 0 % p o wer t o detect a 
dif fere nce i n mea ns of -7. 4 (t he dif fere nce bet wee n a Gr o u p 1 mea n of 3 8. 5 a n d a Gr o u p 2 
mea n of 4 5. 9).

Page 63 of 75
Assuming that the common standard deviation is 15.2 using a two group t-test with a 0.05 
one-sided significance level.
Assuming a 10% dropout rate, 59 subjects per group (up to 177 in total) will be randomized.
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16
ADMINISTRATIVE PROCEDURES
16.1
Regulatory and Ethical Compliance
This clinical trial will be conducted in accordance with the principles of the Declaration of 
Helsinki, and in compliance with ISO 14155:2011 Clinical investigation of medical device 
for human subjects, GCP, the Code of Federal Regulations (CFR), Alcon’s Standard 
Operating Procedures (SOPs), and all other applicable regulations. The Investigator and all 
clinical trial staff will conduct the clinical trial in compliance with this protocol. The 
Investigator will ensure that all personnel involved in the conduct of the clinical trial are 
qualified to perform their assigned duties through relevant education, training, and 
experience.
16.2
Informed Consent Procedures
Voluntary informed consent will be obtained from every subject (and/or legal representative, 
as applicable) prior to the initiation of any screening or other clinical trial-related procedures. 
The Investigator must have a defined process for obtaining consent. Specifically, the 
Investigator, or designee, will explain the clinical trial 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 will provide subjects with 
information regarding the purpose, procedures, requirements, and restrictions of the clinical 
trial, along with any known risks and potential benefits associated with the investigational 
product, the available compensation, and the established provisions for maintaining 
confidentiality of personal, protected health information. Subjects will be told about the 
voluntary nature of participation in the clinical trial and will be provided with contact 
information for the appropriate individuals should questions or concerns arise during the 
clinical trial. The subject also will be told that their records may be accessed by appropriate 
authorities and Sponsor-designated personnel. The Investigator must keep the original, signed 
copy of the consent and must provide a duplicate copy to each subject.
16.3
Responsibilities of the Investigator and IRB/IEC
Before clinical trial initiation, this protocol, the informed consent form (and assent form, if 
applicable), any other written information provided to subject, and any advertisements 
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planned for subject recruitment must be approved by an Institutional Review Board / 
Independent Ethics Committee (IRB/IEC). A master list of IRBs/IECs for this clinical trial 
can be found in the Trial Mater File. The Investigator must provide documentation of 
IRB/IEC approval to the Sponsor. The approval must be dated and must identify the 
applicable protocol, amendments (if any), informed consent form, assent form (if any), all 
applicable recruiting materials, written information for subjects, and subject compensation 
programs. The IRB/IEC must be provided with a copy of the Investigator’s Brochure, any 
periodic safety updates, and all other information as required by local regulation and/or the 
IRB/IEC. At the end of the clinical trial or in the case of early termination, the Investigator 
will notify the IRB/IEC of the clinical trial’s final status. Finally, the Investigator will report 
to the IRB/IEC on the progress of the clinical trial at intervals stipulated by the IRB/IEC.
16.4
Sponsor and Monitoring Responsibilities
The Sponsor will designate a monitor to conduct the appropriate site visits at the appropriate 
intervals. The clinical investigation will be monitored to ensure that the rights and wellbeing 
of the subjects are protected; the reported data are accurate, complete, and verifiable from the 
source documents; and the study is conducted in compliance with current approved protocol 
(and amendment[s], if applicable), with current GCP, and with applicable regulatory 
requirements.
All sites will have a site initiation. Monitoring will be conducted periodically while the 
clinical study is ongoing. Monitoring methods may include site visits, telephone, written, and 
fax correspondence. The Global Clinical Site Management (GCSM) personnel and/or the 
assigned Clinical Monitor will contact each site at appropriate intervals. The GCSM 
representative will determine the frequency of site visits. Close-out visits will take place after 
the last visit of the last subject. The Sponsor reserves the right to attend surgeries and/or 
subject examinations where required for investigative site training and/or education.
Enrollment will be tracked and reported at regular intervals. Details regarding enrollment (eg, 
number of subjects pre-screened, screened, reasons for screen failures) may be requested of 
the investigative site and should be within a reasonable time period.
The Sponsor will be responsible for implementing and maintaining quality assurance and 
quality control systems to ensure the study is conducted and data are generated, documented 
and reported in compliance with the protocol, GCP and applicable regulatory requirements. 
The Sponsor will secure agreement from all involved parties to ensure direct access to all 
study related sites, source data and documents, and reports for the purpose of monitoring and 
auditing by the Sponsor, and inspection by domestic and foreign regulatory authorities.
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Quality control will be applied to each stage of data handling to ensure that all data are 
reliable and have been processed correctly. Agreements made by the Sponsor with the 
Investigator/Institution and any other parties involved in the clinical study will be provided in 
writing as part of the protocol or as a separate agreement.
16.5
Regulatory Documentation and Records Retention
The Investigator is accountable for the integrity, retention, and security of all study related 
data. The Investigator must maintain accurate, complete, and current records relating to the 
clinical study. The Investigator must maintain the required records during the investigation 
and for a period of time specified by local law or per the Clinical Study Agreement, 
whichever is longer. If the Investigator retires, relocates, or for any other reason withdraws 
from responsibility of keeping the study records, the Sponsor must be notified and suitable 
arrangements made for retention of study records and source documents needed to comply 
with national and international regulations.
16.6
Publication of the Clinical Trial
Any information other than that which is disclosed upon registration should not be discussed 
with persons outside the study. The protocol, study data, and information related to the study 
or to Alcon’s products or research programs that is provided by Alcon (Confidential 
Information) is to be kept confidential, and not disclosed directly or indirectly to any third 
party other than those involved in the study who has a need to know.
All data and discoveries arising out of the study, patentable or non-patentable, shall be the 
sole property of Alcon, Inc. Alcon reserves the right of prior review of any publication or 
presentation of information related to the study. Alcon may use these data now and in the 
future for presentation or publication at Alcon’s discretion or for submission to government 
regulatory agencies.
The existence of this clinical study is confidential and should not be discussed with persons 
outside of the study. You shall hold confidential, and not disclose directly or indirectly to any 
third party other than those persons involved in the study who have a need to know, the 
protocol, the data arising out of the study, and any other information related to the study or to 
Alcon’s products or a research program that is provided by Alcon to you (the “Confidential 
Information”). All such persons must be instructed not to further disseminate this information 
to others. You shall not use the Confidential Information for any purpose other than the study. 
The foregoing obligations of confidence and non-use assumed by you shall not apply to: (a) 
information which at the time of disclosure is in the public domain; (b) information which 
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thereafter lawfully becomes part of the public domain other than through disclosure by or 
through you; (c) information which, as evidenced by your written records, was known by you 
prior to Alcon’s disclosure; (d) information which is lawfully disclosed to you by a third party 
not under any obligation of confidence to Alcon; or (e) information which is required to be 
disclosed by law or government regulatory agency, provided reasonable advance notice of 
such disclosure is given to Alcon.
In signing this protocol, you agree to the release of the data from this study and acknowledge 
the above confidentiality and publication policy. The provisions of this Statement shall 
survive the completion of the study.
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17
REFERENCES
Liu Y, Zeng M, Liu X, Luo L, Xia Y, Zeng Y. Torsional mode versus conventional ultrasound 
mode phacoemulsification: Randomized comparative clinical study. J Cataract Refract Surg.
2007;33(2):287-92.
Rekas M, Montes-Mico R, Krix-Jachym K, Klus A, Stankiewicz A, Ferrer-Blasco T. 
Comparison of torsional and longitudinal modes using phacoemulsification parameters. J 
Cataract Refract Surg. 2009;35(10):1719-24.
Vasavada AR, Raj SM, Patel U, Vasavada V, Vasavada V. Comparison of torsional and 
microburst longitudinal phacoemulsification: a prospective, randomized, masked clinical 
trial. Ophthalmic Surg Lasers Imaging. 2010;41(1):109-14.
Wang Y, Xia Y, Zeng M, Liu X, Luo L, et al. Torsional ultrasound efficiency under different 
vacuum levels in different degrees of nuclear cataract. J Cataract Refract Surg.
2009;35(11):1941-5.
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18
APPENDICES
Attachment follows.
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Date/Time 
(mm/dd/yyyy GMT):
Signed by:
Justification:
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