Next Generation Cataract and Vitreoretinal Surgery Study
Phase: NA
Conditions: Vitreoretinal Disease With or Without Cataracts
Sponsor: Alcon Research

 
 
 
 
 
Next Generation Cataract and Vitreoretinal Surgery Study 
 
 
STUDY ID  
CTV678-E001 
 
 
PROTOCOL 
 
 
NCT06165744 
 

Document ID: 
V-CLN-0179892 
Status: Approved, Version: 2.0 
Approved Date: 04 Feb 2024 
Page 1 of 61 
 
Alcon – Business Use Only 
 
 
 
 
Device Protocol for CTV678-E001 
Title: Next Generation Cataract and Vitreoretinal Surgery Study 
Protocol Number: 
CTV678-E001 
Clinical Investigation 
Type:  
Traditional Feasibility 
Test Product: 
UNITY™ Vitreoretinal Cataract System (VCS) 
Sponsor Name and 
Address: 
Alcon Research, LLC, and its affiliates (“Alcon”) 
6201 South Freeway 
Fort Worth, Texas 76134-2099 
 
 
 
 
 
 
 
 
 
 
Property of Alcon 
Confidential 
May not be used, divulged, published, or otherwise disclosed without the consent of Alcon 

Document ID: 
V-CLN-0179892 
Status: Approved, Version: 2.0 
Approved Date: 04 Feb 2024 
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Investigator Agreement: 
• 
I have read the clinical study described herein, recognize its confidentiality, and agree 
to conduct the described trial in compliance with Good Clinical Practices; applicable 
international and national regulations, laws, guidelines, and standards; the conditions 
of approval imposed by the reviewing IRB or regulatory authority; and in accordance 
with the ethical medical research principles outlined in the Declaration of Helsinki.  
• 
I will supervise all testing of the device involving human subjects and ensure that the 
requirements relating to obtaining informed consent and IRB review and approval are 
met in accordance with applicable local and governmental regulations. 
• 
I have read and understand the appropriate use of the investigational product(s) as 
described in the protocol, current investigator’s brochure, product information, or 
other sources provided by the sponsor. 
• 
I understand the potential risks and side effects of the investigational product(s). 
• 
I agree to maintain adequate and accurate records in accordance with government 
regulations and to make those records available for inspection. 
• 
I agree to comply with all other requirements regarding the obligations of clinical 
investigators and all other pertinent requirements of the sponsor and government 
agencies. 
• 
I agree to ensure that all associates, colleagues, and employees assisting in the 
conduct of the study are informed of their obligations in meeting the above 
commitments. 
Have you ever been disqualified as an investigator by any Regulatory Authority? 
 No        Yes 
Have you ever been involved in a study or other research that was terminated? 
 No        Yes 
If yes, please explain here: 
Principal investigator: 
 
Signature 
 
 
 
 
 
Date 
Name and professional 
position: 
 
Address: 
Phone Number:  
Off-hours Emergency 
Phone Number: 
 
 
 

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Table of Contents 
Device Protocol for CTV678-E001 ........................................................................................... 1 
Table of Contents ....................................................................................................................... 3 
List of Tables .............................................................................................................................. 6 
List of Figures ............................................................................................................................ 6 
1 
GLOSSARY OF TERMS .................................................................................................... 7 
2 
LIST OF ACRONYMS AND ABBREVIATIONS ........................................................... 12 
3 
PROTOCOL SUMMARY ................................................................................................. 14 
4 
PROTOCOL AMENDMENTS ......................................................................................... 21 
5 
INTRODUCTION ............................................................................................................. 21 
5.1 
Rationale and Background ................................................................................. 21 
5.2 
Purpose of the Study .......................................................................................... 23 
5.3 
Risks and Benefits ............................................................................................. 24 
6 
STUDY OBJECTIVES...................................................................................................... 26 
6.1 
Primary Objective(s) .......................................................................................... 26 
6.2 
Secondary Objective(s) ...................................................................................... 26 
 
 
6.4 
Safety Objective(s) ............................................................................................ 27 
7 
INVESTIGATIONAL PLAN ............................................................................................ 27 
7.1 
Study Design...................................................................................................... 27 
7.2 
Rationale for Study Design................................................................................ 27 
7.2.1 
Purpose and Timing of Interim Analyses and Resulting Design 
Adaptations ........................................................................................ 28 
7.3 
Rationale for Duration of Treatment/Follow-up ............................................... 28 
7.4 
Rationale for Choice of Comparator Product .................................................... 28 
7.5 
Data Monitoring Committee .............................................................................. 28 
8 
STUDY POPULATION .................................................................................................... 28 
8.1 
Inclusion Criteria ............................................................................................... 29 
8.2 
Exclusion Criteria .............................................................................................. 29 
8.3 
Rescreening of Subjects ..................................................................................... 30 
9 
TREATMENTS ADMINISTERED................................................................................... 30 

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9.1 
Investigational Product(s) .................................................................................. 30 
 
 
9.3 
Treatment Assignment/Randomization ............................................................. 34 
9.4 
Treatment Masking ............................................................................................ 34 
9.5 
Accountability Procedures ................................................................................. 34 
9.6 
Changes to Concomitant Medications, Treatments/Procedures ........................ 35 
10 STUDY PROCEDURES AND ASSESSMENTS ............................................................. 35 
10.1 Informed Consent and Screening ...................................................................... 36 
10.2 Description of Study Procedures and Assessments ........................................... 36 
10.2.1 
Demographics .................................................................................... 36 
10.2.2 
Medical and Ocular History .............................................................. 36 
10.2.3 
Adverse Event Collection: Safety Assessment .................................. 37 
10.2.4 
Slit Lamp Biomicroscopy: Safety Assessment .................................. 37 
10.2.5 
Device Deficiencies: Safety Assessment ........................................... 37 
10.2.6 
Dilated Fundus: Safety Assessment ................................................... 37 
10.2.7 
Best Corrected Distance Visual Acuity: Safety Assessment ............. 37 
10.2.8 
Intraocular Pressure: Safety Assessment ........................................... 38 
10.2.9 
Urine Pregnancy Test: Other Assessment .......................................... 38 
10.2.10 Keratometry: Eligibility Assessment ................................................. 38 
10.2.11 Pupil Size: Eligibility Assessment ..................................................... 38 
10.2.12 Biometry: Eligibility Assessment ...................................................... 38 
10.2.13 Total Time in the Eye: Secondary Performance Assessment ............ 38 
 
 
10.3 Unscheduled Visits ............................................................................................ 38 
10.4 Discontinued Subjects ....................................................................................... 40 
10.4.1 
Screen Failures .................................................................................. 40 
10.4.2 
Discontinuations ................................................................................ 40 
10.4.3 
Schedule of Procedures and Assessments for Subjects Discontinued 
from Investigational Product ............................................................. 41 
10.5 Clinical Study Termination ............................................................................... 41 
10.5.1 
Follow-up of Subjects after Study Participation has Ended .............. 41 
11 ADVERSE EVENTS AND DEVICE DEFICIENCIES ................................................... 41 
11.1 General Information .......................................................................................... 41 
11.2 Monitoring for Adverse Events ......................................................................... 44 

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11.3 Procedures for Recording and Reporting .......................................................... 44 
11.4 Return Product Analysis .................................................................................... 46 
11.5 Unmasking of the Study Treatment ................................................................... 47 
11.6 Follow-Up of Subjects with Adverse Events .................................................... 47 
11.7 Pregnancy in the Clinical Study ........................................................................ 47 
12 ANALYSIS PLAN ............................................................................................................ 47 
12.1 Subject Evaluability ........................................................................................... 47 
12.2 Analysis Sets...................................................................................................... 48 
12.2.1 
Full Analysis Set ................................................................................ 48 
12.2.2 
Safety Analysis Set ............................................................................ 48 
12.3 Demographic and Baseline Characteristics ....................................................... 48 
12.4 Effectiveness Analyses ...................................................................................... 48 
12.4.1 
Analysis of Primary Effectiveness Endpoint(s)................................. 48 
12.4.1.1 
Statistical Hypotheses ........................................................ 48 
12.4.1.2 
Analysis Methods............................................................... 48 
12.4.2 
Analysis of Secondary Effectiveness Endpoints ............................... 49 
12.4.2.1 
Statistical Hypotheses ........................................................ 49 
12.4.2.2 
Analysis Methods............................................................... 49 
12.5 Handling of Missing Data .................................................................................. 49 
12.6 Safety Analyses ................................................................................................. 50 
12.6.1 
Analysis of Primary Safety Endpoint(s) ............................................ 50 
12.7 Interim Analyses and Reporting ........................................................................ 51 
12.8 Sample Size Justification ................................................................................... 51 
13 DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS ............................... 51 
13.1 Subject Confidentiality ...................................................................................... 51 
13.2 Completion of Source Documents and Case Report Forms .............................. 51 
13.3 Data Review and Clarifications ......................................................................... 52 
13.4 Sponsor and Monitoring Responsibilities.......................................................... 52 
13.5 Regulatory Documentation and Records Retention .......................................... 54 
13.6 Quality Assurance and Quality Control ............................................................. 54 
14 ETHICS ............................................................................................................................. 54 
15 REFERENCES .................................................................................................................. 56 
15.1 Regulations and Standards................................................................................. 56 

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15.2 Scientific and Other References ........................................................................ 57 
 
 
List of Tables 
Table 2-1 
List of Acronyms and Abbreviations Used in This Protocol ............................. 12 
Table 3-1 
Schedule of Study Procedures and Assessments ............................................... 19 
Table 6-1 
Primary Objective(s) .......................................................................................... 26 
Table 6-2 
Safety Objective(s)............................................................................................. 27 
Table 9-1 
Test Product ....................................................................................................... 31 
 
List of Figures 
Figure 7-1 
Study Design Flow ............................................................................................. 27 
Figure 11-1 
Categorization of All Adverse Events ................................................................ 42 
 
 
 

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1 GLOSSARY OF TERMS 
Names of Test Product(s) 
Throughout this document, test product(s) will be referred to 
as the UNITY Vitreoretinal Cataract System (VCS). 
Name of Comparator 
Product(s) 
N/A 
Adverse Device Effect 
(ADE) 
 
Adverse event related to the use of an investigational 
medical device or comparator. 
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.  
Adverse Event (AE) 
 
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 or comparator 
and whether anticipated or unanticipated.  
Note: For subjects, this definition includes events related to 
the investigational medical device, comparator, or the 
procedures involved. For users or other persons, this 
definition is restricted to the use of the investigational 
medical device or comparator. 
Requirements for reporting adverse events in the study can 
be found in Section 11. 
Anticipated Serious 
Adverse Device Effect 
(ASADE) 
 
An effect which by its nature, incidence, severity, or 
outcome has been identified in the risk assessment. 
Clinical Investigation Plan 
(CIP) 
 
The document(s) stating the rationale, objectives, design, 
and prespecified analysis, methodology, organization, 
monitoring, conduct, and record-keeping of the clinical 

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investigation.  
Note: The protocol and other documents referenced in the 
protocol (for example, the statistical analysis plan, the 
manual of procedures, the deviations and evaluability plan, 
and the protocol monitoring plan) comprise the CIP. 
Clinical Investigation 
Report (CIR)/Clinical 
Study Report 
The document describing the design, execution, statistical 
analysis, and results of a clinical investigation. The clinical 
investigation report is synonymous with the clinical study 
report. 
Device Deficiency 
 
Inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, usability, safety, or 
performance.  
Note: This definition includes malfunctions, use errors, and 
inadequacy in the information supplied by the manufacturer 
including labelling related to the investigational medical 
device or the comparator. 
Requirements for reporting device deficiencies in the study 
can be found in Section 11. 
Enrolled Subject 
Any subject who signs an ICF for participation in the study. 
Point of Enrollment 
The time at which, following recruitment and before any 
clinical investigation-related procedures are undertaken, a 
subject signs and dates the informed consent form. 
Interventional Clinical Trial  A pre- or postmarket clinical investigation where the 
assignment of a subject to a particular medical device is 
decided in advance by a clinical investigation plan, or 
diagnostic or monitoring procedures requested in the CIP are 
in addition to those available as normal clinical practice and 
burden the subject. 
Investigational Product 
A preventative (vaccine), a therapeutic (drug or biologic), 
device, diagnostic, or palliative used as a test or comparator 
product in a clinical trial, including a product with a 

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marketing authorization when used or assembled 
(formulated or packaged) in a way different from the 
authorized form, or when used for an unauthorized 
indication, or when used to gain further information about 
the authorized form. 
Malfunction 
 
Failure of 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 (CIP), or investigator’s brochure (IB). 
Nonserious Adverse Event 
Adverse event that does not meet the criteria for a serious 
adverse event. 
Serious Adverse Device 
Effect (SADE) 
 
Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
Serious Adverse Event 
(SAE) 
 
Adverse event that led to any of the following:  
• Death. 
• A serious deterioration in the health of the subject, users 
or other persons as defined by one or more of the 
following:  
a) a life-threatening illness or injury   
Note: Life-threatening means that the individual was 
at immediate risk of death from the event as it 
occurred, i.e., it does not include an event which 
hypothetically might have caused death had it 
occurred in a more severe form. 
b) any potentially sight-threatening event or permanent 
impairment to a body structure or a body function 
including chronic diseases. 
c) inpatient hospitalization or prolonged 
hospitalization. 
d) a medical or surgical intervention to prevent a) or b). 
This includes any ocular secondary surgical 

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intervention excluding posterior capsulotomy. 
e) any indirect harm as a consequence of incorrect 
diagnostic test results when used within 
manufacturer’s instructions for use. 
• Fetal distress, fetal death, congenital abnormality or 
birth defect including physical or mental impairment. 
Note: Planned hospitalization for a preexisting condition, or 
a procedure required by the CIP, without serious 
deterioration in health, is not considered a serious adverse 
event.  
Refer to Section 11 for additional SAEs. 
Serious Health Threat 
 
Signal from any adverse event or device deficiency that 
indicates an imminent risk of death or a serious deterioration 
in the health in subjects, users, or other persons, and that 
requires prompt remedial action for other subjects, users, or 
other persons. 
Note: This would include events that are of significant and 
unexpected nature such that they become alarming as a 
potential serious health hazard or possibility of multiple 
deaths occurring at short intervals.  
Study Start 
The start of the study is considered to coincide with the 
enrollment of the first patient.  
Study Completion 
The completion of the study is considered to coincide with 
the study-level last subject last visit or the decision to 
terminate the trial, whichever is later. 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
 
Serious adverse device effect which by its nature, incidence, 
severity, or outcome has not been identified in the risk 
assessment.  
Use Error 
User action or lack of user action while using the medical 
device that leads to a different result than that intended by 

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the manufacturer or expected by the user.  
Note: 
a) Use error includes the inability of the user to 
complete a task. 
b) Use errors can result from a mismatch between the 
characteristics of the user, user interface, task, or 
use environment. 
c) Users might be aware or unaware that a use error 
has occurred. 
d) An unexpected physiological response of the patient 
is not by itself considered a use error. 
e) A malfunction of a medical device that causes an 
unexpected result is not considered a use error. 
Vulnerable Subject 
 
An individual who is unable to fully understand all aspects 
of the investigation that are relevant to the decision to 
participate, or who could be manipulated or unduly 
influenced as a result of a compromised position, 
expectation of benefits or fear of retaliatory response. 
 
 
 

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2 LIST OF ACRONYMS AND ABBREVIATIONS 
Table 2-1 
List of Acronyms and Abbreviations Used in This Protocol 
Abbreviation 
Definition 
ACD 
Anterior chamber depth 
ADE  
Adverse device effect 
AL 
Axial length 
AE 
Adverse event 
ASADE 
Anticipated serious adverse device effect 
AUS 
Australia 
BCDVA 
Best corrected distance visual acuity 
BSS 
Balanced salt solution 
C 
Celsius 
cc 
Cubic centimeter 
CDE 
Cumulative dissipated energy  
CFR 
Code of Federal Regulations 
CIP 
Clinical investigation plan 
CIR 
Clinical investigation report 
CRF 
Case report form 
cpm 
Cycle per minute 
CSR 
Clinical study report 
D 
Diopter 
ECCE 
Extracapsular cataract extraction  
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EU 
European union 
EUREQUO 
European Registry of Quality Outcomes for Cataract and Refractive 
Surgery  
F 
Fahrenheit 
FLACS 
Femtosecond laser-assisted cataract surgery  
FMS 
Fluid management system 
Frag 
Fragmentation 
GA 
Gauge 
GCP 
Good clinical practice 
HP 
Hand piece 
I/A 
Irrigation/aspiration 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
IEC 
Independent ethics committee 
IFC 
Illuminated flex curve 
IOL 
Intraocular lens 
IOP 
Intraocular pressure 
IP 
Investigational product 
IRB 
Institutional review board 

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Abbreviation 
Definition 
ISO 
International Organization for Standardization 
mL 
Milliliter 
mm 
millimeter 
mmHg 
Millimeters of Mercury 
MDR 
Medical device reporting 
MOP 
Manual of procedures 
N/A 
Not applicable 
N 
Number 
Nd:YAG 
Neodymium-doped yttrium aluminum garnet 
PCO 
Posterior capsule opacification 
Phaco 
Phacoemulsification 
Preop 
Preoperative 
Postop 
Postoperative 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SICS 
Small incision cataract surgery 
SLE 
Slit lamp examination 
SOC 
Standard of care 
SOP 
Standard operating procedure 
SSI 
Secondary surgical intervention 
TASS 
Toxic anterior segment syndrome 
USA 
United States of America 
USADE 
Unanticipated serious adverse device effect 
USV 
Unscheduled visit 
VA 
Visual acuity 
VCS 
Vitreoretinal Cataract System  
VFC 
Viscous Fluid Control 
WHO 
World Health Organization 
 
 

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3 PROTOCOL SUMMARY 
Investigational 
product type 
Device 
Study type 
Interventional, traditional feasibility  
Investigational 
products 
UNITY VCS consisting of: 
1. Console including remote control and foot controller 
2. UNITY Anterior Vitrectomy Kit 
3. UNITY TOTAL PLUS Combined Procedure Pack 
4. 25GA/27GA Entry System 
5. High Performance Viscous Fluid Control Pack 
6. 25GA/27GA TETRASPOT Multi-spot Laser Probe 
7. 27GA Illuminated Flexible Curved Laser Probe 
8. 27GA Chandelier 
9. 22GA Ozil Frag Pack 
10. Ozil Frag Handpiece 
For more details regarding IP, please see IB and MOP. 
Comparator Product: N/A 
Purpose and 
Scientific Rationale 
for the Study 
The purpose of this study is to obtain device-specific safety and 
performance clinical data to support marketability in Europe and 
to collect formal user feedback.  
Brief Summary of 
the Protocol 
This is a prospective, single arm, nonrandomized, multicenter 
study of adults with clinically documented diagnosis of 
vitreoretinal disease(s) with or without cataract and who meet the 
inclusion/exclusion criteria. 
Objective(s) 
The objective is to obtain device-specific safety and performance 
clinical data to support marketability in Europe and to collect 
formal user feedback. 
Endpoint(s)  
 
Primary Performance Endpoint 
• Percent of ‘yes’ responses to the binary question of: “Did 
UNITY VCS using vitreoretinal or combined surgical 
functionality perform per the intended use as defined in 
protocol Section 5.1?” 
 

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Secondary Performance Endpoints 
• Total time in the eye 
• Achievement of anatomical success at 3 months postop 
• Change in BCDVA at 3 months postop when compared to 
preop 
Safety Endpoints 
• Ocular and nonocular AEs and SAEs 
• Device deficiencies  
• Secondary surgical interventions 
• Unplanned intraoperative procedures 
Study Design 
This is a prospective, single arm, nonrandomized, unmasked, 
multicenter study.  
Subject population 
Adults ≥ 18 years requiring posterior segment surgery in the 
operating room with or without simultaneous cataract surgery. 

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Planned number of subjects enrolled/consented: Approximately 
120 subject eyes (unilateral subjects) 
Planned number of completed subjects: Approximately 100 
subject eyes (unilateral subjects) 
Sites and Locations 
Planned number of clinical sites: up to 8 sites 
Planned locations (initial list of locations, which may change 
during start up or conduct according to study needs): Australia 
and/or United States  
Key inclusion 
criteria 
(See Section 8.1 for a 
complete list of 
inclusion criteria) 
• Adults ≥ 18 years requiring posterior segment surgery in 
the operating room with or without simultaneous cataract 
surgery 
• Clear media except for cataract and vitreous hemorrhage 
• In simultaneous cataract and vitreoretinal surgery, eligible 
to undergo primary hydrophobic acrylic IOL implantation 
into the capsular bag 
• For those with planned simultaneous cataract and 
vitreoretinal surgery, keratometry of 41 to 46 D, anterior 
chamber depth of greater than 2.5 mm, and axial length of 
22 to 28 mm 
Key exclusion 
criteria 
(See Section 8.2 for a 
complete list of 
exclusion criteria) 
• Previous vitrectomy in the operative eye aside from those 
requiring silicone oil removal 
• Neovascular or uncontrolled glaucoma (IOP > 21 mmHg 
despite maximally tolerated medications/surgical 
interventions) 
• Preoperative hypotony (< 6 mmHg) 
• Planned glaucoma or postoperative surgeries during study 
aside from silicone oil removal (e.g., corneal refractive 
surgery) 
• Laser-assisted lens fragmentation 
• Inadequate pupil dilation (< 6 mm) 
• Unpredictable cases that would severely confound the 
results of the study per investigator’s clinical judgment 
(e.g., endophthalmitis, TASS, tumor, complex dislocated 
IOL, penetrating or severe ocular trauma such as globe 
rupture, zonular instability, pseudoexfoliation, use of 
systemic medications known to complicate surgery, Coat’s 
disease, Vogt-Koyanagi-Harada disease, or Bechet’s 
disease) 
 

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Data analysis and 
sample size 
justification 
The primary analysis set for effectiveness outcomes will be the full 
analysis set. The full analysis set includes all eyes with successful 
completion of surgery. The safety analysis set will include all eyes 
with attempted use of the UNITY VCS (successful or aborted after 
contact with the eye) and will be used for the safety outcomes. 
Attempted use of the UNITY VCS is defined as any time the 
device makes contact with the eye. 
There will be no hypothesis testing for any study outcome. All 
study outcomes will be presented as data listings or with summary 
statistics that are appropriate to the scale of the endpoint 
(continuous, dichotomous, etc.). 
Based on a sample of 100 surgeries, the expected half-width of the 
95% confidence interval for the percentage of surgeons reporting 
‘yes’ to the question “Did UNITY VCS using vitreoretinal or 
combined surgical functionality perform per the intended use as 
defined in protocol Section 5.1?" will be 1.96∙√(p(1-p)/100. This 
half-width is widest at p = 50%. Under this conservative 
assumption, the expected half-width is < 10% given the sample 
size of 100. 
Allow enrolment for an additional 10% for screen failure and 10% 
for loss to follow-up to ensure 100 completed subjects. 

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Table 3-1 
Schedule of Study Procedures and Assessments 
 
Nominal Time ± Window Limits 
 
 
Visit 0 
(Screening) 
Visit 00  
(Operative)  
Visit 1 
(1 Day) 
Visit 2 
(1 week) 
Visit 3 
(1 month) 
Visit 4/Exit 
(3 month) 
Early 
Exit3 
Unscheduled 
Visit 3 
Procedure/ Assessment 
Day -30 to 0  
Day 0  
Day 1 + 2 
Days  
Day 7 ± 3 
Days 
Day 30 ± 14 
Days 
Day 90 ±14 
Days   
N/A 
N/A 
Eye 
Both eyes 
Study eye 
Study eye 
Study eye 
Study eye 
Study eye 
Study 
eye 
Study eye 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
Urine Pregnancy Test2 
X 
 
 
 
 
 
 
 
Dilated Pupil Size 
X 
 
 
 
 
 
 
 
Keratometry* 
X 
 
 
 
 
 
 
 
Biometry (ACD, AL)* 
X 
 
 
 
 
 
 
 
Slit lamp exam 
X 
 
X 
X 
X 
X 
X 
 
Monocular BCDVA  
Using Snellen chartc 
X  
 
X a 
X a 
X  
X  
X  
 
IOP 
X 
 
X 
X 
X 
X 
X 
 
Dilated Fundus Exam 
X 
 
X b 
X 
X 
X 
X 
 
Total time in eye 
 
X 
 
 
 
 
 
 

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Nominal Time ± Window Limits 
 
 
Visit 0 
(Screening) 
Visit 00  
(Operative)  
Visit 1 
(1 Day) 
Visit 2 
(1 week) 
Visit 3 
(1 month) 
Visit 4/Exit 
(3 month) 
Early 
Exit3 
Unscheduled 
Visit 3 
Procedure/ Assessment 
Day -30 to 0  
Day 0  
Day 1 + 2 
Days  
Day 7 ± 3 
Days 
Day 30 ± 14 
Days 
Day 90 ±14 
Days   
N/A 
N/A 
Eye 
Both eyes 
Study eye 
Study eye 
Study eye 
Study eye 
Study eye 
Study 
eye 
Study eye 
User Questionnaire  
 
X 
 
 
 
 
 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
Device Deficiencies 
 
X 
 
 
 
 
 
 
 
2 Women of child-bearing potential only 
3 Unscheduled/Early Exit Visit – additional study assessments may be performed per investigator’s discretion 
 
ª Visual acuity (VA) to be conducted per site’s standard of care using Snellen chart 
 
c BCDVA is done using manifest refraction 
*As applicable 
 

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4 PROTOCOL AMENDMENTS 
Modification of the protocol is prohibited without prior written agreement in the form of a 
protocol amendment. All amendments must be created by the study sponsor and must be 
approved by the IRB/IEC and global and regional health authorities, as applicable, prior to 
implementation except when required to mitigate immediate safety risks or when the changes 
involve only logistical or administrative revisions.  
Amendments may necessitate that the informed consent and other study-related material be 
revised. If the consent form is revised, all subjects currently enrolled in the study must sign the 
approved, revised informed consent (re-consent), as required by the IRB/IEC. 
  
5 INTRODUCTION 
5.1 Rationale and Background 
To meet the demands of increasing number of cataract and vitreoretinal surgeries coupled with 
high patient expectations, ophthalmic surgeons desire the safest and most efficient device to 
remove the crystalline lens and complete vitreoretinal surgeries. The investigational device 
was developed to meet these needs by improving occlusion break surge responses, supporting 
smaller incision vitreoretinal surgeries, increasing vitrectomy cut speed, reducing scleral 
insertion force, improving instrument entry and tissue visualization while providing greater 
flow and IOP control as well as reducing phaco time and energy. 
The intended purpose of UNITY VCS, in general, is to facilitate management of fluid and 
gases, as well as removal, grasping, cutting, illumination, and coagulation of ocular materials. 
The target patient population for this study are those undergoing vitreoretinal surgery with or 
without simultaneous cataract surgery.  
Modern cataract procedures usually involve the use of an ultrasonic device that breaks up the 
crystalline lens (often cloudy) into small pieces, which are then gently removed from the eye 
with suction; this procedure is called phacoemulsification. Standard extracapsular cataract 
extraction (ECCE) and manual small incision cataract surgery (SICS) are other surgical 
methods that remove the cataract without an ultrasonic device. Phacoemulsification, or 
"phaco", is the surgical technique most often employed based on the European Registry of 
Quality Outcomes for Cataract and Refractive Surgery (EUREQUO) (Lundström 2012). 
Phacoemulsification is also the SOC based on guidelines from the American Academy of 
Ophthalmology (AAO 2016). Femtosecond laser-assisted cataract surgery (FLACS) uses a 

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femtosecond laser to create incisions, capsulotomies, and/or fragmentation patterns where only 
the laser fragmentation step assists in breaking up the cloudy lens into small pieces before 
removal, but the phacoemulsification machine would still be required to remove the lens. 
Vitreoretinal surgery had its beginnings in the 1970’s and has been improved with many 
technological advancements that make it a more predictable, safe, and effective procedure 
(Ribeiro 2022). Modern vitreoretinal surgeries performed in the operative room involve 
vitrectomy and subsequent interventions as needed per the presenting patient condition 
including, but not limited to, epiretinal membrane, macular hole, vitreous hemorrhage, floaters, 
dislocated lens, retinal detachment, and diabetic retinopathy. Vitrectomy involves the removal 
of the vitreous humor while replacing it with BSS. Depending on the patient condition, 
tamponades such as air, gas, or other viscous fluid may also be used after the vitrectomy. An 
intraocular light source is always needed for visualization of the posterior segment of the eye. 
Abnormal tissue including tractional fibrous bands can be grasped, cut, and released. 
Coagulation is often employed under different situations; diathermy is used to stop bleeding 
while photocoagulation is used to reduce retinal detachment or formation of new retinal blood 
vessels. Combined or sequential vitreoretinal and cataract surgery can be performed and the 
decision is often based on multiple factors such as cost, convenience, and outcomes (Daud 
2023). The intended clinical benefit of UNITY VCS is to aid in the execution of anterior and 
posterior segment ophthalmic surgery.  
According to the World Health Organization (WHO), cataract is one of the leading causes of 
visual impairment and blindness, impacting 94 million globally (WHO 2022). Visual 
impairment is expected to continue to increase due to population growth and aging (WHO 
2022). Cataract surgery is the only way to treat cataracts (NEI 2023). The most commonly 
performed ophthalmic procedure is cataract surgery (AAO 2023). While vitreoretinal surgery 
is less common than cataract surgery, surgical intervention is important in treating otherwise 
vision threatening posterior segment conditions. With improving diagnostics, an aging 
population and advances in ophthalmic surgical technology, the rate of patients requiring 
vitreoretinal surgeries is greatly increasing with one large study noting a 31% increase over 
approximately a decade (Wubben 2016). The advances in ophthalmic surgical technology in 
specific has been a big contributor to the increase in predictability of these procedures (Ribeiro 
2022). As such, this study is relevant as it aims to enhance equipment used to perform cataract 
and vitreoretinal surgery with the potential to benefit a very large patient population globally.  

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 Available alternative treatment options to UNITY VCS include other phacoemulsification and 
vitreoretinal systems. Cataract surgery is either performed manually or with a 
phacoemulsification system where only the latter uses ultrasound energy. Phacoemulsification 
is considered standard of care (AAO 2016) and is the preferred surgical technique in the 
majority of cases (Lundström 2012). While other interventions, such intravitreal injections, 
may be utilized, vitreoretinal surgery in the form of pars plana vitrectomy using a vitreoretinal 
machine remains a necessary step for many vitreoretinal conditions (Omari 2023).  
The CENTURION and CONSTELLATION Vision Systems, the predecessors to UNITY VCS, 
are the most utilized anterior and posterior segment ophthalmic surgical systems in the world 
(2022 Cataract Surgical Equipment Market Report and 2023 Retinal Surgical Device Market 
Report). The CENTURION Vision System is Alcon’s premium phacoemulsification system 
launched in 2013, with the addition of Active Sentry in 2019. The CONSTELLATION Vision 
System is Alcon’s combined cataract and vitreoretinal system first launched in 2008 with many 
technological advancements made throughout its history with most notable being IOP control 
in 2009 and 20K cuts per minute with HYPERVIT probe added in 2019. The UNITY VCS was 
designed to improve upon the latest iteration of the CENTURION and CONSTELLATION 
Vision Systems currently used successfully in the market. As such, the UNITY VCS is 
intended to provide greater benefits than the current standard of care.  
5.2 Purpose of the Study 
The study aims to:  
(1) Obtain device-specific safety and performance clinical data to support marketability in 
Europe 
(2) Collect formal user feedback  
At the end of the study, a clinical study report and lay summary, if applicable, will be prepared 
in accordance with applicable regulatory requirements and standards. The informed consent 
will specify that a lay summary, if applicable, will be made available after the study is 
completed.  
There are no immediate plans to submit the results of this traditional feasibility study for 
publication; however, the results may be offered for publication if they are of scientific 
interest, or if the results relate to a product that is subsequently approved or cleared for 
marketing. Alcon reserves the right of prior review of any publication or presentation of 
information related to the study. The author(s) of the publication will be the individual with 
substantial contribution to the conception or design of the work, OR the acquisition, analysis, 

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or interpretation of data. Additionally, the author will draft the work or revise it critically for 
important intellectual content; provide final approval of the version to be published; and agree 
to be accountable for all aspects of the work, ensuring that questions related to the accuracy or 
integrity of any part of the work are appropriately investigated and resolved. 
5.3 Risks and Benefits 
The intended clinical benefit of UNITY VCS is to aid in the execution of anterior and posterior 
segment ophthalmic surgery which include the removal of the opacified, cloudy crystalline 
lens and to manage vitreoretinal disease. In comparison with predecessor systems, the UNITY 
VCS provides enhancements that are designed to benefit patients. The UNITY VCS has many 
enhancements in key areas including fluidics, energy delivery, higher vitrectomy cut speed and 
allowing greater use of higher gauge sizes. Use of higher gauge sizes may reduce time to close 
incision, lower surgically induced astigmatism, provide quicker VA improvements, less change 
in IOP, decreased hypotony, and less need for sutures (
 Lubiński 
2020, and Saleh 2020). UNITY VCS innovations have made design enhancements to the 
illumination output, viscous fluid control as well as vitrectomy and laser probes to overcome 
some of the reduction in efficiency currently observed with smaller gauge vitreoretinal surgery 
(Lee 2023). Higher vitrectomy cut speed in both clinical and simulated settings may improve 
safety by reducing retinal traction and improve efficiency due to greater aspiration flow (Doi 
2023, Steel 2022). The fluidics enhancement was designed with the intent to allow improved 
control of flow for vitreous cutting and surgeons to operate at lower IOP and higher vacuum 
while maintaining chamber stability. In specific, operating at lower, more physiological IOP 
may be associated with greater reported patient comfort during surgery (Hou 2012), improved 
visual recovery due to better preservation of corneal endothelial health, and less macular 
edema postoperatively (Suzuki 2009, Chen 2012) as well as reduced complications due to less 
impact on retinal blood flow/reduction of ischemia (Findl 1997, Takhtaev 2019). The 
ultrasound energy enhancement was designed to improve crystalline lens cutting efficiency 
and reduce energy. The overall potential benefit would be a safer and more efficient procedure. 
The clinical investigation process risks are managed through appropriate training and 
monitoring according to the protocol-specific monitoring plan. 
 
 
 
  
Complications may occur on the surgery day or throughout the postop period. As with any type 
of intraocular surgery, there is a possibility of complications due to anesthesia, drug reactions, 
and/or surgical problems. The surgical procedure can exacerbate a preexisting ocular condition 

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and can also lead to potential procedure related postop adverse events. 
 
In addition, a secondary surgical intervention (SSI) may be required following the initial 
surgery. SSIs include, but are not limited to vitreous aspirations, iridectomy for pupillary 
block, wound leak repair, intracameral and intravitreal antibiotic injections, additional 
posterior segment surgery including retinal detachment repair, and pars plana vitrectomy. 
All the above-mentioned complications, adverse events, SSIs, and postoperative reported 
events have been reported because of the ophthalmic surgical procedures with use of a 
combined anterior and posterior segment surgical system. The UNITY VCS, the 
investigational device, is not expected to increase any harms or the likelihood of those harms 
when compared to predecessor devices. 
 
. Any risk to subjects in this clinical study will be minimized by 
compliance with the eligibility criteria and study procedures, and by clinical oversight and 
monitoring.  
The UNITY VCS is expected to provide greater benefits and no additional harms or likelihood 
of harms when compared to the widely and successfully marketed predecessor devices, the 
CENTURION and CONSTELLATION Vision Systems. As such, the expected benefits of 
using the UNITY VCS anterior and posterior segment functions are expected to outweigh the 
risks of ADEs for subjects that qualify for cataract surgery in this study. 
Refer to the IB for additional information. 

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6 STUDY OBJECTIVES 
6.1 Primary Objective(s) 
Table 6-1 
Primary Objective(s) 
Objective(s) 
Endpoint(s) 
Performance:  
To obtain device-specific performance 
clinical data and to collect user feedback 
Primary Performance Endpoint: 
Percent of ‘yes’ responses to the binary 
question of: “Did UNITY VCS using 
vitreoretinal or combined surgical 
functionality perform per the intended use 
as defined in protocol Section 5.1?” 
 
 
Secondary Performance Endpoints: 
1. Total time in the eye  
From first entry into eye/first trocar in, to 
incision closure/last trocar out 
2. Achievement of anatomical success at 3 
months postop 
Percent of ‘yes’ responses to the question 
“Was anatomical success achieved for 
intended treatment (ex: macular hole 
closure, retinal attachment, etc. as 
applicable for the patient’s condition)?” 
3. Change in BCDVA at 3 months postop 
when compared to preop 
 
 
 
6.2 Secondary Objective(s) 
Not Applicable 

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6.4 Safety Objective(s)  
Table 6-2 
Safety Objective(s) 
Objective(s) 
Endpoint(s) 
To obtain device-specific safety clinical 
data  
• Ocular and nonocular AEs and SAEs 
• Device deficiencies  
• Secondary surgical interventions 
• Unplanned intraoperative procedures 
7 INVESTIGATIONAL PLAN 
7.1 Study Design 
This is a prospective, single arm, nonrandomized and multicenter clinical study in Australia 
(AUS) and/or the United States of America (USA) with approximately a 3-month follow-up.  
Figure 7-1 
Study Design Flow 
 
 
7.2 Rationale for Study Design  
The UNITY VCS is a Class IIb nonimplantable medical device in the EU and AUS and a Class 
II nonimplantable medical device in the USA. For this class category, there are no currently 
well-established study designs governed by health authorities or international standards. The 
prospective design of this traditional feasibility study will reduce sources of bias and 
confounding variables. The intended patient population represents the majority of patients that 
will require use of the investigational device for posterior segment surgery in the operating 

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room with or without simultaneous cataract surgery.  The inclusion/exclusion criteria were 
carefully selected to reduce the likelihood of severely confounding the study outcomes.  
The study design was also carefully thought out to allow it to represent a real world setting to 
ensure minimal intervention to the site’s standard of care; this ensures the study gains the most 
realistic response regarding device performance and safety. 
 
 
 
 
A potential weakness of the current study design is the fact that it is a single arm study. 
However, this single arm design is justified given that there are well established data regarding 
safety and performance of vitreoretinal surgery as well as combined vitreoretinal and cataract 
surgery. As such, the safety and performance results from this study can be compared against 
this rich body of evidence to ensure the device meets state of the art standards. 
7.2.1 
Purpose and Timing of Interim Analyses and Resulting Design 
Adaptations 
Not applicable. There are currently no planned interim analyses. 
7.3 Rationale for Duration of Treatment/Follow-up 
The follow-up schedule was designed to allow collection of data at key time points that yield 
relevant performance and safety outcomes. The follow-up period will allow for adequate safety 
monitoring of adverse events; if patients develop complications, those will typically be present 
within approximately 1 month of cataract surgery and 3-months of vitreoretinal surgery. 
7.4 Rationale for Choice of Comparator Product 
There is no comparator in this study due to the nature of the study being a feasibility study. 
7.5 Data Monitoring Committee 
Not applicable 
8 STUDY POPULATION 
The study population will consist of male and female subjects (18 years or older) requiring 
posterior segment surgery in the operating room with or without simultaneous cataract surgery 
(unilaterally). It is aimed to enroll (consent) approximately 120 subjects in up to 8 sites in AUS 
and/or the USA with a target of 100 subjects treated, with approximately 10 to 40 subjects per 

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site. Site-specific targets may vary based upon individual site capabilities and each site may 
include more than one surgeon. Estimated time needed to recruit subjects for the study is 
approximately 3 months; however, unanticipated circumstances may shorten or lengthen this 
time and would not require amendment of this protocol. Because a 10% screening failure rate 
is expected and 10% for loss to follow-up, approximately 120 subjects are expected to be 
enrolled to ensure 100 completed subjects.  
8.1 Inclusion Criteria 
Written informed consent must be obtained before any study specific assessment is performed. 
Upon signing informed consent, the subject is considered enrolled in the study. 
Subjects eligible for inclusion in this study must fulfill all of the following criteria: 
1. Subject must be able to understand and sign an IRB/IEC approved informed consent 
form.  
2. Willing and able to attend all scheduled study visits as required per protocol. 
3. Adults ≥ 18 years requiring posterior segment surgery in the operating room without or 
with simultaneous cataract surgery 
4. Clear media except for cataract and vitreous hemorrhage 
5. In simultaneous cataract and vitreoretinal surgery, eligible to undergo primary 
hydrophobic acrylic IOL implantation into the capsular bag 
6. For those with planned simultaneous cataract and vitreoretinal surgery, keratometry of 
41 to 46 D  
7. For those with planned simultaneous cataract and vitreoretinal surgery, with following 
biometry, anterior chamber depth of greater than 2.5 mm, and axial length of 22 to 28 
mm 
8.2 Exclusion Criteria 
Subjects fulfilling any of the following criteria are not eligible for participation in this study. 
1. Women of childbearing potential, defined as all women who are physiologically capable 
of becoming pregnant and who are not postmenopausal for at least 1 year or are less 
than 6 weeks since sterilization, are excluded from participation if any of the following 
apply: 
a. they are currently pregnant, 

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b. have a positive urine pregnancy test result at Screening, 
c. intend to become pregnant during the study period, 
d. are breastfeeding. 
Subjects who become pregnant during the study will not be discontinued; however, data 
will be excluded from the effectiveness analyses because pregnancy can alter refraction and 
visual acuity results. 
2. Previous vitrectomy in the operative eye aside from those requiring silicone oil removal 
3. Neovascular or uncontrolled glaucoma (IOP > 21 mmHg despite maximally tolerated 
medications/surgical interventions 
4. Preop hypotony (<6 mmHg) 
5. Planned glaucoma or postoperative surgeries during study aside from silicone oil 
removal (e.g., corneal refractive surgery) 
6. Laser-assisted lens fragmentation 
7. Inadequate pupil dilation (< 6 mm) 
8. Unpredictable cases that would severely confound the results of the study per 
investigator’s clinical judgment (e.g., endophthalmitis, TASS, tumor, complex 
dislocated IOL, penetrating or severe ocular trauma such as globe rupture, zonular 
instability, pseudoexfoliation, use of systemic medications known to complicate surgery, 
Coat’s disease, Vogt-Koyanagi-Harada disease, or Bechet’s disease) 
9. Currently participating in another drug or device clinical trial, or having participated in 
another drug or device clinical trial within 30 days of enrolment into this study 
8.3 Rescreening of Subjects 
Rescreening of subjects is not allowed in this study. 
9 TREATMENTS ADMINISTERED 
9.1 Investigational Product(s) 
Test Product(s): 
UNITYTM Vitreoretinal Cataract System (VCS) 
Comparator Product(s) (If applicable): 
Not applicable 
 

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Table 9-1 
Test Product 
Test Product: 
UNITY VCS consisting of: 
1. Console including remote control and foot controller 
2. UNITY Anterior Vitrectomy Kit 
3. UNITY TOTAL PLUS Combined Procedure Pack 
4. 25GA/27GA Entry System 
5. High Performance Viscous Fluid Control Pack 
6. 25GA/27GA TETRASPOT Multi-spot Laser Probe 
7. 27GA Illuminated Flexible Curved Laser Probe 
8. 27GA Chandelier 
9. 22GA Ozil Frag Pack 
10. Ozil Frag Handpiece 
Manufacturer: 
Alcon Laboratories, Inc. 
6201 South Freeway 
Fort Worth, TX 76134 
USA 
Indication for use 
and intended 
purpose in the 
current study:  
Indications for Use 
The Unity VCS, consisting of the console and compatible devices, 
is indicated for use during anterior and posterior segment 
ophthalmic surgery.  
 
Intended Use 
The Unity VCS, consisting of the console and compatible devices, 
is intended to facilitate management of fluid and gases, as well 
as removal, grasping, cutting, illumination, and coagulation of 
ocular materials.  
Product description 
and parameters 
available for this 
study: 
The UNITY VCS in this study is a surgical instrument for use in 
anterior and posterior segment ophthalmic surgeries. The 
product’s capabilities include driving a variety of surgical 
instruments that provide the ability to facilitate management of 
fluid and gases, as well as removal, grasping, cutting, 
illumination, and coagulation of ocular materials. Full product 
parameters are available for the current study. 
Formulation: 
N/A 
Usage: 
UNITY VCS will be used as directed in the user manual.  
Packaging 
description: 
Each UNITY VCS console and all compatible investigational 
devices will be packaged individually and have an 
investigational product specific serial or lot number. 

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Labeling 
description: 
Investigational labeling regulations apply for: 
• UNITY VCS console 
• Remote control 
• Foot controller  
• UNITY Anterior Vitrectomy Kit 
• UNITY TOTAL PLUS Combined Procedure Pack 
• 25GA/27GA Entry System  
• High Performance Viscous Fluid Control Pack  
• 25GA/27GA TETRASPOT Multi-spot Laser Probe 
• 27GA Illuminated Flexible Curved Laser Probe  
• 27GA Chandelier  
• 22GA Ozil Frag Pack  
• Ozil Frag Handpiece  
 
These devices will be labeled appropriately (e.g., “CAUTION – 
Investigational device. Limited by Federal [or United States] law to 
investigational use” or “Exclusively for Clinical Investigation” or 
“For Clinical Trial Use Only”). Each unit will be identifiable via a 
serial or lot number. 
Training and/or 
experience 
requirements for 
device: 
UNITY VCS should only be used by ophthalmic surgeons and 
operating room staff. It should only be operated according to the 
operating instructions as listed in the associated manuals. 
 
Storage conditions: 
Temperature and humidity apply to room environmental conditions 
preceding and during device use. 
Temperature: 
• 
10 to 35°C (50 to 95°F) Operating 
• 
-10 to 55°C (14 to 131° F) Nonoperating 
 

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Relative humidity: 10% to 95% without condensation  
See user manual for complete requirements and instructions. 
Additional 
information: 
Not applicable 
 
Supply: 
UNITY VCS and compatible devices will be shipped to the site by 
the sponsor.  
 
Refer to the MOP for a detailed description. 
 
More information on the test product can be found in the IB and directions for use for UNITY 
VCS. 

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9.3 Treatment Assignment/Randomization 
Only after signing the ICF, a subject will be assigned a subject number by the electronic data 
capture system.  
All subjects who meet the inclusion/exclusion criteria and sign informed consent will undergo 
posterior segment surgery in without or with simultaneous cataract surgery with the UNITY 
VCS. Bias will be minimized as this is a single arm study.  If both eyes qualify for the study, 
the study eye will be determined per investigator’s discretion.  
There will be no randomization of subjects.  
9.4 Treatment Masking 
Not applicable as this is an open label, single arm study. 
9.5 Accountability Procedures 
Upon receipt of IPs, the investigator or delegate must conduct an inventory of equipment and 
accessories by serial or lot number, complete study-specific confirmation of receipt procedures 
as described in the MOP and retain any required documentation in the investigator’s clinical 
study records.  
Throughout the study, the investigator or delegate must maintain records of IP use for each 
subject. This record must be made available to the study monitor for the purposes of verifying 
the accounting of IP supplies. Any discrepancies and/or deficiencies between the observed 
disposition and the written account must be recorded along with an explanation.  
• 
All IPs sent to the investigator must be accounted for by study sponsor personnel, and in 
no case be used in an unauthorized manner. 

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• 
Refer to Section 11  for additional information on the reporting of device deficiencies 
and to the MOP for information on return of IPs associated with these events. 
The investigator is responsible for allowing de-installation of the provided UNITY VCS 
console, return of all unused devices, and proper discarding of all used devices as directed. 
Please refer to MOP for additional details.  
9.6 Changes to Concomitant Medications, Treatments/Procedures 
After the subject is enrolled into the study, the investigator must instruct the subject to notify 
the study site about: 
• 
Any new medications  
• 
Alterations in dose or dose schedules for current medications,  
• 
Any medical procedure or hospitalization that occurred or is planned 
• 
Any nondrug therapies (including physical therapy and blood transfusions).  
The investigator must document this information. 
10 STUDY PROCEDURES AND ASSESSMENTS 
Study assessments will be obtained prior to vitreoretinal with or without simultaneous cataract 
surgery with the UNITY VCS and postoperatively at the study visits outlined below: 
• 
Screening – Visit 0 (Day -30 to 0 prior to treatment) 
• 
Surgery – Visit 00 (Day 0) 
• 
1 Day – Visit 1 (Day 1 to 3) 
• 
1 Week – Visit 2 (Day 4 to 10) 
• 
1 Month – Visit 3 (Day 16 to 44) 
• 
3 Month/Exit – Visit 4 (Day 76 to 104) 
In addition to the scheduled visits listed above, the following visit may apply as needed: 
• 
USV (completed when a treated subject reports for additional follow-up) 
• 
Early Termination Visit (when subject would like to withdraw from the study 
participation) 
Clinical assessments to be obtained at study visits are outlined in 
 Schedule of Study 
Procedures and Assessments and are defined in the sections below.  

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10.1 Informed Consent and Screening 
The investigator or delegate must explain the purpose and nature of the study and have the 
subject read, sign, and date the IRB/IEC-approved informed consent document. The subject 
must sign the ICF BEFORE any study-specific procedures or assessments can be performed, 
including study-specific screening procedures. Additionally, have the individual obtaining 
consent from the subject and a witness, if applicable, sign and date the informed consent 
document.  
The investigator or delegate must provide a copy of the signed document to the subject and 
place the original signed document in the subject’s chart, or provide documentation as required 
by local regulations. 
If a patient has reported for routine vitrectomy and/or cataract screening, then data obtained 
from the routine evaluation can be used for screening data as long as protocol requirements for 
timeframe (within 30 days of surgery) and required details have been met. Routine 
vitreoretinal and/or cataract screening data include, but are not limited to SLE, IOP, dilated 
pupil size, keratometry, biometry (ACD, AL), Snellen BCDVA with manifest refraction, and 
dilated fundus exam. 
10.2 Description of Study Procedures and Assessments 
Study-specific procedures and assessments described here may include standard of care; other 
standard of care procedures performed in the clinical management of the subject are not 
excluded. 
Detailed descriptions of assessments and procedures are provided in the MOP. The investigator 
is responsible for ensuring responsibilities for all procedures and assessments are delegated to 
appropriately qualified site personnel. 
The enrollment on this study is competitive and once the target number of subjects is achieved, 
sponsor will close the enrollment. 
10.2.1 Demographics 
Obtain demographic information including age, race, ethnicity, and sex. 
10.2.2 Medical and Ocular History 
Collect medical history information, including information on all medications used within the 
past 30 days. Include herbal therapies, vitamins, and all over-the-counter as well as 

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prescription medications. Throughout the subject’s participation, obtain information on any 
changes in medical health and/or the use of concomitant medications. 
Medical history and concomitant medications will be collected in the eCRF as outlined in the 
MOP. 
10.2.3 Adverse Event Collection: Safety Assessment 
Assess and record any adverse events that are observed or reported since the previous visit, 
including those associated with changes in concomitant medication dosing. 
Note: AEs and device deficiencies must be recorded for all enrolled subjects from the time of 
signature of informed consent, regardless of subject enrollment status (screen failure or 
randomized). 
10.2.4 Slit Lamp Biomicroscopy: Safety Assessment 
SLE of the cornea, iris/anterior chamber and lens must be performed before instillation of any 
diagnostic eye drops. 
Refer to the MOP for grading scales for study specific assessments. 
10.2.5 Device Deficiencies: Safety Assessment 
Assess and record any device deficiencies that are reported or observed since the previous 
visit. Requirements for reporting device deficiencies in the study can be found in Section 11. 
Note: AEs and device deficiencies must be recorded for all enrolled subjects from the time of 
signature of informed consent, regardless of subject enrollment status (screen failure). 
10.2.6 Dilated Fundus: Safety Assessment 
Dilated fundus examination includes ophthalmoscopic assessments of the vitreous, retina, 
macula, choroid, and optic nerve. 
10.2.7 Best Corrected Distance Visual Acuity: Safety Assessment 
Snellen visual acuity testing with manifest refraction must be performed prior to any 
assessment requiring administration of eye drops to dilate the eye, or any assessment requiring 
contact with the eye.  

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10.2.8 Intraocular Pressure: Safety Assessment 
Intraocular pressure must be measured using SOC. 
10.2.9 Urine Pregnancy Test: Other Assessment 
A urine pregnancy test is required for female subjects of childbearing potential that are not 
postmenopausal or surgically sterile.  
10.2.10 Keratometry: Eligibility Assessment 
Capture keratometry measurements of the central cornea using SOC. This assessment is 
required only when subjects are undergoing cataract surgery. 
10.2.11 Pupil Size: Eligibility Assessment 
Measure dilated pupil size under photopic condition using SOC.  
10.2.12 Biometry: Eligibility Assessment 
Perform biometry using SOC. Document the following: ACD, AL. This assessment is required 
only when subjects are undergoing cataract surgery. 
10.2.13 Total Time in the Eye: Secondary Performance Assessment 
Obtain time from first entry into eye/first trocar into incision closure/last trocar out using a 
stopwatch. 
10.3 Unscheduled Visits 
An Unscheduled Visit (USV) is defined as follows: 

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• 
Ocular examination that is not SOC and not required by the protocol 
• 
Examination conducted by the study staff 
• 
New findings, or change to a previous finding was discovered 
If a subject visit occurs between any regularly scheduled visit and the visit is conducted by 
study personnel, this visit must be documented as an Unscheduled Visit. If the subject seeks 
medical attention outside the clinic (for example, at an emergency room) or at the clinic but is 
seen by non-study personnel, the investigator is to capture adverse event-related information 
on the adverse event form upon becoming aware. 
During all unscheduled visits, the investigator must conduct the following procedures:  
• 
Collect adverse event information, if applicable 
• 
Collect device deficiency information, if applicable 
• 
Collect SSI information, if applicable 
• 
Record changes in medical condition or concomitant medication 
The investigator may perform additional procedures for proper diagnosis and treatment of the 
subject. These include but are not limited to those noted in Table 3-1 Schedule of Study 
Procedures and Assessments. The investigator must document this information in the subject’s 
case history source documents. 
If during a USV the subject is discontinuing from the study, the investigator must conduct Exit 
procedures according to Table 3-1 Schedule of Study Procedures and Assessments and Section 
10.4.3, as possible. 

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10.4 Discontinued Subjects 
10.4.1 Screen Failures 
Subjects who were excluded from the study after signing the informed consent and prior to 
exposure to IP. 
The investigator must document the reason for screen failure in the subject’s case history 
source documents. 
Subject numbers must not be reused. 
10.4.2 Discontinuations 
Discontinued subjects are individuals who voluntarily withdraw or are withdrawn from the 
study by the investigator after signing informed consent, meeting eligibility criteria, and are 
exposed to IP. 
Subject numbers of discontinued subjects must not be reused (i.e., subject replacement is not 
allowed). 
Subjects may discontinue from study or study treatment at any time for any reason. Subjects 
may also be discontinued from study treatment at any time if, in the opinion of the investigator, 
continued treatment poses a risk to their health. 
For subjects choosing to discontinue from the study after exposure to IP, the investigator must 
complete all Exit procedures according to Table 3-1 Schedule of Study Procedures and 
Assessments, if the subject is willing and able, and if in the opinion of the investigator it is safe 
for the subject to do so. 
The investigator must document the reason for study or treatment discontinuation in the 
subject’s case history source documents. 
To ensure the safety of all subjects who discontinue early, investigators must assess each 
subject and, if necessary, advise them of any therapies and/or medical procedures that may be 
needed to maintain their health. 

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10.4.3 Schedule of Procedures and Assessments for Subjects Discontinued 
from Investigational Product  
If a subject discontinues from study treatment, every effort must be made to keep the subject in 
the study and to continue with the study assessments as specified in the schedule of study 
procedures and assessments until the final visit. 
10.5 Clinical Study Termination 
The study sponsor reserves the right to suspend or close the investigational site or suspend or 
terminate the study in its entirety at any time. 
If the clinical study is prematurely terminated or suspended by the study sponsor:  
• 
The study sponsor must: 
o Immediately notify the investigator(s) and subsequently provide instructions 
for study termination. 
o Inform the investigator and the regulatory authorities of the 
termination/suspension and the reason(s) for the termination/suspension.  
• 
The investigator must: 
o Promptly notify the IRB/IEC of the termination or suspension and of the 
reasons.  
o Provide subjects with recommendations for poststudy treatment options as 
needed. 
The investigator may terminate the site’s participation in the study for reasonable cause. 
10.5.1 Follow-up of Subjects after Study Participation has Ended  
Following this study, the subject will return to their eye care professional for their routine eye 
care. 
11 ADVERSE EVENTS AND DEVICE DEFICIENCIES 
11.1 General Information 
An AE is any untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs (including abnormal laboratory findings) in subjects, users, or other persons, whether or 
not related to the investigational medical device (test product). Refer to the Glossary of Terms 
and figures below for categories of AEs and SAEs. 

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Figure 11-1 
Categorization of All Adverse Events  
 
*In this study, only AEs related to the IP/device (i.e., UNITY VCS) are considered as device 
related ADE.  
Specific Events Relevant to this Protocol  
In addition to reporting all AEs (serious and nonserious) meeting the definitions, the 
investigator must report any occurrence of the following as an SAE including but not limited 
to: 
Serious Adverse Events 
• 
Corneal incision site leakage 
• 
Sclerotomy site leakage 

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• 
Toxic anterior segment syndrome 
• 
Posterior capsular tear 
• 
Vitreous prolapse 
• 
Iridodialysis 
• 
Iatrogenic retinal tear 
• 
Chronic corneal edema (corneal stromal or epithelial swelling resulting in BCDVA of 
≤ 20/40 at ≥ 1 month) 
• 
Clinically significant cystoid macular edema 
• 
Uncontrolled increase in IOP ≥ 10 mmHg over baseline and at least 25 mmHg 
• 
Endophthalmitis 
• 
Retinal detachment  
• 
Retinal vascular occlusion 
• 
Pupillary block 
• 
Suprachoroidal hemorrhage 
• 
Vitreous hemorrhage  
• 
Secondary surgical intervention (excluding posterior capsulotomy, planned surgical 
intervention such as laser photocoagulation and silicone oil removal) 
NOTE: Wound burps during the first week postoperatively, suture removal, planned surgical 
interventions such as blepharoplasty, laser photocoagulation, silicone oil removal, and 
Nd:YAG capsulotomy (for PCO) are not considered adverse events for this study. 
AEs occurring in association with a device that is used in conjunction with the UNITY VCS 
(e.g. gas, and silicone oil) will be classified separately from those associated with the 
investigational device itself. Expected complications from use of femtosecond laser-assisted 
procedures as noted in Section 5.3  and additional medical interventions (e.g. ocular injections) 
will not be considered device related AEs. 
In addition, aqueous cells and flare, corneal edema, eye redness, raised IOP, subconjunctival 
hemorrhage, and superficial punctate keratitis are examples of early postop findings that are 
typically observed following ocular surgery. These are not considered AEs if they can be 
reasonably expected to resolve within 2 weeks and not result in any untoward long term visual 
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Any other potentially sight-threatening event may also be considered serious based on the 
judgment of the investigator and should be reported appropriately as delineated in Section 
11.3. 
Device Deficiencies  
A device deficiency may or may not be associated with subject harm (i.e., ADE or SADE); 
however, not all ADEs or SADEs are due to a device deficiency. The investigator should 
determine the applicable category for the identified or suspect device deficiency and report any 
patient harm separately. 
 
11.2 Monitoring for Adverse Events 
At each visit, after the subject has had the opportunity to spontaneously mention any problems, 
the investigator should inquire about AEs by asking the standard questions shown below and 
report as applicable: 
• 
“Have you had any health problems since your last study visit?” 
• 
“Have there been any changes in the medicines you take because of a new health issue 
since your last study visit?” 
In addition, changes in any protocol-specific parameters and/or questionnaires evaluated 
during the study are to be reviewed by the investigator. Any untoward (unfavorable and 
unintended) change in a protocol-specific parameter or questionnaire response that is clinically 
relevant, in the opinion of the investigator, is to be reported as an AE. These clinically relevant 
changes will be reported regardless of causality.  
11.3 Procedures for Recording and Reporting 
AEs are collected from the time of informed consent. Any preexisting medical conditions or 
signs/symptoms present in a subject prior to the start of the study (i.e., before informed consent 

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is signed) are not considered AEs in the study and should be recorded in the medical history 
section of the eCRF. 
For each recorded event, the ADEs and SAEs documentation must include: date of occurrence, 
severity, treatment (if applicable), outcome, and assessments of the seriousness and causality. 
In addition, the investigator must document all device deficiencies reported or observed with 
the test product on the device deficiency eCRF. The site must submit all available information 
on ADEs, SAEs, and device deficiencies to the study sponsor immediately as follows: 
• 
ADEs or SAEs are documented on the Serious Adverse Event and Adverse Device 
Effect eCRF within 24 hours of the investigator’s or site’s awareness.  
• 
Device deficiencies are documented on the Device Deficiency eCRF within 24 hours of 
the investigator’s or site’s awareness.  
• 
Additional relevant information after initial reporting must be entered into the eCRF as 
soon as the data become available.   
• 
Document any changes to concomitant medications on the appropriate eCRFs. 
• 
Document all relevant information from discharge summary, autopsy report, certificate 
of death etc., if applicable, in the narrative section of the Serious Adverse Event and 
Adverse Device Effect eCRF. 
Note: Should the EDC system become nonoperational, the site must complete the appropriate 
paper serious adverse event and adverse device effect and/or device deficiency form. The 
completed form is emailed to the study sponsor at msus.safety@Alcon.com for USA-based 
sites and at Australia.auff-complaints@alcon.com for AUS-based sites, according to the 
timelines outlined above; however, the reported information must be entered into the EDC 
system once it becomes operational. 
In addition to recording all AEs into the EDC system, any AEs and device deficiencies for non-
study marketed devices/products (e.g., Alcon’s or other manufacturers’ products used 
concomitantly during the study will be considered and processed as spontaneous following the 
post market vigilance procedures) and should be communicated to the device’s/product’s 
manufacturer as per local requirements. 
Study sponsor representatives may be contacted for any protocol related question and 
their contact information is provided in the MOP that accompanies this protocol. 
Further, depending upon the nature of the AE or device deficiency being reported, the study 
sponsor may request copies of applicable portions of the subject’s medical records. The 

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investigator must also report all AEs and device deficiencies that could have led to a SADE 
according to the requirements of regulatory authorities or the IRB/IEC. 
Intensity and Causality Assessments 
Where appropriate, the investigator must assess the intensity (severity) of the AE based on 
medical judgment with consideration of any subjective symptom(s), as defined below: 
Intensity (Severity) 
Mild  
An AE is mild if the subject is aware of but can easily tolerate the sign or 
symptom. 
Moderate  
An AE is moderate if the sign or symptom results in discomfort significant 
enough to cause interference with the subject’s usual activities. 
Severe  
An AE is severe if the sign or symptom is incapacitating and results in the 
subject’s inability to work or engage in their usual activities. 
For every AE in the study, the investigator must assess the causality (related or not related to 
the medical device or study procedure). An assessment of causality will also be performed by 
study sponsor utilizing the same definitions, as shown below: 
Causality 
Related 
An AE classified as related may be either definitely related or possibly related 
where a direct cause and effect relationship with the medical device or study 
procedure has not been demonstrated, but there is a reasonable possibility that 
the AE was caused by the medical device or study procedure. 
Not Related  An AE classified as not related may either be definitely unrelated or simply 
unlikely to be related (i.e., there are other more likely causes for the AE). 
The study sponsor will assess the AEs and may upgrade the investigator’s assessment of 
seriousness and/or causality. The study sponsor will notify the investigator of any AEs that are 
upgraded from nonserious to serious or from unrelated to related. 
11.4 Return Product Analysis 
Study sponsor representatives and their contact information are provided in the MOP that 
accompanies this protocol.  

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Alcon study products associated with device deficiencies and/or product related AEs should be 
returned and must include the complaint number which will be provided by study sponsor after 
the case is entered in the study sponsor’s Global Product Complaint Management System 
(GPCMS).  
11.5 Unmasking of the Study Treatment  
Not applicable; this study is an open label study. 
11.6 Follow-Up of Subjects with Adverse Events 
The investigator is responsible for adequate and safe medical care of subjects during the study 
and for ensuring that appropriate medical care and relevant follow-up procedures are 
maintained after the study.  
The investigator should provide the study sponsor with any new safety information (which 
includes new AEs and changes to previously reported AEs) that may affect the safety 
evaluation of the device. For AEs that are unresolved/ongoing at time of discontinuation, any 
additional information received at follow-up should be documented in the eCRFs up to study 
completion (i.e., database lock). Any additional data received up to 6 months after a subject 
completed the study should be documented and available upon the study sponsor’s request.    
All complaints received after this time period will be considered and processed as spontaneous 
(following the post market vigilance procedures) and should be communicated to the medical 
device’s manufacturer as per local requirements. The investigator should also report 
complaints on non-Alcon products directly to the manufacturer as per the manufacturer’s 
instructions or local regulatory requirements. 
11.7 Pregnancy in the Clinical Study 
Pregnancy is not reportable as an AE; however, complications may be reportable and will be 
decided on a case-by-case basis. An Alcon form will be utilized to capture all pregnancy-
related information until birth of the child. 
12 ANALYSIS PLAN 
12.1 Subject Evaluability 
Final subject evaluability must be determined prior to locking the database, based upon the 
deviations and evaluability plan. 

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12.2 Analysis Sets 
All eligible subjects will be screened to determine if they meet all inclusion and no exclusion 
criteria. Subjects who provide informed consent will be considered enrolled in the study.  
12.2.1 Full Analysis Set 
The primary analysis set for the effectiveness outcomes will be the full analysis set. The full 
analysis set includes all eyes with successful completion of surgery. 
12.2.2 Safety Analysis Set 
The safety analysis set will include all eyes with attempted use of the UNITY VCS (successful 
or aborted after contact with the eye) and will be used for the safety outcomes. Attempted use 
of the UNITY VCS is defined as any time the device makes contact with the eye. 
12.3 Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized for each subject. Counts and 
percentages will be presented for categorical variables such as sex, age, race, and ethnicity. 
Count (n), mean, standard deviation, median, minimum, and maximum will be presented for 
continuous variables such as age. 
12.4 Effectiveness Analyses 
12.4.1 Analysis of Primary Effectiveness Endpoint(s) 
The primary performance endpoint is the percentage of surgeons reporting ‘yes’ to the binary 
question of: “Did UNITY VCS using vitreoretinal or combined surgical functionality 
perform per the intended use as defined in protocol Section 5.1?"  
12.4.1.1 Statistical Hypotheses 
No hypothesis testing of the primary effectiveness endpoint(s) is planned. 
12.4.1.2 Analysis Methods 
After each surgery, the surgeon completes a user questionnaire.  For subjects in the full 
analysis set, the rate of ‘yes’ responses to the question listed above will be presented with a 
count and percentage and will be accompanied by a two-sided exact binomial 95% confidence 
interval. 

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12.4.2 Analysis of Secondary Effectiveness Endpoints 
The secondary endpoints are: 
• 
Total time in the eye from first entry into eye/first trocar in, to incision closure/last 
trocar out 
• 
Achievement of anatomical success at 3 months postop, i.e., percent of ‘yes’ responses 
to the question “Was anatomical success achieved for intended treatment (e.g., macular 
hole closure, retinal attachment, etc. as applicable for the patient’s condition)?” 
• 
Change in BCDVA at 3 months postop when compared to preop 
12.4.2.1 Statistical Hypotheses 
No hypothesis testing of the secondary effectiveness endpoint(s) is planned. 
12.4.2.2 Analysis Methods 
At the surgical visit, the total time in the eye will be recorded as the time from first entry into 
eye/first trocar in, to incision closure/last trocar out. The total time in eye will be summarized 
with the number of observations, mean, standard deviation, median, minimum, and maximum 
times in minutes. A listing will accompany this summary.  
At the end of follow-up for each patient, surgeons will evaluate the success of the surgery. For 
subjects in the full analysis set, the rate of ‘yes’ responses to the question “was anatomical 
success achieved for intended treatment (e.g., macular hole closure, retinal attachment, etc. as 
applicable for the patient’s condition)?” will be presented with a count and percentage and will 
be accompanied by a two-sided exact binomial 95% confidence interval. 
BCDVA will be recorded in Snellen and collected at screening, 1 month, and 3 months. 
BCDVA will be converted to decimal VA. Observed decimal BCDVA values at each study visit 
and change from 3 months postoperative visit to screening value for the study eye will be 
presented descriptively (count, mean, median, standard deviation, minimum, and maximum). A 
categorical summary of Snellen values (not converted to decimal VA) will be produced and 
will include counts and percentages for each category at screening, 1 month, and 3 months. A 
listing will be provided which presents visual acuity results at each visit, including data from 1 
day and 1 week visits, where uncorrected data may be recorded per standard of care.   
12.5 Handling of Missing Data 
No imputation of missing data is planned. 

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12.6 Safety Analyses 
The safety endpoints are:  
• 
Ocular and nonocular AEs and SAEs 
• 
Device deficiencies 
• 
Secondary surgical interventions 
• 
Unplanned intraoperative procedures 
There are no safety hypotheses planned in this study. The focus of the safety analysis will be a 
comprehensive descriptive assessment of occurrence of adverse events as well as the other 
listed parameters. 
All adverse events occurring from the time a subject sign informed consent to study exit will 
be accounted for in the reporting. Safety analyses will be conducted using the safety analysis 
set on a treatment-emergent basis. Descriptive summaries (counts and percentages) and listings 
will be presented. Individual subject listings will be provided for AEs that occur after signing 
informed consent but prior to exposure to IP. 
12.6.1 Analysis of Primary Safety Endpoint(s) 
All adverse events reported to Alcon will be accounted for in the reporting. Descriptive 
summaries (counts and percentages) and listings will be presented. The applicable definition of 
an adverse event is in the study protocol. A listing of all adverse events will be constructed to 
provide further details. 
The applicable definition of a device deficiency is in the study protocol. A frequency table 
showing counts for each device deficiency category will be presented. In addition, a listing of 
all device deficiencies will be provided. 
Descriptive statistics (counts, percentages, and two-sided 95% exact binomial confidence 
intervals) of eyes with secondary surgical interventions (SSIs) will be presented. In addition, a 
listing of subjects with SSIs will be produced. 
Unplanned intraoperative procedures that occur during surgery will be recorded. Descriptive 
statistics including the count, percentage, and a two-sided 95% exact binomial confidence 
interval for the percentage will be produced and will be accompanied by a listing. 

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12.7 Interim Analyses and Reporting 
No interim analyses are planned. 
12.8 Sample Size Justification 
Based on a sample of 100 surgeries, the expected half-width of the 95% confidence interval for 
the percentage of surgeons reporting ‘yes’ to the question “Did UNITY VCS using 
vitreoretinal or combined surgical functionality perform per the intended use as defined in 
protocol Section 5.1?" will be 1.96∙√(p(1-p)/100). This half-width is widest at p = 50%. Under 
this conservative assumption, the expected half-width is < 10% given the sample size of 100.  
Allow enrollment for an additional 10% for screen failure and 10% for loss to follow-up to 
ensure 100 completed subjects. 
13 DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS 
13.1 Subject Confidentiality 
The investigator must ensure that the subject’s identity is kept confidential throughout the 
course of the study. In particular, the investigator must keep an enrollment log with 
confidential identifying information that corresponds to the subject numbers and initials of 
each study participant. The study sponsor may collect a copy of the enrollment log without 
any directly identifying subject information.  
The study sponsor may share patient-level data collected in this trial with qualified researchers 
to help facilitate product development or enhancements in research that is not directly related 
to the study objectives. The informed consent explains this to the study subject.  
13.2 Completion of Source Documents and Case Report Forms 
The nature and location of all source documents will be identified to ensure that original data 
required to complete the CRFs exist and are accessible for verification by the site monitor, and 
all discrepancies shall be appropriately documented via the query resolution process. Site 
monitors are appointed by the study sponsor and are independent of study site staff. 
If electronic records are maintained, the method of verification must be determined in advance 
of starting the study.  
At a minimum, source documents include the following information for each subject: 
• 
Subject identification (name, sex, race/ethnicity) 

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• 
Documentation of subject eligibility 
• 
Date of informed consent 
• 
Dates of visits 
• 
Documentation that protocol specific procedures were performed 
• 
Results of study parameters, as required by the protocol 
• 
IP accountability records 
• 
Documentation of AEs and other safety parameters (if applicable) 
• 
Records regarding medical histories and the use of concomitant therapies prior to and 
during the study 
• 
Date of study completion and reason for early discontinuation, if applicable 
It is required that the author of an entry in the source documents be identifiable. Direct access 
to source documentation (medical records) must be allowed for the purpose of verifying that 
the data recorded on the CRF are consistent with the original source data. 
Only designated individuals at the site will complete the CRFs. The CRFs must be completed 
at regular intervals following the clinical study visit schedule. It is expected that all data 
reported have corresponding entries in the source documents. The principal investigator is 
responsible for reviewing and certifying that the CRFs are accurate and complete. The only 
subject identifiers recorded on the CRFs will be subject number, and subject demographic 
information.  
13.3 Data Review and Clarifications 
A review of CRF data to the subject’s source data will be completed by the site monitor to 
ensure completeness and accuracy. After the CRFs have been completed, additional data 
clarifications and/or additions may be needed as a result of the data cleaning process. Data 
clarifications are documented and are part of each subject’s CRF. 
13.4 Sponsor and Monitoring Responsibilities 
The study sponsor will select principal investigators that are qualified by education, training, 
and experience to assume responsibility for the proper conduct of this clinical trial. For this 
study, the principal investigator and sub investigators must be health care professionals 
appropriately licensed to perform vitreoretinal and cataract surgery. 

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The study sponsor is financially funding this clinical trial and will compensate the investigator 
and/or the institution(s) at which the study is conducted in accordance with a signed clinical 
trial agreement. 
The study sponsor will designate a monitor to conduct the appropriate site visits at the 
appropriate intervals according to the study monitoring plan. The clinical investigation will be 
monitored to ensure that the rights and 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 the current approved protocol (and amendments[s], if 
applicable), with current GCP, and with applicable regulatory requirements. 
The site may not screen subjects or perform the informed consent process on any subject until 
it receives a notification from an appropriate study sponsor representative that the site may 
commence conducting study activities. Monitoring will be conducted periodically while the 
clinical study is ongoing. Monitoring methods may include site visits, telephone, written, and 
fax correspondence. Close-out visits will take place after the last visit of the last subject at the 
site. 
Videos of surgery should be maintained with subject records for verification as source data and 
sent to sponsor for review as requested. Such data will be coded with a subject number only 
and will not contain subject personal information.  
A coordinating investigator may be identified by the study sponsor to review and endorse the 
final study report. In cases where a coordinating investigator is engaged, the study sponsor will 
select the coordinating investigator based upon their experience, qualifications, active study 
participation, and their willingness and availability to take on this role. 

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13.5 Regulatory Documentation and Records Retention 
The investigator is required to maintain up-to-date, complete regulatory documentation as 
indicated by the study sponsor and the investigator’s files will be reviewed as part of the 
ongoing study monitoring. Financial information is to be kept separately.  
Additionally, the investigator must keep study records and source documents consistent with 
the terms of the clinical study agreement with the study sponsor. If the investigator retires, 
relocates, or for any other reason withdraws from responsibility of keeping the study records, 
then the study sponsor must be notified, and suitable arrangements made for retention of study 
records and source documents needed to comply with national and international regulations. 
13.6 Quality Assurance and Quality Control 
The study sponsor will secure agreement from all involved parties to ensure direct access to all 
study related sites, source data and documents, and reports for the purpose of monitoring and 
auditing by the study sponsor, and inspection by domestic and foreign regulatory authorities. 
Quality control will be applied to each stage of data handling to ensure that all data are reliable 
and have been processed correctly. Agreements made by the study sponsor with the 
investigator/institution and any other parties involved in the clinical study will be provided in 
writing as part of the protocol or as a separate agreement. 
14 ETHICS 
Investigations are conducted in compliance with GCP; international and national regulations, 
laws and guidelines; ISO 14155:2020; the conditions of approval imposed by reviewing 
IRBs/IECs or regulatory authorities; and in accordance with the ethical medical research 
principles outlined in the Declaration of Helsinki.  
• The SOPs of the study sponsor and contract research organizations participating in the 
conduct of the clinical study and all other applicable regulations shall apply.  
• 
Notifications and timelines for reporting protocol deviations should be based upon 
applicable ethics committee requirements. 

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The investigator must ensure that all personnel involved in the conduct of the study are 
qualified to perform their assigned responsibilities through relevant education, training, and 
experience. The investigator and all clinical study staff must conduct the clinical study in 
compliance with the protocol. The investigator is not allowed to deviate from the protocol 
except to protect the rights, safety, and wellbeing of human subjects under emergency 
circumstances. Emergency deviations may proceed without prior approval of the sponsor and 
the IRB/IEC but shall be documented and reported to the sponsor and the IRB/EC as soon as 
possible. Deviations from this protocol, regulatory requirements, and/or GCP must be recorded 
and reported to the sponsor prior to database lock. If needed, corrective and preventive action 
should be identified, implemented, and documented within the study records. Failure to 
implement identified corrective and preventative actions may result in site closure by the 
sponsor. Use of waivers to deviate from the clinical protocol is prohibited. 
Before clinical study initiation, this protocol, the informed consent form, if applicable, any 
other written information given to subjects, and any advertisements planned for subject 
recruitment must be approved by an IRB/IEC. The investigator must provide documentation of 
the IRB/IEC approval to the study sponsor. The approval must be dated and must identify the 
applicable protocol, amendments (if any), informed consent form, assent form (if any), all 
applicable recruiting materials, written information for subject, and subject compensation 
programs. The IRB/IEC must be provided with a copy of the investigator’s brochure, any 
periodic safety updates, and all other information as required by local regulation and/or the 
IRB/IEC. Any additional requirements imposed by the EC or regulatory authority shall be 
followed. At the end of the study, the investigator must notify the IRB/IEC about the study’s 
completion. The IRB/IEC also must be notified if the study is terminated prematurely. Finally, 
the investigator must report to the IRB/IEC on the progress of the study at intervals stipulated 
by the IRB/IEC. 
Voluntary informed consent must be obtained in writing from every subject. The obtaining of 
consent shall be documented before any procedure specific to the clinical investigation is 
applied to the subject.  
The investigator must have a defined process for obtaining the required consent. Specifically, 
the investigator, or their delegate, must explain the clinical study to each potential subject and 
the subject must indicate voluntary consent by signing and dating the approved informed 
consent form. The subject must be provided an opportunity to ask questions of the investigator, 
and if required by local regulation, other qualified personnel. The investigator must provide the 
subject with a copy of the consent form written in a language the subject understands. The 
consent document must meet all applicable local laws and provide subjects with information 

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regarding the purpose, procedures, requirements, and restrictions of the study, along with any 
known risks and potential benefits associated with the IP and the study, the available 
compensation, and the established provisions for maintaining confidentiality of personal, 
protected health information. Subjects will be told about the voluntary nature of participation 
in the study and must be provided with contact information for the appropriate individuals 
should questions or concerns arise during the study. The subject also must be told that their 
records may be accessed by appropriate authorities and sponsor-designated personnel. The 
investigator must keep the original, signed copy of the consent (file in subject’s medical 
records) and must provide a duplicate copy to each subject according to local regulations.  
The investigator must have a defined process in case a subject would like to withdraw their 
consent (s). The investigator is the designated contact point for any such withdrawals. 
The investigator must have a defined process in case a subject would like to exercise any of 
their rights under applicable data protection laws. The investigator is the designated contact 
point for any such requests.  
The study sponsor assures that the key designs of this protocol will be registered on public 
databases where required by current regulations, and, as applicable, results will be posted.   
15 REFERENCES 
15.1 Regulations and Standards 
The following references may be applicable in whole or in part for this clinical trial. 
• 
EN ISO 14155:2020 - Clinical Investigation of Medical Devices for Human Subjects - 
Good Clinical Practice 
• 
EU MDR: Regulation (EU) 2017/745 of the European Parliament and of the Council 
• 
21 CFR Part 11 - Electronic Records; Electronic Signatures 
• 
21 CFR Part 50 - Protection of Human Subjects 
• 
21 CFR Part 56 - Institutional Review Boards 
• 
21 CFR Part 812 - Investigational Device Exemptions 
• 
21 CFR Part 54 - Financial Disclosure by Clinical Investigators 
• 
The California Bill of Rights, if applicable 

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15.2 Scientific and Other References 
American Academy of Ophthalmology (AAO). Cataract in the Adult Eye Preferred Practice 
Pattern. AAO Journal. 2016. Accessed June 21, 2021. Cataract in the Adult Eye Preferred 
Practice Pattern® (aaojournal.org) 
American Academy of Ophthalmology. What to Expect: The Practice of Ophthalmology. 
Retrieved from: Ophthalmic Practice - American Academy of Ophthalmology (aao.org). 2023. 
Accessed July 07, 2023. 
Chen D, Zhu J, Li J, Ding X, Lu F, Zhao Y. Effect of simulated dynamic intraocular pressure 
on retinal thickness measured by optical coherence tomography after cataract surgery. Int J 
Ophthalmol. 2012;5(6):687-93. 
Daud F, Daud K, Popovic MM, Yeung S, You Y, Cruz Pimentel M, Yan P. Combined versus 
Sequential Pars Plana Vitrectomy and Phacoemulsification for Macular Hole and Epiretinal 
Membrane: A Systematic Review and Meta-Analysis. Ophthalmol Retina. 2023 Aug;7(8):721-
731.   
Doi Y, Muraoka Y, Tsujikawa A. Evaluation of the Efficiency and Safety of a 27-Gauge 20,000 
Cuts per Minute Vitreous Cutter. Clin Ophthalmol. 2023 Jul 18;17:2037-2043.  
Findl O, Strenn K, Wolzt M, Menapace R, Vass C, Eichler HG, Schmetterer L. Effects of 
changes in intraocular pressure on human ocular haemodynamics. Curr Eye Res. 1997 
Oct;16(10):1024-9. 
Hou, C. H., Lee, J. S., Chen, K. J. & Lin, K. K. The sources of pain during 
phacoemulsification using topical anesthesia. Eye (Lond). 2012 May;26(5):749-750. 
Lee S, Choi KS. Experimental Assessment of the Performance of Dual PneumaticVitreous 
Cutters According to Gauge and Cut Rate. Korean J Ophthalmol. 2023 Aug;37(4):307-313.  
Lubiński W, Gosławski W, Podborączyńska-Jodko K, Mularczyk M, Post M. Comparison of 
27-gauge versus 25-gauge vitrectomy results in patients with epiretinal membrane: 6-month 
follow-up. Int Ophthalmol. 2020 Apr;40(4):867-875. 

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Lundström M, Barry P, Henry Y, Rosen P, Stenevi U. Evidence-based guidelines for cataract 
surgery: guidelines based on data in the European Registry of Quality Outcomes for Cataract 
and Refractive Surgery database. J Cataract Refract Surg. 2012 Jun;38(6):1086-93. 
Market Scope, LLC. Cataract Surgical Equipment Market Report, Global Analysis for 2021 to 
2027. July 2022. Market Scope (market-scope.com) 
Market Scope, LLC. 2023 Retinal Surgical Device Market Report, Global Analysis for 2022 to 
2028. March 2023. Market Scope (market-scope.com) 
National Eye Institute. Cataracts| National Eye Institute. 2023. Accessed July 07, 2023. 
Cataracts | National Eye Institute (nih.gov) 
Omari A, Mahmoud TH. Vitrectomy. 2023 Jul 25. In: StatPearls [Internet]. Treasure Island 
(FL): StatPearls Publishing; 2023 Jan–. PMID: 31869132.  
Ribeiro L, Oliveira J, Kuroiwa D, Kolko M, Fernandes R, Junior O, Moraes N, Vasconcelos H, 
Oliveira T, Maia M. Advances in Vitreoretinal Surgery. J Clin Med. 2022 Oct 30;11(21):6428.  
Saleh OA, Alshamarti SA, Abu-Yaghi NE. Comparison of Characteristics and Clinical 
Outcomes in 27-Gauge versus 23-Gauge Vitrectomy Surgery. Clin Ophthalmol. 2020 Jun 
9;14:1553-1558.  
Steel DH, Charles M, Zhu Y, Tambat S, Irannejad AM, Charles S. FLUIDIC PERFORMANCE 
OF A DUAL-ACTION VITRECTOMY PROBE COMPARED WITH A SINGLE-ACTION 
PROBE. Retina. 2022 Nov 1;42(11):2150-2158.  
Suzuki, H., Oki, K., Shiwa, T., Oharazawa, H. & Takahashi, H. Effect of bottle height on the 
corneal endothelium during phacoemulsification. J Cataract Refract Surg. 2009 
Nov;35(11):2014-7. 
Takhtaev YV, Kiseleva TN, Shliakman B. The effect of preset intraoperative intraocular 
pressure during phacoemulsification on the blood flow velocity in the central retinal artery. 
Ophthalmology Reports. 2019;12(4):5-12. 
World Health Organization. Blindness and Vision Impairment. Retrieved from: Blindness and 
vision impairment (World Health Organization (WHO)). 13 Oct 2022. Accessed July 7, 2023. 
Wubben TJ, Talwar N, Blachley TS, Gardner TW, Johnson MW, Lee PP, Stein JD. Rates of 
Vitrectomy among Enrollees in a United States Managed Care Network, 2001-2012. 
Ophthalmology. 2016 Mar;123(3):590-8.   

Document ID: 
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Status: Approved, Version: 2.0 
Approved Date: 04 Feb 2024 
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Document ID: 
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Status: Approved, Version: 2.0 
Approved Date: 04 Feb 2024 
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Document ID: 
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Status: Approved, Version: 2.0 
Approved Date: 04 Feb 2024 
Page 61 of 61 
 
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