An Investigation of the Impact of Localized Topical Anesthesia of the Ocular Surface on End-of-day Contact Lens Discomfort
Phase: NA
Conditions: Visual Acuity
Sponsor: Johnson & Johnson Vision Care, Inc.

JOHNSON & JOHNSON VISION CARE, 
INC.
Clinical Study Protocol
An investigation of the impact of localized topical anesthesia of the ocular surface on end-of-
day contact lens discomfort
Protocol CR-6292
Version: 1.0
Date: 24 September 2018
Investigational Products: Proxymetacaine hydrochloride 0.5%, Sodium chloride 0.9%
Key Words: anesthesia, eyelid margin, cornea, contact lens comfort, end-of-day, symptomatic, 
non-dispensing, daily wear
Statement of Compliance to protocol, GCP and applicable regulatory guidelines:
This trial will be conducted in compliance with the protocol, ISO 14155,1 the International 
Conference on Harmonization Good Clinical Practice E6 (ICH-GCP),2 the Declaration of 
Helsinki,3 and all applicable regulatory requirements.
Confidentiality Statement:
This document contains confidential information, which should not be copied, referred to, 
released or published without written approval from Johnson & Johnson Vision Care, Inc.  The 
information may not be disclosed to others except to the extent necessary to obtain Institutional 
Review Board/Independent Ethics Committee approval and informed consent, or as required 
by International, Federal and State Laws, as applicable. Persons to whom this information is 
disclosed must be informed that this information is privileged and confidential and that it 
should not be further disclosed without the written permission of Johnson & Johnson Vision 
Care, Inc.  Any supplemental information that may be added to this document is also 
confidential and proprietary to Johnson & Johnson Vision Care, Inc. and must be kept in 
confidence in the same manner as the contents of this document.
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TABLE OF CONTENTS
Johnson & Johnson Vision Care, Inc........................................................................................ 1 
PROTOCOL TITLE, NUMBER, VERSION........................................................................... 6 
SPONSOR NAME AND ADDRESS....................................................................................... 6 
MEDICAL MONITOR............................................................................................................. 6 
AUTHORIZED SIGNATURES............................................................................................... 7 
CHANGE HISTORY................................................................................................................ 8 
SYNOPSIS................................................................................................................................ 9 
COMMONLY USED ABBREVIATIONS AND DEFINITIONS OF TERMS.................... 14 
1. 
INTRODUCTION AND BACKGROUND ................................................................... 15 
1.1. 
Name and Descriptions of Investigational Products ................................................ 15 
1.2. 
Intended Use of Investigational Products................................................................. 15 
1.3. 
Summary of Findings from Nonclinical Studies...................................................... 16 
1.4. 
Summary of Known Risks and Benefits to Human Subjects................................... 16 
1.5. 
Relevant Literature References and Prior Clinical Data Relevant to Proposed Clinical 
Study ……………………………………………………………………………………...16 
2. 
STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES ...................................... 16 
2.1. 
Objectives................................................................................................................. 16 
2.2. 
Endpoints.................................................................................................................. 17 
2.3. 
Hypotheses ............................................................................................................... 17 
3. 
TARGETED STUDY POPULATION........................................................................... 17 
3.1. 
General Characteristics ............................................................................................ 17 
3.2. 
Inclusion Criteria...................................................................................................... 18 
3.3. 
Exclusion Criteria..................................................................................................... 18 
3.4. 
Enrollment Strategy.................................................................................................. 19 
4. 
STUDY DESIGN AND RATIONALE.......................................................................... 19 
4.1. 
Description of Study Design .................................................................................... 19 
4.2. 
Study Design Rationale............................................................................................ 20 
4.3. 
Enrollment Target and Study Duration .................................................................... 20 
5. 
TEST ARTICLE ALLOCATION AND MASKING..................................................... 20 
5.1. 
Test Article Allocation............................................................................................. 20 
5.2. 
Masking.................................................................................................................... 21 
5.3. 
Procedures for Maintaining and Breaking the Masking........................................... 21 
6. 
STUDY INTERVENTION............................................................................................. 21 
6.1. 
Identity of Test Articles............................................................................................ 21 
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6.2. 
Ancillary Supplies/Products..................................................................................... 21 
6.3. 
Administration of Test Articles................................................................................ 21 
6.4. 
Packaging and Labeling ........................................................................................... 21 
6.5. 
Storage Conditions................................................................................................... 21 
6.6. 
Collection and Storage of Samples .......................................................................... 21 
6.7. 
Accountability of Test Articles ................................................................................ 21 
7. 
STUDY EVALUATIONS.............................................................................................. 22 
7.1. 
Time and Event Schedule......................................................................................... 22 
7.2. 
Detailed Study Procedures ....................................................................................... 23 
VISIT 0 ........................................................................................................................... 23 
VISIT 1 ........................................................................................................................... 23 
VISITS 2 - 4.................................................................................................................... 25 
FINAL EVALUATION.................................................................................................. 29 
7.3. 
Unscheduled Visits................................................................................................... 29 
7.4. 
Laboratory Procedures ............................................................................................. 30 
8. 
SUBJECTS COMPLETION/WITHDRAWAL.............................................................. 30 
8.1. 
Completion Criteria.................................................................................................. 30 
8.2. 
Withdrawal/Discontinuation from the Study ........................................................... 30 
9. 
PRE-STUDY AND CONCOMITANT INTERVENTION/MEDICATION ................. 31 
10. 
DEVIATIONS FROM THE PROTOCOL.................................................................. 31 
11. 
STUDY TERMINATION ........................................................................................... 31 
12. 
PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS.............. 32 
13. 
ADVERSE EVENTS................................................................................................... 33 
13.1. 
Definitions and Classifications............................................................................. 33 
13.2. 
Assessing Adverse Events.................................................................................... 35 
13.2.1. 
Causality Assessment.................................................................................... 36 
13.2.2. 
Severity Assessment...................................................................................... 36 
13.3. 
Documentation and Follow-Up of Adverse Events.............................................. 36 
13.4. 
Reporting Adverse Events.................................................................................... 38 
13.4.1. 
Reporting Adverse Events to Sponsor .......................................................... 38 
13.4.2. 
Reporting Adverse Events to the Responsible IEC/IRB and Health Authorities
………………………………………………………………………………39 
13.4.3. 
Event of Special Interest ............................................................................... 39 
13.5. 
Reporting of Pregnancy........................................................................................ 39 
14. 
STATISTICAL METHODS........................................................................................ 39 
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14.1. 
General Considerations......................................................................................... 39 
14.2. 
Sample Size Justification...................................................................................... 40 
14.3. 
Analysis Populations ............................................................................................ 41 
14.4. 
Level of Statistical Significance........................................................................... 41 
14.5. 
Primary Analysis .................................................................................................. 41 
14.6. 
Secondary Analysis .............................................................................................. 43 
14.7. 
Other Exploratory Analyses ................................................................................. 44 
14.8. 
Interim Analysis ................................................................................................... 44 
14.9. 
Procedure for Handling Missing Data and Drop-Outs ......................................... 44 
14.10. 
Procedure for Reporting Deviations from Statistical Plan ................................... 44 
15. 
DATA HANDLING AND RECORD KEEPING/ARCHIVING................................ 44 
15.1. 
Electronic Case Report Form/Data Collection ..................................................... 44 
15.2. 
Subject Record...................................................................................................... 45 
16. 
DATA MANAGEMENT............................................................................................. 45 
16.1. 
Access to Source Data/Document ........................................................................ 45 
16.2. 
Confidentiality of Information.............................................................................. 45 
16.3. 
Data Quality Assurance........................................................................................ 45 
17. 
MONITORING............................................................................................................ 46 
18. 
ETHICAL AND REGULATORY ASPECTS ............................................................ 46 
18.1. 
Study-Specific Design Considerations ................................................................. 46 
18.2. 
Investigator Responsibility................................................................................... 47 
18.3. 
Independent Ethics Committee or Institutional Review Board (IEC/IRB).......... 47 
18.4. 
Informed Consent ................................................................................................. 48 
18.5. 
Privacy of Personal Data ...................................................................................... 48 
19. 
STUDY RECORD RETENTION................................................................................ 49 
20. 
FINANCIAL CONSIDERATIONS ............................................................................ 50 
21. 
PUBLICATION........................................................................................................... 50 
22. 
REFERENCES ............................................................................................................ 51 
APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES)..... 52 
APPENDIX B: PATIENT INSTRUCTION GUIDE ............................................................. 58 
APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT)......................................... 59 
APPENDIX D: CLINICAL TECHNICAL PROCEDURES (CTP) ...................................... 66 
, SUBJECT REPORTED OCULAR SYSTEMS................................................... 67 
 PATIENT REPORTED OUTCOMES ................................................................ 69 
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EXAMINATION 
OF 
THE 
ANTERIOR 
SEGMENT 
USING 
SLIT 
LAMP 
BIOMICROSCOPY................................................................................................................ 71 
THE SET-UP, MEASUREMENT OF VISUAL ACUITY AND PROCEDURES FOR 
CARRYING OUT AN OVER-REFRACTION USING THE EUROLENS COMPUTERIZED
LOGMAR VA CHART.......................................................................................................... 76 
PROCEDURE FOR SELECTIVELY ANESTHETISING THE CORNEA AND EYELID 
MARGINS.............................................................................................................................. 88 
APPENDIX E: VAS SCALE.................................................................................................. 94 
PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE .......................... 96 
TABLE OF CONTENTS
Figure 1: Study Flowchart ...................................................................................................... 13 
TABLE OF CONTENTS
Table 1: Ancillary Supplies .................................................................................................... 21 
Table 2: Time and Events ....................................................................................................... 22 
Table 3: Power Analysis for the Primary Hypothesis (Superiority)....................................... 40 
Table 4: Power Analysis for the Primary Hypothesis (Equivalence) ..................................... 40 
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PROTOCOL TITLE, NUMBER, VERSION
Title: An investigation of the impact of localized topical anesthesia of the ocular surface on 
end-of-day contact lens discomfort.
Protocol Number: CR-6292
Version: 1.0
Date:  24 September 2018
SPONSOR NAME AND ADDRESS
Johnson & Johnson Vision Care (JJVC)
7500 Centurion Parkway 
Jacksonville, FL 32256
MEDICAL MONITOR
Name:  Kristy Canavan
Title: Senior Principal Research Optometrist 
Address: 7500 Centurion Parkway, Suite 100, Mail W-2A, Jacksonville, FL 32256
The Medical Monitor must be notified by the clinical institution/site by e-mail, fax, or 
telephone within 24 hours of learning of a Serious Adverse Event. The Medical Monitor may 
be contacted during business hours for adverse event questions. General study related questions 
should be directed towards your assigned clinical research associate.
The Medical Monitoring Plan is maintained as a separate document and included in the Trial 
Master File.
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SYNOPSIS 
Protocol Title
An investigation of the impact of localized topical anesthesia
of the ocular surface on end-of-day contact lens discomfort.
Sponsor
JJVC, 7500 Centurion Parkway, Jacksonville, FL  32256
Clinical Phase
Development phase, phase 0
Trial Registration
This study will be registered on ClinicalTrials.gov
Test Article(s)
None (habitual contact lenses)
Wear and Replacement 
Schedules
Habitual lenses will be worn for 14 ± 2 hours on study days
Objectives 
Primary Objective
To evaluate the effect of topical anesthesia of the upper lid 
margin, lower lid margin and cornea on end-of-day discomfort 
in symptomatic contact lens wearers.
Secondary Objective
To determine the effect of contact lens removal on end-of-day 
discomfort in symptomatic soft contact lens wearers.
Study Endpoints
Primary endpoint:
Subjective scores of comfort (VAS scale) collected at various 
time points:
x
Immediately prior to lens application
x
5 minutes after lens application
x
14 hours after lens application (i.e. pre-treatment)
x
Immediately after lens removal prior to treatment 
application, only for the cornea.
x
5 minutes post-treatment
x
10 minutes post-treatment
Other observations: none.
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Study Design
This is a controlled, randomized, subject-masked, 3x3 
crossover, non-dispensing, contralateral study. Twenty 
subjects will be recruited based on their scores (with their 
habitual lenses) from the Contact 
Lens Dry Eye 
Questionnaire-8 (CLDEQ-8 score of 20-37) and examined on 
four occasions:
Visit 1: Screening
Visit 2-4: At each study visit, an ocular region (upper lid 
margin, lower lid margin or cornea) will be anesthetized on 
one eye, whilst the fellow eye will receive a saline placebo 
treatment at the same ocular location. Subjective comfort 
scores (VAS scale) will be collected prior to and following the 
treatment on each eye.
See the flow chart at the end of the synopsis table for the 
schematic of the study visits and procedures of main 
observations (Figure 1).
Sample Size
Up to 20 eligible subjects will be enrolled into the study with 
a target of 15 to complete.
Study Duration
Five months
Anticipated Study 
Population
Habitual soft contact lens wearers aged 18 and above who
are classified as symptomatic based on a CLDEQ-8 score of
20-37
Eligibility Criteria
Potential subjects must satisfy all of the following criteria to 
be enrolled in the study:
Inclusion Criteria after Screening
1. They are of legal age (18 years) and capacity of 
volunteer.
2. The subject must read, understand, and sign the 
STATEMENT OF INFORMED CONSENT and 
receive a fully executed copy of the form.
3. They must appear able and willing to adhere to the 
instructions set forth in this clinical protocol.
4. They have worn the same brand of soft spherical 
contact lenses for at least the previous three months,
by self-report.
5. They are defined as ‘symptomatic’ contact lens 
wearers (CLDEQ-8 score of 20-37) with their habitual 
contact lenses.
6. They are willing to wear their lenses for approximately
14 hours on study days.
7. They have a wearable pair of spectacles, if 
applicable.
8. They agree not to participate in other clinical research 
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for the duration of this study.
Inclusion Criteria after Baseline
9. They can attain high contrast logMAR visual acuity 
of 0.20 or better in their habitual contact lenses in 
each eye.
Potential subjects who meet any of the following criteria will 
be excluded from participating in the study:
Exclusion Criteria after Screening:
1. They have an ocular disorder, which would normally 
contra-indicate contact lens wear.
2. They have a systemic disorder, which would normally 
contra-indicate contact lens wear.
3. They are using any topical medication such as eye 
drops or ointment.
4. They have had cataract or corneal refractive surgery.
5. They are pregnant or breast-feeding by self-report.
6. They have any infectious disease (e.g. hepatitis) or any 
immunosuppressive disease (e.g. HIV), by self-report.
7. They have any known hypersensitivity or allergic 
reaction to any of the known ingredients in the 
anesthetic.
8. They have a history of severe allergic reaction or 
anaphylaxis.
9. They have a history of cardiac disease or 
hyperthyroidism.
10. They have taken part in any other contact lens or care 
solution clinical trial or research, within two weeks 
prior to starting this study.
11. They are an employee or immediate family member of 
an employee of clinical site (e.g., Investigator, 
Coordinator, Technician).
Exclusion Criteria after Baseline
12. They have any corneal distortion resulting from 
previous hard or rigid lens wear or have keratoconus.
13. They have grade 3 or greater of any of the following 
ocular surface signs which would contraindicate 
contact 
lens 
wear: 
corneal 
oedema, 
corneal 
vascularisation, corneal staining, tarsal conjunctival 
changes or any other abnormality which would 
normally contraindicate contact lens wear.
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Disallowed 
Medications/Interventions 
No ocular topical medications
No systemic medications that in the view of the investigator 
may affect the ocular surface or contact lens wear from 24 
hours prior to study visits
Measurements and 
Procedures
Subjective comfort scores (VAS scale) and safety parameters
(visual acuity and biomicroscopy)
Microbiology or Other 
Laboratory Testing
None
Study Termination
The occurrence of one or more Unanticipated Serious 
Adverse Device Effect (USADE), or any SAE where 
relationship to study agent cannot be ruled out, will result in 
stopping further study procedures.  In the event of a UADE 
or SAE, the Sponsor Medical Monitor may unmask the 
treatment regimen of subject(s) and may discuss this with the 
Principal Investigator before any further subjects are 
enrolled.
Ancillary Supplies/ Study-
Specific Materials
Topical anesthetic: proxymetacaine hydrochloride 0.5%
(Chauvin Pharmaceuticals Ltd)
Crest Medical Ltd Saline Pods (or other sponsor-approved 
material)
Principal Investigator(s) 
and Study 
Institution(s)/Site(s)
A full list of Principal Investigators, clinical sites, and 
institutions is kept separately from the Study Protocol and is 
included in the study Trial Master File.  
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COMMONLY USED ABBREVIATIONS AND DEFINITIONS OF TERMS
ADD
Plus Power Required For Near Use
ADE
Adverse Device Effect
AE
Adverse Event/Adverse Experience
BCVA
Best Corrected Visual Acuity
BSCVA
Best Spectacle Corrected Visual Acuity
CFR
Code of Federal Regulations
CLUE
Contact Lens User Experience
COAS
Complete Ophthalmic Analysis System
COM
Clinical Operations Manager
CRA
Clinical Research Associate
CRF
Case Report Form
CRO
Contract Research Organization
CT
Center Thickness
D
Diopter
DMC
Data Monitoring Committee
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
ETDRS
Early Treatment Diabetic Retinopathy Study
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HIPAA
Health Insurance Portability and Accountability Act
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonization
IDE
Investigational Device Exemption
IEC
Independent Ethics Committee
IRB
Institutional Review Board
ISO
International Organization for Standardization
ITT
Intent-to-Treat
JJVC
Johnson & Johnson Vision Care, Inc.
LC
Limbus Center
LogMAR
Logarithm of Minimal Angle of Resolution
MedDRA©
Medical Dictionary for Regulatory Activities
MOP
Manual of Procedures
NIH
National Institutes of Health
OD
Right Eye
OHRP
Office for Human Research Protections
OHSR
Office for Human Subjects Research
OS
Left Eye
OU
Both Eyes
PD
Protocol Deviation
PHI
Protected Health Information
PI
Principal Investigator
PIG
Patient Instruction Guide
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PQC
Product Quality Complaint
PRO
Patient Reported Outcome
QA
Quality Assurance
QC
Quality Control
SAE
Serious Adverse Event/Serious Adverse Experience
SAP
Statistical Analysis Plan
SAS
Statistical Analysis System
SD
Standard Deviation
SOP
Standard Operating Procedure
UADE
Unanticipated Adverse Device Effect
USADE
Unanticipated Serious Adverse Device Effect
VA
Visual Acuity
1.
INTRODUCTION AND BACKGROUND
Previous work 
has shown that we are able to successfully and selectively 
anesthetize the entire cornea, upper lid margin and lower lid margin in the majority of subjects 
whilst keeping the other ocular regions relatively unaffected. Isolating specific regions of the 
anterior ocular surface in this manner is potentially useful for systematically investigating 
whether or not contact lens discomfort can be improved when any of these areas are ‘numbed’.
The aim of this study is to evaluate the effect of topical anesthesia on the upper eyelid margin,
lower eyelid margin and the cornea in wearers suffering from end-of-day contact lens 
discomfort.
1.1.
Name and Descriptions of Investigational Products 
The following products will be used in this study:
x
Single use Minims of proxymetacaine hydrochloride, 0.5% (a commercially available 
topical anesthetic) will be used to temporarily numb selective areas of the ocular 
surface (lower lid margin, upper lid margin and cornea). 
x
Sodium chloride 0.9% will be used as a placebo treatment. 
1.2.
Intended Use of Investigational Products
The intended use of proxymetacaine hydrochloride, 0.5% is to numb selective areas of the
ocular surface. It is a topical ocular anesthetic. Typically, a drop which is ~30μl in size is used 
to numb the cornea in everyday clinical practice but in this work smaller amounts than this will 
be used in one eye on three different study days. The amounts used are detailed in the Eurolens 
Research Standard Operating Procedure ‘Procedure for selectively anaesthetizing the cornea 
and eyelid margins’ (Appendix D). 
Sodium chloride 0.9% will be used as a placebo treatment in one eye on three different study 
days.
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1.3.
Summary of Findings from Nonclinical Studies
Not Applicable – Marketed product only.
1.4.
Summary of Known Risks and Benefits to Human Subjects
There is no direct benefit to the subject from participation in the study.  The information 
obtained from this study will aid in the development of improved contact lenses in the future.
Proxymetacaine hydrochloride, 0.5%: see electronic Medicines Compendium (eMC) entry 
for this drug (Summary of Product Characteristics) and the Patient Information leaflet in 
Appendix C.
Sodium chloride 0.9%: see Material Safety Data Sheet in Appendix C.
1.5.
Relevant Literature References and Prior Clinical Data Relevant to Proposed 
Clinical Study
One previously completed sponsored clinical study:
Navascues-Cornago M.
Clinical Study Report #(VIS-CR-5876) Project Lennon: 
Understanding Contact Lens Comfort. June 6, 2017. 6
Also, previous pilot wok on anesthetizing parts of the ocular surface was presented at the 
following conference:
Navascues-Cornago M, Maldonado-Codina C and Morgan PB. Effect of selective topical
anesthesia on initial comfort of rigid contact lenses. British Contact Lens Association 39th
Annual Clinical Conference and Exhibition. May 29-31, 2015, ACC, Liverpool, UK.7
2.
STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES
2.1.
Objectives 
Primary Objective
To evaluate the effect of topical anesthesia of the upper lid margin, lower lid margin and cornea 
on end-of-day discomfort in symptomatic contact lens wearers.
Secondary Objective
To determine the effect of contact lens removal on end-of-day discomfort in symptomatic soft 
contact lens wearers.
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2.2.
Endpoints 
Primary Endpoint(s)
The primary endpoint is the subjective scores of comfort (VAS scale) collected at various time 
points:
x
Immediately prior to lens application
x
5 minutes after lens application
x
14 hours after lens application (i.e. pre-treatment)
x
Immediately after lens removal prior to treatment application, only for the cornea.
x
5 minutes post-treatment
x
10 minutes post-treatment
2.3.
Hypotheses
Primary Hypotheses
1. Post-treatment subjective scores of comfort (VAS scale) for anesthetized eyes are
superior to eyes that received the placebo for at least one of the ocular regions (upper 
lid margin, lower lid margin, or cornea).
2. Comfort change from pre-treatment for anesthetized eyes is superior to eyes that 
received the placebo for at least one of the ocular regions (upper lid margin, lower lid 
margin, or cornea).
3. Post-treatment subjective scores of comfort (VAS scale) for anesthetized eyes are 
equivalent to 5-minute post lens application levels in the morning for at least one of the 
ocular regions (upper lid margin, lower lid margin, or cornea). An equivalence margin 
of 10 points will be used. 
Secondary Hypotheses
1. Post-treatment subjective scores of comfort (VAS scale) for eyes with the cornea 
anesthetized are superior to eyes with the upper or lower lid margins anesthetized.
2. Comfort change from pre-treatment for eyes with the cornea anesthetized is superior to 
eyes with the upper or lower lid margins anesthetized.
3. Subjective scores of comfort (VAS scale) at lens removal are equivalent to baseline 
levels (i.e. immediately prior to lens application in the morning) when the cornea is 
anesthetized. An equivalence margin of 10 points will be used. 
Other Hypotheses
None.
3.
TARGETED STUDY POPULATION
3.1.
General Characteristics 
Symptomatic contact lens wearers who report a CLDEQ-8 score of 20-37 will be recruited.
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3.2.
Inclusion Criteria
Potential subjects must satisfy all of the following criteria to be enrolled in the study:
Inclusion Criteria after Screening
1. They are of legal age (18 years) and capacity of volunteer.
2. The subject must read, understand, and sign the STATEMENT OF INFORMED 
CONSENT and receive a fully executed copy of the form.
3. They must appear able and willing to adhere to the instructions set forth in this clinical 
protocol.
4. They have worn the same brand of soft spherical contact lenses for at least the previous
three months, by self-report.
5. They are defined as ‘symptomatic’ contact lens wearers (CLDEQ-8 score of 20-37) 
with their habitual contact lenses.
6. They are willing to wear their lenses for approximately 14 hours on study days.
7. They have a wearable pair of spectacles, if applicable.
8. They agree not to participate in other clinical research for the duration of this study.
Inclusion Criteria after Baseline
9. They can attain high contrast logMAR visual acuity of 0.20 or better in their habitual 
contact lenses in each eye.
3.3.
Exclusion Criteria
Potential subjects who meet any of the following criteria will be excluded from participating
in the study: 
Exclusion Criteria after Screening:
1. They have an ocular disorder, which would normally contra-indicate contact lens wear.
2. They have a systemic disorder, which would normally contra-indicate contact lens 
wear.
3. They are using any topical medication such as eye drops or ointment.
4. They have had cataract or corneal refractive surgery.
5. They are pregnant or breast-feeding by self-report.
6. They have any infectious disease (e.g. hepatitis) or any immunosuppressive disease
(e.g. HIV), by self-report.
7. They have any known hypersensitivity or allergic reaction to any of the known
ingredients in the anesthetic.
8. They have a history of severe allergic reaction or anaphylaxis.
9. They have a history of cardiac disease or hyperthyroidism.
10. They have taken part in any other contact lens or care solution clinical trial or research,
within two weeks prior to starting this study.
11. They are an employee or immediate family member of an employee of clinical site 
(e.g., Investigator, Coordinator, Technician).
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Exclusion Criteria after Baseline
12. They have any corneal distortion resulting from previous hard or rigid lens wear or 
have keratoconus.
13. They have grade 3 or greater of any of the following ocular surface signs which would
contraindicate contact lens wear: corneal oedema, corneal vascularisation, corneal
staining, tarsal conjunctival changes or any other abnormality which would normally
contraindicate contact lens wear.
3.4.
Enrollment Strategy
Study subjects will be recruited from the University of Manchester, UK’s subject database 
and/or utilizing Independent Ethics Committee (IEC) or Institutional Review Board (IRB) 
approved materials. 
4.
STUDY DESIGN AND RATIONALE
4.1.
Description of Study Design
The study design is controlled, randomized, subject-masked, 3 treatment ×3 period, non-
dispensing, contralateral study. 
After a pre-screening assessment, eligible subjects will be invited to attend an initial visit. 
Subjects will be prescreened using the CLDEQ-8 questionnaire with their habitual lenses and 
those who are classified as symptomatic (CLDEQ-8 score of 20-37) will be scheduled for Visit 
1.
At study Visit 1, subjects will be consented and screened for inclusion/exclusion criteria. If a 
subject is found to meet all eligibility criteria, they will be asked to attend Visit 2 which will 
take place on a different day. Subjects will be asked to wear their contact lenses early in the 
morning (at home) on the day of Visit 2 and to rate subjective comfort on a paper VAS scale 
immediately prior to lens application and 5 minutes post-application. They will be asked to 
attend the study visit having worn their habitual lenses for 14 ± 2 hours. At Visit 2, one of three 
areas (upper lid margin, lower lid margin or cornea) will be anesthetized on one eye, whilst the 
fellow eye will receive a saline placebo treatment in the same location. The ocular surface 
region and treatment will be randomly assigned. The right eye will always be assessed first. 
Subjective comfort scores (VAS scale) will be collected prior to and following the treatment 
on each eye (5 and 10 minutes post-treatment). On the day of corneal treatment, VAS comfort 
scores will also be collected immediately after lens removal prior to treatment application.
Subjects will be asked to return for Visit 3 on a different study day, again having worn their 
lenses for 14 ± 2 hours and the same procedures as at Visit 2 will take place. The same 
procedures as for Visit 3 will be repeated for Visit 4. Visits 2-4 will be scheduled 1-14 days
apart.
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4.2.
Study Design Rationale
Crossover designs are a well-established cost-effective study design in which subjects are 
exposed to multiple treatments during different time periods. The study design allows for a 
direct and meaningful comparison of three anesthesia treatments. A minimum period of 24
hours between visits (i.e. between each treatment) was implemented to reduce any potential 
carry-over effect that may bias the results.
4.3.
Enrollment Target and Study Duration
A total of up to 20 subjects will be enrolled (informed consent signed) at a single clinical site 
(University of Manchester) in the UK, with a target of 15 to complete. 
Subjects will be considered to be enrolled onto the study when they have signed the informed 
consent. A replacement subject will be enrolled if a subject discontinues from the study before 
completing the study visits. 
Each subject will attend for four visits of up to 1 hour in duration. The study is expected to last 
approximately 5 months and include a 1-month enrollment period.
5.
TEST ARTICLE ALLOCATION AND MASKING
5.1.
Test Article Allocation 
An ocular surface region (upper lid margin, lower lid margin or cornea) will be randomly 
allocated to each visit and a treatment (anesthesia or placebo) will be randomly allocated to 
each eye using a randomization scheme supplied by the study biostatistician. A single ocular 
region will be investigated at each visit and a single treatment will be applied to each eye at 
each visit. The clinical site will follow the randomization scheme provided and will complete 
enrollment according to the randomization list and will not pre-select or assign subjects. The 
assignment of the subjects must be performed at Visit 1. The following must have occurred 
prior to randomization:
• Informed consent has been obtained
• Subject meets all the inclusion / exclusion criteria
• Subject history and baseline information has been collected
The randomization scheme will be generated using the PROC PLAN procedure from the SAS 
Software Version 9.4 or higher (SAS Institute, Cary, NC).
The regions (upper lid margin, lower lid margin, or cornea) will be treated in a bilateral and 
random fashion using a Williams design with 3 regions and 3 periods. Each subject will be 
randomly assigned to one of six unique sequences (U/L/C, L/C/U, C/U/L, C/L/U, U/C/L,
L/U/C). For each region within a sequence, the two treatments will be randomly assigned to 
the left and right eye (anesthesia left eye/placebo right eye or placebo left eye/anesthesia left 
eye).
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5.2.
Masking
This is a single masked study, where subjects will be unaware of the treatment (anesthesia or 
placebo) applied to each eye, since the Investigator will be preparing the treatment out of sight 
of the subject. Investigators and clinical site personnel involved in the data collection will not
be masked as to the identity of the treatment.
5.3.
Procedures for Maintaining and Breaking the Masking
Study codes will not be used for masking.
6.
STUDY INTERVENTION
6.1.
Identity of Test Articles 
None.
6.2.
Ancillary Supplies/Products 
Table 1: Ancillary Supplies
Solution Name/Description
Proxymetacaine 
hydrochloride 0.5% (local 
anesthetic)
0.9% w/v sodium chloride 
solution
Manufacturer
Chauvin Pharmaceuticals 
Ltd (a subsidiary of Bausch 
+ Lomb)
Crest Medical Ltd (or
alternative sponsor-
approved product)
Preservative
None
None
Other distinguishing items (dye, 
packaging, approval status, etc.
Single-use minims (0.5ml)
Single-use pods (20ml)
6.3.
Administration of Test Articles
Not applicable.
6.4.
Packaging and Labeling
Not applicable.
6.5.
Storage Conditions
Not applicable.
6.6.
Collection and Storage of Samples
No samples will be collected as part of the study procedures.
6.7.
Accountability of Test Articles
Not applicable.  Subjects will be using their habitual lenses.
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+1 = Slightly Excessive
+2 = Extremely Excessive
Movement
-2 = Extremely Inadequate
-1 = Slightly Inadequate
0 = Optimum
+1 = Slightly Excessive
+2 = Extremely Excessive
2.11
Subjective comfort
Subjective comfort scores (vertical VAS scale) 
will be collected for each eye.
2.12
Right eye
Application of 
topical treatment
One ocular region (upper lid margin, lower 
lid margin or cornea) of the right eye will be 
anesthetized or will receive a saline placebo 
treatment, based on the randomization 
scheme.
The procedures will take place with the 
subject’s lenses in situ when the lid margins
are treated.  When the cornea is anesthetized, 
the subject’s habitual lens will be removed 
and immediately dosed with the anesthetic as
outlined in SOP #54.  The lens will not be 
spun to removed excess liquid and will not be 
soaked in any solution prior to re-insertion.  
The dosing/re-application procedure should 
take place as quickly as possible to avoid the 
lens from dehydrating excessively.
If any problems with the application of the 
treatment occur, subjects are eligible to repeat 
the visit on another day only once.
Eurolens 
Research
SOP #54
2.13
Right eye
Subjective comfort
Subjective comfort scores (vertical VAS 
scale) will be collected for the right eye after 
5 and 10 minutes post-treatment.
For the cornea, the contact lens is removed 
and then reapplied as part of the treatment 
application procedures. Comfort scores will 
also be collected immediately (ideally within 
30 seconds) after lens removal prior to 
treatment application.
2.14
Left eye
Application of 
topical treatment
The same ocular region (upper lid margin, 
lower lid margin or cornea) of the left eye 
will be anesthetized or will receive a saline 
placebo treatment, based on the 
randomization scheme.
Eurolens 
Research
SOP #54
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The procedures will take place with the 
subject’s lenses in situ when the lid margins 
are treated.  When the cornea is anesthetized, 
the subject’s habitual lens will be removed 
and immediately dosed with the anesthetic as 
outlined in SOP #54.  The lens will not be 
spun to removed excess liquid and will not be 
soaked in any solution prior to re-insertion.  
The dosing/re-application procedure should 
take place as quickly as possible to avoid the 
lens from dehydrating excessively.
If any problems with the application of the 
treatment occur, subjects are eligible to repeat 
the visit on another day only once.
2.15
Left
Subjective comfort
Subjective comfort scores (vertical VAS 
scale) will be collected for the left eye after 5
and 10 minutes post-treatment.
For the cornea, the contact lens is removed 
and then reapplied as part of the treatment 
application procedures. Comfort scores will 
also be collected immediately (ideally within 
30 seconds) after lens removal prior to 
treatment application.
2.16
Contact lens removal
Contact lenses will be removed and 
discarded.
2.17
Exit Slit Lamp 
Biomicroscopy
(Visits 2-3 only)
Efron Slit Lamp Classification Scale will be 
used to grade the findings.
Adverse events shall be documented and 
followed to resolution.
If the clearance of the fluorescein needs to be 
expedited, preservative-free rewetting drops 
or saline may be instilled.  
Eurolens 
Research 
SOP #13
2.18
Exit VA
(Visits 2-3 only)
Record subjects’ distance high contrast visual
acuity to the nearest letter (OD and OS) with
their habitual spectacle correction in place (or 
unaided if applicable).
Eurolens 
Research 
SOP # 12a 
2.19
End of Visit
(Visits 2-3)
Subject discharged and asked to return for 
next visit. Subjects can leave wearing 
spectacles or unaided as determined by the
investigator.
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x
Investigator’s clinical judgment regarding the subject safety reasons (that it is in the 
best interest of the subject to stop treatment)
x
Subject missed two study visits
x
Subject not compliant with lens wear schedule
For discontinued subjects, the Investigator will:
x
Complete the current visit (scheduled or unscheduled)
x
Complete the Final Evaluation, indicating the reason that the subject was discontinued 
from the study
An additional subject will be enrolled if a subject discontinues from the study prematurely. 
In cases where a subject is lost to follow-up, every possible effort must be made to contact the 
subject and determine the reason for discontinuation/withdrawal.  The measures taken to 
follow up must be documented including two written attempts and a certified letter (or 
equivalent) as the final attempt. 
9.
PRE-STUDY AND CONCOMITANT INTERVENTION/MEDICATION
Concomitant medications will be documented during screening and updated during the study.  
Disallowed medications or therapies for this study include: any topical medication such as 
eye drops or ointment or any medications that in the opinion of the investigator would affect 
contact lens wear.
10. DEVIATIONS FROM THE PROTOCOL
Investigator will notify study sponsor upon identification of a protocol deviation. Major 
protocol deviations must be reported to the sponsor within 24 hours after discovery of the 
protocol deviation.  The Investigator will report deviations per IRB/IEC requirements.  All 
deviations will be tracked and corrective actions implemented as appropriate. 
If it becomes necessary for the Investigator to implement a deviation in order to eliminate an 
immediate hazard to the trial subject, the Investigator may implement the deviation 
immediately without notification to the sponsor. Within 24 hours after the implemented 
deviation, the Investigator must notify and provide the rationale to the Sponsor and, as 
required, the IEC/IRB.
11. STUDY TERMINATION
The occurrence of one or more Unanticipated Serious Adverse Device Effect (USADE), or 
any SAE where the relationship to study agent cannot be ruled out, may result in stopping 
further study procedures.  In the event of a USADE or SAE, the Sponsor may unmask the 
treatment regimen for the subject(s) and will discuss this with the Investigator before any 
further subjects are enrolled.
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The Sponsor will determine when a study will be stopped.  The Principal Investigator always 
has the discretion to initiate stopping the study based on patient safety or if information 
indicates the study’s results are compromised.
JJVC reserves the right to terminate the study at any time for any reason.  Additionally, the 
IEC/IRB reserves the right to terminate the study if an unreasonable risk is determined.  The 
study can be terminated by the Principal Investigator at the individual clinical site due to 
specific clinical observations, if in their opinion, after a discussion with JJVC, it is determined 
that it would be unwise to continue at the clinical site.   
JJVC (and the IEC/IRB and DMC, if applicable) will evaluate all adverse events.  If it is 
determined that an adverse event presents an unreasonable risk, the investigation, or that part 
of the investigation presenting the risk, will be terminated, as soon as possible.
Should the study be terminated (either prematurely or as scheduled), the Investigator will 
notify the IEC/IRB and Regulatory Authority as required by local regulatory requirements.
12. PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS
A Product Quality Complaint (PQC) refers to any written, electronic, or oral communication 
that alleges deficiencies related to the identity, quality, durability, reliability, safety, 
effectiveness or performance of test articles after they have been released for clinical trial use.  
Potential complaints may come from a variety of sources including but not limited to subjects, 
clinical research associates (CRA), clinical operations managers (COM), medical monitors, 
and site personnel, etc. The following are not considered product quality complaints:
x
Subject satisfaction inquiries reported via “Subjective Questionnaires” and “Patient 
Reported Outcomes (PRO)”
x
Clinical test articles that are stored improperly or damaged after receipt at the 
investigational site
x
Lens replacements that occur due to drops/fall-outs
x
Damage deemed by clinicians or clinical staff to be caused by handling by the user, 
and not indicative of a quality deficiency (i.e. tears, rips, etc.), only in situations where 
there is no deficiency alleged by the subject
Within 24 hours of site personnel becoming aware that a PQC has occurred, the PQC must be 
recorded in the EDC system, which will trigger an automatic email notification to the 
appropriate COM/CRA and Clinical QA representative. In cases where the EDC system in use 
is not configured to send automatic notifications or when an EDC system is not used, the 
COM/CRA is responsible for notifying Clinical QA upon discovery that a PQC has occurred.  
Upon receipt of the EDC notification, the COM/CRA will contact the study site to collect 
additional information which will include:
x
Date the complaint was received/recorded in the EDC System (Date of Sponsor 
Awareness)
x
Who received the complaint
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x
Study number
x
Clinical site information (contact name, site ID, telephone number)
x
Lot number(s)
x
Unique Subject Identifier(s)
x
Indication of who first observed complaint (site personnel or subject)
x
OD/OS indication, along with whether the lens was inserted
x
Any related AE number if applicable
x
Detailed complaint description (scheduled/unscheduled visit, wear time, symptoms, 
resolution of symptoms, etc.)
x
Eye Care Provider objective (slit lamp) findings if applicable
x
Confirmation of product availability for return (and tracking information, if available), 
or rationale if product is not available for return 
Once a complaint is received, it will be assessed by the COM, CRA, or trained site personnel 
to determine if it is an Adverse Event/Serious Adverse Event (AE/SAE).  If the complaint 
results in an AE/SAE, the COM/CRA, or trained site personnel will follow Section 13 of this 
protocol. If the AE/SAE was potentially the result of a product quality related deficiency, these 
procedures also applies and will be executed in parallel.  
In some cases, a PQC form may be generated in EDC by the site in error.  In this event, the 
PQC forms will be marked “Intentionally Left Blank” or “ILB”.  Justification for ILB must be 
documented.
13. ADVERSE EVENTS
13.1. Definitions and Classifications
Adverse Event (AE) – 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. 
Note 1 to entry: This definition includes events related to the investigational medical device 
or the comparator.
Note 2 to entry: This definition includes events related to the procedures involved.
Note 3 to entry: For users or other persons, this definition is restricted to events related to 
investigational medical devices.”1
An AE includes any condition (including a pre-existing condition) that:
1. Was not present prior to the study, but appeared or reappeared following initiation of 
the study 
2. Was present prior to the study, but worsened during the study. This would include any 
condition resulting from concomitant illnesses, reactions to concomitant medications, 
or progression of disease states 
3. Pregnancy must be documented as an adverse event and must be reported to the clinical 
monitor and to the Sponsor immediately upon learning of the event
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Serious Adverse Event (SAE) – An SAE is any untoward medical occurrence that:
x
Results in death
x
Is life threatening
x
Requires in-patient hospitalization or prolongation of existing hospitalization
x
Results in persistent or significant disability/incapacity (e.g., a sight threatening event, 
a significant persistent or permanent change, impairment, damage, or disruption to the 
subject’s body)
x
Is a congenital anomaly/birth defect, or
x
Requires intervention to prevent permanent damage (the use of the test article resulting 
in a condition which requires medical or surgical intervention to preclude permanent 
impairment of the body structure or a body function).  Important medical events that 
may not result in death, be life-threatening, or require hospitalization may be 
considered an SAE when, based upon appropriate medical judgment, they may 
jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in the above definition
Diagnoses and conditions that are considered Ocular Serious Adverse Events include, but not 
limited to:
x
Microbial Keratitis (MK)
x
Iritis (including cells in the anterior chamber)
x
Permanent decrease in best spectacle corrected visual acuity equivalent to 2 acuity lines 
or greater
x
Central Corneal Opacity
x
Central Corneal Neovascularization
x
Uveitis
x
Endophthalmitis
x
Hypopyon
x
Hyphemia
x
Penetration of Bowman’s Membrane
x
Persistent Epithelial Defect
x
Limbal cell Damage leading to Conjunctivalization
Significant Adverse Events – Those events that are usually symptomatic and warrant 
discontinuation (temporary or permanent) of the test article (excluding Serious Adverse 
Events).  
Diagnoses and conditions that are considered Ocular Significant Adverse Events include, but 
not limited to the following:
x
Contact Lens Induced Peripheral Ulcer (CLPU)
x
Significant Infiltrative Events (SIE)
x
Superior Epithelial Arcuate Lesions (SEALs)
x
Any Temporary Loss of > 2 Lines of BSCVA
x
Other grade 3 or higher corneal findings, such as abrasions or edema
x
Non-contact lens related corneal events - e.g. Epidemic Keratoconjunctivitis (EKC)
x
Asymptomatic Corneal Scar
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x
Any corneal event which necessitates temporary lens discontinuation > 2 weeks
Non-Significant Adverse Events – Those conditions that are usually asymptomatic and 
usually do not warrant discontinuation (temporary or permanent) of the test article.  However, 
the Investigator may choose to treat as a precautionary measure.  
Diagnoses and conditions that are considered Ocular Non-Significant Adverse Events include, 
but not limited to the following:
x
Non-significant Infiltrative Event (NSIE)
x
Contact Lens Papillary Conjunctivitis (CLPC)
x
Superficial Punctate Keratitis (SPK)
x
Conjunctivitis: Bacterial, Viral, Allergic
x
Blepharitis
x
Meibomianitis
x
Contact Dermatitis
x
Localized Allergic Reactions
x
Any corneal event not explicitly defined as serious or significant adverse event, which 
necessitates temporary lens discontinuation < 2 weeks
Adverse Device Effect (ADE) – An ADE is an “adverse event related to the use of an 
investigational medical device.
Note 1 to entry: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device.
Note 2 to entry: This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device.”1
Unanticipated Adverse Device Effect (UADE) – Any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, the test article, 
if that effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the investigational plan, Investigator’s Brochure or protocol, or any other 
unanticipated serious problem associated with the test article that relates to the rights, safety 
and welfare of subjects.
13.2. Assessing Adverse Events
In conjunction with the medical monitor, the Investigator will evaluate adverse events to ensure 
the events are categorized correctly.  Elements of categorization will include:
x
Seriousness/Classifications (see definition in Section 13.1)
x
Causality or Relatedness – i.e. the relationship between the test article, study treatment 
or study procedures and the adverse event (not related; unlikely related; possibly
related; related - see definition in Section 13.2.1)
x
Adverse Event Severity – Adverse event severity is used to assess the degree of 
intensity of the adverse event (mild; moderate; severe for all events - see definition in 
Section 13.2.2)
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x
Outcome – not recovered or not resolved; recovering or resolving; recovered or 
resolved with sequelae; recovered or resolved; death related to adverse event; unknown
x
Actions Taken – none; temporarily discontinued; permanently discontinued; other
13.2.1. Causality Assessment
Causality Assessment – A determination of the relationship between an adverse event and the 
test article. The test article relationship for each adverse event should be determined by the 
investigator using these explanations:
x
Not Related- An adverse event that is not related to the use of the test article, study 
treatment or study procedures
x
Unlikely Related – An adverse event for which an alternative explanation is more 
likely, e.g. concomitant treatment, concomitant disease(s), or the relationship of time 
suggests that a causal relationship is not likely
x
Possibly Related – An adverse event that might be due to the use of the test article, or 
to the study treatment or study procedures. An alternative explanation, e.g. concomitant 
treatment, concomitant disease(s), is inconclusive.  The relationship in time is 
reasonable.  Therefore, the causal relationship cannot be excluded
x
Related – An adverse event that is listed as a possible adverse effect (device) or adverse 
reaction (drug) and cannot be reasonably explained by an alternative explanation, e.g. 
concomitant treatment of concomitant disease(s).  The relationship in time is very 
suggestive, e.g. it is confirmed by de-challenge and re-challenge
13.2.2. Severity Assessment
Severity Assessment – A qualitative assessment of the degree of intensity of an adverse event 
as determined by the Investigator or reported to him/her by the subject.  The assessment of 
severity is made irrespective of test article, study treatment or study procedure relationship or 
seriousness of the event and should be evaluated according to the following scale:
x
Mild – Event is noticeable to the subject, but is easily tolerated and does not interfere 
with the subject’s daily activities
x
Moderate – Event is bothersome, possible requiring additional therapy, and may 
interfere with the subject’s daily activities
x
Severe – Event is intolerable, necessitates additional therapy or alteration of therapy 
and interferes with the subject’s daily activities
13.3. Documentation and Follow-Up of Adverse Events
The recording and documenting of adverse events (ocular and non-ocular) begins when the 
subjects are exposed to the test article, study treatment or study procedure.  Adverse events 
reported before the use of test article, start of study treatment, or study procedures will be 
recorded as medical history. However, if the condition deteriorates at any time during the study 
it will be recorded and reported as an AE. Untoward medical events reported after the subject’s 
exit from the study will be recorded as adverse events at the discretion of the Investigator.
Upon finding an adverse event, the Principal Investigator will document the condition in the 
subject record and in the eCRFs. He/she will complete the Adverse Event /eCRF.  
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Complete descriptions of all adverse events must be available in the subject record. All 
Adverse Events including local and systemic reactions not meeting the criteria for “serious 
adverse events” shall be captured on the appropriate case report form or electronic data system. 
All adverse events occurring while the subject is enrolled in the study must be documented 
appropriately regardless of relationship.  
It is the Investigator’s responsibility to maintain documentation of each reported adverse event. 
All adverse events will be followed in accordance with applicable licensing requirements.  
Such documentation will include the following:
x
Adverse event (diagnosis not symptom)
x
Drawings or photographs (where appropriate) that detail the finding (e.g., size, 
location, and depth, etc.) 
x
Date the clinical site was notified 
x
Date and time of onset
x
Date and time of resolution
x
Adverse event classification, severity, and relationship to test articles, as applicable
x
Treatment regimen instituted, including concomitant medications prescribed, in 
accordance with applicable licensing requirements
x
Any referral to another health care provider if needed
x
Outcome, ocular damage (if any)
x
Likely etiology
x
Best corrected visual acuity at the discovery of the event and upon conclusion of the 
event
In addition, if an infiltrate(s) is present, he/she will complete the Corneal Infiltrate Assessment 
eCRF.  Where necessary, a culture of the corneal lesion will be collected to determine if the 
infection is microbial in nature.  If cultures are collected, the date of culture collection and 
laboratory utilized will be recorded. 
Changes in the severity of an AE shall be documented to allow an assessment of the duration 
of the event at each level of intensity to be performed.  Adverse events characterized as 
intermittent require documentation of the onset and duration of each episode. Changes in the 
assessment of relationship to the Test Article shall also be clearly documented.
Subjects who present with an adverse event shall be followed by the Investigator, within 
licensure, until all signs and symptoms have returned to pre-treatment status, stabilized, or 
been satisfactorily resolved.  If further treatment beyond licensure is required, the patient will 
be referred to the appropriate health care provider.  The Investigator will use his/her clinical 
judgment as to whether a subject reporting with an adverse event will continue in the study.  If 
a subject is discontinued from the study, it will be the responsibility of the Investigator to 
record the reason for discontinuation.  The Investigator will also document the adverse event 
appropriately and complete the Adverse Event eCRF. Any subjects with ongoing adverse 
events related to the test article, study treatment or study procedures, as of the final study visit 
date, should be followed to resolution of the adverse event or until referral to an appropriate 
health care provider, as recommended by the Investigator. Non-ocular adverse events that are 
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not related to the test article, study treatment, or study procedures may be recorded as 
“ongoing” without further follow-up.
13.4. Reporting Adverse Events 
The Investigator will notify the Sponsor of an adverse event by e-mail, facsimile, or telephone 
as soon as possible and no later than 24 hours from discovery for any serious /significant 
adverse events, and 2 days from discovery for any non-significant adverse event.  In addition, 
a written report will be submitted by the Principal Investigator to the IEC/IRB according to 
their requirements (Section 13.4.2).  The report will comment whether the adverse event was 
considered to be related to the test article, study treatment or study procedures.
13.4.1. Reporting Adverse Events to Sponsor
Serious/Significant Adverse Events
The Investigator will inform the sponsor of all serious/significant adverse events occurring 
during the study period as soon as possible by e-mail, fax, or telephone, but no later than 24 
hours following discovery of the event.  The Investigator is obligated to pursue and obtain 
information requested by the Sponsor in addition to that information reported on the eCRF. All 
subjects experiencing a serious/significant adverse event must be followed up and all outcomes 
must be reported.
In the event of a serious/significant adverse event, the Investigator must:
x
Notify the Sponsor immediately
x
Obtain and maintain in the subject’s records all pertinent medical information and 
medical judgment for colleagues who assisted in the treatment and follow-up of the 
subject
x
Provide the Sponsor with a complete case history which includes a statement as to 
whether the event was or was not related to the use of the test article
x
Notify the IEC/IRB as required by the IEC/IRB reporting procedure according to 
national regulations
Unanticipated (Serious) Adverse Device Effect (UADE)
In the event of an Unanticipated (Serious) Adverse Device Effect (UADE), the Investigator 
will submit a report of the UADE to the Sponsor and IEC/IRB as soon as possible, but no later 
than 24 hours after the Investigator first learns of the effect.  This report is in addition to the 
immediate notification mentioned above.
The Sponsor must conduct an evaluation of the UADE and must report the results of the 
evaluation to FDA, the IEC/IRB and participating Investigators within 10 working days after 
the Sponsor first receives notification of the effect.
Non-Serious Adverse Events
All non-serious adverse events, including non-serious adverse device effects, will be reported 
to the sponsor by the Investigator no later than 2 days from discovery.
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13.4.2. Reporting Adverse Events to the Responsible IEC/IRB and Health Authorities
Adverse events that meet the IEC/IRB requirements for reporting must be reported within the 
IEC/IRB’s written guidelines. Each clinical site will refer to and follow any guidelines set forth 
by their Approving IEC/IRB. Each clinical site will refer to and follow any guidelines set forth 
by their local governing Health Authorities.
The Sponsor will report applicable Adverse Events to the local health authorities according the 
written guidelines, including reporting timelines. 
13.4.3. Event of Special Interest
None.
13.5. Reporting of Pregnancy
Subjects reporting pregnancy (by self-report) during the study will be discontinued after the 
event is recorded as an Adverse Event.  Once discontinued, pregnant participants and their 
fetuses will not be monitored for study related purposes.  At the Investigator’s discretion, the 
study participant may be followed by the Investigator through delivery. However, this data will 
not be collected as part of the clinical study database.  Pregnant participants are not 
discontinued from contact lens or solution related studies for safety concerns, but due to 
general concerns relating to pregnancy and contact lens use.  Specifically, pregnant women are 
discontinued due to fluctuations in refractive error and/or visual acuity that occur secondary to 
systemic hormonal changes, and not due to unforeseen health risks to the mother or fetus.
14. STATISTICAL METHODS
14.1. General Considerations
Statistical Analysis will be undertaken by the sponsor or under the authority of the sponsor. A 
general description of the statistical methods to be implemented in this clinical trial is outlined 
below.
All data summaries and statistical analyses will be performed using the SAS software Version 
9.4 (SAS Institute, Cary, NC). Throughout the analysis of data, the results for each subject/eye 
will be used when available for summarization and statistical analysis.  Unscheduled visits will
be summarized separately if applicable and will be excluded from the statistical analysis.
Summary tables (descriptive statistics and/or frequency tables) will be provided for all baseline 
variables, efficacy variables and safety variables as appropriate.  Continuous variables will be 
summarized with descriptive statistics (n, mean, standard deviation (SD), median, minimum 
and maximum). Frequency count and percentage of subjects or eyes within each category will 
be provided for categorical data.
This is a feasibility study and further exploratory analysis can be undertaken if necessary at 
the discretion of the study responsible clinician.
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14.2. Sample Size Justification
The plan is to enroll 20 subjects with a target of 15 subjects to complete the study. This is a 
pilot study and the sample size was not based on any empirical power calculation.
The tables below, provided using the POWER procedure in SAS 9.4, summarizes statistical 
power based on the following assumptions:
x
Testing for superiority with 0 VAS points and equivalence with +/- 10 VAS points
x
True difference for superiority: 5, 7.5, 10 points and for equivalence: -5, 0, -5 points
x
Estimated standard deviations of 15 and 20 points
x
Intraclass correlations of 0.4, 0.6, and 0.8
x
Two-sided type I error rate of 0.05
x
15 subjects successfully complete the study
Table 3: Power Analysis for the Primary Hypothesis (Superiority)
Intraclass Correlation
Difference
(Test-Control)
Estimated
Standard Deviation
0.4
0.6
0.8
5.0
15
0.300
0.393
0.617
5.0
20
0.211
0.269
0.425
7.5
15
0.515
0.661
0.897
7.5
20
0.351
0.460
0.705
10.0
15
0.724
0.864
0.987
10.0
20
0.515
0.661
0.897
The study is appropriately powered (power above 80%) to show superiority of anesthetized 
eyes over eyes that received the placebo when the difference in VAS comfort is at least 7.5 
points and the intraclass correlation is at least 0.8.
Table 4: Power Analysis for the Primary Hypothesis (Equivalence)
Intraclass Correlation
Difference
(Test-Control)
Estimated
Standard Deviation
0.4
0.6
0.8
-5.0
15
0.259
0.386
0.617
-5.0
20
0.081
0.202
0.422
0.0
15
0.453
0.728
0.974
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Intraclass Correlation
Difference
(Test-Control)
Estimated
Standard Deviation
0.4
0.6
0.8
0.0
20
0.117
0.334
0.794
5.0
15
0.259
0.386
0.617
5.0
20
0.081
0.202
0.422
The study is appropriately powered (power above 80%) to show equivalence between comfort 
scores at post-treatment and 5-minute post-application when there is no difference (0 VAS 
points) and the intraclass correlation is at least 0.8.
14.3. Analysis Populations
Safety Population:
All subjects that complete any study procedures after signing the Informed Consent form 
(subjects will be wearing their habitual contact lenses in this study). At least one observation 
should be recorded.
Per-Protocol Population: 
All subjects who have successfully completed all visits and did not substantially deviate from 
the protocol as determined by the trial cohort review committee prior to database hard lock 
(Per-Protocol Population). Justification of excluding subjects with protocol deviations in the 
per-protocol population set will be documented in a memo to file.
Intent-to-Treat (ITT) Population:
All randomized subjects regardless of actual treatment and subsequent withdrawal from study 
or deviation from protocol. At least one observation should be recorded.
14.4. Level of Statistical Significance
All planned analysis for this study will be conducted with an overall type I error rate of 5%. 
14.5. Primary Analysis 
VAS Comfort 
VAS Comfort score at 5 and 10 minutes post treatment will be analyzed separately using a 
linear mixed model. The model will include the following experimental design factors: 
treatment, sequence of treatment, region, sequence of region, period, time event, and first-order 
carryover as fixed effects. Baseline characteristics such as age and gender may be included as 
covariates when appropriate. The covariance between residual errors for the same subject 
across periods will be modeled using one of the following covariance structures: Compound 
Symmetry (CS) or Unstructured (UN). The covariance structure that returns the lowest Akaike 
Information Criteria Corrected (AICC) will be selected as the structure that best fits the data. 
The Kenward and Roger method8 will be used for the calculation of denominator degrees of 
freedom. 
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The null and alternative hypothesis for superiority of anesthetized eyes compared to eyes that 
received the placebo with respect to VAS comfort at post treatment, where ߤ஺െߤ௉is the 
difference in VAS comfort between anesthesia and placebo treatments, is as follows:
ܪ଴ǣ ߤ஺െߤ௉൑Ͳ
ܪ஺ǣ ߤ஺െߤ௉൐Ͳ
The hypothesis will be tested via corresponding two-sided 95% confidence interval for least-
squares mean difference (anesthesia minus placebo) of VAS comfort. Superiority will be 
concluded if the lower limit is greater than 0 for at least one of the three ocular regions (upper 
lid margin, lower lid margin, or cornea).
The null and alternative hypothesis for equivalence of VAS comfort scores at post-treatment 
and 5-minutes post-application, where ߤଵെߤଶis the difference in VAS comfort score between 
post-treatment and 5-minutes post-application, is as follows:
ܪ଴ǣ ȁߤଵെߤଶȁ ൒ͳͲ
ܪ஺ǣ ȁߤଵെߤଶȁ ൏ͳͲ
The hypothesis will be tested via corresponding two-sided 95% confidence interval for least-
squares mean difference (post treatment minus post application) in VAS comfort score. 
Equivalence will be concluded if the upper limit is less than ͳͲ and the lower limit is greater 
than െͳͲ.
VAS Comfort (Change)
VAS Comfort score change from pre-treatment to 5 and 10 minute post-treatment values will 
be analyzed separately using a linear mixed model. The model will include the following 
experimental design factors: treatment, sequence of treatment, region, sequence of region, 
period, and first-order carryover as fixed effects; subject as a random effect. Baseline 
characteristics such as age and gender may be included as covariates when appropriate. The 
covariance between residual errors for the same subject across periods will be modeled using
one of the following covariance structures: Compound Symmetry (CS) or Unstructured (UN).
The covariance structure that returns the lowest Akaike Information Criteria Corrected (AICC) 
will be selected as the structure that best fits the data. The Kenward and Roger method8 will 
be used for the calculation of denominator degrees of freedom. 
The null and alternative hypothesis for superiority of anesthetized eyes compared to eyes that 
received the placebo with respect to VAS comfort change from pre-treatment, where ο஺െο௉
is the difference in VAS comfort change from pre-treatment between anesthesia and placebo 
treatments, is as follows:
ܪ଴ǣ ο஺െο௉൑Ͳ
ܪ஺ǣ ο஺െο௉൐Ͳ
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The hypothesis will be tested via corresponding two-sided 95% confidence interval for least-
squares mean difference (anesthesia minus placebo) of VAS comfort change from pre-
treatment. Superiority will be concluded if the lower limit is greater than 0 for at least one of 
the three ocular regions (upper lid margin, lower lid margin, or cornea).
14.6. Secondary Analysis 
VAS Comfort 
The null and alternative hypothesis for superiority of eyes with the cornea anesthetized 
compared to with upper or lower lid margin anesthetized with respect to VAS comfort at post 
treatment, where ߤ஼െߤ௅is the difference in VAS comfort between cornea and either lower 
or upper lid margins, is as follows: 
ܪ଴ǣ ߤ஼െߤ௅൑Ͳ
ܪ஺ǣ ߤ஼െߤ௅൐Ͳ
The hypothesis will be tested via corresponding two-sided 95% confidence interval for least-
squares mean difference (cornea minus upper or lower lid margin) of VAS comfort. Superiority 
will be concluded if the lower limit is greater than 0 for at least one of the two differences 
(cornea minus upper lid margin or cornea minus lower lid margin).
The null and alternative hypothesis for equivalence of VAS comfort scores at lens removal and 
prior to lens application, where ߤଵെߤଶis the difference in VAS comfort score between lens 
removal and prior to lens application, is as follows:
ܪ଴ǣ ȁߤଵെߤଶȁ ൒ͳͲ
ܪ஺ǣ ȁߤଵെߤଶȁ ൏ͳͲ
The hypothesis will be tested via corresponding two-sided 95% confidence interval for least-
squares mean difference (lens removal minus prior to lens application) in VAS comfort score. 
Equivalence will be concluded if the upper limit is less than ߜand the lower limit is greater 
than െͳͲ.
VAS Comfort (Change)
The null and alternative hypothesis for superiority of eyes with the cornea anesthetized 
compared to with upper or lower lid margin anesthetized with respect to VAS comfort change 
from pre-treatment, where ο஼െο௅is the difference in VAS comfort change from pre-
treatment between cornea and either lower or upper lid margins, is as follows: 
ܪ଴ǣ ο஼െο௅൑Ͳ
ܪ஺ǣ ο஼െο௅൐Ͳ
The hypothesis will be tested via corresponding two-sided 95% confidence interval for least-
squares mean difference (cornea minus upper or lower lid margin) of VAS comfort change 
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from pre-treatment. Superiority will be concluded if the lower limit is greater than 0 for at least 
one of the two differences (cornea minus upper lid margin or cornea minus lower lid margin).
14.7. Other Exploratory Analyses
Not applicable.
14.8. Interim Analysis
No interim analysis is planned.
14.9. Procedure for Handling Missing Data and Drop-Outs
Missing or spurious values will not be imputed. The count of missing values will be included 
in the summary tables and listings. 
14.10. Procedure for Reporting Deviations from Statistical Plan
The analysis will be conducted according to that specified in above sections.  There are no 
known reasons for which it is planned to deviate from these analysis methods.  If for any reason 
a change is made, the change will be documented in the study report along with a justification 
for the change.
15. DATA HANDLING AND RECORD KEEPING/ARCHIVING
15.1. Electronic Case Report Form/Data Collection
The data for this study will be captured on electronic case report forms (eCRFs) using an EDC 
system (Bioclinica). An authorized data originator will enter study data into the eCRFs using 
the EDC system. Data collected on equipment that is not captured in EDC will be formatted to 
the specification of the JJVC database manager and sent to JJVC for analysis. 
External Date Sources for this study include: Not Applicable
The clinical data will be recorded on dedicated eCRFs specifically designed to match the study 
procedures for each visit.  Once completed, the eCRFs will be reviewed for accuracy and 
completeness and signed by the Investigator.  The sponsor or sponsor’s representatives will be 
authorized to gain access to the subject recordation for the purposes of monitoring and auditing 
the study. 
Edit checks, electronic queries, and audit trails are built into the system to ensure accurate and 
complete data collection. Data will be transmitted from the clinical site to a secure central 
database as forms are completed or updated, ensuring information accuracy, security, and 
confidentiality. After the final database lock, the Investigator will be provided with Individual 
Patient Profiles (IPP) including the full audit trail on electronic media in PDF format for all of 
the study data. The IPP must be retained in the study files as a certified copy of the source data 
for the study. 
The content and structure of the eCRFs are compliant with ISO14155:2011.1
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15.2. Subject Record
At a minimum, subject record should be available for the following:
x
subject identification
x
eligibility
x
study identification
x
study discussion
x
provision of and date of informed consent
x
visit dates
x
results of safety and efficacy parameters as required by the protocol
x
a record of all adverse events
x
follow-up of adverse events
x
medical history and concomitant medication
x
date of study completion
x
reason for early discontinuation of test article or withdrawal from the study, if 
applicable
The subject record is the eCRF or an external record.  The author of an entry in the subject
record must be identifiable.  The first point of entry is considered to be the source record.
Adverse event notes must be reviewed and initialed by the Investigator.
16. DATA MANAGEMENT
16.1. Access to Source Data/Document
The Investigator/Institution will permit trial-related monitoring, audits, IEC/IRB review and 
regulatory inspection(s) by providing direct access to source data/documents.  Should the 
clinical site be contacted for an audit by an IEC/IRB or regulatory authority, JJVC must be 
contacted and notified in writing within 24 hours.
16.2. Confidentiality of Information
Information concerning the investigational product and patent application processes, scientific 
data or other pertinent information is confidential and remains the property of JJVC.  The 
Investigator may use this information for the purposes of the study only. It is understood by 
the Investigator that JJVC will use information developed in this clinical study in connection 
with the development of the investigational product and therefore may disclose it as required 
to other clinical investigators and to regulatory agencies. In order to allow the use of the 
information derived from this clinical study, the Investigator understands that he/she has an 
obligation to provide complete test results and all data developed during this study to the 
Sponsor.
16.3. Data Quality Assurance
Steps will be taken to ensure the accuracy and reliability of data, include the selection of 
qualified investigators and appropriate clinical sites and review of protocol procedures with
the Principal Investigator.  The Principal Investigator, in turn, must ensure that all Sub-
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Investigators and clinical site personnel are familiar with the protocol and all study-specific 
procedures and have appropriate knowledge of the study article.
Training on case report form completion will be provided to clinical site personnel before the 
start of the study.  The Sponsor will review case report forms for accuracy and completeness 
remotely during the conduct of the study, during monitoring visits, and after transmission to 
data management.  Any data discrepancies will be resolved with the Investigator or designee, 
as appropriate.
Quality Assurance representatives from JJVC may visit clinical sites to review data produced 
during the study and to access compliance with applicable regulations pertaining to the conduct 
of clinical trials.  The clinical sites will provide direct access to study-related source 
data/documents and reports for the purpose of monitoring and auditing by JJVC and for 
inspection by local and regulatory authorities.
17. MONITORING
The study monitors will maintain close contact with the Principal Investigator and the 
Investigator’s designated clinical site personnel.  The monitor’s responsibilities will include:
x
Ensuring that the investigation is being conducted according to the protocol, any 
subsequent amendments, and regulatory requirements are maintained
x
Ensuring the rights and wellbeing of subjects are protected
x
Ensuring adequate resources, including facilities, laboratories, equipment, and 
qualified clinical site personnel
x
Ensuring that protocol deviations are documented with corrective action plans, as 
applicable
x
Ensuring that the clinical site has sufficient and supplies
x
Clarifying questions regarding the study
x
Resolving study issues or problems that may arise
x
Reviewing of study records and source documentation verification in accordance with 
the monitoring plan
18. ETHICAL AND REGULATORY ASPECTS
18.1. Study-Specific Design Considerations
Potential subjects will be fully informed of the risks and requirements of the study and, during 
the study, subjects will be given any new information that may affect their decision to continue 
participation.  Subjects will be told that their consent to participate in the study is voluntary 
and may be withdrawn at any time with no reason given and without penalty or loss of benefits 
to which they would otherwise be entitled.  Only subjects who are fully able to understand the 
risks, benefits, and potential adverse events of the study, and provide their consent voluntarily 
will be enrolled.
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18.2. Investigator Responsibility
The Principal Investigator is responsible for ensuring that the clinical study is performed in 
accordance with the signed agreement, the investigational plan, Section 4 of the ICH E6 
guidelines on Good Clinical Practice (GCP),2 and applicable regulatory requirements.  GCP is 
an international ethical and scientific quality standard for designing, conducting, recording, 
and reporting studies that involve the participation of human subjects. Compliance with this 
standard provides public assurance that the rights, safety, and well-being of study subjects are 
protected, consistent with the principles of the Declaration of Helsinki 64th WMA General 
Assembly 20133 and that the clinical study data are credible.  The Investigator must maintain 
clinical study files in accordance with Section 8 of the ICH E6 guidelines on Good Clinical 
Practice (GCP),2 and applicable regulatory requirements.
18.3. Independent Ethics Committee or Institutional Review Board (IEC/IRB)
Before the start of the study, the Investigator (or Sponsor when applicable) will provide the 
IEC/IRB with current and complete copies of the following documents (where applicable):
x
Final protocol and, if applicable, amendments
x
Sponsor-approved informed consent form (and any other written materials to be 
provided to the subjects)
x
Investigator’s Brochure (or equivalent information) and amendments
x
Sponsor-approved subject recruitment materials
x
Information on compensation for study-related injuries or payment to subjects for 
participation in the study
x
Investigator’s curriculum vitae, clinical licenses, or equivalent information (unless not 
required, as documented by IEC/IRB)
x
Information regarding funding, name of the Sponsor, institutional affiliations, other 
potential conflicts of interest, and incentives for subjects
x
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after IEC/IRB has given full approval of the final protocol, 
amendments (if any), the informed consent form, applicable recruiting materials, and subject 
compensation programs, and the Sponsor has received a copy of this approval. This approval 
letter must be dated and must clearly identify the documents being approved.
During the study, the Investigator (or Sponsor when applicable) will send the following 
documents to the IEC/IRB for their review and approval, where appropriate:
x
Protocol amendments
x
Revision(s) to informed consent form and any other written materials to be provided to 
subjects
x
If applicable, new or revised subject recruitment materials approved by the Sponsor
x
Revisions to compensation for study-related injuries or payment to subjects for 
participation in the study
x
Investigator’s Brochure amendments or new edition(s)
x
Summaries of the status of the study (at least annually or at intervals stipulated in 
guidelines of the IEC/IRB)
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x
Reports of adverse events that are serious, unanticipated, and associated with the test 
articles, according to the IRB’s requirements
x
New information that may adversely affect the safety of the subjects or the conduct of 
the study
x
Major protocol deviations as required by the IEC/IRB
x
Report of deaths of subjects under the Investigator's care
x
Notification if a new Investigator is responsible for the study at the clinical site
x
Any other requirements of the IEC/IRB
For protocol amendments that increase subject risk, the amendment and applicable informed 
consent form revisions must be submitted promptly to the IEC/IRB for review and approval 
before implementation of the change(s).
At least once a year, the IEC/IRB will review and reapprove this clinical study. This request 
should be documented in writing.
At the end of the study, the Investigator (or Sponsor where required) will notify the IEC/IRB 
about the study completion.  Documentation of this notification must be retained at the clinical 
site and a copy provided to the CRO or Sponsor as applicable.
18.4. Informed Consent
Each subject must give written consent according to local requirements after the nature of the 
study has been fully explained. The consent form must be signed before performance of any 
study-related activity. The consent form that is used must be approved by both the Sponsor 
and by the reviewing IEC/IRB. The informed consent is in accordance with principles that 
originated in the Declaration of Helsinki,3 current ICH2 and ISO 141551 guidelines, applicable 
regulatory requirements, and Sponsor Policy.
Before entry into the study, the Investigator or an authorized member of the clinical site
personnel must explain to potential subject the aims, methods, reasonably anticipated benefits, 
and potential hazards of the study, and any discomfort it may entail. Subjects will be informed 
that their participation is voluntary and that they may withdraw consent to participate at any 
time. 
The subject will be given sufficient time to read the informed consent form and the opportunity 
to ask questions. After this explanation and before entry into the study, consent should be 
appropriately recorded by means of the subject's dated signature. After having obtained the 
consent, a copy of the informed consent form must be given to the subject.
18.5. Privacy of Personal Data
The collection, processing and disclosure of personal data and medical information related to
the Study Subject, and personal data related to Principal Investigator and any clinical site 
personnel (e.g., name, clinic address and phone number, curriculum vitae) is subject to 
compliance with the General Data Protection Regulation5 and other applicable personal data 
protection and security laws and regulations.  Appropriate measures will be employed to 
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safeguard these data, to maintain the confidentiality of the person’s related health and medical 
information, to properly inform the concerned persons about the collection and processing of 
their personal data, to grant them reasonable access to their personal data and to prevent access 
by unauthorized persons.
All information obtained during the course of the investigation will be regarded as confidential. 
All personal data gathered in this trial will be treated in strictest confidence by Investigators, 
monitors, Sponsor’s personnel and IEC/IRB.  No data will be disclosed to any third party 
without the express permission of the subject concerned, with the exception of Sponsor 
personnel (monitor, auditor), IEC/IRB and regulatory organizations in the context of their 
investigation related activities that, as part of the investigation will have access to the CRFs 
and subject records.
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to investigate the efficacy, safety, quality, and utility of 
the investigational product(s) used in this study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations.
The Sponsor ensures that the personal data will be:
x
processed fairly and lawfully
x
collected for specified, explicit, and legitimate purposes and not further processed in a 
way incompatible with these purposes
x
adequate, relevant, and not excessive in relation to said purposes
x
accurate and, where necessary, kept current
Explicit consent for the processing of personal data will be obtained from the participating 
subject before collection of data. Such consent should also address the transfer of the data to 
other entities and to other countries.
The subject has the right to request through the Investigator access to his personal data and the 
right to request rectification of any data that are not correct or complete. Reasonable steps 
should be taken to respond to such a request, taking into consideration the nature of the request,
the conditions of the study, and the applicable laws and regulations.
Appropriate technical and organizational measures to protect the personal data against 
unauthorized disclosures or access, accidental or unlawful destruction, or accidental loss or 
alteration must be put in place. Sponsor personnel whose responsibilities require access to 
personal data agree to keep the identity of study subjects confidential.
19. STUDY RECORD RETENTION
In compliance with the ICH/GCP guidelines,2 the Investigator/Institution will maintain all 
CRFs and all subject records that support the data collected from each subject, as well as all 
study documents as specified in ICH/GCP2 and all study documents as specified by the 
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applicable regulatory requirement(s). The Investigator/Institution will take measures to prevent 
accidental or premature destruction of these documents.
Essential documents must be retained until at least two (2) years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least two (2) years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These 
documents will be retained for a longer period if required by the applicable regulatory 
requirements or instructed by the Sponsor. It is the responsibility of the Sponsor to inform the 
Investigator/Institution as to when these documents no longer need to be retained.
If the responsible Investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The Sponsor must be notified in writing of the name and address of 
the new custodian. Under no circumstance shall the Investigator relocate or dispose of any 
study documents before having obtained written approval from the Sponsor.
If it becomes necessary for the Sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the Investigator must permit access to such reports.
If the Investigator has a question regarding retention of study records, he/she should contact 
JJVC.
20. FINANCIAL CONSIDERATIONS
Remuneration for study services and expenses will be set forth in detail in the Clinical Research 
Agreement.  The Research Agreement will be signed by the Principal Investigator and a JJVC 
management representative prior to study initiation.
JJVC reserves the right to withhold remuneration for costs associated with protocol violations 
such as:
x
Continuing an ineligible subject in the study
x
Scheduling a study visit outside the subject’s acceptable visit range
JJVC reserves the right to withhold final remuneration until all study related activities have 
been completed, such as:
x
Query resolution
x
Case Report Form signature
x
Completion of any follow-up action items 
21. PUBLICATION
This study will be registered on ClinicalTrials.gov.
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22. REFERENCES
1. ISO 14155:2011: Clinical Investigation of Medical Devices for Human Subjects — Good
Clinical Practice. Retrieved September 12, 2018, from 
https://www.iso.org/standard/45557.html
2. International Conference on Harmonization Good Clinical Practice E6 (ICH-GCP). 
Retrieved September 12, 2018, from 
http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html
3. Declaration of Helsinki - Ethical principles for Medical Research Involving Human 
Subjects. Retrieved September 12, 2018, from https://www.wma.net/policies-post/wma-
declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-
subjects/
4. United States (US) Code of Federal Regulations (CFR). Retrieved September 12, 2018, 
from https://www.gpo.gov/fdsys/browse/collectionCfr.action?collectionCode=CFR
5. General Data Protection Regulation. Retrieved September 12, 2018, from
http://www.eugdpr.org/
6. Navascues-Cornago M. Clinical Study Report
 June 27, 2018.
7. Navascues-Cornago M, Maldonado-Codina C and Morgan PB. Effect of selective topical 
anesthesia on initial comfort of rigid contact lenses. British Contact Lens Association 39th
Annual Clinical Conference and Exhibition. May 29-31, 2015, ACC, Liverpool, UK.
8. Kenward, M. G., and Roger, J. H.  Small Sample Inference for Fixed Effects from 
Restricted Maximum Likelihood.Biometrics; 1997, 53:983–997.
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APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES)
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PRO SPECIFICATION Version 1 Final  2018-09-05
Protocol 6292
Johnson & Johnson Vision Care, Inc.
Confidential
1
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PRO SPECIFICATION Version 1 Final  2018-09-05
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2
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PRO SPECIFICATION Version 1 Final  2018-09-05
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PRO SPECIFICATION Version 1 Final  2018-09-05
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PRO SPECIFICATION Version 1 Final  2018-09-05
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5
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APPENDIX B: PATIENT INSTRUCTION GUIDE 
Not Applicable - study will use habitual contact lenses only.
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APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT)
1. Minims Proxymetacaine hydrochloride 0.5% (Chauvin Pharmaceuticals Ltd)
2. Sterile Saline Pod Material Safety Data Sheet (Crest Medical Ltd)
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APPENDIX D: 
x
Subject Reported Ocular Symptoms
x
Patient Reported Outcomes
x
Eurolens Research SOP #13: Examination of the anterior segment using slit lamp
biomicroscopy. Version 4, Feb 5, 2018.
x
Eurolens Research SOP #12a: The set-up, measurement of visual acuity and procedures 
for carrying out an over-refraction using the Eurolens computerized LogMAR VA 
chart. Version 2, Dec 19, 2017.
x
Eurolens Research SOP #54: Procedure for selectively anesthetising the cornea and 
eyelid margins. Version 1, June 1, 2017.
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SUBJECT REPORTED OCULAR SYSTEMS
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PATIENT REPORTED OUTCOMES
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Page 1 of 1
Patient Reported Outcomes 
OVERVIEW
This document contains instructions for the collection of patient reported outcomes. A patient 
reported outcome (PRO) is an umbrella term that covers a whole range of potential types of 
measurement but is used specifically to refer to self-reports by the patient in a clinical study. 
The objective of a PRO is to quantify subjective responses.  
MATERIALS
Case report form modules (developed by the clinical lead and PRO lead).
PROCEDURE
Specific instructions will be given to the investigator for all questionnaires used in a study. 
GRADING
SCALE
The grading scale will be specific to each questionnaire used.
ADDITIONAL
INFORMATION
All questionnaires as defined by the current revision of VCCL-0034 must be requested 
through the PRO lead.
REFERENCES
x
FDA Guidance For Industry – Patient Reported Outcome Measures:  Usein Medical
Product Development to Support Labeling Claims.
http://www fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM193282.pdf
x
Current revision of VCCL-0034.
TRAINING
REQUIRE-
MENTS
The training requirement for this document is “Read Only.”
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EXAMINATION 
OF 
THE 
ANTERIOR 
SEGMENT 
USING 
SLIT 
LAMP 
BIOMICROSCOPY
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Eurolens Research 
 
 
 
 
Clinical 
Standard Operating Procedure 
 
 
 
 
Examination of the anterior segment 
using slit lamp biomicroscopy 
 
 
Carole Maldonado-Codina 
Associate Director 
 
 
First issued: v0; May 20, 2002 
Reviewed (with changes): v2; June 26, 2009 
Reviewed (no changes): v2; October 14, 2011 
Reviewed (with changes): v3; March 4, 2014 
Reviewed (with changes): v4; February 2, 2016 
Reviewed (no changes): v4; February 5, 2018 
 
 
 
 
 
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Eurolens Research                     Slit lamp biomicroscopy (v4) 
   February 2, 2016 
 
 
 
                                           
          
 Confidential 
3 
Summary 
The slit lamp biomicroscope is a high quality illuminating observation system which 
allows the external and internal ocular structures to be assessed in detail. The Efron 
Grading Scales for Contact Lens Complications1 will be used to quantify most of the 
observations made.  If an alternative grading scale is to be used this will be detailed in 
the study protocol. 
 
Definitions 
External ocular structures in this procedure refer to the following structures: conjunctiva, 
sclera, limbus and associated blood vessels, cornea, lids, lashes and tear film.  
Internal ocular structures in this procedure refer to the anterior chamber. 
Wratten 12 filter – A yellow filter which enhances the contrast of fluorescein staining 
when viewed using cobalt blue light. 
 
Procedure 
1. Using the recommended settings for slit width, magnification and filter, examine 
the external and internal ocular structures2. The following primary signs should 
be graded using the Efron Grading Scales: conjunctival redness, limbal redness, 
corneal neovascularisation, epithelial microcysts, corneal oedema and corneal 
infiltrates. The following secondary signs are also usually graded using the Efron 
Grading Scales: blepharitis and meibomian gland dysfunction. The number of 
mucin balls present are counted and recorded. 
2. Instil sodium fluorescein (using a fluorescein ophthalmic strip wetted with saline) 
in both eyes and using cobalt blue light and a Wratten 12 filter or similar yellow 
filter, examine and grade the following: corneal and conjunctival staining.  The 
location and ‘type’ of any staining is also usually recorded. Corneal staining type 
is usually divided into the following categories: no staining, toxicity, SEAL, foreign 
body/abrasion, inferior dehydration and non-specific. 
3. The upper eyelid should then be everted and examined both with cobalt blue light 
(with the yellow filter in place) and with white light (no filter in place).  The grading 
of upper palpebral conjunctivitis should then be made with the Efron Grading 
Scales.   
4. If a soft contact lens needs to be applied after the examination, irrigate the eye 
with unpreserved sterile saline once the examination has been completed in 
order to remove excess sodium fluorescein. 
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THE SET-UP, MEASUREMENT OF VISUAL ACUITY AND PROCEDURES FOR 
CARRYING 
OUT 
AN 
OVER-REFRACTION 
USING 
THE 
EUROLENS 
COMPUTERIZED LOGMAR VA CHART
CR-6292, v1.0
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12a 
 
 
 
 
 
 
 
 
Eurolens Research 
 
Clinical 
Standard Operating Procedure 
 
 
 
 
 
The set up, measurement of visual acuity and 
procedures for carrying out an over refraction 
using the Eurolens computerised logMAR  
VA chart  
 
 
 
 
 
Neil Chatterjee 
Research Optometrist 
 
 
First issued: v0; July 8, 2009 
Reviewed (with changes): v1; February 7, 2014 
Reviewed (no changes): v1; February 2, 2016 
Reviewed (with changes): v2; December 19, 2017 
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Eurolens Research 
Computer logMAR VA chart (v2) 
December 19, 2017 
4 
Confidential 
 
Microsoft Excel software.  The chart is displayed through an external monitor 
connected to the Apple Mac via its monitor socket and appropriate cable. 
2. The Eurolens chart is similar in design to the traditional Bailey-Lovie logMAR chart, 
however it uses a reversed Sloan font as the optotype.  The need for the reversed 
font is due to the chart being viewed indirectly in a mirror in a 3m consulting room.  
The chart is mounted on an adjustable mount, above the subject’s head. 
3. The indirect viewing makes the effective distance of the chart 6m from the subject.  
This 6m distance is the standard testing distance in optometric practice. 
4. High (100%) and low (10%) contrast VA measurements can be taken with the chart. 
5. The VA measurement from the Eurolens chart is intended to be equivalent to that 
obtained from the traditional Bailey-Lovie logMAR charts at 6m.  The Eurolens chart 
has two advantages over the Bailey-Lovie.  The Eurolens chart does not fade or 
discolour (which reduces legibility).  Further, unlike the fixed Bailey-Lovie chart, the 
letters can be randomised on the Eurolens chart, which reduces the effect of memory 
influencing the subject’s VA score. 
 
Initial computer set up 
1. 
The Apple Macintosh should have the following installed:  
a. Reversed Sloan font (otf file, which should be copied to the Macintosh 
HD/Library/Fonts/ folder) 
b. Microsoft Office 2011 or later 
c. Eurolens chart v5 software 
2. 
The external monitor should be connected to the Mac.  It will require the use of an 
appropriate adaptor and cable. 
3. 
The additional monitor should be recognised automatically by the Mac.  The Mac 
should configure the monitor as a second desktop.  To verify this, move the mouse 
pointer across the screen.  It should be possible to move the mouse pointer off the 
edge of the main screen and it should appear on the external monitor. 
4. 
The Eurolens Chart software is an Excel file called Eurolens Research chart.xls.  
This, for convenience, is located on the desktop. 
5. 
To run the chart, open the Excel file.  Click on “enable macros”. 
6. 
The chart should be displayed on the external monitor and the chart’s control panel 
should appear on the Mac’s main screen (Figure 1). 
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Eurolens Research 
Computer logMAR VA chart (v2) 
December 19, 2017 
5 
Confidential 
 
 
Figure 1.  Chart control panel 
 
7. 
If the letter chart appears on the Mac’s main screen, it will need to be “dragged” onto 
the external monitor.  To do this the chart control box must be closed.  The main 
chart can now be dragged onto the second screen and maximised. 
8. 
To restart the control panel, click on the Excel icon in the dock.  Then in Excel’s 
menu, select.: Tools -> Macro-> Macros.  A macro box should appear, select the 
macro entitled ‘showform’ and click on run.  The chart’s control panel can be 
reopened if closed (e.g. accidentally) by repeating this step. 
 
Chart calibration procedure 
1. 
It is important the charts are calibrated before first use, to ensure the optotypes are 
of the correct size and contrast.  Minute adjustments of monitor contrast or 
brightness can affect the contrast of the letters (especially low). 
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Eurolens Research 
Computer logMAR VA chart (v2) 
December 19, 2017 
6 
Confidential 
 
2. 
If the chart distance is set to 6m, the 0.8 letter on the computer chart should be the 
same height as that on the Bailey-Lovie chart, measuring just under 55mm high. 
3. 
The chart distance should then be set to the distance of the subject’s head to the 
chart. 
4. 
The monitor should be inclined downwards at an angle of approximately five 
degrees from the vertical.  The reason being the contrast of an LCD monitor can 
vary with tilt.  At five degrees of inclination, the monitor will be ‘straight on’ for the 
subject sat on the chair below. (see Appendix A) 
5. 
The monitor should then be calibrated using a Datacolor Spyder 4. Whilst 
calibrating, the room lights should be on full illumination and the monitor set to 
factory default values (all setting “standard”).  The corresponding monitor profile file 
generated should be saved and then used as the profile for the external monitor. 
6. 
The contrast of the low contrast chart should be measured.  The test spreadsheet 
(low contrast grey test.xlsx) should be displayed on the monitor with room lights on.  
Measurements of the luminance of the grey and white halves are taken with the 
spyder.  The luminance measurements are then averaged.  The contrast of the grey 
to white backgrounds is calculated as follows: 
 
% contrast = 
 
white lum – grey lum  x 100 
 
 
 
 
white lum  
7. 
The RGB vales of the grey background should be altered until the contrast is 
calculated to be approximately 10%.  This value is usually between 240 and 245 
units. 
8. 
Acuity measurements on the freshly calibrated chart should then be compared to 
those taken with two already calibrated charts.  This is done by measuring high and 
low contrast visual acuity with all three charts (in a randomised order on around 
eight subjects).  The acuity measurements of the three charts should all agree within 
two letters (0.04 logMAR) for high and low contrast acuity. 
9. 
If the high contrast acuity on the test chart does not agree with that of the control 
charts, then the “chart distance” value should be altered on the test chart, until it is in 
agreement with the controls. 
10. Once the high contrast acuity values are in agreement, the test chart’s low contrast 
acuity should be in agreement with the control.  If not then the “LC grey” value 
should be altered on the test chart until agreement is reached. 
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Eurolens Research 
Computer logMAR VA chart (v2) 
December 19, 2017 
7 
Confidential 
 
11. Final settings for each monitor on 11 October 2017 are contained in Appendix B. 
 
Measurement of VA using the Eurolens chart 
General instructions 
 
1. 
The subject should be seated in the chair 3m from the mirror.  This will place the 
chart at a 6m testing distance. 
2. 
The default test chart for standard testing should be a 7-line chart ranging from 0.4 
to -0.2 (Figure 1). 
3. 
The subject’s acuity can be tested monocularly and/or binocularly according to the 
study protocol. 
4. 
If the subject cannot read the top line then increase letter size in 0.1 steps until the 
subject can see the top line.   
5. 
Adjusting the “number of lines” box can alter the number of rows of letters displayed 
on the chart.  Please note to display larger letters (over 0.4), then only one or three 
rows should be selected.  
6. 
Letters can be increased in size by 0.1 steps, by clicking on the “+0.1” box.  Letters 
can be increased in size to a maximum of 1.0. 
7. 
Letters can be decreased in size by clicking on “-0.1”. 
8. 
The control panel displays information on the optotypes currently displayed on the 
chart and their size in logMAR. 
9. 
The VA score is calculated using the same method as a traditional Bailey-Lovie 
chart, with each letter scoring 0.02 units and each complete line scoring 0.1 (see 
below). 
10. To display the high contrast chart select “high contrast”, similarly to display the low 
contrast chart select “low contrast”.  This will display letters of 100% and 10% 
contrast respectively 
11. The Mac generates the sequence of letters used in the chart randomly.  Clicking on 
“shuffle letters” can change the sequence of letters. 
12. Letters should be shuffled after each VA measurement to avoid the subject learning 
the chart. 
13. As the chart is at 6m, any over-refraction performed can be considered to be 
equivalent to that performed on a 6m Snellen chart i.e. at infinity. 
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Eurolens Research 
Computer logMAR VA chart (v2) 
December 19, 2017 
8 
Confidential 
 
14. The 6m testing distance should also be taken into account when comparing logMAR 
scores obtained with the Bailey-Lovie chart at 3m.  The Bailey-Lovie scores should 
differ by -0.3. 
 
Subject instructions (standard chart display) 
After positioning the subject at the desired test distance, initiate the testing as follows: 
1. 
Ask the subject to read the smallest line where they feel they can easily read all the 
letters.  If the subject reads all the letters on the initial line, encourage them to 
continue reading the smaller lines until three or more letters on a 5- letter line are 
incorrectly identified. 
2. 
If the subject identifies one letter incorrectly on the initial line, ask them to read the 
line(s) above until one complete line has been identified correctly. Then encourage 
the subject to continue reading the smaller lines/letters until three or more letters on 
a 5-letter line are incorrectly identified. Note: The subject is to be encouraged to 
read and even guess at the letters until three or more letters are incorrectly 
identified. 
Scoring 
To determine the VA unit score for a given line: Take the maximum VA for the last line 
read (i.e. the line on which three or more letters were missed) and add +0.02 for every 
letter missed on the chart. 
For example: 
i) 
 0.00 line 
3 letters missed 
logMAR score +0.06 
 
ii) 
+0.20 line 
0 letters missed 
+0.10 line 
2 letters missed 
  
 0.00 line 
3 letters missed 
logMAR score +0.10 
 
iii) 
-0.20 line 
0 letters missed 
-0.30 line 
2 letter missed 
-0.40 line 
4 letters missed 
logMAR score –0.28 
 
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Eurolens Research 
Computer logMAR VA chart (v2) 
December 19, 2017 
9 
Confidential 
 
Over-refraction 
Unless the clinical study protocol states otherwise the following procedures should be 
carried out: 
1. 
Visual acuity using the Eurolens chart will be measured with no over-refraction in 
place.  The study protocol may require that this be carried out monocularly or 
binocularly. 
2. 
A binocular over-refraction should be carried out using the chart at 6m.  This 
procedure will control accommodation and allow accurate assessment of the 
subject’s visual status.  These results will allow the Investigator to judge whether or 
not the contact lens BVP is acceptable. 
Bailey Lovie chart 
LogMAR visual acuity can also be measured on a card-based Bailey-Lovie chart.  The 
use of this chart is covered in more detail in the relevant SOP1.  In summary the 
differences are: 
1. 
Unless specified the Bailey-Lovie chart is used at a testing distance of 3m as it is 
viewed directly. 
2. 
The font used (5x5 sans-serif font)2 is that defined in the British Standard: BS 4274.  
3. 
If the Bailey-Lovie is used at 3m, then it should not be used as a target to determine 
over-refraction.  Instead an alternative chart (e.g. Snellen) positioned at 6m should 
be used. 
 
References 
1. 
Eurolens Research Standard Operating Procedure.  Assessment of visual 
performance using the Bailey-Lovie logMAR visual acuity test chart and procedures 
for carrying out an over-refraction. 
2. 
BS 4274-1:2003.  Visual acuity test types. Test charts for clinical determination of 
distance visual acuity – Specification.   
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Eurolens Research 
Computer logMAR VA chart (v2) 
December 19, 2017 
10 
Confidential 
 
 
Appendix A.  Screen inclination calculation 
 
To calculate chart inclination 
 
Tan (angle of chart inclination) = Subject’s distance below chart 
 
 
 
     Subject to chart distance (parallel to floor) 
Room 
1.015  
1.014  
1.013 
1.012 
Subject’s 
distance below 
chart (eye to top 
of monitor) (cm)* 
50 
65 
 
65 
65 
Subject to chart 
distance (parallel 
to floor) (cm) 
600 
605 
610 
600 
Calculated chart 
inclination 
(degrees) 
4.7 
6.1 
6.1 
6.2 
Table 2: Eurolens clinic room screen inclination. 
 
* Subject with Eurolens ID 2023 of  average UK male height (175cm, ONS data) was 
used 
 
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Eurolens Research 
Computer logMAR VA chart (v2) 
December 19, 2017 
11 
Confidential 
 
Appendix B.  Example of chart settings (11 October 2017) 
 
Clinic room 
1.012 
1.013 
1.014 
1.015 
1.018 
Monitor number  4 
5 
3 
1 
2 
Chart distance 
(m) 
6.0 
6.1 
6.05 
6.0 
6.1 
LC grey 
240 
240 
243 
240 
237 
 
Table 3: Eurolens clinic room chart settings 
All monitors calibrated were a BenQ G2255 displaying the chart at native resolution 
(1920x1080). 
 
Appendix C.  Revisions to chart software 
2008 
Initial clinic version of computer chart software 
 
01/02/2013 v5 
2013 version of chart software was rewritten for compatibility with Office 2011 and Mac 
OSX10.8.  Contains the following amendments: 
 - Colours of the control box have been altered for better legibility with office 2011 
 - Chart letter display was updated for 16:9 monitors 
 - Letter size is calculated correctly for chart distance 
 - Low contrast letters contrast adjustable from chart control panel.  
 
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PROCEDURE FOR SELECTIVELY ANESTHETISING
THE CORNEA AND 
EYELID MARGINS
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Eurolens Research 
 
Clinical 
Standard Operating Procedure 
 
 
 
 
 
Procedure for selectively anaesthetising the 
cornea and eyelid margins 
 
 
 
 
 
 
 
Associate Director 
Carole Maldonado-Codina 
 
 
First issued: v0; October 20, 2015 
Current revision: v0; October 20, 2015 
Reviewed (with changes): v1; June 1, 2017
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Eurolens Research 
Anaesthesia SOP v1  
 
June 1, 2017 
3 
Confidential 
Summary 
These guidelines describe how small quantities of topical anaesthetic can be used to 
selectively anaesthetise individual areas on the ocular surface. 
 
Responsibilities 
This procedure can be performed by clinical investigators.  
 
List of equipment 
Proxymetacaine hydrochloride 0.5% (Chauvin Pharmaceuticals Ltd) 
Cotton bud 
Eyelid retractor (EyegenieTM, Wilson Ophthalmic Corp.) (optional) 
Any soft contact lens 
 
Procedure 
This procedure can take place either for the cornea or the eyelid margins (upper and 
lower).  
1. 
Cornea 
Two methods for anaesthetising the cornea can be used: 
a. ‘Contact lens’ method: 
i. A soft contact lens is removed from its blister packaging and 
placed into a lens holder (from a barrel contact lens case) and 
centrifuged for 2 seconds using a custom low‐speed centrifuge to 
remove surface packaging solution from the contact lens surface.  
ii. A 10 μl drop of anaesthetic is dispensed onto the back surface of 
the contact lens using an automated micropipette and a sterile 
pipette tip.  
iii. The subject is asked to face downwards. 
iv. The upper and lower eyelids are retracted using fingers or an 
Eyegenie (Eyelid retractor).   
v. The investigator applies the dosed contact lens directly onto the 
cornea, whilst the eyelids are held apart for a further minute to 
allow the anaesthetic to be absorbed and avoid spreading to other 
parts of the ocular surface.  
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Eurolens Research 
Anaesthesia SOP v1  
 
June 1, 2017 
4 
Confidential 
vi. The contact lens is removed, the  eyelids are then released and 
the subject is allowed to blink normally. 
b. ‘Drop’ method: 
i. The subject is asked to lift the chin and lean the head backward 
during the procedure. 
ii. The upper and lower eyelids are retracted using fingers or an 
Eyegenie (Eyelid retractor).   
iii. A 3μl drop of anaesthetic is dispensed onto the central cornea 
using an automated micropipette and a sterile pipette tip. Flexible 
silicone tubing will be attached to the pipette tip.  
iv. The eyelids are held apart for a minute to allow the anaesthetic to 
be absorbed and avoid spreading to other parts of the ocular 
surface. 
v. The eyelids are then released and the subject is allowed to blink 
normally. 
 
2. 
Eyelid margins 
This procedure can be carried out on the upper and lower eyelid margins.  
a. A soft contact lens is applied to the eye to shield the cornea. 
b. A cotton bud is manipulated until a fine thread is created at the tip.  
c. This tip is saturated with the anaesthetic. 
d. The saturated cotton bud tip is then used to ‘brush’ the full length of the 
upper or lower lid margin for 30 seconds.   
e. The upper lid margin should be completely everted whilst the lower lid 
margin needs only to be partially everted.  
f. 
The eyelid is kept fully or partially everted (whichever is relevant) for 30 
seconds. 
g. A second application of anaesthetic using the saturated cotton bud is 
performed for 30 seconds.  
h. The eyelid is kept fully or partially everted (whichever is relevant) for a 
further minute to allow the anaesthetic to be absorbed and avoid 
spreading to other parts of the ocular surface.  
i. The contact lens is removed, the eyelids are then released and the 
subject is allowed to blink normally 
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Eurolens Research 
Anaesthesia SOP v1  
 
June 1, 2017 
5 
Confidential 
The anaesthetic effect lasts between 15 minutes and one hour. The subject should be 
advised not to wear their own contact lenses for at least two hours after the procedure.. 
 
Appendix A  
Minims Proxymetacaine hydrochloride 0.5% Eye Drops – Chauvin Pharmaceuticals Ltd 
(Patient Information Leaflet)              
• 
Proxymetacaine hydrochloride 0.5% will be stored as indicated: at 2° to 8° C, 
refrigerated (not frozen). 
 
 
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APPENDIX E: VAS SCALE
CR-6292, v1.0
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PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE
Protocol Number and Title: CR-6292 An investigation of the impact of localized topical 
anesthesia of the ocular surface on end-of-day contact lens discomfort
Version and Date: 1.0 24 September 2018
I have read and understand the protocol specified above and agree on its content.  
I agree to conduct this study according to ISO 14155,1 GCP and ICH guidelines,2 the
Declaration of Helsinki,3 United States (US) Code of Federal Regulations (CFR),4 and the 
pertinent individual country laws/regulations and to comply with its obligations, subject to 
ethical and safety considerations. The Principal Investigator is responsible for ensuring that all 
clinical site personnel, including Sub-Investigators adhere to all ICH2 regulations and GCP 
guidelines regarding clinical trials during and after study completion.
I will assure that no deviation from, or changes to the protocol will take place without prior
agreement from the Sponsor and documented approval from the Institutional Review Board 
(IRB), except where necessary to eliminate an immediate hazard(s) to the trial participants.
I am responsible for ensuring that all clinical site personnel including Sub-Investigators adhere 
to all ICH2 regulations and GCP guidelines regarding clinical trials during and after study 
completion.
All clinical site personnel involved in the conduct of this study have completed Human 
Subjects Protection Training. 
I agree to ensure that all clinical site personnel involved in the conduct of this study are 
informed about their obligations in meeting the above commitments.
I shall not disclose the information contained in this protocol or any results obtained from this 
study without written authorization.
Principal 
Investigator:
Signature
Date
Name and Professional Position (Printed)
Institution/Site:
Institution/Site Name
Institution/Site Address
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