Clinical Evaluation of Two Marketed Artificial Tears in Non-contact Lens Wearing Patients
Phase: PHASE4
Conditions: Visual Acuity
Sponsor: Johnson & Johnson Vision Care, Inc.

 
 
 
 
 
Johnson & Johnson Vision Care, Inc. 
 
Clinical Study Protocol 
 
 
Clinical Evaluation of two marketed artificial tears in non-contact lens wearing patients 
 
Protocol Number CR-6013 (J17-626)    
 
Version: 3.0 
                            
Date: 03 January 2018 
 
 
Investigational Products:  blink® intensive TRIPLE ACTION 3 in 1 eye drops and 
Systane® BALANCE eye drops 
 
Key Words: artificial tears, dispensing, Visual Analogue Scale (VAS) comfort, Ocular 
Surface Disease Index (OSDI), Dry Eye Questionnaire (DEQ)-5, dry eye 
 
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 for 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  
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 ............... 15 
1. 
INTRODUCTION AND BACKGROUND .............................................................. 16 
1.1. 
Name and Descriptions of Investigational Products ........................................... 16 
1.2. 
Intended Use of Investigational Products............................................................ 16 
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................................................................................................................. 17 
2. 
STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES ................................. 17 
2.1. 
Objectives ............................................................................................................ 17 
2.2. 
Endpoints ............................................................................................................. 17 
2.3. 
Hypotheses .......................................................................................................... 18 
3. 
TARGETED STUDY POPULATION ...................................................................... 18 
3.1. 
General Characteristics ....................................................................................... 18 
3.2. 
Inclusion Criteria ................................................................................................. 18 
3.3. 
Exclusion Criteria ................................................................................................ 19 
3.4. 
Enrollment Strategy............................................................................................. 19 
4. 
STUDY DESIGN AND RATIONALE ..................................................................... 20 
4.1. 
Description of Study Design ............................................................................... 20 
4.2. 
Study Design Rationale ....................................................................................... 20 
4.3. 
Enrollment Target and Study Duration ............................................................... 20 
5. 
TEST ARTICLE ALLOCATION AND MASKING ................................................ 21 
5.1. 
Test Article Allocation ........................................................................................ 21 
5.2. 
Masking ............................................................................................................... 21 
5.3. 
Procedures for Maintaining and Breaking the Masking...................................... 22 
6. 
STUDY INTERVENTION ........................................................................................ 22 
6.1. 
Identity of Test Articles....................................................................................... 22 
6.2. 
Ancillary Supplies/Products ................................................................................ 23 
6.3. 
Administration of Test Articles ........................................................................... 23 
6.4. 
Packaging and Labeling ...................................................................................... 23 
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6.5. 
Storage Conditions .............................................................................................. 24 
6.6. 
Collection and Storage of Samples ..................................................................... 24 
6.7. 
Accountability of Test Articles ........................................................................... 24 
7. 
STUDY EVALUATIONS ......................................................................................... 25 
7.1. 
Time and Event Schedule .................................................................................... 25 
7.2. 
Detailed Study Procedures .................................................................................. 26 
VISIT 0 ...................................................................................................................... 26 
VISIT 1 ...................................................................................................................... 26 
VISIT 2 ...................................................................................................................... 29 
VISIT 3 ...................................................................................................................... 31 
VISIT 4 ...................................................................................................................... 33 
FINAL EVALUATION ............................................................................................. 35 
7.3. 
Unscheduled Visits .............................................................................................. 35 
7.4. 
Laboratory Procedures ........................................................................................ 36 
8. 
SUBJECTS COMPLETION/WITHDRAWAL......................................................... 36 
8.1. 
Completion Criteria ............................................................................................. 36 
8.2. 
Withdrawal/Discontinuation from the Study ...................................................... 36 
9. 
PRE-STUDY AND CONCOMITANT INTERVENTION/MEDICATION ............ 37 
10. 
DEVIATIONS FROM THE PROTOCOL ............................................................. 37 
11. 
STUDY TERMINATION ...................................................................................... 37 
12. 
PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS ......... 38 
13. 
ADVERSE EVENTS .............................................................................................. 39 
13.1. 
Definitions and Classifications ........................................................................ 39 
13.2. 
Assessing Adverse Events ............................................................................... 41 
13.2.1. 
Causality Assessment ............................................................................... 42 
13.2.2. 
Severity Assessment ................................................................................. 42 
13.3. 
Documentation and Follow-Up of Adverse Events ......................................... 42 
13.4. 
Reporting Adverse Events ............................................................................... 43 
13.4.1. 
Reporting Adverse Events to Sponsor ..................................................... 44 
13.4.2. 
Reporting Adverse Events to the Responsible IEC/IRB and Health 
Authorities.................................................................................................................. 44 
13.4.3. 
Event of Special Interest .......................................................................... 45 
13.5. 
Reporting of Pregnancy ................................................................................... 45 
14. 
STATISTICAL METHODS ................................................................................... 45 
14.1. 
General Considerations .................................................................................... 45 
14.2. 
Sample Size Justification ................................................................................. 45 
14.3. 
Analysis Populations ....................................................................................... 46 
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14.4. 
Level of Statistical Significance ...................................................................... 46 
14.5. 
Primary Analysis ............................................................................................. 46 
14.6. 
Secondary Analysis ......................................................................................... 47 
14.7. 
Other Exploratory Analyses ............................................................................ 47 
14.8. 
Interim Analysis .............................................................................................. 47 
14.9. 
Procedure for Handling Missing Data and Drop-Outs .................................... 47 
14.10. 
Procedure for Reporting Deviations from Statistical Plan .............................. 47 
15. 
DATA HANDLING AND RECORD KEEPING/ARCHIVING ........................... 48 
15.1. 
Electronic Case Report Form/Data Collection ................................................ 48 
15.2. 
Subject Record ................................................................................................. 48 
16. 
DATA MANAGEMENT........................................................................................ 49 
16.1. 
Access to Source Data/Document ................................................................... 49 
16.2. 
Confidentiality of Information......................................................................... 49 
16.3. 
Data Quality Assurance ................................................................................... 49 
17. 
MONITORING ....................................................................................................... 49 
18. 
ETHICAL AND REGULATORY ASPECTS ....................................................... 50 
18.1. 
Study-Specific Design Considerations ............................................................ 50 
18.2. 
Investigator Responsibility .............................................................................. 50 
18.3. 
Independent Ethics Committee or Institutional Review Board (IEC/IRB) ..... 50 
18.4. 
Informed Consent ............................................................................................ 51 
18.5. 
Privacy of Personal Data ................................................................................. 52 
19. 
STUDY RECORD RETENTION........................................................................... 53 
20. 
FINANCIAL CONSIDERATIONS ....................................................................... 53 
21. 
PUBLICATION ...................................................................................................... 54 
22. 
REFERENCES ....................................................................................................... 54 
APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES) 55 
APPENDIX B: PATIENT INSTRUCTION GUIDE ........................................................ 61 
APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT) .................................... 62 
APPENDIX D: LIPIVIEW II® II ASSESSMENT PROCEDURE .................................. 65 
APPENDIX E: MEDMONT ASSESSMENT PROCEDURE ........................................ 113 
APPENDIX F: CLINICAL TECHNICAL PROCEDURES 
................................ 118 
 EXPANDED CORNEAL STAINING ASSESSMENT ................................ 119 
SUBJECT REPORTED OCULAR SYMPTOMS/PROBLEMS ................... 124 
 
DETERMINATION 
OF 
DISTANCE 
SPHEROCYLINDRICAL 
REFRACTIONS .............................................................................................................. 126 
 BIOMICROSCOPY SCALE ......................................................................... 133 
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EUROLENS RESEARCH SOP #12A (DISTANCE AND NEAR VISUAL ACUITY 
EVALUATION) .............................................................................................................. 139 
 PATIENT REPORTED OUTCOMES........................................................... 151 
PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE ................... 153 
 
TABLE OF CONTENTS  
Figure 1: Study Flowchart ................................................................................................. 14 
 
TABLE OF CONTENTS  
Table 1: Target number of subjects by arm and site .......................................................... 20 
Table 2: Ancillary Supplies ............................................................................................... 23 
Table 3: Time and Events .................................................................................................. 25 
Table 4: Power Analysis for VAS comfort ........................................................................ 45 
 
 
 
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AUTHORIZED SIGNATURES 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable U.S. federal 
regulations,4 ICH guidelines,2 ISO 14155,1  and the Declaration of Helsinki.3 
 
 
Author/Study 
Responsible 
Clinician 
 
 
See Electronic Signature Report 
 
 
 
Meredith Bishop, OD, MS, FAAO 
Principal Research Optometrist 
 
DATE 
 
Clinical Operations 
Manager 
 
See Electronic Signature Report 
 
 
 
 
 
 
DATE 
 
 
Biostatistician 
 
See Electronic Signature Report 
 
 
 
 
 
 
DATE 
 
 
Data Management  
 
See Electronic Signature Report 
 
 
 
 
 
 
DATE 
 
 
Fellow Reviewer 
 
See Electronic Signature Report 
 
 
 
 
 
 
 
 
 
 
DATE 
 
 
Approver 
 
See Electronic Signature Report 
 
 
 
 
 
 
 
DATE 
 
 
 
 
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SYNOPSIS  
Protocol Title 
Clinical Evaluation of two marketed artificial tears in non-
contact lens wearing patients 
Sponsor 
JJV, 7500 Centurion Parkway, Jacksonville, FL  32256 
Clinical Phase 
Post Marketing, Phase 4 
Trial Registration 
This study will be registered on ClinicalTrials.gov based 
on the following: the study will be utilizing marketed 
products to assess endpoints related to comfort. 
Test Article(s) 
Two artificial tears products:  
• blink® intensive TRIPLE ACTION 3 in 1 eye drops 
(Test) 
• Systane® BALANCE eye drops (Control) 
Treatment dosage 
Dosage: Instill 1-2 drops OU at least three times a day.   
Objectives  
The primary objective of this study is to gain clinical 
insights of the products with respect to ocular comfort after 
one week of use.  
Study Endpoints 
Primary endpoint: VAS comfort score 
Secondary endpoint: OSDI score  
Other endpoints:  
DEQ-5, LipiView II®, NITBUT, ocular physiology, 
subject’s reported ocular symptoms, adverse events 
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Study Design 
The study design is a randomized, double-masked, 
bilateral, 2 treatment × 2 period, dispensing, 4-visit study:  
 
Visit 0: pre-screening with completion of DEQ-5 
 
Visit 1: Baseline and eligibility, randomization.  Dispense 
first eye drop solution. LipiView II® measurement at 
approx.5 mins, 30 mins, 1 hour, and 2 hours post-drops.  
VAS comfort. 
 
Study drops used at least 3x per day for 7-9 days. 
 
Visit 2: One-week follow-up - Questionnaires, LipiView 
II®, NITBUT, slit lamp findings. VAS comfort. 
 
Washout period: 
7-9 days (habitual artificial tear usage)   
 
Visit 3: Baseline, confirm eligibility, dispense second eye 
drop solution. LipiView II® measurement at approx..5 
mins, 30 mins, 1 hour, and 2 hours post drop. VAS comfort.  
 
Study drops used at least 3x per day for 7-9 days. 
 
Visit 4: One-week follow up, Questionnaires, ®, NITBUT, 
slit lamp findings, final evaluation.  VAS comfort. 
 
See the Summary of Visits table at the end of the synopsis 
for the schematic of the study visits and procedures of main 
observations. 
Sample Size 
Approximately 60 non-contact lens wearing subjects are 
targeted to be enrolled and approximately 50 subjects are 
targeted to complete the study. 
Study Duration 
The study will last approximately 3 months and include a 
2-month enrollment period. 
Anticipated Study 
Population 
Non-contact lens wearers 18-69 years of age with 
occasional symptoms of dry eye and/or signs based on a 
DEQ-5 score of greater than 6.   
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Eligibility Criteria 
Potential subjects must satisfy all the following criteria to 
be enrolled in the study: 
1. Subjects must be at least 18 years of age and no 
more than 69 years of age (inclusive) 
2. Subjects must be non-contact lens wearers 
3. Subjects must have a DEQ-5 score of >6 at either 
Visit 0 (pre-screen) or Visit 1 (screening) 
4. Subjects must achieve visual acuity of 20/30 
(equivalent to 0.18logMAR) or better in each eye, 
either unaided or best corrected 
5. Subjects must possess a functional/ usable pair of 
spectacles and bring them to the visit (only if 
applicable - to the investigators discretion).  
6. Subjects must read, understand, and sign the 
Statement of Informed Consent 
7. Subjects must appear able and willing to adhere to 
the instructions set forth in this clinical protocol 
Potential subjects who meet any of the following criteria 
will be excluded from participating in the study:  
1. Currently pregnant or breast-feeding  
2. Diabetes 
3. Any ocular or systemic allergies or disease which 
may interfere with the clinical trial (at the 
discretion of the investigator).  
4. Any systemic disease, autoimmune disease, or use 
of medication which may interfere with the clinical 
trial (at the discretion of the investigator), 
5. Any infectious diseases (e.g. hepatitis, 
tuberculosis) or a contagious immunosuppressive 
disease (e.g. HIV), by self-report 
6. Any Grade 3 or greater biomicroscopy findings 
(this includes, corneal edema, corneal staining, 
corneal vascularization, conjunctival injection, 
tarsal abnormalities, bulbar injection) on the FDA 
classification scale 
7. Any active ocular abnormalities/conditions that 
may interfere with the clinical trial (this includes, 
but not limited to, chalazia, recurrent styles, 
pterygium, infection, etc). 
8. Any corneal distortion due to previous rigid gas 
permeable lens wear, surgery or pathology. 
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9. History of any ocular or corneal surgery (e.g. RK, 
PRK, LASIK)  
10. Participation in any pharmaceutical or medical 
device related clinical trial within 14 days prior to 
study enrollment. 
11. History of binocular vision abnormality or 
strabismus. 
12. Habitual wearers of soft contact lenses within the 
past 1 month or rigid gas permeable lens within the 
past 3 months 
13. Current habitual use of Prescription Only 
Medication (POM) to treat dry eye or ocular 
dryness symptoms that would interfere with the 
clinical study (at the discretion of the investigator) 
14. Employees of investigational clinic (investigator, 
coordinator, and technician etc) or family members 
of an employee of the clinical site by self-report. 
In addition to the above criteria, patients with any 
allergy or sensitivity to ingredients that this product 
may contain (liposomes, sodium hyaluronate, vitamin E 
polyethylene glycol succinate (TPGS), polyethylene 
glycol 400 (PEG 400), disodium edetate, polyhexanide 
methylbiguanide, 
propylene 
glycol, 
boric 
acid, 
dimyristoyl phosphatidylglycerol, edetate disodium, 
hydroxypropyl guar, mineral oil, polyoxyl 40 sterate, 
polyquaternium-1, 
sorbitan 
tristearate, 
sorbitol, 
hydrochloric acid and/or sodium hydroxide) should not 
participate in the study. 
 
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Disallowed 
Medications/Interventions  Current habitual use of Prescription Only Medicines 
(POM) to treat dry eye or ocular discomfort, ocular 
steroids, or any medication (RX or OTC) that would 
interfere with the clinical study (at the discretion of the 
investigator). 
Measurements and 
Procedures 
VAS Scale Comfort, OSDI, DEQ-5, ocular physiology, 
LipiView II®, and safety parameters. 
Microbiology or Other 
Laboratory Testing 
None 
Study Termination 
The occurrence of one or more Unanticipated Adverse 
Device Effect (UADE), or any SAE where relationship to 
study agent cannot be ruled out, will result in stopping 
further dispensing investigational product.  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 
BlueDot Saline Pods (or other sponsor-approved material), 
FluStips 
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 
CE 
 
 
Conformité Européene 
CFR 
 
 
Code of Federal Regulations 
COAS  
 
Complete Ophthalmic Analysis System 
COM  
 
Clinical Operations Manager 
CRA  
 
Clinical Research Associate 
CRF 
 
 
Case Report Form 
CRO  
 
Contract Research Organization 
CT 
 
 
Center Thickness 
CTP 
 
 
Clinical Technical Procedure 
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 Council for Harmonization 
IDE 
 
 
Investigational Device Exemption 
IEC 
 
 
Independent Ethics Committee 
IRB 
 
 
Institutional Review Board 
ISO 
 
 
International Organization for Standardization 
ITT 
 
 
Intent-to-Treat 
JJV 
 
 
Johnson & Johnson Vision, 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 
OSDI  
 
Ocular Surface Disease Index 
OU 
 
 
Both Eyes 
PD 
 
 
Protocol Deviation 
PHI 
 
 
Protected Health Information 
PI 
 
 
Principal Investigator 
PIG 
 
 
Patient Instruction Guide 
PQC  
 
Product Quality Complaint 
PRO  
 
Patient Reported Outcome 
QA 
 
 
Quality Assurance 
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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 
It is estimated that over 16 million US adults have been diagnosed with dry eye5. Artificial 
tears are often used to treat symptoms of ocular dryness and discomfort.  Most of the major 
artificial tear companies have some type of lipid product to address lipid deficient tear 
films, however JJV CEH does not currently have a lipid-like drop in our portfolio. 
Additionally, JJV acquired TearScience Q3 2017 to address Meibomian gland disease 
resulting in lipid deficiencies.  
This study will be conducted at a single clinical site (University of Manchester) in the 
United Kingdom (UK) and will include two marketed (CE marked) artificial tears (blink® 
intensive TRIPLE ACTION 3 in 1 and Systane® BALANCE) to gain clinical insights with 
respect to ocular comfort after 1 week of use.  By exploring a lipid-like drop addition to 
the CEH portfolio it would continue to live into the JJV Eye Health Mission. 
1.1. Name and Descriptions of Investigational Products  
The products used in this clinical study are two CE marked/approved artificial tears eye 
drops:  
 
• blink® intensive TRIPLE ACTION 3 in 1 eye drops (Test) 
• Systane® BALANCE eye drops (Control)   
1.2. Intended Use of Investigational Products 
The products are marketed products, available over the counter (without a prescription).  
They will be used as indicated on-label to reduce symptoms of ocular dryness. Subjects 
will be required to use the 1-2 drops in both eyes at least 3 times a day.  There is no 
maximum number of drops per day.   
The proposed intended use of all the study artificial tears are subjects with symptoms of 
ocular dryness.  For this study, we will use a cut off DEQ-5 score of 6.  A score of greater 
than 6 indicates the presence of ocular discomfort and/or dryness and subject eligibility.   
1.3. Summary of Findings from Nonclinical Studies 
Not Applicable - Marketed products only. 
1.4. Summary of Known Risks and Benefits to Human Subjects 
The following risks/adverse events can be associated with using artificial tears, in general: 
• There may be less comfort than when the drop was first placed on the eye. 
• The eyes may burn, sting and/or itch. 
• There may be a feeling of something in the eye (foreign body, scratched area). 
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• There may be the potential for some temporary impairment due to peripheral 
infiltrates, peripheral corneal ulcers and corneal erosion.   
• There may be the potential for other physiological observations, such as local or 
generalized edema, corneal neovascularization, corneal staining, injection, tarsal 
abnormalities, iritis and conjunctivitis, some of which are clinically acceptable in 
low amounts. 
• There may be excessive watering, unusual eye secretions, or redness of the eye. 
• Poor visual acuity, blurred vision, rainbows or halos around objects, photo-phobia, 
or dry eyes may also occur if the drops are used continuously or for too long a time. 
 
There is no direct benefit to the subject for participating in the study, although they will be 
able to try out new artificial tears.  The information from this study will aid if the further 
development and design of new artificial tears.   
 
For the most comprehensive clinical information regarding the artificial tears refer to the 
package inserts (Appendix C). 
1.5. Relevant Literature References and Prior Clinical Data Relevant to Proposed 
Clinical Study 
All artificial tears evaluated in this study are CE marked/approved and marketed products.  
Refer to package inserts (Appendix C) for additional information.   
2. STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES 
2.1. Objectives  
The primary objective of this study is to gain clinical insights of the products with respect 
to ocular comfort after 1 week of use.  
2.2. Endpoints  
Primary Endpoint: 
The primary endpoint is ocular comfort score at 1-week follow-up using Visual Analogue 
Scale (VAS) of comfort. VAS of comfort consists of a vertical line which represents 
continuous scale from 0 (extremely uncomfortable) to 100 (extremely comfortable). 
Secondary endpoint: 
The secondary endpoint is subjective assessment of dry eye symptoms at 1-week follow-
up using Ocular Surface Disease Index (OSDI©) instrument.  The OSDI© is assessed on a 
scale of 0 to 100, with higher scores representing greater disability. The index demonstrates 
sensitivity and specificity in distinguishing between normal subjects and patients with dry 
eye disease. The OSDI© is a reliable instrument for measuring dry eye disease (normal, 
mild to moderate, and severe) and effect on vision-related function OSDI© questionnaire.6 
 
Other Endpoints:   
• DEQ-5 score at 1-week follow-up 
• LipiView II® lipid layer measurement at 5 min, 30 min, 60 min, and 120 min 
post drop instillation.   
• Non-invasive tear break-up time (NITBUT) 
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• Expanded corneal staining 
) 
• Slit-Lamp findings 
 
• Subject’s reported ocular symptoms 
 
• Adverse events 
 
DEQ-5 questionnaire is a subset of Dry Eye Questionnaire (DEQ) items that discriminate 
across self-assessed severity and various diagnoses of dry eye. It is comprised of 5 items: 
frequency of watery eyes, discomfort, and dryness (0-4 scale) and late day discomfort and 
dryness intensity (0-5 scale). The DEQ-5 score is the sum of scores for frequency and late 
day intensity of dryness and discomfort plus frequency of watery eyes. DEQ-5 scores 
greater than 6 suggest dry eye is present and results greater than 12 may require further 
testing to rule out Sjögren's syndrome.7 
 
2.3. Hypotheses 
This is a pilot study and all the hypotheses are exploratory in nature. 
 
Primary hypothesis: 
The Test eye drop is superior to the Control eye drop with respect to ocular comfort as 
measured using VAS comfort at 1-week follow-up 
 
Secondary hypothesis: 
The Test eye drop is superior to the Control eye drop in reducing dry eye symptoms as 
measured using OSDI at 1-week follow-up. 
3. TARGETED STUDY POPULATION 
3.1. General Characteristics  
The study populations will be healthy non-contact lens wearers between 18-69 years of age 
from a single site in the UK.   
3.2. Inclusion Criteria 
Potential subjects must satisfy all the following criteria to be enrolled in the study: 
1. Subjects must be at least 18 years of age and no more than 69 years of age 
(inclusive) 
2. Subjects must be non-contact lens wearers 
3. Subjects must have a DEQ-5 score of >6 at either Visit 0 (pre-screen) and/or Visit 
1 (screening).   
4. Subjects must achieve visual acuity of 20/30 (equivalent to 0.18 logMAR) or better 
in each eye, either unaided or best corrected. 
5. Subjects must possess a functional/usable pair of spectacles and bring them to every 
visit (only if applicable - to the investigators discretion).  
6. Subjects must read, understand, and sign the Statement of Informed Consent. 
7. Subjects must appear able and willing to adhere to the instructions set forth in this 
clinical protocol 
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3.3. Exclusion Criteria 
Potential subjects who meet any of the following criteria will be excluded from 
participating in the study:  
 
1. Currently pregnant or breast-feeding. 
2. Diabetes. 
3. Any ocular or systemic allergies or disease which may interfere with the clinical 
trial (at the investigator’s discretion).  
4. Any systemic disease, autoimmune disease, or use of medication which may 
interfere with the clinical trial (at the investigator’s discretion). 
5. Any infectious diseases (e.g. hepatitis, tuberculosis) or a contagious 
immunosuppressive disease (e.g. HIV), by self-report 
6. Any Grade 3 or greater biomicroscopy findings (this includes, corneal edema, 
corneal 
staining, 
corneal 
vascularization, 
conjunctival 
injection, 
tarsal 
abnormalities, bulbar injection) on the FDA scale 
7. Any active ocular abnormalities/conditions that may interfere with the clinical trial 
(this includes, but not limited to, chalazia, recurrent styles, pterygium, infection, 
etc)  
8. Any corneal distortion due to previous rigid gas permeable lens wear, surgery or 
pathology  
9. History of any ocular or corneal surgery (e.g. RK, PRK, LASIK)  
10. Participation in any pharmaceutical or medical device related clinical trial within 
14 days prior to study enrollment. 
11. History of binocular vision abnormality or strabismus. 
12. Habitual wearers of soft contact lenses in the past 1 month or rigid gas permeable 
lens within the past 3 months 
13. Current habitual use of Prescription Only Medicines (POM) to treat dry eye or 
ocular discomfort, ocular steroids, or any medication (RX or OTC) that would 
interfere with the clinical study (at the discretion of the investigator).) 
14. Employees of investigational clinic (investigator, coordinator, and technician etc) 
or family member of an employee of the clinical site by self-report. 
In addition to the above criteria, patients with any allergy or sensitivity to ingredients 
that this product may contain (liposomes, sodium hyaluronate, vitamin E polyethylene 
glycol succinate (TPGS), polyethylene glycol 400 (PEG 400), disodium edetate, 
polyhexanide 
methylbiguanide, 
propylene 
glycol, 
boric 
acid, 
dimyristoyl 
phosphatidylglycerol, edetate disodium, hydroxypropyl guar, mineral oil, polyoxyl 40 
sterate, polyquaternium-1, sorbitan tristearate, sorbitol, hydrochloric acid and/or 
sodium hydroxide) should not participate in the study. 
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.  
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4. STUDY DESIGN AND RATIONALE 
4.1. Description of Study Design 
The study design is a randomized, double-masked, bilateral, 2 treatment × 2 period, 
dispensing, 4-visit study. 
 
After a pre-screening assessment, eligible subjects will be invited to attend an initial visit.  
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 dispensed with the first 
artificial tears eye drops based on the randomization scheme; otherwise, the subject will be 
discontinued from the study.  After dispensing of the first eye drop solution; NITBUT, 
LipiView II® measurement at taken at approximately 5 mins, 30 mins, 1 hour, and 2 hours 
post drop 
 
Subjects will be dispensed with their randomly assigned eye drops and instructed to use 
them OU at least 3 times a day over a 7-9 day period. The follow-up evaluation (Visit 2) 
will occur 7-9 days after the initial visit.  At this visit questionnaires, LipiView II®, 
NITBUT, slit lamp findings will be captured. 
 
After completion of Visit 2, there is a 7-9 day washout period during which subjects may 
use their habitual products, if any, but they will be advised not use any eye drops on the 
day of Visit 3   
 
 Following the washout period, the subject returns for Visit 3 and is dispensed with the 
second randomized eye drop with NITBUT, LipiView II® measurements at approximately 
5 mins, 30 mins, 1 hour, and 2 hours post drop.  Subjects will be dispensed with their second 
randomly assigned eye drops and instructed to use them OU at least 3 times a day over a 
7-9 day period.  Visit 4 takes place 7-9 days after visit 3, at which questionnaires, LipiView 
II®, NITBUT, slit lamp findings, final evaluation will take place.   
 
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. This design was considered 
because patient-specific factors that might affect comfort are well controlled. A washout 
period of 7-9 days was implemented between each treatment exposure to reduce any 
potential carry-over effect that may bias the results. 
4.3. Enrollment Target and Study Duration 
A total of up to 60 subjects will be enrolled (informed consent signed) at a single clinical 
site (University of Manchester) in the UK. The goal is for a sample size of approximately 
50 subjects after subjects who withdraw or are lost to follow-up. 
 
The Investigator is responsible for ensuring that all subjects entering the study conform to 
subject selection criteria. The number of subjects targeted for randomization and 
completion are as follows: 
 
Table 1: Target number of subjects by arm and site 
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Test/Control 
Control/Test 
Total 
Randomization  
30 
30 
60 
Completion 
25 
25 
50 
Number of sites 
  
  
1 
Number of 
subjects/site  
Min-Max 
25-30 
25-30 
50-60 
 
The study will last approximately 3 months and include a 2-month enrollment period. 
 
Once the informed consent has been signed the subject will be considered enrolled. 
 
An additional subject may be enrolled if a subject discontinues from the study prematurely.  
 
5. TEST ARTICLE ALLOCATION AND MASKING 
5.1. Test Article Allocation  
Eligible subjects will sequentially try the Test and Control eye drops in a random order. A 
computer-generated randomization scheme will be used to randomly assign subjects, in 
block size of 2, to one of the two possible treatment sequences: Test/Control or 
Control/Test.  
 
The study 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 the first baseline visit (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).  
 
5.2. Masking 
This is a double-masked study where subjects, investigators are masked to the identity of 
the eye drops during the study period. Every attempt will be made to keep the other 
clinical trial personnel involved in the study (e.g., Data management, Biostatistician) 
unaware of the identity of the test articles.  
 
The identity of the investigational products will be masked by over labeling the eye drop 
bottles with a label containing the study number, expiration date and the randomization 
codes. Only the personnel involved in the over labeling and the Statistician generating the 
randomization scheme will have access to the decode information translating the 
randomization codes into Test and Control treatment. The medical monitor will also have 
access to the decode information in case breaking the mask is necessary for the urgent 
medical treatment of a subject.  
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5.3. Procedures for Maintaining and Breaking the Masking 
Under normal circumstances, the mask should not be broken until all subjects have 
completed the study and the database is finalized. Otherwise, the mask should be broken 
only if specific emergency treatment/course of action would be dictated by knowing the 
treatment status of the subject. In such cases, the Investigator may, in an emergency, contact 
the medical monitor.  In the event the mask is broken, the Sponsor must be informed as 
soon as possible. The date, time, and reason for the unmasking must be documented in the 
subject record. The Investigator is also advised not to reveal the study treatment assignment 
to the clinical site or Sponsor personnel.  
 
When dispensing test articles, the following steps should be followed to maintain 
randomization codes: 
1. Investigator or designee (documented on the Delegation Log) will consult the 
randomization scheme to obtain the test article assignment for that subject prior to 
dispensing 
2. Investigator or designee will record the subject’s number on the appropriate line of 
the randomization scheme  
3. Investigator or designee will pull the appropriate test articles from the study supply.  
All test articles that are opened, whether dispensed (placed/fit on eye or dispensed 
outside the clinical site) or not, must be recorded on the Test Article Accountability 
Log in the “Dispensed” section 
6. STUDY INTERVENTION 
6.1. Identity of Test Articles 
Table 2: Artificial Tears   
 
Test  
Control  
Solution 
Name/Description 
blink® 
intensive 
TRIPLE 
ACTION 3 in 1 eye drops 
Systane® 
BALANCE 
eye 
drops 
Manufacturer 
Johnson & Johnson Vision, 
Inc 
Alcon 
Ingredients 
liposomes, sodium 
hyaluronate, vitamin E 
polyethylene glycol succinate 
(TPGS), polyethylene glycol 
400 (PEG 400), disodium 
edetate, polyhexanide 
methylbiguanide and purified 
water.  
Propylene Glycol 0.6%, boric 
acid, dimyristoyl 
phosphatidylglycerol, edetate 
disodium, hydroxypropyl guar, 
mineral oil, polyoxyl 40 
stearate, POLYQUAD® 
(polyquaternium-1) 0.001% 
preservative, sorbitan 
tristearate, sorbitol and 
purified water. May contain 
hydrochloric acid and/or 
sodium hydroxide to adjust 
pH. 
Packaging Form 
Over-Labeled 
Over-Labeled 
 
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6.5. Storage Conditions 
Test articles will be maintained at ambient temperatures at the clinical site. Test articles 
must be kept under secure conditions. 
6.6. Collection and Storage of Samples 
When possible, any test article associated with an Adverse Events and/or a Product Quality 
Complaint must be retained pending directions from the sponsor for potential return back 
to JJV. 
6.7. Accountability of Test Articles 
JJV will provide the Investigator with sufficient quantities of study articles and supplies to 
complete the investigation.  The Investigator is asked to retain all shipment documentation 
for the test article accountability records.  
 
Test article must be kept in a locked storage room, accessible only to those assigned by the 
Investigator for dispensing. The Investigator may delegate this activity to authorized study 
site personnel listed on the Site Delegation Log.  All test articles must be accounted.  This 
includes: 
1. What was dispensed for the subject  
2. What was returned to the Investigator unused 
3. The number and reason for unplanned replacements   
 
The Investigator will collect all unused test articles from the subjects at the end of the 
subject’s participation. Subject returned unused test articles must be separated from the 
clinical study inventory of un-dispensed test articles, and must be labeled with the subject 
number and date of return.  Following final reconciliation of test articles by the monitor, 
the Investigator or monitor will return all unused test articles to JJV. 
 
If there is a discrepancy between the shipment documents and the contents, contact the 
study monitor immediately. 
 
Reference 
  Site Instructions for Test Article Receipt and Test Article 
Accountability for additional information. 
 
 
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• Investigator’s clinical judgment regarding the subject safety reasons (that it is in the 
best interest of the subject to stop treatment) 
• Subject not successfully dispensed due to lack of efficacy or safety 
 
For discontinued subjects, the Investigator will: 
• Complete the current visit (scheduled or unscheduled) 
• Complete the Final Evaluation, indicating the reason that the subject was 
discontinued from the study 
• Collect used test article(s) (brought to the visit) from the subject and discard them, 
unless otherwise stated in Section 7.2 
• Collect all unused test article(s) from the subject 
 
An additional subject may 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 for this study include: Current habitual use of Prescription 
Only Medicines for dry eye or ocular discomfort, ocular steroids, or any medication (RX 
or OTC) that would interfere with the clinical study (at the discretion of the investigator). 
  
Concomitant therapies that are disallowed include: Current habitual use of Prescription 
Only Medicines for dry eye or ocular discomfort, ocular steroids, or any medication (RX 
or OTC) that would interfere with the clinical study (at the discretion of the investigator). 
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 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 dispensing of test article.  In the event of a USADE or SAE, the Sponsor may 
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unmask the treatment regimen for the subject(s) and will discuss this with the Investigator 
before any further subjects are enrolled. 
 
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. 
 
JJV 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 JJV, it is 
determined that it would be unwise to continue at the clinical site.    
 
JJV (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: 
• Subject satisfaction inquiries reported via “Subjective Questionnaires” and “Patient 
Reported Outcomes (PRO)” 
• Clinical test articles that are stored improperly or damaged after receipt at the 
investigational site 
• Artificial tear replacements that occur due to loss/run out 
• Damage deemed by clinicians or clinical staff to be caused by handling by the user, 
and not indicative of a quality deficiency, 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:  
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• Date the complaint was received/recorded in the EDC System (Date of Sponsor 
Awareness) 
• Who received the complaint 
• Study number 
• Clinical site information (contact name, site ID, telephone number) 
• Lot number(s) 
• Unique Subject Identifier(s) 
• Indication of who first observed complaint (site personnel or subject) 
• OD/OS indication, along with whether the drops were inserted 
• Any related AE number, if applicable 
• Detailed complaint description (scheduled/unscheduled visit, symptoms, resolution 
of symptoms, etc.) 
• Eye Care Provider objective (slit lamp) findings if applicable 
• Confirmation of product availability for return (and tracking information, if 
available), or rationale if product is not available for return (Refer to 
 
 for test article return instructions) 
 
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: 
• Results in death 
• Is life threatening 
• Requires in-patient hospitalization or prolongation of existing hospitalization 
• 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) 
• Is a congenital anomaly/birth defect, or 
• 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: 
• Microbial Keratitis (MK) 
• Iritis (including cells in the anterior chamber) 
• Permanent decrease in best spectacle corrected visual acuity equivalent to 2 acuity 
lines or greater 
• Central Corneal Opacity 
• Central Corneal Neovascularization 
• Uveitis 
• Endophthalmitis 
• Hypopyon 
• Hyphemia 
• Penetration of Bowman’s Membrane 
• Persistent Epithelial Defect 
• 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: 
• Significant Infiltrative Events (SIE) 
• Keratoconjunctivitis (toxic or infectious) 
• Chemical Keratitis  
• Any Temporary Loss of >2 Lines of BSCVA 
• Other Grade 3 or higher corneal findings, such as abrasions or edema 
• Corneal events - e.g. Epidemic Keratoconjunctivitis (EKC) 
• Asymptomatic Corneal Scar 
• Any corneal event which necessitates temporary lens discontinuation >2 weeks 
 
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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: 
• Non-signifiant Infiltrative Event (NSIE) 
• Papillary Conjunctivitis 
• Corneal abrasions 
• Superficial Punctate Keratitis (SPK) 
• Conjunctivitis: Bacterial, Viral, Allergic 
• Blepharitis 
• Meibomianitis 
• Contact Dermatitis 
• Localized Allergic Reactions or infections 
• Temporary visual disturbances (blurriness) 
• Any corneal event not explicitly defined as serious or significant adverse event, 
which necessitates temporary discontinuation of the drops <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: 
• Seriousness/Classifications (see definition in Section 13.1) 
• 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) 
• 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 0)   
• Outcome – not recovered or not resolved; recovering or resolving; recovered or 
resolved with sequelae; recovered or resolved; death related to adverse event; 
unknown 
• Actions Taken – none; temporarily discontinued; permanently discontinued; other 
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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: 
• Not Related- An adverse event that is not related to the use of the test article, study 
treatment or study procedures 
• 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 
• 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 
• 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: 
• Mild – Event is noticeable to the subject, but is easily tolerated and does not 
interfere with the subject’s daily activities 
• Moderate – Event is bothersome, possible requiring additional therapy, and may 
interfere with the subject’s daily activities 
• 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.   
 
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.   
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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: 
• Adverse event (diagnosis not symptom) 
• Drawings or photographs (where appropriate) that detail the finding (e.g., size, 
location, and depth, etc.)  
• Date the clinical site was notified  
• Date and time of onset 
• Date and time of resolution 
• Adverse event classification, severity, and relationship to test articles, as applicable 
• Treatment regimen instituted, including concomitant medications prescribed, in 
accordance with applicable licensing requirements 
• Any referral to another health care provider if needed 
• Outcome, ocular damage (if any) 
• Likely etiology 
• 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 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 
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IEC/IRB according to their requirements (Section 13.4.2).  The report will comment 
whether or not 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. 
 
When medically necessary, the Investigator may break the randomization code to 
determine the identity of the treatment that the subject received.  The Sponsor and study 
monitor should be notified prior to unmasking the test articles. 
 
In the event of a serious/significant adverse event, the Investigator must: 
• Notify the Sponsor immediately 
• 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 
• 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 
• 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. 
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.  
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13.4.3. Event of Special Interest 
None. 
13.5. Reporting of Pregnancy 
Subjects reporting pregnancy (by self-report) during the course of 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 or higher (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.   
 
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. 
14.2. Sample Size Justification 
The plan is to enroll 60 subjects with a target of 50 subjects to complete the study. This is 
a pilot study and the sample size was not based on any empirical power calculation. The 
power analysis for different scenarios of size effects (Δ) and inter-subject correlation (ρ), 
assuming a common VAS comfort score variance of 25, are summarized below: 
 
Table 4: Power Analysis for VAS comfort  
Δ 
ρ 
Power (%) 
 
5 
 
.30 
21.6 
.50 
 28.4 
.80 
59.2 
 
10 
.30 
64.9 
.50 
79.2 
.80 
99.2 
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The power analysis was conducted the SAS procedure PROC POWER procedure for paired 
tests. 
14.3. Analysis Populations 
Safety Population: 
All subjects who were administered any test article excluding subjects who drop out prior 
to administering any test article. 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 scores will be analyzed using a multivariate Bayesian model for repeated 
measures to test for the difference between the Test and Control eye drops. The regression 
model will include sequence and solution as fixed effects. The correlation between 
measurements across periods will be modeled using unstructured variance-covariance 
matrix. 
 
The Model: 
Let yijk = (y1ij, y2ij) T denote the comfort scores for the ith subject, from ith site at 1week 
follow-up. The likelihood of yij is constructed as follow: 
 
yij ~ N(µ, Σ),  
 
 where μ = (μ1, μ2)T and Σ is a 2x2 variance-covariance matrix. Here μi, i =1, 2, are given 
by: 
 
μ1 = μ0 + β1BASE + β2sequence + β3Test, 
μ2 = μ0 + β1BASE + β2sequence - β3Test, 
 
 
Other baseline characteristics such as age, gender DEQ-5 score will also be included as 
fixed effects when appropriate. 
 
Non-informative prior distributions will be used for the coefficients in the models as well 
as for the error terms: Independent vague normal N(0,1000) priors for the regression 
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coefficients (μ0  and β ) and inverse Wishart IW(R,2) for Σ. R is determined by S = E[Σ] = 
4R where S is the sample variance-covariance matrix of the yij. The Metropolis sampler 
algorithm as implemented in the MCMC Procedure (SAS 9.4, SAS Institute, Cary, NC) 
will be used to estimate the posterior distributions of the unknown parameters. Inferences 
will be made based on a posterior credible interval for the relevant parameters. Results will 
be reported as regression coefficient mean estimates with 95% credible intervals. 
  
Hypothesis Testing:  
The null and alternative hypotheses for superiority is as follows: H0: β3 ≤ 0, Ha: β3 > 0. 
Superiority will be declared if the lower bound of the 2-sided 95% credible interval of the 
difference between Test and Control is greater than 0: P(β3 > 0|y) ≥ 0.95.  
 
14.6. Secondary Analysis  
OSDI scores will be analyzed using the same model described in the primary analysis.  
The null and alternative hypotheses for superiority is as follows: H0: β3 ≥ 0, Ha: β3 < 0. 
Superiority will be declared if the upper bound of the 2-sided 95% credible interval of the 
difference between Test and Control is less than 0: P(β3 < 0|y) ≥ 0.95.  
14.7. Other Exploratory Analyses  
If superiority cannot be concluded, the predictive probability of trial success (PPOS) will 
be calculated for different scenarios of sample size (n) to support the planning for future 
studies. 
Given the historical data from this pilot study, the PPOS will be estimated using a 
simulation based algorithm. We will simulate 1000 trials of 120 subjects from the 
predictive density function of y, then we will assess if success criterion β3 > 0 is met for 
each trial. The PPOS is estimated by the proportion of runs where the success criterion is 
met. The same algorithms will be used to calculate the PPOS for n = 150, 200.   
 
Further exploratory analysis will be conducted on DEQ-5 scores, LipiView II® lipid layer 
measurements, non-invasive tear break-up time (NITBUT), corneal staining and subject’s 
reported ocular symptoms (CTP-2009) at the discretion of the Study Responsible Clinician.  
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. 
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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 JJV database manager and sent to JJV 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 
15.2. Subject Record 
At a minimum, subject record should be available for the following:  
• subject identification 
• eligibility 
• study identification 
• study discussion 
• provision of and date of informed consent 
• visit dates 
• results of safety and efficacy parameters as required by the protocol 
• a record of all adverse events 
• follow-up of adverse events 
• medical history and concomitant medication 
• test article receipt/dispensing/return records 
• date of study completion 
• 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. 
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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, JJV 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 
JJV.  The Investigator may use this information for the purposes of the study only. It is 
understood by the Investigator that JJV 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-
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 JJV 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 JJV 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: 
• Ensuring that the investigation is being conducted according to the protocol, any 
subsequent amendments, and regulatory requirements are maintained 
• Ensuring the rights and wellbeing of subjects are protected 
• Ensuring adequate resources, including facilities, laboratories, equipment, and 
qualified clinical site personnel 
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• Ensuring that protocol deviations are documented with corrective action plans, as 
applicable 
• Ensuring that the clinical site has sufficient test article and supplies 
• Clarifying questions regarding the study 
• Resolving study issues or problems that may arise 
• 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. 
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): 
• Final protocol and, if applicable, amendments 
• Sponsor-approved informed consent form (and any other written materials to be 
provided to the subjects) 
• Investigator’s Brochure (or equivalent information) and amendments 
• Sponsor-approved subject recruitment materials 
• Information on compensation for study-related injuries or payment to subjects for 
participation in the study 
• Investigator’s curriculum vitae, clinical licenses, or equivalent information (unless 
not required, as documented by IEC/IRB) 
• Information regarding funding, name of the Sponsor, institutional affiliations, other 
potential conflicts of interest, and incentives for subjects 
• Any other documents that the IEC/IRB requests to fulfill its obligation 
 
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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: 
• Protocol amendments 
• Revision(s) to informed consent form and any other written materials to be provided 
to subjects 
• If applicable, new or revised subject recruitment materials approved by the Sponsor 
• Revisions to compensation for study-related injuries or payment to subjects for 
participation in the study 
• Investigator’s Brochure amendments or new edition(s) 
• Summaries of the status of the study (at least annually or at intervals stipulated in 
guidelines of the IEC/IRB) 
• Reports of adverse events that are serious, unanticipated, and associated with the 
test articles, according to the IRB’s requirements 
• New information that may adversely affect the safety of the subjects or the conduct 
of the study 
• Major protocol deviations as required by the IEC/IRB 
• Report of deaths of subjects under the Investigator's care 
• Notification if a new Investigator is responsible for the study at the clinical site 
• 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.  
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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 Health Information Portability and Accountability Act (HIPAA) in the 
United States9 and other applicable personal data protection and security laws and 
regulations.  Appropriate measures will be employed to 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: 
• processed fairly and lawfully 
• collected for specified, explicit, and legitimate purposes and not further processed 
in a way incompatible with these purposes 
• adequate, relevant, and not excessive in relation to said purposes 
• 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. 
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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 
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 
JJV. 
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 JJV management representative prior to study initiation. 
 
JJV reserves the right to withhold remuneration for costs associated with protocol 
violations such as: 
• Continuing an ineligible subject in the study 
• Scheduling a study visit outside the subject’s acceptable visit range 
 
JJV reserves the right to withhold final remuneration until all study related activities have 
been completed, such as: 
• Query resolution 
• Case Report Form signature 
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• Completion of any follow-up action items  
21. PUBLICATION 
This study will be registered on ClinicalTrials.gov based on the following: This study is a 
post-market study with approved products assessing endpoints associated with ocular 
comfort. While the study in exploratory in nature, the data generated (for both the drops 
and the LipiViewII®) could be used for scientific materials. 
22. REFERENCES 
1. ISO 14155:2011: Clinical Investigation of Medical Devices for Human Subjects 
— Good Clinical Practice. Available at: https://www.iso.org/standard/45557.html  
2. International Conference on Harmonization Good Clinical Practice E6 (ICH-
GCP). Available at: 
http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html  
3. Declaration of Helsinki - Ethical principles for Medical Research Involving 
Human Subjects. Available at: 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). Available at: 
https://www.gpo.gov/fdsys/browse/collectionCfr.action?collectionCode=CFR  
5. Farrand KF, Fridman M, Stillman IO, Schaumberg DA.  Prevalence of Diagnosed 
Dry Eye Disease in the United States Among Adults Aged 18 Years and Older.  
Am J Ophthalmol. 2017;182-190.  
6. Schiffman RM, Christianson MD, Haconsen G, Hirsch JD, Reis BL. Reliability 
and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 
2000;118:615621 
7. Validation of the 5-Item Dry Eye Questionnaire (DEQ-5): Discrimination across 
self-assessed severity and aqueous tear deficient dry eye diagnoses; Chalmers RL, 
Begley CG, and Caffery B, Contact Lens & Anterior Eye 33 (2010) 55-60 
8. Health Information Portability and Accountability Act (HIPAA). Available at: 
https://www.hhs.gov/hipaa/for-professionals/privacy/index.html  
 
 
 
 
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APPENDIX 
A: 
PATIENT 
REPORTED 
OUTCOMES 
(STUDY 
QUESTIONNAIRES) 
 
 
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APPENDIX B: PATIENT INSTRUCTION GUIDE  
 
Patient Instruction Guide will be provided separately.  
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APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT) 
 
 
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APPENDIX D: LIPIVIEW II® II ASSESSMENT PROCEDURE 
 
 
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012051-US Rev C   
 2016 TearScience, Inc.  
“TearScience” and “LipiView” are registered trademarks of TearScience, Inc. in the United States and other 
jurisdictions.  All other product or company names that may be mentioned in this publication are trade names, 
trademarks or registered trademarks of their respective owners. 
 
 
Revision History 
Revision 
Date 
Description of Changes 
ECR # or PCR # 
A 
19 Nov 2014 
Initial release of Instructions for Use for LipiView 
II/3.x software. 
P1407211 
B 
31 July 2015 
Made updates for software version 3.11.  Replaced 
Figure 6. Fixed minor typographical and formatting 
errors. 
P1502121 
C 
1 February 2016 
Previous revisions of this document were numbered 
012051-ENG. To accommodate the release of varied 
English versions, this document is now numbered as 
012051-US with the following applicable changes: 
Removed phrase "All of these image types can be 
photographically documented and visually 
monitored" from Indications for Use. 
Removed information pertaining to Model LVI-1001.  
Updated phototoxicity warning with ISO 15004-2 
required information.  
Clarified patient contact components and added 
disinfection of Lid Everter to Device Description and 
Warning sections (already described in Cleaning and 
Instructions sections of the manual).  
Added inspection of Lid Everter to Device 
Description and Instructions.  
Added USB mouse and keyboard to Accessory 
Support.  
Updated recording time from 10 to 5 seconds in 
Capture Ocular Images procedure.  
Updated document copyright date to 2016. 
P1601281 
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TearScience® LipiView® II Instructions for Use 
012051-US Rev C 
 2016 TearScience, Inc. 
   
 
 
 
 
 
 
Page 3 of 47  
Contents 
1 INTRODUCTION .........................................................................................................5 
2 IMPORTANT DEVICE INFORMATION ...........................................................................6 
2.1 
Indications for Use ................................................................................................................. 6 
2.2 
Contraindications ................................................................................................................... 6 
2.3 
Precautions ............................................................................................................................... 6 
2.4 
Warnings .................................................................................................................................. 6 
2.5 
Potential Adverse Effects ....................................................................................................... 9 
2.6 
Labeling .................................................................................................................................... 9 
2.7 
Device Description and Overview ..................................................................................... 10 
2.7.1 
Base with Computer System and Electronics ............................................................. 13 
2.7.2 
Forehead and Chin Rest with Fluted Roller ............................................................... 14 
2.7.3 
Motion Stage .................................................................................................................... 14 
2.7.4 
Camera and Attached Lens ........................................................................................... 14 
2.7.5 
Illuminator ........................................................................................................................ 14 
2.7.6 
Pushbutton Controls ...................................................................................................... 14 
2.7.7 
Touchscreen Display with Pivoting Arm .................................................................... 14 
2.7.8 
USB Ports ......................................................................................................................... 15 
2.7.9 
Handheld Near Infrared (IR) Lid Everter .................................................................. 15 
2.7.10 Operating Environment and Specifications ............................................................... 15 
2.7.11 Accessory Support ........................................................................................................... 15 
2.8 
Storage and Transport ......................................................................................................... 16 
2.9 
Installation, Maintenance and Servicing .......................................................................... 16 
2.10 
Cleaning.................................................................................................................................. 16 
2.11 
Disposal .................................................................................................................................. 17 
2.12 
Warranty ................................................................................................................................ 17 
3 INSTRUCTIONS FOR USE ........................................................................................... 18 
3.1 
Startup and Login ................................................................................................................. 18 
3.2 
First Time Device Setup ...................................................................................................... 19 
3.3 
Menu Bar ................................................................................................................................ 20 
3.4 
Enter and Select a Patient and Imaging Mode ................................................................. 21 
3.5 
Capture Tear Film Images (Lipid Imaging Mode) ......................................................... 22 
3.6 
Review Tear Film Images (Lipid Imaging Mode) ........................................................... 24 
3.7 
Capture Gland Images (Gland Imaging Mode) .............................................................. 27 
3.8 
Review Gland Images (Gland Imaging Mode) ................................................................ 31 
3.9 
Capture Ocular Images (Ocular Imaging Mode) ............................................................ 34 
3.10 
Review Ocular Images (Ocular Imaging Mode) .............................................................. 36 
3.11 
Log Out and Power Off ....................................................................................................... 37 
4 TROUBLESHOOTING GUIDE ..................................................................................... 38 
APPENDIX: ELECTROMAGNETIC COMPATIBILITY REQUIREMENTS .................................. 44 
 
 
 
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Figures 
Figure 1. Front (Patient) View of LipiView II ..................................................................................... 11 
Figure 2. Rear (User) View of LipiView II ........................................................................................... 12 
Figure 3. Handheld Near Infrared (IR) Lid Everter ........................................................................... 13 
Figure 4. External Connectors on Underside of Base ........................................................................ 13 
Figure 5. Warning Screen ........................................................................................................................ 18 
Figure 6. Initialization Screen ................................................................................................................. 18 
Figure 7. Login Screen .............................................................................................................................. 18 
Figure 8. Patient Records Screen ............................................................................................................ 19 
Figure 9. Main Admin Screen ................................................................................................................. 19 
Figure 10. Menu Bar ................................................................................................................................. 20 
Figure 11. Patient Records Screen ......................................................................................................... 21 
Figure 12. Patient Entry Screen .............................................................................................................. 21 
Figure 13. Capture/View Screen ............................................................................................................ 21 
Figure 14. Lipid Image Capture Screen with Labeled Controls ....................................................... 23 
Figure 15. Export Dialog ......................................................................................................................... 24 
Figure 16. Interferometric Colors .......................................................................................................... 24 
Figure 17. Review Lipid Images Screen with Labeled Controls ....................................................... 25 
Figure 18. Example OD Image – Average Lipid Layer Thickness 39 nm ...................................... 26 
Figure 19. Example OS Image – Average Lipid Layer Thickness 100+ nm .................................. 26 
Figure 20. Everting Lower Eyelid using Handheld Near IR Lid Everter ........................................ 28 
Figure 21. Everting Upper Eyelid using Cotton Swab ....................................................................... 28 
Figure 22. Gland Image Capture Screen with Labeled Controls ..................................................... 29 
Figure 23. Pushbutton Controls (on top of unit) ............................................................................... 30 
Figure 24. Properly Focused Lower Lid Images: Reflected IR and Trans IR ................................. 31 
Figure 25. Gland Example Images:  No Dropout, Medium Dropout, High Dropout ................ 32 
Figure 26. Gland Dilation Example, Lower Lid .................................................................................. 32 
Figure 27. Review Gland Images Screen with Labeled Controls...................................................... 33 
Figure 28. Ocular Image Capture Screen with Labeled Controls .................................................... 35 
Figure 29. Review Ocular Images with Labeled Controls ................................................................. 36 
 
Tables 
Table 1: General and Operation Warnings ........................................................................................... 7 
Table 2. Symbols Used on LipiView II Labeling ................................................................................... 9 
Table 3. System and Environmental Specifications ............................................................................ 15 
Table 4: LipiView II Cleaning Information ........................................................................................ 16 
Table 5. Main Admin Functions ........................................................................................................... 20 
Table 6: Troubleshooting Unexpected Events .................................................................................... 38 
Table 7. Operational System Messages and Descriptions.................................................................. 39 
Table 8: Guidance and Manufacturers Declaration-Electromagnetic Emissions ......................... 44 
Table 9: Guidance and Manufacturers Declaration-Electromagnetic Immunity (part 1) .......... 45 
Table 10: Guidance and Manufacturers Declaration-Electromagnetic Immunity (part 2)........ 46 
Table 11: Recommended Separation Distances Between Portable and Mobile RF 
Communications Equipment and LipiView II .......................................................................... 47 
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1 
Introduction 
This manual provides the indications, contraindications, warnings, precautions, potential 
adverse effects and instructions for use for the TearScience® LipiView® II Ocular Surface 
Interferometer.  Carefully read this manual in its entirety before using LipiView II.  Failure 
to follow these instructions may result in improper use of the device. 
This manual provides essential information for safe and proper use of LipiView II.  
• Section 2 (Important Device Information:  indications, contraindications, warnings, 
precautions, potential adverse effects, device description, storage and transport, service and 
maintenance, cleaning, disposal and warranty) 
• Section 3 (Instructions for Use for Start-up, First Time Setup, Lipid Imaging, Gland 
Imaging and Ocular Imaging)  
• Section 4 (Troubleshooting Guide) 
The LipiView II Administrator’s Guide contains information about the setup and 
administration of LipiView II.  
• Prior to initial use of LipiView II, refer to Section 3.2 of this manual and/or the 
Administrator’s Guide to ensure proper setup (including requirements for operator 
(user) names, passwords, network connections and file storage.) 
NOTE: LipiView II has a firewall and disabled remote access to protect the device and ensure 
privacy of patient records over a network. However, if LipiView II is connected to a non-secure 
wireless network, exported patient data will not be protected from unauthorized access. 
TearScience recommends the LipiView II be connected to a password-protected wireless router 
utilizing the WPA or WPA2 security protocols to ensure protection of the device and patient 
records.  
 
Strong passwords do not contain words that appear in a dictionary, are at least six characters 
long, and consist of a mixture of letters and numbers. TearScience recommends that you choose 
a strong password and change it regularly (for example, every 90 days.) 
Contact TearScience (in North America, at +1 919 459 4891 or by email at 
customerservice@tearscience.com) with any questions about the information contained in this 
manual or for additional information on the safe and proper operation of LipiView II.  
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2 
Important Device Information 
2.1 
Indications for Use 
The LipiView II Ocular Surface Interferometer is an ophthalmic imaging device intended for 
use by a physician in adult patients to capture, archive, manipulate and store digital images of: 
• Specular (interferometric) observations of the tear film. Using these images, LipiView 
II measures the absolute thickness of the tear film lipid layer. 
• Meibomian glands under near-infrared (NIR) illumination 
• The ocular surface and eyelids under white illumination 
2.2 
Contraindications 
Contraindications are conditions in which the device should not be used because the risk of use 
clearly outweighs any benefit. No contraindications have been identified for LipiView II. 
2.3 
Precautions 
The following patient conditions may affect the interferometry assessment of a patient’s tear 
film using LipiView II: 
• Use of ophthalmic drops such as artificial tear lubricants, ointments, and medications. 
Advise patients not to instill oil-based ophthalmic drops (e.g., Soothe, Restasis, Systane 
Balance) for at least 12 hours prior to device use and not to instill ointments for at least 24 
hours prior to device use. Wait at least 4 hours after instillation of all other ophthalmic 
drops prior to device use. 
• Soft or rigid contact lens wear. Advise patients to remove contact lenses at least 4 hours 
prior to device use. 
• Use of oil-based facial cosmetics around the eye.  
• Eye rubbing.  
• Recent swimming in a chlorinated pool. Advise patients not to swim for at least 12 hours 
prior to device use. 
• Any ocular surface condition that affects the stability of the tear film. These conditions 
include disease, dystrophy, trauma, scarring, surgery, or abnormality. 
2.4 
Warnings 
Review the warnings in Table 1 prior to using LipiView II. 
 
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6CDNG)GPGTCNCPF1RGTCVKQP9CTPKPIU
 GENERAL WARNINGS
WARNING: No modification of this equipment is allowed. 
Caution: Power Requirements. The LipiView II is a continuous operation device which 
requires a power source of 100-240 Volts AC r 10%, 50/60 Hz single phase, 4 Amps. 
Connection to a power supply other than a supply mains with protective earth may result in 
electric shock. 
Caution: The LipiView II has protection against electric shock of applied part 
classified as Type B. This device is classified as an IEC Class 1 product. 
Caution:  Voltage Protection and Fuse Selection. Contact TearScience to replace a blown 
fuse. TearScience personnel must replace only with a 5 x 20 mm, 4 A, 300 ms, 40 A breaking 
capacity fuse to avoid risk of fire. TearScience personnel must disconnect from power before 
servicing to avoid risk of electrical shock. 
Caution:  Backup Battery Replacement.  Backup battery cannot be replaced.
Caution:  Keep the LipiView II away from strong magnetic fields as it could damage the 
device’s hard drive, but is not a safety hazard to the user or patient. 
Caution:  This equipment is intended for use by healthcare professionals only. This 
equipment may cause radio interference or may disrupt the operation of nearby equipment. 
It may be necessary to take mitigation measures, such as re-orienting or relocating the 
LipiView II or shielding the location. 
Caution:  Portable and mobile RF communications equipment can affect MEDICAL 
ELECTRICAL EQUIPMENT. 
Caution:  The use of ACCESSORIES, transducers and cables other than those specified, 
with the exception of transducers and cables sold by the manufacturer of the EQUIPMENT 
or DEVICE as replacement parts for internal components, may result in increased 
EMISSIONS or decreased IMMUNITY of the EQUIPMENT or DEVICE. 
Caution:  The EQUIPMENT or DEVICE should not be used adjacent to or stacked with 
other equipment and if adjacent or stacked use is necessary, the EQUIPMENT or DEVICE 
should be observed to verify normal operation in the configuration in which it will be used. 
Caution: Degree of protection against harmful ingress of liquid: IPX0. This equipment has 
no protection against ingress of liquids. 
Caution: This device is not suitable for use in the presence of flammable mixtures. 
Caution: This device is not suitable for use in oxygen rich environments. 
Caution: The device monitor and base unit may exceed 41°C. Device will remain within safe 
momentary contact temperature, below 51°C. 
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OPERATION WARNINGS 
Caution: Federal law restricts this device to sale by or on the order of a physician. 
Caution:  The chin and forehead rest surfaces and Handheld Near IR Lid Everter must be 
disinfected with alcohol immediately prior to use and prior to storage.
Caution:  Photo-toxicity hazard. No acute optical radiation hazards have been identified 
for LipiView II under intended use conditions. Since prolonged intense light exposure can 
damage the retina, the use of the device for ocular examination should not be unnecessarily 
prolonged. The retinal exposure dose for a photochemical hazard is a product of the radiance 
and the exposure time. Aphakes and persons with diseased eyes will be at greater risk. The 
risk may also be increased if the person being examined has had any exposure with the same 
instrument or any other ophthalmic instrument using a visible or near-infrared light source 
during the previous 24 hours. 
Caution:  The light emitted from this instrument is potentially hazardous. The longer the 
duration of exposure, the greater the risk of ocular damage. Exposure to light from the 
instrument when operated at maximum intensity will exceed the safety guideline after 8 
hours. 
Caution: To prevent pinching, do not put fingers near illuminator, lens or chin rest during 
focusing. Instruct patient not to place hands on LipiView II during operation, and not to put 
fingers near illuminator, lens or chin rest. 
Caution: If a problem occurs with LipiView II, identify the symptom then attempt to resolve 
the problem as indicated in Section 4, Troubleshooting Guide.  If the problem cannot be 
resolved, stop using the device and contact TearScience.  
Caution: To prevent electric shock or performance alteration, do not attempt to service the 
device or remove the cover. No maintenance is required for LipiView II, and the device and 
all of its associated parts are not serviceable by the user. 
Caution: In order to isolate this equipment from supply mains the equipment must be 
unplugged from the wall.  Do not position the equipment in a location which would prevent 
the unit from being unplugged in an emergency. 
Caution: Do not store this instrument in conditions where the temperature may rise above 
55°C or fall below -10°C. 
Caution: When lifting or handling LipiView II, caution should be taken to prevent injury or 
damage to the device. Prior to moving the device, put the monitor arm into a locked position 
and unplug the power cord from the wall. If an external monitor is attached, disconnect the 
external monitor prior to moving the device.
Caution: Shock hazard. Do not touch patient and device under top cover simultaneously. 
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Figure 3. Handheld Near Infrared (IR) Lid Everter 
 
Figure 4. External Connectors on Underside of Base 
 
Key 
1 
Hardwired HDMI connection for external monitor 
2 
Connector for Handheld Near IR Lid Everter 
3 
Connector for Power Cord 
 
2.7.1 
Base with Computer System and Electronics 
The base houses the power connection and computer hardware. The base connects with the 
forehead and chin rest, motion stage and touchscreen display.  The on/off power switch (Figure 
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2) is located on the base opposite the chin rest.  An external monitor connection is hardwired 
into the base, as is a connection point for the Near IR lid everter.   
2.7.2 
Forehead and Chin Rest with Fluted Roller  
The adjustable forehead and chin rest is designed to allow proper positioning of the patient’s 
head to capture images.  To ensure a properly focused image, the patient must place his/her 
forehead and chin firmly against the forehead and chin rests. The chin rest may be raised or 
lowered to accommodate different facial dimensions by spinning the fluted roller.  The chin 
rest has a 2-position adjust (toward the device for Lipid imaging and away from the device for 
Gland and Ocular Imaging.)  
Two canthus alignment marks are located on the left and right sides of the forehead rest. 
Adjusting the chin rest to position the lateral canthus of the patient’s eye at these marks will 
optimize the range of camera motion.  
The forehead and chin rest come in contact with the patient. Disinfect the forehead and chin 
rest surfaces with alcohol immediately prior to use and prior to storage. 
2.7.3 
Motion Stage 
The motion stage contains the camera, illuminator and motor controls used to adjust the 
camera and illuminator. The height of the motion stage is adjusted as part of the image capture 
process, to position the camera correctly. 
2.7.4 
Camera and Attached Lens 
The camera is located inside the motion stage and is not visible externally. The height of the 
camera is adjusted as part of the motion stage. The camera can also be adjusted left and right 
and backwards and forwards with separate controls. 
2.7.5 
Illuminator 
The grid-like fixture attached to the motion stage is the illuminator. The height of the 
illuminator is adjusted as part of the motion stage. There are no separate controls for the 
illuminator. 
2.7.6 
Pushbutton Controls  
LipiView II includes a pushbutton control keypad on top of the unit that may be used in all 
modes, to make it easier for the operator to capture images. 
2.7.7 
Touchscreen Display with Pivoting Arm 
The touchscreen display is on a pivoting arm, which allows it to be positioned ± 45 degrees or ± 
90 degrees from its location shown in Figure 1.  To reposition the screen, press the button 
under the pivoting arm while moving the arm left or right to the approximate 45 or 90 degree 
location.  Release the button and continue moving the arm until it locks into place.  
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In addition to displaying images and information to the operator, the screen functions as a 
touchscreen user interface to the LipiView II.  The operator touches the screen to operate the 
motion stage and camera controls and capture images.  
2.7.8 
USB Ports 
The lower base of the touchscreen display contains three USB ports, located as shown in Figure 
2.  These ports may be used to connect a printer or storage device.  
2.7.9 
Handheld Near Infrared (IR) Lid Everter  
The Handheld Near Infrared (IR) Lid Everter is both a near-infrared light source and a shaped 
instrument that aids in the proper eversion of the lower eyelid.  The Near IR Lid Everter 
contacts the patient’s lower eyelid. Inspect the Near IR Lid Everter to ensure it is intact prior to 
use.  Disinfect the Near IR Lid Everter with alcohol immediately prior to use and prior to 
storage. Place the Near IR Lid Everter slightly below the lash line and move the instrument 
slightly inward and upward to evert the entire length of the lower eyelid. 
2.7.10 Operating Environment and Specifications 
System and environmental specifications are displayed in Table 3. 
Table 3. System and Environmental Specifications 
Input Voltage 
100 – 240 VAC, 50 – 60 Hz 
Product Safety Classification 
Type B Applied Part 
IEC 60601-1— Medical electrical equipment—Part 1: 
General requirements for safety 
 
IEC 60601-1-2 — Medical electrical equipment—Part 1: 
General requirements for safety—Section 2: Collateral 
standard—Electromagnetic compatibility—Requirements 
and tests; 
CISPR 11 (Class A, Group 1) 
Accuracy of lipid layer thickness measurement 
±10 nm 
Operating Temperature 
10°C to 35°C 
Operating Relative Humidity 
Up to 90% non-condensing 
Atmospheric Pressure 
700 hPa to 1060 hPa 
Storage Temperature 
-10°C to 55°C 
Transport Temperature 
5°C to 60°C 
 
2.7.11 Accessory Support 
LipiView II may be used with the following USB accessories that are compatible with Windows 
7 and USB 2.0: 
• USB printer (Printer Support) 
• USB external hard drive (External Backup Support) 
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• USB flash drive (USB / Thumb Drive Support) 
• USB mouse and keyboard (support for optional alternative to touchscreen controls) 
LipiView II is designed to operate wirelessly with other network devices, such as a printer.  
Placement of LipiView II should be within range of the network, if a network system is used. 
LipiView II may be used with an external monitor. The hardwired connection in the base will 
support HDMI or DVI inputs for an off-the-shelf external monitor, which has at least 1280 x 
1024 resolution and supports 60Hz frame rates. 
2.8 
Storage and Transport  
Before storage, ensure the power switch is off, and the chin and forehead rest surfaces, as well as 
the Near  IR Lid Everter, are cleaned according to the instructions in Section 2.10, Cleaning.  
Store LipiView II in a way that prevents contamination and damage between uses.  
 
For transport, ensure power cord is unplugged and secured off the ground. Grip onto metal 
portion of the device in two locations: 1) under the base or under the head containing the 
motion stage; and 2) monitor arm behind the screen. Carefully lift and move the device in an 
upright position. 
2.9 
Installation, Maintenance and Servicing 
There are no specific installation requirements for LipiView II, other than unpacking the device 
from its carton and connecting power and accessories (the external monitor and Near IR Lid 
Everter.) The device is installed and ready to use safely and correctly if it passes its Power-On 
Self Test with no system errors. 
LipiView II performs a calibration process at startup.  LipiView II does not require preventive 
maintenance or scheduled calibration. If the touchscreen gets out of calibration, refer to the 
LipiView II Administrator’s Guide for instructions on how to recalibrate the touchscreen using 
the built-in utility. 
Expected life of LipiView II is 5 years. Note that no user serviceable components are inside the 
unit.   For Field Service, contact TearScience in North America at +1 919 459 4891 or by email 
at customerservice@tearscience.com.   
2.10 
Cleaning 
Table 4 identifies the components of LipiView II that require cleaning. For each component, 
the frequency and method of cleaning is provided. 
 
Table 4: LipiView II Cleaning Information 
Component 
Frequency 
Method 
Chin rest and 
forehead rest 
Immediately prior to 
use and prior to storage 
Alcohol 
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surfaces 
 Handheld Near IR 
Lid Everter 
Immediately prior to 
use and prior to storage 
Alcohol 
Camera lens and 
Illuminator 
Monthly 
Wipe with a lint-free photographic quality 
lens cloth 
Touchscreen 
Display Monitor 
When soiled or as 
needed 
• Power off the device. 
• Apply window or glass cleaner to a 
cloth rag and wipe the screen  
• Do not apply cleaner directly to the 
screen 
• Do not clean the monitor with 
alcohol, paint thinner, benzene or 
compressed air 
LipiView II 
exterior, including 
keypad 
When soiled or as 
needed 
• Wipe down exterior of the device with 
a mild soapy cloth 
• Do not use bleach, chlorine or 
acetone-based solutions to clean any 
part of the chin rest or the system 
enclosure 
External monitor  
Follow manufacturer’s 
cleaning instructions 
Follow manufacturer’s cleaning 
instructions 
 
2.11 
Disposal 
LipiView II consists of an ABS plastic enclosure, aluminum chassis, circuit boards, and electrical 
components. In the unlikely event that the device is damaged and cannot be repaired, never 
dispose of the device.  Return LipiView II to TearScience using the contact information on the 
first page of this manual. 
2.12 
Warranty 
TearScience, Inc. warrants that each LipiView II:   1) is free from defects in materials and 
workmanship; and 2) conforms to TearScience Inc.’s official specifications.  The warranty 
period for each LipiView II is one year commencing on the date of purchase. Any tampering or 
modifications to the device by the user will void the warranty. 
 
 
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3 
Instructions for Use 
3.1 
Startup and Login 
At startup, LipiView II performs a self-test, confirms camera connection, verifies system 
voltages, checks remaining hard drive space, and calibrates camera motors. 
 
Figure 5. Warning Screen 
 
 
Figure 6. Initialization Screen 
 
 
Figure 7. Login Screen 
1. Ensure the power cord is plugged into an 
electrical outlet. The power cord connection is 
located underneath the base of the device. 
2. Power on LipiView II by pressing the rocker 
switch on the device base (refer to Figure 2).  
The touchscreen display is initially blank and 
then displays a “Welcome” message and other 
messages related to self-test and initialization.   
3. Press the OK button to acknowledge the 
warning (Figure 5) after ensuring the patient 
and operator are clear of the chinrest area.  The 
motion stage moves during system hardware 
self-test, which takes about 20 seconds. 
4. Touch the screen to continue when Figure 6 is 
displayed indicating that the device is ready for 
use. (Note that the software version displayed 
may differ from Figure 6.) 
5. When the Login screen (Figure 7) is displayed, 
enter the operator name and password using the 
onscreen keyboard. (Operator name and 
password are provided by the Administrator or 
TearScience trainer.)  Press Log In. 
 
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3.2 
First Time Device Setup 
Prior to initial use, ensure that the following instructions are completed by an Administrator.  
Other administrative functions, detailed in LipiView II Administrator’s Guide, can be 
completed at the discretion of the Administrator. LipiView II has been set up with a default  
Operator Name (LIPIVIEW) and Password (LIPIVIEW) that has administrator privileges.   
After initial login, it is recommended but not required that the Administrator reset the 
password. 
 
 
Figure 8. Patient Records Screen 
 
 
Figure 9. Main Admin Screen 
 
 
1. Power on the system. 
2. When the Login screen (Figure 7) is 
displayed, enter LIPIVIEW for both the 
Username and Password. (The onscreen 
keyboard only supports uppercase characters.)  
Press Log In. The Patient Records screen 
(Figure 8) is displayed. 
3. Press the Gear icon [
] on Menu bar (Figure 
10) located in the upper right corner of the 
screen.  The Main Admin screen (Figure 9) is 
displayed. 
4. Press Operator Setup. Add additional operator 
usernames and set or change passwords as 
needed. 
Before capturing images, it is also recommended 
that the following items be set up using the 
functions on the Main Admin screen (Table 5).  
 
 
From Main Admin screen (Figure 9): 
5. Press Practice Info to enter Practice 
Information. 
6. Press System Info, then Press Set Date and 
Time to set System Date and Time.  
7. Press Network to set up network connections. 
8. Press Close to return to the Patient Records 
screen (Figure 8). 
 
 
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Table 5. Main Admin Functions 
System Info 
System information, including software versions and important utilities 
(Calibrate Touchscreen, Set Date and Time, Set Up System for Packaging, 
Launch Remote Support, Software Update, Save Changes and Shut Down, Save 
as PDF) 
Practice Info 
Enter the name and business information for the medical practice 
System Log 
View the system log, which collects information about key system events and 
errors (useful for troubleshooting and technical support) 
Operator Setup 
Add or delete Operators (users) and/or Administrator 
Export Setup 
Select file formats for records export 
Network 
View network information 
Hardware Status 
See comprehensive status information for the hardware and software 
Traceability Log 
View records of all traceable events to ensure data integrity (e.g., users 
added/deleted, treatment records moved from one patient to another) 
System Options 
Set the automatic logout timer, choose display options 
Modality 
Configuration 
Set options for Lipid Imaging or Gland Imaging modes 
Usage Summary 
View statistics about use, selected by configurable criteria 
Data Management 
Delete or move patient records (creates a permanent record in the Traceability 
Log) 
Backup/Restore 
Backs up or restores LipiView II patient and treatment data to networked drive 
or other media 
 
3.3 
Menu Bar 
The menu bar (Figure 10), shown at the top of the screen, has the following icons. 
 
 
Figure 10. Menu Bar 
 
Key 
1 
Patients Button – Touch to return to Patient Records screen (Figure 11) 
2 
Drawer Dropdown – Contains information on current patient and active imaging session 
(if any). Pull down to access patient history. 
When on Image Capture screens or Review Image screens, press Capture/View Button on 
menu bar to return to Capture/View screen (Figure 13). 
3 
Admin – Touch to access Administrator screens (requires access privileges) 
4 
Log Out 
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3.4 
Enter and Select a Patient and Imaging Mode 
After Login, enter a new patient or search for an existing patient.  Select the patient to capture 
new images or view prior images. Then, select an imaging mode.  
 
 
Figure 11. Patient Records Screen 
 
 
Figure 12. Patient Entry Screen 
 
 
Figure 13. Capture/View Screen 
1. For a New Patient, select Add Patient on 
Patients Records screen (Figure 11) to display 
Patient Entry screen (Figure 12). 
2. Using onscreen keyboard, enter patient 
information, then press Save.  Patient records 
must include at a minimum: 
1) Patient ID or 
2) Last Name, First Name and Date of Birth 
(enter the month and date as two-digit 
numbers, and the year as a four-digit number: 
MM/DD/YYYY). 
3. For an Existing Patient, enter patient data 
(patient ID or name) in Search field on Patient 
Records screen (Figure 11) to locate the record. 
To edit patient data, press Pencil icon to the 
right of the list. 
4. Select the desired patient record from the 
patient listing table.  
NOTE: The step keys can be used to move 
backwards or forwards through the table.  When 
the list spans multiple pages, sort the table by 
pressing the header field by the desired column. 
Press the same header a second time to sort the 
table in the reverse order. A small triangle in the 
column header indicates the table is being 
displayed by this column. The triangle points 
down or up to specify the sorting direction. 
5. When Capture/View screen (Figure 13) 
displays, select an imaging mode (Lipid 
Imaging, Gland Imaging or Ocular Imaging) to 
capture new images or view prior images for 
that patient. Select All Exams to view all images 
in the patient’s history. 
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3.5 
Capture Tear Film Images (Lipid Imaging Mode) 
1. To image the tear film lipid layer by specular reflection of light, select Lipid Imaging from the 
Capture/View screen (Figure 13) and press New. 
2. Disinfect the forehead and chin rest with alcohol prior to use. 
3. Ensure the chin rest is in closest position toward the device. 
4. Place the patient’s chin fully forward into chin rest and forehead firmly against forehead rest. 
Adjust the height of the chin rest by spinning the fluted roller until the temporal canthus is 
aligned with the marks on the left and right sides of the forehead rest. Instruct the patient to 
look at the orange fixation light. 
CAUTION:  To prevent pinching, do not put fingers near illuminator, lens or chin rest 
during focusing. Instruct patient not to place hands on LipiView II during operation, and 
not to put fingers near illuminator, lens or chin rest. 
5. Select OD (right eye) or OS (left eye) to image by touching the right or left side of the Lipid 
Image Capture screen (Figure 14).   
6. Position the camera using one or a combination of methods:  1) If the pupil is visible on 
screen, press autoposition reticle to automatically center the camera on the pupil.  2) Touch 
the desired location (toward pupil) on screen, which will automatically move the camera and 
center on the location.  3) Press the manual position buttons, as needed, until the pupil 
appears in the center of the screen.  (You may also use the keypad to position the camera.) 
NOTE:  Ensure the lower lid margin is visible to evaluate partial blinking   
7. Focus the camera using one or a combination of methods: 1) Press autofocus reticle to focus 
(not necessary if reticle was already pressed to position camera); 2) press fine focus buttons to 
adjust the focus until the tear film image is clear.  (You may also use the keypad to focus the 
camera.) 
NOTE:  If the tear film image is not in focus, invalid video data may be saved.  
8. Press Capture button to begin recording approximately 20 seconds of video. The blinking red 
light indicates LipiView II is recording.  Press Capture button again to stop recording prior to 
20 seconds, if desired. 
9. Instruct the patient to blink naturally or to perform a squeezed blink, as desired. 
10. When recording is complete, the illuminator turns off.  Press Notes to add any notes to 
images, if desired. 
11. Review video using onscreen playback button. If image quality is suboptimal, delete video 
using Trashcan icon and recapture another image. 
12. Repeat steps 5 to 11 to capture an image of the other eye, if desired.   
13. Press Analyze to save and process the image(s). 
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Figure 14. Lipid Image Capture Screen with Labeled Controls 
 
Key 
1 
Magnify View Icon - OD (right eye) is currently in view. OS (left eye) side is currently 
greyed out. Touch icon to capture images for OS (left eye). 
2 
Capture Video Button – Press to begin recording. Appears as a rectangle during recording; 
press rectangle to stop recording before 20 seconds. 
3 
Select Position/Focus Button – Press to toggle display of manual focusing and positioning 
button controls on or off. 
4 
Autoposition/Autofocus Reticle – Once the pupil is visible on screen, press the reticle to 
automatically center and focus the image. 
5 
Manual Fine Focus Buttons  - Press plus or minus to focus image 
6 
Manual Positioning Buttons – Press to move camera left, right, up or down 
7 
Eye Position Indicator – Indicates the eye being imaged (OD in figure) 
8 
Analyze Button – Press to save, process and analyze captured imagery 
9 
Notes Button – Press to open notes field for text entry 
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1 Finis D, Pischel N, Schrader S, Geerling G. Evaluation of lipid layer thickness measurement of the tear film as a 
diagnostic tool for Meibomian gland dysfunction.  Cornea. 2013; 32(12):1549-53. 
 
The first images, labeled as “Example” on the Capture/View screen (Figure 13), are standard 
reference video images of eyes with different lipid layer thickness values, provided for purposes 
of comparison.  These videos allow the physician to observe differences in interference colors 
for a variety of tear films.  As shown in Figure 18, the thin lipid example image is an example of 
an average tear film lipid layer thickness of 39 nm, which is relatively thinner lipid layer with 
very little color appearing mostly gray.  Conversely, the thick lipid example image (Figure 19) is 
an example of an average tear film lipid layer thickness above 100, where brown and blue colors 
are visible indicating a relatively thicker lipid layer.   
 
Figure 18. Example OD Image – Average Lipid Layer Thickness 39 nm 
 
Figure 19. Example OS Image – Average Lipid Layer Thickness 100+ nm 
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3.7 
Capture Gland Images (Gland Imaging Mode) 
 
NOTE:  One person can both evert the lids and operate the device, using the pushbutton 
controls on the top panel with an external monitor positioned behind the patient where the 
operator can easily see it. Alternatively, imaging the meibomian glands can be easier to perform 
as a two-person procedure: one person everting the eyelids, and one person operating and 
focusing LipiView II.  
 
1. To image the meibomian glands, select Gland Imaging from the Capture/View screen (Figure 
13) and press New. 
2. Turn the room lights off (or down sharply) prior to imaging to ensure good contrast in the 
image quality. 
3. Disinfect the forehead and chin rest and Handheld Near IR Lid Everter with alcohol prior to 
use. Inspect Handheld Near IR Lid Everter to ensure it is intact prior to use. 
4. Ensure the chin rest is in the extended position away from the device (closer to the patient). 
5. Place the patient’s chin fully forward into chin rest and forehead firmly against forehead rest. 
Adjust the height of the chin rest by spinning the fluted roller until the temporal canthus is 
aligned with the marks on the left and right sides of the forehead rest. 
6. Select the upper or lower eyelid of the OD (right eye) or OS (left eye) to image  by touching 
the magnify view icon in the applicable quadrant on Gland Image Capture screen (Figure 22). 
(You may also use the buttons on the keypad.) 
7. Carefully evert the eyelid and ensure that the full extent of the meibomian glands is visible 
over the entire nasal to temporal length of the eyelid.  
a. Evert entire length of lower eyelid:  place Handheld Near IR Lid Everter (Figure 20) 
slightly below lash line; while maintaining contact, pull the lid down and then roll 
instrument slightly inward and upward. 
b. Evert upper lid at the top of the tarsal plate:  use a cotton swab, finger or other handheld 
instrument (Figure 21). Ensure the fingertip or cotton swab is not blocking the inner 
surface of the eyelid before capturing the image. 
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Figure 20. Everting Lower Eyelid using 
Handheld Near IR Lid Everter  
 
Figure 21. Everting Upper 
Eyelid using Cotton Swab 
8. Position the camera using onscreen or pushbutton controls (Figure 23) on top of the unit to 
center the image of the everted eyelid on the screen. Alternatively, when using the 
touchscreen, touch the desired location to center the image on the screen and the device will 
automatically center the image in that location. 
9. Press the autofocus reticle to focus the image using onscreen or pushbutton controls. If 
needed, press fine focus onscreen controls until the image is clear. (The F3 and F4 buttons on 
the keypad can also be used for fine focus.) 
NOTE: Ensure full extent of the glands is visible over entire nasal to temporal length of the 
eyelid. When imaging lower eyelid, toggle between Reflected IR and Trans IR views (Figure 
24) to ensure both views are of good image quality.  
10. Press Capture button using onscreen or pushbutton controls to capture image. 
11. Review gland image to ensure good image quality, including in both Reflected IR and Trans 
IR views for lower lid images (as shown in Figure 24).  If the image is suboptimal (e.g., blurred 
focus, poor centration, only a partial lid eversion, finger obscuring view, washed out), delete 
image by selecting the Trashcan icon and recapture the image.   Press Notes to add any notes 
to images, if desired. 
12. Repeat steps 6 to 11 to capture the remaining images of other eyelid locations until all four 
eyelid images (i.e., upper and lower eyelid of the right and left eyes) are captured for the 
patient, if desired.   
13. Press Analyze to save the image(s). 
NOTE:  PRESSING ANALYZE IS REQUIRED TO SAVE ALL IMAGES.           
 If Analyze is not pressed before exiting the imaging screen, a message will appear as a 
reminder to save the images. 
 
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Figure 22. Gland Image Capture Screen with Labeled Controls 
Key 
1 
Autofocus Reticle - Press the reticle to automatically focus the image 
2 
Select Position/Focus Button – Press to toggle display of manual focusing and positioning 
button controls on or off 
3 
Camera Button – Press to capture still image 
4 
Magnify View Icon - OD (right eye) lower lid is currently in view 
Touch to image OD (right eye) upper lid. 
5 
Magnify View Icon - Touch to image OS (left eye) upper lid 
6 
Magnify View Icon - Touch to image OS (left eye) lower lid 
7 
Light Source - Toggle between Reflected IR and Trans IR illumination views to image 
lower lid. Only Reflected IR illumination is used for upper lid. 
8 
Review Image Mode - Preview Captured Reflected IR, Trans IR and Merged images (after 
image capture, these small windows are populated with thumbnails of the different images) 
9 
Analyze Button – Press to save captured imagery 
10 Notes Button – Press to open notes field for text entry 
11 Manual Fine Focus Buttons  - Press plus or minus to focus image 
12 Manual Positioning Buttons – Press to move camera left, right, up or down 
 
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Gland Image Modes: 
• Reflected IR view is shown for both upper and lower eyelid gland images. 
• Trans (Transillumination) IR view is shown only for lower eyelid gland images, if 
images were captured using Handheld Near IR Lid Everter. 
• Merged view is the combination of the Reflected IR and Trans IR views and is shown 
only for the lower eyelid gland images. 
 
 
Figure 23. Pushbutton Controls (on top of unit) 
 
Key  
1 
Function Keys  
F1: In pre-capture view, toggles between Reflected IR and Trans IR mode 
F2: In post-capture review, changes view mode to captured Reflected IR image 
F3: In pre-capture mode, focuses in; post-capture review, changes view mode to captured 
Trans IR image 
F4: In pre-capture mode, focuses out; In post-capture review, changes view mode to 
captured Merged image 
2 
Select Eye/Lid - OD for right eye or OS for left eye and upper or lower lid 
3 
Position/Autofocus Buttons – Press up, down, right and left buttons to center on the 
desired lid. Tap to move in small increments or hold button down to move until released. 
Once lid is positioned, press reticle to autofocus. 
4 
Camera Button – Press to capture an image  
 
 
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OD Lower, Reflected IR View 
OS Lower, Reflected IR View 
 
 
OD Lower, Trans IR View 
OS Lower, Trans IR View 
 
Figure 24. Properly Focused Lower Lid Images: Reflected IR and Trans IR 
3.8 
Review Gland Images (Gland Imaging Mode) 
1. To review prior gland images for an existing patient: 
a. Select the patient from the Patient Records screen (Figure 11).   
b. On the Capture/View screen (Figure 13), select Gland Imaging to view prior gland 
images or select All Exams to view all prior images.   
c. A list of prior images is shown on the Capture/View screen (Figure 13).  Drag and drop 
the desired images from the list to the sides of the screen marked “Drop Here”.  Touch 
the image again to display the Review Gland Images screen (Figure 27). 
2. If desired, press the Export icon at the bottom of the Review Gland Images screen (Labeled 4 
in Figure 27) to export or print images or report.  
3. From the Export dialog (Figure 15), press the button to save images or report to an external 
medium or network, or print a report.  Exported images can be displayed with or without 
patient demographics. 
The first images, labeled as “Example” on the Capture/View screen (Figure 13), are standard 
reference images of upper and lower eyelids with different gland findings, provided for purposes 
of comparison.  As shown in Figure 25, the image set labeled high dropout is an example of an 
eye with severely truncated meibomian glands.  The image set labeled as medium dropout is an 
example of an eye with some evidence of gland loss.  The image set labeled as no dropout is an 
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example of an eye with no signs of gland loss.  In Figure 26, the lower lid image labeled as 
dilation is an example of glands that appear dilated (enlarged), indicating a possible structural 
change or blockage.  
No Dropout 
Medium Dropout 
High Dropout 
 
Figure 25. Gland Example Images:  
No Dropout, Medium Dropout, High Dropout  
 
 
Figure 26. Gland Dilation Example, Lower Lid 
 
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Figure 27. Review Gland Images Screen with Labeled Controls 
 
Key 
1 
Full Screen Mode – Press to view screen in full screen mode 
2 
Image Details – Timestamp date of image collection and Operator name 
3 
Select View Mode:  Press to toggle between views; 
• Reflected IR view (Light from above icon) 
• Trans IR view (Light from below icon) – only displayed for lower lid images 
captured using Handheld Near IR Lid Everter 
• Merged view (Lower Eyelid icon) – only displayed for lower lid images captured 
using Handheld Near IR Lid Everter 
• Notes (Notepad icon) 
4 
Export Icon – Export saved images or report to external medium or print report 
 
 
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3.9 
Capture Ocular Images (Ocular Imaging Mode) 
In Ocular Imaging mode, high-resolution images of the surface of the eye or the eyelids can be 
taken.  White-light illumination may be switched on or off. 
1. To image the ocular surface or eyelids, select Ocular Imaging from the Capture/View screen 
(Figure 13) and press New.    
2. Disinfect the forehead and chin rest with alcohol prior to use. 
3. Ensure the chin rest is in the extended position away from the device. 
4. Place the patient’s chin fully forward into chin rest and forehead firmly against forehead rest. 
Adjust the height of the chin rest by spinning the fluted roller until the temporal canthus is 
aligned with the marks on the left and right sides of the forehead rest. Instruct the patient to 
look at the orange fixation light. 
CAUTION:  To prevent pinching, do not put fingers near illuminator, lens or chin rest 
during focusing. Instruct patient not to place hands on LipiView II during operation, and 
not to put fingers near illuminator, lens or chin rest. 
5. Select OD (right eye) or OS (left eye) to image by touching the right or left side of the Ocular 
Image Capture screen (Figure 28).   
6. Select to turn white light illumination on, or turn off to capture images using room 
illumination only. 
7. Position the camera by touching the desired location to be imaged on screen, which will 
automatically move the camera and center on the location. Press the position keys, as needed, 
until the location appears in the center of the screen. 
8. Press the reticle to autofocus, or press the fine focus buttons to adjust the focus until the 
image is clear.  
9. Press Camera icon to capture a still image. Press Capture Video button to begin recording 
approximately 5 seconds of video.  The blinking red light indicates LipiView II is recording 
video. Press Capture Video button again to stop recording prior to 5 seconds, if desired. You 
can capture up to 10 still images and one video per eye. 
10. When recording is complete, the illuminator turns off (if white illumination was turned on 
during imaging). Press Notes to add any notes to images, if desired. 
11. Review still image or video using onscreen playback button. If image quality is suboptimal, 
delete image using Trashcan icon and recapture another image. 
12. Repeat steps 5 to 11 to capture an image of the other eye, if desired.   
13. Press Save to save the video or image(s). 
 
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Figure 28. Ocular Image Capture Screen with Labeled Controls 
 
Key 
1 
Eye Position Indicator – Indicates the eye being imaged (OD in figure) 
2 
Magnify View Icon – OD (right eye) is currently in view. OS (left eye) side is currently 
greyed out. Touch icon to capture images for OS (left eye). 
3 
Capture Video Button – Press to begin recording. Appears as a rectangle during 
recording; press rectangle to stop recording before 10 seconds. 
4 
Camera Button – Press to capture still image 
5 
Full Screen Mode – Press to view screen in full screen mode 
6 
Manual Positioning Buttons – Press to move camera left, right, up or down 
7 
Manual Fine Focus Buttons  - Press plus or minus to focus image 
8 
Autofocus Reticle - Press the reticle to automatically focus the image 
9 
Save Button – Press to save captured imagery 
10 Notes Button – Press to open notes field for text entry 
11 White Light Illumination – Press to toggle illuminator on or off 
 
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3.10 
Review Ocular Images (Ocular Imaging Mode) 
1. To review prior ocular images or video for an existing patient: 
a. Select the patient from the Patient Records screen (Figure 11).   
b. On the Capture/View screen (Figure 13), select Ocular Imaging to view prior ocular 
images or select All Exams to view all prior images.   
c. A list of prior images is shown on the Capture/View screen (Figure 13).  Drag and drop 
the desired images from the list to the sides of the screen marked “Drop Here”.  Touch 
the image again to display the Review Ocular Images screen (Figure 29). 
2. If desired, press the Export icon on the Review Ocular Images screen (Labeled 6 in Figure 29) 
to export or print images or report.  
3. From the Export dialog save, (Figure 15), press the icon to save images, video or report to an 
external medium or network, or print a report.  Exported images can be displayed with or 
without patient demographics. 
 
Figure 29. Review Ocular Images with Labeled Controls 
 
Key 
1 
Video Playback Controls – Press to play, pause, forward step, reverse step (for captured video 
only) 
2 
Full Screen Mode – Press to view screen in full screen mode 
3 
Video Preview 
4 
Image Preview 
5 
Notes Button – Press to open and view notes field for text entry 
6 
Export Icon – Export saved images, video or report to external medium or print report 
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3.11 
Log Out and Power Off 
Press the Log Out tab (Labeled 4 in Figure 10) on the menu bar to log out when the device is 
not is use.  
 
Power off LipiView II overnight to allow the device to cool down.  The device does not need to 
be powered off between patient examinations during the day. 
 
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Appendix: Electromagnetic Compatibility 
Requirements 
 
Table 8: Guidance and Manufacturers Declaration-Electromagnetic 
Emissions 
 
 
LipiView II is intended for use in the electromagnetic environment specified below. The customer 
or the user of LipiView II should assure that it is used in such an environment. 
Emissions Test 
Compliance 
Electromagnetic Environment-Guidance 
RF emissions 
CISPR 11 
Group 1 
LipiView II uses RF energy only for its internal 
function. Therefore, its RF emissions are very low and 
are not likely to cause any interference in nearby 
electronic equipment. 
RF emissions 
CISPR 11 
Class A 
NA 
Harmonic emissions 
IEC 61000-3-2 
Class A 
NA 
Voltage fluctuations 
Flicker emissions 
IEC 61000-3-3 
Complies 
LipiView II is suitable for use in all establishments 
other than domestic and those directly connected to 
the public low-voltage power supply network that 
supplies buildings for domestic purposes. 
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Table 9: Guidance and Manufacturers Declaration-Electromagnetic 
Immunity (part 1) 
LipiView II is intended for use in the electromagnetic environment specified below. The customer or the 
user of LipiView II should assure that it is used in such an environment. 
Immunity Test 
IEC 60601  
Test Level 
Compliance Level 
Electromagnetic Environment-
Guidance 
Electrostatic 
discharge (ESD) 
IEC 61000-4-2 
±6 kV contact 
±8 kV air 
±6 kV contact 
±8 kV air 
Floors should be wood, concrete or 
ceramic tile.  If floors are covered with 
synthetic material, the relative humidity 
should be at least 30% 
Electrical fast 
transient/burst 
IEC 61000-4-4 
±2 kV for power 
supply lines 
±1 kV for 
input/output 
lines 
±2 kV for power 
supply lines 
±1 kV for 
input/output lines 
Mains power quality should be that of a 
typical commercial or hospital 
environment 
Surge 
IEC 61000-4-5 
±1 kV 
differential 
mode 
±2 kV common 
mode 
±1 kV differential 
mode 
±2 kV common 
mode 
Mains power quality should be that of a 
typical commercial or hospital 
environment. 
Voltage dips, short 
interruptions and 
voltage variations 
on power supply 
input lines 
IEC 61000-4-11 
<5 % UT 
(>95 % dip in 
UT for 0,5 cycle 
40 % UT 
(60 % dip in UT) 
for 5 cycles 
 
70% UT 
(30% dip in UT) 
 for 25 cycles 
 
<5% UT 
(>95 % dip in 
UT) 
for 5 sec 
<5 % UT 
(>95 % dip in UT for 
0,5 cycle 
40 % UT 
(60 % dip in UT) 
for 5 cycles 
 
70% UT 
(30% dip in UT) 
 for 25 cycles 
 
<5% UT 
(>95 % dip in UT) 
for 5 sec 
Mains power quality should be that of a 
typical commercial or hospital 
environment.  If the user of the 
equipment requires continued operation 
during power mains interruptions, it is 
recommended that the equipment be 
powered from an uninterruptible power 
supply or a battery. 
 
Power frequency 
(50/60 Hz) 
magnetic field 
IEC 61000-4-8 
3 A/m 
3 A/m 
Power frequency magnetic fields should 
be at levels characteristic of a typical 
location in a typical commercial or 
hospital environment. 
*NOTE:  UT is the a.c. mains voltage prior to application of the test level. 
 
 
 
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Table 10: Guidance and Manufacturers Declaration-Electromagnetic 
Immunity (part 2) 
LipiView II is intended for use in the electromagnetic environment specified below. The customer or 
the user of LipiView II should assure that it is used in such an environment. 
Immunity Test 
IEC 60601 Test 
Level 
Compliance 
Level 
Electromagnetic Environment-Guidance 
 
 
 
 
 
 
 
 
 
Conducted RF 
IEC 61000-4-6 
 
 
 
Conducted RF 
IEC 61000-4-3 
 
 
 
 
 
 
 
 
 
3 Vrms 
150 kHz to 80 
MHz 
 
 
 
3 Vrms 
80 MHz to 2,5 
GHz 
 
 
 
 
 
 
 
 
 
 
10 V  
 
 
 
 
3 V/m  
Portable and mobile RF communications 
equipment should be used no closer to any part 
of the LipiView II, including cables, than the 
recommended separation distance calculated 
from the equation applicable to the frequency of 
the transmitter. 
 
Recommended Separation Distance 
 
d =  [3.5/V1]√ P   
d =  [3.5/E1]√ P  80MHz to 800MHz 
d =  [7.0/E1]√ P  800MHz to 2.5GHz 
 
Where P is the maximum output power rating of 
the transmitter in watts (W) according to the 
transmitter manufacturer and d is the 
recommended separation distance in meters (m). 
Field strengths from fixed RF transmitters, are 
determined by an electromagnetic site survey, a 
should be less than the compliance level in each 
frequency range. b 
Interference may occur in the vicinity of 
equipment marked with the following symbol: 
NOTE 1 At 80 MHz and 800 MHz, the higher frequency range applies. 
 
NOTE 2 These guidelines may not apply in all situations.  Electromagnetic propagation is affected by 
absorption and reflection from structures, objects and people. 
a    Field strengths from fixed transmitters, such as base stations for radio (cellular/cordless) telephones and 
land mobile radios, amateur radio, AM and FM radio broadcast and TV broadcast cannot be predicted 
theoretically with accuracy.  To assess the electromagnetic environment due to fixed RF transmitters, an 
electromagnetic site survey should be considered.  If the measured field strength in the location in which the 
LipiView II is used exceeds the applicable RF compliance level above, the LipiView II should be observed to 
verify normal operation.  If abnormal performance is observed, additional measures may be necessary, such as 
re-orienting or relocating the LipiView II. 
b    Over the frequency range 150 kHz to 80 MHz, field strengths should be less than 3 V/m. 
 
 
 
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Table 11: Recommended Separation Distances Between Portable and 
Mobile RF Communications Equipment and LipiView II  
 
 
LipiView II is intended for use in an electromagnetic environment in which radiated RF 
disturbances are controlled. The customer or the user of  LipiView II can help prevent 
electromagnetic interference by maintaining a minimum distance between portable and mobile 
RF communications equipment (transmitters) and LipiView II as recommended below, 
according to the maximum output power of the communications equipment. 
  
Separation distance according to frequency of transmitter 
m 
  
Rated maximum 
output power of 
transmitter            
W                      
150 kHz to 80 MHz 
 
d=[3.5/V1]√ P 
80 MHz to 800 MHz 
 
d=[3.5/ E1]√ P    
800 MHz to 2,5 
GHz 
d=[7/E1]√ P 
0,01 
0.12 
0.12 
0.23 
0,1 
0.37 
0.37 
0.74 
1 
1.2 
1.2 
2.3 
10 
3.7 
3.7 
7.4 
100 
12 
12 
23 
For transmitters rated at a maximum output power not listed above, the recommended 
separation distance d in meters (m) can be estimated using the equation applicable to the 
frequency of the transmitter, where P is the maximum output power rating of the transmitter in 
watts (W) according to the transmitter manufacturer. 
 
NOTE 1 At 80 MHz and 800 MHz, the separation distance for the higher frequency range 
applies. 
 
NOTE 2 These guidelines may not apply in all situations.  Electromagnetic propagation is 
affected by absorption and reflection from structures, objects and people.  
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APPENDIX E: MEDMONT ASSESSMENT PROCEDURE 
 
 
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Page 1 of 4 
Work Aid: NIBUT Measurement using Medmont E300 Corneal Topographer     
 
WORK AID: NON-INVASIVE TEAR BREAK-UP TIME (NIBUT) 
MEASUREMENT USING THE MEDMONT E300 CORNEAL TOPOGRAPHER 
 
1.0 OBJECTIVES 
Tear break-up time is a standard clinical measurement used to indicate the stability of the pre-
ocular tear film.   An individual with an unstable tear film can experience symptoms of visual 
disturbances or discomfort.  The Medmont videokeratoscope is one type of instrument which may 
be used to view the regularity of the tear film, since it displays a live video image of a set of 
illuminated rings reflected by the eye surface.  Disturbances to the tear film can be visualized as 
disruptions to the reflected ring pattern.  This measurement is a form of non-invasive tear break-
up time (NIBUT), since the instrument does not touch the eye and there is no use of topical dyes. 
 
2.0 MATERIALS 
The Medmont E300 Corneal Topographer is a computerized videokeratometer which uses 
Placido rings to map the surface of the human cornea. 
SOFTWARE VERSION 
The E300 Software is part of the Medmont Studio integrated software environment.  The 
instructions in this Appendix apply to Medmont Studio 4 software version 4.14.1.  Other versions 
of the software are unlikely to have substantial difference in basic function or data integrity. 
 
3.0 DATA MANAGEMENT 
The Medmont videokeratoscope consists of a light source made up of a series of concentric rings, 
and a video camera for recording the reflected image of these rings.  For tear break-up time 
measurement, it is not necessary to save the series of images, but this may be done as an optional 
step for proof of performance or if needed for further analysis.  Tear break-up time is measured 
with a stopwatch and the results are recorded on paper CRF forms or an eCRF data entry screen. 
 
4.0 PROCEDURES 
 
MEDMONT SOFTWARE SETUP 
If videokeratoscope images are not being saved, it is not necessary to enter a new patient name or 
date of birth.  Selecting video data collection mode will ensure that a continuous live video view 
of the participant’s eye is shown on the computer monitor. 
 
 
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Work Aid: NIBUT Measurement using Medmont E300 Corneal Topographer     
 
Figure 1. Selecting Normal (single frames) or Video capture control 
 
 
PARTICIPANT SETUP 
While instrument and participant alignment is being set up, the participant should be instructed to 
continue blinking normally. 
The patient should sit comfortably in the chair. Ask the participant to put their chin onto the 
chinrest and put their forehead firmly against the forehead rest.  Adjust the chinrest height until 
the eye is approximately level with the mark on the vertical bar of the headrest.  The participant 
should push their chin forward slightly on the chinrest.   Ask the participant to look into the 
centre of the green central illuminated ring and keep their gaze on this target during the 
measurement.   The investigator will use the instrument joystick to move the instrument to the 
correct distance from the eye, and to align the instrument axis (shown as a green cross overlay) 
with the reflection of the central reflected ring.   A red line indicates whether the instrument is too 
close or too far away from the participant’s eye.   
Figure 2: Focus examples showing Too Far, In Focus, and Too Near 
.
 
  
If it is not possible to move the instrument in to best focus due to obstruction by the eyebrow, 
instruct the participant to move their chin slightly further forward on the chinrest, or their 
forehead slightly back from the headrest.  If the instrument is obstructed by the side of the nose, 
ask the participant to turn their head so that their nose moves further away from the instrument. 
 
MEASURING TEAR BREAK-UP TIME 
When the examiner is ready to commence the measurement, the participant is instructed to have a 
final blink (the blink should be natural, not forceful) and then to stop blinking for as long as 
possible and continue to look straight ahead at the central green ring.  NIBUT is measured as the 
time interval in seconds after the final blink to the first appearance of distortion in the reflected 
rings; or to the time that the participant has to blink due to discomfort.  The investigator must 
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Page 3 of 4 
Work Aid: NIBUT Measurement using Medmont E300 Corneal Topographer     
 
watch for a change in the appearance of the ring pattern compared to the immediate post-blink 
appearance.  Events that are considered distortions and thus endpoints include: debris that causes 
a break in the grid pattern, localized bending or blurring of a section of the ring pattern, or a 
distinct doubling of any lines. 
The standard measurement of tear film break-up time involves three measurements on each eye.  
Between measurements, ask the participant to sit back from the chinrest for at least 30 seconds 
and to blink naturally.   Taking measurements too rapidly without a sufficient rest period can 
result in a gradually worsening (ie. decreasing) tear film break-up time. 
 
Figure 3: An example of the appearance of tear breakup 
 
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Page 4 of 4 
Work Aid: NIBUT Measurement using Medmont E300 Corneal Topographer     
 
SAVING THE SERIES OF IMAGES (OPTIONAL) 
The raw images may be saved using “File/Save All Images”. 
In order to also save the series of topography maps, click on “File/Analyze All” before “File/Save 
All Images”. 
   
5.0 
PHOTODOCUMENTATION 
 
Not applicable 
 
6.0 
ADDITIONAL INFORMATION 
 
Not applicable 
 
7.0 
TRAINING REQUIREMENTS 
 
Read only 
 
8.0 
CASE REPORT FORM MODULE 
 
The standard Bioclinica eCRF screen will record three measurements of NIBUT (in 
seconds) for each eye.  
 
DOCUMENT CHANGE HISTORY 
 
Originator 
Change Description 
Effective Date 
R. Franklin 
New specification. 
October 21, 2014 
 
 
 
 
 
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APPENDIX F: CLINICAL TECHNICAL PROCEDURES (CTP) 
 
• 
 Expanded Corneal Staining assessment 
• 
 Subject reported Ocular Symptoms/Problems 
• 
 Determination of Distance Spherocylindrical Refractions 
• 
 Biomicroscopy Scale 
• EUROLENS RESEARCH SOP 
 (DISTANCE AND NEAR VISUAL 
ACUITY EVALUATION) 
• 
 Patient Reported Outcomes 
 
 
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 EXPANDED CORNEAL STAINING ASSESSMENT 
 
 
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Page 4 of 4 
 
 
 
 
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 SUBJECT REPORTED OCULAR SYMPTOMS/PROBLEMS 
 
 
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DETERMINATION 
OF 
DISTANCE 
SPHEROCYLINDRICAL 
REFRACTIONS 
 
 
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 BIOMICROSCOPY SCALE 
 
 
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EUROLENS RESEARCH SOP 
 (DISTANCE AND NEAR VISUAL ACUITY 
EVALUATION) 
 
 
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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  
 
 
 
 
 
 
 
 
First issued: v0; July 8, 2009 
Reviewed (with changes): v1; February 7, 2014 
Reviewed (no changes): v1; February 2, 2016 
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JJVC CONFIDENTIAL

Eurolens Research 
Computer logMAR VA chart v1 
February 7, 2014 
4 
Confidential 
 
Microsoft Excel software.  The chart is displayed through an external LCD 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 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 2008 or later 
c. Eurolens chart v5 software 
2. 
The external monitor should be connected to the Mac.  It will require the use of a 
DVI 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 v1 
February 7, 2014 
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 to within 95% confidence on the t-test. 
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. 
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Eurolens Research 
Computer logMAR VA chart v1 
February 7, 2014 
7 
Confidential 
 
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. 
11. Final settings for each monitor on 1/10/13 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. 
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Eurolens Research 
Computer logMAR VA chart v1 
February 7, 2014 
8 
Confidential 
 
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. 
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 v1 
February 7, 2014 
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 is that defined in BS 4274, a 5x5 sans-serif font.2 
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 v1 
February 7, 2014 
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 used was Subject AM, (Eurolens ID 2023) of average UK male height (175cm, 
ONS data) 
 
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Eurolens Research 
Computer logMAR VA chart v1 
February 7, 2014 
11 
Confidential 
 
Appendix B.  Chart settings on 1/10/2013 
 
 
1.015 
1.014 
1.013 
1.012 
Monitor number  
1 
3 
5 
4 
Clinic computer 
iMac 9.1 
iMac 4.2 
iMac 4.2 
iMac 5.2 
Chart distance (m) 
6 
6.05 
6.1 
6 
LC grey 
240 
241 
240 
240 
 
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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 PATIENT REPORTED OUTCOMES 
 
 
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PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE 
Protocol Number and Title: CR-6013 (J17-626) Clinical Evaluation of two marketed 
artificial tears in non-contact lens wearing patients 
 
Version and Date: 3.0 03 January 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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