MiBo ThermoFlo Lid Temperature Evaluation
Phase: NA
Conditions: Dry Eye
Sponsor: Johnson & Johnson Vision Care, Inc.

Johnson & Johnson Vision Care, Inc.
Clinical Study Protocol
MiBo ThermoFlo Lid Temperature Evaluation
Protocol CR-6281
Version: 2.0, Amendment 1.0
Date: 15 November 2018
Investigational Products: MiBo ThermoFlo; Bruder mask
Key Words: Meibomian glands, eyelid temperature, Bruder mask, hot compress, lipid layer, 
tear break up time
Statement of Compliance to protocol, GCP and applicable regulatory guidelines:
This trial will be conducted in compliance with the protocol, ISO 14155,1 the International 
Conference on Harmonization Good Clinical Practice E6 (ICH-GCP),2 the Declaration of 
Helsinki,3 and all applicable regulatory requirements.
Confidentiality Statement:
This document contains confidential information, which should not be copied, referred to, 
released or published without written approval from Johnson & Johnson Vision Care, Inc.  The 
information may not be disclosed to others except to the extent necessary to obtain Institutional 
Review Board/Independent Ethics Committee approval and informed consent, or as required 
by International, Federal and State Laws, as applicable. Persons to whom this information is 
disclosed must be informed that this information is privileged and confidential and that it 
should not be further disclosed without the written permission of Johnson & Johnson Vision 
Care, Inc.  Any supplemental information that may be added to this document is also 
confidential and proprietary to Johnson & Johnson Vision Care, Inc. and must be kept in 
confidence in the same manner as the contents of this document.
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TABLE OF CONTENTS
SPONSOR NAME AND ADDRESS....................................................................................... 6 
MEDICAL MONITOR............................................................................................................. 6 
AUTHORIZED SIGNATURES............................................................................................... 7 
CHANGE HISTORY................................................................................................................ 8 
SYNOPSIS................................................................................................................................ 9 
1.1. 
Inclusion Criteria...................................................................................................... 10 
COMMONLY USED ABBREVIATIONS AND DEFINITIONS OF TERMS .................... 13 
1. INTRODUCTION AND BACKGROUND ....................................................................... 14 
1.2. 
Name and Descriptions of Investigational Products ................................................ 15 
1.3. 
Intended Use of Investigational Products................................................................. 15 
1.4. 
Summary of Findings from Nonclinical Studies...................................................... 15 
1.5. 
Summary of Known Risks and Benefits to Human Subjects................................... 15 
1.6. 
Relevant Literature References and Prior Clinical Data Relevant to Proposed Clinical 
Study ……………………………………………………………………………………...15 
2. 
STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES ...................................... 16 
2.1. 
Objectives................................................................................................................. 16 
2.2. 
Endpoints.................................................................................................................. 16 
2.3. 
Hypotheses ............................................................................................................... 16 
3. 
TARGETED STUDY POPULATION........................................................................... 17 
3.1. 
General Characteristics ............................................................................................ 17 
3.2. 
Inclusion Criteria...................................................................................................... 17 
3.3. 
Exclusion Criteria..................................................................................................... 17 
3.4. 
Enrollment Strategy.................................................................................................. 18 
4. 
STUDY DESIGN AND RATIONALE.......................................................................... 18 
4.1. 
Description of Study Design .................................................................................... 18 
4.2. 
Study Design Rationale............................................................................................ 18 
4.3. 
Enrollment Target and Study Duration .................................................................... 18 
5. 
TEST ARTICLE ALLOCATION AND MASKING..................................................... 19 
5.1. 
Test Article Allocation............................................................................................. 19 
5.2. 
Masking.................................................................................................................... 19 
5.3. 
Procedures for Maintaining and Breaking the Masking........................................... 19 
6. 
STUDY INTERVENTION............................................................................................. 19 
6.1. 
Identity of Test Articles............................................................................................ 19 
6.2. 
Ancillary Supplies/Products..................................................................................... 20 
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6.3. 
Administration of Test Articles................................................................................ 20 
6.4. 
Packaging and Labeling ........................................................................................... 20 
6.5. 
Storage Conditions................................................................................................... 20 
6.6. 
Accountability of Test Articles ................................................................................ 20 
7. 
STUDY EVALUATIONS.............................................................................................. 20 
7.1. 
Time and Event Schedule......................................................................................... 20 
7.2. 
Detailed Study Procedures ....................................................................................... 21 
VISIT 1 ........................................................................................................................... 21 
FINAL EVALUATION.................................................................................................. 24 
7.3. 
Unscheduled Visits................................................................................................... 25 
7.4. 
Laboratory Procedures ............................................................................................. 26 
8. 
SUBJECTS COMPLETION/WITHDRAWAL.............................................................. 26 
8.1. 
Completion Criteria.................................................................................................. 26 
8.2. 
Withdrawal/Discontinuation from the Study ........................................................... 26 
9. 
PRE-STUDY AND CONCOMITANT INTERVENTION/MEDICATION ................. 26 
10. 
DEVIATIONS FROM THE PROTOCOL.................................................................. 26 
11. 
STUDY TERMINATION ........................................................................................... 27 
12. 
PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS.............. 27 
13. 
ADVERSE EVENTS................................................................................................... 27 
13.1. 
Definitions and Classifications............................................................................. 27 
13.2. 
Assessing Adverse Events.................................................................................... 29 
13.2.1. 
Causality Assessment.................................................................................... 30 
13.2.2. 
Severity Assessment...................................................................................... 30 
13.3. 
Documentation and Follow-Up of Adverse Events.............................................. 30 
13.4. 
Reporting Adverse Events.................................................................................... 32 
13.4.1. 
Reporting Adverse Events to Sponsor .......................................................... 32 
13.4.2. 
Reporting Adverse Events to the Responsible IEC/IRB and Health Authorities
………………………………………………………………………………33 
13.4.3. 
Event of Special Interest ............................................................................... 33 
13.5. 
Reporting of Pregnancy........................................................................................ 33 
14. 
STATISTICAL METHODS........................................................................................ 33 
14.1. 
General Considerations......................................................................................... 33 
14.2. 
Sample Size Justification...................................................................................... 34 
14.3. 
Analysis Populations ............................................................................................ 34 
14.4. 
Level of Statistical Significance........................................................................... 34 
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14.5. 
Primary Analysis .................................................................................................. 34 
14.6. 
Secondary Analysis .............................................................................................. 35 
14.7. 
Other Exploratory Analyses ................................................................................. 35 
14.8. 
Interim Analysis ................................................................................................... 35 
14.9. 
Procedure for Handling Missing Data and Drop-Outs ......................................... 35 
14.10. 
Procedure for Reporting Deviations from Statistical Plan ................................... 35 
15. 
DATA HANDLING AND RECORD KEEPING/ARCHIVING................................ 35 
15.1. 
Electronic Case Report Form/Data Collection ..................................................... 35 
15.2. 
Subject Record...................................................................................................... 36 
16. 
DATA MANAGEMENT............................................................................................. 36 
16.1. 
Access to Source Data/Document ........................................................................ 36 
16.2. 
Confidentiality of Information.............................................................................. 36 
16.3. 
Data Quality Assurance........................................................................................ 37 
17. 
MONITORING............................................................................................................ 37 
18. 
ETHICAL AND REGULATORY ASPECTS ............................................................ 37 
18.1. 
Study-Specific Design Considerations ................................................................. 37 
18.2. 
Investigator Responsibility................................................................................... 38 
18.3. 
Independent Ethics Committee or Institutional Review Board (IEC/IRB) .......... 38 
18.4. 
Informed Consent ................................................................................................. 39 
18.5. 
Privacy of Personal Data ...................................................................................... 39 
19. 
STUDY RECORD RETENTION................................................................................ 41 
20. 
FINANCIAL CONSIDERATIONS ............................................................................ 41 
21. 
PUBLICATION........................................................................................................... 42 
22. 
REFERENCES ............................................................................................................ 42 
APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES)..... 43 
APPENDIX B: PATIENT INSTRUCTION GUIDE ............................................................. 44 
APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT)......................................... 45 
APPENDIX D: 
...................................... 46 
, BIOMICROSCOPY SCALE ............................................................................... 47 
, DISTANCE AND NEAR VISUAL ACUITY EVALUATION.......................... 53 
, DETERMINATION OF DISTANCE SPHEROCYLINDRICAL REFRACTIONS
................................................................................................................................................. 58 
OCULUS KERATOGRAPH...................................................................... 65 
THERMOGRAPHY ................................................................................... 72 
BRUDER MASK.................................................................................... 77 
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_EYELID PHOTOGRAPHY ................................................................... 80 
_LIPIVIEW II LIPID LAYER THICKNESS .......................................... 82 
 MIBOFLO ............................................................................................... 84 
PULT MEIBOSCALE............................................................................................................ 86 
 THERMAL CAMERA 510(K) SUMMARY.......................................................... 87 
 THERMAL CAMERA SCIENTIFIC SPECIFICATIONS .................................... 95 
PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE .......................... 97 
TABLE OF CONTENTS
Figure 1: Study Flowchart ...................................................................................................... 12 
TABLE OF CONTENTS
Table 1: Test Articles.............................................................................................................. 19 
Table 2: Ancillary Supplies .................................................................................................... 20 
Table 3: Time and Events ....................................................................................................... 21 
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PROTOCOL TITLE, NUMBER, VERSION
Title: MiBo ThermoFlo Lid Temperature Evaluation
Protocol Number: CR-6281
Version: 2.0, Amendment 1.0
Date: 15 November 2018
SPONSOR NAME AND ADDRESS
Johnson & Johnson Vision Care (JJVC)
7500 Centurion Parkway 
Jacksonville, FL 32256
MEDICAL MONITOR
Name: Chantal Coles-Brennan, OD
Title: Principal Research Optometrist
Address: Johnson & Johnson Vision Care (JJVC)
7500 Centurion Parkway 
Jacksonville, FL 32256
The Medical Monitor must be notified by the clinical institution/site by e-mail, fax, or 
telephone within 24 hours of learning of a Serious Adverse Event. The Medical Monitor may 
be contacted during business hours for adverse event questions. General study related questions 
should be directed towards your assigned clinical research associate.
The Medical Monitoring Plan is maintained as a separate document and included in the Trial 
Master File.
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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,8 ICH guidelines,2 ISO 14155,1
and the Declaration of Helsinki.3
Author
Eric Ritchey, OD, PhD
Assistant Professor, University of 
Houston
DATE
Study Responsible 
Clinician
See Electronic Signature Report 
Chantal Coles-Brennan, OD
Principal Research Optometrist
DATE
Clinical Operations
Manager
See Electronic Signature Report
Clinical Operations Department
DATE
Biostatistician
See Electronic Signature Report
Biostatistician II, Clinical Sciences 
DATE
See Electronic Signature Report
Biostatistics
Reviewer
.
Senior Manager of Biostatistics, Clinical 
Sciences 
DATE
Data Management 
See Electronic Signature Report
Clinical Project Manager – Data & 
Systems, Clinical Operations
DATE
Approver:
See Electronic Signature Report
Director of Global Medical Affairs
DATE
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SYNOPSIS 
Protocol Title
MiBo ThermoFlo Lid Temperature Evaluation
Sponsor
JJVC, 7500 Centurion Parkway, Jacksonville, FL  32256
Clinical Phase
Phase 4 
Trial Registration
This study will be registered on ClinicalTrials.gov by the Sponsor
Test Article(s)
Investigational Product:  MiBo ThermoFlo
Control Product: Bruder Moist Heat Single Eye Compress
Wear and Replacement 
Schedules
N/A
Objectives 
Determine anterior and posterior eyelid temperature after use of the 
MiBo ThermoFlo following standard clinical protocol and evaluate 
changes to the tear film with one MiBo ThermoFlo treatment session.
Primary Objective: Determine the temperature of the palpebral 
conjunctiva after MiBo ThermoFlo treatment and Bruder Mask (i.e. hot 
compress) treatment using the ICI-7320 infrared camera (Infrared 
Cameras Inc., Beaumont, TX)
Secondary Objectives: Tear Film Lipid Layer Thickness and Non-
Invasive Tear Break Up Time post treatment 
Study Endpoints
Primary endpoint(s): Palpebral Conjunctival Temperature
Secondary endpoint(s): Tear Film Lipid Layer Thickness, Non-invasive 
tear break up time (NITBUT)
Study Design
This study is a prospective, contralateral, single-site, single-visit 
unmasked evaluation of external and internal eyelid temperature after 
treatment with the MiBo ThermoFlo. Approximately 20 subjects will 
be evaluated for enrollment in the study, with a goal of a minimum of
12 subjects completed. Subjects will be randomly assigned to receive
12 minutes of MiBo ThermoFlo treatment (treatment) on 1 eye and 10
minutes of Bruder mask treatment (control) on the fellow eye. 
See the flow chart at the end of the synopsis table for the schematic of 
the study visits and procedures of main observations (Figure 1).
Sample Size
Up to 20 subjects will be enrolled with a goal of a minimum of target 
of 12 subjects to complete
Study Duration
The study will last approximately 1.5 months and include a
1-month enrollment period
Anticipated Study 
Population
Individuals between the ages of 18-80 years old (inclusive) with less 
than grade 3 partial Meibomian glands on the Pult 5-point grading 
scale.
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Eligibility Criteria
Potential subjects must satisfy all the following criteria to be enrolled 
in the study:
1.1.
Inclusion Criteria
Potential subjects must satisfy all the following criteria to be enrolled in 
the study:
1. The subject must read, understand, and sign the STATEMENT 
OF INFORMED CONSENT and receive a fully executed copy 
of the form 
2. Appear able and willing to adhere to the instructions set forth in 
this clinical protocol
3. Between 18 and 80 (inclusive) years of age at the time of 
screening
4. Subjects must possess a functional/usable pair of spectacles and 
bring them to the visit (only if applicable - to the investigators 
discretion)
Potential subjects who meet any of the following criteria will be 
excluded from participating in the study: 
1. Currently pregnant or lactating
2. Any systemic disease (e.g., Sjögren’s Syndrome), allergies, 
infectious disease (e.g., hepatitis, tuberculosis), contagious 
immunosuppressive diseases (e.g., HIV), autoimmune disease 
(e.g. rheumatoid arthritis), or other diseases, by self-report, 
which are known to interfere with participation in the study
3. Clinically significant (Grade 3 or 4 on the FDA classification 
scale) slit lamp findings (e.g. corneal edema, neovascularization 
or staining, tarsal abnormalities or bulbar injection) 
4. Grade 3-4 Percentage of Partial Meibomian Glands on the Pult 
5-point grading scale 
5. Significant conjunctivitis (Grade 3 or greater)
6. Active Ocular Infection or Inflammation (Grade 3 or greater)
7. Any history of eyelid surgery or abnormality
8. History of Metal Implants in the Eyelids
9. Any known hypersensitivity or allergic reaction to ultrasound 
coupling gel
10. LASIK Surgery within 2 weeks of the Baseline Visit 
11. Participation in any contact lens or lens care product clinical trial
within 14 days prior to study enrollment
12. History of MiBo ThermoFlo or Lipiflow treatment Within the 
Last 6 months
13. Employee or immediate family member of an employee of 
clinical site (e.g., Investigator, Coordinator, Technician)
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Disallowed 
Medications/Interventions 
History of MiBo ThermoFlo or Lipiflow treatment within the last 6 
months
Measurements and 
Procedures
ICI-7320 infrared camera (Infrared Cameras Inc., Beaumont, TX)
Tear Film Lipid Layer (Lipiview)
Non-invasive Tear Break Up Time
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
Aquasonic 100 Ultrasound Transmission Gel, Bruder Moist Heat 
Single Eye Compress
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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Figure 1: Study Flowchart
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COMMONLY USED ABBREVIATIONS AND DEFINITIONS OF TERMS
ADD
Plus Power Required For Near Use
ADE
Adverse Device Effect
AE
Adverse Event/Adverse Experience
BCVA
Best Corrected Visual Acuity
BSCVA
Best Spectacle Corrected Visual Acuity
CFR
Code of Federal Regulations
CLUE
Contact Lens User Experience
COAS
Complete Ophthalmic Analysis System
COM
Clinical Operations Manager
CRA
Clinical Research Associate
CRF
Case Report Form
CRO
Contract Research Organization
CT
Center Thickness
D
Diopter
DMC
Data Monitoring Committee
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
ETDRS
Early Treatment Diabetic Retinopathy Study
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HIPAA
Health Insurance Portability and Accountability Act
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonization
IDE
Investigational Device Exemption
IEC
Independent Ethics Committee
IRB
Institutional Review Board
ISO
International Organization for Standardization
ITT
Intent-to-Treat
JJVC
Johnson & Johnson Vision Care, Inc.
LC
Limbus Center
LogMAR
Logarithm of Minimal Angle of Resolution
MedDRA©
Medical Dictionary for Regulatory Activities
MGD
Meibomian Gland Dysfunction
MOP
Manual of Procedures
NIH
National Institutes of Health
OD
Right Eye
OHRP
Office for Human Research Protections
OHSR
Office for Human Subjects Research
OS
Left Eye
OU
Both Eyes
PD
Protocol Deviation
PHI
Protected Health Information
PI
Principal Investigator
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PIG
Patient Instruction Guide
PQC
Product Quality Complaint
PRO
Patient Reported Outcome
QA
Quality Assurance
QC
Quality Control
SAE
Serious Adverse Event/Serious Adverse Experience
SAP
Statistical Analysis Plan
SAS
Statistical Analysis System
SD
Standard Deviation
SOP
Standard Operating Procedure
UADE
Unanticipated Adverse Device Effect
USADE
Unanticipated Serious Adverse Device Effect
VA
Visual Acuity
1. INTRODUCTION AND BACKGROUND
Several approaches have been used to treat Meibomian Gland Disease (MGD), including 
physical expression of the Meibomian glands alone or in conjunction with the use of various 
devices to heat the eyelids. The methods used to heat the eyelid tissue, colloquially referred to 
as hot compresses, include using hot water soaked cloths, exothermic chemical reactions 
(EyeGeine Wafers), heated flax seeds (MGDRx), heated rice, and proprietary bead technology 
(e.g. Bruder MediBeads).4-7 Reports in the scientific literature indicate that for effective 
liquefaction of meibum in eyes with Meibomian Gland Dysfunction (MGD), a minimum 
temperature of approximately 40°C must be reached at the inner eyelid. Traditional treatments 
for MGD fail to reach this internal eyelid temperature, while therapy that applies sufficient 
heat to the inner eyelid surface can reach this temperature threshold.6
One device that attempts to liquefy inspissated meibum in patients with MGD is the MiBo 
ThermoFlo. The MiBo Thermoflo uses a thermoelectric probe coupled to the eyelid using 
ultrasound transmission gel after a system initiation/warm up period that heats a silver eye pad 
to a temperature of approximately 42°C. Upon starting treatment, the MiBo ThermoFlo eye 
pad is moved along the eyelid surface using a gentle circular motion, combining eyelid 
massage with controlled heat to the eyelid. Per the manufacturer, typical treatment duration 
ranges from 5 minutes to 12 minutes per session, with 3 treatment sessions over 2 weeks 
recommended 
to 
obtain 
maximum 
therapeutic 
effect 
(http://www.mibomedicalgroup.com/miboThermoFlo.html). Using the MiBo ThermoFlo Elite 
Eye Pad, upper and lower eyelids can be treated simultaneously.
Previous pilot data (TearScience; JJVC Confidential) suggests that treatment with the MiBo 
ThermoFlo does not adequately raise Meibomian gland temperature at the inner eyelids to 
therapeutic levels. This study will evaluate inner and outer eyelid temperature obtained with 
use of the MiBo ThermoFlo, as well as look at changes in the tear film after 1 treatment session.
Temperature will be measured via thermography (see SOP_C31_Thermography_v1.0).
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1.2.
Name and Descriptions of Investigational Products 
This study will evaluate the MiBo ThermoFlo, a therapeutic medical device for dry eye 
therapy. It uses a proprietary thermoelectric heat pump to help liquefaction of meibum in the 
Meibomian glands. The contralateral control article is the Bruder Moist Heat Eye Compresses. 
The Bruder mask uses MediBead technology, which absorbs water from the air and stores it 
inside the beads. When microwaved, the absorbed water is released as moist heat. 
1.3.
Intended Use of Investigational Products
The intended use of the MiBo ThermoFlo is the treatment of chronic dry eye by heating 
inspissated Meibomian glands, combined with gentle lid massage. Subjects will receive 12 
minutes of treatment. The Bruder Moist Heat Eye Compresses is intended for the treatment of 
chronic dry eye and MGD and will be applied for 10 minutes.
1.4.
Summary of Findings from Nonclinical Studies
Not Applicable – Marketed product only.
1.5.
Summary of Known Risks and Benefits to Human Subjects
The risks of treatment with the MiBo Lipiflow are minimal. These risks include discomfort or 
sensation of pressure on the eyelids related to the procedure or irritation secondary to use of 
ultrasound coupling gel. These risks are self-limiting and typically resolve without treatment. 
The risk of thermal burn with normal use of the MiBo Lipiflow or the Bruder mask is minimal. 
The temperature of the MiBo ThermoFlo treatment paddle is 108 degrees Fahrenheit (42
degrees Celsius), under the temperature required to cause a thermal burn with prolonged 
exposure to heat. The Bruder mask utilizes proprietary beads heated using a microwave oven 
to provide heat to the eyelid surface. The instructions for use limit the heating time to 20 
seconds, with 2 additional 5 second heating sessions (maximum 30 seconds total) to achieve 
the required treatment temperature. Subjects will be educated to inform the study personnel if 
the device becomes too warm or if the treatment becomes painful.
The benefit to either treatment is that the surface heating treatments of the eyelid and 
Meibomian glands may lead to increase of available lipid to the tear film. This could transiently 
increase the thickness of the tear lipid layer or transiently increase tear break up time. 
1.6.
Relevant Literature References and Prior Clinical Data Relevant to Proposed 
Clinical Study
Selected references regarding the inner eyelid temperature required to effectively liquefy 
meibum can be found in the following peer reviewed literature:
Olson MC, Korb DR, Greiner JV. Increase in Tear Film Lipid Layer Thickness Following 
Treatment with Warm Compresses in Patients with Meibomian Gland Dysfunction. Eye 
Contact Lens 2003; 29:96-9.
Kenrick CJ, Alloo SS. The Limitation of Applying Heat to the External Lid Surface: A Case 
of Recalcitrant Meibomian Gland Dysfunction. Case Rep Ophthalmol 2017;8:7-12.
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Murakami DK, Blackie CA, Korb DR. All Warm Compresses Are Not Equally Efficacious. 
Optom Vis Sci 2015;92: e327-33.
Wang MT, Jaitley Z, Lord SM, Craig JP. Comparison of Self-Applied Heat Therapy for 
Meibomian Gland Dysfunction. Optom Vis Sci 2015;92: e321-6.
2.
STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES
2.1.
Objectives 
The primary study objective of this pilot study is to measure posterior eyelid temperature 
(palpebral conjunctiva) to determine the ability of the MiBo ThermoFlo to raise posterior 
eyelid temperature to levels sufficient to provide a therapeutic effect in the treatment of MGD. 
Other observations in this study include testing whether the MiBo ThermoFlo treatment can 
induce a change in tear lipid layer thickness and/or non-invasive tear break up time after (1) 
12-minute treatment session.
2.2.
Endpoints 
The primary study endpoint is posterior eyelid temperature (palpebral conjunctiva) using the
ICI-7320 infrared camera (Infrared Cameras Inc., Beaumont, TX). This metric has been 
selected as the ICI-7320 is FDA-approved [510(k) clearance] for use in medical imaging of 
any part of the body’s surface. Collection of surface temperature with infrared video will allow 
for capture of the inner eyelid temperature while eyelids are inverted to access the palpebral 
conjunctiva. Other observations endpoints are Topography, Tear Lipid Layer thickness and 
Non-invasive Tear Break Up Time after treatment. 
2.3.
Hypotheses
1. After 12 minutes of treatment, the MiBo ThermoFlo will not heat the posterior eyelid
palpebral conjunctiva to a temperature of 40°C.
Background: Ocular surface temperature is usually 34.03 ±0.51 ºC in the ‘normal’ eye. 
The temperature required to melt obstructive secretions in the Meibomian glands ranges 
from 32-45°C but the more severely obstructed glands present in MGD would require a 
temperature of >40°C, for effective treatment. there is an approximate 5°C difference in 
temperature between heat applied on the external eyelid surfaces and that which reaches 
the inner surface of the lids (palpebral conjunctiva), where the meibomian glands are
located. This difference is due to both dissipation of heat while passing through the lid
tissues and to constant movement of blood through vasculature wicking heat away
from the lids. Therefore, achieving the desired temperature of 40°C at the palpebral
conjunctiva requires a constant heat of at least 45°C be maintained on the outer lid
surface, a temperature which may be both uncomfortable and risk causing thermal
injury to the eyelid skin.
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Other Observations 
1. After 10 minutes of treatment, the Bruder Mask will not heat the posterior eyelid 
palpebral conjunctiva to a temperature of greater than 40°C.
2. There is no difference in posterior eyelid palpebral conjunctiva between the Bruder 
Mask and the MiBo ThermoFlo
3.
TARGETED STUDY POPULATION
3.1.
General Characteristics 
The study population are individuals between the ages of 18 to 80 years old (inclusive) with 
sufficient Meibomian gland anatomy to qualify for MiBo ThermoFlo treatment. This is defined 
as having Grade 0-2 Percentage of Partial Meibomian Glands on the Pult 5-point grading scale. 
Subjects with Grade 3-4 Percentage of Partial Meibomian Glands will be excluded. 
3.2.
Inclusion Criteria
Potential subjects must satisfy all the following criteria to be enrolled in the study:
1. The subject must read, understand, and sign the STATEMENT OF INFORMED 
CONSENT and receive a fully executed copy of the form 
2. Appear able and willing to adhere to the instructions set forth in this clinical protocol
3. Between 18 and 80 (inclusive) years of age at the time of screening
4. Subjects must possess a functional/usable pair of spectacles and bring them to the visit 
(only if applicable - to the investigators discretion)
3.3.
Exclusion Criteria
Potential subjects who meet any of the following criteria will be excluded from participating 
in the study: 
Exclusion Criteria after Screening and Baseline:
1. Currently pregnant or breastfeeding
2. Any systemic disease (e.g., Sjögren’s Syndrome), allergies, infectious disease (e.g., 
hepatitis, tuberculosis), contagious immunosuppressive diseases (e.g., HIV), 
autoimmune disease (e.g. rheumatoid arthritis), or other diseases, by self-report, which 
are known to interfere with participation in the study
3. Clinically significant (Grade 3 or 4 on the FDA classification scale) slit lamp
findings (e.g. corneal edema, neovascularization or staining, tarsal abnormalities or
bulbar injection)
4. Grade 3-4 Percentage of Partial Meibomian Glands on the Pult 5-point grading scale 
5. Giant Papillary Conjunctivitis (Grade 3 or greater)
6. Active Ocular Infection or Inflammation (Grade 3 or greater)
7. Any history of eyelid surgery or abnormality
8. History of Metal Implants in the Eyelids
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9. Any known hypersensitivity or allergic reaction to ultrasound coupling gel
10. LASIK Surgery within 2 weeks of the Baseline Visit 
11. Participation in any contact lens or lens care product clinical trial within 14 days prior 
to study enrollment
12. History of MiBo ThermoFlo or Lipiflow treatment Within the Last 6 months
13. Employee or immediate family member of an employee of clinical site (e.g., 
Investigator, Coordinator, Technician)
3.4.
Enrollment Strategy
Study subjects will be recruited from the Institution/clinical site’s subject database and/or 
utilizing Independent Ethics Committee (IEC) or Institutional Review Board (IRB) approved 
materials. 
4.
STUDY DESIGN AND RATIONALE
4.1.
Description of Study Design
This study is a prospective, contralateral, single-site, single-visit unmasked evaluation of 
external and internal eyelid temperature after treatment with the MiBo ThermoFlo.
Approximately 20 subjects will be evaluated for enrollment in the study, with a goal of a 
minimum of 12 subjects completed. If a subject meets all eligibility criteria then the subject
will be randomly assigned to 1 of 2 treatment sequences in a contralateral fashion, (1) MiBo 
ThermoFlo (left eye) / Bruder mask (right eye) or (2) Bruder mask (left eye) / MiBo 
ThermoFLo (right eye). Subjects will undergo each treatment for a period of 12 minutes for 
the MiBo ThermoFlo and 10 Minutes for the Bruder mask, per the manufacturer 
recommendations.
The study visit is expected to last approximately 2.5 hours. Subjects will undergo 
Meibography, tear lipid layer measurements, non-invasive tear break-up time, eyelid 
photography and the study treatments (MiBo ThermoFlo and Bruder mask).  
4.2.
Study Design Rationale
Previous work suggests that treatment with the MiBo ThermoFlo does not adequately raise 
Meibomian gland temperature at the inner eyelids to therapeutic levels therefore, this study 
explores the ability of the MiBo ThermoFlo to increase posterior eyelid temperature over 1 
treatment session. A contralateral design was considered the most efficient design to assess the 
primary endpoint of the study. Given the nature of the treatment, masking of the investigator 
and the subjects is not feasible.
4.3.
Enrollment Target and Study Duration
The target enrollment is 20 subjects, with a minimum of 12 subjects completing the 1-visit 
study, which will last for approximately 2.5 hours.
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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 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.
JJVC reserves the right to terminate the study at any time for any reason.  Additionally, the 
IEC/IRB reserves the right to terminate the study if an unreasonable risk is determined.  The 
study can be terminated by the Principal Investigator at the individual clinical site due to 
specific clinical observations, if in their opinion, after a discussion with JJVC, it is determined 
that it would be unwise to continue at the clinical site.   
JJVC (and the IEC/IRB and DMC, if applicable) will evaluate all adverse events.  If it is 
determined that an adverse event presents an unreasonable risk, the investigation, or that part 
of the investigation presenting the risk, will be terminated, as soon as possible.
Should the study be terminated (either prematurely or as scheduled), the Investigator will 
notify the IEC/IRB and Regulatory Authority as required by local regulatory requirements.
12. PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS
N/A
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
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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
Serious Adverse Event (SAE) – An SAE is any untoward medical occurrence that:
x
Results in death
x
Is life threatening
x
Requires in-patient hospitalization or prolongation of existing hospitalization
x
Results in persistent or significant disability/incapacity (e.g., a sight threatening event, 
a significant persistent or permanent change, impairment, damage, or disruption to the 
subject’s body)
x
Is a congenital anomaly/birth defect, or?
x
Requires intervention to prevent permanent damage (the use of the test article resulting 
in a condition which requires medical or surgical intervention to preclude permanent 
impairment of the body structure or a body function).  Important medical events that 
may not result in death, be life-threatening, or require hospitalization may be 
considered an SAE when, based upon appropriate medical judgment, they may 
jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in the above definition
Diagnoses and conditions that are considered Ocular Serious Adverse Events include, but not 
limited to:
x
Microbial Keratitis (MK)
x
Iritis (including cells in the anterior chamber)
x
Permanent decrease in best spectacle corrected visual acuity equivalent to 2 acuity lines 
or greater
x
Central Corneal Opacity
x
Central Corneal Neovascularization
x
Uveitis
x
Endophthalmitis
x
Hypopyon
x
Hyphemia
x
Penetration of Bowman’s Membrane
x
Persistent Epithelial Defect
x
Limbal cell Damage leading to Conjunctivization
Significant Adverse Events – Those events that are usually symptomatic and warrant 
discontinuation (temporary or permanent) of the test article (excluding Serious Adverse 
Events).  
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Diagnoses and conditions that are considered Ocular Significant Adverse Events include, but 
not limited to the following:
x
Significant Infiltrative Events (SIE)
x
Superior Epithelial Arcuate Lesions (SEALs)
x
Any Temporary Loss of > 2 Lines of BSCVA
x
Other grade 3 or higher corneal findings, such as abrasions or edema
x
Non-contact lens related corneal events - e.g. Epidemic Keratoconjunctivitis (EKC)
x
Asymptomatic Corneal Scar
x
Any corneal event which necessitates temporary lens discontinuation > 2 weeks
Non-Significant Adverse Events – Those conditions that are usually asymptomatic and 
usually do not warrant discontinuation (temporary or permanent) of the test article.  However, 
the Investigator may choose to treat as a precautionary measure.  
Diagnoses and conditions that are considered Ocular Non-Significant Adverse Events include, 
but not limited to the following:
x
Non-significant Infiltrative Event (NSIE)
x
Superficial Punctate Keratitis (SPK)
x
Conjunctivitis: Bacterial, Viral, Allergic
x
Blepharitis
x
Meibomianitis
x
Contact Dermatitis
x
Localized Allergic Reactions
x
Any corneal event not explicitly defined as serious or significant adverse event, which 
necessitates temporary lens discontinuation < 2 weeks
Adverse Device Effect (ADE) – An ADE is an “adverse event related to the use of an 
investigational medical device.
Note 1 to entry: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device.
Note 2 to entry: This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device.”1
Unanticipated Adverse Device Effect (UADE) – Any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, the test article, 
if that effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the investigational plan, Investigator’s Brochure or protocol, or any other 
unanticipated serious problem associated with the test article that relates to the rights, safety 
and welfare of subjects.
13.2. Assessing Adverse Events
In conjunction with the medical monitor, the Investigator will evaluate adverse events to ensure 
the events are categorized correctly.  Elements of categorization will include:
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x
Seriousness/Classifications (see definition in Section 13.1)
x
Causality or Relatedness – i.e. the relationship between the test article, study treatment 
or study procedures and the adverse event (not related; unlikely related; possibly
related; related - see definition in Section 13.2.1)
x
Adverse Event Severity – Adverse event severity is used to assess the degree of 
intensity of the adverse event (mild; moderate; severe for all events - see definition in 
Section 0)
x
Outcome – not recovered or not resolved; recovering or resolving; recovered or 
resolved with sequelae; recovered or resolved; death related to adverse event; unknown
x
Actions Taken – none; temporarily discontinued; permanently discontinued; other
13.2.1. Causality Assessment
Causality Assessment – A determination of the relationship between an adverse event and the 
test article. The test article relationship for each adverse event should be determined by the 
investigator using these explanations:
x
Not Related- An adverse event that is not related to the use of the test article, study 
treatment or study procedures
x
Unlikely Related – An adverse event for which an alternative explanation is more 
likely, e.g. concomitant treatment, concomitant disease(s), or the relationship of time 
suggests that a causal relationship is not likely
x
Possibly Related – An adverse event that might be due to the use of the test article, or 
to the study treatment or study procedures. An alternative explanation, e.g. concomitant 
treatment, concomitant disease(s), is inconclusive.  The relationship in time is 
reasonable.  Therefore, the causal relationship cannot be excluded
x
Related – An adverse event that is listed as a possible adverse effect (device) or adverse 
reaction (drug) and cannot be reasonably explained by an alternative explanation, e.g. 
concomitant treatment of concomitant disease(s).  The relationship in time is very 
suggestive, e.g. it is confirmed by de-challenge and re-challenge
13.2.2. Severity Assessment
Severity Assessment – A qualitative assessment of the degree of intensity of an adverse event 
as determined by the Investigator or reported to him/her by the subject.  The assessment of 
severity is made irrespective of test article, study treatment or study procedure relationship or 
seriousness of the event and should be evaluated according to the following scale:
x
Mild – Event is noticeable to the subject, but is easily tolerated and does not interfere 
with the subject’s daily activities
x
Moderate – Event is bothersome, possible requiring additional therapy, and may 
interfere with the subject’s daily activities
x
Severe – Event is intolerable, necessitates additional therapy or alteration of therapy 
and interferes with the subject’s daily activities
13.3. Documentation and Follow-Up of Adverse Events
The recording and documenting of adverse events (ocular and non-ocular) begins when the 
subjects are exposed to the test article, study treatment or study procedure.  Adverse events 
reported before the use of test article, start of study treatment, or study procedures will be 
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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.  
It is the Investigator’s responsibility to maintain documentation of each reported adverse event. 
All adverse events will be followed in accordance with applicable licensing requirements.  
Such documentation will include the following:
x
Adverse event (diagnosis not symptom)
x
Drawings or photographs (where appropriate) that detail the finding (e.g., size, 
location, and depth, etc.) 
x
Date the clinical site was notified 
x
Date and time of onset
x
Date and time of resolution
x
Adverse event classification, severity, and relationship to test articles, as applicable
x
Treatment regimen instituted, including concomitant medications prescribed, in 
accordance with applicable licensing requirements
x
Any referral to another health care provider if needed
x
Outcome, ocular damage (if any)
x
Likely etiology
x
Best corrected visual acuity at the discovery of the event and upon conclusion of the 
event
In addition, if an infiltrate(s) is present, he/she will complete the Corneal Infiltrate Assessment 
eCRF.  Where necessary, a culture of the corneal lesion will be collected to determine if the 
infection is microbial in nature.  If cultures are collected, the date of culture collection and 
laboratory utilized will be recorded. 
Changes in the severity of an AE shall be documented to allow an assessment of the duration 
of the event at each level of intensity to be performed.  Adverse events characterized as 
intermittent require documentation of the onset and duration of each episode. Changes in the 
assessment of relationship to the Test Article shall also be clearly documented.
Subjects who present with an adverse event shall be followed by the Investigator, within 
licensure, until all signs and symptoms have returned to pre-treatment status, stabilized, or 
been satisfactorily resolved.  If further treatment beyond licensure is required, the patient will 
be referred to the appropriate health care provider.  The Investigator will use his/her clinical 
judgment as to whether a subject reporting with an adverse event will continue in the study.  If 
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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 IEC/IRB according to 
their requirements (Section 13.4.2).  The report will comment whether the adverse event was 
considered to be related to the test article, study treatment or study procedures.
13.4.1. Reporting Adverse Events to Sponsor
Serious/Significant Adverse Events
The Investigator will inform the sponsor of all serious/significant adverse events occurring 
during the study period as soon as possible by e-mail, fax, or telephone, but no later than 24 
hours following discovery of the event.  The Investigator is obligated to pursue and obtain 
information requested by the Sponsor in addition to that information reported on the eCRF. All 
subjects experiencing a serious/significant adverse event must be followed up and all outcomes 
must be reported.
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:
x
Notify the Sponsor immediately
x
Obtain and maintain in the subject’s records all pertinent medical information and 
medical judgment for colleagues who assisted in the treatment and follow-up of the 
subject
x
Provide the Sponsor with a complete case history which includes a statement as to 
whether the event was or was not related to the use of the test article
x
Notify the IEC/IRB as required by the IEC/IRB reporting procedure according to 
national regulations
Unanticipated (Serious) Adverse Device Effect (UADE)
In the event of an Unanticipated (Serious) Adverse Device Effect (UADE), the Investigator 
will submit a report of the UADE to the Sponsor and IEC/IRB as soon as possible, but no later 
than 24 hours after the Investigator first learns of the effect.  This report is in addition to the 
immediate notification mentioned above.
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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. 
13.4.3. Event of Special Interest
None
13.5. Reporting of Pregnancy
Subjects reporting pregnancy (by self-report) during the study will be discontinued after the 
event is recorded as an Adverse Event.  Once discontinued, pregnant participants and their 
fetuses will not be monitored for study related purposes.  At the Investigator’s discretion, the 
study participant may be followed by the Investigator through delivery. However, this data will 
not be collected as part of the clinical study database.  Pregnant participants are not 
discontinued from device or solution related studies for safety concerns, but due to general 
concerns relating to pregnancy and device use.  Specifically, pregnant women are discontinued 
due to fluctuations in refractive error and/or visual acuity that occur secondary to systemic 
hormonal changes, and not due to unforeseen health risks to the mother or fetus.
14. STATISTICAL METHODS
14.1. General Considerations
Statistical Analysis will be undertaken by the sponsor or under the authority of the sponsor. A 
general description of the statistical methods to be implemented in this clinical trial is outlined 
below.
All data summaries and statistical analyses will be performed using the SAS software Version 
9.4 (SAS Institute, Cary, NC). Throughout the analysis of data, the results for each subject/eye 
will be used when available for summarization and statistical analysis.  Unscheduled visits will 
be summarized separately and will be excluded from the statistical analysis.
Summary tables (descriptive statistics and/or frequency tables) will be provided for all baseline 
variables, efficacy variables and safety variables as appropriate.  Continuous variables will be 
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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
Inner eyelid palpebral temperature has not previously been collected with the ICI-7320 infrared 
camera (Infrared Cameras Inc., Beaumont, TX) and a search of the peer reviewed literature 
failed to show published results with the device. Previous evaluations of inner eyelid 
temperature have focused primarily on the lower eyelid using infrared pyrometers. Given the 
lack of previous data, a formal sample size calculation cannot be completed. The sample size 
selected approaches the sample size required to meet the Central Limit Theorem and provide 
data for future sample size calculations.
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.
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.
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.
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 
Eyelid Temperature will be analyzed using a linear or generalized linear mixed model 
depending on the distribution of temperatures. Treatment sequence, treatment, eyelid location 
(inner and outer) and the interaction between treatment and eyelid location will be included as 
fixed effects. Age and gender may also be included as covariates when necessary. Subject will 
be included as a random effect. An appropriate covariance structure will be used to model the 
residual errors between measurements within same subject across eyes (R-side). The 
covariance structure will be selected based on the finite-sample corrected Akaike’s Information 
Criterion. Covariance structures considered include:
x
Unstructured Covariance Structure (UN)
x
Homogenous Compound symmetry (CS)
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Comparisons between the two treatments will be carried out using two-sided 95% confidence 
intervals constructed for least-square mean differences (MiBo ThermoFlo minus Bruder 
mask).
14.6. Secondary Analysis 
N/A.
14.7. Other Exploratory Analyses 
N/A.
14.8. Interim Analysis
There will not be an interim analysis performed on this study. 
14.9. Procedure for Handling Missing Data and Drop-Outs
Missing or spurious values will not be imputed. The count of missing values will be included 
in the summary tables and listings. 
14.10. Procedure for Reporting Deviations from Statistical Plan
The analysis will be conducted according to that specified in above sections.  There are no 
known reasons for which it is planned to deviate from these analysis methods.  If for any reason 
a change is made, the change will be documented in the study report along with a justification 
for the change.
15. DATA HANDLING AND RECORD KEEPING/ARCHIVING
15.1. Electronic Case Report Form/Data Collection
The data for this study will be captured on electronic case report forms (eCRFs) using an EDC 
system (Bioclinica). An authorized data originator will enter study data into the eCRFs using 
the EDC system. Data collected on equipment that is not captured in EDC will be formatted to 
the specification of the JJVC database manager and sent to JJVC for analysis. In the event that 
data is collected using paper Case Report Forms, double data entry will be utilized to prevent 
data entry error. 
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 
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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: 
x
subject identification
x
eligibility
x
study identification
x
study discussion
x
provision of and date of informed consent
x
visit dates
x
results of safety and efficacy parameters as required by the protocol
x
a record of all adverse events
x
follow-up of adverse events
x
medical history and concomitant medication
x
study supplies receipt/dispensing/return records
x
date of study completion
x
reason for early discontinuation of subject 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 the source record.
Adverse event notes must be reviewed and initialed by the Investigator.
16. DATA MANAGEMENT
16.1. Access to Source Data/Document
The Investigator/Institution will permit trial-related monitoring, audits, IEC/IRB review and 
regulatory inspection(s) by providing direct access to source data/documents.  Should the 
clinical site be contacted for an audit by an IEC/IRB or regulatory authority, JJVC must be 
contacted and notified in writing within 24 hours.
16.2. Confidentiality of Information
Information concerning the investigational product and patent application processes, scientific 
data or other pertinent information is confidential and remains the property of JJVC.  The 
Investigator may use this information for the purposes of the study only. It is understood by 
the Investigator that JJVC will use information developed in this clinical study about the 
development of the investigational product and therefore may disclose it as required to other 
clinical investigators and to regulatory agencies. 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.
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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 JJVC may visit clinical sites to review data produced 
during the study and to access compliance with applicable regulations pertaining to the conduct 
of clinical trials.  The clinical sites will provide direct access to study-related source 
data/documents and reports for monitoring and auditing by JJVC and for inspection by local 
and regulatory authorities.
17. MONITORING
The study monitors will maintain close contact with the Principal Investigator and the 
Investigator’s designated clinical site personnel.  The monitor’s responsibilities will include:
x
Ensuring that the investigation is being conducted according to the protocol, any 
subsequent amendments, and regulatory requirements are maintained
x
Ensuring the rights and wellbeing of subjects are protected
x
Ensuring adequate resources, including facilities, laboratories, equipment, and 
qualified clinical site personnel
x
Ensuring that protocol deviations are documented with corrective action plans, as 
applicable
x
Ensuring that the clinical site has sufficient test article and supplies
x
Clarifying questions regarding the study
x
Resolving study issues or problems that may arise
x
Reviewing of study records and source documentation verification in accordance with 
the monitoring plan
18. ETHICAL AND REGULATORY ASPECTS
18.1. Study-Specific Design Considerations
Potential subjects will be fully informed of the risks and requirements of the study and, during 
the study, subjects will be given any new information that may affect their decision to continue 
participation.  Subjects will be told that their consent to participate in the study is voluntary 
and may be withdrawn at any time with no reason given and without penalty or loss of benefits 
to which they would otherwise be entitled.  Only subjects who are fully able to understand the 
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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):
x
Final protocol and, if applicable, amendments
x
Sponsor-approved informed consent form (and any other written materials to be 
provided to the subjects)
x
Investigator’s Brochure (or equivalent information) and amendments
x
Sponsor-approved subject recruitment materials
x
Information on compensation for study-related injuries or payment to subjects for 
participation in the study
x
Investigator’s curriculum vitae, clinical licenses, or equivalent information (unless not 
required, as documented by IEC/IRB)
x
Information regarding funding, name of the Sponsor, institutional affiliations, other 
potential conflicts of interest, and incentives for subjects
x
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after IEC/IRB has given full approval of the final protocol, 
amendments (if any), the informed consent form, applicable recruiting materials, and subject 
compensation programs, and the Sponsor has received a copy of this approval. This approval 
letter must be dated and must clearly identify the documents being approved.
During the study, the Investigator (or Sponsor when applicable) will send the following 
documents to the IEC/IRB for their review and approval, where appropriate:
x
Protocol amendments
x
Revision(s) to informed consent form and any other written materials to be provided to 
subjects
x
If applicable, new or revised subject recruitment materials approved by the Sponsor
x
Revisions to compensation for study-related injuries or payment to subjects for 
participation in the study
x
Investigator’s Brochure amendments or new edition(s)
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x
Summaries of the status of the study (at least annually or at intervals stipulated in 
guidelines of the IEC/IRB)
x
Reports of adverse events that are serious, unanticipated, and associated with the test 
articles, according to the IRB’s requirements
x
New information that may adversely affect the safety of the subjects or the conduct of 
the study
x
Major protocol deviations as required by the IEC/IRB
x
Report of deaths of subjects under the Investigator's care
x
Notification if a new Investigator is responsible for the study at the clinical site
x
Any other requirements of the IEC/IRB
For protocol amendments that increase subject risk, the amendment and applicable informed 
consent form revisions must be submitted promptly to the IEC/IRB for review and approval 
before implementation of the change(s).
At least once a year, the IEC/IRB will review and reapprove this clinical study. This request 
should be documented in writing.
At the end of the study, the Investigator (or Sponsor where required) will notify the IEC/IRB 
about the study completion.  Documentation of this notification must be retained at the clinical 
site and a copy provided to the CRO or Sponsor as applicable.
18.4. Informed Consent
Each subject must give written consent according to local requirements after the nature of the 
study has been fully explained. The consent form must be signed before performance of any 
study-related activity. The consent form that is used must be approved by both the Sponsor 
and by the reviewing IEC/IRB. The informed consent is in accordance with principles that 
originated in the Declaration of Helsinki,3 current ICH2 and ISO 141551 guidelines, applicable 
regulatory requirements, and Sponsor Policy.
Before entry into the study, the Investigator or an authorized member of the clinical site 
personnel must explain to potential subject the aims, methods, reasonably anticipated benefits, 
and potential hazards of the study, and any discomfort it may entail. Subjects will be informed 
that their participation is voluntary and that they may withdraw consent to participate at any 
time. 
The subject will be given sufficient time to read the informed consent form and the opportunity 
to ask questions. After this explanation and before entry into the study, consent should be 
appropriately recorded by means of the subject's dated signature. After having obtained the 
consent, a copy of the informed consent form must be given to the subject.
18.5. Privacy of Personal Data
The collection, processing and disclosure of personal data and medical information related to 
the Study Subject, and personal data related to Principal Investigator and any clinical site 
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personnel (e.g., name, clinic address and phone number, curriculum vitae) is subject to 
compliance with the Health Information Portability and Accountability Act (HIPAA) 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, except for Sponsor personnel 
(monitor, auditor), IEC/IRB and regulatory organizations in the context of their investigation 
related activities that, as part of the investigation will have access to the CRFs and subject 
records.
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to investigate the efficacy, safety, quality, and utility of 
the investigational product(s) used in this study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations.
The Sponsor ensures that the personal data will be:
x
processed fairly and lawfully
x
collected for specified, explicit, and legitimate purposes and not further processed in a 
way incompatible with these purposes
x
adequate, relevant, and not excessive in relation to said purposes
x
accurate and, where necessary, kept current
Explicit consent for the processing of personal data will be obtained from the participating 
subject before collection of data. Such consent should also address the transfer of the data to 
other entities and to other countries.
The subject has the right to request through the Investigator access to his personal data and the 
right to request rectification of any data that are not correct or complete. Reasonable steps 
should be taken to respond to such a request, taking into consideration the nature of the request, 
the conditions of the study, and the applicable laws and regulations.
Appropriate technical and organizational measures to protect the personal data against 
unauthorized disclosures or access, accidental or unlawful destruction, or accidental loss or 
alteration must be put in place. Sponsor personnel whose responsibilities require access to 
personal data agree to keep the identity of study subjects confidential.
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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 
JJVC.
20. FINANCIAL CONSIDERATIONS
Remuneration for study services and expenses will be set forth in detail in the Clinical Research 
Agreement.  The Research Agreement will be signed by the Principal Investigator and a JJVC 
management representative prior to study initiation.
JJVC reserves the right to withhold remuneration for costs associated with protocol violations 
such as:
x
Continuing an ineligible subject in the study
x
Scheduling a study visit outside the subject’s acceptable visit range
JJVC reserves the right to withhold final remuneration until all study related activities have 
been completed, such as:
x
Query resolution
x
Case Report Form signature
x
Completion of any follow-up action items 
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21. PUBLICATION
This study will be registered on ClinicalTrials.gov by the Sponsor.
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. Olson MC, Korb DR, Greiner JV. Increase in Tear Film Lipid Layer Thickness 
Following Treatment with Warm Compresses in Patients with Meibomian Gland 
Dysfunction. Eye Contact Lens 2003;29:96-9.
5. Kenrick CJ, Alloo SS. The Limitation of Applying Heat to the External Lid Surface: 
A Case of Recalcitrant Meibomian Gland Dysfunction. Case Rep Ophthalmol 
2017;8:7-12.
6. Murakami DK, Blackie CA, Korb DR. All Warm Compresses Are Not Equally 
Efficacious. Optom Vis Sci 2015;92:e327-33.
7. Wang MT, Jaitley Z, Lord SM, Craig JP. Comparison of Self-Applied Heat Therapy 
for Meibomian Gland Dysfunction. Optom Vis Sci 2015;92:e321-6.
8. United States (US) Code of Federal Regulations (CFR). Available at: 
https://www.gpo.gov/fdsys/browse/collectionCfr.action?collectionCode=CFR
9. Health Information Portability and Accountability Act (HIPAA). Available at: 
https://www.hhs.gov/hipaa/for-professionals/privacy/index.html
10. Data Protection Act. Available at: 
http://www.legislation.gov.uk/ukpga/1998/29/contents
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APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES)
Not applicable 
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APPENDIX B: PATIENT INSTRUCTION GUIDE 
Not Applicable - no study lenses on eye.
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APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT)
Not Applicable 
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APPENDIX D: 
x
x
x
x
TOSI SOP_C12_Oculus Keratograph
x
TOSI SOP_C31_Thermography
x
TOSI Work Aid_Bruder Mask
x
TOSI Work Aid_Eyelid Photography
x
TOSI Work Aid_LipiView II Lipid Layer Thickness
x
TOSI Work Aid_MiBoFlo
x
Pult Meiboscale
x
ICI 7320 Thermal Camera 510(K) Summary
x
ICI 7320 Thermal Camera Scientific Specifications
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, BIOMICROSCOPY SCALE
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DISTANCE AND NEAR VISUAL ACUITY EVALUATION 
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Page 4 of 4
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DETERMINATION OF DISTANCE SPHEROCYLINDRICAL 
REFRACTIONS 
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OCULUS KERATOGRAPH
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Standard Operating Procedure for Oculus Keratograph 5 
 
Date Finalized: 08/17/2017 Version: 2.0 Page 1 of 6 
 
 
DOCUMENT CHANGE SUMMARY 
VERSION 
DATE 
SUMMARY 
1.0 
05/10/2011 
SOP Finalized 
2.0 
08/17/2017 
Revised for the Keratograph 5 (E. Ritchey) 
 
A. Description 
System for measuring and analyzing the cornea topography, including topographic measurement, near 
portion height measurement, lid angle measuring, imaging, pupillometry measuring, and measuring the 
back surface of a contact lens. 
 
B. Procedure: Topographic Measurement 
Note: If the Keratograph is moved to a different location, position the device so that direct light cannot 
influence measurements. The Keratograph should be operated in a dark room to ensure that the 
examination is conducted without interference from reflections. 
1. Switch on the PC or laptop. 
2. Switch on the Keratograph at the power supply (position ON). The LED on the switch will light up in 
green. 
3. The PC will display the Keratograph icon on the desktop. Double click to open the program. 
4. The program opens to “Patient Data Management”. A patient list is displayed on the left hand side. 
5. If examining a new patient, enter the patient information into the “Patient” box above the patient 
list. The new patient will then appear in the patient list. 
6. Select the patient to be examined from the list. (Clicking [Search] provides search function by first 
name, last name, date of birth, or by assigned ID number.) 
7. This will transfer to the patient window. A list of any previous examinations for this patient is in the 
examination window on the bottom right. 
8. Click [Keratograph] to start the Keratograph software. 
9. Select the menu “Examination”. 
10. Click on “New examination (eye)”. 
11. The Measuring window appears. The keratograph starts the illuminated Placido ring system 
automatically. 
12. Clean the chin and forehead rest of the keratograph with an alcohol pad. A clean chin rest paper can 
also be used. 
13. Position the patient in the keratograph instrument. Adjust the height of the stage so that the chin 
and forehead rests are comfortable for the patient. The black ring marking should be used to gauge 
the required height of the patient’s eyes. 
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Standard Operating Procedure for Oculus Keratograph 5 
 
Date Finalized: 08/17/2017 Version: 2.0 Page 2 of 6 
 
14. Instruct the patient to focus on the red light in the center of the Placido ring system for the whole 
examination. 
15. Ask the patient to open his/her eye wide while looking into the red fixation spot. 
16. Align the keratograph so that the patient’s eye being examined appears sharply focused in the 
camera image. To do this, slide the slide rest toward the patient until the Placido rings that are 
projected onto the eye appear as sharply focused as possible. Focus the projected Placido rings by 
moving the joystick towards or away from the keratograph. 
17. Adjust the keratograph according to the arrows shown in the measuring window. 
18. A red cross replaces the directional arrow when the correct alignment position has been reached. 
19. When all alignment positions are reached, the keratograph automatically initiates the measurement. 
NOTE: If the measurement does not start automatically, it can be initiated by pressing the Return key. 
20. The overview display “Topography” appears on the screen. 
 
C. Procedure: Near Portion Height Measurement (used to determine separator positions for bifocal 
spectacles  and RGP lenses) 
1. Start the Keratograph software. 
2. Position the patient as in a normal topographic measurement. 
3. Select the menu “Examination”. 
4. Click “New examination” 
5. Enable the Near Portion Height radio button. 
6. Center and focus the eye in the camera image 
7. Enable the Ring Illumination radio button. The lighting will be brighter and the pupil size will 
decrease. 
8. Press the Capture Image button or use the foot pedal to trigger the recording. The image is stored 
automatically. 
9. Press the button in the left hand column that correspondes with the contact lens diameter (8.8, 9.2, 
9.6 or 10.0) 
10. Click on the Blue lens contour/outline and hold down the mouse button. Move the outline down 
until the lens truncation line aligns with the lower lid margin. 
11. Move the cursor to the red-dashed line (the dividing line) until a vertical double arrow appears. 
12. Press and hold the mouse button to place the red dividing line at the pupil margin. 
13. Release the mouse button and read the suitable dividing line position. This is relative to the 
geometric center of the lens (in mm). 
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Standard Operating Procedure for Oculus Keratograph 5 
 
Date Finalized: 08/17/2017 Version: 2.0 Page 3 of 6 
 
14. The correct position of the dividing line can be gauged according to the + or – readings, in relation 
to the desired lens diameter and its central axis. 
 
D. Procedure: Lid Angle Measurement 
1. Start the Keratograph software. 
2. Position the patient as in a normal topographic measurement. 
3. Select the menu “Examination”. 
4.Enable the Eyelid Angle radio button. 
5.Center and focus the eye in the camera image 
6.Press the Capture Image button or use the foot pedal to trigger the recording. The image is stored 
automatically. 
7. An overview image will appear on the screen. 
8. Select the Eyelid Angle button in the left hand column 
9. Select the lowest point of the lower lid margin by pressing the mouse button. 
10. Move the cursor to the approximate position of the lacrimal point, which is approximately located 
at the highest point of the nasal course of the lid, and press the mouse button. 
11. The angle measure appears. Record the angle. 
 
E. Procedure: General Imaging Measurement 
Note: The imaging software can be used to make video and image files of the contact lens on the eye. 
1. Start the Keratograph software. 
2. Position the patient as in a normal topographic measurement. 
3. Select the menu “Examination”. 
4. Click “New examination”. 
5. Select the New Picture/Video radio button in the left hand column.  
6. Adjust the Illumination settings in the right hand column per the study protocol (options include IR-
Top, IR-Central, Blue for Fluorescein evaluation, White, Placido White, Placido IR, Inner Ring and 
Fixation). Refer to the Keratograph 5 Instruction Manual for Illumination details.  
7. Adjust the Magnification Settings by selecting the appropriate radio button.  
8. Adjust the Camera Exposure and Gain using the slider control in the right hand column. 
9. Use the Image, Record and Stop buttons to record still/video images. 
10. Both video recordings and single images are saved automatically. 
 
F. Procedure: Meibography (Meibo-Scan Examination). 
1. Start the Keratograph software. 
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Standard Operating Procedure for Oculus Keratograph 5 
 
Date Finalized: 08/17/2017 Version: 2.0 Page 4 of 6 
 
2. Position the patient as in a normal topographic measurement. 
3. Select the menu “Examination”. 
4. Click “New examination”. 
5. Enable the Meibog. Upper/Lower Lid radio button. If a single image is desired, select the 
Meibography Single Image radio button 
6. Evert the upper eyelid and position the camera so that the upper eyelid fits in the red-framed 
recording box 
7. Press the Image button or use the foot pedal to start recording. 
8. Repeat for the lower lid, if applicable. 
9. Images are saved automatically, along with date and time information. To view previous images, 
choose the menu “Examination” and select “Load an old examination.” 
 
G. Procedure: Pupillometry Measuring Procedure 
1. Start the Keratograph software. 
2. Position the patient as in a normal topographic measurement. 
3. Select the menu “Examination”. 
4. Select the appropriate measuring program in the “Pupillometer Programs” box: 
a. [Pupillogram] is the automatic, standard pupillometry program. 
b. [Asymmetric Test] is the automatic pupillometry program for detection of unequal pupils. 
c.
Manual option for regulating glare intensity. 
7.   Adjust to view to the center of the pupil by moving the slide rest and joystick accordingly. Sharply 
focus the image of the pupil by moving the slide rest or joystick towards or away from the 
keratograph. (The blue bar indicates sharpness of the image; the higher the bar, the sharper the 
camera image.) 
8.   To perform an automatic measurement, click the desired program in the measurement menu. The 
measuring procedure starts automatically. (If performing manual pupillometry, click on the program 
[Manual] and adjust using “Glare” and “Min. glare”.) 
9.   The measuring procedure ends automatically when the measurement reaches the right-hand side of 
the graph. You can also end the automatic measurement procedure by pressing the “Stop” button. 
10. The overview screen will automatically appear, and measured data can be analyzed. 
 
H. Procedure: Measuring the Back Surface of a Contact Lens 
Note: If unfamiliar with the mounting parts and the contact lens holder during set-up, see images on 
pages 29-30 in the Keratograph Instruction Manual. 
1. Fill the contact lens holder with water: 
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Standard Operating Procedure for Oculus Keratograph 5 
 
Date Finalized: 08/17/2017 Version: 2.0 Page 5 of 6 
 
a. To do this, open the contact lens holder by unscrewing the lock nut. Pour in the water and close 
the holder by screwing the lock nut back on. Make sure as little air as possible gets trapped inside. 
b. Hold the CL holder so that the adjusting screw points downward. 
c.
Screw the adjusting screw into the holder until the top part of the CL holder is fully wetted with 
water. 
d. Screw out the adjusting screw again until the surface of the water takes on a slightly concave 
curvature. 
2.   Clean and dry the CL that is to be measured with a soft cloth. There should be no moisture or residual 
dust, especially on the concave inside surface. 
3.   To secure the CL, place between your thumb and index finger and carefully lay it on the surface of 
the water on the CL holder. Screw the adjusting screw of the CL holder out until the CL sits securely 
in the holder. (Make sure no air bubbles are produced and no water gets onto the back surface.) 
4.   Fasten the mounted CL holder by screwing the reference sphere holder to the chin rest. 
5.   Plug the CL holder onto the mounting clip. Adjust the mounting arm so that the optical axes of the 
CL roughly coincide with those of the keratograph. 
6.   Start the Keratograph software. 
7.   Select New Examination 
8.   In the Topography field, enable the “CL Back Surface” radio button. 
 
9. Measurement takes place in the same way as the topography measurement. 
 
I.
Procedure: Non-Invasive Keratograph Break Up Time (NIKBUT) 
1. Switch on the PC or laptop. 
2. Switch on the Keratograph at the power supply (position ON). The LED on the switch will light up in 
green. 
3. The PC will display the Keratograph icon on the desktop. Double click to open the program. 
4. The program opens to “Patient Data Management”. A patient list is displayed on the left hand side. 
5. If examining a new patient, enter the patient information into the “Patient” box above the patient 
list. The new patient will then appear in the patient list. 
6. Select the patient to be examined from the list. (Clicking [Search] provides search function by first 
name, last name, date of birth, or by assigned ID number.) 
7. This will transfer to the patient window. A list of any previous examinations for this patient is in the 
examination window on the bottom right. 
8. Click “Keratograph” to start the Keratograph software. 
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Standard Operating Procedure for Oculus Keratograph 5 
 
Date Finalized: 08/17/2017 Version: 2.0 Page 6 of 6 
 
9. Select the menu “Examination”. 
10. Click on “New examination”. 
11. Enable the NIKBUT radio button in the left hand column. 
12. Select IR or White lighting in the column on the right. 
13. Clean the chin and forehead rest of the keratograph with an alcohol pad. A clean chin rest paper can 
also be used. 
14. Position the patient in the keratographer. Adjust the height of the stage so that the chin and forehead 
rests are comfortable for the patient. The black ring marking should be used to gauge the required 
height of the patient’s eyes. 
15. Instruct the patient to focus on the red light in the center of the Placido ring system for the whole 
examination.. 
16. Adjust the keratograph according to the arrows shown in the measuring window. 
17. A red cross replaces the directional arrow when the correct alignment position has been reached. 
18. When all alignment positions are reached, the keratograph automatically initiates the measurement. 
The screen will indicate for the examiner to direct the patient to blink 2 times.   
19. Following the blinks, the patient should keep their eyes open for as long as possible or until the 
automatic measure is complete. 
20. The keratograph automatically detects the blinks and begins recording tear break-up time across all 
sections of the cornea. 
21. When the measure is complete, or the patient cannot keep their eyes open any longer, the measure 
is finished and the overview display appears on the screen.  
J.
References
Oculus Keratograph 5M User Guide 
Oculus Keratograph 5M Instruction Manual 
 
 
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THERMOGRAPHY
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Noncontact Infrared Thermography  
 
Date Finalized: 04/28/2016 
 
Version: 3.0 
Page 1 of 4 
 
DOCUMENT CHANGE SUMMARY 
VERSION 
DATE 
SUMMARY 
1.0 
12/17/2013 
SOP Finalized (Daniel Powell) 
2.0 
05/17/2015 
Minor changes to document (Daniel Powell) 
3.0 
04/28/2016 
Added section for backup storage of captured data (Daniel Powell) 
 
A. Description 
Thermography is used to measure the surface temperature of objects, including the skin and ocular 
surface in humans and other animals. It is postulated that the overall ocular surface temperature in dry 
eye is greater than in non-dry eye states; this is most likely explained by the increased amount of 
inflammation in the region. In situations such as the evaporative form of dry eye, the corneal surface 
may actually be cooler than in non-dry eye cases because the increased evaporation allows for cooling. 
 
B. Equipment/Camera 
The device used to capture thermographic images is the ICI-7320 infrared camera (Infrared Cameras Inc., 
Beaumont, TX). This camera is FDA-approved [510(k) clearance] for use in medical imaging of any part 
of the body’s surface. A USB cable connects the camera to a computer. Using a software program 
provided by the camera manufacturer, the examiner can adjust the camera settings as well as capture 
single or multiple images taken in series. In addition, the camera can send data to a computer where a 
software program can determine the overall surface temperature and other variables. The camera is 
mounted in an apparatus similar to a biomicroscope. 
 
C. Procedure: Subject Alignment 
1. Position the subject comfortably in the chin rest and direct them to place their forehead against the 
forehead rest. 
2. Adjust the height of the chin rest so that the subject’s lateral canthus is aligned with the black line 
on the upright bar. 
3. If necessary, move the table to adjust for subject comfort. 
4. On the computer desktop, click the IR Flash icon:  
 
5. Under the Video tab, depending on whether a single or series of images will be captured, select either 
“Capture Single Image” or “Capture Image Series” (yellow arrow, Fig. 1). 
Note: If “Capture Image Series” is selected, you must also specify how the images will be captured. 
To do this, select “Configure Series Image Capture” under the Video tab and make the appropriate 
selections. 
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Noncontact Infrared Thermography  
 
Date Finalized:  04/28/2016 
Version: 3.0 
Page 3 of 4 
8. To the right of the image of the person in Figure 2, there are settings where you can set the maximum 
and minimum temperature range that you expect to find in the area of the eye you want to capture 
the reading. A preset setting is indicated if the box marked AGC is checked. If you want to insert your 
own maximum and minimum setting, deselect the AGC box and slide the max and/or min boxes up 
or down to adjust the ranges. You can also enter the temperatures in the gray boxes at the top 
(maximum temperature) and bottom (minimum) of the sliding scale figure. To measure the ocular 
surface temperatures, a recommended maximum and minimum setting would be 105 and 80 
degrees Fahrenheit, respectively. 
9. When you are ready to capture a single image or an image series click on the Camera icon 
 (for 
single image capture only) or the red recording icon 
(for image series capture only) directly 
beneath the active image. 
10. To exit the program, click on the File tab and then click “Exit”. 
Note: If you are using the capture image series option and need to stop image capture, click on the 
black box icon immediately to the right of the red recording icon directly beneath the active image:  
 
11. Captured images will appear in the lower left-hand side of the screen. Click on the images to save 
and then click on “Save Image”. To save all images, click on “Save All”. Save images under a file name 
specific for the particular study and subject (and eye, if both eyes are evaluated). 
12. Repeat Steps 6-9 above for the fellow eye. 
Note: DO NOT unplug the USB cable from the camera or computer as this may affect calibration, 
particularly the emissivity correction (which is set to 0.98 as the surface of the human skin has a 
emissivity of 0.97-1.00; a value of 1.00 is a perfect radiator, or black body). To check for this, click on 
the Temperatures tab and select “Emissivity Correction”. 
D. Procedure: Data Backup 
1. Data should be backed up after each subject has been completed but at least once per day. 
2. Copy files requiring backup: Click on the icon “Shortcut to My Passport” which is located on the 
desktop.  
3. Check to be sure the files have indeed been transferred to the My Passport external hard drive. 
E. Procedure: Image Analysis 
1. Under the File tab, select the “Load Image” option. 
2. Select the area of the image to be analyzed using the options (box, circle, point, line, or none) located 
in the Analysis box located at left-hand margin of the screen (yellow arrow, Fig. 3). 
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BRUDER MASK
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Date Revised: 06/07/2018 Version: 1.0 Page 1 of 2 
 
 
Work Aid: Bruder Mask 
 
The following work aid to prepare a Bruder Mask for treatment of Meibomian Glands.  
1. Shake the Bruder Mask to evenly distribute the MediBeads within the mask 
2. Place the mask in a microwave and heat for 20 seconds 
3. Remove the mask from the microwave, shake the mask to evenly distribute the 
MediBeads. 
4. Measure the mask temperature  
a. If the temperature is greater than 42 degrees Celsius (108 degrees 
Fahrenheit), shake the Bruder Mask to redistribute the MediBeads and 
re-measure the temperature. If the temperature continues to be greater 
than 42 degrees Celsius, measure the temperature every 60 seconds until 
the target temperature of 42 degrees Celsius or less is obtained. 
b. If Bruder Mask temperature is under 37 degrees Celsius (100 degrees 
Fahrenheit), place in the microwave for an additional 5 seconds, remove 
from the Microwave and re-measure 
i. If the new temperature is between 37 and 42 degrees, proceed 
ii. If the temperature exceeds 42 degrees, go to step 4a 
iii. NOTE: Step 4b may be repeated one additional time. Total heating 
time of the Bruder Mask shall not exceed 30 seconds. 
5. Place the Bruder Mask on/in the Bruder Mask Sleeve 
6. Apply the Bruder Mask and Sleeve to the closed eye(s). The mask should not be 
applied tightly. 
7. The mask should be applied for 10 minutes, or as specified in the protocol. 
 
References: 
1. Bruder Eye Compress Moist Heat Instruction Sheet 
 
DOCUMENT CHANGE SUMMARY 
VERSION 
DATE 
SUMMARY 
1.0 
06-July-2018 
Original Work Aid (Eric Ritchey) 
 
 
 
CR-6281, v2.0
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Date Revised: 06/07/2018 Version: 1.0 Page 2 of 2 
 
 
Sample Bruder Mask Temperature Log 
 
Subject ID 
 
Date 
(DDMMMYYYY) 
Time (24 Hr) 
Microwave 
Time (sec) 
Temperature 
(C) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page ______ of ______ 
 
CR-6281, v2.0
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EYELID PHOTOGRAPHY
CR-6281, v2.0
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Date Revised: 06/07/2018 
Version: 1.0 
Page 1 of 1 
 
 
Work Aid: Eyelid Photography 
 
Equipment: Haag-Streit BQ-900 Biomicroscope, Cannon EOS Digital Camera 
 
1. Turn on computer and monitor 
2. Turn on digital camera (lower right hand corner of camera, mounted above 
slit lamp oculars) 
3. Double click on EOS Utility. Icon on computer desktop. 
a.
Select “Camera Setting/Remote Shooting” option on menu 
4. Turn on Digital Photo Professional software. Icon on computer desktop. 
 
EOS Utility Set Up 
1. Click on File Folder icon 
2. Confirm Destination folder for the study 
3. Click FILE NAME tab 
4. Select file name format pull-down for the study 
a.
Look at the example line to tell if the name string is for OD or OS 
b. Each eye (OD/OS) has it’s own pull down selection. 
 
Camera Set Up 
1. Turn Room lights ON 
2. Confirm aperture knob in front of slit lamp oculars is set to “2” 
3. Set Slit Lamp Mag to setting specified by the project 
4. Set Illumination tower 25-30 degrees temporal.  
a.
Make sure tower is not visible in the right ocular. 
b. Illumination tower position may be changed to avoid excessive 
reflection off the tissue of interest 
5. Set 5mm vertical beam 
6. Place flip up diffuser in the beam path 
7. Set tower illumination to “Half Open” illumination 
8. Take photo by pressing blue button in front of the slip lamp joystick. 
 
DOCUMENT CHANGE SUMMARY 
VERSION 
DATE 
SUMMARY 
1.0 
07-June-2018 
Original Work Aid (Eric Ritchey) 
 
CR-6281, v2.0
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JJVC CONFIDENTIAL

LIPIVIEW II LIPID LAYER THICKNESS
CR-6281, v2.0
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Date Revised: 06/07/2018 Version: 1.0 Page 1 of 1 
 
 
Work Aid: TearScience LipiView II Lipid Layer Thickness 
Measurement 
 
1. Turn on the LipiView II power button at the base of the unit 
2. Log into the LipiView II 
3. At the subject page, select “add patient” 
4. To identify subjects 
a. Last name = study name; first name = subject number, Date of Birth = 
date of the examination OR 
b. Enter a subject ID in the Patient ID field. 
5. Select the Lipid Imaging test from the Capture/View screen and press “new” 
6. Make sure the chin rest is in the proper position. The position for lipid layer 
analysis is the position closest to the device. Clean with an alcohol pad. 
7. Adjust chin rest height so that the lateral canthus of the subject is aligned with 
the marks on the LipiView II headrest. 
8. Instruct the subject to look at the orange fixation light 
9. Touch the side of the screen corresponding with the eye to be imaged 
10. Using the touch screen, position the image of the eye so that the pupil is 
centered 
11. Use the target icon on the touch screen to auto-focus the image 
12. Tell the patient to blink normally and fixate on the orange light 
13. Press “Capture” on the touch screen. The video will record for 20 seconds 
a. Use the play button to review the video quality 
b. If the video quality is unacceptable, use the “trash can” icon to delete and 
take another recording 
14. Record the other eye using the procedure above 
15. Press “Analyze” 
16. Record the following values 
a. Average Lipid Layer Thickness (nm) 
b. Minimum Lipid Layer Thickness (nm) 
c.
Maximum Lipid Layer Thickness (nm; this may reach a ceiling value of 
“100+nm”) 
d. C Factor 
e. Standard Deviation 
 
References: 
1. LipiView II Device Training Video 
 
DOCUMENT CHANGE SUMMARY 
VERSION 
DATE 
SUMMARY 
1.0 
06-July-2018 
Original Work Aid (Eric Ritchey) 
 
CR-6281, v2.0
Page 83 of 97
JJVC CONFIDENTIAL

 MIBOFLO
CR-6281, v2.0
Page 84 of 97
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Date Revised: 06/07/2018 Version: 1.0 Page 1 of 1 
 
 
Work Aid: MiBoFlo 
 
1. Verify that the appropriate treatment eyepad to be used per the study 
instructions is inserted in the unit 
2. Clean the MiBoFlo Pad with an alcohol swab 
3. Turn on MiBoFlo power key the on position and wait until the pre-treatment 
warm up timer is complete 
4. Place some ultrasound transmission gel on the eyepad 
5. Instruct the subject to close his/her eyes 
6. Press start on the touchpad 
7. Place the eyepad on the eye and slowly move side to side laterally to disperse 
the ultrasound transmission gel 
8. With light pressure, massage the lids with a gentle circular motion.  
9. Apply additional ultrasound transmission gel as needed, disrupting treatment as 
minimally as possible 
10. End treatment when the timer expires 
11. Using a facial tissue, remove any excess ultrasound transmission gel 
12. Perform the procedure on the other eye, if needed. 
 
 
References: 
1. MiBoFlo Manual 
2. MiBoFlo Training Video 
 
DOCUMENT CHANGE SUMMARY 
VERSION 
DATE 
SUMMARY 
1.0 
08-July-2018 
Original Work Aid (Eric Ritchey) 
 
 
CR-6281, v2.0
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PULT MEIBOSCALE
CR-6281, v2.0
Page 86 of 97
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THERMAL CAMERA 510(K) SUMMARY
CR-6281, v2.0
Page 87 of 97
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 THERMAL CAMERA SCIENTIFIC SPECIFICATIONS 
CR-6281, v2.0
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CR-6281, v2.0
 
Page 96 of 97
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PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE
Protocol Number and Title: CR-6281 MiBo ThermoFlo Lid Temperature Evaluation
Version and Date: 2.0, Amendment 1.0 15 November 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),8 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
CR-6281, v2.0
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