An Open-Label, Multicenter, Phase 4 Study to Evaluate Early Treatment Outcomes With Miebo™ in Subjects With Dry Eye Disease
Phase: PHASE4
Conditions: Dry Eye
Sponsor: Bausch & Lomb Incorporated

Protocol #937 Miebo Early Treatment Response 
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An Open-Label, Multicenter, Phase 4 Study to Evaluate Early 
Treatment Outcomes With Miebo™ in Subjects With Dry Eye 
Disease 
CLINICAL STUDY PROTOCOL 
STUDY #937 
Developmental phase of study: 4 
Study design: 
Open-label, multicenter trial 
Date: 
 15 Mar 2024 (Version  2.0, Amendment 1) 
Sponsor  
ClinicalTrials.gov ID: 
NCT06309953 
Bausch & Lomb Incorporated 
1400 North Goodman Street 
Rochester, NY 14609 US 
Corporate Headquarters  
Main Office Phone: (908) 927-1400 
This clinical investigation is being conducted in accordance with the Declaration of Helsinki 
on Ethical Principles for Medical Research Involving Human Subjects and with Good Clinical 
Practice (GCP), as required by the US Code of Federal Regulations applicable to clinical 
studies (21CFR Parts 11, 50, 54, 56, 312, 314; 42 USC 282(j); International Conference on 
Harmonisation (ICH) Harmonised Tripartite Guideline E6(R2): GCP and applicable local 
regulations.  
CONFIDENTIAL 
This protocol contains confidential, proprietary information of Bausch & Lomb Incorporated. 
Further dissemination, distribution or copying of this protocol or its contents is strictly 
prohibited. 

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Protocol Review and Approvals 
 
An Open-Label, Multicenter, Phase 4 Study to Evaluate Early Treatment 
Outcomes With Miebo™ in Subjects With Dry Eye Disease 
 
Reviewed and approved: 
 
 
Executive Director, Global Clinical Operations 
Bausch & Lomb Incorporated 
400 Somerset Corporate Boulevard 
Bridgewater, NJ 08807   
 
 
 
 
 
 
Signature 
 
 
Executive Director, Medical and Clinical Affairs 
Bausch & Lomb Incorporated 
400 Somerset Corporate Boulevard 
Bridgewater, NJ 08807 
 
 
 
 
 
 
Signature 
 
Director, Biostatistics  
Bausch & Lomb Incorporated 
1400 North Goodman Street 
Rochester, NY 14609 
 
 
 
 
 
 
Signature 
 
Associate Director, Global Regulatory Affairs 
Bausch & Lomb Incorporated 
400 Somerset Corporate Boulevard 
Bridgewater, NJ 08807 
 
 
 
 
 
Signature 
 
Director, Pharmacovigilance Global ICSR 
Bausch & Lomb Incorporated 
400 Somerset Corporate Boulevard 
Bridgewater, NJ 08807 
 
 
 
 
Signature 
 
 

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Investigator Statement of Agreement 
 
An Open-Label, Multicenter, Phase 4 Study to Evaluate Early Treatment 
Outcomes With Miebo™ in Subjects With Dry Eye Disease 
 
PROTOCOL 
STUDY #937 
I have read the attached protocol and I agree that it contains all information necessary to 
conduct this study as described and agree to abide by all provisions set forth therein.  
I agree to conduct this study properly, ethically, and safely in accordance with internationally 
recognized code of International Council for Harmonisation Good Clinical Practice (GCP), as 
required by applicable local laws and regulations. I will not initiate the study until I have 
obtained written approval by the appropriate Institutional Review Board (IRB)/Ethics 
Committee (EC) and have complied with all financial and administrative requirements of the 
governing body of the clinical institution and the Sponsor. I will obtain written informed 
consent (and, if applicable, assent for children) from each study subject prior to performing 
any study specific procedures which are not my routine standard of care.  
I understand that my signature/e-signature on a case report form (CRF)/electronic case report 
form (eCRF) indicates that the data therein has been reviewed and accepted by me. I understand 
that this document and related information is subject to confidentiality terms found in my 
signed Confidentiality or Clinical Services Agreement. I agree to protect the confidentiality of 
my patients, as required by all local privacy regulations, when allowing the Sponsor of this 
study, and/or relevant regulatory authorities and IRB/ECs, direct access to my medical records 
for study subjects. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by the Sponsor that is necessary for the proper conduct of this study. I 
will discuss this material with them to ensure that they are fully informed about the test article 
and all study-related procedures and required documentation. 
__________________________________________________ 
_______________________ 
Principal Investigator, Printed Name 
Date 
 
__________________________________________________ 
_______________________ 
Signature 
Site Number 
Upon signing, provide a copy of this page to the Sponsor and retain a copy for your files.  

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1 Synopsis 
Name of Sponsor: 
Bausch & Lomb Incorporated 
Study Treatment: 
Miebo™ (perfluorohexyloctane ophthalmic solution) 
Study Control: 
None (single-arm study) 
Protocol Title: 
An Open-Label, Multicenter, Phase 4 Study to Evaluate 
Early Treatment Outcomes With Miebo™ in Subjects 
With Dry Eye Disease 
Protocol Number: 
#937  
Number of Clinical Sites: 
Up to 8 clinical sites in the United States 
Study Phase: 
4 
Primary Objective: 
To evaluate early outcomes with Miebo treatment in 
subjects with dry eye disease (DED)  
Overall Study Design: 
Structure: 
This single-arm, open-label, multicenter, prospective 
study will consist of 4 study visits in subjects with DED. 
Subjects who sign the informed consent form at the 
Screening/Baseline Visit (Visit 1; Day 1) will be enrolled 
in the study and screened for eligibility to participate in 
the study.  
  
 
 
. Following 
subjects’confirmation of eligibility and at least 15 minutes 
after the completion of the Schirmer’s test, site staff will 
instill the first dose of Miebo and dispense Miebo to 
subjects. 
 
 
 
Subjects will then commence at-home treatment with 
Miebo 4 times daily (QID) bilaterally and will continue 
this for approximately 14 days. At Visits 2, 3, and 4 
(Days 3, 7, and 14, respectively), subjects will complete 
1  
 Follow-up Visit in the clinic 
at least 30 minutes and no longer than 4 hours post-dose.   
Subject Duration: 
This study consists of 4 study visits over a period of 
approximately 14 days. 
Study Duration: 
The entire duration of the study (from first subject first 
visit to last subject last visit) is expected to take 
approximately 5 months. 

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Dosage Instillation: 
Site staff will instill the first dose of Miebo in the clinic at 
Visit 1. After that, subjects will self-administer Miebo 
QID bilaterally for approximately 14 days. The last dose 
prior to Visits 2, 3, and 4 will be instilled at least 
30 minutes and no longer than 4 hours prior to the start of 
the visit. 
Measures Taken to Reduce 
Bias: 
Not applicable 
Study Population Characteristics 
Number of Subjects: 
Approximately 100 subjects will be treated with Miebo. 
Condition/Disease: 
Subjects with DED  
Inclusion Criteria: 
1. At least 18 years of age at the time of consent 
2. Able to provide written voluntary informed consent 
3. The same eye must satisfy the below inclusion 
criteria (a–e): 
a. Subject-reported history of DED in at least 
1 eye for at least 6 months prior to Visit 1 
b. Tear-film break-up time ≤5 seconds at Visit 1 
c. Total corneal fluorescein staining score ≥4 and 
≤11 (ie, sum of inferior, superior, central, nasal, 
and temporal) according to the National Eye 
Institute scale at Visit 1 
d. Total meibomian gland dysfunction score ≥3 
(range, 0–15) 
e. Unanesthetized Schirmer’s test I score ≥5 mm 
4. 
 
5. Able and willing to follow instructions, including 
participation in all trial assessments and visits 
Exclusion Criteria: 
Note: Ocular exclusion criteria are relevant to both eyes, 
such that meeting a criterion in either eye excludes the 
subject from the study  
1. Had received Miebo as a prescription or as a study 
treatment in previous Miebo clinical studies 
2. Have any clinically significant ocular surface slit-
lamp findings at Visit 1 and/or, in the opinion of the 
Investigator, have any findings that could interfere 
with trial parameters, including:  
a. History of eye trauma  
b. History of Stevens-Johnson syndrome 
c. Active blepharitis or lid margin inflammation  

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d. DED secondary to scarring, irradiation, alkali 
burns, cicatricial pemphigoid, or destruction of 
conjunctival goblet cells (as with vitamin A 
deficiency) 
e. Abnormal lid anatomy causing incomplete 
eyelid closure  
f. Abnormal cornea shape (keratoconus) 
g. Corneal epithelial defect or significant confluent 
staining or filaments 
h. History of herpetic keratitis  
i. Pterygium  
j. Ocular or periocular rosacea 
3. Use of any of the following ocular therapies within 
60 days prior to Visit 1: Vuity®, any topical ocular 
steroid treatments, prescription dry eye therapy 
including varenicline nasal spray, or topical 
anti-glaucoma medication  
4. Had a LipiFlow® procedure, intense pulse light 
procedure, or any kind of other procedure affecting 
meibomian glands within 6 months prior to Visit 1 
5. Had received or removed a permanent punctum plug 
within 3 months (6 months for dissolvable plugs) 
prior to Visit 1 
6. Use of any eye drops (prescription or over-the-
counter, such as artificial tears or Lumify®) and/or 
TrueTear™ device (intranasal tear neurostimulator) 
within 24 hours prior to Visit 1 
7. Have active ocular allergies or ocular allergies that 
are expected to be active during the trial period 
8. Have worn contact lenses within 1 month prior to 
Visit 1 or planned wear during the study  
9. Have undergone intraocular surgery or ocular laser 
surgery within 3 months prior to Visit 1; have 
undergone refractive surgery within 2 years prior to 
Visit 1 
10. Have active ocular or systemic infection (bacterial, 
viral, or fungal), including fever 
11. Female subjects who are pregnant, nursing, or 
planning a pregnancy 
12. Female subjects of childbearing potential who are 
not using an acceptable means of birth control; 
acceptable methods of contraception include 
hormonal 
(oral, 
implantable, 
injectable, 
or 

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2 Table of Contents  
1 
SYNOPSIS ...............................................................................................................5 
2 
TABLE OF CONTENTS .......................................................................................10 
3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................13 
4 
INTRODUCTION .................................................................................................14 
4.1 
Indication ...................................................................................................14 
4.2 
Background ................................................................................................14 
5 
STUDY OBJECTIVES AND PURPOSE .............................................................15 
5.1 
Objectives ..................................................................................................15 
5.2 
Endpoints ...................................................................................................15 
5.2.1 Efficacy… ......................................................................................15 
5.2.2 Safety…… .....................................................................................15 
6 
INVESTIGATIONAL PLAN ................................................................................15 
6.1 
Overall Study Design and Plan: Description .............................................15 
6.2 
Investigators ...............................................................................................16 
6.3 
Subject Duration ........................................................................................16 
6.4 
Study Duration ...........................................................................................16 
7 
SELECTION AND WITHDRAWAL OF SUBJECTS .........................................16 
7.1 
Subject Inclusion Criteria ..........................................................................16 
7.2 
Subject Exclusion Criteria .........................................................................17 
7.3 
Subject Disposition Criteria .......................................................................19 
7.3.1 Subject Enrollment.........................................................................19 
7.3.2 Subject Screen Failures ..................................................................19 
7.3.3 Subject Completion ........................................................................19 
7.3.4 Subject Discontinuation .................................................................19 
7.3.5 Lost to Follow-Up ..........................................................................19 
8 
TREATMENT PLAN ............................................................................................20 
8.1 
Methods of Assigning Subjects to Treatment Groups ...............................20 
8.1.1 Treatment Allocation .....................................................................20 
8.1.2 Randomization Method ..................................................................20 
8.2 
Masking......................................................................................................20 
8.3 
Concomitant Medications and Treatments ................................................20 
8.4 
Protocol Deviations ....................................................................................20 
9 
STUDY MATERIALS AND MANAGEMENT ...................................................21 
9.1 
Description of Study Treatment and Intended Use ....................................21 
9.2 
Packaging and Labeling .............................................................................21 

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9.2.1 Packaging …………………………………………………………21 
9.2.2 Labeling… .....................................................................................21 
9.3 
Storage of Study Treatment .......................................................................21 
9.4 
Directions for Use and Administration ......................................................21 
9.5 
Study Treatment Accountability ................................................................21 
9.6 
Other Materials ..........................................................................................22 
10 
STUDY PROCEDURES AND EVALUATIONS ................................................22 
10.1 
Schedule of Evaluations and Procedures ...................................................22 
10.1.1 Screening/Baseline Visit (Visit 1): Day 1 ......................................22 
10.1.2 Visit 2: Day 3 + 1 day ....................................................................23 
10.1.3 Visit 3: Day 7 ± 1 day ....................................................................23 
10.1.4 Visit 4: Day 14 ± 2 days ................................................................24 
10.1.5 Unscheduled Visit(s) ......................................................................24 
10.1.6 Missed Visits ..................................................................................24 
10.1.7 Post-Study Follow-Up ...................................................................24 
10.2 
Study Completion ......................................................................................24 
10.2.1 Early Study Termination ................................................................25 
11 
PRIMARY AND SECONDARY SAFETY AND EFFICACY VARIABLES .....25 
11.1 
Evaluation of Efficacy ...............................................................................25 
11.2 
Evaluation of Safety ...................................................................................25 
11.3 
Adverse Events ..........................................................................................25 
11.3.1 Adverse Events Definitions ...........................................................25 
11.3.2 Identification and Collection..........................................................26 
11.3.3 Evaluations .....................................................................................26 
11.3.4 Reporting........................................................................................27 
11.3.5 Adverse Events at Subject Exit ......................................................28 
11.3.6 Pregnancy .......................................................................................28 
12 
STATISTICS .........................................................................................................29 
12.1 
Study Endpoints .........................................................................................29 
12.1.1 Efficacy Endpoints .........................................................................29 
12.1.2 Safety Outcomes ............................................................................29 
12.2 
Hypotheses .................................................................................................29 
12.3 
Sample Size Determination........................................................................29 
12.4 
Analysis Populations ..................................................................................30 
12.5 
Statistical Analysis .....................................................................................30 
12.5.1 General Considerations ..................................................................30 
12.5.2 Primary Effectiveness Analyses ....................................................30 
 

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12.5.3 Safety Analyses ..............................................................................30 
12.5.3.1 Adverse Events..............................................................30 
12.5.3.2 Subject Demographics and Baseline Characteristics ....30 
12.5.3.3 Prior and Concomitant Medications..............................30 
12.5.3.4 Subject Disposition .......................................................31 
12.5.3.5 Treatment Adherence ....................................................31 
12.5.3.6 Treatment Exposure ......................................................31 
12.6 
Additional Statistical Considerations .........................................................31 
12.6.1 Handling of Missing Data ..............................................................31 
12.6.2 Multicenter Issues ..........................................................................31 
12.6.3 Multiplicity Issues ..........................................................................31 
12.6.3.1 Interim Analysis ............................................................31 
12.6.3.2 Protocol Deviations .......................................................31 
13 
QUALITY CONTROL AND QUALITY ASSURANCE .....................................31 
13.1 
Study Monitoring .......................................................................................31 
13.2 
Source Documentation ...............................................................................32 
13.3 
Case Report Forms and Data Verification .................................................32 
13.4 
Recording of Data and Retention of Documents .......................................33 
13.5 
Audits and Inspections ...............................................................................33 
14 
ETHICS AND ADMINISTRATIVE ISSUES ......................................................34 
14.1 
Ethical Conduct of the Study .....................................................................34 
14.2 
Ethics Review ............................................................................................34 
14.3 
Written Informed Consent .........................................................................34 
14.4 
Financial Disclosure, Clinical Trial Agreements, and Site Contact 
Information ................................................................................................34 
14.5 
Confidentiality/Publication of the Study ...................................................35 
15 
REFERENCES ......................................................................................................35 
16 
APPENDICES .......................................................................................................37 
16.1 
Appendix A  Study Flow Chart .................................................................37 
16.2 
Appendix B  Methods of Clinical Evaluations ..........................................38 
 
 
 
 
16.5 
Appendix E  Miebo Prescribing Information.............................................48 
 
List of Tables 
Table 1.   In-Clinic Visit Details ........................................................................................22 

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3 List of Abbreviations and Definitions of Terms 
Abbreviation or specialist term 
Definition or explanation 
AE Adverse event 
CFB Change from baseline 
CFS Corneal fluorescein staining 
CRF Case Report Form 
CRO Contract Research Organization 
DED Dry eye disease 
FAS Full Analysis Set 
FDA Food and Drug Administration 
FDF Financial disclosure form 
GCP Good Clinical Practice 
HIPAA Health Insurance Portability and Accountability Act 
ICF Informed consent form 
IRB 
MGD 
NEI 
 
Institutional Review Board 
Meibomian gland dysfunction 
National Eye Institute 
 
PP Per Protocol 
QID 4 times daily 
SAE Serious adverse event 
TBUT Tear film break-up time  
TEAE Treatment-emergent adverse event 
US United States 
VA Visual acuity 
 
 
 

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4 Introduction 
4.1 
Indication  
Miebo™ is indicated for the treatment of the signs and symptoms of dry eye disease (DED).1 
4.2 
Background 
Dry eye disease is defined by the International Dry Eye Workshop as a multifactorial disease 
of the ocular surface characterized by a loss of homeostasis of the tear film and is accompanied 
by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface 
inflammation and damage, and neurosensory abnormalities play etiological roles.2 Symptoms 
of DED, such as feeling of dryness, burning, sandy/gritty sensation, foreign body sensation, 
pain, and itchiness, can be debilitating. In addition, visual function–related symptoms, such as 
fluctuating vision with blinking, blurred vision, and difficulty with reading despite adequate 
visual acuity (VA), are an important and underestimated aspect of the disease. Therefore, DED 
negatively impacts quality of life comparably to other severe diseases,3 and adverse effects on 
mental health including depression and anxiety have been observed.4 Dry eye disease is a 
serious and chronic disorder that, if left untreated or undertreated, progressively damages the 
ocular surface and may lead to permanent vision loss due to corneal complications.5 
Miebo™ is a sterile ophthalmic eye drop formulation, approved for the treatment of the signs 
and symptoms of DED associated with meibomian gland dysfunction (MGD). It is a single-
component product consisting of 100% perfluorohexyloctane. Miebo addresses DED 
associated with MGD via a new physicochemical mode of action. Due to its low surface 
tension, it rapidly spreads across the ocular surface and interacts with the lipophilic part of the 
tear film forming a layer at the tear film air interface. Such a layer prevents excessive 
evaporation of the aqueous tear film component. In addition, perfluorohexyloctane penetrates 
meibomian glands, where it potentially interacts with and dissolves the altered, viscous 
meibum secreted in the glands. As a water-free, single-component product, it is free of 
excipients like oils, surfactants, and preservatives. Related advantages include convenient 
handling, improved tolerability, and a decrease in the visual disturbance upon instillations. Due 
to this mode of action, subjects with DED associated with MGD were considered to experience 
the greatest benefit from the treatment.1  
 
 
 
 
 
 
 
 
 
 
This Phase 4 study is designed to evaluate early Miebo treatment perception and satisfaction 
in subjects with DED.  
In lieu of an Investigator’s Brochure, the Investigator is referred to the Miebo prescribing 
information for risk and benefit details (see Appendix D).1 

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5 Study Objectives and Purpose 
5.1 
Objectives 
The primary objective of the study is to evaluate early outcomes with Miebo treatment in 
subjects with DED.  
5.2 
Endpoints 
5.2.1 Efficacy   
The primary efficacy endpoint is the mean change from baseline (CFB) in dry eye symptom 
severity at Visit 3 (Day 7 ± 1 day). 
 
 
 
 
 
 
  
 
 
  
 
 
  
 
 
 
 
 
5.2.2 Safety 
The safety outcomes are as follows: 
 Adverse events (AEs; reported, elicited, and observed) 
 Visual acuity 
6 Investigational Plan 
6.1 
Overall Study Design and Plan: Description 
This single-arm, open-label, multicenter, prospective study will consist of 4 study visits in 
subjects with DED. Subjects who sign the informed consent form (ICF) at the 
Screening/Baseline Visit (Visit 1; Day 1) will be enrolled in the study and screened for 
eligibility to participate in the study.  Subjects will be asked to complete an Early  Outcomes  
Survey -  Baseline Visit 1 (Pre-dosing) to obtain baseline data at the start of Visit 1, after Ocular 
Surface Disease Index Questionnaire administration. Following subjects’confirmation of 
eligibility and at least 15 minutes after the completion of Schirmer’s test , site staff will instill 
the first dose of Miebo and dispense Miebo to subjects. Subjects will then complete 2 additional 
Early Outcomes  Surveys - Baseline Visit 1 (Post-dosing) at 5 minutes and 1 hour post-dose. 

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Subjects will then commence at-home treatment with Miebo 4 times daily (QID) bilaterally 
and will continue this for approximately 14 days. At Visits 2, 3, and 4 (Days 3, 7, and 14, 
respectively), subjects will complete 1 Early Outcomes Survey - Follow-up Visit in the clinic 
at least 30 minutes and no longer than 4 hours post-dose.  
6.2 
Investigators 
The study will be conducted in up to 8 investigative sites in the United States (US).  
The study will be conducted by Investigators who are determined by the Sponsor to be suitably 
qualified by training and experience to conduct this study in compliance with Good Clinical 
Practice (GCP) and US Food and Drug Administration (FDA) Federal Regulations or local 
regulations and who are willing to demonstrate use of Miebo, if they have not already done so. 
Additionally, the Investigator Agreement (on file for each site) also verifies Investigator 
obligations.  
In the event that selected sites do not meet expected enrollment rates, the Sponsor may decide 
to increase enrollment as needed at other currently active sites, replace non-enrolling sites, 
and/or add additional site(s), to satisfy study enrollment requirements.  
6.3 
Subject Duration 
Eligible subjects who are enrolled in this study will be followed for approximately 14 days 
following initiation of study treatment. 
6.4 
Study Duration 
The entire duration of the study (from first subject first visit to last subject last visit) is expected 
to take approximately 5 months. 
7 Selection and Withdrawal of Subjects 
Approximately 100 subjects at up to 8 clinical sites in the US will be enrolled and treated with 
Miebo in this clinical study.  
The study purpose, procedures, and subject responsibilities will be explained to the subject. 
The subject’s willingness and ability to meet the follow-up requirements will be determined. 
When it has been established that the subject is willing to participate, written informed consent 
will be obtained (Section 14.3). In order to determine eligibility, written informed consent must 
be obtained from each subject prior to performing any study-specific procedures that are not 
part of the Investigator’s routine standard of care. An ophthalmic examination will be done at 
the Screening/Baseline Visit on Day 1. 
Subjects will be eligible to participate in this trial if they meet all of the following inclusion 
criteria and none of the following exclusion criteria. 
7.1 
Subject Inclusion Criteria 
This study will include subjects who meet all of the following inclusion criteria: 
1. At least 18 years of age at the time of consent 
2. Able to provide written voluntary informed consent 

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3. The same eye must satisfy the below inclusion criteria (a–e): 
a. Subject-reported history of DED in at least 1 eye for at least 6 months prior to Visit 1 
b. Tear film break-up time (TBUT) ≤5 seconds at Visit 1 
c. Total corneal fluorescein staining (CFS) score ≥4 and ≤11 (ie, sum of inferior, 
superior, central, nasal, and temporal) according to the National Eye Institute (NEI) 
scale at Visit 1 
d. Total MGD score ≥3 (range, 0–15) 
e. Unanesthetized Schirmer’s test I score ≥5 mm 
4. Ocular Surface Disease Index ≥25 at Visit 1 
5. Able and willing to follow instructions, including participation in all trial assessments 
and visits 
7.2 
Subject Exclusion Criteria 
This study will exclude subjects who meet any of the following exclusion criteria (Note: Ocular 
exclusion criteria are relevant to both eyes, such that meeting a criterion in either eye excludes 
the subject from the study): 
1. Had received Miebo as a prescription or as a study treatment in previous Miebo clinical 
studies  
2. Have any clinically significant ocular surface slit-lamp findings at Visit 1 and/or, in the 
opinion of the Investigator, have any findings that could interfere with trial parameters, 
including:  
a. History of eye trauma  
b. History of Stevens-Johnson syndrome 
c. Active blepharitis or lid margin inflammation  
d. Dry eye disease secondary to scarring, irradiation, alkali burns, cicatricial 
pemphigoid, or destruction of conjunctival goblet cells (as with vitamin A 
deficiency) 
e. Abnormal lid anatomy causing incomplete eyelid closure  
f. Abnormal cornea shape (keratoconus) 
g. Corneal epithelial defect or significant confluent staining or filaments 
h. History of herpetic keratitis  
i. Pterygium  
j. Ocular or periocular rosacea 
3. Use of any of the following ocular therapies within 60 days prior to Visit 1: Vuity®, 
any topical ocular steroid treatments, prescription dry eye therapy including varenicline 
nasal spray, or topical anti-glaucoma medication  

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4. Had a LipiFlow® procedure, intense pulse light procedure, or any kind of other 
procedure affecting meibomian glands within 6 months prior to Visit 1 
5. Had received or removed a permanent punctum plug within 3 months (6 months for 
dissolvable plugs) prior to Visit 1 
6. Use of any eye drops (prescription or over-the-counter, such as artificial tears or 
Lumify®) and/or TrueTearTM device (intranasal tear neurostimulator) within 24 hours 
prior to Visit 1 
7. Have active ocular allergies or ocular allergies that are expected to be active during the 
trial period 
8. Have worn contact lenses within 1 month prior to Visit 1 or planned wear during the 
study 
9. Have undergone intraocular surgery or ocular laser surgery within 3 months prior to 
Visit 1; have undergone refractive surgery within 2 years prior to Visit 1 
10. Have active ocular or systemic infection (bacterial, viral, or fungal), including fever 
11. Female subjects who are pregnant, nursing, or planning a pregnancy 
12. Female subjects of childbearing potential who are not using an acceptable means of 
birth control; acceptable methods of contraception include hormonal (oral, implantable, 
injectable, or transdermal) contraception; mechanical (spermicide in conjunction with 
a barrier such as a diaphragm or condom) contraception; intrauterine device; or surgical 
sterilization of partner. For non–sexually active female subjects, abstinence may be 
regarded as an adequate method of birth control; however, if the subject becomes 
sexually active during the trial, she must agree to use adequate birth control as defined 
above for the remainder of the trial 
13. Have an uncontrolled systemic disease that, in the opinion of the Investigator, will 
interfere with the trial 
14. Have a known allergy and/or sensitivity to the study treatment 
15. Use of any oral medications known to cause ocular drying (eg, antihistamines, 
antidepressants, etc.) on a non-stable regimen within 1 month prior to Visit 1 or is 
expected to be unstable during the trial 
16. Have taken isotretinoin (eg, Accutane, Myorisan, Claravis, Amnesteem) within 
6 months prior to Visit 1 
17. Have corrected VA worse than or equal to +0.7 logarithm of the minimum angle of 
resolution (logMAR), as assessed with Snellen chart at Visit 1 
18. Are currently enrolled in an investigational drug or device study or had used an 
investigational drug or device within 60 days prior to Visit 1  

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7.3 
Subject Disposition Criteria 
7.3.1 
Subject Enrollment 
The subject is considered enrolled in the study after signing the ICF at the Screening/Baseline 
Visit (Visit 1).  
7.3.2 
Subject Screen Failures 
A subject who fails to meet eligibility criteria will be considered a screen failure.  
7.3.3 
Subject Completion 
For those subjects who are eligible and have consented to participate, Visit 4 will be the final 
visit to complete their participation.  
A subject who has missed visits or is missing study measurements will remain in the study. 
Subjects who require further follow-up for an AE will be followed according to Section 11.3.5.  
7.3.4 
Subject Discontinuation 
A subject MUST be discontinued prior to the final study visit for any of the following reasons: 
 Voluntary withdrawal  
 Death  
 Investigator decision that it is not in the best medical interest of the subject to continue 
participation in the study 
A subject MAY be discontinued (at the discretion of the Investigator, the Sponsor, and/or the 
Institutional Review Board [IRB]) prior to the final study visit for several reasons, including 
but not limited to:  
 Serious adverse event (SAE) and/or AE occurring during the course of the study that 
precludes continued follow-up  
 Noncompliance with required study procedures 
 Occurrence of a relevant exclusion criterion 
Prior to discontinuing a subject from the study, every effort should be made to contact the 
subject, schedule a final study visit, and obtain as much follow-up data as possible. Whenever 
possible, subjects who have discontinued study treatment should be followed through the last 
scheduled study visit. Ongoing AEs will be followed as described in Section 11.3.5. Subject 
withdrawals will be documented clearly on the source document and applicable Case Report 
Form (CRF). Subjects who discontinue from the study should be seen for routinely scheduled 
visits according to the standard of care by the Investigator or their ophthalmologist. 
Notification of subject withdrawals will be made immediately to the Sponsor.  
7.3.5 
Lost to Follow-Up 
Subjects who do not return for scheduled visits, as defined by the visit window, and cannot be 
contacted may be considered lost to follow-up. The Investigator will try at least twice to reach 
the subject by telephone and/or email and will send a follow-up letter by certified mail before 

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considering the subject lost to follow-up. All follow-up attempts will be documented and kept 
with the subject’s source documentation, and the applicable CRFs will be completed. The date 
a subject will be considered lost to follow-up will be the date of the last completed visit.  
Efforts shall be made to keep the number of subjects lost to follow-up to a minimum, below 
10% of the number of subjects treated.  
8 Treatment Plan 
8.1 
Methods of Assigning Subjects to Treatment Groups 
Approximately 100 subjects will receive Miebo (this is a single-arm study). 
8.1.1 
Treatment Allocation 
All subjects will receive Miebo QID bilaterally for approximately 14 days.  
8.1.2 
Randomization Method 
Not applicable; this is a single-arm study. 
8.2 
Masking  
Not applicable; this is an open-label study. 
8.3 
Concomitant Medications and Treatments 
Documentation of all medications and ocular therapies used by the subject within 30 days of 
informed consent and during the study will be made in study source documents.  
Use of any topical ocular therapies, either prescription or over-the-counter, are prohibited 
during the course of the study. Contact lens wear during the study is prohibited. 
8.4 
Protocol Deviations  
A deviation from the protocol is an unintended and/or unanticipated departure from the 
procedures and/or processes approved by the Sponsor and the IRB and agreed to by the 
Investigator.  
The Investigator or designee must document and explain in the subjects’ source documentation 
any deviation from the approved protocol. Protocol waivers will not be allowed under any 
circumstances. The Investigator may implement a deviation from, or a change of, the protocol 
to eliminate an immediate hazard to study subjects without prior IRB approval. As soon as 
possible after such an occurrence, the implemented deviation or change, the reasons for it, and 
any proposed protocol amendment(s) should be submitted to the IRB for review and approval, 
to the Sponsor for agreement, and to the regulatory authorities, if required. 
Deviation impact on data analysis is described in Section 12.6.3.2. The date of and reason for 
deviations in all cases will be documented. Protocol deviations affecting the safety of the 
subject or the integrity of the study must be reported promptly by the Investigator to the IRB. 
Reporting of all other protocol deviations must adhere to the requirements of the governing 
IRB.  

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Protocol assessments will continue for a subject until the end of the study, unless the protocol 
deviation puts the subject at risk or the subject’s condition requires that he/she be discontinued 
from the study.  
Scheduled assessments missed or conducted out of window due to Coronavirus Disease 2019 
(COVID-19) disruption will be recorded as protocol deviations. 
9 Study Materials and Management 
9.1 
Description of Study Treatment and Intended Use 
Miebo (100% perfluorohexyloctane ophthalmic solution) is a semifluorinated alkane indicated 
for the treatment of the signs and symptoms of DED. Each multiple-dose bottle contains 3 mL 
of 100% perfluorohexyloctane, 1.338 g/mL, as a clear and colorless liquid. 
Miebo is manufactured for Bausch & Lomb Incorporated. 
9.2 
Packaging and Labeling 
9.2.1 Packaging  
To maintain product integrity and sterility, Miebo will be supplied in its original primary 
packaging container (bottle) as part of a kit (2 bottles per kit) and labeled per Section 9.2.2.  
9.2.2 Labeling  
Study treatment labeling will include the following information:  
 Protocol number 
 Kit number 
 Caution statement 
 Storage conditions 
 Name and address of the Sponsor 
9.3 
Storage of Study Treatment  
Study treatment will be stored at 15ºC to 25ºC (59–77ºF).  
9.4 
Directions for Use and Administration 
Miebo will be used according to the Miebo prescribing information (Appendix E). 
9.5 
Study Treatment Accountability 
A dedicated team member at each site will be responsible for keeping current and accurate 
records of the study treatment received and dispensed and its disposition. Study treatment must 
be stored under the appropriate conditions in a secure area and is to be used only by subjects 
enrolled in the study, in accordance with the conditions specified in this protocol. During the 
course of the study, the dedicated team member must maintain an inventory of all study 
treatment, including subject identifiers.  

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 Demographics 
 Medical/Surgical history 
 Urine pregnancy test (for female subjects of childbearing potential) 
 Previous/Concomitant medication 
 
 
 
 
 Visual acuity 
 Tear film break-up time 
 Total CFS score 
 Meibomian gland dysfunction (MGD score) 
 Schirmer’s test 
 Inclusion/Exclusion criteria 
 
Following subject’s confirmation of eligibility, the following will take place starting from at 
least 15 minutes after the completion of Schirmer’s test: 
 Instillation of study treatment (instilled bilaterally by site staff) 
 
  
 Dispensation of study treatment 
 Dispensation of dosing diary 
 Adverse event query 
10.1.2 
Visit 2: Day 3 + 1 day 
The following study measurements will be collected: 
 Concomitant medication 
 Adverse event query 
 Early  Outcomes  Survey – Follow-up Visit 
 Dosing diary review by dedicated team member 
10.1.3 
Visit 3: Day 7 ± 1 day 
The following study measurements will be collected: 
 Concomitant medication 
 Adverse event query 

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 
  
 Dosing diary review by dedicated team member 
10.1.4 
Visit 4: Day 14 ± 2 days 
The following study measurements will be collected:  
 Concomitant medication 
 Adverse event query 
 
  
 
 
 Visual acuity  
 Dosing diary review by dedicated team member 
 Collection of study treatment and dosing diary 
 Trial exit 
10.1.5 
Unscheduled Visit(s) 
Additional visits may be scheduled, as necessary, to ensure the safety and well-being of 
subjects. All additional examinations should be fully documented in the source documents and 
on Unscheduled Visit CRFs, as appropriate. Visits intended to fulfill scheduled visit 
requirements that fall outside the designated scheduled visit window will be collected and 
transcribed to the appropriate visit CRF.  
If a subject is seen for multiple visits during a given visit timeframe, the data from the visit 
that are intended to meet the protocol requirements for the scheduled visit will be captured on 
the visit CRF. Where such a determination cannot be made, the first visit within the scheduled 
visit interval will be used for completion of the protocol-required scheduled visit CRF. Data 
from any additional visits within a scheduled visit interval will be captured on an Unscheduled 
Visit CRF. 
10.1.6 
Missed Visits 
If a subject misses any scheduled follow-up visit and cannot be seen prior to the start of the 
visit range for the next scheduled follow-up visit, the visit is considered missed.  
10.1.7 
Post-Study Follow-Up 
If a subject requires further follow-up upon discontinuation or completion of the study, the 
Investigator should schedule post-study follow-up visits, as necessary. Refer to Section 11.3.5 
for follow-up of AEs following study exit. 
10.2 Study Completion 
The Sponsor or its representative will notify the Investigator or the IRB, as applicable, to 
inform them when the study is complete (last subject last visit). 

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10.2.1 
Early Study Termination 
If during the study it becomes evident to the Sponsor that the study should be stopped 
prematurely, the study will be terminated and appropriate notification will be given to the 
Investigators, IRB, and FDA or Local Health Authority, as applicable. The Sponsor or its 
representative will instruct the Investigators to stop enrolling and dispensing study 
materials/treatment and to arrange for study closeout at each site as appropriate. 
11 Primary and Secondary Safety and Efficacy Variables 
11.1 Evaluation of Efficacy  
Efficacy will be evaluated using the following assessments: 
 
 
 
 
11.2 Evaluation of Safety 
Safety will be evaluated using the following assessments: 
 Adverse events 
 Visual acuity 
11.3 Adverse Events 
Both eyes must be examined for the presence/absence of AEs at all visits, whether scheduled 
or not. If an AE occurs, the first concern will be the safety and welfare of the subject; treatment 
should be provided as appropriate for the event.  
11.3.1 
 Adverse Events Definitions 
For the purposes of this study, AEs include all ocular AEs/SAEs, and all non-ocular SAEs. 
Adverse events and SAEs are defined as follows. 
An AE is any untoward medical occurrence, unintended disease or injury, or untoward clinical 
sign (including abnormal laboratory finding) in a subject, user, or other persons, whether or 
not related to the study treatment. For users or other persons, this definition is restricted to 
events related to the study treatment. 
An SAE is an AE that leads to one or more of the following:  
 Death 
 A life-threatening illness or injury 
 A permanent or significant disability/impairment of a body structure or body function 
(eg, blindness) 
 In-patient or prolonged hospitalization 
 Medical or surgical intervention to prevent life- or vision-threatening illness or injury 
or permanent impairment to a body structure or a body function  

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 Fetal distress, fetal death, or a congenital abnormality or birth defect  
11.3.2 
Identification and Collection 
Identification and collection of an AE begins after informed consent has been obtained and 
documented. Standard sources of identifying AEs include:  
 
Direct observation by the Investigator  
 
Asking the study participant a non-specific question (eg, “Have you had any problems 
since the last visit?”)  
 
Unsolicited volunteering of information by the study participant (eg, “Doctor, I have 
had blurred vision since I started using this lens.”)  
 
Test results that meet protocol requirements for classification as an AE  
Specific to this protocol, ocular AEs and all SAEs (ocular and non-ocular) observed or elicited 
by the Investigator, reported by the subject, or resulting from a test result, etc., occurring during 
the clinical study must be reported on the CRF. During the study, the Investigator should treat 
the study subject as appropriate to ensure his/her safety and welfare. Refer to Section 11.3.5 
for additional information pertaining to ongoing AEs at subject exit.  
Pre-existing conditions will not be considered AEs but will be collected at the 
Screening/Baseline Visit as medical history. A worsening of a pre-existing condition during 
the study should be documented as an AE and evaluated accordingly.  
Hospitalizations for admission without a medical AE should be captured as an SAE until the 
cause of hospitalization can be identified. However, the following reports of hospitalization 
without a medical AE should not be considered either serious or an AE: 
 Admission for treatment of a pre-existing condition not associated with the 
development of a new AE or with worsening of the pre-existing condition (eg, for 
work-up of persistent pretreatment lab abnormality)  
 Social admission (eg, subject has no place to sleep)  
 Administrative admission (eg, for yearly physical exam)  
 Optional admission not associated with a precipitating medical AE (eg, for elective 
cosmetic surgery)  
11.3.3 
Evaluations 
When evaluating AEs, the Investigator must determine if the event is serious (refer to 
Section 11.3.1 for criteria), assess the severity of symptoms, and determine the relationship of 
the event to study treatment, using the following guidelines:  
Severity  
 Mild: Subject awareness of a sign or symptom that is easily tolerated, requires no 
treatment, and does not interfere with subject’s daily activities  
 Moderate: Subject awareness of a sign or symptom which may be a low level of 
concern to the subject and may interfere with daily activities, but can be relieved by 
simple therapeutic care  

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 Severe: A sign or symptom that interrupts the subject’s daily activity and requires 
systemic therapy or other treatment 
Relationship to Study Treatment 
 Related: There is at least a reasonable possibility the AE is related to the study 
treatment. Reasonable possibility means there is evidence to suggest either a causal 
relationship or association between the study treatment and the AE  
 Not related: There is little or no reasonable possibility the AE is related to the study 
treatment. No reasonable possibility means there is no evidence to suggest either a 
causal relationship or association between the study treatment and the AE 
11.3.4 
Reporting 
Actions required by Investigators for reporting non-serious ocular AEs are to record them on 
AE CRFs only. Neither expedited report to the Sponsor nor report to the IRB is required for 
non-serious AEs. 
Any SAE must be reported to the Sponsor/Contract Research Organization (CRO), 
independent of the circumstance or suspected cause, within 24 hours from the time the event 
was reported to the Investigator. All SAEs experienced between the date of consent and 
30 days after the last administered dose of study treatment must be reported to the 
Sponsor/CRO regardless of the relationship to the study treatment or protocol. For events 
occurring beyond the 30-day period after the last administration of study treatment or for any 
timeframe greater than 30 days deemed medically significant, only SAEs considered related to 
the study treatment should be reported promptly to the Sponsor/CRO. 
Within 24 hours of notification, the Investigator will fax or email a completed SAE Form to 
the Sponsor and CRO contact listed below. For SAEs with fatal outcomes, a summary of 
available autopsy findings should be submitted as soon as possible.  
Care should be taken to ensure that the subject's identity is protected (personal identifiers are 
redacted), and the date and subject identifier in the clinical study (ie, subject number) are 
clearly visible on every page/copy of source document provided to the Sponsor. For laboratory 
results, the laboratory normal ranges should be included. 
Investigators should not wait to receive additional information before notifying the 
Sponsor/CRO of an SAE. If only limited information is initially available, follow-up reports 
are required. 
The Investigator will notify their IRB in writing of any SAE in accordance with the IRB 
requirements. Sponsor or its designee will be responsible for submitting SAE reports to 
regulatory authorities based on applicable regulations. The CRO will be responsible to send a 
notification to all participating Investigators of any SAE that is unexpected and associated with 
the study. If the Investigator becomes aware of any new information regarding an SAE (eg, 
resolution, change in condition, or new treatment), a new SAE Form must be completed and 
faxed/emailed to the Sponsor/CRO within 24 hours. The original SAE Form is not to be altered. 
The report should be marked as a “follow-up report” and should describe whether the event 
has resolved or continues and how the event was treated.  

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Serious AEs that have previously been reported and that continue after the subject’s 
discontinuation or completion of the study will be followed until their medical endpoints are 
determined or until no further change in the conditions is expected. The events and endpoints 
will be reported in writing by the Investigator to the CRO. Following the subject's 
discontinuation or completion of the study, for any timeframe thereafter deemed medically 
significant, any SAEs that are assessed as causally related to study treatment should also be 
reported to the Sponsor/CRO.  
The contacts for reporting SAEs are: 
 
 
 
Contact information for the CRO will be provided on the SAE Form.  
11.3.5 
Adverse Events at Subject Exit 
Ongoing AEs will be followed until resolution, until no further change in the condition is 
expected (ie, event stabilized), or as dictated by standard of care. Documentation on the CRF 
of this follow-up is not required, although subject care should continue as appropriate.  
11.3.6 
Pregnancy 
All female subjects of childbearing potential and male subjects with female partners of 
childbearing potential must use an effective method of birth control during the course of the 
study, in a manner such that risk of contraceptive failure is minimized. 
Before enrolling a female subject of childbearing potential or a male subject with a female 
partner of childbearing potential, the Investigator must review the following information about 
study participation: 
 Informed consent requirement 
 Contraceptives in current use 
By signing the ICF, the Investigator or designee asserts that he/she has discussed this 
information with the subject and provided appropriate counseling. Following the review of this 
information, the subject must sign the ICF to enroll in the study. 
During the study, all female subjects of childbearing potential should be instructed to contact 
the Investigator immediately if they suspect they might be pregnant (eg, missed or late 
menstrual period).  
If a subject or Investigator suspects that the subject may be pregnant prior to treatment, the 
study treatment must be withheld until the results of laboratory pregnancy testing are available. 
If pregnancy is confirmed, the subject is considered to be a screen failure, must not continue 
in the study, and must not receive study treatment. If pregnancy is suspected while the subject 
is receiving study treatment, the study treatment must immediately be withheld until the result 
of pregnancy testing is known. If pregnancy is confirmed, the study treatment will be 
permanently discontinued, and the subject and neonate will be followed until 30 days after the 
pregnancy comes to term. 

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Female subjects who become pregnant during the study will be followed until completion of 
pregnancy. Every effort will be made to obtain the health status of the mother and infant or 
fetus (in cases of miscarriage or therapeutic abortion) at term. Pregnancy itself is not 
considered an AE. 
All confirmed pregnancies must be immediately reported to the Medical Monitor, Sponsor, 
and CRO contact within 24 hours of the Investigator’s awareness of the pregnancy. All 
confirmed pregnancies must be reported via confirmed facsimile or email transmission and 
must be submitted on a Pregnancy Report Form to the Sponsor or designee within 24 hours of 
the Investigator’s awareness of the pregnancy. A Pregnancy Report Form will be submitted to 
the Sponsor, both when pregnancy is confirmed, and 30 days after the delivery date. 
Information provided on the Pregnancy Report Form must include the outcome of the 
pregnancy and any complications occurring during the pregnancy or the delivery. If a 
pregnancy is associated with an SAE, an SAE Form should also be submitted to the 
Sponsor/designee and Medical Monitor within 24 hours of the Investigator’s awareness. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
The contacts for reporting pregnancies are: 
 
 
 
Contact information for the CRO will be provided on the Pregnancy Report Form.  
12  Statistics 
12.1 Study Endpoints 
12.1.1 
Efficacy Endpoints 
 
12.1.2 
Safety Outcomes 
The safety outcomes are detailed in Section 5.2.2. 
12.2 Hypotheses 
The null hypothesis (H0) is that the mean difference between the dry eye symptom severity 
values on Day 7 and at baseline (µ) is equal to zero. The alternative hypothesis (H1) is that the 
mean difference is not equal to zero. 
𝐻଴: 𝜇= 0 
𝐻ଵ: 𝜇≠0 
12.3 Sample Size Determination 
A sample size of 75 subjects will have 80% power to detect a difference in means of 8.194, 
assuming a standard deviation of differences of 25, using a paired t-test with a 5% two-sided 

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significance level. To allow for dropouts of up to 25%, approximately 100 subjects will be 
treated. 
12.4 Analysis Populations 
Full Analysis Set (FAS): The FAS will consist of all subjects who receive at least 1 drop of 
study treatment. 
Per Protocol (PP) Set: The PP Set will consist of all subjects in the FAS with no protocol 
deviations expected to affect efficacy outcomes.  
12.5 Statistical Analysis 
12.5.1 
General Considerations 
Summaries for continuous variables will include the sample size (n), mean, standard deviation, 
median, minimum, and maximum. Summaries for categorical variables will include 
frequencies and percentages. Missing safety data will not be imputed. 
12.5.2 
Primary Effectiveness Analyses 
 
 
  
 
 
 
 
12.5.3 
Safety Analyses 
12.5.3.1 Adverse Events  
The number and percent of subjects with specific treatment-emergent adverse events (TEAEs) 
and the total number of occurrences of each TEAE will be summarized for the FAS. The 
number of subjects will be tabulated by Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class and preferred term within each system organ class.  
12.5.3.2 Subject Demographics and Baseline Characteristics 
Race, sex, and age groups will be presented using discrete summary statistics. Age will also 
be presented using continuous summary statistics. Medical history data will be presented in a 
listing. 
12.5.3.3 Prior and Concomitant Medications 
Concomitant medication use will be summarized using the number and percentage of subjects 
using each type of medication by drug class and preferred term. Ocular and non-ocular 
medications will be presented in separate tables. Prior medications will be included in a listing 
but not included in the concomitant medication summary. 

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12.5.3.4 Subject Disposition 
Subject disposition will be summarized using number and percentage of subjects. The reasons 
for study discontinuation will also be summarized.  
12.5.3.5 Treatment Adherence 
Treatment adherence will be computed as the number of doses administered divided by the 
number of doses expected × 100%. Adherence will be summarized using continuous and 
categorical (less than 80%, 80% to 120%, greater than 120%) summary statistics by treatment 
group.  
12.5.3.6 Treatment Exposure 
Duration of treatment exposure will be defined as the total number of days from treatment 
initiation until last dose date, as recorded at Visit 1 and the study exit CRF page. Duration of 
exposure to study treatment will be calculated as: 
Duration = date of last dose – date of treatment initiation + 1. 
12.6 Additional Statistical Considerations 
12.6.1 Handling of Missing Data 
Unless otherwise specified in the statistical analysis plan, missing data will not be imputed. 
12.6.2 Multicenter Issues 
Data will be collected from multiple sites under the same protocol with the intention of pooling 
the data.  
12.6.3 Multiplicity Issues 
No adjustment of the primary endpoint analysis for multiplicity is required. 
12.6.3.1 Interim Analysis 
No interim analysis is planned for this study. 
12.6.3.2 Protocol Deviations 
The number of subjects within each type of important protocol deviation will be presented 
using discrete summary statistics. Important protocol deviations will be identified prior to 
locking the database. 
13 Quality Control and Quality Assurance 
13.1 Study Monitoring 
The Sponsor and its representatives must be allowed to visit all study site locations to assess 
the data, quality, and study integrity in a manner consistent with applicable health authority 
regulations and the procedures adopted by the Sponsor or its representative. If due to 
unforeseen situations, access to study site locations may be restricted, remote monitoring 
methods may be implemented to ensure data quality and integrity, as per the monitoring plan. 

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Prior to the start of the study, member(s) of the Sponsor (or designees) will review the protocol, 
CRF, regulatory obligations, and other material or equipment relevant to the conduct of the 
study with the Investigator/sub-Investigator and relevant site personnel.  
Monitoring visits and telephone consultations will occur as necessary, as per the monitoring 
plan, during the course of the study to verify the following: 
 The rights and well-being of subjects are protected 
 The conduct of the study is in compliance with the currently approved 
protocol/amendment; 21 Code of Federal Regulations Parts 11, 50, 54, 56, 312, 314; 
42 USC 282(j); ICH GCP E6 (R2) (International Council for Harmonisation, Guidance 
E6); 42 USC 282(j); and IRB requirements 
 The integrity of the data, including adequate study documentation  
 The facilities remain acceptable 
 The Investigator and site personnel remain qualified and able to conduct the study 
 Study treatment accountability  
During the study, if the Sponsor (or designee) determines that an Investigator is noncompliant 
with the study plan and/or applicable regulatory requirements, the Sponsor (or designee) will 
take remediation action to secure compliance. In addition, the Sponsor may terminate the 
Investigator’s participation in the study, if appropriate, if the Investigator remains 
noncompliant despite the remediation actions. 
13.2 Source Documentation 
All medical information obtained at each study visit must be recorded in the subject’s record 
(source documentation) in real time as it is collected. Source documentation consists of original 
subject documents, as well as data and records with information relevant to the subject and 
his/her participation in the study.  
Source documentation worksheets may be provided by the Sponsor or its designee to record 
pertinent information. The completed worksheets can then be incorporated into the subject’s 
medical chart. If it is preferred not to use the worksheets in the subject’s permanent record, 
then the worksheets should be used as a reference to determine the type of study data to record 
in the subject’s permanent record. 
13.3 Case Report Forms and Data Verification 
As used in this protocol, the term CRF should be understood to refer to an electronic data 
record developed as part of the electronic data capture method utilized in this study. 
Subject data required by this protocol are to be recorded on CRFs. The Investigator and site 
personnel will be responsible for completing the CRFs in a timely manner. The Investigator is 
required to verify that all of the requested information is accurately recorded on the CRFs. All 
information requested on the CRFs needs to be supplied, including subject identification and 
initials, date(s), assessment values, etc., and any omission or discrepancy will require 
explanation. All information on CRFs must be traceable to source documents.  

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The study monitor will be responsible for reviewing and verifying the data recorded on the 
CRFs, utilizing the original or certified copies of all source documentation, and querying 
discrepant findings. 
The Investigator and site personnel will be responsible for answering all queries in a timely 
manner.  
13.4 Recording of Data and Retention of Documents 
Subject data recorded on CRFs during the study will be documented in a coded fashion. The 
subject will only be identified by the unique subject number. Confidentiality of subject records 
must be maintained to ensure adherence to applicable local privacy regulations.  
The Investigator must retain essential documents indefinitely after the completion of the study, 
unless otherwise notified by the Sponsor.  
Essential documents include but are not limited to the following: 
 Institutional Review Board approvals of the study protocol, all amendments, ICF(s), 
and advertisements  
 Institutional Review Board annual study review  
 Institutional Review Board correspondence and reports (eg, SAE reports, protocol 
deviations, and safety updates)  
 Regulatory documents (eg, financial disclosure and delegation of authority forms)  
 All source documents  
 Case Report Forms  
 Subjects’ signed ICFs  
 Principal Investigator Protocol Agreement Page  
 Accountability records for the study treatment  
 Correspondence from and to the Sponsor and CRO 
 Any other documents relevant to the conduct of the study  
In the event the Investigator withdraws from the study (eg, retirement or relocation), study 
records will be transferred to a mutually agreed-upon designee (eg, another Investigator or the 
site IRB). The Investigator will provide notice of such transfer in writing to the Sponsor and/or 
its representative. 
13.5 Audits and Inspections 
Audits of clinical research activities in accordance with the Sponsor’s internal Standard 
Operating Procedures to evaluate compliance with the principles of GCP may take place. A 
regulatory authority also may wish to conduct an inspection during the study or after its 
completion. If an inspection is requested by a regulatory authority and/or IRB, the Investigator 
must inform the Sponsor and its representative immediately that this request has been made. 

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14 Ethics and Administrative Issues 
It is the responsibility of the site’s Principal Investigator to assure that all aspects of the ethics 
review are conducted in accordance with ICH GCP E6 (R2). The protocol and any information 
supplied to the subject to obtain informed consent, including written ICFs, subject recruitment 
procedures (eg, advertisements), and written information to be provided to subjects (eg, 
information leaflets), will be reviewed and approved by a qualified IRB prior to enrollment of 
participants in the study. Prior to initiation of the study and release of study treatment to a 
clinical site, the Sponsor or its designee will receive documentation of the IRB approval, which 
specifically identifies the approved study/protocol and a list of the IRB committee members. 
Protocol amendments will be reviewed and approved by the IRB prior to implementation of 
any changes made to the study design in the amendment. Investigators will submit progress 
reports to the IRB in accordance with the IRB requirements. 
14.1 Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol and GCP, applicable regulations 
and guidelines governing clinical study conduct, and the ethical principles that have their origin 
in the Declaration of Helsinki. 
14.2 Ethics Review 
The Investigator should ensure his/her participation in the study, the protocol, subject 
recruitment materials (eg, written information or materials including web pages, radio 
advertisements, television spots, or written text developed to encourage subject enrollment), 
and the ICF to be used in this study are approved by his/her institution’s IRB, or, if not using 
his/her institution’s IRB, by the reviewing central IRB prior to entering any subjects in the 
study. Documentation of IRB approval of the study protocol and informed consent must be 
provided to the Sponsor and any designee prior to initiation of the study. In addition, the 
Investigator must ensure that the reviewing IRB has provided approval for any protocol 
amendments prior to their implementation. If the amendment necessitates a revision to the ICF, 
the Investigator should ensure the revised form is also submitted to and approved by the 
Sponsor or its designee and the IRB prior to its implementation.  
14.3 Written Informed Consent 
Before entry into the study, the Investigator or an authorized member of the site personnel will 
explain to potential subjects the aims, methods, reasonably anticipated benefits and potential 
hazards of the study, and any discomfort it may entail. The subject will be given sufficient time 
to read the ICF and the opportunity to ask questions. After this explanation and before entry 
into the study, consent will be appropriately recorded by means of either the subject’s dated 
signature. After having obtained the consent, a copy of the signed and dated ICF will be given 
to the subject. 
The ICF will be signed before the performance of any study-related activity.  
14.4 Financial Disclosure, Clinical Trial Agreements, and Site Contact Information 
An original financial disclosure form (FDF) must be completed, signed, and dated by the 
Investigator and any sub-Investigators and study personnel listed on the Delegation of 

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Authority Log. All FDFs will be collected by the Sponsor or its designee and filed in the study 
Trial Master File. A copy of all FDFs will be retained in the Investigator Site Binder. All 
contractual and financial agreements between clinical sites and the Sponsor will be 
administrated by the CRO as designated by the Sponsor and approved at a minimum by both 
Investigators and the Sponsor in writing. Indemnification information is included in 
contractual agreements with sites. 
14.5 Confidentiality/Publication of the Study 
All study data generated as a result of this study will be regarded as confidential until 
appropriate analysis and review by the Sponsor or its designee and the Investigator(s) are 
completed. The results of the study may be published or presented by the Investigator(s) after 
the review by, and in consultation and agreement with, the Sponsor, and such that confidential 
or proprietary information is not disclosed.  
Prior to any publication or presentation, a copy of the final text should be forwarded by the 
Investigator(s) to the Sponsor or its designee, for comment. Such comments shall aim to ensure 
the scientific integrity of the proposed publications and/or presentations and ensure that the 
data and material referring to Bausch & Lomb Incorporated products and activities receive fair, 
accurate, and reasonable presentation.  
15 References 
1. Miebo [prescribing information]. Bridgewater, NJ: Bausch & Lomb Incorporated; May 
2023. 
2. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and Classification 
Report. Ocul Surf. 2017;15:276–283. 
3. Schiffman RM, Walt JG, Jacobsen G, Doyle JJ, Lebovics G, Sumner W. Utility 
Assessment among patients with dry eye disease. Ophthalmology. 2003;110:1412–
1419. 
4. Le Q, Zhou X, Ge L, Wu L, Hong J, Xu J. Impact of dry eye syndrome on vision-
related quality of life in a non-clinic-based general population. BMC Ophthalmol. 
2012;12(22):1–8 
5. Lemp M. Report of the National Eye Institute/Industry Workshop on Clinical Trials in 
Dry Eyes. CLAO J. 1995;21(4):221–232.  
6. Tauber J, Berdy GJ, Wirta DL, Krösser S, Vittitow JL; GOBI Study Group. NOV03 
for dry eye disease associated with meibomian gland dysfunction: results of the 
randomized phase 3 GOBI study. Ophthalmology. 2023;130(5):516–524.  
7. Sheppard JD, Kurata F, Epitropoulos AT, Krösser S, Vittitow JL; MOJAVE Study 
Group. NOV03 for signs and symptoms of dry eye disease associated with meibomian 
gland dysfunction: the randomized phase 3 MOJAVE study. Am J Ophthalmol. 
2023;252:265–274.  
8. Tauber J, Wirta DL, Sall K, et al; SEECASE study group. A randomized clinical study 
(SEECASE) to assess efficacy, safety, and tolerability of NOV03 for treatment of dry 
eye disease. Cornea. 2021;40(9):1132-1140.  

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9. Protzko E, Segal B, Korenfeld M, Krösser S, Vittitow J. Long-term safety and efficacy 
of perfluorohexyloctane ophthalmic solution for the treatment of patients with dry eye 
disease: the KALAHARI study. Cornea. 2023 Nov 3. Epub ahead of print.  

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16.2 Appendix B  Methods of Clinical Evaluations 
Any changes to the procedures described in this appendix will be provided under separate 
cover. 
 
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 

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16.5 Appendix E  Miebo Prescribing Information 
 
 
 

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