A Prospective Evaluation of Infraorbital Filler Injection
Phase: NA
Conditions: Dermal Filler, Rejuvenation
Sponsor: University of Pennsylvania

Infraorbital Filler Study 
 
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This material is the property of the University of Pennsylvania.   
 
 
 
A Prospective Evaluation of Infraorbital Filler 
 
 
 
Study Product 
JUVÉDERM® VOLBELLA® XC 
Protocol Number IRB Number 
852212 
 
 
Clinicaltrials.gov NCT05694286 
 
 
Initial version [11.21.2022] 
Amended 
[Date] 
Amended 
[Date] 

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Table of Contents 
BACKGROUND AND STUDY RATIONALE ......................................................................................... 5 
1 
INTRODUCTION ................................................................................................................................ 5 
1.1 
BACKGROUND AND RELEVANT LITERATURE .................................................................................. 5 
2 
STUDY OBJECTIVES ........................................................................................................................ 6 
2.1 
PRIMARY OBJECTIVE ....................................................................................................................... 6 
3 
INVESTIGATIONAL PLAN .............................................................................................................. 6 
3.1 
GENERAL DESIGN ........................................................................................................................... 6 
3.2 
ALLOCATION TO INTERVENTIONAL GROUP ..................................................................................... 6 
3.3 
STUDY MEASURES .......................................................................................................................... 6 
3.4 
STUDY ENDPOINTS .......................................................................................................................... 6 
3.4.1 Primary Study Endpoint ............................................................................................................. 6 
3.4.2 Secondary Study Endpoints ........................................................................................................ 7 
4 
STUDY POPULATION AND DURATION OF PARTICIPATION .............................................. 8 
4.1 
DURATION OF STUDY PARTICIPATION ............................................................................................. 8 
4.2 
TOTAL NUMBER OF SUBJECTS AND SITES ....................................................................................... 8 
4.3 
INCLUSION CRITERIA ...................................................................................................................... 8 
4.4 
EXCLUSION CRITERIA ..................................................................................................................... 8 
4.5 
SUBJECT RECRUITMENT .................................................................................................................. 8 
4.6 
VULNERABLE POPULATIONS: .......................................................................................................... 8 
5 
STUDY PROCEDURES ...................................................................................................................... 8 
5.1 
SCREENING ..................................................................................................................................... 8 
5.2 
STUDY INTERVENTION OR OBSERVATIONAL PHASE ........................................................................ 9 
RANDOMIZED CONTROLLED SINGLE BLINDED STUDY ........................ ERROR! BOOKMARK NOT DEFINED. 
5.2.1 Visit 1 (sometimes referred to as the baseline visit) .................................................................. 9 
5.2.2 Visit 2 ......................................................................................................................................... 9 
5.2.3 Visit 3 ......................................................................................................................................... 9 
5.2.4 End of Study Visit 4 .................................................................................................................... 9 
TABLE 1  SCHEDULE OF STUDY PROCEDURES ............................................................................. 9 
5.3 
UNSCHEDULED VISITS .................................................................................................................. 10 
5.4 
SUBJECT WITHDRAWAL ................................................................................................................ 10 
5.4.1 Data Collection and Follow-up for Withdrawn Subjects ......................................................... 10 
5.5 
EARLY TERMINATION VISITS ........................................................................................................ 10 
6 
STATISTICAL PLAN ....................................................................................................................... 10 
6.1 
SAMPLE SIZE AND POWER DETERMINATION ................................................................................. 10 
6.2 
STATISTICAL METHODS ................................................................................................................ 10 
6.3 
CONTROL OF BIAS AND CONFOUNDING ......................................................................................... 10 
6.3.1 Baseline Data ........................................................................................................................... 10 
6.3.2 Analysis of Primary Outcome of Interest ................................................................................. 11 
7 
SAFETY AND ADVERSE EVENTS ............................................................................................... 11 

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7.1 
DEFINITIONS ................................................................................................................................. 11 
7.1.1 Adverse Event ........................................................................................................................... 11 
7.1.2 Serious Adverse Event .............................................................................................................. 11 
7.2 
RECORDING OF ADVERSE EVENTS ................................................................................................ 11 
7.3 
RELATIONSHIP OF AE TO STUDY ................................................................................................... 12 
7.4 
REPORTING OF ADVERSE EVENTS, ADVERSE DEVICE EFFECTS AND UNANTICIPATED PROBLEMS 12 
7.4.1 Follow-up report ...................................................................................................................... 12 
7.4.2 Investigator reporting: notifying the study sponsor ................................................................. 13 
7.4.3 Investigator reporting: notifying the Penn IRB ....................................................................... 13 
7.4.4 Sponsor reporting: Notifying Participating Investigators ....................................................... 13 
7.5 
MEDICAL MONITORING ................................................................................................................. 13 
7.6 
CONFIDENTIALITY ......................................................................................................................... 13 
7.7 
DATA COLLECTION AND MANAGEMENT ....................................................................................... 14 
7.8 
RECORDS RETENTION ..................................................................................................................... 14 
8 
STUDY MONITORING, AUDITING, AND INSPECTING ......................................................... 14 
8.1 
STUDY MONITORING PLAN ........................................................................................................... 14 
8.2 
AUDITING AND INSPECTING .......................................................................................................... 14 
9 
ETHICAL CONSIDERATIONS ...................................................................................................... 15 
9.1 
RISKS ............................................................................................................................................ 15 
9.2 
BENEFITS ...................................................................................................................................... 15 
9.3 
RISK BENEFIT ASSESSMENT .......................................................................................................... 16 
9.4 
INFORMED CONSENT PROCESS / HIPAA AUTHORIZATION ............................................................ 16 
10 STUDY FINANCES ........................................................................................................................... 16 
10.1 
FUNDING SOURCE ......................................................................................................................... 16 
10.2 
CONFLICT OF INTEREST ................................................................................................................. 16 
10.3 
SUBJECT STIPENDS OR PAYMENTS ................................................................................................ 16 
11 PUBLICATION PLAN ...................................................................................................................... 16 
12 REFERENCES ................................................................................................................................... 16 
13 ATTACHMENTS .............................................................................................................................. 17 
 

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Study Summary 
 
Title 
Prospective Evaluation of Infraorbital Filler 
Short Title 
Infraorbital Filler Study 
IRB Number 
TBD 
Protocol Number 
TBD 
Methodology 
Prospective Case Series / Descriptive Study  
Study Duration 
3 months  
Study Center(s) 
Single-center 
Objectives 
To quantify under eye volume changes over time and patient 
satisfaction with infraorbital dermal filler injections 
Number of Subjects Approximately 10 
Main Inclusion and 
Exclusion Criteria 
Inclusion criteria:  
1) Female  
2) Age 22-65 
3) Interested in filler injections to reduce undereye volume loss 
4) Participants must sign the informed consent form 
 
 
Exclusion:  
1) Prior filler in tear trough/midface 
2) Filler/neurotoxin injection within the past 12 months or during 
duration of study 
3) Prior facial cosmetic surgery (ie. facelift) 
4) Prior facial trauma (ie. orbital fracture) 
5) Pregnant or breastfeeding  

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Intervention  
 
Injection of Juvéderm Volbella XC into undereye/infraorbital region   
Statistical 
Methodology 
Descriptive statistics will be used to describe changes in volume over 
time and PRO’s 
Data and Safety 
Monitoring Plan  
PI: Dr. Ivona Percec will oversee the study, protocol, and data 
monitoring and storage.  
 
Background and Study Rationale 
1 
Introduction 
This study will be conducted in full accordance with all applicable University of Pennsylvania Research 
Policies and Procedures and all applicable Federal and state laws and regulations.  
 
The purpose of the study is to use 3D imaging to evaluate the effects of Juvéderm Volbella XC filler that 
is FDA approved for injection in infraorbital region. Participation is available to women ages 22 to 65 
who have never received filler injections. All subjects will undergo 3D imaging using the VECTRA M3 
(Canfield Scientific, Inc, Fairfield, NJ) prior to treatment with a Juvéderm filler in order to determine their 
baseline volumetric measurements and dimensions. Imaging will be repeated post injection to determine 
change over time (over a 3-month time period). 
 
1.1 
Background and Relevant Literature  
Juvéderm Volbella XC is a gel implant or dermal filler that consists of crosslinked hyaluronic acid made 
by a Streptococcal bacteria species intended to temporarily add fullness to the facial soft tissues. It was 
originally approved for injection into the lips for lip augmentation and correction of perioral rhytids. It has 
since been FDA-approved for injection into the undereye hollows to improve the appearance of undereye 
hollows in adults over the age of 21 [1]. 
 
The “Zoom Effect” describes the recent upsurge in demand for cosmetic procedures during the COVID-
19 pandemic. The reason for this appears to be that people are now constantly seeing their own and other 
faces on the screen, making them particularly conscious of potential facial irregularities, aging changes, 
and asymmetries. According to statistics from the Aesthetic Society, facial procedures have increased 
55% in 2021 [2]. Soft tissue filler injections are the 2nd most common non-surgical cosmetic procedure 
performed in the US and have increased 42% in 2021 [2,3].  
 
Undereye or infraorbital hollowing is a result of a loss of volume causing shadowing and darkness of the 
infraorbital region often interpreted as a tired, stressed, and aged appearance. The Allergan Infraorbital 
Hollows Scale is a validated scale for objective and reproducible comparisons of infraorbital hollows 

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before and after dermal filler injection [4]. The Tear Trough Rating Scale (TTRS) is another validated 
method of evaluating tear trough deformities that measures depth of trough, degree of hyperpigmentation, 
prolapse of nasal fat pads/pockets, and lower eyelid skin rhytidosis [6]. 3D photogrammetry technology 
allows for high level feature enhancement and microscopic anatomical evaluation that was not previously 
possible and can be used to make volumetric measurements at injection sites to evaluating minimally 
invasive injection efficacy. [7-9]. In this study, we aim to use these volumetric measurements to describe 
undereye volume after infraorbital dermal filler injection and further understand the behavior of the 
product in soft tissues over time.  
2 
Study Objectives 
2.1 
Primary Objective 
The primary objective of the study is to quantify and describe under eye volume changes over time after 
infraorbital hyaluronic acid filler injections. 
3 
Investigational Plan  
3.1 
General Design 
This study is a prospective case series/descriptive study – 10 patients will be enrolled to receive 
hyaluronic acid filler injections (Juvéderm Volbella XC). Each patient will receive FDA approved 
dosages of filler to the infraorbital region to treat undereye, as per FDA approved indications. All 
injections will be performed by an Allergan-trained physician (Ivona Percec, MD, PhD) according to a 
preset injection plan per FDA approved administration guidelines. Prior to injection patients will be 
imaged with 3-dimensional photogrammetry. Subjects will return post-injection in 2 weeks, 1 month, and 
3 months for re-imaging. The study drug will be stored in a locked room that is only accessible to the 
research team. 
3.2 
Allocation to Interventional Group 
All subjects will receive filler injections to the infraorbital region at standardized injection sites 
3.3 
Study Measures 
3D photogrammetry imaging of each subject at the pre-determined time points will be obtained using the 
VECTRA M3 (Canfield Scientific, Inc., Fairfield, NJ) which allows for volumetric measurements. Three-
dimensional coordinates will be calculated to generate each subject’s topographic configuration, 
displacement, and volume of each detected point on the surface of the face relative to its original 
reference image.  
3.4 
Study Endpoints  
3.4.1 
Primary Study Endpoint 
The primary endpoint is volume changes of the infraorbital area over time after injection of filler 
quantified using 3D facial imaging measurements.  
 
 
 
 
 

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3.4.2 
Secondary Study Endpoints 
1) Correlation of patient satisfaction with undereye volume changes as determined by PRO’s (via 
FACE-Q) 
2) Allergan Infraorbital Hollow Scale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3) Tear Trough Rating Scale  
 
 
 
 
 
 
 
 
 
 
 
 
 

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4 
Study Population and Duration of Participation  
4.1 
Duration of Study Participation  
The duration of study participation is 90 days. Subjects will receive injections on day 1, and follow up 
imaging will occur on day 14, 30, and 90 post intervention. Each individual subject’s participation time in 
the study will consist of the duration of the initial imaging session (approximately 20 minutes), procedure 
(15 minutes), follow up imaging (20 min). 
4.2 
Total Number of Subjects and Sites  
We anticipate about 10 patients from at a single location, the Hospital of the University of Pennsylvania.  
Subjects will include females, ages 22-65, who are interested in infraorbital filler injection (FDA 
approved use).  
4.3 
Inclusion Criteria 
Adult female subjects, ages 22-65, who are interested in infraorbital filler injection FDA approved use. 
Each participant will participate for 90 days.   
• Female 
• 22-65 years of age 
• Interested in filler injections to reduce undereye volume loss 
• Participants must sign the informed consent form  
4.4 Exclusion Criteria 
• Female under 22 or above 65 years of age 
• Male 
• Prior filler in tear trough/midface 
• Filler/neurotoxin injections within 12 months or during duration of study 
• Prior facial cosmetic surgery 
• Prior facial trauma (ie. orbital fracture) 
• Pregnant or breastfeeding  
4.5 
Subject Recruitment  
Patients will be recruited through the plastic surgery clinic, which is a high-volume practice for those who 
may be interested in cosmetic injections. Additionally, we plan to use of a flyer posted throughout the 
health system and campus. Filler injections to the infraorbital region to reduce undereye volume loss are a 
popular procedure and we do not anticipate significant difficulty in recruiting about 10 willing 
participants.  
4.6 
Vulnerable Populations:  
Children, pregnant women, fetuses, neonates, or prisoners are not included in this research study. 
5 
Study Procedures  
5.1 
Screening  
The screening visit involves patient evaluation of inclusion and exclusion criteria. This information is 
readily available on the intake visit and does not deviate from standard of care for a clinic visit, including 

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age and past medical history. Once patients are deemed eligible, the process of informed consent will 
begin. Informed consent will take place. 
5.2 
Study Intervention or Observational Phase  
5.2.1 
Visit 1 (sometimes referred to as the baseline visit)  
Visit 1 involves screening, consent, baseline imaging, randomization, intervention. The subject will be 
photographed using 3D imaging to measure baseline undereye volume. After these images, subjects will 
complete a FACE-Q questionnaire and then be injected with Juvéderm Volbella XC filler in the 
infraorbital region according to a preset injection plan per FDA approved administration guidelines. 
Medication will be prepared as described on the FDA approved medication guide. A second set of 3D 
images will be taken after filler injection to measure starting infraorbital volume.  
5.2.2 
Visit 2  
Visit 2 which will occur 14-days post-injection, will consist of a repeat of the above measurements using 
3D imaging. Subjects will also complete the FACE-Q via electronic REDCap survey and communicate 
any questions or concerns. 
5.2.3 
Visit 3  
Visit 3 which will occur 30-days post-injection, will consist of a repeat of the above measurements using 
3D imaging. Subjects will also complete the FACE-Q via electronic REDCap survey and communicate 
any questions or concerns. 
5.2.4 
Visit 4  
Visit 4 which will occur 90-days post-injection, will consist of a repeat of the above measurements using 
3D imaging. Subjects will also complete the FACE-Q via electronic REDCap survey and communicate 
any questions or concerns. 
TABLE 1  SCHEDULE OF STUDY PROCEDURES  
 
Baseline 
Visit 1 
Intervention 
 
Follow-up 
Visit  2 Day 14 
Follow-up Visit  3 
Day 30 
Follow-up Visit 4 
Day 90 
Visit Window 
Day 1 
Day 1 
Day 14 ± 5 
Day 30  ± 5 
Day 90 ± 7 
Eligibility 
X 
 
 
 
 
Informed Consent 
X 
 
 
 
 
Demographic 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
Consultation 
X 
 
 
 
 
Vectra Photography 
 
X  
(pre and post 
injection) 
X 
X 
X 

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FACE-Q 
 
X 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
 
5.3 
Unscheduled Visits 
Unscheduled visits will be handled on a case by case basis dependent upon the reasoning for the patients’ 
visit. If subjects are displaying signs of immediate danger or instability, they will be referred to 
emergency department or directly admitted. However, unscheduled visits are rare for this type of 
procedure.  
5.4 
Subject Withdrawal  
Subjects may withdraw from the study at any time without impact to their care.  They may also be 
discontinued from the study at the discretion of the Investigator.  Subjects may also be withdrawn 
following an adverse event that does not allow them to continue with the study. It will be documented 
whether or not each subject completes the study. Subjects who withdraw early will have one final 
communication to collect final evaluations and assess for adverse events.   
5.4.1 Data Collection and Follow-up for Withdrawn Subjects 
Patients must document in a letter asking not to use the data collected and formalize the withdrawal.  
Otherwise, data up until withdrawal will be available for analysis.   
5.5 
Early Termination Visits   
This may be due to the subjects’ own choice or the investigator’s decision. If the investigator makes the 
decision, subjects will be contacted and reasons for study termination will be thoroughly explained.  
6 
Statistical Plan 
6.1 
Sample Size and Power Determination 
The sample size of this case series will be 10 female patients between the ages 22 and 65.   
6.2 
Statistical Methods 
Descriptive statistics will be used to describe volume changes of undereye hollows over time. The results 
of this study will not have true statistical significance.  
6.3 
Control of Bias and Confounding  
All patients will be injected with the same filler product in the same locations.  
6.3.1 
Baseline Data 
Baseline and demographic characteristics will be summarized by standard descriptive statistics (including 
mean and standard deviation for continuous variables such as age and standard percentages for categorical 
variables such as race). 

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6.3.2 
Analysis of Primary Outcome of Interest 
The primary analysis of volumetric measurements will be done using the Allergan Infraorbital Hollow 
Scale and the Tear Trough Rating Scale. 
7 
Safety and Adverse Events 
7.1 
Definitions 
7.1.1 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
 
For FDA regulated studies the FDA defines an adverse event as the following: any untoward medical 
occurrence associated with the use of a drug in humans whether or not considered drug related.  
7.1.2 
Serious Adverse Event 
Adverse events are classified as serious or non-serious. A serious adverse event is any AE that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance. They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above. For example, drug overdose or abuse, a seizure that did not result in 
in-patient hospitalization or intensive treatment of bronchospasm in an emergency department would 
typically be considered serious.  
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
7.2 
Recording of Adverse Events 
At each contact with the subject, the investigator will seek information on adverse events by specific 
questioning and, as appropriate, by examination.  Information on all adverse events will be recorded 
immediately in the source document, and also in the appropriate adverse event module of the case report 
form (CRF).  All clearly related signs, symptoms, and abnormal diagnostic procedures results should be 
recorded in the source document, though should be grouped under one diagnosis. 
 

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All adverse events occurring during the study period will be recorded.  The clinical course of each event 
will be followed until resolution, stabilization, or until it has been determined that the study intervention 
or participation is not the cause.  Serious adverse events that are still ongoing at the end of the study 
period will be followed up to determine the final outcome.  Any serious adverse event that occurs after the 
study period and is considered to be possibly related to the study intervention or study participation will 
be recorded and reported immediately. 
7.3 
Relationship of AE to Study  
The relationship of each adverse event to the study procedures should be characterized. The PI or medical 
monitor will determine how the relationship of the AE will be classified as: 
• likely related – a well-known effect of the device or clearly not related to the subject or 
environmental factors 
• probably related – is known or suspected effect of device or cannot be readily explained by 
subject or study procedures  
• possibly related – is a possible effect of the device or can be explained by the subject or study 
procedures 
• unlikely related – is not a suspected effect of the device or can readily be explained by the 
subject or environmental factors  
• unrelated – is not a known effect of the device and can readily be readily and easily explained 
by the subject or environmental factors 
7.4 
Reporting of Adverse Events, Adverse Device Effects and Unanticipated Problems 
Investigators and the protocol sponsor (which may or may not be a Penn Investigator) must conform to 
the adverse event reporting timelines, formats and requirements of the various entities to which they are 
responsible,  
 
If the report is supplied as a narrative, the minimum necessary information to be provided at the time of 
the initial report includes: 
• Study identifier 
• Study Center 
• Subject number 
• A description of the event 
• Date of onset 
• Current status 
• Whether study intervention was discontinued 
• The reason why the event is classified as 
serious 
• Investigator assessment of the association 
between the event and study intervention 
 
Additionally, all other events (unanticipated problems, adverse reactions, unanticipated adverse device 
effects) and subject complaints will be recorded and reported with respect to institutional and federal 
policies.  
 
7.4.1 Follow-up report 
If an SAE has not resolved at the time of the initial report and new information arises that changes the 
investigator’s assessment of the event, a follow-up report including all relevant new or reassessed 
information (e.g., concomitant medication, medical history) should be submitted to the IRB. The 
investigator is responsible for ensuring that all SAE are followed until either resolved or stable.  

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7.4.2 
Investigator reporting: notifying the study sponsor 
Investigators from all participating sites should report all unexpected and related adverse events, 
regardless of whether they are serious or not, and all unanticipated problems to the sponsor. 
 
Any study-related unanticipated problem posing risk to subjects or others, and any type of serious adverse 
event, will be reported to the study sponsor by telephone within 24 hours of the event.  To report such 
events, a Serious Adverse Event (SAE) form will be completed by the investigator and emailed to the 
study sponsor within 24 hours.  The investigator will keep a copy of this SAE form on file at the study 
site.  Report serious adverse events by sending via email to: [Evolus., Company Call Center:  1-877-
EVOLUS1 (1-877-386-5871), Company Email:  EvolusMI@druginfo.com] 
 
Within the following 48 hours, the investigator will provide further information on the serious adverse 
event or the unanticipated problem in the form of a written narrative.  This should include a copy of the 
completed Serious Adverse Event form, and any other diagnostic information that will assist the 
understanding of the event.  Significant new information on ongoing serious adverse events should be 
provided promptly to the study sponsor. 
7.4.3 
Investigator reporting: notifying the Penn IRB 
For single and multi-site studies each site PI will need to follow their local IRB reporting requirements in 
addition to the protocol outlined reporting.  
7.4.4 
Sponsor reporting: Notifying Participating Investigators  
For clinical trials, in addition to reporting certain unanticipated problems and adverse events noted above 
to the FDA, it is the responsibility of the study sponsor to report those same adverse events or findings to 
participating investigators. 
7.5 
Medical Monitoring 
It is the responsibility of the site Principal Investigator to oversee the safety of the study at his/her site.  
This safety monitoring will include careful assessment and appropriate reporting of adverse events as 
noted above. The lead PI will monitor all AEs reported.   
7.6 
Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
period. 

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7.7 
Data Collection and Management  
REDCap will be used to store and maintain the primary study records. The data entered into REDCap will 
be obtained from the study-relevant patient EMRs.  Study personnel will be granted access to this project 
created in REDCap with each user obtaining individual access authenticated by a login system.  Minimal 
patient identifiers will be collected and stored in the REDCap database. Patient name and date of birth 
will be collected in REDCap.   
 
Source data will mainly be from the patient’s EMR. When the study requires data not normally collected 
in the patient’s EMR, the case report forms will also be the source document. Data from source 
documents (Appendix15.4, case report forms (case report forms definition- Appendix 15.5), will be 
entered into an electronic data capturing system. All source documents should be secure in private spaces 
with restricted access.  After Visit 1 the FACE-Q will be sent electronically to the subject for each follow-
up visit via a REDCap survey.   
 
During procurement of data charts will be reviewed in private spaces to ensure the confidentiality of 
acquired data. Data will be stored for up to 7 years after completion of the last follow-up visit of the last 
patient randomized.  Data may be collected for up to two years following the treatment.     
7.8 
Records Retention  
The Principal Investigator at each site is responsible for storing regulatory documents, subject files and 
financial records for the period specified by law.  The time period for maintaining research records is 
defined first by HIPAA regulations that require any HIPAA-regulated information, authorizations, 
waivers, etc. must be maintained for at least 6 years subsequent to the Institutional Review Board (IRB) 
acknowledgement of the termination of the research project and secondly by DHHS regulations (45 CFR 
46.115) and FDA regulations (21 CFR 56.115) state that IRB records relating to research shall be retained 
for at least 3 years after completion of the research.   
8 
Study Monitoring, Auditing, and Inspecting 
8.1 
Study Monitoring Plan 
This study will be closely monitored by the PI and the project manager.  The PI will be participating and 
the data will be collected by the PI and one other study steam member from the patient’s EMR.  The study 
team member will enter the data into the REDCap and the project manager will monitor the entry to verify 
the compliance with respect to the protocol, data collection, and source documents.     
8.2 
Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the EC/IRB, the sponsor, 
government regulatory bodies, and University compliance and quality assurance groups of all study 
related documents (e.g. source documents, regulatory documents, data collection instruments, study data 
etc.).  The investigator will ensure the capability for inspections of applicable study-related facilities (e.g. 
pharmacy, diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 

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9 
Ethical Considerations 
This study is to be conducted in accordance with applicable US government regulations and international 
standards of Good Clinical Practice, and applicable institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted independent Ethics 
Committee (EC) or Institutional Review Board (IRB), in agreement with local legal prescriptions, for 
formal approval of the study conduct.  The decision of the EC/IRB concerning the conduct of the study 
will be made in writing to the investigator and a copy of this decision will be provided to the sponsor 
before commencement of this study.  
 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study.  This consent 
form will be submitted with the protocol for review and approval by the EC/IRB for the study.  The 
formal consent of a subject, using the EC/IRB-approved consent form, must be obtained before that 
subject undergoes any study procedure.  The consent form must be signed by the subject or legally 
acceptable surrogate, and the investigator-designated research professional obtaining the consent. 
9.1 
Risks 
All treatments used in this protocol will be used according to the FDA approved intended use.  No 
unexpected risks should occur.  Risks/side effects of injections include skin infection, redness, swelling, 
pain, tenderness, firmness, lumps/bumps, bruising, discoloration, itching, and dryness.  Specific risks 
from dermal filler injections include unintentional injection into a blood vessel. This is a serious 
complication and may be permanent, although rare. Sequela of this complication can include vision 
abnormalities, blindness, stroke, skin necrosis or scarring.  
 
There is minimal risk from the 3D imaging involved in this study to make volumetric measurements. The 
images will be identifying as they are of the face. All identifying images will be stored on a database or 
computer behind the firewall and a password. 
 
Subjects should not be injected if they are allergic to lidocaine or Gram-positive bacterial proteins used in 
Juvéderm products or if they have had a previous allergic reaction to hyaluronic acid fillers.  
 
The product has not been studied in pregnancy or breastfeeding patients, so these patients will be 
excluded.  
9.2 
Benefits 
Subjects participating in this trial may benefit from improvement of undereye hollows from participating 
in this study. Although the benefits may not be readily apparent on an individual basis, the advancement 
of knowledge gained will serve the medical society and community.  
 
There is financial compensation for participation in this study. Subjects will be compensated $15 for each 
follow-up visit and questionnaire completed. The payment will be administered after completion of the 
final follow-up visit for a maximum total of $45. The subjects will receive the dermal filler injections for 
no charge.  

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9.3 
Risk Benefit Assessment 
Subjects participating in this trial will unlikely experience an increase in risk as this is an observational 
study of FDA approved dermal filler injections. No change in patient care will happen if the subject is 
consented.  All subjects will be asked to return for four follow-up visits for observation and surveys.  
9.4 
Informed Consent Process / HIPAA Authorization  
All subjects for this study will be provided a consent form describing this study providing sufficient 
information for subjects to make an informed decision about their participation in this study.  This consent 
form will be submitted with the protocol for review and approval by the IRB for the study.  The formal 
consent of a subject, using the IRB-approved consent form, must be obtained before that subject 
undergoes any study procedure.  The subject, or legally acceptable surrogate, must sign the consent form, 
and the investigator-designated research professional obtaining the consent. Subjects will be consented by 
the study Principal Investigator, or appropriate designee, in a room we have selected in which to perform 
consent, which is located outside of the clinic. Potential subjects will review the consent form in detail 
with the person designated to consent (either PI or CRC) and have the ability to take the consent home for 
further review.  
10 Study Finances 
10.1 
Funding Source 
Funding Sources pending  
10.2 
Conflict of Interest 
None 
10.3 
Subject Stipends or Payments 
There are no subject payments or stipends. 
11 Publication Plan 
Following data analysis and summary, data may be presented to relevant conferences and submitted for 
publication. Once published, data will be destroyed.  
12 References 
1. Filler for Wrinkles | JUVÉDERM® (Juvéderm.com) 
2. The Aesthetic Society. Aesthetic Plastic Surgery National Databank Statistics; 2020-2021. 
3. American Society of Plastic Surgeons. Plastic Surgery National Statistics; 2020.  
4. Donofrio L, Carruthers J, Hardas B, Murphy DK, Jones D, Sykes JM, Carruthers A, Creutz L, 
Marx A, Dill S. Development and Validation of a Photonumeric Scale for Evaluation of 
Infraorbital Hollows. Dermatol Surg. 2016 Oct;42 Suppl 1(Suppl 1):S251-S258. doi: 
10.1097/DSS.0000000000000856. PMID: 27661748; PMCID: PMC5671793. 
5. Hou X, Rokohl AC, Meinke MM, Li S, Liu J, Fan W, Lin M, Jia R, Guo Y, Heindl LM. A 
novel standardized distraction test to evaluate lower eyelid tension using three-dimensional 
stereophotogrammetry. Quant Imaging Med Surg. 2021 Aug;11(8):3735-3748. doi: 
10.21037/qims-20-1016. PMID: 34341746; PMCID: PMC8245927. 

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6. Sadick, N.S., Bosniak, S.L., Cantisano-Zilkha, M., Glavas, I.P. and Roy, D. (2007), Definition 
of the tear trough and the tear trough rating scale. Journal of Cosmetic Dermatology, 6: 218-
222. https://doi.org/10.1111/j.1473-2165.2007.00336.  
7. Ho OA, Saber N, Stephens D, et al. Comparing the Use of 3D Photogrammetry and Computed 
Tomography in Assessing the Severity of Single-Suture Nonsyndromic 
Craniosynostosis. Plast Surg (Oakv). 2017;25(2):78–83. doi:10.1177/2292550317694845 
8. Mathys A, Semal P, Brecko J, Van den Spiegel D. Improving 3D photogrammetry models 
through spectral imaging: Tooth enamel as a case study. PLoS One. 2019;14(8):e0220949. 
Published 2019 Aug 13. doi:10.1371/journal.pone.0220949 
9. Schendel SA. Enriched autologous facial fat grafts in aesthetic surgery: 3D volumetric 
results. Aesthet Surg J. 2015;35(8):913–919. 
13 Attachments