A Post-Market Study In Greece Of A Minimally Invasive Lower Eyelid Treatment Utilizing The Renuvion System
Phase: NA
Conditions: Skin Laxity
Sponsor: Apyx Medical

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 1 of 50 
 
 
 
CLINICAL TRIAL PROTOCOL NUMBER: APX-22-04-GR 
 
A POST-MARKET STUDY IN GREECE OF A MINIMALLY INVASIVE 
LOWER EYELID TREATMENT UTILIZING THE RENUVION SYSTEM 
 
SPONSOR: APYX MEDICAL 
FUNDED BY: APYX MEDICAL 
 
DATE: OCTOBER 2, 2023 
DRAFT OR VERSION: 4.0 
 
CONFIDENTIAL – PROPRIETARY INFORMATION 
 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 2 of 50 
SPONSOR STATEMENT AND SIGNATURE PAGE 
Company Name:  
 
Apyx Medical 
Address: 
 
 
5115 Ulmerton Rd. 
 
 
 
 
Clearwater, FL 33760 
Telephone: 
 
 
800.537.2790 
Study Device: 
 
 
Apyx APR System 
Protocol Title: 
A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing 
the Renuvion System 
Protocol Number: 
 
APX-22-04-GR 
Revision / Date:  
 
v.4.0 10022023 
 
The investigation will be conducted in compliance with the clinical investigation plan (CIP), GCP, EN ISO 14155, the Declaration 
of Helsinki, and regulatory authority requirements. 
 
Apyx Medical (hereinafter “Study Sponsor”) maintains responsibility for the ongoing safety of this clinical trial involving the 
evaluation of the Renuvion APR system.  Study Sponsor will promptly notify all investigators, the responsible IRB(s), and the 
regulatory authorities of any findings from ongoing trial monitoring activities that could adversely affect the safety of subjects, 
impact the conduct of the clinical study, or alter the IRB’s approval to continue the study, specifically within 5 working days 
of making an Unanticipated Adverse Device Effect (UADE) determination or 15 working days after first receiving notice of the 
UADE, within 10 days for Serious Adverse Event reports, and at least annually for routine reports.  In the event that participant 
safety could be directly affected by study results after the study has ended, Study Sponsor will notify all investigators of these 
results to enable investigators to consider informing participants as soon as possible or at least within one year of study 
closure.   
 
The following individuals are responsible for the content of the CIP: 
 
______________________________________________ 
 
_____________________________ 
Emily Hughes 
 
 
 
 
 
 
Date 
Senior Manager, Clinical Affairs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Kari Larson 
 
 
 
 
 
 
Date 
Sr. Director, Clinical Affairs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Shawn Roman 
 
 
 
 
 
 
Date 
Vice-President, R&D 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Kim Hanson 
 
 
 
 
 
 
Date 
Director, Clinical Operations & Medical Affairs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Terrence Sullivan  
 
 
 
 
 
Date 
Vice-President, Quality Assurance & Regulatory Affairs 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 3 of 50 
STATEMENT OF COMPLIANCE 
I have thoroughly read and reviewed this clinical investigation plan (CIP) and hereby agree to participate in this 
clinical trial sponsored by Study Sponsor. I agree to conduct this investigation according to the requirements of the 
CIP provided by the Study Sponsor and in accordance with Good Clinical Practice (GCP) as required by EN ISO 14155, 
the Declaration of Helsinki, Investigational Device Exemption (21 CFR Part 812), Protection of Human Subjects (45 
CFR Part 46), and other applicable FDA regulations, and regulations of other relevant regulatory authorities and 
conditions imposed by the reviewing Institutional Review Board (IRB) or Ethics Committee (EC). I agree that no 
deviation from, or changes to the CIP will take place without prior agreement from the sponsor and documented 
approval from the Institutional Review Board (IRB), except where necessary to eliminate an immediate hazard(s) to 
the trial participants. I agree to ensure that appropriate informed consent is obtained from all subjects prior to 
inclusion in this study.  I also agree to supervise all testing of the device involving human subjects, and to report to 
the Study Sponsor, within 24 hours, any adverse event that is serious, whether considered treatment-related or not.  
I am aware that the Study Sponsor reserves the right to discontinue this investigation at any time. 
 
I understand that this investigation will be monitored by the Study Sponsor and/or a designee employed by the Study 
Sponsor. This monitoring will involve periodic inspection of my investigational site and ongoing review of the data 
that is submitted by me to the Study Sponsor. All study data will be entered within 3 days after the study visit.  
 
I am also aware that I may be inspected by a representative of the relevant regulatory authorities, including the 
United States Food and Drug Administration, to verify compliance with applicable regulations related to clinical 
research on human subjects. 
 
My current curriculum vitae and the curriculum vitae of physicians/licensed practitioners at this institution who will 
participate as co-investigators/sub-investigators (if any) in this study will be provided to the Study Sponsor. The 
curriculum vitae will include the extent and type of our relevant experience with pertinent dates and locations. All 
personnel involved in the conduct of this study have completed Human Subjects Protection Training. 
 
I certify that I have not been involved in an investigation that was terminated for non-compliance at the insistence 
of the Study Sponsor, the IRB or EC, or other regulatory authorities. I agree to provide the Study Sponsor sufficient, 
accurate financial disclosure information.  I also agree to update financial disclosure information if any relevant 
changes occur during the investigation and for one year following the completion of the study. 
 
I understand that this CIP and the trial results are confidential, and I agree not to disclose any such information to 
any person other than a representative of the Study Sponsor or the relevant competent authorities without the prior 
written consent of the Study Sponsor. 
 
Accepted by: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator Signature 
 
Principal Investigator Name 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Co-/Sub-Investigator Signature 
 
Co-/Sub-Investigator Name 
 
 
Date 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 4 of 50 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Co-/Sub-Investigator Signature 
 
Co-/Sub-Investigator Name 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Co-/Sub-Investigator Signature 
 
Co-/Sub-Investigator Name 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Co-/Sub-Investigator Signature 
 
Co-/Sub-Investigator Name 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 5 of 50 
LIST OF ABBREVIATIONS 
AE 
Adverse Event 
CRF 
Case Report Form 
CRO 
Clinical Research Organization  
DCF 
Data Clarification Form 
DRM 
Data Review Meeting  
ESU 
Electrosurgical Generator Unit 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GAIS 
Global Aesthetic Improvement Scale 
GCP 
Good Clinical Practice 
ICH  
International Conference for Harmonization of Technical Requirements of Pharmaceuticals 
for Human Use  
IFU 
Instructions for Use 
IPR 
Independent Photographic Reviewer 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
NRS 
Numeric Rating Scale 
NSAID 
Non-steroidal Anti-Inflammatory Drug 
PP 
Per Protocol 
PPS 
Per Protocol Set 
RF 
Radiofrequency 
SAE 
Serious Adverse Event 
SAL 
Suction-Assisted Liposuction 
UADE 
Unanticipated Adverse Device Effect 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 6 of 50 
PROTOCOL SYNOPSIS 
Protocol Title: 
A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing 
the Renuvion System 
Study Device: 
The Renuvion Generator (K192867) is indicated for delivery of radiofrequency energy 
and/or helium plasma to cut, coagulate and ablate soft tissue during open and 
laparoscopic surgical procedures. The Renuvion APR Handpiece (K191542) is intended to 
be used with compatible electrosurgical generators for the delivery of radiofrequency 
energy and/or helium plasma for cutting, coagulation and ablation of soft tissue during 
open surgical procedures. 
 
Together, the Renuvion Generator and Handpiece are referred to as the Renuvion APR 
System. 
Development Phase: 
Post-Market 
Study Purpose: 
To evaluate the use of the Renuvion APR System as a minimally invasive lower eyelid 
procedure. 
Brief Study Overview: 
This is a prospective, multi-center, non-randomized, single-arm study of up to 16 subjects 
treated with the Renuvion APR System. Subjects will receive treatment with the Renuvion 
APR System in the lower periorbital area on both sides of the face. 
 
At baseline, images will be taken utilizing the site’s private practice camera system. 
Baseline images will be used as comparator images for follow-up images for Independent 
Photographic Reviewer evaluation and subject/investigator assessments.  
 
The treatment area will be tumesced with 20 - 25ml of fluid on each side of the periorbital 
area.  
 
Study treatment will be performed by the principal investigator only. The treatment of the 
periorbital area will be accessed from an incision placed in the crease of the lower lid.  Two 
incisions will be placed in both the medial and lateral crease of the lower lid.  Treatment 
will be performed through one incision and the second incision will be used to allow for 
adequate venting of helium gas.  Care will be taken to undermine the tissue and to ensure 
the incisions communicate with each other to allow adequate venting.  An optional third 
lower lid incision may be made as needed. The treatment plane will be above the 
orbicularis muscle. The treatment settings will be 60-70% Power, 1 LPM, and 3 Passes.  
Procedure data and adverse events will be captured. 
 
Follow-up will occur 1 day, 3 days, 7 days, 30 days, 90 days, and 180 days post-procedure; 
images will be taken at all visits.  Investigator/subjects assessments will be completed at 
D30, D90, and D180 visits. Subjects may also be seen back for follow-up at the 
investigator’s discretion.  
Number of Sites Enrolling 
Participants: 
Subjects will be recruited from one study site in Greece. 
Sample Size:  
N = 16 treated subjects; subjects enrolled may be greater than subjects treated. 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 7 of 50 
Subject Population: 
Healthy, female and male adult subjects ages 18 – 75 years old who meet the 
inclusion/exclusion criteria.  
Inclusion Criteria: 
• 
Male or female subjects, ages 18 – 75 years old. 
• 
ASA Physical Status Classification System Class I and Class II subjects. 
• 
Complaint of skin laxity or lines in the lower eyelid area. 
• 
Understands and accepts the obligation not to undergo any other procedures or 
treatments in the areas to be treated during study participation. 
• 
Absence of physical conditions unacceptable to the investigator. 
• 
Females of childbearing potential who are sexually active must be willing to use 
an approved method of birth control during study participation. 
• 
Willing and able to comply with protocol requirements, including study-required 
images/photos, assessments/measurements, and returning for follow-up visits. 
• 
Willing to release rights for the use of study photos, including in publication. 
• 
Able to read, understand, sign, and date the informed consent. 
• 
Able to communicate with the site via video and/or photographs, in the event of 
a virtual follow-up visit. 
Exclusion Criteria: 
• 
Subjects presenting with ASA Physical Status Classification System Classes III or 
higher. 
• 
Festoons in the periorbital area. 
• 
Prior cosmetic/aesthetic fillers (hyaluronic acid, poly-l-lactic acid, calcium 
hydroxylapatite, et.)  in the study treatment area within the past 12 months. 
• 
Pregnant, lactating, or plans to become pregnant during study participation. 
• 
Known hypersensitivity or allergy to tumescent anesthetic (lidocaine/ 
epinephrine). 
• 
Known hypersensitivity or allergy to ibuprofen or other NSAIDS. 
• 
Previous surgery in the study treatment area. 
• 
Active systemic or local skin disease that may alter wound healing. 
• 
Significant or uncontrolled medical condition that in the opinion of the 
investigator participation in the study may compromise the patient’s health. 
• 
History of autoimmune disease (excluding Hashimoto’s thyroiditis). 
• 
Known susceptibility to keloid formation or hypertrophic scarring. 
• 
Cancerous or pre-cancerous lesions in the area to be treated. 
• 
Possesses a surgically implanted electronic device (i.e., pacemaker). 
• 
Serious mental health illness such as dementia or schizophrenia; psychiatric 
hospitalization in the past two years. 
• 
Participation in any other investigational study within 30 days prior to consent 
and throughout study participation. 
• 
Subject who, in the opinion of the investigator, is not an appropriate candidate 
for the study. 
Primary Outcome 
Measures: 
Improvement in the lower eyelid area as determined by a masked, qualitative assessment 
of photographs at 180-days post-treatment compared to baseline. Improvement will be 
assessed based on photographs taken at all visits using the site’s 2D camera system. 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 8 of 50 
Secondary Outcome 
Measures: 
1. Improvement in the lower eyelid area as determined by a masked, qualitative 
assessment of photographs at 90-days post-treatment compared to baseline. 
2. Analysis of change from baseline to D30, D90, & D180 in Snap-back Test Grade 
(Bashour14). 
3. Analysis of change from baseline to D30, D90, & D180 in Medial Canthal Laxity Test 
Grade (Bashour14). 
4. Analysis of change from baseline to D30, D90, & D180 in Lateral Canthal Laxity Test 
Grace (Bashour14). 
5. The Principal Investigator will complete a GAIS13 assessing overall aesthetic 
improvement at day 30, 90, and 180 post-treatment. 
6. The subject will complete a GAIS13 assessing overall aesthetic improvement at day 
30, 90, and 180 post-treatment. 
7. The subject will complete a patient satisfaction questionnaire at the 180-day follow-
up visit. 
8. During study treatment, the subject’s pain levels will be monitored using the 11-point 
Numeric Rating Scale (NRS)20. The average pain score for the entire region treated 
will be recorded. Pain scores will be recorded at all follow-up visits. 
Safety Variables: 
 Prior to treatment, the subject’s medical history will be reviewed, a urine pregnancy 
test will be performed (if applicable), and a physical examination will be conducted.  
 Following study treatment and at each subsequent visit, the subject will be queried 
about adverse events, expected treatment effects, and changes in concomitant 
medications, and the treatment area will be visually examined.  
Study Duration: 
The duration from when the study opens to enrollment until completion of data analyses 
is anticipated to be 12 months. 
 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 9 of 50 
TABLE OF CONTENTS 
Sponsor Statement and Signature Page ................................................................................. 2 
Statement of Compliance....................................................................................................... 3 
List of Abbreviations .............................................................................................................. 5 
Protocol Synopsis .................................................................................................................. 6 
1. 
KEY ROLES .................................................................................................................. 13 
1.1 
Internal Responsibilities ....................................................................................................................... 13 
1.2 
External Responsibilities ....................................................................................................................... 13 
2. 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE .............. 14 
2.1 
Background Information & Rationale ................................................................................................... 14 
2.1.1 
Device Name and Indications for Use .................................................................................................. 16 
2.1.2 
Preclinical Studies ................................................................................................................................ 17 
2.2 
Potential Risks and Benefits ................................................................................................................. 18 
2.2.1 
Potential Risks ...................................................................................................................................... 18 
2.2.1.1 
 Minimization of Potential Risks ...................................................................................................... 18 
2.2.2 
Potential Benefits ................................................................................................................................ 18 
3. 
STUDY PURPOSE......................................................................................................... 19 
4. 
STUDY DESIGN AND ENDPOINTS ................................................................................. 19 
4.1 
Description of the Study Design ............................................................................................................ 19 
4.2 
Duration of Study ................................................................................................................................. 19 
4.3 
Study Endpoints.................................................................................................................................... 19 
4.3.1 
Primary Effectiveness Endpoint ........................................................................................................... 19 
4.3.2 
Primary Safety Endpoint ...................................................................................................................... 20 
4.3.3 
Additional Outcome Measures ............................................................................................................ 20 
4.3.4 
Evaluation Tools ................................................................................................................................... 20 
4.3.4.1 2-Dimentional Photography ................................................................................................................ 20 
4.3.4.1.1 Independent Photographic Assessments ..................................................................................... 20 
4.3.4.1.2 Independent Photographic Review Evaluation Process ............................................................... 21 
4.3.4.1.3 Independent Photographic Review Training Process ................................................................... 21 
4.3.4.2 Snap-Back Test Grade .......................................................................................................................... 22 
4.3.4.3 Medial Canthal Laxity Test Grade ........................................................................................................ 22 
4.3.4.4 Lateral Canthal Laxity Test Grade ........................................................................................................ 22 
4.3.4.5 Global Aesthetic Improvement Scale (GAIS) ........................................................................................ 23 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 10 of 50 
4.3.4.6 Subject Satisfaction Survey .................................................................................................................. 24 
4.3.4.7 Numeric Rating Scale (NRS) ................................................................................................................. 24 
4.3.4.8 Adverse Event Reporting ..................................................................................................................... 24 
4.3.4.9 ASA Physical Status Classification System ........................................................................................... 25 
5. 
SUBJECT ENROLLMENT AND WITHDRAWAL ................................................................ 25 
5.1 
Study Population .................................................................................................................................. 25 
5.1.1  
Informed Consent ................................................................................................................................ 25 
5.1.2  
Pre-treatment Recruiting/Screening ................................................................................................... 26 
5.1.3.1 
Screen Failures ................................................................................................................................. 26 
5.2 
Inclusion Criteria................................................................................................................................... 26 
5.3 
Exclusion Criteria .................................................................................................................................. 27 
5.4 
Strategies for Recruitment and Retention ............................................................................................ 27 
5.5  
Participant Withdrawal or Termination ................................................................................................ 27 
5.5.1 
Reasons for Withdrawal or Termination ............................................................................................. 27 
5.5.2 
Handling of Withdrawals or Termination ............................................................................................ 28 
5.6 
Premature Termination or Suspension of the Study or a Study Site ...................................................... 28 
6. 
STUDY DEVICE ............................................................................................................ 28 
6.1 
Packaging & Storage ............................................................................................................................. 28 
6.2 
Accountability ...................................................................................................................................... 29 
6.3 
Device Malfunction/Observation.......................................................................................................... 29 
7. 
STUDY PROCEDURES AND SCHEDULE .......................................................................... 29 
7.1 
Pre-Procedure ...................................................................................................................................... 29 
7.2 
Study Procedure ................................................................................................................................... 30 
7.3 
Follow-up Procedures ........................................................................................................................... 30 
7.3.1 Immediately Post-Procedure ...................................................................................................................... 30 
7.3.2 Follow-up Visits & Subject Contact outside of Follow-up Visits ................................................................. 30 
7.4 
Subject Randomization and Treatment Group Assignment................................................................... 32 
7.3 
Study Schedule ..................................................................................................................................... 32 
7.3.1 
Screening ............................................................................................................................................. 32 
7.3.2 
Baseline Assessment ............................................................................................................................ 32 
7.3.3 
Treatment Visit .................................................................................................................................... 33 
7.3.4 
Follow-up ............................................................................................................................................. 33 
7.3.5 
Unscheduled Visit ................................................................................................................................ 33 
7.3.6 
End of Study (Completion) ................................................................................................................... 33 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 11 of 50 
8. 
ASSESSMENT OF SAFETY ............................................................................................. 33 
8.1 
Specifications of Safety Parameters ...................................................................................................... 33 
8.1.1 
Definition of an Expected Treatment Effect (ETE) and an Adverse Event (AE) .................................... 33 
8.1.2 
Definition of Serious Adverse Event (SAE) ........................................................................................... 34 
8.1.3 
Definition of Unanticipated Adverse Device Effects (Events) .............................................................. 34 
8.2 
Classification of an Event ...................................................................................................................... 35 
8.2.1 
Severity of Event .................................................................................................................................. 35 
8.2.2 
Relationship to the Study Device and Procedure ................................................................................ 35 
8.3 
Time Period and Frequency for Event Assessment and Follow-up ........................................................ 35 
8.4 
Reporting Procedures ........................................................................................................................... 36 
8.4.1 
Adverse Event Reporting ..................................................................................................................... 36 
8.4.2 
Serious Adverse Event Reporting ......................................................................................................... 36 
8.4.3 
Unanticipated Adverse Device Effect Reporting .................................................................................. 37 
8.4.4 
Reporting of Pregnancy ....................................................................................................................... 37 
8.4.5  
Reporting of Deaths ............................................................................................................................. 37 
8.5 
Study Halting Rules ............................................................................................................................... 37 
9. 
CLINICAL MONITORING .............................................................................................. 38 
10. 
STATISTICAL METHODOLOGY ..................................................................................... 38 
10.1 
Statistical and Analytical Plans ............................................................................................................. 38 
10.2 
Sample Size........................................................................................................................................... 38 
11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/ DOCUMENTS .......................... 38 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL ........................................................... 38 
13. 
ETHICS/PROTECTION OF HUMAN SUBJECTS ................................................................ 39 
13.1 
Ethical Standard ................................................................................................................................... 39 
13.2 
Institutional Review Board ................................................................................................................... 39 
13.3 
Participant and Data Confidentiality ..................................................................................................... 39 
14. 
DATA HANDLING AND RECORD KEEPING .................................................................... 40 
14.1 
Data Collection and Management Responsibilities ............................................................................... 40 
14.2 
Investigator Records and Reports ......................................................................................................... 41 
14.2.1 
Investigator Records ............................................................................................................................ 41 
14.2.2 
Investigator Reports ............................................................................................................................ 42 
14.3 
Study Records Retention ...................................................................................................................... 42 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 12 of 50 
14.4 
Protocol Deviations .............................................................................................................................. 43 
14.5 
Publication and Data Sharing Policy...................................................................................................... 43 
15. 
STUDY ADMINISTRATION ........................................................................................... 43 
15.1 
 Study Investigators .............................................................................................................................. 43 
15.2 
Amendment Policy ............................................................................................................................... 44 
16. 
CONFLICT OF INTEREST POLICY ................................................................................... 44 
17. 
LITERATURE REFERENCES ........................................................................................... 45 
Appendix A: Patient Satisfaction Questionnaire ................................................................... 46 
Appendix B:  Pre-Screening Questionnaire ........................................................................... 47 
Appendix C:  Frankfurt Plane Positioning ............................................................................. 48 
Appendix D: Protocol Revisions Log ..................................................................................... 50 
 
LIST OF TABLES 
Table 1: Internal Responsibilities ................................................................................................................................. 13 
Table 2: External Responsibilities................................................................................................................................. 13 
Table 3: Modified Global Aesthetic Improvement Scale Evaluation - Investigator ...................................................... 23 
Table 4: Modified Global Aesthetic Improvement Scale Evaluation - Subject ............................................................. 24 
Table 5: ASA PS Classification ...................................................................................................................................... 25 
Table 6: Study Required Procedures ............................................................................................................................ 32 
Table 7: Protocol Revisions Log ................................................................................................................................... 50 
 
LIST OF FIGURES 
Figure 1: Renuvion APR Handpiece .............................................................................................................................. 16 
Figure 2: Electrosurgical Unit and Helium Tank ........................................................................................................... 16 
Figure 3: Snap-Back Test .............................................................................................................................................. 22 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 13 of 50 
1. 
KEY ROLES 
Persons, companies, and/or groups serving in key roles in the conduct or oversight of this clinical trial are listed in 
Table 1 and Table 2 below, including sponsor, clinical project manager for the trial, investigator responsible for 
conducting the trial.  
1.1 
INTERNAL RESPONSIBILITIES 
TABLE 1: INTERNAL RESPONSIBILITIES 
Name 
Function 
Address 
Apyx Medical 
Sponsor 
5115 Ulmerton Road 
Clearwater, FL 
Emily Hughes 
Sr. Manager, Clinical Affairs 
Phone: 731.414.2603 
Email: Emily.Hughes@apyxmedical.com 
Kari Larson 
Sr. Director, Clinical Affairs 
Phone: 801.244.0058 
Email: Kari.Larson@apyxmedical.com 
Shawn Roman 
VP, R&D and Clinical Affairs 
Phone: 904.382.4857 
Email: Shawn.Roman@apyxmedical.com 
Kim Hanson 
Director, Clinical Operations & 
Medical Affairs 
Phone: 720-480-6584 
Email: Kim.Hanson@apyxmedical.com 
Terrence Sullivan 
VP, Quality Assurance and 
Regulatory Affairs 
Phone: 508.918.0812 
Email: Terry.Sullivan@apyxmedical.com 
1.2 
EXTERNAL RESPONSIBILITIES 
The administrative structure for external responsibilities includes, but is not limited to, the participants in Table 2. 
TABLE 2: EXTERNAL RESPONSIBILITIES 
Name 
Function 
Address 
Dr. Aris Sterodimas 
Site Principal Investigator 
Address: 264 Mesogeion Ave, 
                 Athens, 15562, Greece 
Phone :+30 210 65 02 936 
Email: aris@sterodimas.com 
 
Castor 
EDC 
Phone: 628-239-3493 
Email: anthony.kurda@castoredc.com 
Technomics Research 
Statistical Analysis of Data 
Phone: 763-473-6374 
Email: mharsch@technomicsresearch.com 
DropBox.com 
Secure cloud-based document 
repository for CRF and images upload 
DropBox.com 
 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 14 of 50 
2. 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
2.1 
BACKGROUND INFORMATION & RATIONALE 
Energy has been applied in some form to tissue since the beginning of recorded history.  The practice of applying 
heat to tissue through the use of cauteries was used for thousands of years as an invaluable method of controlling 
hemorrhage.  Continuous improvement of methods for utilizing the beneficial effects of heat on tissue eventually 
led to the development of the basic concepts of electrosurgery we know today.  In October of 1926, Dr. Harvey 
Cushing used an electrosurgical unit developed by Dr. William T. Bovie to successfully remove a highly vascularized 
brain tumor from a patient after previous failed attempts.  Today, electrosurgical instruments are used in almost 
every surgical procedure performed worldwide.1 
Through this long history, the heat effects of the radiofrequency (RF) alternating current used in electrosurgery on 
cells and tissue have been well established.  Normal body temperature is 37°C and, with normal illness, can increase 
to 40°C without permanent impact or damage to the cells of our body.  However, when the temperature of cells in 
tissue reaches 50°C, cell death occurs in approximately 6 minutes2.  When the temperature of cells in tissue reaches 
60°C, cell death occurs instantaneously.3 Between the temperatures of 60°C and just below 100°C, two simultaneous 
processes occur.1 The first is protein denaturation leading to coagulation which will be discussed in more detail 
below.  The second is desiccation or dehydration as the cells lose water through the thermally damaged cellular wall.  
As temperatures rise above 100°C, intracellular water turns to steam and tissue cells begin to vaporize as a result of 
the massive intracellular expansion that occurs.  Finally, at temperatures of 200°C or more, organic molecules are 
broken down into a process called carbonization.  This leaves behind carbon molecules that give a black and/or 
brown appearance to the tissue. 
 
Understanding these heat effects of RF energy on cells and tissue can allow the predictable changes to be used to 
accomplish beneficial therapeutic results.  Protein denaturation leading to soft tissue coagulation is one of the most 
versatile and widely utilized tissue effects.  Protein denaturation is the process in which hydrothermal bonds 
(crosslinks) between protein molecules, such as collagen, are instantaneously broken and then quickly reformed as 
tissue cools.  This process leads to the formation of uniform clumps of protein typically called coagulum through a 
subsequent process known as coagulation.  In the process of coagulation, cellular proteins are altered but not 
destroyed and form protein bonds that create homogenous, gelatinous structures.  The resulting tissue effect of 
coagulation is extremely useful and most commonly used for occluding blood vessels and causing hemostasis. 
 
In addition to causing hemostasis, coagulation results in predictable contraction of soft tissue.  Collagen is one of the 
main proteins found in human skin and connective tissue.  The coagulation/denaturation temperature of collagen is 
conventionally stated to be 66.8°C, although this can vary for different tissue types.4  Once denatured, collagen 
rapidly contracts as fibers shrink to one-third of their overall length.5  This principal of thermally-induced contraction 
of collagen through denaturation and coagulation of soft tissue is well known in medicine and is used to achieve 
beneficial results in ophthalmology, orthopedic applications, and the treatment of varicose veins.  Once tissue is 
heated to the appropriate temperature, protein denaturation and collagen contraction occur resulting in a reduction 
of volume and surface area of the heated tissue.  Noninvasive use of RF devices, lasers, and plasma devices have 
been used for the reduction of facial wrinkles and rhytides by utilizing thermal-induced collagen/tissue contraction 
since the mid-1990s.6-11 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 15 of 50 
Recently, the use of thermal-induced collagen/tissue contraction has been expanded to minimally invasive 
procedures.  Laser-assisted lipolysis (LAL) and radiofrequency-assisted lipolysis (RFAL) devices have combined the 
removal of subcutaneous fat with soft tissue heating to reduce the skin laxity that often results from fat volume 
removal.  These devices are placed in the same subcutaneous tissue plane as a standard suction-assisted lipolysis 
(SAL) cannula and are used to deliver thermal energy to coagulate the subcutaneous tissue including the underside 
of the dermis, the fascia, and the septal connective tissue.  The coagulation of the subcutaneous tissue results in 
collagen/tissue contraction that reduces skin laxity.   
 
Laxity of the skin is part of the normal aging process, which results in characteristic changes in the skin and underlying 
connective tissue of the face. Aging is both intrinsic, an inevitable physiological process, and extrinsic, caused by 
external environmental factors such as air pollution and sun exposure12.  Aging processes create phenotypic changes 
in cutaneous cells as well as structural and functional changes in extracellular matrix components such as collagens, 
elastin, and proteoglycans which provide tensile strength, elasticity, and hydration to the skin12. The result of aging 
is biologic changes to the skin, which include thin, dry skin, fine wrinkles, gradual dermal atrophy, loss of elasticity, 
and laxity12. Specifically, lower eyelid blepharoplasty is a common surgical technique for addressing the undesirable 
progression of the aging lower eyelids, specifically lower eyelid wrinkles and skin redundancy19. This study is utilizing 
a minimally invasive technique to address the same items of concern. 
 
Apyx Medical Corporation’s product family of helium-based plasma technology (Renuvion/J-Plasma family of 
devices) has FDA clearance for the cutting, coagulation, and ablation of soft tissue.  All devices in the product family 
system are a part of a system that consists of an electrosurgical generator unit, a handpiece, and a supply of helium 
gas.  RF energy is delivered to the handpiece by the generator and used to energize an electrode.  When helium gas 
is passed over the energized electrode, a helium plasma is generated which allows heat to be applied to tissue in 
two different and distinct ways.  First, heat is generated by the actual production of the plasma beam itself through 
the ionization and rapid neutralization of the helium atoms.  Second, since plasmas are very good electrical 
conductors, a portion of the RF energy used to energize the electrode and generate the plasma passes from the 
electrode to the patient and heats tissue by passing current through the resistance of the tissue, a process known 
as Joule heating.  These two sources of tissue heating give the Renuvion APR device some advantages during use as 
a surgical tool for the coagulation and contraction of subcutaneous soft tissue.   
 
This helium-based plasma device has technological features that result in an effective method of action for 
coagulation and contraction of soft tissue.  These features and benefits are as follows: 
1. The Renuvion APR Handpiece device achieves soft tissue coagulation and contraction by rapidly heating the 
treatment site to temperatures greater than 85°C for between 0.040 and 0.080 seconds.   
2. The tissue surrounding the treatment site remains at much cooler temperatures resulting in rapid cooling 
after the application of the energy through conductive heat transfer. 
3. Focused delivery of energy on immediate heating of the fibroseptal network resulting in immediate soft 
tissue coagulation and contraction without unnecessarily heating the full thickness of the dermis. 
4. 360° tissue treatment without the need for the user to redirect the flow of energy due to electrical energy 
taking the path of least resistance. 
5. Unencumbered delivery of power regardless of the tissue impedance due to the unique power output from 
the electrosurgical generator. 
6. Low current RF energy resulting in minimal depth of thermal effect and prevention of over-treating tissue 
when performing multiple passes. 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 16 of 50 
 
2.1.1 DEVICE NAME AND INDICATIONS FOR USE 
The Renuvion APR system consists of a handpiece (Figure 1), an electrosurgical unit (ESU, Figure 2), and a supply of 
helium gas (Figure 2).  RF energy is delivered to the handpiece by the ESU and used to energize an electrode.  When 
helium gas is passed over the energized electrode, a helium plasma is generated which allows for conduction of the 
RF energy from the electrode to the subject in the form of a precise helium plasma beam.   
 
 
FIGURE 1: RENUVION APR HANDPIECE 
 
FIGURE 2: ELECTROSURGICAL UNIT AND HELIUM TANK 
The Apyx Medical Corporation Renuvion/J-Plasma helium plasma family of products has received FDA clearance 
under 510(k) numbers K090586, K112233, K142975, K151325, K152570, K170188, K170777, K183610, K191542, and 
K192867 for the cutting, coagulation, and ablation of soft tissue.   

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 17 of 50 
2.1.2 PRECLINICAL STUDIES 
During the use of the Renuvion system in open surgical procedures involving subdermal tissue coagulation, the tip 
of the Renuvion handpiece is placed in the subcutaneous tissue plane through the same access ports used during 
suction assisted lipolysis procedures (liposuction).  In this use, it is important to establish that both the external 
epidermal tissue temperatures and the internal subdermal tissue temperatures remain within safe limits.  The 
following pre-clinical studies were conducted to measure these temperatures on both live porcine skin tissue and ex 
vivo human skin tissue:  
1. RP-18032301:  Evaluation of Porcine Skin Tissue Epidermal Temperature During Subdermal J-Plasma 
(Renuvion) Application (Non-GLP) 
This was a pre-clinical study in which the Renuvion system was used to coagulate the subdermal tissue of 
porcine skin at various treatment parameters in order to measure the maximum temperature on the 
surface of the epidermis.  In this study, the maximum recorded epidermal surface temperatures were 
39.1oC and 40.2oC.  These temperatures were recorded after performing six consecutive passes of the 
Renuvion system under the same area of tissue.  Six consecutive passes under the same tissue was included 
in the study to represent a “worst case” scenario.  Six passes are not commonly performed clinically.  
However, even in this “worst case” scenario the epidermal surface temperature remained within safe limits.  
Pedroso, et.al, reported that because of superficial thermal safety concerns, the skin surface temperature 
should be maintained below 45oC.  This study was subsequently published1.  The summary of the published 
study is as follows: 
J-Plasma helium was used in porcine, liver, kidney, and muscle tissue at 20%, 50% and 100% power 
and 1 L/min and 3 L/min gas flow at 1, 5, and 10 second intervals.  J-Plasma was then used in 
ovarian and uterine tissue at maximum power and gas flow settings in intervals of 1, 5, 10 and 30 
seconds.  Concluded that J-Plasma has predictable thermal spread in a variety of tissue types.  
Thermal depth of spread increased linearly with increased power setting, gas flow rate, and 
exposure time.  Even at settings that greatly exceeded the manufacturer’s recommendation, the 
depth of thermal spread associated with the J-Plasma device was less than 3 mm (regardless of the 
type of tissue) and the diameter of lateral spread was 12 mm or less.  
2. RP-18040201:  A Study Evaluating Tissue Contraction, External Tissue Temperature, and Internal Tissue 
Temperature When Using J-Plasma (Renuvion) on Ex Vivo Abdominoplasty Tissue (non-GLP) 
This was a pre-clinical study that was performed on ex vivo human tissue collected by a surgeon during 
previously conducted abdominoplasty procedures.  The Renuvion system was used to coagulate the 
subdermal tissue of the human skin samples at various treatment parameters.  During treatment, both the 
maximum external epidermal tissue temperatures and the maximum internal subdermal tissue 
temperatures were measured and recorded.  The maximum external tissue temperatures ranged from 
24.9oC to 37.8oC.  This data serves to validate the maximum external tissue temperatures of 39.1oC and 
40.2oC reported in RP-18032301 measured in a live porcine model.  The maximum internal tissue 
temperatures ranged from 40oC to 80oC.  It is known from the literature that the reported range of 
temperatures causing collagen shrinkage varies from 60oC to 80oC.  Therefore, in order to cause soft tissue 
coagulation and collagen contraction, the target internal tissue temperature should be within this range.  
Both the external and internal temperatures remained within safe limits when using the Renuvion system 
to coagulate the subdermal tissue of human skin samples. 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 18 of 50 
The results of the above summarized pre-clinical testing support the safe and effective use of the Renuvion® system 
in dermatological and general surgical procedures involving subdermal tissue coagulation.   
2.2 
POTENTIAL RISKS AND BENEFITS 
2.2.1 POTENTIAL RISKS 
This treatment modality was designed to inherently minimize the risk to the subject. However, treatment with 
energy-based modalities (laser, radiofrequency, and plasma devices) produce subsequent heating of the soft tissue 
that could involve the following commonly Expected Treatment Effects (ETEs): discomfort/pain, edema, erythema, 
ecchymosis, hypoesthesia, temporary sensory nerve injury (touch sensitivity, itching, temporary numbness/tingling), 
transient migratory firmness, and temporary and/or transient crepitus. 
 
In addition to commonly expected treatment effects, treatment with the Renuvion APR device could involve the 
following risks: helium embolism into the surgical site due to inadvertent introduction into the venous or arterial 
blood supply system, unintended burns (deep or superficial), pneumothorax, temporary or permanent motor nerve 
injury, ischemia, fibrosis, infection, gas buildup, bleeding, hematoma, seroma, subcutaneous induration, 
pigmentation changes, increased healing time, unsatisfactory scarring, asymmetry and/or unacceptable cosmetic 
result. 
 
Subjects using drugs that reduce coagulation (aspirin or NSAIDs) may experience increased bruising or bleeding at 
the treatment site. Any other medications prescribed for the procedure or after-procedure by the investigator have 
their own risks; these risks should be discussed with the subject. 
 
A grounding pad is used to ground/neutralize the electrical current. Subjects undergoing radiofrequency treatment 
will be kept away from contact with metal parts which are grounded, or which have appreciable capacitance to 
earth. 
 
Risks associated with tumescent anesthesia (lidocaine and epinephrine) include blurred vision, mental/mood 
changes, drowsiness, dizziness, unusually slow heartbeat, rash, itching, swelling, anxiety, apprehensiveness, 
restlessness, tremor, weakness, sweating, palpitations, pallor, nausea and vomiting, headache, and respiratory 
difficulties. 
 
Any unexpected or unforeseen complications will be managed by the investigator throughout the conduct of the 
study. Unforeseen or unexpected side effects not listed above will be reported to the sponsor and regulatory 
representatives as they occur. 
 
2.2.1.1  MINIMIZATION OF POTENTIAL RISKS 
These risks are mitigated by utilizing qualified clinical Investigators who have training and are experienced in 
subdermal Renuvion procedures. In addition, risks are mitigated by including only those subjects that meet the study 
eligibility criteria.  
2.2.2 POTENTIAL BENEFITS 
A possible benefit of using the Renuvion APR device in the lower eyelid area is the potential for improvement in the 
appearance of lax tissue in the lower eyelid region utilizing a minimally invasive technique.   

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 19 of 50 
3. 
STUDY PURPOSE 
The purpose of this study is to evaluate the use of the Renuvion APR System as a minimally invasive lower eyelid 
procedure.  
4. 
STUDY DESIGN AND ENDPOINTS 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
This is a prospective, multi-center, non-randomized, single-arm study of up to 16 subjects treated with the Renuvion 
APR System. Subjects will receive treatment with the Renuvion APR System in the lower periorbital area on both 
sides of the face. 
 
At baseline, images will be taken utilizing the site’s camera system. Baseline images will be used as comparator 
images for follow-up images for Independent Photographic Reviewer evaluation and subject/investigator 
assessments.  
 
The treatment area will be tumesced with 20 - 25ml of fluid on each side of the periorbital area.  
 
The treatment of the periorbital area will be accessed from an incision placed in the crease of the lower lid.  Two 
incisions will be placed in both the medial and lateral crease of the lower lid.  Treatment will be performed through 
one incision and the second incision will be used to allow for adequate venting of helium gas.  Care will be taken to 
undermine the tissue and to ensure the incisions communicate with each other to allow adequate venting.  An 
optional third lower lid incision may be made as needed. The treatment plane will be above the orbicularis muscle. 
The treatment settings will be 60-70% Power, 1 LPM, and 3 Passes.  Procedure data and adverse events will be 
captured. 
 
Follow-up will occur 1 day, 3 days, 7 days, 30 days, 90 days, and 180 days post-procedure; images will be taken at all 
visits.  Investigator/subjects assessments will be completed at D30, D90, and D180 visits. Subjects may also be seen 
back for follow-up at the investigator’s discretion.  
4.2 
DURATION OF STUDY 
Recruitment for this study may take approximately four months. Following the treatment visit, subjects will be 
followed for a total duration of 180-days, after which, data will be analyzed. Therefore, the anticipated total duration 
of the study is approximately twelve months. 
4.3 
STUDY ENDPOINTS 
4.3.1 PRIMARY EFFECTIVENESS ENDPOINT 
Improvement in the lower eyelid area as determined by a masked, qualitative assessment of photographs at 180-
days post-treatment compared to baseline. Improvement based on 2D photographs taken at all visits using the site’s 
photography system. 
 
Three experienced, blinded independent photographic reviewers (IPR) will perform a qualitative analysis/review of 
the pre-treatment and post-treatment sets of images of each subject in a blinded and randomized order. Each 
blinded reviewer will choose which image is the post-treatment image. Success will be correct post-treatment image 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 20 of 50 
selection by at least 2 of the 3 reviewers.  The percentage of subjects with a correct post-treatment image selection 
will be calculated. 
4.3.2 PRIMARY SAFETY ENDPOINT 
The primary safety endpoint is an analysis of adverse events through the D180 post-treatment visit. 
4.3.3 ADDITIONAL OUTCOME MEASURES 
1. Improvement in the lower eyelid area as determined by a masked, qualitative assessment of photographs 
at 90-days post-treatment compared to baseline. 
2. Analysis of change from baseline to D30, D90, & D180 in Snap-back Test Grade (Bashour14). 
3. Analysis of change from baseline to D30, D90, & D180 in Medial Canthal Laxity Test Grade (Bashour14). 
4. Analysis of change from baseline to D30, D90, & D180 in Lateral Canthal Laxity Test Grace (Bashour14). 
5. The investigator will complete a GAIS13 assessing overall aesthetic improvement in the treatment area at 
day 30, 90, and 180 post-treatment. 
6. The subject will complete a GAIS13 assessing overall aesthetic improvement in the treatment area at day 30, 
90, and 180 post-treatment. 
7. The subject will complete a Patient Satisfaction Questionnaire (PSQ) at the 180-day follow-up visit. 
8. During study treatment, the subject’s pain levels will be monitored using the 11-point Numeric Rating Scale 
(NRS)20. The average pain score for the entire region treated will be recorded. Pain scores will be recorded 
at all follow-up visits. 
4.3.4 EVALUATION TOOLS 
The following evaluation tools will be used in this study: 
4.3.4.1 2-DIMENTIONAL PHOTOGRAPHY 
Two-dimensional (2D) photographic images will be captures utilizing the site’s camera system.  The same 
standardized photography views will be used throughout the study. Images will be captured as follows: 
• 
With the subject’s entire face freshly washed and clear of eye makeup. Permanent make-up tattoos, if any, 
will be noted in the Case Report Form. 
• 
With no jewelry (eyebrow rings, nose rings, earrings, necklace, etc.). 
• 
With the subject’s eyes open. 
• 
With no expression on the subject’s face (smiling, smirking, etc.). 
• 
Aligned to the Frankfurt Plane (see Appendix C). 
 
Images will be monitored for quality to ensure standardized images and subject alignment between baseline and 
follow-up visits. A reshoot may be requested is images are poor photographic quality and/or changes in subject 
positioning or alignment. Study staff should review photos with particular care during each visit to ensure consistent 
alignment to prevent having to bring the subject back for a reshoot. If a reshoot is required, the reshoot should be 
taken within the visit window. Study staff should review Photography Result Reports (provided within 48 hours of 
image upload) for all images taken to check for reshoot requests.  
Baseline images may be taken within 30 days prior to study treatment. Subject baseline photos are reviewed by Apyx 
staff prior to study treatment to ensure proper subject selection. 
4.3.4.1.1 INDEPENDENT PHOTOGRAPHIC ASSESSMENTS 
Three experienced, blinded photographic reviewers will perform a qualitative analysis/review of the pre-
treatment and post-treatment sets of images of each subject in a blinded and randomized order. Each 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 21 of 50 
blinded reviewer will choose which image is the post-treatment image. Success will be correct post-
treatment image selection by at least 2 out of 3 reviewers.  The percentage of subjects with a correct post-
treatment image selection will be calculated. 
Assessment of each subject’s baseline and follow-up images viewed simultaneously will be performed by 
the Independent Photographic Reviewers (IPR) who will be blinded to the study subject’s visit (baseline and 
follow-up visit).  Each IPR will view each subject’s randomized pre-treatment and post-treatment images 
and assess which set of images represent the subject’s post-treatment images. Each photograph will have 
a unique identification number, but the sets of images will not be arranged in any specific order (i.e., 
randomized order). The Sponsor will prepare and administer the IPR. 
4.3.4.1.2 INDEPENDENT PHOTOGRAPHIC REVIEW EVALUATION PROCESS 
Each blinded assessor will be provided with identical photos to be assessed.  The pre-treatment and post-
treatment photos will be consistent in lighting, subject positioning, and focus.  Each photo’s visit interval, 
i.e., pre-treatment and post-treatment, will NOT be marked. The images placement (right or left) will be 
randomly ordered for pre-treatment and post-treatment images. Images for each subject will be grouped 
together into one set with all pre-treatment and post-treatment images in the same location (right/left) for 
the subject set. 
Each blinded assessor will conduct their assessment independently with no input from another blinded 
assessor. 
Each blinded assessor compares the Left and Right photo for change that may be striking (substantial and 
immediately noticeable), readily apparent but modest in nature, or slight and subtle in nature that may 
require close examination. Assessors should look through each view and assess change.  Enough time 
should be allowed to do this for each subject, so the assessments are not rushed. 
The assessor chooses which photo they believe to be the post-treatment photo (i.e., Left photo or Right 
photo) once all images in the subject set have been reviewed. 
Post-Analysis Coding of Masked Assessment: 
• 
If the assessor incorrectly chooses the post-treatment photo, this will be coded as an “Incorrect 
post-treatment selection”. 
• 
If the assessor correctly chooses the post-treatment photo, this will be coded as a “Correct post-
treatment selection”. 
• 
Success will be determined by correct identification of post-treatment photographs by at least two 
out of three blinded, independent reviewers.  
4.3.4.1.3 INDEPENDENT PHOTOGRAPHIC REVIEW TRAINING PROCESS 
IPR assessors will participate in a training session prior to completing the IPR. The purpose of the training is 
to provide guidance to the IPR assessors on the methods for reviewing the study images. Instructions will 
include that each blinded assessor should pay close attention to changes in: 
• 
Lower Eyelid laxity 
• 
Lower Eyelid fine lines and wrinkles 
• 
Overall appearance of the treatment area 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 22 of 50 
4.3.4.2 SNAP-BACK TEST GRADE 
Analysis of change from baseline to D30, D90, and D180 in the Snap-back Test Grade14. This test provides relative 
lower lid laxity. In normal lids, the skin snaps-back to the original position immediately; the longer it takes, the more 
laxity is present.  
To perform the snap-back test, pull the lower lid away and down from globe for several seconds and wait to see how 
long it returns to the original position without the subject blinking. 
Grade 0 – IV (0 = normal, IV = severe laxity: 
• 
Grade 0 – Normal lid that returns to position immediately on release. 
• 
Grade I – Approximately 2-3 seconds to return to original position. 
• 
Grade II – 4-5 seconds to return to original position. 
• 
Grade III - >5 seconds but does return to original position with blinking. 
• 
Grade IV – Never returns to original position and continues to hang down in frank ectropion after the snap-
back test. 
 
FIGURE 3: SNAP-BACK TEST 
4.3.4.3 MEDIAL CANTHAL LAXITY TEST GRADE 
Analysis of change from baseline to D30, D90, and D180 in the Medial Canthal Laxity Test14. This test provides medial 
canthal laxity by means of measuring displacement. The greater the distance, the more the laxity.  
 
To perform the medial canthal laxity test, pull the lower lid laterally away from the medial canthus and measure 
displacement of medial punctum. 
 
Grade 0 – IV (0 = normal, IV = severe laxity: 
• 
Grade 0 – <2mm displacement. 
• 
Grade I – Approximately 2mm displacement. 
• 
Grade II – Approximately 3mm displacement. 
• 
Grade III - >3mm displacement. 
• 
Grade IV – Does not return to baseline after release and blinking 
4.3.4.4 LATERAL CANTHAL LAXITY TEST GRADE 
Analysis of change from baseline to D30, D90, and D180 in the Medial Canthal Laxity Test14. This test provides lateral 
canthal laxity by means of measuring displacement. The greater the distance, the more the laxity.  
 
To perform the lateral canthal laxity test, pull the lower lid medially away from the lateral canthus and measure 
displacement of lateral canthal corner. 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 23 of 50 
 
Grade 0 – IV (0 = normal, IV = severe laxity: 
• 
Grade 0 – <2mm displacement. 
• 
Grade I – 2-4mm displacement. 
• 
Grade II – 4-6mm displacement. 
• 
Grade III - >6mm displacement. 
• 
Grade IV – Does not return to baseline after release and blinking 
4.3.4.5 GLOBAL AESTHETIC IMPROVEMENT SCALE (GAIS) 
The Global Aesthetic Improvement Scale (GAIS) is a scale that rates global aesthetic improvement from the 
pretreatment appearance13. In this study both live observation and photo review are utilized by the physician or a 
qualified, delegated clinician and subject in order to assign a score. The PGAIS (Physician Global Aesthetic 
Improvement Scale) must be performed by the principal investigator. Both the PGAIS and SGAIS (Subject Global 
Aesthetic Improvement Scale) should be completed in two steps: 
• 
Based on a live assessment of the subject while referring to the subject’s pre-treatment photographs 
(subjects should be given a hand mirror for assessment); and 
• 
Based on a comparison of the subject’s pre-treatment photographs to the current post-treatment 
photographs. 
The Investigator will grade the overall improvement of treatment area as indicated in Table 3 by comparing the 
subject’s appearance at follow-up visits against a photograph taken prior to procedure.  Likewise, the subject will 
also rate their improvement compared to pre-treatment as shown in Table 4.  The modified GAIS results will be 
collected at the 30-day, 90-day, and 180-day follow-up visits.   
TABLE 3: MODIFIED GLOBAL AESTHETIC IMPROVEMENT SCALE EVALUATION - INVESTIGATOR 
Rating 
Description  
Very much improved 
Optimal cosmetic result from this procedure in this subject 
Much improved 
Marked improvement in appearance from the initial condition, but not completely optimal for this 
subject 
Improved 
Obvious improvement in appearance from the initial condition 
No change 
The appearance is essentially the same as the original condition 
Worse 
 
The appearance is worse than the original condition 
Much worse 
The appearance is much worse than the original condition 
Very much worse 
The appearance is very much worse than the original condition 
 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 24 of 50 
TABLE 4: MODIFIED GLOBAL AESTHETIC IMPROVEMENT SCALE EVALUATION - SUBJECT 
Rating 
Very much improved 
□ 
Much improved 
□ 
Improved 
□ 
No change 
□ 
Worse 
 
□ 
Much worse 
□ 
Very much worse 
□ 
 
4.3.4.6 SUBJECT SATISFACTION SURVEY 
The study subjects will be asked to complete a Subject Satisfaction Survey (Appendix A) at the 180-day follow-up 
visit. The subject should complete this assessment while referring to baseline photos, current photos, and a hand 
mirror. 
4.3.4.7 NUMERIC RATING SCALE (NRS) 
The study subjects will be asked to complete a 11-point Numeric Rating Scale (NRS)20 for the level of pain and 
discomfort associated with the study procedure. The average pain score for the entire region treated will be 
recorded. Directions to subject will be: “Please rate the average pain you are experiencing in the treatment area on 
a scale of 0-10, with 0 being ‘Best/No Pain’ and 10 being the ‘Worst Possible Pain’.” 
 
 
Pain will be defined in this study as the average pain reported in the treatment area using the following categories: 
None (Score of 0), Mild (Score of 1-5), Moderate (Score of 6-7), and Severe (Score of 8-10). Classifications of NRS 
pain scores have been documented in literature20.  Moderate and severe pain/discomfort are considered Adverse 
Events (AE). Severe subject reported pain does not necessarily correlate to a “severe” adverse event classification. 
Events will be classified by investigator based on clinical evaluation, the effect to daily activities, and mitigation 
needed as per Section 8 of this protocol. 
Subjects experiencing pain adverse events will be considered resolved when their pain score is documented as 
returning to a 0 score. 
Numeric Rating Scale will be completed pre-treatment, post-treatment, and at all follow-up visits to capture pain 
scores. 
4.3.4.8 ADVERSE EVENT REPORTING 
The definitions of Adverse Events (AEs) and the subtypes are provided in Section 8 of the study protocol.  Adverse 
events will be classified by the investigator as to: 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 25 of 50 
• 
Anticipated vs unanticipated 
• 
Serious vs not serious 
• 
Expected Treatment Effect (ETE) vs Adverse Event (AE) 
• 
Severity:  mild, moderate, severe 
• 
Device and/or procedure causality:  not related, related, undetermined 
4.3.4.9 ASA PHYSICAL STATUS CLASSIFICATION SYSTEM 
The ASA Physical Status Classification System has been in use for over 60 years19. The purpose of the system is to 
assess and communicate a patient’s pre-anesthesia medical co-morbidities. The classification system alone does not 
predict the perioperative risks, but used with other factors (e.g., type of surgery, frailty, level of deconditioning), it 
can be helpful in predicting perioperative risks, see Table 5. 
TABLE 5: ASA PS CLASSIFICATION 
ASA PS Classification 
Definition 
Adult Examples, Including, but not Limited to: 
ASA I 
A normal healthy patient 
Healthy, nonsmoking, no or minimal alcohol use. 
ASA II 
A patient with mild systemic disease 
Mild diseases only without substantive functional limitations. Current 
smoker, social alcohol drinker, pregnancy, obesity (30<BMI<40), well-
controlled DM/HTN, mild lung disease. 
ASA III 
A patient with severe systemic disease 
Substantive functional limitations; One or more moderate to severe 
diseases. Poorly controlled DM or HTN, COPD, morbid obesity (BMI ≥40), 
active hepatitis, alcohol dependence or abuse, implanted pacemaker, 
moderate reduction of ejection fraction, ESRD undergoing regularly 
scheduled dialysis, history (>3 months) of MI, CVA, TIA, or CAD/stents. 
ASA IV 
A patient with severe systemic disease 
that is a constant threat to life 
Recent (<3 months) MI, CVA, TIA or CAD/stents, ongoing cardiac ischemia 
or severe valve dysfunction, severe reduction of ejection fraction, shock, 
sepsis, DIC, ARD or ESRD not undergoing regularly scheduled dialysis. 
ASA V 
A moribund patient who is not expected 
to survive without the operation 
Ruptured abdominal/thoracic aneurysm, massive trauma, intracranial 
bleed with mass effect, ischemic bowel in the face of significant cardiac 
pathology or multiple organ/system dysfunction. 
ASA VI 
A declared braindead patient whose 
organs 
(Intentionally left blank) 
5. 
SUBJECT ENROLLMENT AND WITHDRAWAL 
5.1 
STUDY POPULATION 
The study population will consist of males and females between 18 – 75 years of age who have chosen to participate 
in this clinical trial as evidenced by execution of the informed consent document and meet eligibility criteria defined 
in this protocol are eligible for participation in this clinical trial. Subjects will be considered enrolled into the study 
when they have signed an approved informed consent form. Subjects who are enrolled and do not meet eligibility 
criteria will be exited as a screen fail without study treatment. A study exit Case Report Form will be completed for 
all enrolled subjects. 
5.1.1  INFORMED CONSENT 
Informed consent will be obtained from all subjects prior to study participation. Informed consent is a process that is 
initiated prior to the individual’s agreeing to participate in the study and continues throughout the individual’s study 
participation. Extensive discussion of risks and possible benefits of participation will be provided to each participant.  
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 26 of 50 
Investigators have ethical and legal responsibilities to ensure that the protocol is clearly explained to each subject 
considered for enrollment in the study. Compliance with this requirement should be documented on a written 
Informed Consent Form approved by the reviewing IRB. Each Informed Consent Form will include the elements 
required by FDA regulations in 21 CFR Part 50/EU MDR Article 63. 
 
Consent forms will be IRB-approved, and the participant will be asked to read and review the document. The investigator, 
or investigator-delegated study personnel, will explain the research study to the participant and answer any questions 
that may arise. All participants will receive a verbal explanation in terms suited to their comprehension of the purposes, 
procedures, and potential risks of the study and of their rights as research participants. Participants will have the 
opportunity to carefully review the written consent form and ask questions prior to signing. The participants should have 
the opportunity to discuss the study with their surrogates or think about it prior to agreeing to participate. The participant 
will sign the informed consent document prior to any procedures being done specifically for the study.  
 
The IRB-approved Informed Consent Form will be signed by the study personnel obtaining consent. A copy of the 
informed consent document will be given to the participants for their records. The investigative site will keep the 
original on file. The rights and welfare of the participants will be protected by emphasizing to them that the quality of 
their medical care will not be adversely affected if they decline to participate in this study. 
 
The participants may withdraw consent at any time throughout the course of the trial without any penalty or loss of 
benefits to which the subject is otherwise entitled. An Investigator may also discontinue a subject from the study without the 
subject’s consent, if the Investigator feels it is in the best medical interest of the subject.  The date and the reason for study 
withdrawal will be indicated on the Study Exit CRF.   
5.1.2  PRE-TREATMENT RECRUITING/SCREENING 
Subjects will be recruited from the study site’s patient database and social media advertising.  Study site personnel 
will explain the design and purpose of the study to potential study subjects and a pre-screening questionnaire 
(Appendix B) will be completed. Subjects interested in participating and who qualify based on the pre-screening 
questionnaire will visit the study site where informed consent will be obtained.   
5.1.3.1 SCREEN FAILURES 
A screen failure subject is one from whom informed consent is obtained and is documented in writing (i.e., subject 
signs an Informed Consent Form), but who does not receive a study treatment because of failure to meet all of the 
eligibility criteria. Screen failure subjects will be included in the total number of subjects enrolled (i.e., all subjects 
consented), but not counted towards the total subjects treated. 
5.2 INCLUSION CRITERIA 
Subjects must meet all of the following criteria for study enrollment: 
• 
Male or female subjects, ages 18 – 75 years old. 
• 
ASA Physical Status Classification System Class I and Class II subjects. 
• 
Complaint of skin laxity or lines in the lower eyelid area. 
• 
Understands and accepts the obligation not to undergo any other procedures or treatments in the areas to 
be treated during study participation. 
• 
Absence of physical conditions unacceptable to the investigator. 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 27 of 50 
• 
Females of childbearing potential who are sexually active must be willing to use an approved method of 
birth control during study participation. 
• 
Willing and able to comply with protocol requirements, including study-required images/photos, 
assessments/measurements, and returning for follow-up visits. 
• 
Willing to release rights for the use of study photos, including in publication. 
• 
Able to read, understand, sign, and date the informed consent. 
• 
Able to communicate with the site via video and/or photographs, in the event of a virtual follow-up visit. 
5.3 
EXCLUSION CRITERIA 
Subjects will be excluded if they meet any of the following criteria: 
• 
Subjects presenting with ASA Physical Status Classification System Classes III or higher. 
• 
Previous surgery in the periorbital area. 
• 
Festoons in the periorbital area. 
• 
Pregnant, lactating, or plans to become pregnant during study participation. 
• 
Known hypersensitivity or allergy to tumescent anesthetic (lidocaine/ epinephrine). 
• 
Known hypersensitivity or allergy to ibuprofen or other NSAIDS. 
• 
Active systemic or local skin disease that may alter wound healing. 
• 
Significant or uncontrolled medical condition that in the opinion of the investigator participation in the 
study may compromise the patient’s health. 
• 
History of autoimmune disease (excluding Hashimoto’s thyroiditis). 
• 
Known susceptibility to keloid formation or hypertrophic scarring. 
• 
Cancerous or pre-cancerous lesions in the area to be treated. 
• 
Possesses a surgically implanted electronic device (i.e., pacemaker). 
• 
Serious mental health illness such as dementia or schizophrenia; psychiatric hospitalization in the past two 
years. 
• 
Participation in any other investigational study within 30 days prior to consent and throughout study 
participation. 
• 
Subject who, in the opinion of the investigator, is not an appropriate candidate for the study. 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Subjects will receive compensation for completion of the Day 1, Day 3, Day 7, Day 14, Day 30, Day 90, and Day 180 
visits. Subject stipend amounts will be outlined in the site specific ICF and approved by the IRB prior to subject 
enrollment. 
5.5  
PARTICIPANT WITHDRAWAL OR TERMINATION 
5.5.1 REASONS FOR WITHDRAWAL OR TERMINATION 
All subjects have the right to withdraw at any point during the study without prejudice. The investigator can 
discontinue any subject, at any time, if medically necessary. Subjects must be discontinued from the investigation 
by the investigator at any time for any of the following reasons: 
• 
Withdrawal of informed consent. 
• 
Pregnancy (no further study-related procedures will be performed). 
• 
Any AEs for which treatment continuation would constitute an unacceptably high risk for the subject. 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 28 of 50 
The reason for subject’s withdrawal should be documented on the appropriate study specific CRF.  
5.5.2 HANDLING OF WITHDRAWALS OR TERMINATION 
The subject must undergo the recommended follow-up assessments specified for the last study visit unless 
contraindicated due to a medical condition. Withdrawn subjects will not be replaced. 
 
Subjects who are discontinued from the study due to an AE(s) will be treated according to standard clinical practice 
and will be followed-up until the final study visit/safety visit as described in Section 7. All pertinent information 
concerning the AE will be documented on the appropriate study specific CRF. 
 
A subject may discontinue from the study at any time without any penalty or loss of benefits to which the subject is 
otherwise entitled. An Investigator may also discontinue a subject from the study without the subject’s consent, if 
the Investigator feels it is in the best medical interest of the subject.  The date and the reason for study withdrawal 
will be indicated on the Study Exit CRF.   
5.6 
PREMATURE TERMINATION OR SUSPENSION OF THE STUDY OR A STUDY SITE 
The study or a study site can be prematurely terminated or suspended by the sponsor. Reasons for termination of 
the study or a study site may include, but are not limited to, the following: 
• 
Subject enrollment is unsatisfactory. 
• 
The risks and benefits of continuing the study have been reassessed, and the risks outweigh any potential 
benefits. 
• 
The incidence of AEs constitutes a potential health hazard to the subjects. 
• 
New scientific data do not justify a continuation of the study. 
• 
The investigator or study site exhibit serious and/or persistent non-adherence to the protocol, the 
Declaration of Helsinki, EN ISO 14155, and/or applicable regulatory requirements. 
• 
The sponsor decides to terminate the study at any time for any other reason. 
Furthermore, the study may be prematurely ended if the regulatory authority or the IRB has decided to terminate 
or suspend approval for the study, the study site, or the investigator. If the study is prematurely terminated or 
suspended for any reason, the investigator must inform the subjects and assure appropriate follow-up treatment. 
Within the timeframes noted in applicable regulations, the sponsor will promptly inform the investigators, study 
sites, the IRB, and regulatory authorities of the termination or suspension of the study, as well as provide reasons 
for the action. 
6. 
STUDY DEVICE 
FDA-cleared devices shipped for use in clinical investigations conform to the applicable general safety and 
performance requirements (GSPR) apart from the aspects covered by the clinical investigation and that, with regard 
to those aspects, every precaution is taken to protect the health and safety of the subjects. This includes, where 
appropriate, technical, and biological safety testing and pre-clinical evaluation as well as provisions in the field of 
occupational safety and accident prevention and taking into consideration the state of the art. Apyx Medical will 
provide devices for use in this clinical investigation. 
6.1 
PACKAGING & STORAGE 
The sponsor will provide appropriate packaging and storage instructions to the study sites. 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
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Title: Clinical Trial Protocol 
Revision: 02 
 
Page 29 of 50 
6.2 
ACCOUNTABILITY 
The investigator, or designee, must maintain an inventory record using the site-specific Device Disposition Form of 
study devices received, used for treatment, and returned to the Sponsor to ensure that the investigational device 
will not be dispensed to any person who is not a subject under the terms and conditions set forth in this protocol. 
There will be 100% accountability for all clinical study devices. The clinical study site shall maintain all devices 
received for clinical trial use in a locked, limited access cabinet or room until the end of the study unless they are 
returned to Apyx while the study is being conducted, such as at the end of study treatments. 
6.3 
DEVICE MALFUNCTION/OBSERVATION 
All malfunctions of, or defects of the delivery system will be reported to the Sponsor by the investigational sites.  
This will include situations where the delivery system did not perform as intended; user errors; study 
device/component being physically defective, including out of the box failure. 
7. 
STUDY PROCEDURES AND SCHEDULE 
7.1 
PRE-PROCEDURE 
Study subjects will have verification of eligibility criteria, a brief general examination including medical history, and 
pre-procedure assessments as detailed below completed within 30 days prior to undergoing the study procedure, 
see Table 6. In response to the ongoing coronavirus disease (COVID-19) pandemic, preoperative testing can be 
completed at the Investigator’s discretion.  Pre-operative testing should be performed as close to the scheduled 
study procedure as feasible, but in time to get the results. Up to two urine pregnancy tests must be obtained prior 
to study procedure for females with child-bearing potential (one at pre-procedure screening and one on the day of 
the procedure prior to the procedure if pre-procedure screening and procedure are not performed on the same 
day).  
The following pre-treatment assessments will be performed:  
• 
Subject ASA will be determined. 
• 
Brief medical history and physical examination per the Investigator’s standard of care. 
• 
Urine pregnancy test (for females of childbearing potential). 
• 
Baseline imaging using the site’s 2D photography system. 
• 
Snap-back Test Grade. 
• 
Medial Canthal Laxity Test Grade. 
• 
Lateral Canthal laxity Test Grade. 
 
Medications the subject is taking upon entry into the study should also be documented in the Case Report Forms 
(CRF). All concomitant prescription medications taken during study participation will be recorded on the appropriate 
study specific CRF. For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician. Medications to be reported on the CRF and entered on the eCRF are 
concomitant prescription medications, over-the-counter medications, and non-prescription medications. 
Medication used for analgesia and/or anesthesia should be recorded as concomitant medication as well. To ensure 
the capture of the foregoing information on pre-existing conditions, sites should also be attentive to the need to 
document without limitation and whenever discovered: (1) all chronic, episodic or ‘as needed’ medications used 
before study enrollment; (2) prior episodic or ‘as needed’ therapeutic interventions, procedures or hospitalizations; 
and (3) recent or planned surgical procedures.  

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 30 of 50 
7.2 
STUDY PROCEDURE 
On the day of the procedure and prior to the study procedure, female subjects with child-bearing potential must 
complete a urine pregnancy test (result must be obtained prior to the procedure), see Table 6. Medications at 
investigator discretion may be provided. The treatment area will be tumesced with 20 - 25ml of fluid on each side of 
the periorbital area.  
 
The treatment of the periorbital area will be accessed from an incision placed in the crease of the lower lid.  Two 
incisions will be placed in both the medial and lateral crease of the lower lid.  Treatment will be performed through 
one incision and the second incision will be used to allow for adequate venting of helium gas.  Care will be taken to 
undermine the tissue and to ensure the incisions communicate with each other to allow adequate venting.  An 
optional third lower lid incision may be made as needed. The treatment plane will be above the orbicularis muscle. 
The treatment settings will be 60-70% Power, 1 LPM, and 3 Passes.  Procedure data and adverse events will be 
captured. 
7.3 
FOLLOW-UP PROCEDURES  
7.3.1 IMMEDIATELY POST-PROCEDURE  
Following the procedure, the research staff and the subject will care for the treated areas using the Post-Procedure 
Care Instructions per the Investigator’s standard clinical practice.  
7.3.2 FOLLOW-UP VISITS & SUBJECT CONTACT OUTSIDE OF FOLLOW-UP VISITS 
Subjects will be asked to return to the study site at the following times post-procedure: 
• 
1 day 
• 
3(±1) days 
• 
7 (±3) days 
• 
30 (±7) days 
• 
90 (±10) days 
• 
180 (±15) days 
Post-procedure assessments and 2D photographic imaging will be performed during the follow-up visits, see Table 
6. The same standardized photography views will be used throughout the study as documented in the image capture 
document developed for the study.  
Due to the challenges of COVID-19, if a subject is unable to return to the office for an in-person visit, follow-up visits 
will be conducted virtually. If a visit is completed virtually, missing assessments such as photographs will be 
documented as a protocol deviation specifically noting COVID-19. Outside of photographs, study investigators and 
study staff will ensure all other assessments related to each follow-up visit are completed virtually if the visit is done 
virtually. For virtual visits, the investigator and/or study staff completing the visit and assessments will be identified 
on the case report form; as well, the manner in which the visit was completed will also be recorded (i.e., video call, 
phone call, etc.). Virtual visits should be done via video call, if possible, to ensure subject identity. If a telephone call 
must be done, the investigator and/or study staff must positively identify the subject prior to conducting the virtual 
visit by requesting the subject to state their address and date of birth. Subjects will be strongly encouraged to come 
in (albeit safely) for their D180 visit; this visit is vitally important as this is the primary endpoint and photographic 
images are needed for many of the assessments. Only investigators and study staff who have been trained and 
delegated to conduct virtual visits as indicated on the delegation log may conduct virtual study visits. 
Subjects may be seen for an unscheduled appointment at any time at investigator’s discretion. 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 31 of 50 
Study staff will contact (phone, text, email, video call at subject’s preference) all subjects with ongoing Adverse 
Events at regular intervals. If the subject is unreachable by the preferred method of contact, another method of 
contact may be attempted.  
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 32 of 50 
TABLE 6: STUDY REQUIRED PROCEDURES 
 
 
Baseline/  
Pre-Procedure 
Screening1 
Procedure 
(Day 0) 
1 Day 
 3 Days 
7 Days 
 30 Days 
 90 Days 
 180 Days 
1 day 
2-4  
days 
4-10  
days 
23-37 
days 
80-100 
days 
165-195 
days 
Informed Consent 
X 
 
 
 
 
 
 
 
Assess Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
Urine Pregnancy Test2 
X 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
General Physical Exam 
X 
 
 
 
 
 
 
 
Review Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Visia Photographic Images3 
X6 
X6 
 
X 
X 
X 
X 
X 
Numeric Rating Scale (11-point NRS)  
 
X4 
X 
X 
X 
X 
X 
X 
Study Procedure 
 
X 
 
 
 
 
 
 
Adverse Event Assessment  
 
X 
X 
X 
X 
X 
X 
X 
Laxity Assessments 
X 
 
 
 
 
X 
X 
X 
Modified Global Aesthetic Improvement 
Scale (GAIS) 5  
 
 
 
 
 
X 
X 
X  
Subject Satisfaction Survey 
 
 
 
 
 
 
 
X 
1 Pre-procedure Screening assessments to take place within 30 days prior to undergoing the procedure. 
2 Up to two urine pregnancy tests must be obtained prior to study procedure for females with child-bearing potential (one at pre-procedure 
screening and one on the day of the procedure prior to the procedure). 
3Digital photographs will be taken and labeled according to Photography Instructions. Standard positioning and lighting will be used for all 
photographs.  
4 NRS pain score will be captured prior to study treatment and immediately (within 60 minutes) after procedure. 
 5 To be completed by Investigator and study subject at day 30, 90, and 180 follow-up visits. 
6 Pre-procedure images may be taken if Baseline/Screening images are not considered acceptable by the quality review team, however if the 
Baseline/Screening image is acceptable by the quality review team, no additional pre-procedure image needs to be taken. 
7.4 
SUBJECT RANDOMIZATION AND TREATMENT GROUP ASSIGNMENT  
No randomization. Subjects will receive treatment with the Renuvion APR System in the lower eyelid area on both 
sides of the face. 
7.3 
STUDY SCHEDULE 
7.3.1 SCREENING 
• 
Obtain informed consent of potential participant verified by signature on study informed 
consent form. 
• 
Verify all preliminary/screening inclusion/exclusion criteria are met. 
• 
Perform screening photography (may be used as baseline images). 
7.3.2 BASELINE ASSESSMENT  
• 
Obtain protocol-required baseline measures (Laxity Tests). 
• 
Document medical history. 
• 
Obtain pregnancy screen (if applicable). 
• 
Perform baseline photography if screening images were not acceptable.  
• 
Document concurrent medications. 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 33 of 50 
7.3.3 TREATMENT VISIT  
• 
Greater than 30 days between baseline and treatment visits will require that the subject be re-screened to 
confirm enrollment eligibility.  
• 
Obtain pregnancy screen (if applicable) prior to study treatment. 
• 
Perform study treatment. 
• 
Provide standard of care post-treatment instructions. 
7.3.4 FOLLOW-UP 
Subjects will be asked to return to the clinic for follow-up visits at 1, 3, 7-, 30-, 90-, and 180-days post-treatment, see 
Table 6. At all visits, subjects will be assessed for safety and pain, standardized images will be taken, adverse events 
and protocol deviations will be assessed. At D30, 90, and 180 visits, study outcome measures (GAIS, Laxity Tests) will 
be completed. At the 180-day follow-up appointment in addition to the above referenced assessments, the subject 
will complete a Patient Satisfaction Questionnaire.   
7.3.5 UNSCHEDULED VISIT 
Any unscheduled visit or examine should be documented in the subject’s medical record and adverse event form 
(if applicable) stating the reason for the visit and any actions taken. The Sponsor should be notified of the 
unscheduled visit. 
7.3.6 END OF STUDY (COMPLETION) 
All subjects who have signed an Informed Consent Form will be considered enrolled in the study. Subjects who 
complete the study duration will be considered to have completed the study. The end of study will be defined as 
completion of all study visits by all enrolled subjects. If a device-related AE, SAE, or unanticipated serious device-
related effect is ongoing at the final study visit, the subject will be followed until resolution, until the condition 
stabilizes, until the event is otherwise explained, or the subject is lost to follow-up.  
 
A study closure visit may be conducted at the study site in order to review record retention requirements, device 
disposition requirements, etc., with site personnel.  The Sponsor may choose to conduct the closure visit via 
telephone contact if appropriate. 
8. 
ASSESSMENT OF SAFETY 
8.1 
SPECIFICATIONS OF SAFETY PARAMETERS 
8.1.1 DEFINITION OF AN EXPECTED TREATMENT EFFECT (ETE) AND AN ADVERSE EVENT (AE) 
An expected treatment effect is defined as any typical treatment side-effect of the Renuvion APR System of mild to 
moderate severity and lasting up to a typical maximum duration.  An adverse event is defined as any new medical 
problem, or exacerbation of an existing problem, experienced by a subject while enrolled in the study, whether or 
not it is considered device-related by the investigator.   
 
An adverse event (AE) is any untoward or unfavorable medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease temporally 
associated with the subject’s participation in the research, whether or not considered related to the subject’s 
participation in the research.  
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 34 of 50 
A preexisting condition (one that is present at the start of the study) will be recorded as an AE only if the frequency, 
intensity, or the character of the condition worsens during the study period. Neither the condition, hospitalization, 
prolonged hospitalization, nor surgery are reported as an AE in the following circumstances: hospitalization or 
prolonged hospitalization for diagnostic or elective surgical procedures for a preexisting condition. Surgery should 
not be reported as an outcome of an AE if the purpose of the surgery was elective or diagnostic and the outcome 
was uneventful. 
 
All ETEs and AEs will be collected during the conduct of this trial.   
8.1.2 DEFINITION OF SERIOUS ADVERSE EVENT (SAE) 
Each adverse event should be assessed for its seriousness. The definition below should be used for this assessment. 
Please note that the term serious adverse event is not synonymous with a “severe” adverse event, which may be 
used to describe the intensity of an event experienced by the subject. (Please refer to Section 8.2.1 for severity 
definitions.) 
 
An adverse event should be classified as serious if it meets any of the following criteria: 
a. Death 
Death was an outcome of the adverse event.  
b. Life-threatening 
The subject was at substantial risk of dying at the time of the adverse event or use or continued use of 
the device. 
c. 
Hospitalization (initial or prolonged) 
Admission to the hospital or prolongation of hospitalization was a result of the adverse event. 
d. Disability or Permanent Damage 
The adverse event resulted in a substantial disruption of a person's ability to conduct normal life 
functions, i.e., the adverse event resulted in a significant, persistent or permanent change, impairment, 
damage or disruption in the patient's body function/structure, physical activities and/or quality of life. 
e. Congenital Anomaly/Birth Defect 
Exposure to a medical product prior to conception or during pregnancy may have resulted in an adverse 
outcome in the child. 
f. 
Required Intervention to Prevent Permanent Impairment or Damage (Devices) 
Medical or surgical intervention was necessary to preclude permanent impairment of a body function, 
or prevent permanent damage to a body structure, either situation suspected to be due to the use of 
a medical product. 
g. 
Other Serious (Important Medical Events) 
The event does not fit the other outcomes, but the event may jeopardize the subject and may require 
medical or surgical intervention (treatment) to prevent one of the other outcomes. 
 
Non-serious adverse events are all events that do not meet the criteria for a “serious” adverse event. 
8.1.3 DEFINITION OF UNANTICIPATED ADVERSE DEVICE EFFECTS (EVENTS) 
An unanticipated adverse device effect is defined as “any serious adverse effect on health or safety, or any life-
threatening problem, or death caused by, or associated with, a device; if that effect, problem, or death was not 
previously identified in nature, severity, or degree of incidence in the investigational plan, or application (including 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 35 of 50 
supplementary application), or any other unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects.” 
8.2 
CLASSIFICATION OF AN EVENT 
8.2.1 SEVERITY OF EVENT 
Each adverse event should be assessed for its severity, or the intensity of an event experienced by the subject, using 
the following classifications: 
• 
Mild: easily tolerated by the subject, causing minimal discomfort, and not interfering with everyday 
activities. These events generally do not require treatment.  
• 
Moderate: sufficiently discomforting to interfere with normal everyday activities.  These events are usually 
relieved by simple therapeutic measures.  
• 
Severe:  prevents normal, everyday activities.  These events may require systemic drug therapy or other 
medical treatment. 
8.2.2 RELATIONSHIP TO THE STUDY DEVICE AND PROCEDURE 
The relationship to the study device and/or procedure and non-related events will be determined by the investigator 
utilizing the following categories: 
• 
Not Related: An event for which an alternative explanation is conclusively identified – e.g., concomitant 
drug(s), concomitant disease(s), and/or the relationship in time suggests that a causal relationship is highly 
unlikely. 
• 
Related: The adverse event follows a reasonable temporal sequence related to treatment by the device 
and/or study procedure, follows a known or suspected response pattern and a plausible alternative etiology 
cannot be identified. 
• 
Undetermined: The relation of the adverse event has some temporal relationship to the device and/or 
study procedure, is not clearly due to another condition and the involvement of the study device and/or 
study procedure is unknown.  
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an AE or SAE may come to the attention of study personnel during a study visit or upon review by 
a study monitor. All ETEs and AEs will be captured on the appropriate CRF. Information to be collected includes event 
description, date of onset, clinician’s assessment of seriousness and severity, relationship to study device/treatment 
(assessed only by those with the training and authority to make a determination), actions taken, and date of event 
resolution. All AEs occurring while on study must be documented appropriately regardless of relationship. All 
ETEs/AEs assessed as “not yet resolved” must continue to be followed via telephone contact, email or clinic visit 
every 7 days or sooner as per the physician’s direction until event resolution or stabilization.   
 
A pre-existing condition should not be reported as an adverse event unless there has been a substantial increase in 
severity or frequency of the problem that has not been attributed to natural history. Changes in the severity of an 
event will be documented to allow for a determination if the event should be re-categorized from an ETE to AE.   
Safety evaluations for this study include an interview with the study subject at each follow-up visit by the Investigator 
or delegated study staff to elicit information about any medical occurrence that meets the definition of Adverse 
Event. This information will be documented in CRF without regard for cause or relation to device and/or procedure. 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 36 of 50 
In addition, study subjects will be instructed in the Informed Consent Form, post-procedure take-home instructions, 
and verbally by study staff to report all complications experienced post study procedure to the site personnel as 
soon as they occur/are observed. Study staff will ensure that monitoring and management of all adverse events is 
prioritized. Subjects may be asked to come into the site at any time to assess adverse events.  
Study investigators are provided liberty to mitigate adverse events as deemed necessary per IHC GCP Guidelines 
E6(R2)4.3.2 which states, “During and following a subject’s participation in a trial, the investigator/institution should 
ensure that adequate medical care is provided to a subject for any adverse events related to the trial”. 
Adverse event resolution dates will be determined by investigator using either in-person or remote (phone, video 
call, text, email, etc.) examinations or communication with the subject.  To ensure the most accurate reporting of 
adverse event durations, investigators are instructed not to wait until scheduled office follow-up visits to assess 
resolution. 
It is the Investigator’s responsibility to determine seriousness, severity, and relatedness of the Adverse Event to the 
device and procedure using the definitions in this protocol. 
The PI will record all reportable events with start dates occurring any time after informed consent is obtained until 
7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation. At each study visit, the 
investigator will inquire about the occurrence of ETEs/AEs/SAEs since the last visit. Events will be followed for 
outcome information until resolution or stabilization. 
8.4 
REPORTING PROCEDURES 
8.4.1 ADVERSE EVENT REPORTING 
All Adverse Events (AEs) and Expected Treatment Effects (ETEs) observed by study subjects, investigators, or other 
study staff from first exposure to the study product through last study follow-up visit will be recorded. If a device-
related AE, ETE, SAE, or unanticipated serious device related effect is ongoing at the final study visit, the subject will 
be followed until resolution, until the condition stabilizes, until the event is otherwise explained, or the subject is 
lost to follow-up. The investigator should make every effort to ensure that follow-up includes any supplemental 
investigations as may be indicated to elucidate, as completely as practical, the nature and/or causality of the AE or 
SAE. This may include unscheduled follow up visits for AE assessment. 
 
Study subjects will be instructed in the ICF, post-treatment take home instructions, and verbally by study staff to 
report all AEs to the clinical study staff.  AE information will be collected throughout the duration of the study and 
recorded on CRFs. Subjects experiencing ongoing adverse events will be contacted as per Section 8.1.                                                         
 
Any new medical problem, or an exacerbation of an existing condition, reported from the time the informed consent 
form is signed must be followed until the last study visit after the last study treatment or until event resolution.   
8.4.2 SERIOUS ADVERSE EVENT REPORTING 
Serious adverse events must be reported to the Sponsor as soon as possible, preferably within 24 hours but in no 
event later than 72 hours. Any AE considered serious by the PI or Sub-investigator, or which meets the definition 
of an SAE included in Definition of Serious Adverse Event must be documented on an SAE CRF.  
 
The Sponsor will conduct an investigation. If the Sponsor determines that the investigation presents an unreasonable 
risk to subjects, all investigations or parts of the investigation presenting that risk will be terminated as soon as 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 37 of 50 
possible. The investigator must report serious adverse events to the reviewing IRB/FDA according to the FDA 
regulations. 
8.4.3 UNANTICIPATED ADVERSE DEVICE EFFECT REPORTING 
If an unanticipated adverse device effect occurs, the study investigator shall complete the appropriate study specific 
CRF and submit to the study sponsor and to the reviewing IRB as soon as possible, but in no event later than 10 
working days after the investigator first learns of the effect. The study sponsor contact information is provided in 
Apyx Medical Study Contact List. The study sponsor is responsible for conducting an evaluation of an unanticipated 
adverse device effect and shall report the results of such evaluation to FDA and to all reviewing IRBs and participating 
investigators within 10 working days after the sponsor first receives notice of the effect. Thereafter the sponsor shall 
submit such additional reports concerning the effect as FDA requests. 
8.4.4 REPORTING OF PREGNANCY 
Each pregnancy that starts during the subject’s study participation must be reported by the investigator to the 
Sponsor within 24 hours of learning of its occurrence. Pregnancies and pregnancy follow-up should be reported on 
an Adverse Event form. Pregnancy follow-up should describe the outcome of the pregnancy, including any voluntary 
or spontaneous discontinuation; details of the birth; the presence or absence of any congenital abnormalities, birth 
defects, maternal or newborn complications, and their relation to the device or treatment. Each pregnancy must be 
reported as a non-serious AE if the subject has received at least one study treatment.  The following criteria should 
be followed: 
• 
If a subject becomes pregnant after the Baseline visit and all study treatments have been completed, the 
subject should continue to be followed for the duration of the pregnancy. 
• 
If a subject becomes pregnant after the Baseline visit but before any study treatments, the subject should 
be exited from the study. 
• 
If a subject becomes pregnant after the Baseline visit but before all study treatments have been completed, 
additional study treatments should be discontinued, and the subject should continue to be followed for the 
duration of the pregnancy. 
8.4.5  REPORTING OF DEATHS 
The investigator must notify the Sponsor as soon as possible, preferably within 24 hours but in no event later than 
48 hours, of learning of a subject’s death, regardless of whether the death is related or unrelated to the 
investigational device. The investigator should attempt to determine, as conclusively as possible, whether the death 
is related to the device. The cause of death and the investigator’s discussion regarding whether or not the death was 
device-related should be described in a written report. The investigator mush report death to the reviewing IRB 
according to the IRB regulations at the study site. 
8.5 
STUDY HALTING RULES 
This clinical trial will be halted if subjects’ safety is questioned based on a reporting of severe, device-related AEs at 
an excessive frequency.  The Sponsor and/or investigator may recommend termination or modification of the study 
if there is an occurrence of any device- or treatment-related Serious Adverse Event, using the clinical protocol 
definitions of Serious Adverse Event. In addition, termination or modification may be recommended for any other 
perceived safety concern based on clinical judgment, including but not limited to a severe burn (anticipated or 
unanticipated), a higher than anticipated rate for any component of the safety measures, device failures resulting in 
Adverse Events, or unexpected SAEs. The study sponsor will notify all investigators to immediately halt any 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 38 of 50 
continuing enrollment activities and not enroll any additional study participants.  The study sponsor will inform the 
IRB/FDA of the temporary halt and the disposition of the study. 
 
The Sponsor and/or investigator may recommend termination or modification of the study if there is an occurrence 
of any device- or treatment-related Serious Adverse Event, using the clinical protocol definitions of Serious Adverse 
Event. In addition, termination or modification may be recommended for any other perceived safety concern based 
on clinical judgment, including but not limited to a severe burn (anticipated or unanticipated), a higher than 
anticipated rate for any component of the safety measures, device failures resulting in Adverse Events, or 
unexpected SAEs. Enrollment and treatment would be suspended during root cause investigation to determine the 
cause of the respective AE. 
9. 
CLINICAL MONITORING 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are protected, that 
the reported trial data are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with 
the currently approved protocol/amendment(s), with GCP, and with applicable regulatory requirement(s). A study-
specific Monitoring Plan will further define responsibilities and details related to clinical site monitoring.   
10. STATISTICAL METHODOLOGY 
10.1 STATISTICAL AND ANALYTICAL PLANS 
For the purposes of this post-market study, descriptive statistics will be performed. For a given parameter, data will 
be summarized for each time point for which data for that parameter are available. Categorical variables will be 
summarized as frequencies and percentages in each category.  Continuous and ordinal variables will be summarized 
as numbers of subjects, means, standard deviations, medians, and ranges. 
 
An interim review and analysis of all study data through Day 90 will be completed once all subjects have passed the 
Day 90 visit window. 
10.2 SAMPLE SIZE 
The study will include up to 16 treated subjects from a single center in Greece.  
11. SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/ 
DOCUMENTS 
Source documents are defined as the results of original observations and activities of a clinical investigation. Source 
documents will include, but are not limited to, study specific CRFs, progress notes, electronic data, computer 
printouts, screening logs, and recorded data from automated instruments. All source documents pertaining to this 
study will be maintained by the investigators and made available for inspection by authorized persons. 
12. QUALITY ASSURANCE AND QUALITY CONTROL 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
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Quality Assurance and Quality Control procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution via data queries. 
 
Following written SOPs, the clinical study monitors will verify that the clinical trial is conducted, and data are 
generated, documented (recorded), and reported in compliance with the protocol, GCP, and the applicable 
regulatory requirements. 
 
The investigational site will provide direct access to all trial related sites, source data/documents, and reports for 
the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory authorities. 
13. ETHICS/PROTECTION OF HUMAN SUBJECTS 
13.1 ETHICAL STANDARD 
This clinical study will be conducted in accordance with the Protection of Human Subjects Regulations, including 
Subpart B Informed Consent of Human Subjects (21 CFR Part 50); the Institutional Review Board Regulations (21 CFR 
Part 56); the Financial Disclosure by Clinical Investigators Regulations (21 CFR Part 54); and the Investigational Device 
Exemptions Regulations (21 CRF Part 812), and the ICH E6. 
13.2 INSTITUTIONAL REVIEW BOARD 
Prior to initiation of any study procedures, the protocol, informed consent, and recruitment materials, and all 
participant materials will be submitted to a duly constituted IRB for view and approval. In addition, any amendments 
to the protocol or Informed Consent Form will be reviewed and approved by the IRB. The Sponsor must receive a 
letter documenting IRB approval at the clinical site prior to the initiation of the study. 
 
The investigator is responsible for providing the appropriate reports to its reviewing IRB during the course of the 
clinical study. These reports will include: 
• 
Informing the IRB of the study progress periodically as required, but at least annually; 
• 
Reporting any unanticipated adverse device effects within 10 working days of first learning of the event; 
• 
Reporting any deviations from the clinical protocol to protect the life or well-being of a subject in the case 
of an emergency within five working days after the emergency occurred; 
• 
Reporting the use of the device without obtaining informed consent from a subject within five working days 
of the event; and  
• 
Providing any other reports requested by the IRB. 
The IRB must be notified of study completion within 30 days of the final visit of the last subject and should be 
provided with a summary of the results of the study by the investigator. 
13.3 PARTICIPANT AND DATA CONFIDENTIALITY 
All information generated in this study must be considered highly confidential and must not be disclosed to any 
persons not directly concerned with the study without prior written permission from the Sponsor. Authorized 
regulatory officials and Sponsor personnel (or its representatives) will be allowed full access to inspect the records. 
Data disclosed outside the study team will be de-identified or will only include general group demographic 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 40 of 50 
information. Protected Health Information and/or identifiable study data will not be shared with anyone outside the 
study team or Health System, with the exception of the study sponsor, and federal regulators/ institutional officials 
for the purposes of auditing. 
 
All investigational devices and/or other materials collected will be used solely in accordance with this protocol, 
unless otherwise agreed to in writing by the Sponsor.  
 
Subjects should be identified only by initials and unique subject numbers on study specific CRFs. If necessary, their 
full names may be made known to a regulatory agency or other authorized officials. Information to be stored on the 
computer will be identified by subject ID and will be password protected. 
14. DATA HANDLING AND RECORD KEEPING 
14.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site PI. The 
investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data reported.  
 
During each subject’s visit to the clinic, study data will be documented by study personnel on study-specific Case 
Report Forms (CRFs) prior to entry into an Electronic Data Capture (EDC) system. Subject demographic information, 
procedural data, adverse events, device observations, and study required assessments will be documented on the 
CRFs by delegated site personnel.  Study subjects will complete Numeric Rating Scale, Laxity Grades, and Modified 
Global Aesthetic Improvement Scale (GAIS) Evaluations at protocol specified follow-up visits. Subjects will complete 
a Satisfaction Survey at the 180-day follow-up visit. In addition, study personnel will record progress notes to 
document all significant observations, and any contact with a subject by telephone or other means that provides 
significant clinical information will also be documented in the progress notes as described above. In this clinical trial, 
study specific CRFs may serve as source documents. 
 
For transmission to the Sponsor, information from the study progress notes and other source documents will be 
promptly transcribed to study specific CRF to the EDC with the CRF attached for remote monitoring of the data. 
Transcription of study data onto study specific CRFs and entry into the EDC should be completed within 3 days of 
the study visit. 
 
Copies of the electronic CRF (eCRF) serving as source documents must be maintained for each participant enrolled in 
the study. Data reported in the eCRF derived from source documents should be consistent with the source documents 
or the discrepancies should be explained and captured in a progress note and maintained in the participant’s official 
electronic study record. 
 
Any changes to information in the study progress notes, other source documents, and CRFs will be initialed and 
dated in ink on the day the change is made by a site study staff member authorized to make the change. Changes 
will be made by striking a single line through erroneous data, and clearly entering the correct data. If the reason for 
the change is not apparent, a brief explanation for the change will be written in the source documentation by the 
investigator and/or delegated staff. 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 41 of 50 
Photographic images will be captured utilizing the site’s camera system as per instructions provided in this protocol. 
Images will be uploaded by the site to Box.com. 
 
Data management and oversight is the responsibility of the Sponsor, details are provided in a study specific Data 
Management Plan.  Responsibilities include, but are not limited to, the following:   
• 
Clinical strategy and oversight. 
• 
Clinical study operations. 
• 
File management and study documentation. 
• 
Site initiation visits and study close-out visits. 
• 
Clinical quality assurance. 
• 
Statistical support and programming. 
• 
Data management, including database development and programming and electronic data capture (EDC) 
programming, training, and management. 
• 
Management and oversight of photographic imaging.   
 
Responsibilities may be delegated to applicable vendors. 
14.2 INVESTIGATOR RECORDS AND REPORTS 
14.2.1 INVESTIGATOR RECORDS 
Prior to participation in the investigation, the investigator must provide the following documentation to the Sponsor:  
• 
Investigator Agreement, signed by the investigator, which lists any physicians who will be involved in 
conducting the investigation under the direction of the primary investigator. 
• 
A copy of the principal investigator’s, sub-investigator’s, other delegated study clinicians’ curriculum vitae. 
• 
A letter signed by the chairperson of the IRB overseeing the conduct of this study indicating that the IRB 
has reviewed and approved this investigational plan. 
• 
A copy of the IRB-approved Informed Consent Form. 
During the study, investigators are required to maintain on file the following accurate, complete, and current records 
relating to this study as described in 21 CFR §812.140. A summary of these records is listed below: 
• 
Executed Clinical Trial Agreement. 
• 
Signed Financial Disclosure. 
• 
All correspondence and required reports, which pertain to the study, including IRB approvals and 
correspondence. 
• 
Shipping documents and Device Disposition Log which records of receipt, use, or disposition of study 
devices, including the type and quantity of devices; the dates of receipt; the identifying product numbers; 
the names of all persons who received, used, or disposed of each device; and why and how many units of 
the device have been returned to the Sponsor, repaired, or otherwise disposed. 
• 
Records of each subject’s case history and exposure to the device. 
• 
Signed and dated consent forms. 
• 
Relevant observations, including records concerning adverse events, condition of each subject upon 
entering and results of diagnostic tests. 
• 
Study-specific CRFs and corrections to the forms. 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 42 of 50 
• 
Protocol and amendments with signed Statement of Compliance. 
• 
IRB-approved subject recruiting materials. 
• 
Investigator curriculum vitae and medical license. 
• 
Monitoring reports and correspondence. 
• 
Study logs including Site Training Log, Site Visit Log, Site Delegation Log, and Subject Enrollment Log. 
14.2.2 INVESTIGATOR REPORTS 
Investigators are required to prepare and submit to the Sponsor the following complete, accurate, and timely reports 
on this investigation when are required. These reports, which are listed below, are required by 21 CFR §812.150; 
additional reports may be requested by the Sponsor: 
• 
The investigator will notify the Sponsor of a subject death occurring during the investigation, as soon as 
possible, preferably within 24 hours of learning of the subject’s death, but in no event later than 48 hours. 
The investigator will notify the reviewing IRB of a subject death as specified by the IRB. 
• 
The investigator will notify the Sponsor of any unanticipated adverse device effects within 48 hours after 
learning of the effect. The investigator will notify its reviewing IRB of any unanticipated adverse device 
effects, as soon as possible, but no later than 10 working days after learning of the effect. 
• 
The investigator will notify the Sponsor of the withdrawal of IRB approval, as soon as possible, but no later 
than five working days after learning of the withdrawal. 
• 
The investigator will provide current progress reports to the Sponsor and reviewing IRB at regular intervals 
and at least on an annual basis. 
• 
The investigator will notify the Sponsor and reviewing IRB of any deviation from the investigational plan to 
protect the life and physical well-being of a subject in an emergency, as soon as possible, but no later than 
five working days after the emergency occurred. 
• 
The investigator will notify the Sponsor and reviewing IRB that an informed consent was not obtained from 
a subject, as soon as possible, but no later than five working days after such an occurrence. 
• 
The investigator will provide a final summary report to the Sponsor and reviewing IRB within three months 
after termination or completion of the study. 
• 
The investigator will provide any other information upon the request of an IRB, FDA, or the Sponsor. 
14.3 STUDY RECORDS RETENTION 
The investigator is responsible for retaining the necessary records, including a copy of the protocol, device labeling, 
study-specific CRFs, medical records, original reports of test results, all study-related correspondence, a record of 
written informed consent, and any other documents pertaining to the conduct of this study. 
 
FDA regulations require all investigators participating in investigational device studies to maintain detailed clinical 
records during the investigation and for a period of at least two years after the latter of the following two dates: 
1. The date on which the investigation is terminated or complete; or 
2. The date the records are no longer required for purposes of supporting a premarket approval application. 
The investigator must not dispose of any records relevant to this study without either: 
1. Obtaining written permission from the Sponsor; or 
2. Providing an opportunity for the Sponsor to collect such records. 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 43 of 50 
The investigator shall take responsibility for maintaining adequate and accurate electronic or hard copy source 
documents of all observations and data generated during this study. Such documentation is subject to inspection by 
the Sponsor and the FDA. 
14.4 PROTOCOL DEVIATIONS 
A protocol deviation is an event in which the investigator or site personnel did not conduct the study in accordance 
with the protocol or the Clinical Trial Agreement. This study should be conducted as described in this protocol, except 
for an emergency situation in which the protection, safety, and well-being of a subject requires a protocol deviation, 
based on the judgment of the investigator (or a responsible, appropriately trained professional designated by the 
investigator). If the deviation from the protocol is necessary to protect the physical well-being of a subject in an 
emergency, such protocol deviations must be reported to the Sponsor and the reviewing IRB as soon as possible, 
but no later than five working days after the emergency occurred.  
 
In the event of a significant deviation from the protocol due to an accident or mistake, the investigator or designee 
must contact the Sponsor at the earliest possible time to discuss the deviation and its impact on the study and 
subject continuation in the study. All protocol deviations and justification for the deviation will be documented on 
the applicable Case Report Form. 
14.5 PUBLICATION AND DATA SHARING POLICY 
The data produced by this Apyx Medical‐sponsored study is the sole property of Apyx Medical.  Thereby, 
abstracts, publications and presentations of this data must be pre‐approved by Apyx in writing (e‐mail approval 
is acceptable).  The Sponsor must also be provided with the opportunity to review all investigator‐prepared 
abstracts, publications, or presentations.  A period of thirty (30) days for presentational materials and abstracts 
and forty‐five (45) days for manuscripts will be required for review and comment by Sponsor’s Clinical and 
Medical Affairs Department. These requirements acknowledge Sponsor's responsibility to evaluate such 
publications for their accuracy, to ascertain whether Confidential Information is being inappropriately released, 
to provide the Principal Investigator with information which may not yet have been available to him/her, and to 
provide input from co‐authors regarding content and conclusions of the publication or presentation. If requested 
in writing by the Sponsor, the Institution will withhold publication to protect the potential patentability of any 
invention described therein and/or made available to fulfill regulatory requirements. 
 
Notwithstanding the foregoing, Institution agrees that if the Study is part of a multi‐center study, the first 
publication of the results of the Study shall be made in conjunction with the results from the investigators at the 
other study centers as a multi‐center publication. 
 
The sponsor ensures that the study is registered, and study results are disclosed in at least one public clinical study 
registry, in accordance with national/international regulations and other requirements. Study registration may 
include a list of the study sites, as applicable. 
15. STUDY ADMINISTRATION  
15.1 
 STUDY INVESTIGATORS 
Participating Investigators will be qualified based on professionals experienced in treatment of skin laxity, such as 
plastic or cosmetic surgeons.  Investigators will be selected based on interest and availability for participation in the 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 44 of 50 
study; ability to provide qualified subjects; adequate support staff; experience conducting clinical research; and 
willingness to comply with the protocol, IRB requirements, regulatory requirements (including the signed 
investigator agreement and statements disclosing any financial relationship investigators might have with Apyx 
Medical Corporation), and applicable regulations. 
15.2 AMENDMENT POLICY 
The investigator will not make any changes to this protocol without prior written consent from the Sponsor and 
subsequent approval by the IRB, except if the deviation from the protocol is necessary to protect the life and physical 
well-being of a subject in an emergency. Such protocol deviations must be reported to the Sponsor and the reviewing 
IRB as soon as possible, but no later than five working days after the emergency occurred. 
 
 Any permanent change to the protocol, whether it is an overall change or a change for specific study center(s), must 
be handled as a protocol amendment. Any amendment to the protocol that appears indicated as the study 
progresses will be fully discussed by the investigator(s) and the Sponsor. If agreement is reached regarding the need 
for an amendment, the Sponsor will write it. The written amendment must be submitted to the chairman of the IRB 
identified with this responsibility. Except for “administrative amendments”, investigators must await IRB approval 
of protocol amendments before implementing the change(s). Administrative amendments are defined to have no 
effect on the validity of the data or information resulting from the completion of the approved protocol, or the 
relationship of likely patient risk to benefit relied upon to approve the protocol; the scientific soundness of the 
investigational plan or protocol; and the right, safety or welfare of the human subjects involved in the investigation. 
When, in judgment of the chairman of the IRB, the investigators and/or the Sponsor, the amendment to the protocol 
substantially alters the study design and/or increases the potential risk to the subject, the currently approved written 
Informed Consent Form will require similar modification. In such cases, repeat informed consent will be obtained 
from subjects enrolled in the study before continued participation. 
16. CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. Therefore, any actual conflict of interest of 
persons who have a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, persons who have a perceived conflict of interest will be required to have such conflicts managed 
in a way that is appropriate to their participation in the trial. The study leadership has established policies and procedures 
for all study group members to disclose all conflicts of interest and will establish a mechanism for the management of all 
reported dualities of interest. 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 45 of 50 
17. LITERATURE REFERENCES 
1. Feldman LS, Fuchshuber PR, Jones DB. The SAGES Manual on the Fundamental Use of Surgical Energy 
(FUSE).  Springer Science+Business Media, LLC.  2012. 
2. Goldberg SN, Gazelle GS, Halpern EF, Rittman WJ, Mueller PR, Rosenthal DI. Radiofrequency tissue ablation: 
importance of local temperature along the electrode tip exposure in determining lesion shape and size.  
Acad Radiol. 1996;3:212-8. 
3. Thomsen S. Pathologic analysis of photothermal and photomechanical effects of laser-tissue interactions.  
Photochem Photobiol.  1991;53:825-35. 
4. Ross EV, McKinlay JR, Anderson RR.  Why does carbon dioxide resurfacing work?  A review.  Arch Dermatol 
1999;135(4):444-454. 
5. Gardner ES, Reinisch L, Stricklin GP, Ellis DL.  In vitro changes in non-facial human skin following CO2 laser 
resurfacing: a comparison study.  Lasers Surg Med 1996;19(4):379-387. 
6. Doshi SN, Alster TS.  Combination radiofrequency and diode laser for treatment of facial rhytides and skin 
laxity.  Cosmet Laser Ther 2005;7:11-15. 
7. Fatemi A, Weiss MA, Weiss RA.  Short-term histologic effects of nonablative resurfacing: results with a 
dynamically cooled millisecond-domain 1320nm Nd:YAG laser.  Dermatol Surg 2002;28(2):172-176. 
8. Mayoral FA.  Skin tightening with a combined unipolar and bipolar radiofrequency device.  J Drugs Dermatol 
2007;6(2):212-215. 
9. Alster TS, Doshi SN, Hpping SB.  Combination surgical lifting with ablative laser skin resurfacing of facial skin: 
a retrospective analysis.  Dermatol Surg 2004;30(9):1191-1195. 
10. Zelickson B, Kist D, Bernstein E, Brown DB, Ksenzenko S, Burns J, Kilmer S, Mehregan D, Pope K.  Histological 
and ultrastructural evaluation of the effects of a radiofrequency-based nonablative dermal remodeling 
device: a pilot study.  Arch Dermatol 2004;140:204-209. 
11. Hsu T, Kaminer M.  The use of nonablative radiofrequency technology to tighten the lower face and neck.  
Semin Cutan Med Surg 2003;22:115-123. 
12. Zhang S, Duan E. Fighting against Skin Aging: The Way from Bench to Bedside. Cell Transplant. 
2018;27(5):729-738. doi:10.1177/0963689717725755 
13. Narins RS, Brandt F, Leyden J, Lorenc ZP, Rubin M, Smith S. A randomized, double-blind, multicenter 
comparison of the efficacy and tolerability of Restylane versus Zyplast for the correction of nasolabial folds. 
Dermatol Surg. 2003 Jun;29(6):588-95. doi: 10.1046/j.1524-4725.2003.29150.x. PMID: 12786700. 
14. Bashour M. Lower Lid Ectropion Blepharoplasty Workup. Medscape, article/1281565. February 24, 2020. 
15. Venkataram J. Tumescent Liposuction: A Review. J Cutan Aesthet Surg. 2008 Jul-Dec; 1(2): 49-57. 
16. Boeni, R. Safety of Tumescent Liposuction under Local Anesthetsia in a Series of 4,380 Patients. 
Dermatology. 2011;222:278-281. 
17. Hurwitz DJ. The Liposuction and Body Contouring. Reconstructive Surgery & Anaplastology. 2016;5:3. 
18. Boonstra et. al. Cut-off Points for Mild, Moderate, and Severe Pain on the Numeric Rating Scale for Pain in 
Patients with Chronic Musculoskeletal Pain: Variability and Influence of Sex and Catastrophizing. Frontiers 
in Psychology, Vol 7, Article 1468, September 2016. 
19. Bhattacharjee K, Ghosh S, Ugradar S, Azhdam AM. Lower eyelid blepharoplasty: An overview. Indian J 
Ophthalmol. 2020;68(10):2075-2083. doi:10.4103/ijo.IJO_2265_19 
20. Pain: clinical manual for nursing practice Pain: clinical manual for nursing practice Margo McCaffery 
Alexander Beebe Mosby Yearbook UK £17.25 0 7234 1992 2. Nurs Stand. 1994 Dec 7;9(11):55. doi: 
10.7748/ns.9.11.55.s69. PMID: 27527475. 
 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 46 of 50 
APPENDIX A: PATIENT SATISFACTION QUESTIONNAIRE 
Please have the subject complete this assessment while referring to their image in the mirror and current post-
treatment photos compared to baseline photos. Provide the subject with a mirror.  
 
Using a mirror and reviewing your post-treatment photos, compare how your treatment area currently 
looks compared to your pre-treatment photos.  
 
1. Do you notice any improvement in how your lower eyelid area? 
 YES → 
 Improvement in wrinkles 
 
 Less sagging skin 
 
 Smoother skin texture 
 
 Other:  
 
 
 
 
 
 NO 
 
2. How would you characterize your satisfaction with the treatment? 
 Very Satisfied  
 
 Satisfied 
        
 Slightly Satisfied  
 Neither Satisfied or Dissatisfied  
 Slightly Dissatisfied 
 Dissatisfied 
 Very Dissatisfied 
 
3. Would you recommend this treatment to your friends and family members (check one)? 
 YES  
 
 NO 
 
Thank you for completing this questionnaire. 
 
Subject Initials: ______________  
Date: _____________________ (DD/MON/YYYY) 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 47 of 50 
APPENDIX B:  PRE-SCREENING QUESTIONNAIRE 
This questionnaire may be emailed to potential subjects and/or asked over a telephone conversation. Answers to 
the following questions will only be used to determine if preliminary criteria for the clinical study is met. Subjects 
meeting the preliminary criteria and remain interested in participating in the study, will be scheduled to attend an 
in-office appointment to further determine your eligibility.  Answers to the questions below may be collected with 
but will not be associated with your personal information.   
 
Subject Initials (use dash if no middle initial): ___ ___ ___ 
 
What is your age? ______ 
 
Are you looking to improve the appearance of lower eyelid (under eye) laxity?    
 Yes 
 No 
 
Have you ever had any cosmetic procedures performed on your eye area?    
 Yes 
 No 
 
Are you willing to return to the clinic for all follow-up visits for 6 months after your procedure?    
 Yes 
 No 
 
Are you willing to have pictures taken of your face and are you willing to allow the study sponsor, Apyx Medical, to 
use these photographs for study purposes?    
 Yes 
 No 
 
Are you taking any blood thinning medications?    
 Yes 
 No 
 
Are you currently pregnant or lactating, have you been pregnant within the past 12 months, or planning to become 
pregnant in the next 6 months?    
 Yes 
 No 
 
Do you have or have you ever had cancer of any type and, if so, what type?    
 Yes 
 No  
 
If yes, what type(s)? ________________________________________________ 
 
Do you have an autoimmune disease?    
 Yes 
 No 
 
Are you sensitive or allergic to anesthesia of any kind?    
 Yes 
 No 
 
Do you have or have you ever had a bleeding disorder?    
 Yes 
 No 
 
Have you ever participated in a clinical study?    
 Yes 
 No 
 
If so, when? ________________________________________________________ 
 
 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 48 of 50 
APPENDIX C:  FRANKFURT PLANE POSITIONING 
 
 
 
 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 49 of 50 
 

Apyx Medical Corporation 
 
Protocol Number:  APX-22-04-GR 
Effective Date: October 2, 2023 
Revision No: 04 
Title: A Post-Market Study in Greece of a Minimally Invasive Lower Eyelid Treatment Utilizing the Renuvion System Clinical Trial Protocol 
 
Form-CLA-003-001                                                
 
Title: Clinical Trial Protocol 
Revision: 02 
 
Page 50 of 50 
APPENDIX D: PROTOCOL REVISIONS LOG 
TABLE 7: PROTOCOL REVISIONS LOG 
VERSION 
DATE 
SIGNIFICANT REVISIONS 
1.0 
02172022 
Initial Release 
2.0 
September 
27, 
2022 
Revise the subject number to 15 
3.0 
020152023 
20% power to 60-70% power. 
4.0 
10022023 
Revise subject number to 16