An Open-Label, Single Center Clinical Study to Evaluate the Efficacy of Periorbital Rejuvenation With a 1927 nm Diode Laser Treatment
Phase: NA
Conditions: Laser, Periorbital
Sponsor: National Taiwan University Hospital

Title page
An Open-Label, Single Center Clinical Study to Evaluate the 
Efficacy of Periorbital Rejuvenation with a 1927 nm Diode 
Laser Treatment
Date: 10 Mar 2023
NCT number: NCT05811026

Introduction 
The chromophore of the 1927 nm diode laser is mainly water, which can be used for 
skin rejuvenation.[1-3] This study intends to use the Solta CLEAR+BRILLIANT Laser 
System, featuring a 1927 nm diode laser with 5 mJ energy, a treatment spot of 140 
μm, a treatment depth of 170 μm, and a treatment coverage of approximately 5% per 
energy level after four rounds of treatment using the patented Intelligent Optical 
Tracking® System (IOTs). The purpose of this research project is to investigate the 
treatment design, therapeutic effects and safety of the 1927 nm laser for the 
rejuvenation of the skin around the eyes. 
 
Study objectives and endpoints 
 
Objectives: The objective of this study is to evaluate the treatment design, 
therapeutic effects and safety of the 1927 nm laser for the rejuvenation of the 
skin around the eyes. 
 
Primary endpoint 
1. 
Change from baseline in texture score at visit 4 (follow-up session) 
 
Secondary endpoints 
1. 
Change from baseline in color measurements (L*) at visit 4 (follow-up 
session) 
2. 
Change from baseline in pigmentation score at visit 4 (follow-up session) 
3. 
Change from baseline in pores' index at visit 4 (follow-up session) 
4. 
Change from baseline in physician assessment of Global Aesthetic 
Improvement Score (GAIS), at visit 4 (follow-up session) 
5. 
Change from baseline in patient assessment of Global Aesthetic 
Improvement Score (GAIS), at visit 4 (follow-up session) 
6. 
Change from baseline in texture score at visit 2 
7. 
Change from baseline in color measurements (L*) at visit 2 
8. 
Change from baseline in pigmentation score at visit 2 
9. 
Change from baseline in pores' index at visit 2 
10. Change from baseline in physician assessment of Global Aesthetic 
Improvement Score (GAIS), at visit 2 
11. Change from baseline in patient assessment of Global Aesthetic 
Improvement Score (GAIS), at visit 2 
12. Change from baseline in texture score at visit 3 
13. Change from baseline in color measurements (L*) at visit 3 
14. Change from baseline in pigmentation score at visit 3 
15. Change from baseline in pores' index at visit 3 
16. Change from baseline in physician assessment of Global Aesthetic 

Improvement Score (GAIS), at visit 3 
17. Change from baseline in patient assessment of Global Aesthetic 
Improvement Score (GAIS), at visit 3 
18. Adverse reaction after each treatment 
19. Visual Analogue Scale (VAS) during treatment 
20. Change from baseline in self-reported satisfaction with the skin around the 
eyes 
 
Investigational plan 
 
Study Design 
This is an open-label, single center clinical study to evaluate the efficacy of periorbital 
rejuvenation with a 1927 nm diode laser treatment. The trial administrator will assign 
the subjects into different treatment groups (Group A: 2-week interval between 
treatments, or Group B: 4-week interval between treatments) . 
 
 
Randomization 
This study is designed as a randomized clinical trial. The randomization of subjects 
will be generated by computer algorithm prior to the start of the trial. The trial 
administrator will assign the subjects into different treatment groups (Group A: 2-
week interval between treatments, or Group B: 4-week interval between treatments) 
based on the order of enrollment and the corresponding randomization code. 
 
 
Screening 
Upon obtaining the signed informed consent form, the trial staff will record the 
subjects' basic information, medical and surgical history, medication history, and 
Fitzpatrick skin type. Women will undergo pregnancy testing, and inclusion and 
exclusion criteria will be reviewed. 
 
 
Treatment Visits 
 
Visit 1 
Before the first treatment, a camera photograph and Antera 3D assessment 
will be performed, and the subjects will complete a self-assessment 
questionnaire for skin conditions. EMLA Cream 5% will be applied 
topically for 20 minutes. Ocular laser shields will then be placed over the 
eyes following the application of Alcaine Ophthalmic Solution 0.5%. Clear 
+ Brilliant™ Permea device periorbital treatment will then be performed. 
After the treatment, the subjects will complete a visual analog scale (VAS) 
for pain and use moisturizing skincare products. 

 
Visit 2 
Before the second treatment, a camera photograph and Antera 3D 
assessment will be performed, and the subjects will complete a self-
assessment questionnaire for skin conditions, the Global Aesthetic 
Improvement Scale (GAIS) for overall aesthetic improvements, and a 
treatment safety questionnaire. EMLA Cream 5% will be applied topically 
for 20 minutes. Ocular laser shields will then be placed over the eyes 
following the application of Alcaine Ophthalmic Solution 0.5%. Clear + 
Brilliant™ Permea device periorbital treatment will then be performed. 
After the treatment, the subjects will use moisturizing skincare products. 
 
Visit 3 
Before the third treatment, a camera photograph and Antera 3D assessment 
will be performed, and the subjects will complete a self-assessment 
questionnaire for skin conditions, GAIS for overall aesthetic improvements, 
and a treatment safety questionnaire. EMLA Cream 5% will be applied 
topically for 20 minutes. Ocular laser shields will then be placed over the 
eyes following the application of Alcaine Ophthalmic Solution 0.5%. Clear 
+ Brilliant™ Permea device periorbital treatment will then be performed. 
After the treatment, the subjects will use moisturizing skincare products. 
 
Visit 4 
Four weeks after the third treatment, a follow-up assessment will be 
performed, including a camera photograph and Antera 3D assessment, self-
assessment questionnaire for skin conditions, GAIS for overall aesthetic 
improvements, and a treatment safety questionnaire. 
 
Time of Each Visit 
Each visit lasts approximately 40 minutes, including 20-minute topical 
anesthesia, 15-minute laser treatment, and 5-minute photography. 
 
 
Laser treatment 
Solta CLEAR+BRILLIANT Laser System, featuring a 1927 nm diode laser with 
5 mJ energy, a treatment spot of 140 μm, a treatment depth of 170 μm, and a 
treatment coverage of approximately 5% per energy level after four rounds of 
treatment using the patented Intelligent Optical Tracking® System (IOTs). We 
will perform laser treatment on the periorbital area. 
 
Imaging Records 
Each visit will include: 
 
Camera photograph: One photograph of periorbital area in half-face 
position (from the eyebrows to the lower nose). 

 
Antera 3D photography: Two photographs of both sides of the periorbital 
area (5.6 x 5.6 cm), along with L*, texture, pigmentation, and pore indices. 
A total of eight photographs will be taken. 
 
Other Study Procedures 
 
Basic information survey, including date of birth, gender, fitzpatrick skin 
type, and medication history. 
 
Height and weight  
 
Medical and surgical history, including a survey of past and current 
illnesses, allergies, and surgical history. 
 
Medication history, concurrent use of medications, or related aesthetic 
treatments 
 
Pregnancy test: urine pregnancy test (only performed on women before 
menopause). 
 
Self-assessment questionnaire for skin condition 
 
Global aesthetic improvement scale (GAIS) from subjects and investigator 
 
Treatment safety questionnaire 
 
Pain VAS (Pain Visual Analogue Scale) 
 
Antera 3D camera 
Antera 3D® (a product of PSET BioMed and Miravex Limited, Ireland) is a 
non-invasive inspection tool that uses "image capture" technology to 
analyze and examine skin. The principle of obtaining the structure of skin 
texture is based on the colorimetric shape-from-shading (SFS) method, 
which is widely used to eliminate strong light on the skin and improve the 
accuracy of the inspection data. With this method, texture reconstruction 
can be used for skin analysis and quantification, such as measuring wrinkle 
depth and width, skin damage, and overall roughness. The captured spectral 
data can also be used to create maps that confirm the distribution and 
concentration of melanin and hemoglobin. The testing method for subjects 
involves comparing a fixed area of skin. 
 
 

 
1st treatment 
(visit 1) 
2nd treatment 
(visit 2) 
3rd treatment 
(visit 3) 
Follow-up 
(visit4) 
Group A 
Week 0 
Week 2 
Week 4 
Week 8 
Group B 
Week 0 
Week 4 
Week 8 
Week 12 
Camera photograph 
V 
V 
V 
V 
Pain VAS 
V 
 
 
 
Antera 3D assessment 
V 
V 
V 
V 
Self-assessment 
questionnaire for skin 
condition 
V 
V 
V 
V 
Investigator Global 
Aesthetic Improvement 
Scale (GAIS)  
 
V 
V 
V 
Subjects Global Aesthetic 
Improvement Scale (GAIS) 
 
V 
V 
V 
Treatment safety 
questionnaire 
 
V 
V 
V 
 
Study activities 
 
Eligibility Criteria 
 
Inclusion Criteria: 
✓ 
aged between 30 and 65 years old; 
✓ 
no significant skin lesions or inflammation on the facial skin; 
✓ 
willing and able to comply with study requirements, instructions, and 
restrictions; 
✓ 
signed informed consent form. 
 
Exclusion Criteria: 
✓ 
underwent facial active treatment, such as using laser, intense pulsed 
light, radiofrequency skin tightening, ultrasound skin tightening, 
botulinum toxin, or dermal fillers injection, within the previous six 
months; 
✓ 
have chronic skin diseases such as atopic dermatitis, psoriasis, chronic 
urticaria, vitiligo, rosacea, or keloid; 
✓ 
pregnant or breastfeeding; 
✓ 
suffered from acute illnesses or infections requiring treatment within 
14 days before entering the study; 
✓ 
have had serious illnesses (such as heart disease, lung disease, brain 
disease, or liver disease) within the previous three months; 

✓ 
allergic to Lidocaine or Prilocaine used in topical anesthetic cream or 
suffer from methemoglobinemia; 
✓ 
used any skin medication on the face within 30 days before the trial, 
deemed by the principal investigator to affect the study results; 
✓ 
deemed unsuitable for the study by the principal investigator. 
 
 
Limitations and Cooperation Requirements for Study Participants 
 
Limitations for study participants during the trial 
✓ 
Participants are not allowed to undergo other chemical peels, beauty 
injections or phototherapy around the eyes during the trial. 
✓ 
Participants should avoid sun exposure or the use of tanning machines 
on their face during the trial. 
✓ 
Participants should maintain their original skincare routine during the 
trial and avoid using new facial skin products or topical/ingested 
whitening agents that claim to have whitening, spot-fading, or wrinkle-
fighting effects. 
 
Cooperation requirements for study participants during the trial 
✓ 
Participants should use umbrellas or wear hats to protect themselves 
from the sun when going outside on days with high UV index. 
✓ 
Participants can clean their faces as usual, but they must maintain a 
similar cleaning pattern every day. 
✓ 
Participants can use facial moisturizers, sunscreens, makeup, and 
makeup removers as usual, but they must maintain a similar pattern 
every day. 
 
Consequences of failure to comply with trial limitations or cooperation 
requirements 
✓ 
If participants use the above limited items or fail to cooperate with the 
above requirements during the trial, they should inform the researchers 
actively. The principal investigator will assess whether the products or 
treatments used by the participants have any impact on the trial's test 
results and safety, as well as the feasibility of the participants 
continuing to participate in the trial. 
 
Adverse Reactions and Management in Clinical Settings 
 
Allergic contact dermatitis caused by topical anesthetic cream has an 
incidence rate of less than 0.1%, which may result in skin redness, swelling, 
mild burning or itching. Topical steroid cream can be used for treatment. 
 
This device may cause local transient pain (lasting about one to several 

hours) and redness and swelling (lasting about one to two days). Most of 
these side effects will disappear on their own. If the symptoms persist, 
symptom relief medication such as oral pain relievers like acetaminophen or 
non-steroidal anti-inflammatory drugs can be used. 
 
Small scabs the size of a needle tip may appear, which will fall off on their 
own within a week. 
 
If inflammation and pigmentation occur due to the constitution or sun 
exposure, topical or oral whitening products can be used for treatment for 1-
3 months. 
 
Data Collection, Processing, Evaluation, and Statistical Analysis 
Methods 
 
Data Confidentiality  
To maintain data confidentiality, data will be entered into a computer using a 
numbering system, and the data will be stored on an encrypted computer in the 
lead investigator's institution. The study lead investigator and research team 
members have a duty of confidentiality regarding information about the subjects 
and follow the rule that data cannot be taken out of the hospital. 
 
Protection of Subjects' Privacy  
The research team will use a study code to represent the identity of the subjects, 
and only the lead investigator and relevant research team members will know the 
link between the code and the name. If the trial/research results are published, 
the subjects' identities will still be kept confidential. 
 
Statistical analysis 
 
For the analysis of numerical data, we will use either an independent t-test 
or Mann-Whitney U test to compare differences between the two groups. 
Additionally, a paired t-test or Wilcoxon signed-rank test will be used to 
compare differences between before and after treatment. 
 
For categorical data, we will present the data in the form of frequency and 
contingency tables. To determine if there are significant differences in rates 
between the two groups, we will use either the chi-square test or Fisher's 
exact test. 
 
All reported P-values will be from two-sided tests, and statistical 
significance will be determined at a threshold of P < 0.05. 
 
 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, Operations Manual, 

International Council for Harmonisation (ICH) guidelines, applicable regulations, and 
guidelines governing clinical study conduct and the ethical principles that have their 
origin in the Declaration of Helsinki. 
 
Completion of the study 
The end-of-study is defined as the date of the last subject's last visit. 
 
References 
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Alharbi MA. 1927 nm Thulium Laser Successfully Treats PostInflammatory 
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2. 
Kim SM, Hwang S, Almurayshid A, Park MY, Oh SH. Non-Ablative 1927 nm 
Fractional Thulium Fiber Laser: New, Promising Treatment Modality for 
Riehl's Melanosis. Lasers Surg Med 2021;53:640-6. 
3. 
Kurmuş G, Tatlıparmak A, Aksoy B, Koç E, Aşiran Serdar Z, Ergin C. 
Efficacy and safety of 1927 nm fractional Thulium fiber laser for the treatment 
of melasma: a retrospective study of 100 patients. J Cosmet Laser Ther 
2019;21:408-11.