Evaluating the Efficacy of Tranexamic Acid Mesotherapy in Treatment of Periorbital Wrinkles: a Randomized Control Trial

Determine the efficacy and safety of intradermal tranexamic acid mesotherapy compared with placebo for the improvement of periorbital wrinkles

A randomized, double-blind, placebo-controlled, parallel-group (split-face design), phase 2 clinical trial on 20 patients (40 periorbital sides). For randomization Sealed Envelope System was used.

This study is conducted at the Dermatology Clinic of Shahid Faghihi Hospital, Shiraz University of Medical SciencesPatients receive 4 weekly periocular injections of tranexamic acid on one side and placebo contralaterally. It is double-blind; patients, clinical evaluators, and image analysts are masked using third-party identically coded syringes

Patients aged 30–60 years with periorbital wrinkles (WSRS≥2). Inclusion criteria: written consent; no cosmetic procedures in past 3 months or eye creams in past week. Exclusion criteria: pregnancy; lactation; coagulopathies; history of thromboembolism;

Intervention Group: Intradermal micro-injections of tranexamic acid (100 mg/mL) into one periorbital side at 0.1 mL per puncture point spaced 1 cm apart (total volume 1.0–1.5 mL per session) using a 30G needle, administered weekly for 4. Control Group: Intradermal micro-injections of normal saline into the contralateral periorbital side with identical injection technique, spacing, volume (0.1 mL per puncture; total 1.0–1.5 mL per session), and 30G needle, administered weekly for 4 consecutive sessions.

Change in periorbital wrinkle volume measured by VisioFace at 1-month post-treatment; change in clinical wrinkle severity based on WSRS; change in wrinkle area and depth via VisioFace analysis; patient satisfaction score using a 5-point Likert scale; incidence of local and systemic adverse events

Side allocation (right vs. left periorbital area receiving intradermal tranexamic acid vs. normal saline) will be determined using a permuted block randomization method with a fixed block size of 4 and an allocation ratio of 1:1. The allocation sequence will be generated using a validated web-based randomization service, Sealed Envelope (www.sealedenvelope.com), with a pre-specified documented random seed to ensure reproducibility. To ensure robust allocation concealment, the randomization key will be securely retained by an independent third party who is not involved in participant recruitment, clinical administration, or outcome evaluation. This individual will prepare identical 1-mL insulin syringes pre-filled with either tranexamic acid or normal saline, labeled uniformly with neutral codes as "Side A" and "Side B" corresponding to sequentially numbered, opaque, sealed envelopes. The treatment allocation will remain completely concealed from the participant, the injector, the outcome assessor, and the image analysis investigator until study completion and database lock.

This clinical trial is designed as a double-blind study where both participants and outcome assessors remain blinded to treatment allocation: Participant Blinding: Participants will remain completely unaware of which periorbital side receives tranexamic acid (TXA) and which side receives normal saline. Both sides will undergo identical intradermal injection protocols using indistinguishable 1-mL insulin syringes with 30-gauge needles, equal injection volumes (0.1 mL per puncture), identical 1-cm spacing, and uniform injection techniques. Outcome Assessor Blinding: The two independent board-certified dermatologists evaluating periorbital wrinkles via the Wrinkle Severity Rating Scale (WSRS) on standardized photographs will be fully blinded to treatment allocation. Furthermore, 3D digital images acquired by the VisioFace system will be independently coded and analyzed by an investigator blinded to intervention assignments. Syringe Preparation & Masking: To eliminate administration bias, pre-filled syringes containing TXA or saline will be prepared by an independent third party who is not involved in treatment delivery or outcome evaluation. Syringes will be identically labeled with neutral designations ("Side A" and "Side B") matching the concealed allocation log, ensuring blinding is maintained until database lock and unblinding.

Data/Document Title: Clinical data and VisioFace 3D images Sharing Details: Anonymized individual participant data (IPD)—including demographic characteristics, WSRS clinical scores, and VisioFace 3D images—will be made available upon reasonable request to the corresponding author following the publication of the main study.

Access begins 6 months after publication of the study results and will remain available for a period of 2 years.

Academic researchers and faculty members affiliated with recognized universities or medical research institutions with an approved protocol and defined research purpose.

Purpose: Permitted exclusively for secondary statistical analyses, systematic reviews, and meta-analyses related to skin rejuvenation. Conditions: Provision of a scientifically approved protocol with institutional ethics clearance; execution of a formal Data Use Agreement (DUA); strict prohibition of any re-identification attempts; prohibition of commercial use; and mandatory citation of the original publication.

Applicants must submit their written request and proposal via email to the student author of the thesis: Contact Person: Dr. Armin Gorjian Address: Dermatology Clinic, Shahid Faghihi Hospital, Zand Street, Shiraz, Shiraz University of Medical Sciences Email: Armingorjian1996@gmail.com Phone: 00987132351087

Submission of formal request, approved protocol, and ethics clearance to the corresponding author via email. Protocol review by the research team within 2–3 weeks.Upon approval, signing of a formal Data Use Agreement (DUA) by the applicant within 1 week.Delivery of de-identified data via secure email within 1 week post-signing (total expected timeframe: 3–5 weeks).