A Randomized Controlled Trial of Botulinum Toxin Combined with Non-Cross-Linked Bovine Collagen for Improving Periorbital Wrinkles
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Updated: Sep 11, 2025

Ultrasound-guided Botulinum Toxin-A Injections: A Method of Treating Sialorrhea
Published on: November 9, 2016
1Central Hospital of Dalian University of Technology (Dalian Municipal Central Hospital), Dalian, 116038, Liaoning, China.
Background:
This study examined the clinical efficacy of botulinum toxin type A (BTX-A) combined with non-cross-linked bovine collagen in improving periorbital wrinkles.
Methods:
Forty participants with periorbital wrinkles were recruited from the Plastic Surgery and Aesthetic Department of the Central Hospital Affiliated to Dalian University of Technology in China between November 2021 and August 2022. Participants were randomly assigned to either an observation group or a control group, with each group comprising 20 participants. The control group received BTX-A injection alone, whereas the observation group received combined injections of BTX-A and collagen filler.
Results:
Standardized photographic images were taken at baseline and at 1-week, 1-month, 3-month, and 6-month follow-ups after the injection. The rejuvenation effect was evaluated using the 5-grade Wrinkle Severity Rating Scale, whereas patient satisfaction was assessed using the Global Aesthetic Improvement Scale. Both groups achieved a total effective rate of 100%. However, the markedly effective rate was significantly higher in the observation group (90%) than in the control group (40%; p < 0.01). Moreover, 95% patients in the observation group reported great satisfaction, and the percentage was significantly higher than that in the control group (20%; p < 0.01). No adverse events were reported during the study.
Conclusion:
BTX-A injections combined with non-cross-linked bovine collagen filler provide a highly effective and safe therapy for improving periorbital wrinkles.
Level Of Evidence Ii:
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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