Application of Botulinum Toxin at the Yonsei Point for the Treatment of Gummy Smile
Condition: Smiling; Botulinum Toxins, Type A
Study type: Interventional

Summary: 
      The purpose of the present study will be to evaluate the efficacy of a single dose of
      botulinum toxin (BTX) at the Yonsei point for the treatment of gummy smile (GS).

      In this double-blind single-site randomized clinical trial, A total number of 36 patients
      with gummy smile will be enrolled in the study at Peking University School and Hospital of
      Stomatology over a period of 12 months. Patients will be included and randomized 1:1 to two
      groups for BTX-A treatment at different injection point. For experimental group, Three units
      of onabotulinumtoxinA (BTX-A) per site (90 hemifaces) will be initially injected at the
      Yonsei point. For control group，the same dose of BTX will be injected into the levator labii
      superioris alaeque nasi muscle, and the injection point is located 3 to 5 mm lateral to each
      nostril, which was a classical injection point of this treatment. The patients will be then
      assessed at 2, 4, 12, 36 and 72 weeks postinjection. All subjects underwent standardized
      measurements by a single examiner, including dynamic and static measurements and a lateral
      cephalometric radiograph. In addition, facial photos and videos and a questionnaire of
      self-assessment will be obtained. The primary outcome measurement is the anterior gingival
      exposure measurements when the subject get an achieve full, unrestricted, spontaneous smiles
      2 weeks postinjection.
    

Detailed description: 
      BACKGROUND:

      Gummy smile (GS), also known as excessive gingival display, is a common unaesthetic clinical
      condition. Recent evidence showed that botulinum type A (BTX-A) injection is a promising,
      simple, corrective method for GS. However, Currently, there is no standardized approach for
      the treatment of excessive gingival exposure with botulinum toxin, and controversies still
      exist and due to different injection methods, the efficiency of BTX-A for GS treatment shows
      great variation in different studies, with the improvement rate of gingival exposure (GE)
      ranging from 62% to 98%.

      The treatment goal is to identify a consistent, minimally invasive alternative for the
      correction of GS caused by hyperfunctional upper lip elevator muscles. In 2009, Hwang et. al.
      described the Yonsei point, which is the confluence of three muscles - the levator labii
      superioris (LLS), the levator labii superioris alaeque nasi (LLSAN), and the zygomaticus
      minor (Zm). These three muscles are primarily responsible for the smile.

      In order to minimize the complications associated with multiple injections of BTX, the
      present study is designed with the prime purpose of evaluating the efficacy of one injection
      of BTX at the Yonsei point as a minimally invasive approach in the treatment of GS.

      In this double-blind single-site randomized clinical trial, A total number of 36 patients
      with gummy smile will be enrolled in the study at Peking University School and Hospital of
      Stomatology over a period of 12 months. Patients will be included and randomized 1:1 to two
      groups for BTX-A treatment at different injection point. For experimental group, Three units
      of onabotulinumtoxinA (BTX-A) per site (90 hemifaces) will be initially injected at the
      Yonsei point. For control group，the same dose of BTX will be injected into the levator labii
      superioris alaeque nasi muscle, and the injection point is located 3 to 5 mm lateral to each
      nostril, which was a classical injection point of this treatment. The patients will be then
      assessed at 2, 4, 12, 36 and 72 weeks postinjection.

      The primary outcome measurement is the anterior gingival exposure measurements when the
      subject get an achieve full, unrestricted, spontaneous smiles 2 weeks postinjection.

      METHODS

        1. Study Design and Participants This double-blind single-site randomized clinical trial
           will be conducted in Peking University School and Hospital of Stomatology from October
           of 2020 to 2021, approved by the Institutional Review Board of the Peking University
           Health Science Center (No: 202056097) and conducted in accordance with the tenets of the
           Declaration of Helsinki.

           A total number of 36 patients with gummy smile will be enrolled in the study. The
           inclusion criteria will be as follows: ≥3.0-mm GE upon unrestricted, "full-blown"
           smiling and age between 18 and 60 years. The exclusion criteria will be contraindication
           of BTX-A, previous diseases or treatments affecting the position of the gingiva or upper
           lips, history of BTX-A injections to the head or neck region, facial paralysis, and/or
           subject's refusal to participate.

        2. Preintervention measurements Before injection, all subjects underwent standardized
           measurements by a single examiner, including dynamic and static measurement. In
           addition, facial photos and videos and a questionnaire of self-assessment will be
           obtained.

           2.1 Dynamic measurements Extremely funny jokes, statements, singing, and/or dancing will
           be played out to the subjects to achieve full, unrestricted, spontaneous smiles as
           described by Sarver and Ackerman.7 The measurements will be taken individually during 3
           different spontaneous smiles to ensure maximal smile for each measured area. Dynamic
           measurements included anterior GE, bilateral posterior GEs, bilateral distance from
           commissures to the dental midline, and bilateral vertical positions of commissures.
           Anterior GE presented the severity of GS as the primary indicator.

           2.2 Static measurements The following measurements will be performed with the patient in
           a relaxed state (resting jaw position). Lip-teeth relationship included the exposed
           medial incisor (the distance between the inferior margin point of the right incisor and
           the lower margin of the upper lip) and the upper lip length. Dental factors included the
           upper right incisor length, width-to-length ratio of the upper medial incisor, and the
           overbite and overjet of the anterior teeth.

        3. Interventions Patients will be included and randomized 1:1 to two groups for BTX-A
           treatment at different injection point. For all patients, Lyophilized 100 U of BTX-A
           (Botox, Allergan, Irvine, CA) will be reconstituted in 2.5 mL of 0.9% sodium chloride
           solution.21 A uniform BTX-A injection technique22 with single-site injection will be
           administered by the same doctor. For experimental group, Three units of
           onabotulinumtoxinA (BTX-A) per site (90 hemifaces) will be initially injected at the
           Yonsei point. For control group，the same dose of BTX will be injected into the levator
           labii superioris alaeque nasi muscle, and the injection point is located 3 to 5 mm
           lateral to each nostril. No anesthesia will be given during the procedure.

        4. Follow-up The patients will be then assessed at 2, 4, 12, 36 and 72 weeks postinjection.
           All dynamic measurements; some static measurements (exposed medial incisor, upper lip
           length, and medial incisor length); and facial photos and videos will be repeated.
           Questionnaires will be provided to patients to determine patient satisfaction, side
           effects, willingness to undergo a repeat treatment, and an improvement in their
           nasolabial fold.

        5. Statistical analysis Data entry will be managed using EpiData 3.1 (EpiData Association,
           Denmark) and accuracy will be ensured by double entry and validation. The normality of
           numerical variables will be assessed using a Shapiro-Wilk test. The mean and standard
           deviation will be used to describe normally distributed numerical values, and an
           independent-samples t test will be used to compare the 2 groups. Non-normally
           distributed numerical values will be described using the median and interquartile range
           (25th percentile, 75th percentile). The difference between the 2 groups will be compared
           using a Mann-Whitney U test. For categorical variables, the fraction of the treatment
           group that belonged to the given category will be used, and the difference between the 2
           groups will be compared using a x2 test (Fisher exact probability method). All
           statistical analyses will be carried out using SPSS(Statistical Product and Service
           Solutions) software v. 20.0 (IBM Corp. Armonk, NY). A 2-tailed P value less than .05
           will be considered to indicate a statistically significant difference. Data will be
           analyzed by the Research Center of Clinical Epidemiology (Peking University, Beijing,
           China).
    

Intervention name(s): the injection of onabotulinumtoxinA at different point
Intervention type(s): Procedure
Intervention description(s): For experimental group, Three units of onabotulinumtoxinA (BTX-A) per site (90 hemifaces) will be initially injected at the Yonsei point. For control group，the same dose of BTX will be injected into the levator labii superioris alaeque nasi muscle, and the injection point is located 3 to 5 mm lateral to each nostril, which was a classical injection point of this treatment.
Intervention MeSH terms: Botulinum Toxins, Type A; abobotulinumtoxinA
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: In this double-blind single-site randomized clinical trial, A total number of 36 patients with gummy smile will be enrolled in the study at Peking University School and Hospital of Stomatology over a period of 12 months. Patients will be included and randomized 1:1 to two groups for BTX-A treatment at different injection point.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: gummy smile; botulinum toxin; Yonsei point