Botulinum toxin treatment of the orofacial region – A narrative review on esthetic aspects

Search strategy

A systematic search of the electronic database PubMed was conducted to identify relevant studies. Keywords related to BoNT-A, gummy smile, cleft lip repair, rehabilitation after facial palsy, and scar prevention or treatment on the lips were employed in the search to ensure extensive coverage of the published literature.

Study selection criteria

The inclusion and exclusion criteria for this study are provided below.

Inclusion criteria

1. Studies investigating the clinical application and indications of BoNT-A for the indications mentioned above

2. Randomized controlled trials for primary analysis to ensure a stringent scientific evaluation

3. Non-randomized trials (prospective clinical studies and cohort studies) and other publications to provide a comprehensive understanding of clinical indications and applications; case reports were considered only if they reported unusual adverse events

4. English and German language studies. This inclusive approach enabled a thorough examination of the efficacy and clinical implications of these treatments in the selected indications.

Exclusion criteria

1. Studies not relevant to the clinical application and indications of BoNT-A in the selected indications

2. Animal studies

3. Studies in languages other than English or German.

Study selection process and data extraction

Two independent reviewers screened the titles and abstracts of retrieved articles. Potentially relevant studies were followed by a complete evaluation of the text to assess their eligibility for inclusion. Data extraction was conducted independently by two reviewers using a standardized data extraction form. The following data were extracted from each included study: Author, publication year, study design, sample size, age of participants, type and dosage of BoNT-A, injection technique, clinical efficacy, safety (adverse effects), and key findings related to the clinical application and indications of BoNT-A in the selected indications.

Data synthesis and analysis

Data synthesis involved a narrative summary of the findings based on the included studies. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.¹² The data analysis aimed to provide an in-depth understanding of the available evidence on the use of BoNT-A in selected indications, highlighting their efficacy, safety profile, and potential clinical implications. The PRISMA flow chart is illustrated in Figure 1. Dosages are provided in units of onabotulinumtoxin A.

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Figure 1:

Preferred reporting items for systematic reviews and meta-analyses flow chart.

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Gummy smile

Excessive gingival display, also known as a “gummy smile,” is often considered detrimental to an aesthetically pleasing smile. Gingival display of more than 3 mm of gingiva is considered by many to be unattractive. The prevalence rate ranges from 10% to 29%, with a female predominance. Gummy smiles have a complex pathogenesis. Factors that contribute to the gummy smile include lip hypermobility due to the hyperactivity of upper lip elevators, altered passive eruption by apical gingival migration, lip length, incisal wear to crown length, vertical maxillary excess, and gingival hyperplasia.¹³ There are 3 Classifications of gummy smiles, based on the involved muscle groups: anterior, posterior, mixed, or asymmetric. The levator labii superioris, levator labii superioris alaeque nasi belong to the anterior muscle groups, while the posterior muscle group includes both the zygomaticus major and the zygomaticus minor [Table 2].¹⁴

BoNT-A is recognized as a non-surgical treatment for a gummy smile.^15,16 Clinical trials and systematic reviews have demonstrated its efficacy in reducing gingival exposure by targeting muscle complexes, including the levator labii superioris alaeque nasi, levator labii superioris, and zygomaticus minor. The dosages used vary between 2 and 5 U per site. The gingival show can be reduced by about 3 mm. The effects typically last between 3 and 6 months, with significant improvement in gingival display and high patient satisfaction.^15,17,18 Table 3 provides a summary of published trials.^19-25 The standard injection points for BoNT-A are shown in the Figure 2.

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Figure 2:

Standard injection points for botulinum neurotoxin-A (star) for the correction of gummy smile. Injections must be performed bilaterally (modified, original from Patrick J. Lynch, medical illustrator; Public domain).

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Treatment of a gummy smile with BoNT-A is a minimally invasive procedure with low complication rates, allowing for anatomical customization in cases of muscle hyperactivity. The major target muscles for injection with BoNT-A are levator labii superioris, levator labii superioris ala nasalis, and zygomaticus minor. The identification of injection points requires a deep understanding of facial anatomy and a steep learning curve to avoid alterations in smile symmetry and facial expression. This would argue for a tailored approach in contrast to standardized injection points [Figure 3].²⁵

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Figure 3:

(a) Female patient with a gummy smile and excessive gingival display while smiling – a combination of types 2 and 3. (b) Three weeks after the injection of 4 units per side of Botulinum neurotoxin-A (Botox®). The levator labii superioris alaeque nasi, levator labii superioris, and zygomaticus minor muscles were treated bilateral.

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BoNT-A can be used as an adjunct to lip reposition surgery (LRS).¹³ The primary goal of BoNT-A in LRS is to reduce muscle tension (i.e., muscular relaxation) during the postoperative healing phase to prevent scarring. To obtain the best results, BoNT-A injections should be performed at least 48 h before LRS.^26,27

The most common adverse events of BoNT-A injections to treat a gummy smile were injection pain and asymmetries.²⁸

Cleft lip repair

Orofacial cleft is one of the most common facial malformations. It results from fusion failures during early embryogenesis caused by complex disturbances of signaling pathways. Orofacial cleft can be classified into cleft lip only, due to a lack of fusion between the medial nasal and maxillary processes, cleft palate only, caused by a lack of fusion of the palatal shelves, or cleft lip and palate. Most cases are non-syndromic and sporadic. Several factors, including genetic, ethnic, sociodemographic, and environmental influences, are involved.²⁹

Epidemiologic data vary remarkably between 1/500 and 1/2500 live births.³⁰ Recent studies from Africa suggest a prevalence of 0.3/1000 live births in the South African public health sector,³¹ while the prevalence was 12.1–34.2% across Rwanda provinces.³² Males are affected twice as much as females by clefts involving the lip.³⁰

BoNT-A has been investigated for its potential to improve scar quality.³³ This indication can be especially useful in surgeries in the oral and perioral region, as in the control of scars after correction of cleft lip repair. The expected effects of using the drug in this condition are the adequate management of post-surgical muscular imbalance, hypertrophic scarring, and aesthetic asymmetry. BoNT-A can be injected either before, during, or shortly after surgery, depending on clinical goals.

We identified five randomized controlled trials in the treatment of unilateral cleft lip repair.^34-38 Outcome was assessed 6 months after surgery. The usual total dosage used was 15 IU of abobotulinum toxin. The predominant site of injection was four points in the subadjacent orbicularis oris muscle. One study compared this technique to a six-point injection in the nasolabial fold region. The outcome was comparable to the standard technique. For details, see Table 4.^34-38

The data suggest that BoNT-A can reduce wound tension, thereby enhancing scar outcomes.

The dermal white adipose tissue is involved in skin fibrosis. These adipocytes have the potential to proliferate or transdifferentiate into other cell types in vivo, including myofibroblasts.³⁹

In vitro studies revealed that BoNT-A effectively inhibits the growth of fibroblasts derived from scar tissue. It also reduced the expression of α-smooth muscle actin and myosin II.⁴⁰ In another investigation, BoNT-A enhanced the expression of both bone marrow protein 4 (BMP4) and p-Smad (1, 5, and 8) and adipocyte markers (i.e., peroxisome proliferator-activated receptor gamma PPAPγ and CCAAT enhancer-binding protein alpha C/EBPα. It also increased the accumulation of lipid droplets. On the other hand, BoNT-A diminished the expression of alpha-smooth muscle actin (α-SMA), collagen I and III in keloid myofibroblasts. In conclusion, BoNT-A promoted the transdifferentiation of myofibroblasts into adipocyte-like cells.⁴¹

A recent systematic review and meta-analysis on this topic confirmed that BoNT-A was superior in preventing and treating scars after cleft lip repair, particularly in terms of scar width (SW) and Visual Analog Scale (VAS), while the change in Vancouver Scar Scale (VSS) did not reach statistical significance.⁴² This treatment can allow better control in the healing process, better symmetry, besides decrease the need for secondary surgeries. On the other side, scar height, pigmentation, vascularity, and pliability of scar do not improve with BoNT-A.³⁸

Since cleft lip repair is performed under general anesthesia, injection pain from BoNT-A is negligible, but further injections after surgery will be temporarily painful. There are no other reports of adverse events.

Typical injection points with 2–5 IU BoNT-A are shown in Figure 4.

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Figure 4:

Typical injection points for botulinum neurotoxin-A (star) after reconstruction of a unilateral complete cleft lip (modified, original from Public domain).

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Rehabilitation after facial palsy

Peripheral facial nerve palsy has an estimated annual incidence of 23 cases per 100,000 inhabitants. The disease is a consequence of a lower motor neuron lesion of the facial nerve. The idiopathic type (Bell’s palsy) is the most common, but it may occur due to various medical conditions, including infection, cholesteatoma, trauma, malignancy, autoimmune issues, and others. Bell’s palsy is likely induced by the reactivation of viral infections caused by herpes simplex virus type 1 and type 2, or varicella zoster virus. Treatment includes drug therapy, surgical nerve decompression, physical therapy, and muscle and nerve transfer.⁴³

Major symptoms of facial palsy include synkinesis, hyperkinesis, and spasm. BoNT-A can be used to manage these symptoms in patients recovering from acute facial nerve palsy and those patients with later paralysis. To create more symmetry at rest and with animation, BoNT-A is injected into the targeted muscles of the unaffected side to reduce hyperkinesis, resulting in a significant esthetic improvement of the face. To improve synkinesis, BoNT-A is injected into the involved muscle to reduce or eliminate the involuntary muscle contraction that is aberrantly triggered. The injection of BoNT-A and the dosage depend on the type of paralysis, the time elapsed since the injury happened, the intensity of the paralysis of the affected muscles, the muscular activity of the affected side of the face and the contralateral side of the face, and the patient’s clinical condition. Another factor to be considered is the expectation of spontaneous improvement of the paralysis or whether the condition is permanent.⁴⁴

Typically, BoNT-A is injected into overactive muscles, commonly the orbicularis oris, depressor anguli oris, and contralateral mimetic muscles, to rebalance facial dynamics. Dosages vary between 5 and 15 U of abobotulinumtoxin A with 0.5–2 U per injection point. Cooled gel packs and vibration provide a significant reduction in injection pain.^45-48 In addition to improving facial symmetry and balance and harmony of muscle activity, treating facial paralysis with botulinum toxin improves self-esteem and interpersonal relationships.^49,50 BoNT-A can be combined with neuromuscular retraining therapy or facial biofeedback rehabilitation with a mirror at home. Table 5 summarizes available clinical studies.^51-71

Furthermore, Amar et al. (2024) investigated the impact of BoNT-A in the management of long-standing facial palsy (<6 months) on various parameters of quality of life (QoL) in 88 patients.⁷² The authors compared the results before treatment with those 1 month and 4 months after BoNT-A using three questionnaires, i.e., the hemifacial spasm questionnaire Hemifacial spasm (HFS)-30, the patient-reported outcome instrument facial clinimetric evaluation (FaCE), and the hospital anxiety and depression scale. One month after BoNT-A injection, significant improvements were noted in hospital anxiety and depression (HAD), HFS-30, and FaCA. The most significant changes were observed for “stigma” and “well-being” (HSF30) and “facial comfort” and “social function” (FaCE). There was no further improvement after 4 months. Patients with a short history of their disease and younger patients experienced a better outcome.⁷²

Typical injection points for BoNT-A on the non-affected facial site are shown in Figure 5.

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Figure 5:

Typical injection points for botulinum neurotoxin-A (star) in facial palsy on the non-affected facial site (modified, original from Patrick J. Lynch, medical illustrator; Public domain).

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In conclusion, BoNT-A injections can be integrated into a holistic approach for treating and rehabilitating patients with facial palsy [Figures 6 and 7]. The major adverse event is injection pain. Since the injections must be done repeatedly, this might be seen as a limitation. The combination with dermal filler injections can be useful in case of associated atrophy.⁵⁰

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Figure 6:

(a) A 26-year-old patient with left-sided permanent facial paralysis of traumatic origin. (b) Three months after treatment with 32 units of botulinum neurotoxin-A (Botox®). The zygomaticus major and minor muscles, risorius, orbicularis oris, levator labii superioris, and levator alae nasi were treated. The appearance has significantly been improved (With permission from Wollina, U.; Goldman, A. Botulinum toxin A and/or soft tissue fillers for facial rehabilitation. Wien Med Wochenschr. 2017, 167, 92-95.).

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Figure 7:

(a) A 62-year-old patient with Wegener’s granulomatosis and a history of two episodes of facial paralysis. (b) Nine weeks after treatment with 35 units of botulinum toxin type A (Botox®). The zygomaticus major and minor muscles, risorius, orbicularis oris, levator labii superioris, levator alae nasi, and orbicularis oris were treated.

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Scar prevention or treatment on the lips

BoNT-A has been investigated for its potential to improve the appearance of scars, particularly in the context of surgical and hypertrophic scars. The mechanism by which BoNT-A improves scar appearance is primarily through the reduction of muscle tension during the healing process, which leads to less tension on the wound edges and, subsequently, more favorable scar formation.⁷³ Table 6 summarizes clinical trials. A clinical example is provided in Figure 8.

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Figure 8:

(a) 66-year-old patient with a long upper lip and minimal vermilion show. (b) Appearance 3 months after a lip lift. A well-healed scar at the base of the nose is visible. The area was treated intraoperatively with 2 units of botulinum neurotoxin-A (Botox®), with an additional 2 units injected on the 10^th post-operative day.

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There is an additional case report about an adult patient with chorea-acanthocytosis, who was treated by surgery and adjuvant onabotulinumtoxin A post-surgery for a lower lip defect.⁷⁴ Bilateral injection points were in the orbicularis oris and the masseter with a total dosage of 100 U.

The drug can be injected within the first few days post-injury or post-surgery.

The use of BoNT-A for the prevention or treatment of scars on the lips is supported by its application in cleft lip repair, where it has been shown to improve scar quality by reducing muscle tension during the healing process. This principle can be extended to other types of lip scars, although specific studies on non-cleft lip scars were not identified. Clinical studies have demonstrated that early post-operative injection of BoNT-A can prevent hypertrophic scarring and improve scar quality. In patients undergoing lip lifting with a scar at the base of the nose, the administration of botulinum toxin may be useful in controlling and improving the quality of the scar.

The most common adverse event is temporary pain during injection. Bruising is also more common on the lips. BoNT-A can be combined with physical therapy.⁷⁵

There are no reports of complications due to BoNT-A use.⁷⁶ BoNT-A reduces the SW and improves the VAS score better than controls. In addition, BoNT-A significantly improves the VSS score compared to controls but less than corticosteroid injections.⁷⁷

The method seems to be of interest also in perioral scars. Figure 8 shows an example of scar prevention by BoNT-A after upper lip lift. However, we found no clinical trials for scar prevention in the perioral area unrelated to cleft lip and palate repair.⁷⁸