Botulinum Toxin and Dermal Fillers for Facial Aging

Course #90200 - $60 -


Study Points

  1. Outline the background of aesthetic medicine and botulinum toxin/filler use.
  2. Describe the process of usual facial aging.
  3. Discuss the mechanism of action and clinical use of botulinum toxin for the treatment of facial aging.
  4. Compare and contrast the classes of dermal filling agents available.
  5. Analyze components that affect the appropriate selection of dermal filling agent.
  6. Describe key aspects of individualized assessment of patients seeking aesthetic treatments for facial aging.
  7. Outline the minimally invasive approach to the treatment of facial aging.
  8. Evaluate patient-related factors affecting suitability for various aesthetic treatments.
  9. Identify acute and potentially severe side effects of botulinum toxin/filler use.
  10. Discuss the role of biofilm infections in delayed reactions to dermal fillers.

    1 . There has been a para­digm shift from "wrinkle-chasing," with isolated clinical benefit, to
    A) a focus on surgical management of facial aging.
    B) recognition of facial aging as the result of extrinsic factors only.
    C) a three-dimensional, multilayered treatment approach.
    D) All of the above

    BACKGROUND

    Studies identified soft tissue volume loss and hard tissue resorption as causal to facial aging. This prompted filler injection into deep tissue for re-volumizing; new fillers designed for specific tissue placement; use of lower-dose botulinum toxin to improve outcomes; advances in lasers and energy devices for resurfacing or tightening with minimal recovery time; and evidence of synergistic efficacy and superior cosmetic outcomes with combined therapies [6,7,8]. These advances brought a paradigm shift from "wrinkle-chasing," with isolated clinical benefit, to recognition of facial aging as a complex interaction of extrinsic and intrinsic factors across multiple tissue planes requiring a three-dimensional, multilayered treatment approach [9,10]. Surgical facelift requires patients to wait until visible aging is sufficient to warrant surgery, often with sudden, sometimes unnatural, changes in appearance. Minimally invasive therapy offers a more gradual, natural-looking harmonization preferred by many patients [7].

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    2 . Among patients treated by members of the American Society of Plastic Surgeons (ASPS) in 2019, what proportion was Caucasian?
    A) 60%
    B) 70%
    C) 80%
    D) 92%

    BACKGROUND

    Botulinum toxin and dermal filler injection techniques are constantly evolving; what was considered state-of-the-art 5 to 10 years ago no longer represents a practice standard [11]. Every year, the American Society of Plastic Surgeons (ASPS) and the American Society for Dermatologic Surgery (ASDS) separately publish the number of procedures performed by their board-certified members. In 2019, ASPS members performed 18.1 million cosmetic procedures—16.3 million nonsurgical (82% female)—at a total cost of $16.7 billion. Among patients who received cosmetic procedures, 70% were Caucasian, 11% were Hispanic, 9% were African American, 7% were Asian, and 3% were other [12]. The 7.7 million botulinum toxin and 2.7 million dermal filler procedures reported by ASPS in 2019 represent an increase of 878% and 312%, respectively, compared with 2000 [12]. ASDS members in 2019 performed an additional 2.3 million botulinum toxin (88% female) and 1.6 million filler (90% female) procedures, a 60% and 78% increase from 2012, respectively [13].

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    3 . In 2019, how many dermal filler procedures were performed by members of ASPS and/or the American Society for Dermatologic Surgery (ASDS)?
    A) 2.1 million
    B) 4.3 million
    C) 7.2 million
    D) 15.7 million

    BACKGROUND

    Botulinum toxin and dermal filler injection techniques are constantly evolving; what was considered state-of-the-art 5 to 10 years ago no longer represents a practice standard [11]. Every year, the American Society of Plastic Surgeons (ASPS) and the American Society for Dermatologic Surgery (ASDS) separately publish the number of procedures performed by their board-certified members. In 2019, ASPS members performed 18.1 million cosmetic procedures—16.3 million nonsurgical (82% female)—at a total cost of $16.7 billion. Among patients who received cosmetic procedures, 70% were Caucasian, 11% were Hispanic, 9% were African American, 7% were Asian, and 3% were other [12]. The 7.7 million botulinum toxin and 2.7 million dermal filler procedures reported by ASPS in 2019 represent an increase of 878% and 312%, respectively, compared with 2000 [12]. ASDS members in 2019 performed an additional 2.3 million botulinum toxin (88% female) and 1.6 million filler (90% female) procedures, a 60% and 78% increase from 2012, respectively [13].

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    4 . The total minimally invasive procedures reported by the ASPS and ASDS in 2019
    A) is not considered reliable.
    B) overestimates the total performed in the United States.
    C) underestimates the total performed in the United States.
    D) accurately reflects the total performed in the United States.

    BACKGROUND

    Between 2012 and 2017, there was a 50% increase in cosmetic procedure requests by persons younger than 30 years of age (90% female), and in 2016, more than 229,000 cosmetic procedures were performed in patients 18 years of age or younger [14,15]. The annual figures by ASPS/ASDS are considered the benchmark for cosmetic procedures, trends, and demand, but they significantly under-represent the actual number of minimally invasive procedures performed outside of their membership [16,17,18,19,20].

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    5 . Age-related changes that involve specific facial tissue levels are best described by
    A) horizontal zones.
    B) the two-dimensional model.
    C) the three-dimensional model.
    D) the aesthetic zones/units model.

    THE PROCESSES OF FACIAL AGING

    Perceptual models used in cosmetic medicine can assist in conceptualizing these changes. Each model views facial aging from a different perspective. Presented in sequence, the models break down the complex, dynamic, multidimensional process into its dimensional components. The predominant models are [4,26,27,28,29,30,31,32]:

    • The two-dimensional (2-D) model: Organizes the surface anatomy and superficial cosmetic defects into horizontal zones that anchor morphologic features to familiar anatomic boundaries

    • The three-dimensional (3-D) model: Delineates facial anatomy into its underlying tissue layers to describe normal and age-related changes in structure/function at each facial tissue level

    • The integrative model: "Zooms out" from the 3-D model to describe how tissue-level changes interact to form the visible features of facial aging

    • The aesthetic zones/units model: Describes cosmetic defects of facial aging as changes in underlying and surrounding tissue within anatomically compartmentalized units

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    6 . In terms of aging and the facial skeleton,
    A) resorption and atrophy are uniform.
    B) greatest resorption occurs with the maxilla.
    C) greatest resorption occurs with the frontal bone (forehead).
    D) the facial skeleton is largely irrelevant to cosmetic concerns.

    THE PROCESSES OF FACIAL AGING

    From prominent bone formation in youth, age-related changes in the relative dynamics of bone expansion and bone loss lead to predominant bone resorption in the aging craniofacial skeleton, an important contributor to facial aging [42,49]. Skeletal resorption and atrophy is uneven, and bone reduction is greatest in facial areas where prominent aging stigmata appear [4,25,31,42,50]. The maxilla has the greatest resorption; substantial reduction in its anterior projection largely contributes to aged appearance. The periorbital bones and anterior and inferior mandible (prejowl area) resorb extensively; the chin becomes shorter. The posterior and superior mandible undergo bone formation, increasing the mandible angle from 97º in younger skulls to 135º in older skulls. Maxilla and mandible resorption appreciably reduces the facial height. The midface recedes, but the forehead continuously expands.

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    7 . Which of the following is TRUE regarding onabotulinumtoxinA?
    A) It was first marketed in Europe.
    B) It is the original, most-studied formulation.
    C) It is the only approved serotype-B formulation.
    D) It is newer and less-studied, and FDA approval is pending.

    BOTULINUM TOXIN

    BOTULINUM TOXIN PRODUCTS AND FORMULATIONS

    Name, SerotypeCommercial ProductFDA-Approved IndicationsComments
    ONA type-A
    Botox
    Botox Cosmetic
    Vistabel
    Vistabex
    Vacuum-dried powder (50 or 100 U/vial)
    Glabellar, lateral canthal, and forehead linesThe original, most-studied formulation. Widely used off-label for treating other lines and facial contouring.
    ABO type-ADysport (300 or 500 U/vial)Glabellar linesFirst marketed in Europe
    INCO type-ABocouture or Xeomin (as lyophilized powder in 50 or 100 U)Glabellar linesNewer formulation. Free of complexing proteins. May reduce risks of sensitization and antibody formation.
    PRA type-AJeuveau (4 U [0.1 mL] IM in each of five sites)Glabellar linesNewer formulation. Similar in efficacy to ONA.
    RIMA type-BMyobloc, in liquid (5,000 U/mL)No cosmetic indicationsLess studied than type-A. Used in off-label facial lines. Distributed in the United States and Canada.
    ABO = abobotulinumtoxinA, INCO = incobotulinumtoxinA, ONA = onabotulinumtoxinA, PRA = prabotulinumtoxinA, RIMA = rimabotulinumtoxinB, U = units.
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    8 . Long-term follow-up of patients treated with botulinum toxin for glabellar lines suggests
    A) efficacy sustained with increased dosing.
    B) the development of antibodies with loss of efficacy.
    C) efficacy sustained with decreasing injection intervals.
    D) patients reported greater reductions in their perceived age with increasingly longer treatment durations.

    BOTULINUM TOXIN

    Long-term outcome data support practice trends in decreased dosing and increased botulinum toxin injection intervals. Patients treated for glabellar lines over an average of nine years reported high levels of satisfaction sustained by repeated treatment and greater reductions in their perceived age with increasingly longer treatment durations [6].

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    9 . In which of the following patient populations is botulinum toxin injection very likely to be effective?
    A) Kinetic
    B) Hypertonic
    C) Hyperkinetic
    D) Deep static lines with loss of skin elasticity

    BOTULINUM TOXIN

    To help determine botulinum toxin suitability, assess facial muscle function and tone in static and dynamic states looking for signs of stronger contraction (e.g., greater dynamic movement, deeper lines, larger apparent mass during use) [67]. Observing dynamic movement of the skin can help identify areas of stronger or weaker muscle contraction, why certain wrinkles are formed, and which muscles are creating them. The findings assign patients to one of the following categories [67]:

    • Kinetic: Regular muscle contraction and wrinkles during active expression, but not at rest. Botulinum toxin very likely effective.

    • Hyperkinetic: More excessive muscle contraction. May require more frequent, higher-dose botulinum toxin to achieve the desired effect.

    • Hypertonic: Inability to relax specific muscles, visible wrinkles at rest. Some benefits may be possible with botulinum toxin, but adding filler injections may be necessary.

    • Deep static lines with loss of skin elasticity: Unsuitable for botulinum toxin injection.

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    10 . Poor botulinum toxin treatment response can result from
    A) anatomical variation.
    B) insufficient or incorrect dosing.
    C) errors in drug handling during preparation, storage, or administration.
    D) All of the above

    BOTULINUM TOXIN

    Poor treatment response can result from insufficient or incorrect dosing, anatomical variation, or errors in drug handling during preparation, storage, or administration. Diffusion of toxin to untargeted areas from improper injection placement can result in excessive muscle weakness, cosmetic disfigurement, and/or functional deficits that persist for months.

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    11 . The only permanent dermal filler approved by the FDA is
    A) hyaluronic acid.
    B) poly-L-lactic acid (PLLA).
    C) calcium hydroxylapatite (CaHA).
    D) polymethylmethacrylate (PMMA).

    SOFT TISSUE (DERMAL) FILLERS

    The FDA designates fillers as either absorbable/temporary (e.g., hyaluronic acid, calcium hydroxyapatite [CaHA], poly-L-lactic acid [PLLA]) or non-absorbable/permanent (e.g., polymethylmethacrylate [PMMA]) based on the agent's biodegradability. If an agent absorbs within 18 months, it is considered temporary; if it does not absorb within 24 months, it is considered permanent. Some agents combine absorbable material for immediate effect and carrier until a nonabsorbable material induces fibroblast stimulatory effects (in more than 18 months). These agents are considered semipermanent. Agents with minimal tissue response are considered volumizers, while those that induce a strong tissue reaction are considered stimulators.

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    12 . Dermal fillers most suitable for deep-tissue placement to re-volumize are characterized by
    A) Low elasticity and high viscosity.
    B) High elasticity and high viscosity.
    C) High elasticity and low viscosity.
    D) Low elasticity and low viscosity.

    SOFT TISSUE (DERMAL) FILLERS

    Clinically, the elasticity of filler reflects the gel's firmness. The level of viscosity will determine the pattern and extent of tissue integration. High-viscosity agents resist tissue spread and shearing. Low-viscosity agents are ideal for superficial placement to treat shallow folds and lines and are best used where spread and softness is more important than volume (e.g., the lips) [52,76,77,78]. Conversely, high-elasticity and high-viscosity gels are best suited for deep placement to treat deep folds and restore volume loss by creating volume and lift in the mid- and lower face.

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    13 . Greater risk of intra-arterial complications may be related to using
    A) Sculptra.
    B) Bellafill.
    C) Radiesse.
    D) Revanesse.

    SOFT TISSUE (DERMAL) FILLERS

    Of note, Radiesse may be more likely than other fillers to result in intra-arterial complications, skin necrosis, and blindness. The increased propensity to cause vascular compromise could be related to particle size, with larger particles resulting in more proximal vessel obstruction. Certain particles may also stimulate the clotting cascade, ultimately resulting in skin necrosis [16]. This seems to elevate precautions in using this product near vascular danger zones.

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    14 . Deoxycholic acid (Kybella) is best described as
    A) an alternative to liposuction.
    B) a volumizer for submental fat atrophy.
    C) extensive in cosmetic medicine following its approval.
    D) a reducer of fat accumulation in any subcutaneous tissue.

    DEOXYCHOLIC ACID

    Kybella is an alternative to liposuction for achieving an aesthetically pleasing jawline by submental fat reduction, but comparisons in clinical trials are lacking. Kybella is given in 0.2-mL injections, spaced 1 cm apart, until all sites in the planned treatment area are injected. Up to 50 injections, or 10 mL, are allowed per session. Several sessions spaced at least four weeks apart are usually required. In phase 3 clinical trials, the drug was effective and safe, although a significant number of patients experienced pain, transient bruising, edema, and numbness [98,99].

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    15 . Which of the following is an important consideration in minimally invasive therapy of male patients?
    A) Understanding sexual dimorphism
    B) Preventing unwanted feminization of male features
    C) Preventing an exaggeration of typical male features
    D) All of the above

    INDIVIDUALIZED ASSESSMENT AND TREATMENT PLANNING

    Understanding sexual dimorphism is crucial to prevent unwanted feminization of male features, a primary concern of male patients seeking aesthetic treatment [52,114,115,116]. In addition, cosmetic intervention that produces an exaggeration, rather than restoration, of typical male features can result in an aggressive or threatening appearance [117]. Of course, some men do wish to attain a more feminine or masculine appearance, but this is beyond the scope of this course, which focuses on cosmetic procedures to address unwanted facial changes associated with aging.

    General approaches to minimally invasive correction of cosmetic concerns in older men vary by the area of the face [52,113,114,115,116].

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    16 . What is the optimal sequence of minimally invasive treatment delivery?
    A) Concurrent fillers with laser resurfacing
    B) Concurrent botulinum toxin with laser resurfacing
    C) All treatments spaced apart at least two weeks, regardless of modality
    D) Same-day treatment to fully capitalize on the synergistic interactions

    THE MINIMALLY INVASIVE TREATMENT APPROACH

    Improved understanding of facial aging and mechanisms of therapies inform their combination and sequence of use. With superior outcomes repeatedly demonstrated with combination therapy over monotherapy, this approach is now recommended for most patients [6,10,33,34,52,120].

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    17 . What feature of facial aging may also result from improper botulinum toxin injection?
    A) Jowls
    B) Brow ptosis
    C) Nasolabial folds
    D) Lateral canthal rhytides

    THE MINIMALLY INVASIVE TREATMENT APPROACH

    Horizontal forehead rhytides require simultaneous botulinum toxin injections of the frontalis and brow depressors. With frontalis muscle injection alone, unopposed activity of depressor muscles will induce a lowered, angry-looking brow ptosis. Frontalis injections are 2–3 cm above the brows; closer brow placement risks inhibition of facial expression and brow ptosis [11,33].

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    18 . Which area of the face is recommended for initial treatment?
    A) Upper
    B) Mid
    C) Lower
    D) Neck

    THE MINIMALLY INVASIVE TREATMENT APPROACH

    In facial aesthetics, the midface is a main determinant of perceptions of facial attractiveness, influenced by synergy of the eyes, nose, lips, and cheekbones (central facial triangle). It is also the focal point for restoration of a youthful topography. As such, the midface should be treated first [4,10,122].

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    19 . What is the recommended approach to a primary complaint of prominent nasolabial folds?
    A) Volumizing the malar area is attempted first.
    B) The nasolabial fold is injected directly with fillers.
    C) Treatment is confined to the lower nasolabial fold.
    D) The nasolabial fold is injected directly with botulinum toxin.

    THE MINIMALLY INVASIVE TREATMENT APPROACH

    Most fillers are indicated for treating nasolabial folds by the FDA, but unlike other midface areas, nasolabial folds hypertrophy with age. Thus, fillers are suggested to soften a prominent fold, not to volumize. First correct deficient malar volume, then soften residual nasolabial folds conservatively using moderate-elasticity and -viscosity filler (e.g., Restylane-L, Juvéderm Ultra XC) injections in the superficial fat just to the dermis [29].

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    20 . Better understanding of adverse events has greatly expanded the contraindications of
    A) patient age.
    B) autoimmune disorders.
    C) skin conditions and disorders.
    D) over-the-counter vitamin and supplement use.

    PATIENT SELECTION AND EVALUATION

    A thorough history of skin conditions, allergies, systemic disease, current medication use, and previous cosmetic procedures is mandatory. Patients may not see important aspects of their history as relevant. To help ensure disclosure, assess skin-related and systemic conditions by linking to potential adverse effects [19,71].

    Some skin disorders and local or remote infections can promote injection seeding of infective agents that populate the filler site, or hematogenous spread to implanted fillers and later biofilm formation or transition from infection to hypersensitivity [19,129,130]. These conditions require careful screening. Fillers have risks of injection-site keloid formation or hyperpigmentation; patients with these conditions should avoid fillers [75].

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    21 . Aggrieved dissatisfaction with cosmetic results is most likely in which patients?
    A) Younger age
    B) Lower education
    C) Body dysmorphic disorder
    D) Those seeking surgical procedures

    PATIENT SELECTION AND EVALUATION

    Understanding the motivations for cosmetic treatment is vital to minimizing inappropriate patient selection. Unrealistic expectations, which are contraindications to cosmetic treatment, are prevalent in some psychological conditions [19,75]. Low self-esteem can lead to unrealistic goals and expectations. High neuroticism and/or anxiety may influence expectations, and outcomes tend to be poorer [131]. The most important mental disorder consideration is body dysmorphic disorder.

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    22 . Which of the following is a positive predictor of patient satisfaction with cosmetic outcomes?
    A) Peer pressure
    B) Low self-esteem
    C) Internal motivation
    D) External motivation

    PATIENT SELECTION AND EVALUATION

    Patient motivation is considered external when expecting physical changes to influence some aspect of their life (e.g., partner will love them more, career success). Unrealistic expectations with external motivation require discussion, as these patients are more likely to be dissatisfied with outcomes. In contrast, internally motivated patients (driven by a desire to look better for themselves) are good candidates [131,138].

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    23 . Which of the following is an essential element of ensuring patients do not envisage an unrealistic outcome?
    A) Confidence-building
    B) Expectation management
    C) Accurate marketing and promotion
    D) Treatment planning guided by the patients' preconceived treatment approach

    PATIENT SELECTION AND EVALUATION

    Patient expectations should be managed so they do not envisage an unrealistic outcome. The treatment of inadequately informed patients is fraught with potential problems and risks of dissatisfaction [71].

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    24 . Most malpractice claims in cosmetic medicine result from
    A) a botched procedure.
    B) adverse complications.
    C) inadequate informed consent.
    D) technique that falls below patient expectations.

    PATIENT SELECTION AND EVALUATION

    The risk of malpractice claims is highest in cosmetic medicine. Most result from inadequate informed consent instead of procedural failures [16]. To fully inform decision-making and consent to treatment of patients, carefully discuss the possible benefits, disadvantages, and limitations over a broad range of options [7,95].

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    25 . Which of the following is TRUE of vascular compromise during filler injections?
    A) It is largely prevented by improved filler rheology.
    B) Complications are now decreasing with better training.
    C) It is a potentially catastrophic complication and a risk even with expert injectors.
    D) It is a potentially catastrophic complication prevented by proper aseptic injection prep.

    ADVERSE EFFECTS

    Vascular occlusion from injected filler material may lead to potentially catastrophic complications of tissue necrosis, blindness, or stroke. Even with advanced knowledge of facial anatomy, vascular injury cannot be avoided with 100% certainty. However, measures can be taken to help reduce risks and mitigate intravascular adverse events if they develop. A key step is understanding the danger zones for vascular occlusion, areas where arteries have little or no collateral circulation, extensive anastomoses with the internal carotid artery, or are prone to external compression. Risk factors for vascular occlusion are summarized in Table 7 [19,146,147]. Table 8 outlines strategies to mitigate these potential complications.

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    26 . If visual impairment and ocular pain occurs during filler injection,
    A) central retinal artery occlusion is likely.
    B) withdraw needle and inject another site.
    C) apply warm compresses until vision returns.
    D) apply nitroglycerin paste 2% to promote vasodilatation.

    ADVERSE EFFECTS

    The most feared complication of filler injections is blindness following occlusion of the central retinal artery, the final branch of the ophthalmic artery. Comparing average diameters, injected hyaluronic acid filler particles (400 mcm) easily move through the ophthalmic artery (2 mm) to block the central retinal artery (160 mcm) [122,154,157].

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    27 . Among filler types, the distinct safety advantage with hyaluronic acid fillers is
    A) lack of migration.
    B) the proven absence of immune responses.
    C) adverse events self-limiting from the brief duration in tissue.
    D) availability of hyaluronidase to reverse many adverse events.

    ADVERSE EFFECTS

    With hyaluronic acid fillers, hyaluronidase injection is the foundation of emergent therapy for most adverse events, a powerful advantage of these products, as no other dermal filler material has a reversing agent [19]. Hyaluronidase injection enzymatically dissolves the hyaluronic acid filler material [68].

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    28 . Which of the following statements regarding acute hypersensitivity reactions is FALSE?
    A) It can represent a medical emergency.
    B) Cold compresses are effective management.
    C) Local angioedema can progress to airway obstruction.
    D) Any systemic manifestation should be treated as impending anaphylaxis.

    ADVERSE EFFECTS

    Type I hypersensitivity reactions, mediated by immunoglobulin E (IgE), may present with angioedema or anaphylaxis. Check vital signs; anaphylactic shock is a medical emergency. Angioedema can also progress to airway obstruction. Any systemic manifestation should be considered impending anaphylaxis and treat as such. This involves immediately administering IV epinephrine; if insufficient to maintain perfusion, consider additional vasopressor agents (e.g., dopamine, norepinephrine, glucagon). H1-receptor antagonists (plus cimetidine) are recommended for histamine-induced hypotension.

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    29 . Biofilm infections are thought to arise from
    A) manufacturing contamination.
    B) foreign body immune responses.
    C) type IV immunological reactions.
    D) skin surface bacteria inserted into tissue during filler injection.

    ADVERSE EFFECTS

    Biofilm as an increasing concern is reflected in surgical and infectious disease practice guidelines; uptake in cosmetic/aesthetic medicine is more recent. The skin is understood as a microbiota ecosystem, colonized by diverse micro-organisms. In normal skin flora, most bacterial constituents are harmless. Some are beneficial, such as Staphylococcus epidermidis, which inhibits the growth of pathogenic Staphylococcus aureus [169,170].

    S. aureus, the most commonly isolated pathogenic bacteria in surgical-site infections, colonizes tissue and artificial surfaces and is found on 30% to 60% of healthy Americans. A disturbed balance of the skin ecosystem can favor S. aureus proliferation and biofilm [171,172,173,174].

    On unbroken skin, S. aureus can remain asymptomatic; on injection sites, it can seed infections. The needle breaks the skin barrier, picking up bacteria that are delivered into the dermal filler and setting up infection in the tissue. Preoperative skin preparation for open surgery fails to remove 20% of resident skin flora [21,165,175].

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    30 . Bacterial biofilm infections are concerning because
    A) biofilms are very difficult to detect.
    B) biofilms are typically very difficult to treat.
    C) filler explant, and risks of scarring and deformity, may be required.
    D) All of the above

    ADVERSE EFFECTS

    Biofilms are very difficult to treat and can require antibiotic concentration over 32 times that necessary for planktonic bacteria. Even the highest tolerable antibiotic dose can be insufficient [176]. Filler explant may be needed, putting the patient at risk for tissue scarring, deformity, and nerve or structural damage. Minimally biodegradable fillers have higher rates of delayed-onset infection [165].

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