Pearls and Pitfalls of Neurotoxins and Facial Fillers

6
Pearls and Pitfalls of Neurotoxins and Facial Fillers


Raffi Der Sarkissian


Boston Facial Plastic Surgery, Boston, MA, USA


Division of Facial Plastic Surgery, Boston University School of Medicine, Boston, MA, USA


Division of Facial Plastic Surgery, Massachusetts Eye and Ear Infirmary, Boston, MA, USA


6.1 Pearls and Pitfalls in Neurotoxin Use


Success in the use of neurotoxins and fillers in the face relies on accurate analysis of the area(s) to be treated and correct application of the appropriate techniques for correction of each proposed area. It is imperative to determine if aging changes are related to textural changes in the skin itself, lines and furrows created by repetitive muscle movement, loss of elasticity with resultant skin and soft tissue ptosis, facial volume loss or redistribution or a combination of these elements. If upon analysis, it is felt that the lines and wrinkles are a result of over activity of certain facial muscles, the benefits of neurotoxins have been well documented [1]. Following certain technical “pearls of wisdom” can mean the difference between a good and an excellent result and can minimize the possibility of an adverse result.


6.2 Neurotoxin Preparation and Storage


Commercially available neurotoxins (Onabotulinum toxin A, Abobotulinum toxin A and Incobotulinum toxin A) are provided in a vacuum dried or lyophilized state. Each requires reconstitution with injectable saline (0.9% sodium chloride). The type of diluent used has been debated with most companies recommending the use of preservative‐free saline while some practitioners preferring preserved saline. As alcohol is used as a preservative in saline, dilution with preserved saline may create more burning on injection. Some practitioners propose the opposite to be true and feel the alcohol acts as an anesthetic resulting in less pain. Preservative‐free saline is this author’s preference for dilution.


While diluting the product, it is imperative to know the concentration of the neurotoxin and attempt to reliably duplicate the required dilution for each vial. The volume used for dilution is not as critical as knowledge of the number of units per unit volume of diluted product (1–5 ml dilutions have been described). The benefit of lower‐volume dilution with higher concentration of toxin is the ability to use smaller volumes of injectate per site with theoretically less pain on injection and a more focused effect. Conversely, a higher volume dilution will allow the practitioner a more widespread distribution of an equivalent number of units of toxin. I have found a 3 ml dilution to be ideal, yielding a concentration of 3.3 Onabotulinum toxin units per 0.1 ml aliquot. Equally important is knowledge of the relative strengths of the commercially available products. As most initial studies of the efficacy of neurotoxins were conducted with Onabotulinum toxin (Botox), this is generally considered as the “standard” strength of toxin.


Conversion ratios have been developed for Abobotulinum toxin A (Dysport) and Incobotulinum A (Xeomin) as follows:



  • 1 Onabotulinum toxin unit = 2.5–3.0 Abobotulinum toxin units
  • 1 Onabotulinum toxin unit = 1.0–1.5 Incobotulinum toxin units

6.3 Choice of Syringes and Needles


There are a number of personal preferences in syringe and needle types for injection of neurotoxins. Most authors agree a small volume syringe 0.3–1.0 ml is ideal. Fixed needle syringes have the advantage of ease of use, however, in drawing up toxin the needles tend to dull easily (Figure 6.1).

Image described by caption.

Figure 6.1 Fixed needle syringes offer the convenience of not needing to change needles. However, if the needle dulls during injection it cannot be changed, thus requiring transfer of toxin to another syringe, which causes associated toxin waste.


Syringes with detachable needles allow changing of needles to fit the practitioners’ preference. Syringes that have a plunger that extends into the hub have the advantage of not wasting any product (Figure 6.2).

Image described by caption.

Figure 6.2 The plunger of the syringe on the right extends into the hub of the syringe assuring only a very small volume of toxin is wasted.


Drawing up toxin can be performed with a larger gauge needle (25–20 gauge) and injection can be performed with a finer gauge needle (33–30 gauge). Be aware that these finer needles are generally less traumatic, however, they do dull easily and if a number of injections will be performed, changing the needle is recommended. (Figure 6.3)

Image described by caption.

Figure 6.3 Very fine gauge needles can help minimize pain associated with toxin injections.


6.4 Basic Injection Principles


Placing needles in a patient’s forehead, around their eyes and in other anatomic sites around the face can induce fear, anxiety, and pain. Patients will often comment on injections being “painful,” “rushed,” “unpleasant” or causing significant post‐injection discomfort and/or bruising. Although bruising is possible even in the hands of the most skilled clinicians, the following techniques can minimize some negative effects and offer patients a more comfortable experience.



  1. Verbalize what to expect and where to expect the pain. “You will feel a pinch between the brows followed by a little burning.”
  2. Counting before injection helps patients anticipate the pain and not move reflexively during the injection.
  3. Use the smallest gauge needle and replace the needle as needed when dull.
  4. Consider using a topical anesthetic or pretreating with ice in extremely sensitive patients.
  5. Use digital pressure prior to injection to alleviate the discomfort in sensitive patients.
  6. Stretching the skin between the fingers allows the needle to penetrate more easily. Think of trying to sew fabric that is loose versus fabric that is stretched taught.
  7. Enter the skin tangentially. This helps to avoid contacting the underlying bone, particularly in areas of thin skin. Additionally, when the needle is placed sub‐dermally at an angle, it becomes easier to enter the subcutaneous muscle and deliver a bolus of toxin rather than entering vertically into relatively thin muscles with less chance of accuracy in toxin delivery. Think of laminated sheets of paper and the middle sheets of paper need to be saturated with liquid. Entering at an angle makes this exercise easier.
  8. Always look for obvious surface vasculature and attempt to avoid penetrating a vessel. Entering the skin tangentially can help here as well as the needle can be oriented away from any visible vessel.
  9. Treat muscles diffusely with small aliquots of toxin in multiple locations rather than larger boluses with the “expectation” that the toxin will diffuse into the target muscle. This leads to more accurate patterns of chemodenervation, minimizes risk of untoward results from diffusion of product away from the target muscle and minimizes the risk of incomplete treatment of a muscle group and its related pattern of rhytids.
  10. Always treat one entire muscle group at a time, starting on one side and treating the contralateral side with the same pattern of injection and the same dose of toxin. For example, treat the procerus in the midline of the glabella followed by the right medial corrugator, the left medial corrugator, the right mid corrugator, left mid corrugator, right distal (lateral) corrugator, and left distal (lateral) corrugator. In so doing, each side of the muscle will have the same injection sites along the muscle and the same dose and treatments with a higher chance of yielding symmetric results.
  11. After injection, apply digital pressure to the injection site in the direction you would like the toxin to diffuse and away from structure you are trying to avoid. This not only helps diffuse the toxin into the muscle more quickly but limits any potential bruising that might occur.
  12. Studies have shown reconstituted neurotoxins to maintain activity up to two weeks after reconstitution. It is recommended, however, to use toxins soon after reconstitution, ideally within the same calendar day.
  13. If storing reconstituted neurotoxin, do not freeze the product as this has been noted to decrease activity, possibly by damaging the carrier protein.
  14. Store the lyophilized product between 2 and 8 °C (36–46 °F)

6.5 Specific Injection Pearls Based on Injection Site


6.5.1 Glabellar Techniques


Obliquely oriented “inverted V shaped” lines are a result of contraction of the paired corrugator supercilii muscles. Horizontally oriented lines across the glabella are a result of contraction of the midline procerus muscle.


The procerus muscle originates on the nasal bone and attaches to the skin of the glabella or low midline forehead [2]. Having patients animate by asking them to “lower their brow” or create an “angry look” will help assess the vertical height of the muscle and help guide the number of injections required. Generally two injections will suffice in this area. The more inferior injection is placed somewhat more deeply and the superior injection more superficially to target the muscle depth more accurately. Small doses in the range of 3–10 Onabotulinum toxin units are usually enough to control the horizontal rhytids.


The corrugator supercilii muscles originate on the supraorbital ridge of the frontal bone and insert onto the skin above the brow generally anywhere between the root of the brow and the midbrow [3]. In treating this area, it is imperative to have the patient create an “angry look” and assess the length of the corrugator. Assessment of the length and bulk of the muscle will help with decisions about dose required and how many injections will be required to adequately decrease movement in the area and improve the appearance of the oblique furrows. At least two points of injection are required on each side. A muscle treated at only a single point can still contract medially or laterally to the point of injection resulting in post injection lines proximal or distal to the pre‐treatment furrows.


Generally three to four points of injection are recommended on each side based on the length of the muscle. The medial injections should be slightly deeper as the muscle originates on the bone and moving laterally, the injections should be more superficial targeting the muscle attachments to the skin (Figures 6.4a and 6.4b).

Image described by caption.

Figure 6.4 (a) Horizontally oriented corrugator supercilii muscle. Injections 1–4 are placed deeper. Sites 7 and 8 are optional only if muscle length extends laterally. The more medial injections are placed deeply, the more lateral superficially. (b) Vertically/obliquely oriented corrugator supercilii muscle. Injections 1–4 are placed deeply, 5 and 6 more superficially.


Injections in the suprabrow region should always be placed at least 1 cm above the supraorbital rim. Placement of the injector’s thumb on the rim helps to respect this anatomic requirement and also increases the resistance to flow of injectate to prevent diffusion to the levator palpebrae muscle minimizing the risk of upper eyelid ptosis.


On an average, approximately 15–30 Onabotulinum toxin A units are generally required to adequately treat the corrugator supercilii muscles and minimize glabellar oblique furrows.


Both the midline procerus and paired corrugators are depressors of the medial brow and medially constrict the brows. As such, successful treatment of this area should yield a “relaxation” of the space between the brows and relative elevation of the root of the brow.


As the muscles in this area are associated with expressions of anger, they are, from an evolutionary standpoint, required for “survival” and hence can be quite strong. Under correction, even with adequate doses of toxin are not uncommon. It is important to remind first‐time‐treatment patients that it may require retreating the area at four month intervals for two or three additional sessions to achieve more significant relaxation of the rhytids. In difficult‐to‐treat glabellar muscles, or in patients with grooves deeply “etched” into the skin, small volumes of low density fillers can help soften the appearance of horizontal or oblique grooves or furrows.


6.5.2 Forehead Techniques


Horizontal lines in the forehead are a result of contraction of the paired frontalis muscles. The frontalis originates from the galea aponeurotica at the level of the frontal hairline. Distally, the muscle attaches to the skin of the brows [2]. Evaluation of the cause of the horizontal furrows is important in treating the forehead region. Some patients have lines simply as a result of frontalis hyperactivity and excess facial animation. More commonly, horizontal lines are a result of chronic elevation of an anatomically low brow or pseudo ptosis or true ptosis of the upper eyelids. As the frontalis is the only true elevator of the brow, proper evaluation of the upper third of the face in repose and in animation is an absolute requirement before treating with neurotoxins. Failure to identify ptosis of the brow or upper eyelids can result in inability to raise the brows and yield an undesirable result.


The female brow should lie above the superior bony orbital rim, the male brow should be at or above the rim. The female brow should have a peak somewhere between the lateral limbus of the iris and the lateral canthus. The male brow tends to remain more horizontal along its length. Ideally the tail of the brow should sit above the position of the root of the brow. When treating the forehead, it is important to treat the entire frontalis muscle. Inadequate treatment of the lateral frontalis can lead to unopposed action of the lateral part of the muscle yielding an abnormally peaked lateral brow.


Although anatomically, there is frequently a gap in the midline between the left and right sided frontalis, treatment should include injections at or near the midline of the forehead to avoid a residual rhytid centrally in an otherwise smooth forehead If the frontalis is noted to extend up to the level of the hairline, it is important to have the injections extend superiorly to the uppermost extent of the muscle. Failure to do so may result in a deep furrow at or just below the hairline which is clearly visible particularly when the remaining forehead is rendered smooth with neurotoxin.


As with glabellar injections, one should not inject within 1 cm of the supraorbital rim [4]. Along the lateral brow, staying above this 1 cm margin can occasionally result in a residual crescent shaped furrow just above the brow that may be bothersome to some patients. Extreme caution should be exercised in further treatment to this area and the risk of lateral brow ptosis as compared with the benefit of further reduction in this furrow should be discussed with each individual patient. Generally, a small remaining lateral brow rhytid is desirable as compared with lateral brow ptosis and lateral canthal hooding.


In patients desiring elevation of the lateral brow, a central “V” shaped pattern of injection can be considered to maintain the position of the central and medial brow while allowing the lateral frontalis to elevate the lateral brow. This pattern of injection may take some trial and error in achieving the ideal amount of lateral lift [5]. Precise documentation of the locations injected and the doses used is imperative.


Although some patients may have a very dominant deep mid forehead furrow and would benefit from a single “row” of injections directly above or below the deep line, most patients have better results with at least two parallel rows of injection with more diffuse denervation of the muscle (Figure 6.5).

Image described by caption.

Figure 6.5 In order to avoid brow ptosis, injections are started 2–3 cm above the orbital rim. Treatment of the lateral frontalis 1,4,7,10 will decrease the chance of excessively elevated lateral brow. Eliminating injections 1 and 4 will create a lift of the lateral brow in patients who desire a temporal brow elevation. Injections 3, 6, 9, and 12 at or near the midline will reduce the chance of leaving a solitary midline rhytid. Injections 13–16 are optional but should be considered in patients who have rhytids at or near the hairline on animation.


As the frontalis is a very superficial muscle, small boluses of toxin should be injected subcutaneously. Here the tangential orientation of the needle is preferred to a more vertical injection technique. In general, 15–30 units of Onabotulinum toxin A are adequate for treatment of the forehead. Overtreatment or treatment too close to the brow complex may lead to brow ptosis and eyelid pseudo ptosis. The “heaviness” associated with overtreatment starts to improve three to four weeks after treatment as some frontalis muscle fibers begin to work. It is always best to “ease” into treatment when chemodenervating the frontalis, keeping in mind one can always add a few more units or treat another site for under correction but overcorrection cannot be improved until the toxin effect reverses.


6.5.3 Periorbital Techniques


Radial periorbital lines are a result of contracture of the orbital portion of the orbicularis oculi muscle. These should not be confused with more inferior periorbital rhytids associated with contraction of the deeper zygomaticus major muscle. The former can be effectively treated with chemodenervation; the latter cannot and attempts to do so may yield decreased lateral commissure elevation and potential distortion of the smile.


A clinical method of differentiating between lines resulting from orbicularis oculi contracture and zygomaticus contracture is to have the patient close the eyes tightly, to illustrate lines caused by the orbicularis, and to smile to show lines caused by zygomaticus contracture. It is helpful to have patients close one eye while looking in a mirror to show the periorbital lines that are effectively treated with neurotoxin. Having them smile will illustrate lines not amenable to treatment.


Injections should be very superficial as the orbicularis lies directly under the thin periorbital skin and superficial to the proximal zygomaticus major muscle. Too deep of an injection can impair zygomatic muscle function. Injections should be 1 cm lateral to the bony rim to avoid diffusion to the levator palpebrae superioris. The periorbital area is highly vascular. Oftentimes, with proper illumination, the superficial vessels are visible and care must be taken to avoid injury. Patients are always warned about the possibility of bruising which is slightly higher in this area than other sites on the face.


Two to four injection are placed starting at about the level of the lateral brow and ending along a vertical line drawn approximately 1 cm below the lateral canthus. Occasionally, an additional injection can be placed slightly medial to this plumb line with caution given to staying superficial and monitoring for any lid retrusion resulting from the medial placement of toxin (Figure 6.6).

Illustration of a human face with lines marking frontalis, orbital obicularis oculi, preseptal obicularis oculi, pretarsal obicularis oculi, levator labii superioris, zygomaticus minor, orbital rim, etc.

Figure 6.6 Injections should be superficial and at least 1 cm lateral to the lateral orbital rim. Injection 4 is optional. Note the proximity of this injection to the head of the zygomaticus major muscle which lies deep to the orbicularis.


Generally speaking, 6–20 units of Onabotulinum toxin A total are injected. As the orbital orbicularis is a lateral depressor of the brow, treatment of this muscle results in a slight elevation of the lateral brow. In patients desiring lateral brow elevation, this technique, combined with not treating the lateral frontalis, is quite effective. Combining this technique with treating the corrugator supercilii and procerus (depressors of the medial brow) can effectively result in an overall brow position elevation.


6.5.4 Treatment of Bunny Lines


Bunny lines are created across the nasal sidewall and dorsum as a function of contraction of the nasalis muscle and the procerus. The area is not commonly treated unless patients are bothered by the appearance or if the force of the contraction significantly depresses the medial brow. As with other anatomic injections of neurotoxins, the muscle should be localized by having the patient “sniff” or be asked to wrinkle their nose “like a rabbit.” The muscle is superficial just beneath the relatively thin nasal sidewall/dorsal skin. Generally, one to three injections of one to three units each are adequate to suppress excess nasalis activity (Figure 6.7).

Image described by caption.

Figure 6.7 Injection for “bunny line” contraction of transverse portion of the nasalis muscle, Injections 1, 2, 4, and 5 are generally adequate for correction. Injections 3 and 6 are optional and only used when the furrows are very deep. Treatment should include the inferior procerus.


Care must be taken to not inject the more laterally based levator labii superioris alaeque nasi muscles which are lip elevators. Diffusion into or direct injection into the levator labii may result in lip ptosis or asymmetric elevation of the lip on smiling.


6.5.5 Depressor Anguli Oris Techniques


The depressor anguli oris (DAO) is responsible for pulling down the lateral commissure of the lip. Treatment of the DAO with neurotoxin will serve to weaken this function and allow for relatively unopposed zygomaticus major muscle contraction resulting in elevation of the corners of the mouth.


Care must be taken not to inject the more medial depressor labii or mentalis muscles [2]. Doing so can create a distorted smile or asymmetry during speech. The patient is asked to frown or “show their lower teeth.” If the belly of the muscle is visible or palpable, a single injection of two to five units is made into the muscle. If the muscle is not apparent on animation, the injection can be made approximately 1 cm superior to the mandibular border just lateral to the point of attachment of the mandibular ligament. If any jowling is present, this point is usually just at the anterior border of the jowl. Anatomically, to avoid treatment of the more medial muscles, injections should be placed at least 1 cm lateral and 1 cm inferior to the oral commissure (Figure 6.8).

Illustration of the preferred injection site for the DAO muscle, 1 cm above the mandibular border, just lateral to a vertical line dropped from the lateral commissure.

Figure 6.8 Preferred injection site for the DAO muscle. 1 cm above the mandibular border, just lateral to a vertical line dropped from the lateral commissure.


6.5.6 Perioral Techniques


Radial wrinkles around the mouth related to puckering, drinking through a straw and, most commonly, smoking are amenable to treatment with very small doses of neurotoxin. Sphincteric contraction of the orbicularis oris muscle is responsible for the perioral lines. Injection of small aliquots of neurotoxin (one to two units per injection) in two to four positions along the upper and lower lip can be effective in “softening” the lines (Figure 6.9). Patients are always warned that even with these small doses, there may be some changes in articulation, the “posture” of the upper or lower lip and that drinking through a straw may be affected. Larger doses can result in significant smile asymmetry and upper or lower lip ptosis. Rather than risking asymmetry or issues with puckering during pursing the lips or drinking, a combination of very low dose neurotoxin treatment in combination with low density fillers or fillers alone may be safer alternatives.

Illustration of the injections sites for radial lines around the lips. Sites 1, 2, 4, and 3 are indicated above the upper lip and sites 5 and 6 below the lower lip.

Figure 6.9 Injection for radial lines around the lips. Lines are generally more apparent on the upper lip. Injections 5 and 6 are beneficial in patients with prominent lower lip lines as well.


6.5.7 Levator Labii Superioris alaeque Nasi

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Jul 24, 2020 | Posted by in Aesthetic plastic surgery | Comments Off on Pearls and Pitfalls of Neurotoxins and Facial Fillers

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