The logical approach to facial rejuvenation is facilitated when one first (through an assessment and diagnosis of the nature of the pathology) differentiates quantitative from qualitative changes in facial soft tissue. Quantitative and malpositional changes have traditionally required a surgical approach: the excision or repositioning of soft tissue (skin, muscle, and fat). Conversely, qualitative changes may require the fortification of the soft tissue by mechanical, chemo- or laserexfoliation, or augmentation of a particular soft-tissue plane. Most recently, a focus has been directed to prevention with sun protection, skin care, and improved nutrition as well as the realization of other causative risk factors that include hyperfunctional and dynamic components of facial lines.
Hyperdynamic (hyperkinetic, hyperfunctional) or long-term facial muscular animation seems to contribute to the etiology of many undesired facial rhytids and furrows. The presumption that facial lines were the result of, in part, forces generated by local muscular actions was first observed post-mortem on a microanatomic basis by Pierard and Lapiere. 1 Focal denervation of particular facial muscles has been shown to improve overall facial appearance not only by temporarily eliminating rhytids but also by improving malpositional changes of the overlying soft tissue and possibly the results of particular facial aesthetic surgical procedures discussed herein.
The interest in chemodenervation and specifically the use of botulinum toxin as a therapeutic agent for weakening particular skeletal muscles dates back to the 1920s. Almost 30 years later, pediatric ophthalmologist Dr. Alan Scott collaborated with Dr. Edward J. Schantz 2 in the preparation of a batch of crystalline toxin to determine its effectiveness as an injectable agent for producing transient weakness of extraocular muscles and permanent changes in ocular alignment. 3 This had remained the source of botulinum toxin type A until 1997 as the commercially available product, Botox (Allergan, Inc., Irvine, Calif.). After many years and experiences with this product, supplies were finally exhausted, and Botox was reformulated to what is currently used worldwide.
The toxins of Clostridium botulinum are classified into eight immunologically distinguishable exotoxins. 4 The type A toxin is most easily produced in culture and was the first one obtained in a highly purified, stable, and crystalline form. The principal effect of muscle paralysis is caused by the inhibition of the release of acetylcholine at the neuromuscular junction. The paralytic effect of the toxin is dose related, with the peak of the effect occurring 5 to 7 days after injection. 5 Denervated muscle histopathology shows muscle atrophy and a mild degree of demyelinative changes at the nerve terminal. 4 Axonal nerve sprouting seems to be a usual response to chemodenervation 6 and may diminish true clinical muscular atrophy (hence long-term beneficial effects in some regions). Single-fiber electromyography studies indicate abnormal neuromuscular transmission in muscles distant from the site of injection despite the absence of clinical weakness, indicating the potential for spread of the toxin that could be significant at higher doses. 5 These observations and effects supported by some good experimental data provide a rationale for treatment protocol for the use of Botox in a variety of disorders.
Botox is presently approved for the treatment of strabismus and blepharospasm associated with dystonia (including benign essential blepharospasm or VII cranial nerve disorders) in patients 12 years of age and above. 7 Although not (FDA) approved for its use, many have experience with a multitude of other clinical applications of botulinum toxin, including the treatment of bruxism, stuttering, painful rigidity, lumbosacral pain and back spasms, radiculopathy with secondary muscle spasm, spastic bladder, achalasis, tremor, involuntary tics, 8 tension headaches, neuromuscular paralysis, lower eyelid spastic entropion, aberrant regeneration of the facial nerve (after Bell’s palsy etc.), acquired nystagmus, corneal pathology/amblyopia therapy aided by the effects of occlusion, 4 and in periorbital reconstructive surgery. 9
Many experienced clinicians had noted the improvement of facial rhytids in their patients who had received Botox for a variety of facial spastic disorders (Fig. 1). This discovery, in conjunction with a prelude to a better understanding of the anatomic basis of several facial frown lines, forced the question of the possible benefit of chemodenervation for certain facial wrinkles.
The treatment of glabellar frown lines (Fig. 2) enjoyed early attention owing to the experience of those who treated patients with benign essential blepharospasm, which typically involved injection of toxin into the medial eyebrows (corrugators). Other targeted facial hyperkinetic lines that gained early popularity included the treatment of lateral canthal rhytids (crow’s feet) and horizontal forehead furrows. More recently, the applications have extended to congenital and traumatic 10 facial asymmetry, postsurgical eyebrow asymmetry (including dyskinesis) and facial paralysis, orbicularis hypertrophy (of the lower eyelids), perioral rhytids, hyperfunctional midfacial animation lines, soft-tissue malposition, and as an adjunct to endoscopic forehead lifts, laser skin resurfacing and injectable agents for soft-tissue augmentation. 11–13
Facial Wrinkle Anatomy and Physiology
Understanding the anatomic relationships and functional features of a variety of facial muscles to the surrounding soft tissue provides the additional necessary groundwork for the treatment rationale of chemodenervation for a variety of aesthetic displeasures 11,12,14 (Fig. 3).
The palpebral component of the orbicularis oculi surrounds the pretarsal and proximal septal aspects and is essentially the “sphincter” muscle of the eyelids responsible for blinking and gentle eyelid closure. Its direct antagonist is the levator palpebrae muscle. Forceful contraction of the orbital component of the orbicularis oculi induces concentric folds emanating from the lateral canthus. Some of the fibers of the superomedial orbital component function as depressors of the medial eyebrow. These fibers constitute the depressor supercilii. 13 The superolateral orbital orbicularis oculi acts, in part, as a depressor of the lateral eyebrow. The corrugator supercilii serves to draw the eyebrow inferiorly and medially, and as such produces the vertical glabellar frown lines. The procerus muscle, in part, draws the medial (head of the) eyebrows inferiorly and produces the transverse wrinkles over the bridge of the nose. The main antagonist of all of the eyebrow depressors is the frontalis muscle. The zygomaticus major muscle draws the angle of the mouth superiorly, laterally, and posteriorly with actions of laughing, smiling, and chewing. The zygomaticus minor muscle functions as one of the lip elevators and with the zygomaticus major contributes to the nasolabial fold. Forceful contraction of the zygomaticus muscles in animation (smiling) produces synergistic effects in the periorbital region, accentuated by the contraction of the orbital orbicularis and enhancing the radially oriented folds at the lateral canthus, exaggeration of the skin tension lines of the midface, and recruitment of lower eyelid soft-tissue redundancy (by elevating the cheek) that is not evident in the nonanimated state. The orbicularis oris is responsible for forceful lip closure and serves as a sphincter to the mouth. Contraction of this muscle induces folds that radiate from the vermilion border. This muscle in part is an antagonist to the lip elevators. An understanding of the basic anatomy of facial expression is essential not only for the appropriate approach to the treatment of hyperkinetic facial lines and furrows but also a methodology to avoid complications discussed later.
Preparation and Dilution
Botulinum toxin A is a labile but highly potent toxin. Each vial (supplied by Allergan) contains approximately 100 units of toxin in a crystalline complex. The toxin should be stored immediately upon receipt in the office freezer at −5°C or lower in this crystalline form. Toxin reconstitution should be performed just before actual injection for maximal potency. Dilution should be followed carefully with the diluent of nonpreserved saline as instructed for specific concentrations as described in the package insert 7; however, most clinical uses of Botox are well suited for a dilution of 2.5 units per 0.1 ml, which is easily obtained by mixing 4.0 ml of nonpreserved saline to the vial. The use of preserved saline has been suggested by some authors 14 for hope of extending the shelf life and potency once reconstituted; however, there has been concern regarding the effect of the preservative, turbulence with dilution, and agitation in denaturing (hence reduced effect) of the delicate toxin.
Once reconstituted, the toxin should be used as quickly as feasible. The package insert suggests that the product be used within 4 hours 7; however, many users have noted reasonable effects with the use of the product for up to 30 days. 14 In my experience, a notable decline in clinical potency occurs after 48 hours of reconstitution that may affect depth of focal paralysis and longevity of effect. Further, the relative stability of the reconstituted toxin is felt to be best maintained by refrigeration (not freezing), and it is suggested that the product be kept cool at every opportunity. To the best of my knowledge, however, there have been no studies to substantiate or refute claims of the duration of potency of the toxin after reconstitution.
Early investigators had suggested up to 10 to 20 units or more per site to affect the targeted muscles of facial expression. 15 However, one can achieve effects with far less toxin (2.5 units per site) and maintain longevity of effect for comparable periods of time. In my experience, this dose is effective for an average of 4 to 6 months. These lower doses in smaller volumes also serve to reduce unwanted effects and complications (see below). Concentrations much less that 2.5 units per 0.1 ml can induce a weakening effect on the targeted muscle but seem to do so for a much shorter duration. Additionally, men (or even women with clinically evident large hypertrophic target muscles—particularly corrugators or frontalis muscles) seem to require a slightly higher dose per injection site (up to 5.0 units per site), otherwise resulting in only mild to moderate improvement of hyperfunctional rhytids with shorter duration of effects. Diluted toxin should be drawn up into 1.0 ml (T.B. syringes) through an 18-gauge needle to minimize physical trauma to the toxin.
Technique of Injection: Glabella, Lateral Canthus, and Forehead
As in all procedures, patients desire maximum benefit with minimal side effects and morbidity. It may therefore be advisable that patients temporarily discontinue aspirin and other drugs that can affect bleeding time before Botox injection, similar to how you might instruct your patients before surgery. This, however, is not mandatory but may reduce or eliminate facial bruising that can last for several weeks. If minimal to no bruising occurs after injection of Botox, patients can typically return to work unnoticed less than 1 hour after treatment.
After the toxin is drawn up by 18-gauge needles into 1.0-ml syringes, the needle is then replaced by a short, 30-gauge needle for injection. The use of local anesthesia is relatively contraindicated and unnecessary. Alcohol may be applied to the injection sites but should be allowed to dry fully before injection of toxin owing to toxin lability. I currently do not employ the use of electromyographic guidance, as I find this cumbersome and unnecessary. Electromyographic guidance may, however, be useful when getting started with chemodenervation for general orientation. Some of the literature on the cosmetic applications of botulinum toxin A describes and illustrates sites for injection with reference points targeted at the actual wrinkle line rather than the causative muscle. 15 Skin demarcations and sites of eventual injections of toxin can be made over the presumed belly or muscle mass of the regional muscle of facial expression and not typically at the site of the maximal dermal depression, which at times may be quite distant from the mass of the effecting muscle. For the larger, deeper muscles such as the corrugator supercilii, it is most useful and efficacious to inject toxin deep to the overlying muscles (frontalis and orbicularis) or directly into the belly of the targeted muscle. Typically, four or five injection sites (Fig. 4) at a dose of 2.5 to 5.0 units per site are satisfactory in eliminating focal muscle tone and voluntary contraction of the corrugators (Fig. 2). More superficial application may affect the more superficial muscles, predominantly, without achieving the desired effect. This is most easily facilitated by familiarization with the pertinent facial soft-tissue anatomy and observing the dermal and muscular effects of the frown line on command. I have found it helpful to isolate the area by placing the thumb of the nondominant hand beneath the eyebrow and superior orbital rim (Fig. 5). This serves to steady the patient’s head and target region, orient the injector to the supraorbital notch and neurovascular bundle, and avoid inadvertent injection into the orbit. The needle is inserted to the presumed level of the muscle mass of the corrugators followed by injection of the toxin. The thinner, orbicularis muscle (and even the procerus muscle) responds favorably to a more superficial, subcutaneous injection of Botox (Fig. 6).
Unlike the other larger muscles of facial expression that may require direct contact of the toxin to the majority of the muscle mass, hence requiring injection more directly into the muscle, the relatively thin orbicularis muscle (and isolated procerus) seems to be satisfactorily affected by injecting the toxin into the subcutaneous space overlying the muscle. This not only reduces the chance of significant ecchymoses but may therefore maintain the potency that could be reduced by bleeding. Additionally, injection into the subcutaneous space may allow for more local (even) diffusion over the targeted muscle and provide an additional safety barrier to structures deep to the muscle. For lateral canthal rhytids (crow’s feet), three or four injections are given with particular avoidance of the pretarsal orbicularis of the upper and lower eyelid (Fig. 7). This is achieved by directing needle insertion temporal to the lateral canthus near the lateral orbital rim (Fig. 4) and distant to the eyelid margin (Fig. 6). The procerus muscle can be injected at one or two sites just beneath the (skin) transverse wrinkle at the nasal bridge. This superficial plane also avoids orbital injection. Hyperkinetic horizontal forehead furrows 11,12,14,16 seem to respond favorably to either subcutaneous or intramuscular injection of the toxin, presumably since the frontalis is the only active muscle in this region. Weakening, rather than complete frontalis denervation, may also be preferable in some individuals to avoid brow ptosis. These injections are most effective by administering a uniform grid, 16 whereby approximately nine or more sites are injected across the forehead (Fig. 8). Three or more sites over each side are positioned in a vertical line above the mid-eyebrow. Additional sites are positioned vertically in the mid-forehead region. This affords focal frontalis muscle weakening at the medial aspects of each muscle group. A more homogeneous treatment of the forehead avoids focal areas of residual function that can become quite noticeable in lieu of complete absence of adjacent furrows. Typically, 2.5 units (0.1 ml) are administered at each site. Injections over the lateral eyebrow are minimized or avoided to reduce the potential for lateral eyebrow ptosis. Contrary to much of the reported concern regarding staying upright or avoiding physical activity for several hours after the injections, 16 I have not found it necessary to instruct patients on this. Cosmetics may be applied immediately after injection.
Although, theoretically, the effect of the toxin is described as occurring between 3 and 7 days after injection, I have noted consistently an earlier onset of effect compared with those patients who experience Botox for the treatment of eyelid and facial spastic disorders such as benign essential blepharospasm and hemifacial spasm. Occasionally, a patient-recipient of Botox for hyperkinetic facial lines experiences the effects within several hours for reasons not well understood. Although the immediate treatment benefits reflect the toxins’ ability to temporarily weaken or paralyze those muscles responsible for the muscular component of the hyperkinetic facial lines, the theoretic suggestion (not yet proven) is that repeated injections into the same muscles over time could produce a sort of disuse atrophy 17 that would limit the development of certain facial lines in younger individuals and possibly eliminate or reduce (over time) established facial lines and furrows.
However, because of the entity of axonal sprouting 6 (discussed earlier) and the fact that patients typically return for additional treatment after the muscles have regained near complete clinical function (i.e., the wrinkle has returned), true long-term muscular atrophy may not be the only possible cause for long-term improvement in some individuals that may also reflect (in part) alteration in facial animation patterns and remodeling of the overlying soft tissue.
Extended Uses of Botox in Facial Aesthetic Surgery
Facial Nerve Disorders
Botulinum toxin A also has been shown to be useful for a variety of other facial cosmetic problems. I have found it useful in even subtle cases of aberrant regeneration of the facial (seventh cranial) nerve (for instance after recovery of a Bell’s palsy), which although it may not induce a significant visual impairment, poses significant embarrassment to some 12,18 (Fig. 9). At times, very low doses are quite effective such as 1.0 unit or less per site administered over the pretarsal orbicularis in the same manner given for the treatment of (benign essential) blepharospasm. 4 Botox can also be used to achieve symmetry in congenital and acquired unilateral facial paralysis by weakening the contralateral side.
Aesthetic Precision in Modification of Facial Animation
Eyebrow asymmetry can be seen in a variety of scenarios including facial nerve trauma after brow lifts, other surgically induced facial paralysis, habit in those with long-standing (even post-corrected) ipsilateral blepharoptosis, asymmetric nonpathologic facial expression, etc. As an alternative to brow lifting the more ptotic eyebrow, one could consider eyebrow (focal frontalis muscle) chemodenervation to enhance symmetry for those who are unwilling to undergo surgery but who desire a more symmetric appearance (Fig. 10). The sites and number of injections depend on where the effect is desired and usually are administered into (or overlying) frontalis muscle approximately 1.0 cm above the eyebrow to avoid the brow depressors.
One can induce creative changes in the eyebrow shape and position. For instance, it is well known that with injection of Botox for glabellar frown lines into the medial eyebrow, the adjacent medial frontalis muscle can at times be affected (by a higher injection that weakens the frontalis muscle focally), inducing a mild relative medial brow ptosis and at times effecting a more pleasing contour to the eyebrow (especially in flat brows). Brow contour can be even more accentuated by effecting a mild lateral brow elevation by injecting the lateral (sub-brow) orbital component of the orbicularis muscle, enhancing the effect of the antagonist lateral frontalis muscle (Fig. 11). This method can be employed when injecting for crow’s feet with extension of the lateral canthal area injections (2.5 units/0.1 ml) into the lateral sub-brow region (Fig. 4).
Orbicularis (oculi) muscle hypertrophy of the lower eyelids may also be effectively treated using very low concentrations (1.0 unit/0.05 ml) of toxin into or overlying the visibly hypertrophic (thickened) muscle. Low doses may still cause a mild but often acceptable degree of lower eyelid retraction. Two or three injections are administered at the central lower eyelid and lateral canthus overlying the affected areas. Higher concentrations, however, may induce significant paralytic eyelid retraction or ectropion and may also impair the nasolacrimal pumping action of the orbicularis muscle, inducing epiphora.
Similar caution and consideration can be applied to tone down the effects of the zygomaticus major and minor muscles. The zygomaticus major muscle not only affects the elevation of the corner of the mouth with smiling but in doing this recruits the enhancement of crow’s feet, which can be quite exaggerated in some individuals. The zygomaticus minor muscle originates similarly to the zygomaticus major muscle and inserts more medially into the upper lip. Both of these muscles, in part, when active, deepen the nasolabial fold. By using low dosages (2.5 units/0.2 ml) in the proximal aspects (far from the mouth) near the areas of origin, with efforts made to inject toxin mostly at the level of the edge of the inferior aspect of the orbicularis of the lower eyelid (Fig. 4), one can soften their additive effect on the lateral canthal rhytids and nasolabial folds (Fig. 12). One or two injections administered over the mid to lateral malar eminence are usually satisfactory in obtaining the desired effect without incurring complications, particularly paralysis of the ipsilateral upper lip.
Finally, Botox has been shown to be useful as a primary treatment in reducing fine perioral rhytids (lip stick lines). 11,12,19 Approximately 1.0 to 1.5 units of toxin is injected adjacent to the fine vertical rhytids overlying the orbicularis oris muscle close to the vermilion ridge. An added noted aesthetic effect at times with this treatment is the appearance of fuller (pseudo-augmented) lips because the sphincter muscle is weakened along the vermilion border to assume a more everted position (Fig. 13).
Enhanced Surgical Results with Chemodenervation
Those experienced with CO2 laser abrasion have noted the first recurrent rhytids in the lower eyelid and lateral canthus. At times, in patients where there is significant hyperdynamics especially at the lateral canthus and perioral region, the rhytids can actually appear worse after laser skin resurfacing by any method (Fig. 14). Pretreatment with Botox may improve the smoothing effect of the new remodeled/resurfaced skin long enough to effect more permanent eradication of wrinkles 11,12 (Fig. 15).
Similarly, this approach may be beneficial in pretreatment for those individuals who will undergo brow lifting procedures by enhancing results from weakening the inferior vector force (lateral orbital orbicularis oculi muscle, the antagonist to the frontalis muscle and eyebrow elevation), which would promote and provide maintenance of the elevated eyebrow position (Fig. 16).
Reinforcement during lateral canthal suspension procedures such as the lateral tarsal strip 20 or the lateral retinacular suspension 21 can be aided by injecting Botox (2.5 units/0.1 ml) around the lateral canthus as in the method described for the treatment of lateral canthal rhytids that not only diminished the regional rhytids but also reduced local orbicularis oculi function that, in part, may compromise the position and security of the lateral canthus with repeated muscular contraction (Fig. 16).
Another very useful application of Botox has been in patients with soft-tissue contour abnormalities or atrophy that benefit from the coincident use of both modalities. Preceding the injection or surgical placement of the soft-tissue augmentation material by approximately 1 week, Botox is administered for focal weakness or paralysis. Injection of the dermal filler, subdermal fat, or surgical implantation (of alloplastic or allogeneic material) is then given into the paralyzed or muscularly weakened area (Fig. 17). The denervation serves at least three purposes. First, it eliminates or reduces the dynamic/muscular component of rhytid formation. Second, there is some theoretic suggestion that it may increase the longevity of the dermal implant by reducing the supposed mechanical inflammatory influence on atrophy of the implant. Third, it may also simply reduce the immediate microextrusion at the injection sites by repetitive muscular action, etc. This can be seen by weakening the medial brow depressors before administering collagen or fat to the glabella or injecting Botox to the lip elevators and depressors before soft-tissue augmentation of the nasolabial folds and in lip augmentation, respectively. Dosages to the glabella are similar to those used in the primary treatment to any particular region. Lower dosages (1.25 units/0.1 ml) may be applied to the lips before augmentation. The combination of chemodenervation and soft-tissue augmentation (particularly autologous collagen) in these areas has been shown to be highly synergistic. 11,12,22
Not uncommonly, patients after receiving Botox (not necessarily particular to one facial region but more prevalent in those injected in or around the eyebrows and forehead) note a generalized (almost euphoric) feeling of improved sense of well being. I have assumed that this could be related to the relief of muscular contraction (tension) etc., similar to that in the classic muscular contraction or tension headaches. This finding has been consistent and possibly suggests even more expanded uses for the toxin. Most effects for the various cosmetic applications of Botox last (as in the functional/spastic disorders) between 4 and 6 months. Patients must be counseled and aware of the typical (transient) effects of chemodenervation on their hyperfunctional lines and the likely need for maintenance treatment.
Reported adverse reactions with the general use of Botox for all approved applications include blepharoptosis, diplopia, globe perforations, retrobulbar hemorrhage, Adies pupil, worsening of dry eye symptoms, lagophthalmos, photophobia, epiphora, ectropion, and exposure keratitis. 7 Complications that have arisen with the cosmetic applications of Botox have included most of the above-noted reactions and additional unwanted temporary effects including ecchymoses, eyebrow ptosis and asymmetry, and mouth drop. Unwanted side effects, such as blepharoptosis and mild lower eyelid retraction (Fig. 10), typically last only a few weeks at most as the dose of migrated toxin to the affected muscle is usually significantly reduced. The temporary use of over the counter ocular decongestants (eyedrops) that contain adrenergic agents (with coincidental side effects of the eyedrops that include temporary contraction of Muller’s muscle and an elevated upper eyelid margin position) for allergy/congestion (Naphcon A, Vasocon A, Opcon A) may prove beneficial to those patients who are significantly symptomatic from the transient blepharoptosis.
The use of Botox for the treatment of hyperkinetic facial lines and furrows is merely another effective primary or adjunctive therapy to offer your cosmetic patients in the spectrum of treatment options for full facial rejuvenation. Unwanted side effects can be minimized and beneficial effects maximized with a thorough understanding of the facial soft-tissue anatomy, proper patient selection, and administration of the lowest effective dosages with minimal volume of delivery. It most often does not replace surgery, skin resurfacing, soft-tissue augmentation, or skin care. However, it has been shown to be quite useful when used alone or in conjunction with the variety of treatment options to give your selected patients the most effective and comprehensive solutions for a more youthful appearance.
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22. Fagien, S. Facial Soft Tissue Augmentation with Autologous and Homologous Injectable Collagen (Autologen and Dermalogen). In A. Klein (Ed.), Tissue Augmentation in Clinical Practice: Procedures and Techniques. New York: Marcel Dekker, Inc. Pp. 87–124, 1998.