Advanced Techniques in Dermatologic Surgery - part 2

22 Carruthers and Carruthers somewhat less albumin in the DysportÕ vial compared to that contained in the BOTOXÕ vial; it has been suggested that this may account for part of the difference in effectiveness between the DysportÕ and BOTOXÕ units. In Europe, DysportÕ is labeled for transport at ambient temperature and storage at 2C to 8C, and the guidelines for reconstitution and use are similar to those of BOTOXÕ (15). Ipsen has an agreement with Inamed Inc., for marketing of DysportÕ in North America, and the two companies are currently working towards regulatory approval. MYOBLOCTM is available in a liquid formulation containing BTX-B 5000U/mL and is available in 0.5, 1.0, and 2.0mL vials containing BTX-B, saline, human serum albumin, and sodium succinate as a buffer to preserve acid pH. The pH is approximately 5.6, accounting for the stinging sensation reported on injection. Since this is a liquid formulation, reconstitution is notrequired;indeed,furtherdilutionisrathercomplicatedinthevialbecause of the ‘‘overfill’’ of the vials. The clinician with the intention to add saline to reduce the stinging (with benzyl alcohol) would be advised to do so in the syringe and mix the solution well. The unopened vial, like the BTX-A pro-ducts, is stable for months or years, but once opened, the lability is similar between the products (16). Immunogenicity Botulinum toxins are proteins capable of producing neutralizing anti-bodies and eliciting an immune response, causing patients to no longer respond to treatment (13). The rate of formation of neutralizing antibodies has not been well studied, and the crucial factors for neutralizing antibody formation have not been well characterized (1). However, the total protein concentration and number of units injected are critical in determining potential immunogenicity, andsomestudiessuggestthatBTX-A injections at more frequent intervals or at higher doses may lead to a greater inci-dence of antibody formation (1). The protein concentration in the current lots of BOTOXÕ is significantly lower than in previous lots, and has been shown to be less antigenic than the original product. Although one of the greatest concerns with the use of BTX-A is the formation of neutralizing antibodies, the overallrisk in using BTX-A at recommended doses for neu-rologic applications is low (less than 5%), and injecting the lowest effective doses, with the longest feasible intervals between injections, will minimize the potential for immunogenicity (1). Lack of effectiveness of BTX-A sec-ondarytothedevelopmentofimmunologicresistanceisexceedingly rarein cosmetic patients, and must be distinguished from a much more common degree of resistance, associated with the need for increased doses and prob-ably not due to immunologic mechanisms. TREATMENT OF THE UPPER FACE Treatment of the upper face has yielded the greatest clinical experience with cosmeticBTX-A.AlthoughthefirstpublishedreportsofBTXapplicationin Advanced Cosmetic Use of Botulinum Toxin Type A 23 thefaceappearedin1990,weknowthatanumberofcliniciansexperimented duringthelate1980s,impressedbyitseaseoftechniqueandobviousbenefits and safety (13). Glabellar Rhytides Muscles controlling the frown include the corrugator and orbicularis, which move the brow medially, and the procerus and depressor supercilii, which pull the brow inferiorly. Since the location, size, and use of the muscles vary greatly between individuals, individualizing treatment sites and doses to match each patient’s needs will optimize the clinical benefits. Althoughavarietyofdifferentinjectiontechniquesanddosesaredescribed in the literature (13), recent studies suggest that higher doses may be more effective. In a randomized, dose-ranging study of 80 women injected with 10 to 40U BTX-A, 30 and 40U produced significantly greater responses with the longest duration on glabellar lines than did 10 or 20U BTX-A, and peak responder rates and duration of benefit increased significantly withincreasingdoses (17).Athigherdoses,many patientsexperiencedclin-ical benefits lasting three to four months, but some continued to benefit for as long as six to eight months. In an objective analysis of the dose-ranging study, the authors measured changes in eyebrow and eyelid height and found an additional benefit of lateral- and mid-pupil elevation at 30 and 40U (Fig. 1) (18). Men injected with current recommended doses may not receive as great a benefit as women. In a study comparing the efficacy and safety of four doses of BTX-A in the treatment of glabellar lines, men were ran-domly assigned to receive a total of 20, 40, 60, or 80U in seven sites (19). Preliminary results show that men injected with 80U achieved a better response rate than those injected with lower doses, and experienced no change in the rate of adverse events, suggesting that male patients are considerably underdosed. Further investigation will determine optimal doses in men; however, we find it useful to halve the volume of saline used to reconstitute the vial when treating males. This technique reduces the injected volume while simply doubling the injected dose. Horizontal Rhytides BTX-A in the forehead lessens undesirable horizontal forehead lines for a period of four to six months (13). Again, treatment must be indivi-dualized for each patient and injection sites kept well above the brow to avoid ptosis or a complete lack of expressiveness. Patients with a nar-row brow (defined as less than 12cm between the temporal fusion lines at mid-brow level) should receive fewer injections (four sites, compared to five) and lower doses than patients with broader brows. We previously injected a total of 10 to 20U in four to five sites horizontally across the mid-brow, 2 to 3cm above the eyebrows (13), but—as seen in the glabella—more recent data suggest that higher doses may be more effec-tive. In a prospective, randomized, double-blind, parallel-group, dose-ranging study of 48 weeks, 60 women received 16, 32, or 48U BTX-A 24 Carruthers and Carruthers Figure 1 Individual before (above) and after (below) 30U of BOTOXÕ injected into the glabella area alone. The lower part of the figure is a computer overlay of the two photographs with before (in black) and after (in red). It can be seen that, although the BOTOXÕ was injected only medial to the pupil majority of the eyebrow elevation is lateral. Advanced Cosmetic Use of Botulinum Toxin Type A 25 in eight sites in the forehead: two in the procerus, four in the frontalis, and two in the lateral orbicularis oculi (half of the doses were injected into the depressors) (20). BTX-A dose of 48U led to the greatest improvement and duration of response, but adverse effects such as head-ache, eyelid swelling, and brow ptosis, were more frequent with the higher doses. Brow Lift Overactivity of the brow depressors leads to a lowered brow and scowling expression. Medial brow depressors include the corrugator supercilii, procerus, and the medial portion of the orbicularis oculi, while the lateral depressor is the lateral portion of the orbicularis oculi. Treating the gla-bellar lines often results in an elevation of the brow (13). Huilgol et al. (23) report treating the brow depressors alone to elevate the brow while preserving its natural shape (21). One injection of 7 to 10U BTX-A in the glabella at the midline (immediately below the line joining the eyebrows), followed by one injection on each side into the supralateral eyebrow (where the orbicularis curves infralaterally, outside the bony orbital rim) resulted in a modest brow elevation (mean, 1mm) in five out of seven patients. Ahn et al. (22) injected 7 to 10U into the supralateral orbicularis oculi at three sites below the lateral third of the brow (but superior and lateral to the orbital rim) and produced average midpupil-lary elevations of 1mm and lateral brow elevations of 4.8mm. Huang et al. (23) injected 10U in four sites along the underside of the lateral half of the brow and 5U into each corrugator muscle just above and medial to the brow. Brow height at rest increased by 1.9mm (on the right side) and 3.1mm (on the left), and the mean increase in brow height on elevation was 2.1mm on the right side and 2.9mm on the left. In a complete analysis of the brow height data from their female glabella dose-ranging study the authors have further explored the benefits and relationship between glabella injection and brow height (24). In this study, injecting a total of 10U BTX-A into the glabella area produced mild medial brow ptosis, which disappeared after two months. However, injecting a total dose of 20 to 40U initially produced a significant lateral eyebrow elevation, followed by central and medial eyebrow elevation. This effect peaked at 12 weeks after injection and remained at a signifi-cant level at 16 weeks. To our knowledge, this is the first time that an effect of BTX-A caused by injection into skeletal muscle has peaked at 12 weeks rather than the usual four weeks. Since the primary effect is at the lateral side—an area that has not been injected—we presume that this brow lift is due to partial inactivation of the frontalis and not due to the action on the brow depressors, as previously thought. The subsequent central and medial eyebrow elevation could be due to the resetting of the ‘‘tone’’ in the frontalis, causing a gradual lift. Although further inves-tigation is necessary to fully understand the complex, functional interre-lationships and, therefore, the control mechanisms involved, we believe that the above data constitute a major advance in our understanding. 26 Carruthers and Carruthers Eyebrow Asymmetry and Shaping Eyebrow asymmetry can be caused by a number of scenarios, including facial nerve trauma following surgical brow lifts, other surgically induced facial paralysis, and habit in those with ipsilateral blepharoptosis and asymmetric nonpathologic facial expression (25). Injection of BTX-A into the frontalis (or overlying) muscle approximately 1cm above the eyebrow can be an alternative to surgery in patients who desire a more symmetrical appearance. Injection of BTX-A for glabellar frown lines can cause a mild medial brow ptosis and induce a lateral brow elevation, which gives a more pleas-ing contour to the eyebrow. Since the lateral, orbital aspect of the orbicu-laris oculi muscle above the lateral retinaculum serves as an antagonist muscle to the lateral frontalis muscle, adept clinicians can procure the effects of mild brow elevation, creativelyimproving the shape and position of the eyebrows (25). CHEMODENERVATION IN THE MID AND LOWER FACE AND NECK The cosmetic injection of BTX-A in the mid- and lower face and neck has opened up a new avenue of artistry in facial contouring and sculpting. However, previous experience in the indications for its use in the upper face, complete understanding of the resting, dynamic muscular anatomy of the face, and location of the neurovascular bundles are mandatory prior to injection. Incorrect injection can result in catastrophic impairment of function and expression, and the use of electromyographic (EMG) guidance in some patients is recommended (26). Mid-Face Crow’s Feet Lateral canthal rhytides are accentuated by contraction of the orbicularis oculi, whose fibers run vertically under the skin at the lateral angles of the eyelids. BTX-A injected subdermally or intradermally relaxes the action of the muscle without completely inactivating the orbicularis oculi, which could interfere with the ability to fully close the eye. Total doses used range from 4 to 5U per eye to 5 to 15U per eye over two or three injec-tion sites. We use 12 to 15U per side, distributed in equal parts over two to four injection sites, and recommend using as few and as superficial injections as possible to minimize bruising (26). Results generally last for three to six months, with few adverse effects noted. Hypertrophic Orbicularis Widening the palpebral aperture is part of the new ‘‘artistry’’ of BTX-A in facial contouring and sculpting. In some patients, the act of smiling transi-ently diminishes the perceived size of the palpebral aperture, especially in ... - tailieumienphi.vn