Journal of Cosmetic and Laser Therapy, 2015; 17: 49–54
REVIEWS OF TREATMENT STUDIES
Are combined same-day treatments the future for photorejuvenation?
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
Review of the literature on combined treatments with lasers, intense pulsed light, radiofrequency, botulinum toxin, and fillers for rejuvenation
ESTHER CUERDA-GALINDO, MARÍA ANGUSTIAS PALOMAR-GALLEGO & RAFAEL LINARES-GARCÍAVALDECASAS Department of Human Anatomy and Embriology, Universidad Rey Juan Carlos, Madrid, Spain Abstract Background: Skin rejuvenation requires a treatment combination including lasers, intense pulsed light (IPL), radiofrequency, botulinum toxin (BT) and fillers. A combined approach is considered optimum but usually same-day combined treatments are avoid and lasers are performed prior to filler or toxin injections owing to the concern that the light may inactivate or degrade them. Objective: To review the literature on the use of combination treatments with radiofrequency, IPL, non ablative and ablative lasers plus fillers or BT. Results: review of the literature identified 15 studies of combination treatments: three of them on animal models and 12 were clinical studies. Seven studies contained combined light system treatments with fillers and eight studies combined physical therapies with botulinum toxin injection. In all of them treatments were used as standard protocols. Six studies documented no histological changes in fillers injected after applying radiofrequency, IPL or laser treatments and one studied documented improvement in collagen after IPL treatment and toxin injection. These studies reported clinical improvement in various features of photodamaged skin, no increase of adverse effects and neither decrease on efficacy of substances injected. Conclusions: review of the literature demonstrates safety of same day combined treatments for rejuvenation, which improve clinical results, are more comfortable for patients have no loss of efficacy or other apparent adverse effect. Key Words: botulinum toxin, combined treatments, fillers, intense pulsed light, laser, radiofrequency
Introduction In recent years, an increasing number of treatments have been developed (1) including botulinum toxin (BT), fillers, and laser or intense pulsed light (IPL) devices to improve the appearance of aging skin. There is a growing demand for noninvasive procedures with both minimal downtime and adverse effects (2). Patients demand for cosmetic improvement of skin texture, pigmentation, and rhytides. A combined treatment is necessary for many patients because it targets various regions of the face and the treatments supplement each other (3). Combined treatments with lasers and injected substances are frequently used. Laser therapy is often administered some days after filler implantation or toxin injection, but the apprehension regarding
concomitant treatment with fillers–BT and laser–IPL– radiofrequency (RF) is not supported by documented research. It has been proposed that light could interact with tissue, filler, or toxin, producing some changes in clinical results or lasting effects. When combining treatments, it is necessary to be sure that this combination improves clinical results without adverse effects. In this article, we examine the existing literatures which evaluate combined treatments with lasers or light systems and fillers or BT.
Treatments combining laser, IPL, and fillers Some authors have researched on the effects of lasers and IPL in animal models when filler is injected.
Correspondence: Dr. Esther Cuerda-Galindo, Department of Human Anatomy and Embriology, Universidad Rey Juan Carlos, Avda Atenas sn 28922 Alcorcón, Madrid, Spain. Tel: ⫹ 0034 914889027. Fax: ⫹ 0034 914888831. E-mail: [email protected] (Received 17 March 2014 ; accepted 10 September 2014 ) ISSN 1476-4172 print/ISSN 1476-4180 online © 2015 Informa UK, Ltd. DOI: 10.3109/14764172.2014.968578
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
50
E. Cuerda-Galindo et al.
England et al. (4). used a monopolar RF treatment over soft-tissue fillers in a juvenile pig model over a period of 4 months. They used a ThermaCool TC system (Thermage, Inc., Hayward CA). Fillers used were Cosmoplast (a highly purified collagen derived from human fibroblast), Restylane (hyaluronic acid), Sculptra (polylactic acid), Radiesse (with spherum of calcium hydroxylapatite), and Silikom (liquid injectable silicone). Fillers were injected immediately preceding or 1 month preceding RF treatment. The authors found no apparent increase in the risk of local burns and no effects of RF treatment on fillers persistence in the tissue. The same research group (5) studied the effects of a monopolar system, ThermaCool TC system, combined with the same fillers: Cosmoplast, Restylane, Sculptra, Radiesse, and Silikom. In this study, histological biopsies were performed at 5 days, 2 weeks, or 1 month after RF treatment and it was concluded that no thermal effect of RF was observed histologically and that RF treatment increased the inflammatory, foreign body, and fibrotic responses associated with fillers. Farkas et al. (6) examined the effect of laser and IPL systems on hyaluronic acid fillers in porcine models. They used three different hyaluronic acids (Restylane, Perlane, and Juvéderm) and light systems used for examination were Sciton IPL with a 560-nm filter (Sciton, Aplo Alto, CA), Sciton Nd:YAG 1064 (Sciton), Profractional (Sciton), Lux1540 Er:Glass, Palomar erbium 2940 (Palomar Medical Technologies, Burlington, MA), and the ActiveFX and DeepFX (Lumenis,Yokneum, Israel). Following laser treatment, punch biopsies were collected. Authors reported that fillers were unaffected by the nonablative laser or light and superficial ablative treatments. The aggressive deeper treatments demonstrated laser–filler interaction with evidence of migration of filler into the ablated microchannels, and microablation columns were in direct contact with filler. When an aggressive deep resurfacing is planned, they recommend treating patients first with laser, before the soft tissue injections, to maximize the treatment effect of each modality. Some authors have reported (7) that exposure of liquid silicone injected in cultured human skin to CO2 laser produces flaring of silicone. They demonstrated histologically that silicone fluid contaminates the full soft tissue through which the needle passes and if tissue is exposed to CO2 laser, injected silicones and contaminated tissue can flare. Alam et al. (8) treated five patients with injections of Restylane (hyaluronic acid derivative) and Radiesse (calcium hydroxyapatite), and applied monopolar RF 2 weeks after using ThermaCool TC system. Skin biopsies were obtained; they concluded that applying RF after deep dermal injection with hyaluronic acid or calcium hydroxyapatite does not appear to cause changes in the filler material.
Some authors (9) performed a randomized trial in 36 patients to determine the influence of laser therapy, monopolar RF, and IPL treatment after hyaluronic gel implantation (Restylane) in nasolabial folds. They treated one-half of the face with only hyaluronic acid and the other side with hyaluronic acid injection and laser light treatment. The devices used were 1320-nm Nd:YAG (CoolTouch, New Star Lasers, Rosemont, CA), 1450-nm diode (Smoothbeam, Candela Laser, Wayland, MA), monopolar RF (ThermaCool TC system, Thermage, Inc., San José, CA), and IPL with 560-nm cutoff filter (Lumenis One, Lumenis, Santa Clara, CA). Skin biopsies were performed at postoperative days 0, 14, and 28 in every patient and histological changes were not apparent. There were no statistically significant differences in wrinkle severity score in those areas treated with hyaluronic acid alone and those treated with concomitant hyaluronic acid, laser, RF, or IPL. The authors concluded that laser, RF, and IPL treatments can be administered immediately after hyaluronic acid injection without reduction in clinical effect. Ribé et al. (10) studied histological and clinical changes after combined therapy with a fractional nonablative laser (Affirm, Cynosure, Inc., Westford, MA, USA) and hyaluronic acid (Restylane Vital Light) for neck skin rejuvenation in 9 patients. Treatment consisted of hyaluronic acid administration immediately followed by laser treatment and they conclude that laser produces epidermal and superficial dermal changes, whereas the injected hyaluronic acid acts deeper. Park et al. (11) performed a split-face randomized study of 12 patients treated with hyaluronic acid on nasolabial folds and with a nonablative infrared device on the experimental side of the face. They used Teosyal (Teoxane) and two sessions of infrared, one of them immediately after filler injection. They did not find collagen fiber increase on histologic assessment immediately after infrared treatment and affirmed that both treatments may be applied safely, but they did not find more improvement when both treatments were used instead of hyaluronic acid injection alone. Recently, a study of 90 patients treated with IPL (560- or 590-nm cutoff filters, Lumenis 1 or Lumenis M22, Lumenis Ltd, Yokneam, Israel) immediately before or 6 days after polylactic acid injection (Sculptra) has been reported (12). Patients received an average of 1.63 (range, 1–5) combined treatments. The authors did not find adverse effects or formation of nodules, and found more patient satisfaction in combined treatment sessions. The number of sessions roughly correlated with patient satisfaction. They concluded that combination of polylactic acid injection and IPL in photorejuvenation of the face is safe and effective.
Review of the literature of combined treatments
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
Treatment combining botulinum toxin and laser/IPL/RF treatments There are several publications discussing the combined use of laser or IPL systems, and BT (13). Carruthers et al. (14) performed a prospective, randomized study of crow’s feet rhytides in 30 women. Half of the subjects were treated with BT and a broad-based light (BBL) and the other half with BBL alone. Their response was assessed clinically and photographically, and skin biopsies of the temporal area were taken from two subjects in each group. Patients treated with a combination of BT and BBL experienced a better response to treatment, as well as a slightly improved response in associated lentigines, telangiectasia, pore size, and facial skin texture compared with patients who received BBL treatment alone. Skin biopsies showed an increase in dermal collagen in each group. A prospective, randomized, placebo-controlled study was performed by Yamauchi (15) in 33 patients. They compared the efficacy and safety of combining BT (18 units per area) with erbium laser treatment versus laser alone in the treatment of periorbital rhytides. The results demonstrated that combining BT with erbium resurfacing significantly improved the periorbital wrinkles more than those in the contralateral area treated with saline and laser. Semchyshyn et al. performed a study to determine whether the use of nonablative laser or IPL immediately following BT injections, inactivated BT (16). Nineteen subjects received BT injections in either the glabellar or crow’s feet areas. One side of the treated glabellar or periorbital area was treated with lasers, IPL, and RF devices within 10 minutes of BT injection. Pretreatment and 2-week posttreatment photographs were compared. Authors concluded that patients may be treated with nonablative lasers, IPL, or RF devices immediately after BT injection without loss of efficacy or other apparent untoward effect. Beer et al. (17) published a case report of a patient who received BT injection one day prior to treatment with a fractionated laser (Palomar Medical Technologies Inc). They noted significant improvement of rhytides. A prospective, randomized, double-blind, splitface study for evaluating combined BT injection and IPL treatment of the cheeks was performed by Khoury et al. (18). Fifteen females received standard IPL treatment and were randomly assigned to receive eight 0.1-mL intradermal injections of BT in one cheek (8U of total dose) and eight injections of saline in the contralateral cheek. A significantly higher proportion of patients showed improvement in small wrinkles and fine lines with IPL plus BT than IPL plus saline. Adjunctive BT also achieved a greater degree of improvement in erythema (although statistical significance was not achieved).
51
The authors concluded that the adjunctive use of BT enhances the improvement in small wrinkles, and possibly erythema, achieved with IPL alone. One interesting research was performed by Paul et al. (19) for studying the possible interference of combined hair removal laser systems and BT injections for the axillary hyperhidrosis treatment. In a prospective, double-blind, randomized cross-over trial, nine patients suffering from primary axillary hyperhidrosis were selected and treated with laser in one randomly assigned axilla. One week later, both axilla were injected with 100 MU of BT per axilla and treated with diode laser. No differences were found regarding the effect of BT on previously laser-treated and laser co-treated sides over time course for any of the outcome parameters. The authors concluded that concomitant laser hair removal does not interfere with BT treatment on axillary hyperhidrosis and may be combined during one treatment session. Recently, Zimbler et al. performed a study of ten female patients (20). Patients had one side of their face injected with BT 1 week before laser resurfacing with either a CO2 and erbium dual-mode laser. Hyperdynamic facial lines, pretreated with BT before laser resurfacing, heal in a smoother rhytiddiminished fashion. The authors found that these results were clinically most significant in the crow’s feet region and even they conclude recommending pretreatment of movement-associated rhytides with BT before laser resurfacing.
Discussion In many cases, patients are candidates for photorejuvenation with laser or light systems and fillers, and BT (21–25). Precautionary statements on the labeling of fillers products advise against the use of laser treatments or any procedures that can induce and dermal response after injection, because of the possible risk of an inflammatory reaction at the implant site. At the same time it is advised that healing of the skin with the procedure can accelerate filler or toxin elimination (26,27). This creates apprehension regarding concomitant administration of injections with laser or light systems, based on the unconfirmed fear of denaturation of the implant material. Thus, laser therapy is often delayed to several days or weeks after the injectable has been placed (12). Fillers Level of deposition of injected substances must be considered. Some substances are deposited in deep layers, while others must be injected in superficial ones. Most of the authors do not find clinical either of the histological changes after laser treatments.
52
E. Cuerda-Galindo et al.
Table I. RF combined with fillers. Authors England et al. (4) Shumaker et al. (5)
Goldman et al. (9)
Cosmoplast Restylane Sculptra Radiesse Silikom Restylane Radiesse Restylane
Park et al. (11)
Teosyal
Alam et al. (8)
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
Treatment
Clinical efficacy
Histological changes
Juvenile pig model
RF increases the inflammatory, foreign body, and fibrotic responses of fillers
Not evaluated
No changes in filler material
No statistically significant differences between wrinkle severity and global esthetic scores Combining treatment does not appear to be superior
No apparent histologic changes
However, some authors have reported interaction between CO2 laser and silicone (7) and recently one author has reported calcium hydroxylapatite nodule resolution after fractional CO2 laser (28). These facts can indicate that type of filler and depth of injection must be considered. Laser, IPL, or RF treatment must be considered. Regarding non-ablative or soft ablative treatments, most of the authors agree that the combination is safe. RF treatment over areas recently injected with fillers does not appear to disrupt the product (Table I). In the same way, fillers combined with IPL in the same session have been proved to be safe without apparent histologic changes, as is summarized in Table II. Some authors find clinical improvement when combining treatments (12). Other authors have only demonstrated no adverse effects or filler degradation, but no clinical improvement has been found when filler and laser are used in same-day treatment (9,11).
Fillers unaffected
Studies of fillers combined with ablative treatments have demonstrated different conclusions. Some authors find some changes in filler when an aggressive ablative laser treatment is applied (7,9), while other others (10) find no changes when combining a nonreticulated filler with a subablative laser. More studies are needed to confirm the safety of combination in the same treatment fillers and ablative lasers, but the risk of an adverse interaction seems to be higher for deeper lasers. Botulinum toxin Treatments combining IPL and BT are summarized in Table III. Authors find more improvement and they argue that the reason is because each treatment acts for different targets such as wrinkles, lentigines, laxity, and telangiectasia. Some authors inject toxin prior to IPL treatment (14,16) and other authors apply IPL prior to toxin injection (18).
Table II. IPL combined with fillers. Authors Farkas et al. (6)
Goldman et al. (9)
Fabi et al. (12)
Treatment
Clinical efficacy
Restylane Perlane Juvederm IPL 560 nm (Sciton) Restylane IPL 560 nm (Lumenis) Sculptra IPL 560 nm or 590 nm (Lumenis)
Histological changes
Porcine models
Fillers unaffected
No statistically significant differences between wrinkle severity and global esthetic scores 86.7% of patients satisfied with combined treatment
No apparent histologic changes
Not evaluated
Table III. IPL combined with toxin. Author Carruthers et al. (14) Semchyshyn et al. (16) Khoury et al. (18)
Treatment Toxin and IPL 10 minutes later Toxin and IPL immediately after treatment First IPL and immediately botulin toxin injection
Location Periocular Glabellar or crow’s feet areas Cheeks
Clinical results Similar results in crow’s feet. Improvement in telangiectasia, pore size, erythema, and lentigo. No loss of efficacy after IPL treatment Improvement in small wrinkles and fine lines with IPL plus BTX. Adjunctive BTX also achieved a greater degree of improvement in erythema.
Review of the literature of combined treatments
53
Table IV. Effectiveness of toxin after laser treatment. Author Semchyshyn et al. (16) Paul et al. (19)
Treatment
Location
Inactivity toxin
Toxine, VBeam laser, Smoothbeam laser, CoolGlide laser, IPL, and RF Toxin treatment for hyperhidrosis and hair removal with diode laser
Glabella, forehead, and crow’s feet Axilas
Not found Not found
Table V. Combined treatment of ablative laser and toxin.
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
Author
Treatment
Location
Results
Glabella, forehead, and crow’s feet Crow’s feet
Improvement of dynamic rhytides. Long-lasting results of CO2 laser. Botox-treated side with laser resurfacing improved more significantly in diminishing periorbital rhytides as well as textural, pigmentation, and other features of periorbital skin aging. Significant improvement in wrinkles after the first treatment. Authors recommend pretreatment of movement-associated rhytides with BT before laser resurfacing. More significant improvement in all sites pretreated with BT, with the crow’s feet region showing the greatest improvement. Authors recommend pretreatment of movement-associated rhytides with BT before laser resurfacing.
West et al. (13)
Toxin and CO2 laser
Yamauchi et al. (15)
Toxin and Er:YAG 2–6 weeks later
Beer et al. (17)
Toxin and CO2 treatment one day after injection
Crow’s feet
Zimbler et al. (20)
Toxin injection one week prior to ablative laser resurfacing Er:YAG, CO2, or dual mode
Glabella, forehead, and periocular region
In Table IV, BT duration when combining light treatments is studied. Authors do not find any differences when toxin is injected prior to laser treatment. When toxin is injected one of the recommendations given to the patient is not to massage the area after 24 h of treatment. Of course when a laser, RF, or IPL treatment is applied, the area is manipulated and massaged, but no dispread of product or adverse effects regarding toxin migration have been reported. It would be helpful to perform more clinical studies to research on the safety, duration, and lack of spreading of product if the area is manipulated after injection. In Table V, a summary of ablative lasers treatments combined with BT injection is detailed. All authors agree with the idea that is mandatory to associate toxin and ablative laser because it improves wound healing and toxin potentiates laser treatment. Toxin paralyzes muscle action and it improves collagen synthesis which potentiates laser effects. In some cases, toxin has been injected prior to ablative treatment (17,20) and other authors have injected toxin after laser treatment (13,15). It is necessary to perform more clinical studies comparing ablative laser combined with toxin injection prior to or after laser treatment.
Conclusions Combined treatments for photorejuvenation are highly demanded by patients (31,32) and same-day treatments are becoming popular (33–35).
Combined treatments in the same session with filler injections and RF, IPL, or nonablative lasers have demonstrated to be safe, but not all authors find clinical improvement when same-day treatments are used. More studies are needed to confirm the safety of aggressive laser treatments combined with fillers because some authors have reported filler degradation or flaring of product. The level of penetration of rejuvenation laser techniques, the level of deposition of injected substance, and the kind of filler must be considered for selecting the most adequate technique and filler. When a laser, RF, or IPL treatment is applied after BT injection, spread and no related adverse effects have been reported. In case of ablative lasers, it is recommended to associate treatment to BT injection because better results are obtained, but more studies are need to confirm the best time for toxin injection, prior to or after ablative laser treatment. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Cuerda E, Linares R, Palomar MA, Lopez Estebaranz JL, Ortonne JP. Hair removal home devices: are they safe? J Eur Acad Dermatol Venereol. 2012;26:1584–1585.
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
54
E. Cuerda-Galindo et al.
2. Bosniak S, Cantisano-Zilkha M, Purewal BK, Zdinak LA. Combination therapies in oculofacial rejuvenation. Orbit. 2006;25:319–326. 3. Tierney EP, Hanke CW. Recent advances in combination treatments for photoaging: review of the literature. Dermatol Surg. 2010;36:829–840. 4. England LJ, Tan MH, Shumaker PR, Egbert BM, Pittelko K, Orentreich D, Pope K. Effects of monopolar radiofrequency treatment over soft-tissue fillers in an animal model. Lasers Surg Med. 2005;37:356–365. 5. Shumaker PR, England LJ, Dover JS, Ross EV, Harford R, Derienzo D, et al. Effect of monopolar radiofrequency treatment over soft-tissue fillers in an animal model: part 2. Lasers Surg Med. 2006;38:211–217. 6. Farkas JP, Richardson JA, Brown S, Hoopman JE, Kenkel JM. Effects of common laser treatments on hyaluronic acid fillers in a porcine model. Aesthet Surg J. 2008;28:503–511. 7. Zager W, Huang J, McCue P, Reitter D. Laser resurfacing of silicone-injected skin. Arch Otolaryngol Head Neck Surg. 2001;127:418–421. 8. Alam M, Levy R, Pajvani U, Ramierez JA, Guitart J, Veen H, Gladstone HB. Safety of radiofrequency treatment over human skin previously injected with medium-term injectable soft-tissue augmentation materials: a controlled pilot trial. Lasers Surg Med. 2006;38:205–210. 9. Goldman MP, Alster TS, Weiss R. A randomized trial to determine the influence of laser therapy, monopolar radiofrequency treatment, and intense pulsed light therapy administered immediately after hyaluronic acid gel implantation. Dermatol Surg. 2007;33:535–542. 10. Ribe A, Ribe N. Neck skin rejuvenation: Histological and clinical changes after combined therapy with a fractional non-ablative laser and stabilized hyaluronic acid-based gel of non-animal origin. J Cosmet Laser Ther. 2011;13: 154–161. 11. Park KY, Park MK, Kapsok L, Seo SJ, Hong CK. Combined treatment with a Nonablative Infrared device and Hyaluronic Acid filler dos not have enhaced efficacy in treating nasolabial fold wrinkles. Dermatol Surg. 2011;37:1770–1775. 12. Fabi SG, Goldman MP. The Safety and Efficacy of Combining Poly-L-Lactic Acid with Intense Pulsed Light in Facial Rejuvenation: A Retrospective Study of 90 Patients. Dermatol Surg. 2012;38:1208–1216. 13. West TB, Alster TS. Effect of botulinum toxin type A on movement-associated rhytides following CO2 laser resurfacing. Dermatol Surg. 1999;25:259–261. 14. Carruthers J, Carruthers A. The effect of full-face broadband light treatments alone and in combination with bilateral crow’s feet Botulinum toxin type A chemodenervation. Dermatol Surg. 2004;30:355–366; discussion 366. 15. Yamauchi PS, Lask G, Lowe NJ. Botulinum toxin type A gives adjunctive benefit to periorbital laser resurfacing. J Cosmet Laser Ther. 2004;6:145–148. 16. Semchyshyn NL, Kilmer SL. Does laser inactivate botulinum toxin? Dermatol Surg. 2005;31:399–404. 17. Beer K, Kaibel J. Botulinum toxin type A enhances the outcome of fractional resurfacing of the cheek. J Drugs Dermatol. 2007;6:1151–1152. 18. Khoury JG, Saluja R, Goldman MP. The effect of botulinum toxin type A on full-face intense pulsed light treatment: a randomized, double-blind, split-face study. Dermatol Surg. 2008;34:1062–1069.
19. Paul A, Kranz G, Schindl A, Kranz GS, Auff E, Sycha T. Diode laser hair removal does not interfere with botulinum toxin A treatment against axillary hyperhidrosis. Lasers Surg Med. 2010;42:211–214. 20. Zimbler M, Undavia S. Update on the effect of botulinum toxin pretreatment on laser resurfacing results. Arch Facial Plast Surg. 2012;14:156–158. 21. Bosniak S. Combination therapies: a nonsurgical approach to oculofacial rejuvenation. Ophthalmol Clin North Am. 2005;18:215–225. 22. Ho SGY, Chan HHL. The Asian dermatologic patient review of common pigmentary disorders and cutaneous diseases. Am J Clin Dermatol. 2009;10:153–168. 23. Shamban AT. Combination hand rejuvenation procedures. Aesthet Surg J. 2009;29:409–413. 24. Obagi S. Correction of surface deformities: Botox, softtissue fillers, lasers and intense pulsed light, and radiofrequency. Atlas Oral Maxillofac Surg Clin North Am. 2004;12:271–297. 25. Paasch U, Anderegg U, Grunewald S, Willenberg A, Bodendorf M, Simon JC. Hyaluronic acid remodelling in response to erbium laser punch ablation. Lasers Surg Med. 2008; 20:21–21. 26. Cho SB, Lee SJ, Kang JM, Kim YK, Ryu DJ, Lee JH. Effective treatment of a injected hyaluronic acid-induced Tyndall effect with a 1064-nm Q-switched Nd:YAG laser. Clin Exp Dermatol. 2009;34:537–638. 27. Beylot C. What’s new in aesthetic dermatology: filler and laser treatments. Ann Dermatol Venereol. 2009;136:S152–S159. 28. Reddy KK, Brauer JA, Anolik R, Bernstein L, Brightman LA, Hale E, et al. Calcium Hydroxylapatite nodule resolution after fractional carbón diode laser therapy. Arch Dermatol. 2012;148:634–636. 29. Cuerda E, López-Estebaranz JL. ¿Existe una ventaja real en alguna de las toxinas botulínicas usadas en Dermatología? Piel. 2013;28:189–191. 30. Hexsel D, Brum C, do Prado DZ, Soirefmann M, Rotta FT, Dal’Forno T, Rodrigues TC. Field effect of two commercial preparations of botulinum toxin type A: A prospective, double-blind, randomized clinical trial. J Am Acad Dermatol. 2012;67:226–232. 31. Campolmi P, Bonan P, Cannarozzo G, Bruscino N, Moretti S. Efficacy and safety evaluation of an innovative CO2 laser/radiofrequency device in dermatology. J Eur Acad Dermatol Venereol. 2013;27:1481–1490. 32. Weinkle S. Facial assessments: identifying the suitable pathway to facial rejuvenation. J Eur Acad Dermatol Venereol. 2006;20:7–11. 33. Ascher B, Talarico S, Cassuto D, Escobar S, Hexsel D, Jaén P, et al. International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit) – part I: upper facial wrinkles. J Eur Acad Dermatol Venereol. 2010;24:1278–1284. 34. Ascher B, Talarico S, Cassuto D, Escobar S, Hexsel D, Jaén P, et al. International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit) – part II: wrinkles on the middle and lower face, neck and chest. J Eur Acad Dermatol Venereol. 2010;24: 1285–1295. 35. Thioly-Bensoussan D. A new option for volumetric restoration: poly-l-lactic acid. J Eur Acad Dermatol Venereol. 2006;20:12–16.
REVIEWS OF TREATMENT STUDIES
Are combined same-day treatments the future for photorejuvenation?
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
Review of the literature on combined treatments with lasers, intense pulsed light, radiofrequency, botulinum toxin, and fillers for rejuvenation
ESTHER CUERDA-GALINDO, MARÍA ANGUSTIAS PALOMAR-GALLEGO & RAFAEL LINARES-GARCÍAVALDECASAS Department of Human Anatomy and Embriology, Universidad Rey Juan Carlos, Madrid, Spain Abstract Background: Skin rejuvenation requires a treatment combination including lasers, intense pulsed light (IPL), radiofrequency, botulinum toxin (BT) and fillers. A combined approach is considered optimum but usually same-day combined treatments are avoid and lasers are performed prior to filler or toxin injections owing to the concern that the light may inactivate or degrade them. Objective: To review the literature on the use of combination treatments with radiofrequency, IPL, non ablative and ablative lasers plus fillers or BT. Results: review of the literature identified 15 studies of combination treatments: three of them on animal models and 12 were clinical studies. Seven studies contained combined light system treatments with fillers and eight studies combined physical therapies with botulinum toxin injection. In all of them treatments were used as standard protocols. Six studies documented no histological changes in fillers injected after applying radiofrequency, IPL or laser treatments and one studied documented improvement in collagen after IPL treatment and toxin injection. These studies reported clinical improvement in various features of photodamaged skin, no increase of adverse effects and neither decrease on efficacy of substances injected. Conclusions: review of the literature demonstrates safety of same day combined treatments for rejuvenation, which improve clinical results, are more comfortable for patients have no loss of efficacy or other apparent adverse effect. Key Words: botulinum toxin, combined treatments, fillers, intense pulsed light, laser, radiofrequency
Introduction In recent years, an increasing number of treatments have been developed (1) including botulinum toxin (BT), fillers, and laser or intense pulsed light (IPL) devices to improve the appearance of aging skin. There is a growing demand for noninvasive procedures with both minimal downtime and adverse effects (2). Patients demand for cosmetic improvement of skin texture, pigmentation, and rhytides. A combined treatment is necessary for many patients because it targets various regions of the face and the treatments supplement each other (3). Combined treatments with lasers and injected substances are frequently used. Laser therapy is often administered some days after filler implantation or toxin injection, but the apprehension regarding
concomitant treatment with fillers–BT and laser–IPL– radiofrequency (RF) is not supported by documented research. It has been proposed that light could interact with tissue, filler, or toxin, producing some changes in clinical results or lasting effects. When combining treatments, it is necessary to be sure that this combination improves clinical results without adverse effects. In this article, we examine the existing literatures which evaluate combined treatments with lasers or light systems and fillers or BT.
Treatments combining laser, IPL, and fillers Some authors have researched on the effects of lasers and IPL in animal models when filler is injected.
Correspondence: Dr. Esther Cuerda-Galindo, Department of Human Anatomy and Embriology, Universidad Rey Juan Carlos, Avda Atenas sn 28922 Alcorcón, Madrid, Spain. Tel: ⫹ 0034 914889027. Fax: ⫹ 0034 914888831. E-mail: [email protected] (Received 17 March 2014 ; accepted 10 September 2014 ) ISSN 1476-4172 print/ISSN 1476-4180 online © 2015 Informa UK, Ltd. DOI: 10.3109/14764172.2014.968578
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
50
E. Cuerda-Galindo et al.
England et al. (4). used a monopolar RF treatment over soft-tissue fillers in a juvenile pig model over a period of 4 months. They used a ThermaCool TC system (Thermage, Inc., Hayward CA). Fillers used were Cosmoplast (a highly purified collagen derived from human fibroblast), Restylane (hyaluronic acid), Sculptra (polylactic acid), Radiesse (with spherum of calcium hydroxylapatite), and Silikom (liquid injectable silicone). Fillers were injected immediately preceding or 1 month preceding RF treatment. The authors found no apparent increase in the risk of local burns and no effects of RF treatment on fillers persistence in the tissue. The same research group (5) studied the effects of a monopolar system, ThermaCool TC system, combined with the same fillers: Cosmoplast, Restylane, Sculptra, Radiesse, and Silikom. In this study, histological biopsies were performed at 5 days, 2 weeks, or 1 month after RF treatment and it was concluded that no thermal effect of RF was observed histologically and that RF treatment increased the inflammatory, foreign body, and fibrotic responses associated with fillers. Farkas et al. (6) examined the effect of laser and IPL systems on hyaluronic acid fillers in porcine models. They used three different hyaluronic acids (Restylane, Perlane, and Juvéderm) and light systems used for examination were Sciton IPL with a 560-nm filter (Sciton, Aplo Alto, CA), Sciton Nd:YAG 1064 (Sciton), Profractional (Sciton), Lux1540 Er:Glass, Palomar erbium 2940 (Palomar Medical Technologies, Burlington, MA), and the ActiveFX and DeepFX (Lumenis,Yokneum, Israel). Following laser treatment, punch biopsies were collected. Authors reported that fillers were unaffected by the nonablative laser or light and superficial ablative treatments. The aggressive deeper treatments demonstrated laser–filler interaction with evidence of migration of filler into the ablated microchannels, and microablation columns were in direct contact with filler. When an aggressive deep resurfacing is planned, they recommend treating patients first with laser, before the soft tissue injections, to maximize the treatment effect of each modality. Some authors have reported (7) that exposure of liquid silicone injected in cultured human skin to CO2 laser produces flaring of silicone. They demonstrated histologically that silicone fluid contaminates the full soft tissue through which the needle passes and if tissue is exposed to CO2 laser, injected silicones and contaminated tissue can flare. Alam et al. (8) treated five patients with injections of Restylane (hyaluronic acid derivative) and Radiesse (calcium hydroxyapatite), and applied monopolar RF 2 weeks after using ThermaCool TC system. Skin biopsies were obtained; they concluded that applying RF after deep dermal injection with hyaluronic acid or calcium hydroxyapatite does not appear to cause changes in the filler material.
Some authors (9) performed a randomized trial in 36 patients to determine the influence of laser therapy, monopolar RF, and IPL treatment after hyaluronic gel implantation (Restylane) in nasolabial folds. They treated one-half of the face with only hyaluronic acid and the other side with hyaluronic acid injection and laser light treatment. The devices used were 1320-nm Nd:YAG (CoolTouch, New Star Lasers, Rosemont, CA), 1450-nm diode (Smoothbeam, Candela Laser, Wayland, MA), monopolar RF (ThermaCool TC system, Thermage, Inc., San José, CA), and IPL with 560-nm cutoff filter (Lumenis One, Lumenis, Santa Clara, CA). Skin biopsies were performed at postoperative days 0, 14, and 28 in every patient and histological changes were not apparent. There were no statistically significant differences in wrinkle severity score in those areas treated with hyaluronic acid alone and those treated with concomitant hyaluronic acid, laser, RF, or IPL. The authors concluded that laser, RF, and IPL treatments can be administered immediately after hyaluronic acid injection without reduction in clinical effect. Ribé et al. (10) studied histological and clinical changes after combined therapy with a fractional nonablative laser (Affirm, Cynosure, Inc., Westford, MA, USA) and hyaluronic acid (Restylane Vital Light) for neck skin rejuvenation in 9 patients. Treatment consisted of hyaluronic acid administration immediately followed by laser treatment and they conclude that laser produces epidermal and superficial dermal changes, whereas the injected hyaluronic acid acts deeper. Park et al. (11) performed a split-face randomized study of 12 patients treated with hyaluronic acid on nasolabial folds and with a nonablative infrared device on the experimental side of the face. They used Teosyal (Teoxane) and two sessions of infrared, one of them immediately after filler injection. They did not find collagen fiber increase on histologic assessment immediately after infrared treatment and affirmed that both treatments may be applied safely, but they did not find more improvement when both treatments were used instead of hyaluronic acid injection alone. Recently, a study of 90 patients treated with IPL (560- or 590-nm cutoff filters, Lumenis 1 or Lumenis M22, Lumenis Ltd, Yokneam, Israel) immediately before or 6 days after polylactic acid injection (Sculptra) has been reported (12). Patients received an average of 1.63 (range, 1–5) combined treatments. The authors did not find adverse effects or formation of nodules, and found more patient satisfaction in combined treatment sessions. The number of sessions roughly correlated with patient satisfaction. They concluded that combination of polylactic acid injection and IPL in photorejuvenation of the face is safe and effective.
Review of the literature of combined treatments
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
Treatment combining botulinum toxin and laser/IPL/RF treatments There are several publications discussing the combined use of laser or IPL systems, and BT (13). Carruthers et al. (14) performed a prospective, randomized study of crow’s feet rhytides in 30 women. Half of the subjects were treated with BT and a broad-based light (BBL) and the other half with BBL alone. Their response was assessed clinically and photographically, and skin biopsies of the temporal area were taken from two subjects in each group. Patients treated with a combination of BT and BBL experienced a better response to treatment, as well as a slightly improved response in associated lentigines, telangiectasia, pore size, and facial skin texture compared with patients who received BBL treatment alone. Skin biopsies showed an increase in dermal collagen in each group. A prospective, randomized, placebo-controlled study was performed by Yamauchi (15) in 33 patients. They compared the efficacy and safety of combining BT (18 units per area) with erbium laser treatment versus laser alone in the treatment of periorbital rhytides. The results demonstrated that combining BT with erbium resurfacing significantly improved the periorbital wrinkles more than those in the contralateral area treated with saline and laser. Semchyshyn et al. performed a study to determine whether the use of nonablative laser or IPL immediately following BT injections, inactivated BT (16). Nineteen subjects received BT injections in either the glabellar or crow’s feet areas. One side of the treated glabellar or periorbital area was treated with lasers, IPL, and RF devices within 10 minutes of BT injection. Pretreatment and 2-week posttreatment photographs were compared. Authors concluded that patients may be treated with nonablative lasers, IPL, or RF devices immediately after BT injection without loss of efficacy or other apparent untoward effect. Beer et al. (17) published a case report of a patient who received BT injection one day prior to treatment with a fractionated laser (Palomar Medical Technologies Inc). They noted significant improvement of rhytides. A prospective, randomized, double-blind, splitface study for evaluating combined BT injection and IPL treatment of the cheeks was performed by Khoury et al. (18). Fifteen females received standard IPL treatment and were randomly assigned to receive eight 0.1-mL intradermal injections of BT in one cheek (8U of total dose) and eight injections of saline in the contralateral cheek. A significantly higher proportion of patients showed improvement in small wrinkles and fine lines with IPL plus BT than IPL plus saline. Adjunctive BT also achieved a greater degree of improvement in erythema (although statistical significance was not achieved).
51
The authors concluded that the adjunctive use of BT enhances the improvement in small wrinkles, and possibly erythema, achieved with IPL alone. One interesting research was performed by Paul et al. (19) for studying the possible interference of combined hair removal laser systems and BT injections for the axillary hyperhidrosis treatment. In a prospective, double-blind, randomized cross-over trial, nine patients suffering from primary axillary hyperhidrosis were selected and treated with laser in one randomly assigned axilla. One week later, both axilla were injected with 100 MU of BT per axilla and treated with diode laser. No differences were found regarding the effect of BT on previously laser-treated and laser co-treated sides over time course for any of the outcome parameters. The authors concluded that concomitant laser hair removal does not interfere with BT treatment on axillary hyperhidrosis and may be combined during one treatment session. Recently, Zimbler et al. performed a study of ten female patients (20). Patients had one side of their face injected with BT 1 week before laser resurfacing with either a CO2 and erbium dual-mode laser. Hyperdynamic facial lines, pretreated with BT before laser resurfacing, heal in a smoother rhytiddiminished fashion. The authors found that these results were clinically most significant in the crow’s feet region and even they conclude recommending pretreatment of movement-associated rhytides with BT before laser resurfacing.
Discussion In many cases, patients are candidates for photorejuvenation with laser or light systems and fillers, and BT (21–25). Precautionary statements on the labeling of fillers products advise against the use of laser treatments or any procedures that can induce and dermal response after injection, because of the possible risk of an inflammatory reaction at the implant site. At the same time it is advised that healing of the skin with the procedure can accelerate filler or toxin elimination (26,27). This creates apprehension regarding concomitant administration of injections with laser or light systems, based on the unconfirmed fear of denaturation of the implant material. Thus, laser therapy is often delayed to several days or weeks after the injectable has been placed (12). Fillers Level of deposition of injected substances must be considered. Some substances are deposited in deep layers, while others must be injected in superficial ones. Most of the authors do not find clinical either of the histological changes after laser treatments.
52
E. Cuerda-Galindo et al.
Table I. RF combined with fillers. Authors England et al. (4) Shumaker et al. (5)
Goldman et al. (9)
Cosmoplast Restylane Sculptra Radiesse Silikom Restylane Radiesse Restylane
Park et al. (11)
Teosyal
Alam et al. (8)
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
Treatment
Clinical efficacy
Histological changes
Juvenile pig model
RF increases the inflammatory, foreign body, and fibrotic responses of fillers
Not evaluated
No changes in filler material
No statistically significant differences between wrinkle severity and global esthetic scores Combining treatment does not appear to be superior
No apparent histologic changes
However, some authors have reported interaction between CO2 laser and silicone (7) and recently one author has reported calcium hydroxylapatite nodule resolution after fractional CO2 laser (28). These facts can indicate that type of filler and depth of injection must be considered. Laser, IPL, or RF treatment must be considered. Regarding non-ablative or soft ablative treatments, most of the authors agree that the combination is safe. RF treatment over areas recently injected with fillers does not appear to disrupt the product (Table I). In the same way, fillers combined with IPL in the same session have been proved to be safe without apparent histologic changes, as is summarized in Table II. Some authors find clinical improvement when combining treatments (12). Other authors have only demonstrated no adverse effects or filler degradation, but no clinical improvement has been found when filler and laser are used in same-day treatment (9,11).
Fillers unaffected
Studies of fillers combined with ablative treatments have demonstrated different conclusions. Some authors find some changes in filler when an aggressive ablative laser treatment is applied (7,9), while other others (10) find no changes when combining a nonreticulated filler with a subablative laser. More studies are needed to confirm the safety of combination in the same treatment fillers and ablative lasers, but the risk of an adverse interaction seems to be higher for deeper lasers. Botulinum toxin Treatments combining IPL and BT are summarized in Table III. Authors find more improvement and they argue that the reason is because each treatment acts for different targets such as wrinkles, lentigines, laxity, and telangiectasia. Some authors inject toxin prior to IPL treatment (14,16) and other authors apply IPL prior to toxin injection (18).
Table II. IPL combined with fillers. Authors Farkas et al. (6)
Goldman et al. (9)
Fabi et al. (12)
Treatment
Clinical efficacy
Restylane Perlane Juvederm IPL 560 nm (Sciton) Restylane IPL 560 nm (Lumenis) Sculptra IPL 560 nm or 590 nm (Lumenis)
Histological changes
Porcine models
Fillers unaffected
No statistically significant differences between wrinkle severity and global esthetic scores 86.7% of patients satisfied with combined treatment
No apparent histologic changes
Not evaluated
Table III. IPL combined with toxin. Author Carruthers et al. (14) Semchyshyn et al. (16) Khoury et al. (18)
Treatment Toxin and IPL 10 minutes later Toxin and IPL immediately after treatment First IPL and immediately botulin toxin injection
Location Periocular Glabellar or crow’s feet areas Cheeks
Clinical results Similar results in crow’s feet. Improvement in telangiectasia, pore size, erythema, and lentigo. No loss of efficacy after IPL treatment Improvement in small wrinkles and fine lines with IPL plus BTX. Adjunctive BTX also achieved a greater degree of improvement in erythema.
Review of the literature of combined treatments
53
Table IV. Effectiveness of toxin after laser treatment. Author Semchyshyn et al. (16) Paul et al. (19)
Treatment
Location
Inactivity toxin
Toxine, VBeam laser, Smoothbeam laser, CoolGlide laser, IPL, and RF Toxin treatment for hyperhidrosis and hair removal with diode laser
Glabella, forehead, and crow’s feet Axilas
Not found Not found
Table V. Combined treatment of ablative laser and toxin.
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
Author
Treatment
Location
Results
Glabella, forehead, and crow’s feet Crow’s feet
Improvement of dynamic rhytides. Long-lasting results of CO2 laser. Botox-treated side with laser resurfacing improved more significantly in diminishing periorbital rhytides as well as textural, pigmentation, and other features of periorbital skin aging. Significant improvement in wrinkles after the first treatment. Authors recommend pretreatment of movement-associated rhytides with BT before laser resurfacing. More significant improvement in all sites pretreated with BT, with the crow’s feet region showing the greatest improvement. Authors recommend pretreatment of movement-associated rhytides with BT before laser resurfacing.
West et al. (13)
Toxin and CO2 laser
Yamauchi et al. (15)
Toxin and Er:YAG 2–6 weeks later
Beer et al. (17)
Toxin and CO2 treatment one day after injection
Crow’s feet
Zimbler et al. (20)
Toxin injection one week prior to ablative laser resurfacing Er:YAG, CO2, or dual mode
Glabella, forehead, and periocular region
In Table IV, BT duration when combining light treatments is studied. Authors do not find any differences when toxin is injected prior to laser treatment. When toxin is injected one of the recommendations given to the patient is not to massage the area after 24 h of treatment. Of course when a laser, RF, or IPL treatment is applied, the area is manipulated and massaged, but no dispread of product or adverse effects regarding toxin migration have been reported. It would be helpful to perform more clinical studies to research on the safety, duration, and lack of spreading of product if the area is manipulated after injection. In Table V, a summary of ablative lasers treatments combined with BT injection is detailed. All authors agree with the idea that is mandatory to associate toxin and ablative laser because it improves wound healing and toxin potentiates laser treatment. Toxin paralyzes muscle action and it improves collagen synthesis which potentiates laser effects. In some cases, toxin has been injected prior to ablative treatment (17,20) and other authors have injected toxin after laser treatment (13,15). It is necessary to perform more clinical studies comparing ablative laser combined with toxin injection prior to or after laser treatment.
Conclusions Combined treatments for photorejuvenation are highly demanded by patients (31,32) and same-day treatments are becoming popular (33–35).
Combined treatments in the same session with filler injections and RF, IPL, or nonablative lasers have demonstrated to be safe, but not all authors find clinical improvement when same-day treatments are used. More studies are needed to confirm the safety of aggressive laser treatments combined with fillers because some authors have reported filler degradation or flaring of product. The level of penetration of rejuvenation laser techniques, the level of deposition of injected substance, and the kind of filler must be considered for selecting the most adequate technique and filler. When a laser, RF, or IPL treatment is applied after BT injection, spread and no related adverse effects have been reported. In case of ablative lasers, it is recommended to associate treatment to BT injection because better results are obtained, but more studies are need to confirm the best time for toxin injection, prior to or after ablative laser treatment. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Cuerda E, Linares R, Palomar MA, Lopez Estebaranz JL, Ortonne JP. Hair removal home devices: are they safe? J Eur Acad Dermatol Venereol. 2012;26:1584–1585.
J Cosmet Laser Ther Downloaded from informahealthcare.com by Osaka University on 04/08/15 For personal use only.
54
E. Cuerda-Galindo et al.
2. Bosniak S, Cantisano-Zilkha M, Purewal BK, Zdinak LA. Combination therapies in oculofacial rejuvenation. Orbit. 2006;25:319–326. 3. Tierney EP, Hanke CW. Recent advances in combination treatments for photoaging: review of the literature. Dermatol Surg. 2010;36:829–840. 4. England LJ, Tan MH, Shumaker PR, Egbert BM, Pittelko K, Orentreich D, Pope K. Effects of monopolar radiofrequency treatment over soft-tissue fillers in an animal model. Lasers Surg Med. 2005;37:356–365. 5. Shumaker PR, England LJ, Dover JS, Ross EV, Harford R, Derienzo D, et al. Effect of monopolar radiofrequency treatment over soft-tissue fillers in an animal model: part 2. Lasers Surg Med. 2006;38:211–217. 6. Farkas JP, Richardson JA, Brown S, Hoopman JE, Kenkel JM. Effects of common laser treatments on hyaluronic acid fillers in a porcine model. Aesthet Surg J. 2008;28:503–511. 7. Zager W, Huang J, McCue P, Reitter D. Laser resurfacing of silicone-injected skin. Arch Otolaryngol Head Neck Surg. 2001;127:418–421. 8. Alam M, Levy R, Pajvani U, Ramierez JA, Guitart J, Veen H, Gladstone HB. Safety of radiofrequency treatment over human skin previously injected with medium-term injectable soft-tissue augmentation materials: a controlled pilot trial. Lasers Surg Med. 2006;38:205–210. 9. Goldman MP, Alster TS, Weiss R. A randomized trial to determine the influence of laser therapy, monopolar radiofrequency treatment, and intense pulsed light therapy administered immediately after hyaluronic acid gel implantation. Dermatol Surg. 2007;33:535–542. 10. Ribe A, Ribe N. Neck skin rejuvenation: Histological and clinical changes after combined therapy with a fractional non-ablative laser and stabilized hyaluronic acid-based gel of non-animal origin. J Cosmet Laser Ther. 2011;13: 154–161. 11. Park KY, Park MK, Kapsok L, Seo SJ, Hong CK. Combined treatment with a Nonablative Infrared device and Hyaluronic Acid filler dos not have enhaced efficacy in treating nasolabial fold wrinkles. Dermatol Surg. 2011;37:1770–1775. 12. Fabi SG, Goldman MP. The Safety and Efficacy of Combining Poly-L-Lactic Acid with Intense Pulsed Light in Facial Rejuvenation: A Retrospective Study of 90 Patients. Dermatol Surg. 2012;38:1208–1216. 13. West TB, Alster TS. Effect of botulinum toxin type A on movement-associated rhytides following CO2 laser resurfacing. Dermatol Surg. 1999;25:259–261. 14. Carruthers J, Carruthers A. The effect of full-face broadband light treatments alone and in combination with bilateral crow’s feet Botulinum toxin type A chemodenervation. Dermatol Surg. 2004;30:355–366; discussion 366. 15. Yamauchi PS, Lask G, Lowe NJ. Botulinum toxin type A gives adjunctive benefit to periorbital laser resurfacing. J Cosmet Laser Ther. 2004;6:145–148. 16. Semchyshyn NL, Kilmer SL. Does laser inactivate botulinum toxin? Dermatol Surg. 2005;31:399–404. 17. Beer K, Kaibel J. Botulinum toxin type A enhances the outcome of fractional resurfacing of the cheek. J Drugs Dermatol. 2007;6:1151–1152. 18. Khoury JG, Saluja R, Goldman MP. The effect of botulinum toxin type A on full-face intense pulsed light treatment: a randomized, double-blind, split-face study. Dermatol Surg. 2008;34:1062–1069.
19. Paul A, Kranz G, Schindl A, Kranz GS, Auff E, Sycha T. Diode laser hair removal does not interfere with botulinum toxin A treatment against axillary hyperhidrosis. Lasers Surg Med. 2010;42:211–214. 20. Zimbler M, Undavia S. Update on the effect of botulinum toxin pretreatment on laser resurfacing results. Arch Facial Plast Surg. 2012;14:156–158. 21. Bosniak S. Combination therapies: a nonsurgical approach to oculofacial rejuvenation. Ophthalmol Clin North Am. 2005;18:215–225. 22. Ho SGY, Chan HHL. The Asian dermatologic patient review of common pigmentary disorders and cutaneous diseases. Am J Clin Dermatol. 2009;10:153–168. 23. Shamban AT. Combination hand rejuvenation procedures. Aesthet Surg J. 2009;29:409–413. 24. Obagi S. Correction of surface deformities: Botox, softtissue fillers, lasers and intense pulsed light, and radiofrequency. Atlas Oral Maxillofac Surg Clin North Am. 2004;12:271–297. 25. Paasch U, Anderegg U, Grunewald S, Willenberg A, Bodendorf M, Simon JC. Hyaluronic acid remodelling in response to erbium laser punch ablation. Lasers Surg Med. 2008; 20:21–21. 26. Cho SB, Lee SJ, Kang JM, Kim YK, Ryu DJ, Lee JH. Effective treatment of a injected hyaluronic acid-induced Tyndall effect with a 1064-nm Q-switched Nd:YAG laser. Clin Exp Dermatol. 2009;34:537–638. 27. Beylot C. What’s new in aesthetic dermatology: filler and laser treatments. Ann Dermatol Venereol. 2009;136:S152–S159. 28. Reddy KK, Brauer JA, Anolik R, Bernstein L, Brightman LA, Hale E, et al. Calcium Hydroxylapatite nodule resolution after fractional carbón diode laser therapy. Arch Dermatol. 2012;148:634–636. 29. Cuerda E, López-Estebaranz JL. ¿Existe una ventaja real en alguna de las toxinas botulínicas usadas en Dermatología? Piel. 2013;28:189–191. 30. Hexsel D, Brum C, do Prado DZ, Soirefmann M, Rotta FT, Dal’Forno T, Rodrigues TC. Field effect of two commercial preparations of botulinum toxin type A: A prospective, double-blind, randomized clinical trial. J Am Acad Dermatol. 2012;67:226–232. 31. Campolmi P, Bonan P, Cannarozzo G, Bruscino N, Moretti S. Efficacy and safety evaluation of an innovative CO2 laser/radiofrequency device in dermatology. J Eur Acad Dermatol Venereol. 2013;27:1481–1490. 32. Weinkle S. Facial assessments: identifying the suitable pathway to facial rejuvenation. J Eur Acad Dermatol Venereol. 2006;20:7–11. 33. Ascher B, Talarico S, Cassuto D, Escobar S, Hexsel D, Jaén P, et al. International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit) – part I: upper facial wrinkles. J Eur Acad Dermatol Venereol. 2010;24:1278–1284. 34. Ascher B, Talarico S, Cassuto D, Escobar S, Hexsel D, Jaén P, et al. International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit) – part II: wrinkles on the middle and lower face, neck and chest. J Eur Acad Dermatol Venereol. 2010;24: 1285–1295. 35. Thioly-Bensoussan D. A new option for volumetric restoration: poly-l-lactic acid. J Eur Acad Dermatol Venereol. 2006;20:12–16.
