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Overview of botulinum toxin for cosmetic indications

Jean Carruthers, MD, FRCSC
Alastair Carruthers, FRCPC
Section Editor
Jeffrey S Dover, MD, FRCPC
Deputy Editor
Abena O Ofori, MD


Botulinum toxin is an injectable neuromodulator derived from neurotoxins produced by Clostridium botulinum, the bacterium responsible for botulism. Through the inhibition of neurotransmission between peripheral nerve endings and muscle fibers, botulinum toxin weakens or paralyzes skeletal muscle. Initially used for medical indications, botulinum toxin injection has now become one of the most requested procedures in facial rejuvenation.

When used appropriately, botulinum toxin injection is an overwhelmingly safe method for improving cosmetic defects that are caused by or exacerbated by muscle contraction, such as prominent glabellar rhytides. The effects of botulinum toxin are transient; muscular function typically returns to baseline within a few months.

The mechanism of action, formulations, clinical use, and safety of botulinum toxin injections for cosmetic indications will be reviewed here. The use of botulinum toxin for specific cosmetic or medical indications is discussed elsewhere. (See "Botulinum toxin for cosmetic indications: Treatment of specific sites" and "Treatment of dystonia", section on 'Botulinum toxin injections' and "Treatment of myoclonus", section on 'Botulinum toxin injections'.)


The clinical relevance of C. botulinum, a gram-positive bacillus, was first recognized in 1897, when the toxin produced by the organism was identified as the etiologic agent of botulism [1,2]. Since then, seven serotypes of botulinum toxin (A, B, C1, D, E, F, and G) produced by different strains of the bacterium have been identified. The pharmacologic properties of the serotypes differ, and only serotypes A and B are available for clinical use [3-5]. Botulinum toxin type A is the most common form of botulinum toxin used in aesthetic clinical practice.

The clinical utility of botulinum toxin initially became evident in the treatment of strabismus [6]. Subsequently, botulinum toxin has been utilized for a variety of other medical conditions characterized by muscular hyperactivity, including blepharospasm [7], hemifacial spasm [8,9], and cervical dystonia [10]. (See "Treatment of dystonia", section on 'Botulinum toxin injections' and "Treatment of myoclonus", section on 'Botulinum toxin injections'.)

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Literature review current through: Nov 2017. | This topic last updated: May 23, 2017.
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  1. DasGupta BR. Structures of botulinum neurotoxin, its functional domains, and perspectives on the crystalline type A toxin. In: Therapy with Botulinum Toxin, Jankovic J, Hallet M (Eds), Marcel Dekker, 1994. p.15.
  2. Schantz EJ, Johnson EA. Botulinum toxin: the story of its development for the treatment of human disease. Perspect Biol Med 1997; 40:317.
  3. Burke GS. Notes on Bacillus botulinus. J Bacteriol 1919; 4:555.
  4. Aoki KR, Guyer B. Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions. Eur J Neurol 2001; 8 Suppl 5:21.
  5. Dolly JO, Lisk G, Foran PG, et al. Insights into the extended duration of neuroparalysis by botulinum neurotoxin A relative to the other shorter-acting serotypes: differences between motor nerve terminals and cultured neurons. In: Scientific and Therapeutic Aspects of Botulinum Toxin, 1st ed, Brin MF, Jankovic J, Hallett M (Eds), Lippincott Williams & Wilkins, Philadelphia, PA 2002. p.91.
  6. Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology 1980; 87:1044.
  7. Wabbels B, Reichel G, Fulford-Smith A, et al. Double-blind, randomised, parallel group pilot study comparing two botulinum toxin type A products for the treatment of blepharospasm. J Neural Transm (Vienna) 2011; 118:233.
  8. Carruthers J, Stubbs HA. Botulinum toxin for benign essential blepharospasm, hemifacial spasm and age-related lower eyelid entropion. Can J Neurol Sci 1987; 14:42.
  9. Borodic GE, Cheney M, McKenna M. Contralateral injections of botulinum A toxin for the treatment of hemifacial spasm to achieve increased facial symmetry. Plast Reconstr Surg 1992; 90:972.
  10. Tsui JK, Eisen A, Mak E, et al. A pilot study on the use of botulinum toxin in spasmodic torticollis. Can J Neurol Sci 1985; 12:314.
  11. Carruthers JD, Carruthers JA. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol 1992; 18:17.
  12. Carruthers A, Carruthers J. Botulinum toxin type A: history and current cosmetic use in the upper face. Semin Cutan Med Surg 2001; 20:71.
  13. Carruthers J, Carruthers A. Botulinum toxin A in the mid and lower face and neck. Dermatol Clin 2004; 22:151.
  14. Lowe NJ, Yamauchi P. Cosmetic uses of botulinum toxins for lower aspects of the face and neck. Clin Dermatol 2004; 22:18.
  15. Dayan SH, Maas CS. Botulinum toxins for facial wrinkles: beyond glabellar lines. Facial Plast Surg Clin North Am 2007; 15:41.
  16. Fagien S, Carruthers JD. A comprehensive review of patient-reported satisfaction with botulinum toxin type a for aesthetic procedures. Plast Reconstr Surg 2008; 122:1915.
  17. Carruthers A, Carruthers J, Lei X, et al. OnabotulinumtoxinA treatment of mild glabellar lines in repose. Dermatol Surg 2010; 36 Suppl 4:2168.
  18. Blitzer A, Brin MF, Keen MS, Aviv JE. Botulinum toxin for the treatment of hyperfunctional lines of the face. Arch Otolaryngol Head Neck Surg 1993; 119:1018.
  19. Giordano CN, Matarasso SL, Ozog DM. Injectable and topical neurotoxins in dermatology: Basic science, anatomy, and therapeutic agents. J Am Acad Dermatol 2017; 76:1013.
  20. Meunier FA, Schiavo G, Molgó J. Botulinum neurotoxins: from paralysis to recovery of functional neuromuscular transmission. J Physiol Paris 2002; 96:105.
  21. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm175013.htm (Accessed on March 28, 2011).
  22. Carruthers JA, Lowe NJ, Menter MA, et al. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol 2002; 46:840.
  23. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm367662.htm (Accessed on September 12, 2013).
  24. Carruthers J, Carruthers A. The evolution of botulinum neurotoxin type A for cosmetic applications. J Cosmet Laser Ther 2007; 9:186.
  25. Jost WH, Blümel J, Grafe S. Botulinum neurotoxin type A free of complexing proteins (XEOMIN) in focal dystonia. Drugs 2007; 67:669.
  26. Frevert J, Dressler D. Complexing proteins in botulinum toxin type A drugs: a help or a hindrance? Biologics 2010; 4:325.
  27. Ramirez AL, Reeck J, Maas CS. Botulinum toxin type B (MyoBloc) in the management of hyperkinetic facial lines. Otolaryngol Head Neck Surg 2002; 126:459.
  28. Alster TS, Lupton JR. Botulinum toxin type B for dynamic glabellar rhytides refractory to botulinum toxin type A. Dermatol Surg 2003; 29:516.
  29. Kim EJ, Ramirez AL, Reeck JB, Maas CS. The role of botulinum toxin type B (Myobloc) in the treatment of hyperkinetic facial lines. Plast Reconstr Surg 2003; 112:88S.
  30. Sadick NS. Prospective open-label study of botulinum toxin type B (Myobloc) at doses of 2,400 and 3,000 U for the treatment of glabellar wrinkles. Dermatol Surg 2003; 29:501.
  31. Brandt F, O'Connell C, Cazzaniga A, Waugh JM. Efficacy and safety evaluation of a novel botulinum toxin topical gel for the treatment of moderate to severe lateral canthal lines. Dermatol Surg 2010; 36 Suppl 4:2111.
  32. Collins A, Nasir A. Topical botulinum toxin. J Clin Aesthet Dermatol 2010; 3:35.
  33. Chajchir I, Modi P, Chajchir A. Novel topical BoNTA (CosmeTox, toxin type A) cream used to treat hyperfunctional wrinkles of the face, mouth, and neck. Aesthetic Plast Surg 2008; 32:715.
  34. https://clinicaltrials.gov/ct2/show/NCT03004248 (Accessed on April 21, 2017).
  35. https://clinicaltrials.gov/ct2/show/NCT02939326 (Accessed on April 21, 2017).
  36. Flynn TC. Botulinum toxin: examining duration of effect in facial aesthetic applications. Am J Clin Dermatol 2010; 11:183.
  37. Murray C, Solish N. Botulinum toxin injections. In: Comprehensive dermatologic drug therapy, 2nd ed, Wolverton, SE (Eds), Elsevier Inc., 2007. p.851.
  38. Carruthers JD, Lowe NJ, Menter MA, et al. Double-blind, placebo-controlled study of the safety and efficacy of botulinum toxin type A for patients with glabellar lines. Plast Reconstr Surg 2003; 112:1089.
  39. Lowe NJ, Ascher B, Heckmann M, et al. Double-blind, randomized, placebo-controlled, dose-response study of the safety and efficacy of botulinum toxin type A in subjects with crow's feet. Dermatol Surg 2005; 31:257.
  40. Grimes PE, Shabazz D. A four-month randomized, double-blind evaluation of the efficacy of botulinum toxin type A for the treatment of glabellar lines in women with skin types V and VI. Dermatol Surg 2009; 35:429.
  41. Carruthers A, Carruthers J, Said S. Dose-ranging study of botulinum toxin type A in the treatment of glabellar rhytids in females. Dermatol Surg 2005; 31:414.
  42. Baumann L, Dayan S, Connolly S, et al. Duration of Clinical Efficacy of OnabotulinumtoxinA in Crow's Feet Lines: Results from Two Multicenter, Randomized, Controlled Trials. Dermatol Surg 2016; 42:598.
  43. Rubin MG, Dover J, Glogau RG, et al. The efficacy and safety of a new U.S. Botulinum toxin type A in the retreatment of glabellar lines following open-label treatment. J Drugs Dermatol 2009; 8:439.
  44. Brandt F, Swanson N, Baumann L, Huber B. Randomized, placebo-controlled study of a new botulinum toxin type a for treatment of glabellar lines: efficacy and safety. Dermatol Surg 2009; 35:1893.
  45. Kane MA, Brandt F, Rohrich RJ, et al. Evaluation of variable-dose treatment with a new U.S. Botulinum Toxin Type A (Dysport) for correction of moderate to severe glabellar lines: results from a phase III, randomized, double-blind, placebo-controlled study. Plast Reconstr Surg 2009; 124:1619.
  46. Xeomin [package insert]. Greensboro, NC: Merz Pharmaceuticals, LLC; 2011.
  47. Carruthers A, Carruthers J, Flynn TC, Leong MS. Dose-finding, safety, and tolerability study of botulinum toxin type B for the treatment of hyperfunctional glabellar lines. Dermatol Surg 2007; 33:S60.
  48. Sadick NS, Faacs . Botulinum toxin type B for glabellar wrinkles: a prospective open-label response study. Dermatol Surg 2002; 28:817.
  49. Flynn TC, Clark RE 2nd. Botulinum toxin type B (MYOBLOC) versus botulinum toxin type A (BOTOX) frontalis study: rate of onset and radius of diffusion. Dermatol Surg 2003; 29:519.
  50. Matarasso SL. Comparison of botulinum toxin types A and B: a bilateral and double-blind randomized evaluation in the treatment of canthal rhytides. Dermatol Surg 2003; 29:7.
  51. Lowe PL, Patnaik R, Lowe NJ. A comparison of two botulinum type a toxin preparations for the treatment of glabellar lines: double-blind, randomized, pilot study. Dermatol Surg 2005; 31:1651.
  52. Lowe NJ, Yamauchi PS, Lask GP, et al. Botulinum toxins types A and B for brow furrows: preliminary experiences with type B toxin dosing. J Cosmet Laser Ther 2002; 4:15.
  53. van Laborde S, Dover JS, Moore M, et al. Reduction in injection pain with botulinum toxin type B further diluted using saline with preservative: a double-blind, randomized controlled trial. J Am Acad Dermatol 2003; 48:875.
  54. Ranoux D, Gury C, Fondarai J, et al. Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry 2002; 72:459.
  55. Simonetta Moreau M, Cauhepe C, Magues JP, Senard JM. A double-blind, randomized, comparative study of Dysport vs. Botox in primary palmar hyperhidrosis. Br J Dermatol 2003; 149:1041.
  56. Trindade de Almeida AR, Marques E, de Almeida J, et al. Pilot study comparing the diffusion of two formulations of botulinum toxin type A in patients with forehead hyperhidrosis. Dermatol Surg 2007; 33:S37.
  57. Cliff SH, Judodihardjo H, Eltringham E. Different formulations of botulinum toxin type A have different migration characteristics: a double-blind, randomized study. J Cosmet Dermatol 2008; 7:50.
  58. Pickett A, Dodd S, Rzany B. Confusion about diffusion and the art of misinterpreting data when comparing different botulinum toxins used in aesthetic applications. J Cosmet Laser Ther 2008; 10:181.
  59. Kane M, Donofrio L, Ascher B, et al. Expanding the use of neurotoxins in facial aesthetics: a consensus panel's assessment and recommendations. J Drugs Dermatol 2010; 9:s7.
  60. Dressler D. [Pharmacological aspects of therapeutic botulinum toxin preparations]. Nervenarzt 2006; 77:912.
  61. Roggenkämper P, Jost WH, Bihari K, et al. Efficacy and safety of a new Botulinum Toxin Type A free of complexing proteins in the treatment of blepharospasm. J Neural Transm (Vienna) 2006; 113:303.
  62. Dressler D. Routine use of Xeomin in patients previously treated with Botox: long term results. Eur J Neurol 2009; 16 Suppl 2:2.
  63. Jankovic J. Clinical efficacy and tolerability of Xeomin in the treatment of blepharospasm. Eur J Neurol 2009; 16 Suppl 2:14.
  64. Dressler D. Comparing Botox and Xeomin for axillar hyperhidrosis. J Neural Transm (Vienna) 2010; 117:317.
  65. Sattler G, Callander MJ, Grablowitz D, et al. Noninferiority of incobotulinumtoxinA, free from complexing proteins, compared with another botulinum toxin type A in the treatment of glabellar frown lines. Dermatol Surg 2010; 36 Suppl 4:2146.
  66. Prager W, Wissmüller E, Kollhorst B, et al. Comparison of two botulinum toxin type A preparations for treating crow's feet: a split-face, double-blind, proof-of-concept study. Dermatol Surg 2010; 36 Suppl 4:2155.
  67. Allergan, Inc. Botox Cosmetic (botulinum toxin type A) purified neurotoxin complex (prescribing information). Allergan, Inc, Irvine, CA 2005.
  68. Feily A, Fallahi H, Zandian D, Kalantar H. A succinct review of botulinum toxin in dermatology; update of cosmetic and noncosmetic use. J Cosmet Dermatol 2011; 10:58.
  69. Klein AW. Complications, adverse reactions, and insights with the use of botulinum toxin. Dermatol Surg 2003; 29:549.
  70. Hsu TS, Dover JS, Arndt KA. Effect of volume and concentration on the diffusion of botulinum exotoxin A. Arch Dermatol 2004; 140:1351.
  71. Liu A, Carruthers A, Cohen JL, et al. Recommendations and current practices for the reconstitution and storage of botulinum toxin type A. J Am Acad Dermatol 2012; 67:373.
  72. Alam M, Dover JS, Arndt KA. Pain associated with injection of botulinum A exotoxin reconstituted using isotonic sodium chloride with and without preservative: a double-blind, randomized controlled trial. Arch Dermatol 2002; 138:510.
  73. Allen SB, Goldenberg NA. Pain difference associated with injection of abobotulinumtoxinA reconstituted with preserved saline and preservative-free saline: a prospective, randomized, side-by-side, double-blind study. Dermatol Surg 2012; 38:867.
  74. Hexsel DM, De Almeida AT, Rutowitsch M, et al. Multicenter, double-blind study of the efficacy of injections with botulinum toxin type A reconstituted up to six consecutive weeks before application. Dermatol Surg 2003; 29:523.
  75. Hui JI, Lee WW. Efficacy of fresh versus refrigerated botulinum toxin in the treatment of lateral periorbital rhytids. Ophthal Plast Reconstr Surg 2007; 23:433.
  76. Lizarralde M, Gutiérrez SH, Venegas A. Clinical efficacy of botulinum toxin type A reconstituted and refrigerated 1 week before its application in external canthus dynamic lines. Dermatol Surg 2007; 33:1328.
  77. Yang GC, Chiu RJ, Gillman GS. Questioning the need to use Botox within 4 hours of reconstitution: a study of fresh vs 2-week-old Botox. Arch Facial Plast Surg 2008; 10:273.
  78. Hexsel D, Brum C, do Prado DZ, et al. 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.
  79. Hexsel D, Dal'Forno T, Hexsel C, et al. A randomized pilot study comparing the action halos of two commercial preparations of botulinum toxin type A. Dermatol Surg 2008; 34:52.
  80. Karsai S, Raulin C. Current evidence on the unit equivalence of different botulinum neurotoxin A formulations and recommendations for clinical practice in dermatology. Dermatol Surg 2009; 35:1.
  81. Flynn TC. Advances in the use of botulinum neurotoxins in facial esthetics. J Cosmet Dermatol 2012; 11:42.
  82. Jandhyala R. Relative potency of incobotulinumtoxinA vs onabotulinumtoxinA a meta-analysis of key evidence. J Drugs Dermatol 2012; 11:731.
  83. Alam M, Geisler A, Sadhwani D, et al. Effect of Needle Size on Pain Perception in Patients Treated With Botulinum Toxin Type A Injections: A Randomized Clinical Trial. JAMA Dermatol 2015; 151:1194.
  84. Giordano CN, Matarasso SL, Ozog DM. Injectable and topical neurotoxins in dermatology: Indications, adverse events, and controversies. J Am Acad Dermatol 2017; 76:1027.
  85. Brin MF, Boodhoo TI, Pogoda JM, et al. Safety and tolerability of onabotulinumtoxinA in the treatment of facial lines: a meta-analysis of individual patient data from global clinical registration studies in 1678 participants. J Am Acad Dermatol 2009; 61:961.
  86. Naumann M, Jankovic J. Safety of botulinum toxin type A: a systematic review and meta-analysis. Curr Med Res Opin 2004; 20:981.
  87. Coté TR, Mohan AK, Polder JA, et al. Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol 2005; 53:407.
  88. LeWitt PA, Trosch RM. Idiosyncratic adverse reactions to intramuscular botulinum toxin type A injection. Mov Disord 1997; 12:1064.
  89. Li M, Goldberger BA, Hopkins C. Fatal case of BOTOX-related anaphylaxis? J Forensic Sci 2005; 50:169.
  90. Nong LB, He WQ, Xu YH, et al. [Severe respiratory failure after injection of botulinum toxin: case report and review of the literature]. Zhonghua Jie He He Hu Xi Za Zhi 2008; 31:369.
  91. Chertow DS, Tan ET, Maslanka SE, et al. Botulism in 4 adults following cosmetic injections with an unlicensed, highly concentrated botulinum preparation. JAMA 2006; 296:2476.
  92. Yiannakopoulou E. Serious and long-term adverse events associated with the therapeutic and cosmetic use of botulinum toxin. Pharmacology 2015; 95:65.
  93. Kuehn BM. FDA requires black box warnings on labeling for botulinum toxin products. JAMA 2009; 301:2316.
  94. US Food and Drug Administration. Information for health care professionals: onabotulinumtoxinA (marketed as Botox/Botox Cosmetic), abobotulinumtoxinA (marketed as Dysport) and rimabotulinumtoxinB (marketed as Myobloc). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174949.htm (Accessed on March 28, 2011).
  95. Food and Drug Administration. Early communication about an ongoing safety review: Botox and Botox Cosmetic (Botulinum toxin Type A) and Myobloc (Botulinum toxin Type B). 2008. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm070366.htm (Accessed on July 02, 2010).
  96. Rzany B, Dill-Müller D, Grablowitz D, et al. Repeated botulinum toxin A injections for the treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients. Dermatol Surg 2007; 33:S18.
  97. Mejia NI, Vuong KD, Jankovic J. Long-term botulinum toxin efficacy, safety, and immunogenicity. Mov Disord 2005; 20:592.
  98. Defazio G, Abbruzzese G, Girlanda P, et al. Botulinum toxin A treatment for primary hemifacial spasm: a 10-year multicenter study. Arch Neurol 2002; 59:418.
  99. Cohen JL, Schlessinger J, Cox SE, et al. An analysis of the long-term safety data of repeat administrations of botulinum neurotoxin type A-ABO for the treatment of glabellar lines. Aesthet Surg J 2009; 29:S43.
  100. Monheit GD, Cohen JL, Reloxin Investigational Group. Long-term safety of repeated administrations of a new formulation of botulinum toxin type A in the treatment of glabellar lines: interim analysis from an open-label extension study. J Am Acad Dermatol 2009; 61:421.
  101. Sattler G. Current and future botulinum neurotoxin type A preparations in aesthetics: a literature review. J Drugs Dermatol 2010; 9:1065.
  102. Jankovic J, Vuong KD, Ahsan J. Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia. Neurology 2003; 60:1186.
  103. Lee SK. Antibody-induced failure of botulinum toxin type A therapy in a patient with masseteric hypertrophy. Dermatol Surg 2007; 33:S105.
  104. Jankovic J, Schwartz K. Response and immunoresistance to botulinum toxin injections. Neurology 1995; 45:1743.
  105. Dressler D. New formulation of BOTOX. Complete antibody-induced therapy failure in hemifacial spasm. J Neurol 2004; 251:360.
  106. Dressler D, Wohlfahrt K, Meyer-Rogge E, et al. Antibody-induced failure of botulinum toxin a therapy in cosmetic indications. Dermatol Surg 2010; 36 Suppl 4:2182.
  107. Naumann M, Carruthers A, Carruthers J, et al. Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX®) across multiple indications. Mov Disord 2010; 25:2211.
  108. Lawrence I, Moy R. An evaluation of neutralizing antibody induction during treatment of glabellar lines with a new US formulation of botulinum neurotoxin type A. Aesthet Surg J 2009; 29:S66.
  109. Greene P, Fahn S, Diamond B. Development of resistance to botulinum toxin type A in patients with torticollis. Mov Disord 1994; 9:213.
  110. Carruthers J, Burgess C, Day D, et al. Consensus Recommendations for Combined Aesthetic Interventions in the Face Using Botulinum Toxin, Fillers, and Energy-Based Devices. Dermatol Surg 2016; 42:586.
  111. Coleman KR, Carruthers J. Combination therapy with BOTOX and fillers: the new rejuvnation paradigm. Dermatol Ther 2006; 19:177.
  112. Fagien S. Botox for the treatment of dynamic and hyperkinetic facial lines and furrows: adjunctive use in facial aesthetic surgery. Plast Reconstr Surg 1999; 103:701.
  113. Fagien S, Brandt FS. Primary and adjunctive use of botulinum toxin type A (Botox) in facial aesthetic surgery: beyond the glabella. Clin Plast Surg 2001; 28:127.
  114. Carruthers J, Carruthers A, Maberley D. Deep resting glabellar rhytides respond to BTX-A and Hylan B. Dermatol Surg 2003; 29:539.
  115. Carruthers J, Carruthers A. A prospective, randomized, parallel group study analyzing the effect of BTX-A (Botox) and nonanimal sourced hyaluronic acid (NASHA, Restylane) in combination compared with NASHA (Restylane) alone in severe glabellar rhytides in adult female subjects: treatment of severe glabellar rhytides with a hyaluronic acid derivative compared with the derivative and BTX-A. Dermatol Surg 2003; 29:802.
  116. Patel MP, Talmor M, Nolan WB. Botox and collagen for glabellar furrows: advantages of combination therapy. Ann Plast Surg 2004; 52:442.
  117. Carruthers A, Carruthers J, Monheit GD, et al. Multicenter, randomized, parallel-group study of the safety and effectiveness of onabotulinumtoxinA and hyaluronic acid dermal fillers (24-mg/ml smooth, cohesive gel) alone and in combination for lower facial rejuvenation. Dermatol Surg 2010; 36 Suppl 4:2121.
  118. Carruthers J, Carruthers A. Combining botulinum toxin injection and laser for facial rhytides. In: Skin Resurfacing, Coleman WP, Lawrence N (Eds), Williams and Wilkins, Baltimore, MD 1998. p.235.
  119. Worcester S. Use of Botox before and after laser facial resurfacing. Skin Allergy News 2000; 31:6.
  120. Zimbler MS, Holds JB, Kokoska MS, et al. Effect of botulinum toxin pretreatment on laser resurfacing results: a prospective, randomized, blinded trial. Arch Facial Plast Surg 2001; 3:165.
  121. Alster TS. Laser resurfacing of rhytides. In: Manual of Cutaneous Laser Techniques, Alster TS (Ed), Lippincott-Raven Publishers, Philadelphia, PA 19997. p.104.
  122. West TB, Alster TS. Effect of botulinum toxin type A on movement-associated rhytides following CO2 laser resurfacing. Dermatol Surg 1999; 25:259.
  123. Yamauchi PS, Lask G, Lowe NJ. Botulinum toxin type A gives adjunctive benefit to periorbital laser resurfacing. J Cosmet Laser Ther 2004; 6:145.
  124. MacGregor JL, Tanzi EL. Microfocused ultrasound for skin tightening. Semin Cutan Med Surg 2013; 32:18.
  125. Gassner HG, Sherris DA, Otley CC. Treatment of facial wounds with botulinum toxin A improves cosmetic outcome in primates. Plast Reconstr Surg 2000; 105:1948.
  126. Sherris DA, Gassner HG. Botulinum toxin to minimize facial scarring. Facial Plast Surg 2002; 18:35.
  127. Gassner HG, Sherris DA. Chemoimmobilization: improving predictability in the treatment of facial scars. Plast Reconstr Surg 2003; 112:1464.
  128. Gassner HG, Brissett AE, Otley CC, et al. Botulinum toxin to improve facial wound healing: A prospective, blinded, placebo-controlled study. Mayo Clin Proc 2006; 81:1023.
  129. Wilson AM. Use of botulinum toxin type A to prevent widening of facial scars. Plast Reconstr Surg 2006; 117:1758.
  130. Flynn TC. Use of intraoperative botulinum toxin in facial reconstruction. Dermatol Surg 2009; 35:182.