title: Botulinum A toxin (BOTOX) in the lower eyelid: dose-finding study.
abstract: BACKGROUND
  Botulinum toxin type A (BTX-A, BOTOX) is an excellent therapeutic option for hyperkinetic facial lines. It improves wrinkles by relaxing the muscles of facial expression, which underlie the rhytids. Periocular wrinkles such as lateral orbital rhytids respond well to treatment. BOTOX can be used in the lower eyelid to improve wrinkles and widen the eye.
  
  
  OBJECTIVE
  To determine whether there is additional benefit in using more than 2 U of BTX-A to improve infraorbital wrinkles and widen the eye.
  
  
  METHODS
  Nineteen women had BTX-A injected into the orbicularis oculi muscle. Eleven women had 4 U injected into the lower eyelid bilaterally, 3 mm below the ciliary margin, and 12 U of BTX-A injected into one lateral orbital (crow's feet) area. Eight patients had 8 U injected bilaterally into the lower eyelid and 12 U placed unilaterally into the crow's feet. Physicians and patients independently evaluated the degree of improvement (grade 3=dramatic improvement, grade 2=moderate improvement, grade 1=mild improvement, and grade 0=no improvement). Single investigator analysis was used to measure, in actual millimeters, the amount of increase in palpebral aperture. Side effects were noted.
  
  
  RESULTS
  Improvement was noted in lower eyelid wrinkles by both physicians and patients at both dose groups. When only the lower lid was injected, patients reported an improvement of 1.18 with 4 U and a grade of 1.63 with 8 U. When both the lower eyelid the lateral orbital area were treated, an improvement of 1.73 was reported with 4 U and a grade of 2.25 reported with 8 U in the lower eyelid. Physician evaluations had grades of 1.85 for 4 U alone and 1.85 with 8 U alone. Grades of 2.35 and 2.25 were obtained for 4 U plus 12 U and 8 U plus 12 U, respectively. An increase in palpebral aperture (IPA) occurred in all subjects. Subjects who received 4 U in the lower eyelid alone had a 1.8-mm IPA at rest and a 2.6-mm increase at full smile. Subjects who received 8 U of BTX-A alone in the lower lid had an IPA of 2.2 mm at rest and 2.9 mm at full smile. Eyes treated with 12 U in the bilateral orbital area plus 4 U in the lower eyelid had an IPA of 2.2 at rest and 4.5 mm at full smile. Those treated with 8 U in the lower lid plus the crow's feet had an IPA of 1.5 at rest and 4.0 at full smile. Side effects increased with dosage, with eight of eight subjects in the 8-U dose groups reporting bothersome side effects such as lower eyelid edema and incomplete sphincter function.
  
  
  CONCLUSIONS
  A dose-response curve is seen with increasing doses of BTX-A used in the lower eyelid. Treatment of the lateral orbital area in combination with the lower lid produces a synergistic response at lower doses, but at higher doses, a plateau effect is suggested. Although increasing doses of BTX-A increases eye widening, unattractive results and side effects are seen at higher doses. The authors recommend that lower 2- or 4-U doses of BTX-A be used in the lower eyelid and specifically discuss techniques.
authors.affiliation: Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. flynn@caryskincenter.com
authors.forename: Timothy Corcoran
authors.initials: TC
authors.lastname: Flynn
authors.forename: Jean A
authors.initials: JA
authors.lastname: Carruthers
authors.forename: J Alastair
authors.initials: JA
authors.lastname: Carruthers
authors.forename: Robert E
authors.initials: RE
authors.lastname: Clark
mesh_terms: D000293:Adolescent; D000328:Adult; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005143:Eyelids / Q000187:drug effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009465:Neuromuscular Agents / Q000008:administration & dosage*; D009801:Oculomotor Muscles / Q000187:drug effects*; D015595:Skin Aging / Q000187:drug effects*
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A