A Small Study of the Relationship Between Abobotulinum Toxin A Concentration and Forehead Wrinkle Reduction FREE

Botulinum toxin A has been used in the cosmetic treatment of facial rhytids for decades. Previous studies have examined the role of volume and concentration on the spread of onabotulinum toxin A, both on and off the face, and on the treatment of dynamic rhytids¹ and muscle spasticity.² Our clinical experience suggests that abobotulinum toxin A may in fact spread differently than its counterparts. To determine if this was true, we treated 10 patients with each of 2 concentrations of abobotulinum toxin A to assess differences in rhytid reduction on contralateral sides of the forehead. We hypothesized that dilution may affect capacity of the toxin to spread to neuromuscular receptors, which may in turn affect surface area of effect.

After the research protocol was approved by the New England institutional review board, 10 patients, aged 35 to 65 years, with moderately severe forehead rhytids (Glogau II and III)³ were recruited to participate in a study involving the delivery of 6 U of abobotulinum toxin A (Dysport; Medicis) to the right and left forehead. On one side, 6 U were diluted in 0.1 mL of sterile preserved saline solution. On the other side, 6 U were diluted in 0.3 mL of sterile preserved saline solution. The product was diluted in a 20-mL syringe after extraction from its original bottle to achieve the dilutions required by the study protocol.

Subjects were randomized with regard to who received which concentration on a particular side, and on both sides the product was delivered to prominent horizontal rhytids measuring between 2.5 and 3.0 cm above the orbital rim in the mid-pupillary line (Figure 1). Abobotulinum toxin A was injected with minimal pressure at a 90 ° angle of incidence to a depth of approximately 1 mm below the surface of the skin. Exclusion criteria included pregnancy; history of botulinum toxin injection to the forehead in the prior 12 months or long-acting dermal filler injection (including silicon, Sculptra [sanofi-aventis], and Radiesse [Merz]) to the forehead at any time; history of neuromuscular disease or palsy; prior hypersensitivity to a botulinum toxin; and concomitant use of medications affecting neuromuscular blockade including aminoglycosides, anticholinesterases, lincosamides, and polymyxins.

All patients were photographed at rest and at maximum brow elevation, and distances from the orbital rim to the injection site were carefully measured. The same unblinded physician (N.R.A.) treated and photographed all subjects, while a separate, blinded physician (K.A.A.) recorded rhytid reduction on actual subjects (ie, not photographs) at 14 days post treatment. The blinded physician marked the horizontal and vertical extent of wrinkle reduction in millimeters around the original injection site with a red pen. Subsequently, wrinkle reduction was measured in millimeters squared on each side of the forehead, and the 2 treated sides were compared.

Nine men and 1 woman between the ages of 35 and 63 years were recruited. All participants experienced visible rhytid reduction to both sides of the forehead, and none had adverse reactions including bruising, headache, and eyebrow or eyelid ptosis.

Statistical analysis of rhytid reduction revealed a marked and statistically significant difference between contralateral sides of the forehead vis- à-vis abobotulinum toxin A concentration. Consistently, the more dilute concentration of the product produced a larger surface area of rhytid reduction. The more concentrated solution produced a mean wrinkle reduction of 476.6 mm², while the more dilute solution produced a mean wrinkle reduction of 794.1 mm² (Figure 2). P values for both data sets supported statistical significance. Paired t tests and box plot analyses confirmed these findings (data not shown).

Photographs revealed that the pattern of wrinkle reduction in most subjects did not exhibit a perfectly circular pattern but rather varied from ovoid to irregular, with some patients clearly exhibiting more wrinkle reduction on one side of the injection site.

There is no standard conversion ratio for comparing different formulations of botulinum toxins, making the comparison of one type with another difficult.⁴ Moreover, there is no consensus among practitioners whether low-volume/high-concentration injections of botulinum toxins or higher-volume/lower-concentration injections produce better clinical outcomes.⁵ While there are data to support the value of lower-concentration/ “more spread ” techniques in particular muscle groups including the frontalis muscle,¹ other studies report no advantage to variations in concentration of onabotulinum toxin A when treating periocular rhytids⁵ or muscle spasticity.² Abobotulinum toxin A diffusion has been little studied owing to its more recent emergence into clinical practice.

In certain clinical situations, such as in the injection of glabellar muscles, clinicians may be rightly concerned about unwanted spread producing complications including muscle ptosis. In the injection of larger or broader muscle complexes, including the frontalis, the concept of spread may prove advantageous to clinical outcome. The variation in spread across patients in a small study such as this one makes generalizations about product spread across a larger population difficult. However, our findings reinforce the principle that product diffusion is a complex phenomenon likely influenced by factors including bulk of muscle mass, dynamic movement of muscles, and actual dose delivered.

This study suggests that dilution of abobotulinum toxin A may help to improve delivery to a wider surface area and thus may allow clinicians to achieve desired clinical outcomes while using modest doses of toxin. Longevity of rhytid reduction on each side of the forehead was not assessed because the treatment resulted in marked asymmetry of rhytids at 2-week follow-up that required correction with additional product. Future studies to assess the relationship between product dilution and longevity would be useful, as would specific comparisons of the diffusion properties of different botulinum toxins used in medical practice.