The Safety and Efficacy of Botulinum Toxin Type A Plus Tazarotene 0.1% Cream in the Treatment of Lateral Canthal Rhytids: A Randomized,Double-Blind,Placebo-Controlled Study

Abstract

Background:

Prior studies have established that botulinum toxin type A (BTX-A) is a safe and effective treatment of coarse dynamic rhytids. However, BTX-A has little known effect on the mottled hyperpigmentation, tactile roughness, skin thinning, and fine wrinkles that develop on periorbital skin as a result of cumulative photodamage. In contrast, topical retinoids have demonstrated the capacity to reverse clinical signs of cumulative photodamage in a number of studies. We hypothesize that the combination of BTX-A plus a topical retinoid (tazarotene 0.1% cream) for the treatment of lateral canthal rhytids (crow's feet) may be synergistic.

Objective:

To evaluate the effect of tazarotene 0.1% cream on crow's feet and mottled hyperpigmentation after a single treatment with BTX-A.

Methods:

This is a 16-week, single-center, double-blind, randomized, placebo-controlled study comparing the safety and efficacy of a single 12-U bilateral injection of BTX-A (Botox, Allergan Inc, Irvine, Calif) into the lateral third of the orbicularis oculi muscle at day 0 followed by nightly application of tazarotene 0.1% cream (Avage, Allergan) to one side and placebo cream to the contralateral side. Lateral canthal rhytids and mottled hyperpigmentation were scored by blinded physician evaluators at baseline and monthly intervals based on physical examination of the subjects and high-quality digital photographs. Overall improvement and adverse side effects were rated by patients at each visit via a patient questionnaire.

Results:

Sixteen of 20 subjects (80%) completed the trial. The mean baseline wrinkle scores for the lateral canthal areas randomized to tazarotene or placebo cream were 3.53 and 3.41, respectively (3 = moderate wrinkling). There were no statistically significant differences in the wrinkle scores between the two groups at baseline (P = .54). According to the blinded physician evaluators, the decreases from baseline of the mean wrinkle scores at the end of the trial (day 112) were 1.37 and 0.75 for the tazarotene-treated and the placebo-treated groups, respectively. There was 1.8-fold greater improvement from baseline of the mean wrinkle score of the tazarotene-treated group compared with placebo at the completion of the trial (P < .001). Treatment satisfaction scores assigned by the subjects were consistent with the physicians' evaluations. At the end of the trial (day 112), the subjects saw 2-fold greater improvement from baseline on the sides treated with tazarotene 0.1% cream versus those treated with placebo cream (P < .001). The mean mottled hyperpigmentation score for the sides randomized to tazarotene treatment improved 40%, from 4.07 (severe) at baseline to 2.4 (2 = mild, 3 = moderate) at the end of the trial (P < .001). Adverse side effects were few and transient and did not cause any subject to discontinue the study.

Conclusion:

Our results suggest that the therapeutic combination of BTX-A plus topical tazarotene 0.1% cream is a safe and more efficacious treatment of crow's feet and mottled hyperpigmentation than BTX-A treatment alone.