Botulinum A Toxin and Laser Therapy: Evidence and Recommendations for Combination Treatment

Botulinum toxin type A (BTX-A) is widely employed in the treatment of facial rhytids, facial asymmetry, and hyperhidrosis. Its pathophysiology involves presynaptic inhibition of acetylcholine release at neuromuscular junctions, causing targeted muscle paralysis. Its ease of use, efficacy, and excellent safety profile make it a popular treatment option in aesthetic practice.

Laser therapy is another widely utilized treatment modality in aesthetic practice, with proven benefit in treating facial rhytids, scars, and skin resurfacing. A variety of lasers are utilized, each targeting particular chromophores such as melanin, water, and hemoglobin, using specific wavelengths of collimated light to induce thermal, chemical, or mechanical changes in the respective tissue.¹ Lasers can be ablative, removing the epidermis and heating the dermis to stimulate collagen formation, as with carbon dioxide (CO2) and erbium lasers, or nonablative lasers, which are less aggressive and do not remove the epidermis, as with pulsed dye, Erbium:YAG lasers, and intense pulsed light (IPL).² Both ablative and nonablative lasers can be fractionated, producing microscopic columns of unaffected tissue within the treatment zone to accelerate recovery and minimize local side effects. There is evidence to suggest that routine adjunctive use of botulinum A toxin and laser therapy is more efficacious, and safer, than a single treatment alone (Table 1).

Table 1.

Literature Review of the Combined Use of Botulinum A Toxin and Laser Therapy

Study	Journal	Author	Year	Methodology	Results
Effect of botulinum toxin pretreatment on laser resurfacing results: a prospective, randomized, blinded trial3	Archives of Facial Plastic Surgery	Zimbler et al	2001	Prospective, randomized, blinded study of 10 patients. Patients had 1 side of their face injected with BTX-A 1 week before laser resurfacing on both sides of the face with either a CO2 Sharplan CO2 Silk Laser or a dual-mode Sciton Erbium Contour Laser. Follow-up was documented at 6 weeks, 3 months, and 6 months after laser resurfacing. Subjective evaluation was performed by a blinded observer using a visual analog scale. Posttreatment photographs were also graded by a blinded panel.	Sites pretreated with BTX-A showed statistically significant improvement vs nontreated side.
Botulinum toxin type A gives adjunctive benefit to periorbital laser resurfacing4	Journal of Cosmetic and Laser Therapy	Yamauchi et al	2009	Single-center, prospective, randomized, placebo-controlled study comparing the efficacy and safety of combining BTX-A injections with ablative laser resurfacing vs laser resurfacing alone in the treatment of periorbital rhytids. Total of 33 patients received intramuscular injections of BTX-A to 1 side of the face and saline injections to the contralateral side. Two to six weeks later, all patients received Erbium:YAG laser resurfacing to both sides of the face. Physician grading of severity was assessed based on an established scoring system.	The periorbital rhytids on the side treated with BTX-A and laser resurfacing improved significantly more than those on the contralateral area, based on physician grading.
Pulsed dye laser followed by intradermal botulinum toxin type-A in the treatment of rosacea-associated erythema and flushing5	Dermatologic Therapy	Al-Niaimi et al	2020	Total of 20 patients treated for acne rosacea with pulsed-dye laser immediately followed by intradermal injections of BTX-A. Three treatments were performed, with 4-6 weeks in between treatments. Standardized photographs compared pretreatment and posttreatment results, and an Antera 3D camera (Miravex, Dublin, Ireland) quantified erythema. Clinician's erythema grading scores were also measured pretreatment and posttreatment. Patients were followed up at 3 months and 9 months posttreatment.	All patients experienced an improvement in symptoms (erythema, telangiectasia, pruritus). Objective erythema measurement showed a marked reduction in erythema posttreatment. One patient experienced mild purpura lasting 10 days.
Prospective randomized controlled study to determine the effect of topical application of botulinum toxin A for crow’s feet after treatment with ablative fractional CO2 laser6	Dermatologic Surgery	Mahmoud et al	2015	Prospective, randomized controlled trial with 10 patients. Treatment to both sides of the face with Ultra-Pulse fractional ablative carbon dioxide laser followed by the application of topical BTX-A on 1 side and normal saline as a control on the other side. Pretreatment assessment was performed, as well as assessment at 1 and 4 weeks after treatment.	Clinically significant greater degree of improvement in wrinkles after treatment with CO2 laser and topical BTX-A.
Clinical assessment of the safety and effectiveness of nonablative fractional laser combined with transdermal delivery of botulinum toxin A in treating periocular wrinkles7	Plastic and Reconstructive Surgery Global Open	Fan et al	2016	Total of 30 patients with periocular wrinkles treated with nonablative fractional laser therapy followed by BTX-A spray to the left periocular region. The right periocular region was sprayed with saline as a control. A VISIA skin detector (Canfield Scientific, Parsippany-Troy Hills, NJ) allowed photographs and comparison of changes. The Global Aesthetic Improvement Scale was utilized. Patients were followed up at 1 week and 1-6 months posttreatment.	Significant improvement of periocular wrinkles and skin flabbiness.

Zimbler et al's randomized blinded study reported a statistically significant improvement in facial rhytids at the different subsites that were treated with botulinum toxin injections followed by ablative laser therapy, compared to those treated with ablative laser therapy alone (P ≤ .05).³ The brands of laser included the Sharplan CO2 Silk Laser (ECS Sharplan Corp., Norwood, MA; λ = 10,600 nm) and the dual-mode Sciton Erbium Contour Laser (Sciton, Palo Alto, CA; λ = 2940 nm), with the choice of laser dependent on patient preference and Fitzpatrick skin type. This improvement in facial rhytids was sustained at the 6 month follow-up, with facial rhytids at the crow's feet subsite showing the most improvement. In a randomized, placebo-controlled study Yamauchi et al also found that periorbital rhytids treated with botulinum toxin and laser resurfacing showed more improvement compared to periorbital rhytids treated with laser resurfacing alone.⁴ The combination of BTX-A and adjunctive laser therapy has also been reported to improve the appearance of acne rosacea, with respect to the erythema, telangiectasias, and pruritus experienced by patients.⁵

Both ablative as well as nonablative laser therapies were considered in the studies. Yamauchi et al employed ablative laser resurfacing with Erbium:YAG (NaturaLase, Bethel, CT; λ = 1064, 532, 585, 650 nm); Zimbler et al utilized the Sharplan CO2 Silk Laser and a dual-mode erbium contour laser (Sciton Erbium Contour Laser); and Mahmoud et al used the Ultra-Pulse fractional ablative carbon dioxide laser (Lumenis Aesthetic, San Jose, CA; λ = 10,600 nm).^3,4,6 Al-Niaimi et al employed a pulsed-dye laser (Vbeam, Candela, MA; λ = 595 nm), and patients in Fan et al's study were treated with nonablative fractional laser therapy (Crown of the King, Lumenis; λ = 1565 nm).^5,7 The dose of botulinum A toxin also varied, ranging from 5 to 50 units, depending on the route of delivery and the brand of BTX-A. Patients in the study conducted by Al-Niaimi et al also received varying doses of BTX-A depending on the extent and severity of their symptoms.⁵

In two studies the topical form of BTX-A was utilized instead of the injected form.^6,7 Fan et al gave the risks associated with subcutaneous botulinum injections to the upper and lower eyelids as reason to assess the efficacy of topical BTX-A in treating facial rhytids in this region.⁷ The authors of the study demonstrated an improvement in the appearance of periocular wrinkles when topical BTX-A was provided in addition to nonablative laser resurfacing. Mahmoud et al reported that topical BTX-A alone was ineffective in treating facial rhytids, which led the authors to investigate whether using topical BTX-A as an adjunct with laser therapy improved its efficacy. The authors confirmed a more positive outcome with topical BTX-A as adjuvant therapy to ablative laser resurfacing.⁶

In both the randomized studies conducted by Yamauchi et al and Zimbler et al, ablative laser therapy was performed after treatment with BTX-A injections. In the study by Yamauchi et al, laser therapy was performed 2 to 6 weeks following injections with BTX-A, and in Zimbler et al's study laser therapy was performed 1 week after BTX-A.^3,4 There has often been uncertainty surrounding the order and temporality of BTX-A and laser therapy given in combination. One view is that laser therapy should be carried out before treatment with BTX-A because of concerns regarding deactivation of the botulinum toxin or diffusion of the BTX-A molecules by the laser, but there is little literature to support one way or the other.

Semchyshyn and Kilmer conducted a prospective study to investigate whether nonablative laser therapy inactivated botulinum toxin in the treatment of facial rhytids.⁸ The following lasers were included in the study: VBeam (Candela), SmoothBeam (Candela; λ = 1450 nm), Quantum IPL (Lumenis; λ = 560–1200 nm), CoolGlide (Cutera, Brisbane, CA; λ = 1064 nm), and the radiofrequency device ThermaCool TC (Solta Medical, Bothell, WA). No decrease in botulinum toxin efficacy was found when patients were treated with laser therapy immediately after BTX-A was injected compared to when laser therapy was performed before BTX-A was injected. Moreover, no other unwanted effects such as muscle paralysis to surrounding muscles occurred as a result of performing laser therapy immediately after BTX-A.

There is some support in the literature for the safe, concomitant use of botulinum toxin A and ablative or nonablative lasers in facial aesthetic practice, with the suggestion that combined use may be of more benefit than a single agent alone. Our report is limited to the limited availability of evidence. Although high-level studies such as prospective randomized control trials have been performed, and their data are included in this report, the patient numbers are too low for the conclusions to be entirely robust. In our experience, combination treatment is practical and safe. The lack of evidence regarding the temporality or order of treatments leaves the decision dependent on patient sensitivity, finances, clinic capacity, and regularity of follow-up. In our practice, we decide which agent to provide based on the patient's most pressing concerns, often with BTX-A treatment carried out first with a patch test, followed by laser therapy 1 week later. For regular patients, we opt for BTX-A injection before immediate laser treatment to minimize discomfort of BTX-A injection into more sensitive skin following laser treatment.

Disclosures

The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article.

Funding

The authors received no financial support for the research, authorship, and publication of this article.