Just Accepted by Journal of Cosmetic and Laser Therapy

Are combined same-day treatments the future

for photorejuvenation? Review of the literature
of combined treatments with lasers, intense
pulsed light, radiofrequency, botulinum toxin
and fillers for rejuvenation
E. Cuerda-Galindo , M.A Palomar-Gallego ,
R. Linares-GarcíaValdecasas
doi: 10.3109/14764172.2014.968578
Abstract
J Cosmet Laser Ther Downloaded from informahealthcare.com by Allergan on 09/29/14

Background: Skin rejuvenation requires a treatment combination

including lasers, intense pulsed light (IPL), radiofrequency, botulinum
toxin (BT) and fillers. A combined approach is considered optimum
but usually same-day combined treatments are avoid and lasers are
performed prior to filler or toxin injections owing to the concern that
the light may inactivate or degrade them.Objective: to review the
literature on the use of combination treatments with radiofrequency,
IPL, non ablative and ablative lasers plus fillers or BT.Results: review
For personal use only.

of the literature identified 15 studies of combination treatments: three

of them on animal models and 12 were clinical studies. Seven
studies contained combined light system treatments with fillers and
eight studies combined physical therapies with botulinum toxin
injection. In all of them treatments were used as standard protocols.
Six studies documented no histological changes in fillers injected
after applying radiofrequency, IPL or laser treatments and one
studied documented improvement in collagen after IPL treatment
and toxin injection. These studies reported clinical improvement in
various features of photodamaged skin, no increase of adverse
effects and neither decrease on efficacy of substances injected.
Conclusions: review of the literature demonstrates safety of same
day combined treatments for rejuvenation, which improve clinical
results, are more comfortable for patients have no loss of efficacy or
other apparent adverse effect.

© 2014 Informa UK, Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and
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 Are combined same-day treatments the future
for photorejuvenation?

Review of the literature of combined treatments with lasers, intense pulsed light,
radiofrequency, botulinum toxin and fillers for rejuvenation

ED
E. Cuerda-Galindo 1, M.A Palomar-Gallego1 , R. Linares-GarcíaValdecasas1

1
Department of Human Anatomy and Embriology, Universidad Rey Juan Carlos, Madrid, Spain
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Corresponding author: Dr. Esther Cuerda-Galindo, Department of Human Anatomy and Embriology,
Universidad Rey Juan Carlos, Avda Atenas sn 28922 Alcorcón, Madrid, Spain, Tel: 0034 914889027,
Fax: 0034 914888831, e-mail: esther.cuerda@urjc.es

Short title: Review of the literature of combined treatments

CE
Abstract
For personal use only.

Background: Skin rejuvenation requires a treatment combination including lasers, intense pulsed light
(IPL), radiofrequency, botulinum toxin (BT) and fillers. A combined approach is considered optimum but
usually same-day combined treatments are avoid and lasers are performed prior to filler or toxin
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injections owing to the concern that the light may inactivate or degrade them.Objective: to review the
literature on the use of combination treatments with radiofrequency, IPL, non ablative and ablative lasers
plus fillers or BT.Results: review of the literature identified 15 studies of combination treatments: three of
them on animal models and 12 were clinical studies. Seven studies contained combined light system
treatments with fillers and eight studies combined physical therapies with botulinum toxin injection. In all
of them treatments were used as standard protocols. Six studies documented no histological changes in
fillers injected after applying radiofrequency, IPL or laser treatments and one studied documented
improvement in collagen after IPL treatment and toxin injection. These studies reported clinical
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improvement in various features of photodamaged skin, no increase of adverse effects and neither
decrease on efficacy of substances injected.Conclusions: review of the literature demonstrates safety of
same day combined treatments for rejuvenation, which improve clinical results, are more comfortable for
patients have no loss of efficacy or other apparent adverse effect.

Keywords: combined treatments; fillers; botulinum toxin; laser; intense pulsed light; radiofrequency
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 Introduction
In recent years an increasing number of treatments to improve the appearance of aging skin have
been developed1 including botulinum toxin, fillers and laser or intense pulsed light (IPL) devices.
There is a growing demand for non-invasive procedures with both minimal downtime and minimal
adverse effects2.
Patients demands for cosmetic improvement of skin texture, pigmentation and rhytides. A combined
treatment is necessary for many patients because it targets various regions of the face and treatments
supplement each other3.

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Combined treatments with lasers and injected substances are frequently used. Laser therapy is often
administered some days after filler implantation or toxin injection, but the apprehension regarding
concomitant treatment with filers-botulinum toxin and laser-IPL-radiofrequency (RF) is not
supported by documented research. It has been proposed that light could interact with tissue, filler or
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toxin, producing some changes in clinical results or effects lasting. When combining treatments it is
necessary to be sure that this combination improves clinical results without adverse effects.
In this paper we examine the existing literature evaluating combined treatments with lasers or lights
systems and fillers or botulinum toxin.
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Treatments combining laser, IPL and fillers
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Some authors have researched on the effects of lasers and IPL in animal models when filler is
injected. England et al. 4 used a monopolar radiofrequency (RF) treatment over soft-tissue filers in a
juvenile pig model over a period of 4 months. They used a ThermalCool TC system (Thermage, Inc.,
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Hayward CA). Fillers used were Cosmoplast (a highly purified collagen derived from human
fibroblast), Restylane (hyaluronic acid), Sculptra (polylactic acid), Radiesse (with spherum of
calcium hydroxylapatite) and Silikom (liquid injectable silicone). Fillers were injected immediately
preceding or 1 month preceding RF treatment. The authors found no apparent increase in the risk of
local burns and no effects of RF treatment on fillers persistence in the tissue.
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The same researcher group 5 studied the effects of a monopolar system, ThermalCool TC system
(Thermage, Inc., Hayward CA), combined with the same fillers: Cosmoplast (a highly purified
collagen derived from human fibroblast), Restylane (hyaluronic acid), Sculptra (polylactic acid),
Radiesse (with spherum of calcium hydroxylapatite) and Silikom (liquid injectable silicone). In this
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study they performed histological biopsies 5 days, 2 weeks or 1 month after radiofrequency
treatment and concluded that no thermal effect of RF was observed histologically and that RF
treatment increased the inflammatory, foreign body and fibrotic responses associated with fillers.
Farkas et al. 6 examined the effect of laser and IPL systems on hyaluronic acid fillers in porcine
models. The used 3 different hyaluronic acids (Restylane, Perlane and Juvéderm) and lights systems
examined were the Sciton IPL with a 560 nm filter (Sciton, Aplo Alto, CA), Sciton Nd:YAG 1064
(Sciton), Profractional (Sciton), Lux1540 Er:Glass, Palomar erbium 2940 (Palomar Medical
Technologies, Burlington, MA) and the ActiveFX and DeepFX (Lumenis, Yokneum, Israel).
 Following laser treatment punch biopsies were collected. Authors reported that fillers were
unaffected by the non-ablative laser or light and superficial ablative treatments. The aggressive
deeper treatments demonstrated laser-filler interaction with evidence of migration of filler into the
ablated microchannels and microablation columns were in direct contact with filler. They
recommend, when an aggressive deep resurfacing is planned, to treat patients first with laser, before
the soft tissue injections, to maximize the treatment effect of each modality.
Some authors have reported 7 that exposure to CO2 laser of liquid silicone injected in cultured
human skin, produces flaring of silicone. They demonstrated histologically that silicone fluid

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contaminates the full soft tissue through which the needle passes and if tissue is exposed to CO2
laser, silicones injected and contaminated tissue can flare.
Alam et al 8 treated five patients with injections of Restylane (hyaluronic acid derivative) and
Radyese (calcium hydroxyapatite) and applied monopolar radiofrequency 2 weeks later ThermalCool
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TC system (Thermage, Inc., Hayward CA). Skin biopsies were obtained and they concluded that
applying RF after deep dermal injection with hyaluronic acid or calcium hydroxyapatite does not
appear to cause changes in the filler material.
Some authors 9 performed a randomized trial in 36 patients to determine the influence of laser
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therapy, monopolar RF and IPL treatment after hyaluronic gel implantation (Restylane) in nasolabial
For personal use only.

folds. They treated one-half face only with hyaluronic acid and other side with hyaluronic acid
injection and laser-light treatment. The devices used were 1320 nm Nd:YAG (CoolTouch, New Star
Lasers, Rosemont, CA), 1450 nm diode (Smoothbeam, Candela Laser, Wayland, MA), monopolar
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RF (ThermalCool TC system,Thermage, Inc., San José, CA) and IPL with 560 nm cutoff filter
(Lumenis One, Lumenis, Santa Clara, CA). Skin biopsies were performed at postoperative days 0, 14
and 28 in every patient and histological changes were not apparent. There were no statistically
significant differences in wrinkle severity score in those areas treated with hyaluronic acid alone and
those treated with concomitant hyaluronic acid, laser, RF or IPL. The authors concluded that laser;
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RF and IPL treatments can be administered immediately after hyaluronic acid injection without
reduction in clinical effect.
Ribé et al 10 studied histological and clinical changes after combined therapy with a fractional non-
ablative laser (Affirm, Cynosure, Inc., Westford, MA, USA) and hyaluronic acid (Restilane Vital
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Light) for neck skin rejuvenation in 9 patients. Treatment consisted of hyaluronic acid administration
immediately followed by laser treatment and they conclude that laser produce epidermal and
superficial dermal changes whereas the hyaluronic acid injected acts deeper.
Park et al 11 performed a split-face ramdomized study with 12 patients treated with hyaluronic acid
on nasolabial folds and with a non-ablative infrared device on the experimental side of the face. They
used Teosysal (Teoxane) and 2 sessions of infrared, one of them immediately after filler injection.
They did not find collagen fiber increase on histologic assessment immediately after infrared
 treatment and affirmed that both treatments may be applied safely but they did not find more
improvement when both treatments were used instead of hyaluronic acid injection alone.
Recently, a study of 90 patients treated with IPL (560 or 590 nm cutoff filters, Lumenis 1 or Lumenis
M22, Lumenis Ltd, Yokneam, Israel) immediately before or 6 days after poly lactic acid injection
(Sculptra) has been reported 12. Patients received an average of 1,63 (range 1-5) combined
treatments. The authors found not adverse effects or formation of nodules and found more patient
satisfaction in combined treatments sessions. Number of sessions roughly correlated with patient
satisfaction. They concluded that combination of poly lactic acid injection and IPL in

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photorejuvenation of the face is safe and effective.
Treatment combining botulinum toxin and laser/IPL/RF treatments
There are several publications discussing the combined use of laser or IPL systems and botulinum
toxin (BT) 13. Carruthers et al 14 performed a prospective, randomized study of 30 women crow’s feet
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rhytides. Half of the subjects were treated with botulinum toxin and a broad-based light (BBL) and
the other half with BBL alone. Their response was assessed clinically and photographically and skin
biopsies of the temporal area were taken from two subjects in each group. Patients treated with a
combination of BT and BBL experienced a better response to treatment, as well as a slightly
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improved response in associated lentigines, telangiectasia, pore size, and facial skin texture
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compared with patients who received BBL treatment alone. Skin biopsies showed an increase in
dermal collagen in each group.
A prospective, randomized, placebo controlled study was performed by Yamauchi 15 in 33 patients.
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They compared the efficacy and safety of combining BT (18 units per area) with erbium laser
treatment versus laser alone in the treatment of periorbital rhytids. The results demonstrated that
combining BT and erbium resurfacing improved significantly more than the contralateral area treated
with saline and laser the periorbital wrinkles.
To determine whether the use of non-ablative laser or IPL immediately following BT injections,
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inactivate BT, Semchyshyn et al. performed a study 16. Nineteen subjects received BT injections to
either the glabellar or crow’s-feet areas. One side of the treated glabellar or periorbital area was
treated with lasers, IPL and radiofrequency devices within 10 minutes of BT injection. Pretreatment
and 2-week post-treatment photographs were compared. Authors concluded that patients may be
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treated with non-ablative lasers, IPL or RF devices immediately after BT injection without loss of
efficacy or other apparent untoward effect.
Beer et al17 published a case report of a patient who received BT injection one day prior to be treated
with a fractionated laser (Palomar Medical Technologies Inc). They noted significant improvement
of rhytides.
A prospective, randomized, double-blind, split-face study to evaluate combined BT injection and IPL
treatment of the cheeks was performed by Khoury et al. 18. Fifteen females received standard IPL
treatment and were randomly assigned to receive eight 0.1-mL intradermal injections of botulinum
 toxin in one cheek (8U total dose) and eight injections of saline in the contralateral cheek. A
significantly higher proportion of patients showed improvement in small wrinkles and fine lines with
IPL plus BT than IPL plus saline. Adjunctive BT also achieved a greater degree of improvement in
erythema (although statistical significance was not achieved). The authors concluded that the
adjunctive use of BT enhances the improvement in small wrinkles, and possibly erythema, achieved
with IPL alone.
One interesting research was performed by Paul et al 19 for studying the possible interference of
combined hair removal laser systems and BT injections for the axillary hyperhidrosis treatment. In a

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prospective, double blind, randomized cross over trial, nine patients were selected suffering from
primary axillary hyperhidrosis were treated with laser on one randomly assigned axilla. One week
later, both axilla were injected with 100 MU per axilla and treated with diode laser. No differences
were found regarding the effect of botulinum toxin on previously laser-treated and laser co-treated
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sides over time course for any of the outcome parameters. The authors concluded that concomitant
laser hair removal does not interfere with BT treatment on axillary hyperhidrosis and may be
combined during one treatment session.
Recently Zimbler et al performed a study with ten female patients 20. Patients had one side of their
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face injected with BT 1 week before laser resurfacing with either a CO2 and erbium dual mode laser.
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Hyperdynamic facial lines, pretreated with botulinum toxin before laser resurfacing, heal in a
smoother rhytid-diminished fashion. The authors found that these results were clinically most
significant in the crow’s feet region and even they conclude recommending pretreatment of
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movement-associated rhytides with BT before laser resurfacing.

Discussion
In many cases, patients are candidates for photorejuvenation with laser or light systems and fillers
and botulinum toxin 21-25.
Precautionary statements on the labeling for fillers products, advice against the use of laser
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treatments or any procedures that can induce and dermal response after injection because of the
possible risk of an inflammatory reaction at the implant site. At the same time is advised that the
healing of the skin with the procedure can accelerate filler or toxin elimination 26,27. This creates
apprehension regarding concomitant administration of injections with laser or light systems, based
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on the unconfirmed fear of denaturation of the implant material. Thus laser therapy is often delayed
to several days or weeks after the injectable has been placed 12.
Fillers
Level of deposit of injected substances must be considered. Some substances are deposited in deep
layers while others must be injected in superficial ones. Most of authors do not find clinical neither
histological changes after laser treatments. However some authors have reported interaction between
CO2 laser and silicone 7 and recently one author has reported calcium hydroxilapatite nodule
 resolution after fractional CO2 laser 28. These facts can indicate that type of filler and deep of
injection must be considered.
Laser, IPL or RF treatment must be considered. Regarding to non-ablative or soft ablative treatments
most of the authors agree that the combination is safe. RF treatment over areas recently injected with
fillers does not appear to disrupt the product (table 1). As the same way, fillers combined with IPL in
the same session have been proved as safety with not apparent histologic changes as is summarize in
table 2.
Some authors find clinical improvement when combining treatments12. Other authors only have

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demonstrated no adverse effects or filler degradation, but no clinical improvement when filler and
laser are used in same-day treatment have been found9,11.
Studies of fillers combined with ablative treatments have demonstrated different conclusions. Some
authors find some changes in filler when an aggressive ablative laser treatment is applied 7,9 while
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other authors 10 find no changes when combining a non-reticulated filler with a subablative laser.
More studies are needed to confirm safety of combination in the same treatment fillers and ablative
lasers but the risk of an adverse interaction seems to be higher for deeper lasers.
Botulinum toxin
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Treatments combining IPL and botulinum toxin are summarized in table 3. Authors find more
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improvement and they argue that the reason is because each treatment acts in different targets such as
wrinkles, lentigines, laxity or telangiectasia. Some authors inject toxin prior IPL treatment 14,16 and
other authors apply IPL prior toxin injection 18.
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In table 4, BT duration when combining light treatments is studied. Authors they do not find any
differences when toxin is injected prior laser treatment. When toxin is injected one of the
recommendations given to the patient is not to massage area after 24 hours treatment. Of course
when a laser, RF or IPL treatment is applied, the area is manipulated and massaged but no dispread
of product or adverse effects regarding toxin migration have been report. It would be helpful to
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perform more clinical studies to research on the safety, duration and lack of spreading of product if
the area is manipulated after injection.
In table 5 a summary of ablative lasers treatments combined with BT injection is detailed. All
authors agree with the idea that is mandatory to associate toxin and ablative laser because it improves
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wound healing and toxin potentiates laser treatment. Toxin paralyzes muscle action and it improves
collagen synthesis which potentiates laser effects. In some cases, toxin has been injected prior
ablative treatment 17,20 and other authors have injected toxin after laser treatment 13,15. It is necessary
to perform more clinical studies comparing ablative laser combined with toxin injection prior or after
laser treatment.
Conclusions
Combined treatments for photorejuvenation are highly demanded by patients 31,32 and same-day
treatments are becoming popular 33-35.
 Combined treatments in the same session with fillers injections and RF, IPL or non- ablative lasers
have demonstrated to be safe but not all authors find clinical improvement when same-day
treatments are used. More studies are needed to confirm safety of combined aggressive laser
treatments are combined with fillers because some authors have reported filler degradation or flaring
product.
The level of penetration of rejuvenation laser techniques, the level of deposit of injected substance
and the kind of filler must be considered for selecting the most adequate technique and filler.
When a laser, RF or IPL treatment are applied after BT injection, spread has not been reported

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neither adverse effected related. In case of ablative lasers is recommended to associate treatment to
BT injection because better results are obtained but more studies are need to confirm the best time
for toxin injection, prior or after ablative laser treatment.
Diclosures: none
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combination with bilateral crow's feet Botulinum toxin type A chemodenervation. Dermatol Surg
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34. Ascher B, Talarico S, Cassuto D, Escobar S, Hexsel D, Jaén P et al. International consensus
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35. Thioly-Bensoussan D. A new option for volumetric restoration: poly-l-lactic acid. J Eur Acad
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 Table Legends
Table 1: radiofrequency combined with fillers
Authors Treatment Clinical efficacy Histological changes
England et al4 Cosmoplast Juvenil pig model RF increases the
Shumaker et al5 Restylane inflammatory, foreign body
Sculptra and fibrotic responses of
Radiesse fillers
Silikom
Alam et al8 Restylane Not evaluated Not changes in filler material
Radiesse
Goldman et al9 Restylane No statistically significant Not apparent histologic
differences between wrinkle changes
severity or global aesthetic

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scores
Park et al11 Teosyal Combining treatment does not Fillers unaffected
appear to be superior
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For personal use only.

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Table 2: IPL combined with fillers

Authors Treatment Clinical Efficacy Histological changes

Farkas et al6 Restylane Porcine models Fillers unaffected
Perlane
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Juvederm
IPL 560 nm (Sciton)
Goldman et al9 Restylane No statistically significant Not apparent histologic
IPL 560 nm (Lumenis) differences between wrinkle changes
severity or global aesthetic
scores
Fabi et al12 Sculptra 86.7% of patients satisfied No evaluated
IPL 560 nm or 590 nm with combined treatment
(Lumenis)
 Table 3: IPL combined with toxin

Author Treatment Location Clinical results

Carruthers et al14 Toxin and IPL Periocular Similar results in crow’s feet. Improvement
10 minutes later in telangiectasia, pore size, erythema and
lentigo.

Semchyshyn et al16 Toxin and IPL Glabellar or No loss of efficacy after IPL treatment
immediately crow’s-feet
after areas
Khoury et al18 First IPL and Cheeks Improvement in small wrinkles and fine
immediately lines with IPL plus BTX. Adjunctive BTX
botulin toxine also achieved a greater degree of
injection improvement in erythema.

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Table 4: effectiveness of toxin after laser treatment

Author Treatment Location Inactivity toxin

Semchyshyn et al16 Toxine, VBeam laser, Glabella, Not founded
Smothbeam laser, Cool forehead and
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Glide laser , IPL and crow’s feet

radiofrequency
Paul et al19 Toxin treatment for Axilas Not founded
hyperhidrosis and hair
removal with diode laser
 Table 5: combination treatment ablative laser and toxin

Author Treatment Location Results

West et al13 Toxin and CO2 Glabella, forehead Improvement of dynamic rhytids.
laser and crow’s feet Long-lasting results of CO2 laser.
Yamauchi et al15 Toxin and Crow’s feet Botox-treated side with laser
Er:YAG 2-6 resurfacing improved significantly
weeks later more in diminishing periorbital rhytids
as well as textural, pigmentation, and
other features of periorbital skin aging.
Beer et al17 Toxin and CO2 Crow’s feet Significant wrinkles improvement after
treatment one day the first treatment.
after injection Authors recommend pretreatment of
movement-associated rhytids with

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botulinum toxin before laser
resurfacing.
Zimbler et al20 Toxin injection Glabella, forehead More significant improvement in all
one week prior and periocular sites pretreated with botulinum toxin,
ablative laser with the crow’s feet region showing the
resurfacing greatest improvement.
J Cosmet Laser Ther Downloaded from informahealthcare.com by Allergan on 09/29/14

Er:YAG, CO2 or Authors recommend pretreatment of

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dual mode movement-associated rhytids with
botulinum toxin before laser
resurfacing.

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For personal use only.

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