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ic A. Narurkar, MD*,†

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he introduction of devices for noninvasive skin rejuve-nation has witnessed an unparalleled renaissance and

ny update in esthetic dermatology would not be completeithout a discussion of the technology available. A spectrumf minimally invasive approaches to device-based rejuvena-ion is available, including photomodulation, selective pho-othermolysis, fractional photothermolysis, and radiofre-uency (RF) skin tightening. This article will review aystematic approach to device based rejuvenation as mono-herapy and the utilization of devices as part of combinationherapy with botulinum toxins and semipermanent fillers.onablative devices can be divided into the following cate-ories (Table 1): (1) devices targeting pigmented lesions; (2)evices targeting vascular lesions; (3) devices targeting water;nd (4) combination devices. The 3 biologically significanthromophores are hemoglobin, melanin, and water. Tradi-ional device-based monotherapy is predicated on the theoryf selective photothermolysis in which devices are tailored toarget melanin, hemoglobin, or water. Coincidental thermalransfer of these targets capitalizes on nonselective heating,hich may contribute to the myriad of devices for nonabla-

ive rejuvenation. Nonablative rejuvenation is better defineds target-specific rejuvenation and nonablative skin remod-ling (NSR)1-3 is optimized when there is an optimal target,nd the goals are 3-fold: reduction in vascular anomalies,igmented anomalies, and improvement of static fine rhyt-

ds. Deeper rhytids are best addressed with ablative devices.

onotherapy for NSRNonablative Skin Rejuvenation)able 2 summarizes a systematic approach for using mono-

herapy for skin rejuvenation. It matches Glogau photoagingypes with additional cutaneous anomalies and creates anlgorithm for using devices either alone or in combination.he definition of photorejuvenation is the use of devices toepair environmental and sun-induced damage to the skin,4

Bay Area Laser Institute, San Francisco, CA.Department of Dermatology, UC Davis Medical School, Davis, CA.ddress correspondence to Vic A. Narurkar, MD, Ste. 505, 2100 Webster

tSt., San Francisco, CA 94115-2381.

085-5629/06/$-see front matter © 2006 Elsevier Inc. All rights reserved.oi:10.1016/j.sder.2006.06.007

ith the primary targets being anomalies of pigment andasculature and secondary targets being structural elementsf the skin such as pores, fine rhytids, distensible scars, skinexture and skin laxity. The mechanisms of NSR are multi-actorial and still controversial, specifically, what elementf NSR stimulates rejuvenation. Most devices use the prin-iples of photothermolysis, either selective or nonselective,hereby thermal destruction of targets produces collagen

timulation whereas newer devices use the principles of pho-omodulation, in which matrix metalloproteinase reductionay produce an upregulation in dermal collagen biosynthe-

is.

32-nm Lasersulsed 532-nm lasers primarily target hemoglobin and sec-ndarily target melanin. The development of continuousontact cooling enables greater epidermal protection. Sec-ndary NSR effects from long pulsed (LP) 532-nm lasers isocumented in the literature5-7 The fluence threshold forlearance of vascular lesions is significantly greater than forigmented lesions, and the primary benefits of these devicesre for vascular anomalies such as facial telangiectasias andosacea. Epidermal cooling is generally accomplished withontinuous contact cooling through as a sapphire window.xamples of 532-nm lasers include the Lasercope Aura andemini at 532 nm, the Lumenis Versapulse at 532 nm, the

ridex 532 diode laser, and the W Medart 532 diode laser.

85-nm/595-nm Lasershe flashlamp pulsed dye lasers (FPDLs) have been the goldtandard for the treatment of benign vascular lesions. Theurrent trend uses the longer wavelengths at 595 nm foreeper penetration. The primary target, like pulsed 532-nm

asers, are vascular targets, but with recent modifications toome FPDLS and with some manipulation of existing FPDLS,ome improvement of pigmented lesions has been observed.8

ooling is accomplished through a dynamic cooling devicer through cold air-refrigerated cooling. Examples includehe Candela V Beam, the Cynosure V Star and the USA Pho-

onics N lite laser. Zelickson and coworkers9 and Bjerring and

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oworkers10 have reported on the successful use of thePDLS for NSR, and histologic studies on dermal collagenemodeling at this wavelength are supported.11

-Switched Lasersswitching of lasers uses an optomechanical shutter to de-

iver ultrashort pulse duration, which produces a photo-coustic effect that is felt to be critical for the disruption ofargets such as dermal tattoos. These photoacoustic effectsay also influence NSR. Wavelengths used in Q switching

nclude 532 nm, 694 nm, 755 nm, and 1064 nm. The QS32-, 694-, and 755-nm wavelengths successfully treat pig-ented lesions12 whereas the QS1064-nm laser primarily

reats decorative tattoos and selected dermal melanocytic le-ions such as the Nevus of Ota/Ito.13 NSR with Q-switchedasers with histologic deposition of new collagen has beenell documented in the literature using a Q-switched064-nm laser.14,15 The shorter wavelength Q-switched la-ers primarily target pigment wherea the QS 1064-nm laserrimarily targets water. Combining QS532-nm/1064-nm la-er can achieve synergy with NSR.16 Examples of QS lasersnclude the Wavelight Sinon at 694 nm, the Candela Tatulazrt 755 nm, the Cynosure QS 755 nm laser, Lumenis VPC atS 532/755/1064 nm, and the Hoya Con Bio MedLite at QS32/1064.

able 1 Summary of Devices Based on Primary Chromophore

Chromophore: Melanin Chromopho

510-nm PL laser 532-nm p532-nm pulsed KTP laser 585nm/59QS 532-nm laser LP 755-nmQS/LP 694-nm laser LP 800-nmQS/LP 755-nm laser LP 1064-nLP 800-nm laser BroadbanBroadband light sources

able 2 Systematic Approach to Monotherapy for NSR

Glogau Type/Lesion I I

None ? LED ? Nonablatarget ?

Vascular Vascular lasers orpulsed light

Vascular lpulsed l

Pigment Pigment lasers orpulsed light

Vascular lpulsed lfraction

Vascular and Pigment Pulsed light Vascular lpulsed l

fractional

P Near Infrared LasersP near infrared lasers originally were developed for haireduction at wavelengths of 694 nm, 755 nm, 800 nm, and064 nm. The first 3 devices also show some improvement ofigmented lesions, although not quite as dramatic as whenhese wavelengths are Q switched.17,18 Improvement ofeeper vascular targets has been reported using a LP 755-nm,00-nm, and 1064-nm laser, with the LP 1064-nm laser pri-arily used for lower leg venulectasias.19 Deeper penetration

f the longer wavelengths, particularly at 1064 nm, makeshis an attractive wavelength for NSR, with lower coinciden-al absorption by melanin or hemoglobin, but also posesreater risk for full thickness scar formation at these longerulse durations if cooling is inadequate.20 NSR at these wave-

engths has been reported.21 Examples of LP near infraredasers include the Palomar Epilaser at 694 nm, CandelaentleLaser 755 nm, Cynosure Apogee at 755 nm and 1064m, Cutera CoolGlide at 1064 nm, Laserscope Lyra at 1064m, and the Wavelight Mydon at 1064 nm.LP mid-infrared lasers have no melanin or hemoglobin

bsorption and target primarily water. Examples include theool Touch 1320-nm laser, Candela Smoothbeam 1450-nm

aser, and Aramis 1540-nm laser. These devices were intro-uced primarily for NSR and initially received a great deal ofttention because of the undesirable side effects of ablative

et for NSR

emoglobin Chromophore: Water

KTP laser QS/LP 1064nm laserPD laser 1320-nm YAG laser

r 1450-nm diode laserr 1540-Er glass laserer 1550-Er doped fraxel lasersources Unipolar radiofrequency

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Lasers, light sources, and RF devices for skin rejuvenation 147

aser resurfacing. Neocollagen synthesis without overlyingpidermal damage has been reported histologically22-24 andubtle rhytids show improvement in the perioral and perior-ital areas. Shallow acne scar improvement has also beenocumented at these wavelengths.25 An interesting coinci-ental observation with the 1450 nm laser was improvementf acute acne,26 with the proposed mechanism being thermalodification of the sebaceous gland and reduction of seba-

eous hyperplasia.27

roadband Light Sourcesnlike lasers, broadband light sources are divergent poly-hromatic sources, which when first introduced were quiteontroversial. The initial device was developed for the treat-ent of leg telangiectasia and initially was met with much

kepticism as a reasonable device for esthetic applications.he versatility of broadband light was then demonstratedlinically and histologically28-31 and the last few years haveitnessed an unparalleled acceptance of these devices for

kin rejuvenation, especially with the development of greaterelectivity in filters and sophisticated platforms and optimalpidermal cooling. Intense pulsed light (IPL) is one of manyxamples of broadband light and is the most universally stud-ed and documented in the literature.32-34 The IPL device usesflashlamp in an optical treatment head and internal filter to

electively eliminate undesirable wavelengths, typically lesshan 500 nm and water surrounding the flashlamp to preventavelengths greater than 900 nm. Optical filters of variousavelengths further refine pulsed light systems. The main

argets for the majority of pulsed light systems are melaninnd hemoglobin, with the former being better resolved withraditional pulsed light systems. The newer generation ofulsed light systems allow for resolution of vascular targetsnly achievable with single wavelength lasers.35,36 These in-lude development of dichroic filters, photon recycling,mooth pulse delivery, and contact cooling with sapphire forptimnal epidermal protection (Fig. 1).NSR with PL systems is very well studied in the literature

nd the term “photorejuvenation” is often associated withPL, describing a nonablative method of using the IPL toeduced mottled pigmentation, telangiectasias and to im-rove textural anomalies of the skin. The term “photofacial”as been utilized to describe this process, particularly by theeneral public. Of all the devices documented for NSR, only

igure 1 Before and after pulsed light with dichroic filters for rosacea

nd telangiectasias. t

he IPL has long-term data of up to 5 years to support lon-evity of effects.37 Simultaneous improvement in pigmentnd vasculature, followed by subtle improvements in texture,ore size, fine rhytids, and shallow scars, is the desired end-oint after 3 to 5 treatments. Examples of PL include theumenis Quantum, Vasculight and Lume I, the DDD Ellipse,he Palomar Medilux and Starlux, the Cutera Xeo, and thelderm Prolite. A recent addition to this technology is the ad-ition of pneumatic energy to broadband light and the introduc-ion of photopneumatic therapy using lower cutoff filters of 400o 500 nm with suction to enhance dermal target delivery ofhotons. These shorter wavelength photons can reach deeperargets and produce excellent NSR results (Fig. 2).

ractional ResurfacingSR with water as the primary target, although promising,as yielded mixed results for resurfacing. Consistent resultsith nonablative devices typically have been for vascular andigmented lesion lasers and broadband light sources. Abla-ive resurfacing is diminishing in popularity because of un-anted risks and recovery time but remains the gold stan-ard to address severe photodamage and deep rhytids. Aovel technology that can be considered intermediary be-ween ablative and nonablative resurfacing is fractional pho-othermolysis. Fractional photothermolysis has been widelyaining clinical acceptance as a result of the plethora of clin-cal studies38-41 and impressive clinical results (Fig. 3) withhis technology. A midinfrarred laser at 1550 nm is employedith variable densities of 100- to 160-�m wide columns oficrothermal zones that can be adjusted to dermal penetra-

ions of 300 to 700 �m based on fluences.42 Treatment iserformed in a pixilated fashion, leaving approximately 70%f the skin undamaged to promote rapid healing. Unlike

igure 2 Before and after photopneumatic therapy for photodamagef chest.

igure 3 Before and after Fraxel fractional laser resurfacing of pho-

odamage of hands.

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onfluent epidermal ablation, which typically is performedy ablative lasers, or sporadic dermal remodeling, which typ-

cally is performed by pure nonablative lasers, fractional re-urfacing produces partial damage, thereby allowing forapid re-epithelialization. The stimulation of epidermal re-eneration and collagen remodeling produce clinically ap-arent rejuvenation that is consistent from patient to patient.linical applications for fractional resurfacing include skin

esurfacing (including nonfacial areas), treatment of acnecars and treatment of melasma. The Reliant Fraxel laser ishe first such device and most widely studied. Other exam-les of devices using fractional photothermolysis that areurrently in clinical trials include the Cynosure Affirm440-nm laser and Palomar Fractional 1540-nm laser. Thelinical studies and results with the Fraxel laser are consistentnd reproducible and may be the choice as monotherapy forSR where water is the primary target.

F and Infrared Heatinghe aforementioned technologies address NSR in a 2-dimen-ional fashion, ie, targeting dermal targets with secondaryffects of skin tightening. The only consistent method forreating soft-tissue redundancy as a primary target has beenurgical treatments such as rhytidectomy or blepharoplasty.he first nonsurgical treatment to address soft-tissue redun-ancy has been readiofrequency, with unipolar RF (Therma-ool by Thermage) the most widely studied and documentedechnology.43-46 RF is “color blind” and is not directed towardpecific dermal targets. Instead, RF produces controlled volu-etric heating of the deep dermis, with subsequent collagenenaturation and tissue shrinkage47 Clinical applications in-lude improvement of laxity of mid-face, lower face, neck,nd off-face areas such as the abdomen and knees.48 Theajor limiting factor for universal acceptance of this tech-ology has been the variability and unpredictability ofesults. Current studies are underway to optimize param-ters and enhance patient selection for greater consistencyf results.Another approach to collagen contraction is to use mid-

nfrared broadband light with epidermal cooling, either byulk heating such as with the Cutera Titan or by fractionaleating, as with the Palomar Lux IR. Limited peer-reviewedtudies exist to date, and clinical outcomes are variable asith unipolar RF.Unipolar RF carries some risks, such as subcutaneous at-

ophy and, thus, another approach for skin tightening is tose bipolar radiofreqency. The most widely studied bipolarF device uses electro-optical synergy with broadband lightSyneron Aurora; Israel) or with a diode laser (Syneron Po-aris)49-51 The theory is that combination of optical and bipo-ar RF energies allow for lower energies of both modalities tochieve target heating, thereby increasing safety and reducingiscomfort. A new technology employs bipolar RF with vac-um (Lumenis Aluma) to further refine bipolar RF and en-

ance safety and comfort. p

hotomodulationhe proposed mechanisms for collagen stimulation by NSRevices are predicated on thermal injury, regardless ofhether they are ablative, nonablative or fractional lasers, orF devices. A unique approach to NSR is nonthermal neo-ollagenesis through photomodulation. The most widelytudied device for photomodulation is a light-emitting diodeGentlewaves 590-nm LED; Light Bioscience LLC, Virginiaeach, VA)52,53 Mechanisms for LED photomodulation areediated by mitochondrial cytochrome light absorption.here is also evidence that combination of NSR thermal pho-

orejuvenation can be enhanced with NSR photomodula-ion54 whereby LED treatments are administered immedi-tely after photorejuvenation or Fraxel laser treatments for aynergistic effect.

ombination Therapyptimization of NSR can be accomplished by combiningevices and by combining NSR devices with botulinum toxinnd semipermanent fillers (Fig. 4). Although this may seemudimentary and is common practice, it has yet to be studiedidely. There is some evidence that there may be synergyetween botulinum toxin and intense pulsed light,55 as dem-nstrated in an elegant study by the Carruthers showing theynergy of broadband light and botulinum toxin A. Althought was obvious that each modality addressed different issuesIPL addressing the facial canvas and botulinum toxin A ad-ressing dynamic lines), what was surprising was the synergyf both and the enhanced photorejuvenation effects in theroup treated with botulinum toxin A. Studies are currentlynderway to determine if longevity of fillers and botulinumoxin A is enhanced after NSR because of enhanced collageneogenesis.

onclusionsSR is enjoying tremendous popularity. NSR monotherapy

s a best addressed in a systematic fashion, where devices,hen used alone, should be used in an appropriate fashionased on a careful interplay between Glogau photoaging anyther facial structural and canvas anomalies. Devices ad-ressing vascular and pigmented targets show the most im-

igure 4 Before and after intense pulsed light photofacials and bot-linum toxin A, synergistic effects.

ressive photographically documentable results whereas

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Lasers, light sources, and RF devices for skin rejuvenation 149

ractional photothermolysis shows the most consistent re-ults when resurfacing is indicated. Results are most variableor pure nonablative devices targeting water and for radiofre-uency technologies. Future refinements in these technolo-ies may address these limitations.

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