Aesth Plast Surg (2009) :28 294 DOI 10.1007/s00266-009-961-9 REVIEW Nonsurgical Nonablative Treatment of Aging Skin: Radiofrequency Technologies Between Aggressive Marketing and Evidence-Based Efficacy Bishara S. Atiyeh Æ Saad A. Dibo Received: 16 August 2008 / Accepted: 6 April 2009 / Published online: 1 May 2009 Ó Springer Science+Business Media, LLC and International Society of Aesthetic Plastic Surgery 2009 Abstract The gold standard treatment for the many aesthetic aspects of aging has for many years been surgery in its many forms. However, with increasing patient demand for cosmetic rejuvenation and with the strong desire and drive by patients to attain aesthetic enhancement with minimal risk and rapid recovery, there has been a strong surge inspiring the field of nonsurgical skin rejuvenation. Traditionally, most of the nonsurgical methods have centered around those that destroy the epidermis and cause a dermal wound, with resultant dermal collagen remodeling and secondary skin tightening and rhytid improvement. Currently, there is growing interest in a wide range of nonablative interventions that, predictably, are claimed to rejuvenate skin and subcutaneous tissue safely and effectively. Although several nonablative systems have been cleared by the U.S. Food and Drug Administration (FDA) for the purpose of skin rejuvenation and despite significant reported improvement in the appearance of signs and symptoms of photoaging by relatively noninvasive means, the clinical results have been generally less than impressive, with most subjects showing only mild improvement. The current review aims at summarizing the various nonablative methods currently in use for skin rejuvenation and to evaluate the evidence-based efficacy of a particular nonablative radiofrequency (NARF) method: monopolar radiofrequency. B. S. Atiyeh (&) Division Plastic and Reconstructive Surgery, American University of Beirut Medical Center, Beirut, Lebanon e-mail: aata@terra.net.lb S. A. Dibo Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon Keywords Thermage Nonablative rejuvenation Radiofrequency With aging, collagen, which comprises more than 90% of the skin s total proteins, becomes disorganized [1]. In chronologically aged skin, atrophic epidermis is noticed, with flattening of the dermal epidermal junction and loss of rete pegs as well as decreased numbers of fibroblasts and levels of collagen. In contrast, photoaged skin can be associated with either increased epidermal thickness or pronounced epidermal atrophy. The most pronounced histologic change, however, is the accumulation of elastincontaining fibrils just below the dermal-epidermal junction known as solar elastosis [1]. Irrespective of the main underlying etiology, the gold standard treatment for the many aesthetic aspects of aging has for many years been surgery in its many forms [2]. However, many of the surgical procedures have significant risks, along with downtime of 2 to 6 weeks [2]. With increasing patient demand for cosmetic rejuvenation and with the strong desire and drive by patients to attain aesthetic enhancement with minimal risk and rapid recovery, there has been a strong surge inspiring the field of nonsurgical skin rejuvenation [2, ], which is gaining rapidly in popularity. Traditionally, most of the nonsurgical methods have centered around those that destroy the epidermis and cause a dermal wound, with resultant dermal collagen remodeling and secondary skin tightening and rhytid improvement [4, 5]. These methods have included dermabrasion, chemical peels, and, more recently, the char-free pulsed carbon dioxide (CO 2 ) and erbium-doped yttrium aluminum garnet (Er:YAG) lasers [4, 6].
284 Aesth Plast Surg (2009) :28 294 Differences in the regulation of pharmaceuticals compared with lasers, lights, and related methods have resulted in a consumer-led market for the latter two groups of treatments [7]. For years, ablative laser resurfacing has been considered the nonsurgical gold standard for improving clinical features of aging, generally referring to treatment with a CO 2 laser (10,600 nm), which works by vaporizing the epidermis and portions of the papillary dermis, inducing neocollagenesis. Such ablative lasers improve fine and some coarse wrinkles as well as overall dyspigmentation, lighten dark discolored under-eye circles, and generally ameliorate skin texture [1, 8]. All ablative methods, however, commonly lead to postoperative complications such as oozing, bleeding, infections, and downtime because the skin needs time to reepithelialize [4]. Another common complication from ablative systems is the occasional incidence of undesirable postinflammatory pigmentary changes [4] and possible scarring. In expert hands, ablative laser resurfacing has a long history of excellent results in the treatment of photo damage and other signs of cutaneous aging [9]. Many laser-, light-, and energy-emitting devices have been and still are used [10]. Recently, the popularity of ablative resurfacing seemed to decline with the public s understanding of the recovery time, potential complications, and sun avoidance required to sustain an optimal result [11]. Both surgeons and patients have become interested in even less invasive methods of rejuvenation [12], and many patients currently seek the least possible invasive treatments [1]. Interest is growing in a wide range of nonablative interventions that, predictably, are claimed to rejuvenate skin and subcutaneous tissue safely and effectively [7]. Many different laser- and light-based systems have been evaluated for more than half a decade for their ability to reduce photo damage and age-induced changes in a nonablative manner [14]. Attention is beginning to focus on the use of wavelengths that preserve the epidermis but deliver enough energy to promote rhytid improvement and skin tightening [4]. Currently, noninvasive, nonablative, no downtime methods of rejuvenation have even surpassed ablative methods in public demand [15]. The ability to produce focused thermal collagen denaturation in the superficial musculo-aponeurotic system (SMAS) to induce shrinkage and tissue tightening is another appealing new probable application of nonablative technologies that may have significant implications for aesthetic facial rejuvenation [16]. In fact, intense ultrasound energy to target the facial SMAS and produce discrete thermal injury zones in the SMAS while sparing adjacent nontargeted layers superficial and deep to the SMAS layer has been tested in human cadaveric facial tissue [16]. Clinical application of this principle surely will follow soon. The introduction of devices for noninvasive skin rejuvenation has witnessed an unparalleled renaissance [17]. Although several nonablative systems have been cleared by the U.S. Food and Drug Administration (FDA) for the purpose of skin rejuvenation [14] and despite significant reported improvement in the appearance of signs and symptoms of photoaging by relatively noninvasive means [1], the clinical results have been generally less than impressive, with most subjects showing only mild improvement [14]. The current review aims to summarize the various nonablative methods currently in use for skin rejuvenation and to evaluate the evidence-based efficacy of a particular nonablative radiofrequency (NARF) method: monopolar radiofrequency (Therma-Cool TC; Thermage, Haywood, CA, USA). Nonablative Rejuvenation: Optical and Radiofrequency Methods Laser resurfacing was introduced in the 1980s with continuous-wave CO 2 lasers. However, due to a high rate of side effects and possible scarring, short-pulse high-peak power and rapidly scanned focused-beam CO 2 lasers and normal-mode Er:YAG lasers were developed to vaporize skin in a precisely controlled manner. However, the prolonged 2-week recovery time and small but significant complication risk of these lasers prompted the development of fractional resurfacing to minimize risks and shorten recovery times [, 18]. Microablative fractional resurfacing thermally ablates microscopic columns of epidermal and dermal tissue in regularly spaced arrays over a fraction of the skin surface [, 10]. This approach has a faster recovery than ablative resurfacing []. Nonablative, or subsurface, remodeling represents the newest approach to improve photodamaged aging skin [4]. Nonablative laser resurfacing procedures are much less invasive than ablative lasers and have attracted much interest [1]. Dermal thermal injury is induced, with preservation of the epidermis []. This stimulates collagen production and remodeling with little or no healing time and less patient discomfort. These laser systems can be classified into three main groups: mid-infrared lasers that target the dermis and are used for nonablative resurfacing; visible lasers such as the pulsed dye laser and the pulsed 52-nm potassium titanyl phosphate laser, alone or in conjunction with the 1,064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser; and intense pulsed light sources [18 21].
Aesth Plast Surg (2009) :28 294 285 Nonablative rejuvenation, better defined as target-specific rejuvenation and nonablative skin remodeling (NSR) [17, 22, 2], is optimized when there is an optimal target [17]. Thus, nonablative devices can be divided into the following categories: devices targeting pigmented lesions, devices targeting vascular lesions, devices targeting water, and combination devices [17]. The three biologically significant chromophores are hemoglobin, melanin, and water [17]. Traditional device-based monotherapy is predicated on the theory of selective photothermolysis, in which devices are tailored to target melanin, hemoglobin, or water. Coincidental thermal transfer of these targets capitalizes on nonselective heating, which may contribute to the myriad of devices for nonablative rejuvenation [17]. Water provides an ideal absorption target for creating an even distribution of heat in the treatment volume [15]. In one of the first studies evaluating a nonablative approach to dermal remodeling, a 1,064-nm Q-switched Nd:YAG laser at 5.5 J/cm 2 and a -mm spot size was used to improve rhytids [4, 24]. The 1,064-nm wavelength results in relatively deep penetration of the skin, which is indicative of minimal laser tissue interaction [4]. The Q- switched Nd:YAG laser energy is not well absorbed by tissue water [4]. It targets primarily pigment in skin and is useful for removing benign pigmented lesions seen in photoaged and aged skin [1]. However, its effect can be potentiated by the use of a topical carbon-assisted solution [4, 25]. Subsequently the 1,20-nm wavelength was chosen because of its high scattering coefficient, which increases the Q-switched Nd:YAG laser subsurface remodeling capacity, improving rhytids without creation of a wound [4, 26]. Other nonablative lasers, such as the pulsed dye laser, also have been shown to improve dermal collagen [4]. An alternative source of energy used for the purpose of skin tightening involves infrared light applied in multisecond pulse width and low fluences in a virtually painless manner [15]. Wavelengths in the infrared light range from 1,100 to 1,800 nm. They have an appropriate penetration depth but require attenuation by filtering of the strongly absorbed wavelengths in the range from 1,400 to 1,500 nm [15]. Intense pulsed light is another light-based treatment, but it is not a true laser because it is composed of several different wavelengths [1]. Intense pulsed light sources are flashlamp devices that emit wavelengths of light between 550 and 1,100 nm [4]. Popular for facial rejuvenation, they are used to lighten lentigines and reduce telangiectases to achieve an overall blending effect. When used with a photosensitizer (photodynamic therapy), intense pulsed light and other light-based therapies may have a greater effect than the light source alone [1, 27]. Although radiofrequency (RF) energy has been used more than a century for a variety of medical applications [28], NARF monopolar RF (MRF) (Therma-Cool [Thermage]; Thermage, Inc., Hayward, CA, USA) is a recent addition to the armamentarium of nonablative devices in use shown to produce skin tightening [1, 15]. High fluences (70 150 J/cm 2 ) delivered in a short fixed pulse (B2. s) are typical NARF Therma-Cool system treatment parameters [29]. Monopolar RF energy has been used successfully to accomplish noninvasive skin tightening of the face, abdomen, and extremities [29]. If used properly, a 0.25-cm 2 treatment tip can be safely used even on human eyelids [11, 29]. Unlike most lasers, which target specific absorption bands of well-localized chromophores, the output of these devices is transformed into heat mainly by tissue water. As a result, the energy is dispersed to three-dimensional volumes of tissue at controlled depths. Epidermal cooling is mandatory with RF devices to ensure preservation of the superficial skin layers. The depth and dimensions of the heated region can be manipulated by varying parameters of the energy source and cooling system [0]. Unfortunately, pain is significant even at the lowest possible fluence capabilities of that machine because heat is delivered in an extremely short pulse (flash heating) [15]. Bipolar RF devices as well as combined approaches using light and RF represent yet a new and innovative approach to whole-body rejuvenation. Claimed synergistic results using combined methods are a major advantage of this technology [17, 28, 1, 2]. In summary, all the nonablative devices are used in a way that causes minimal or no injury to the epidermis, focusing the energy primarily in the dermis [14]. The full armamentarium of nonablative technologies includes lasers of several wavelengths, including 52 nm and shorter pulse widths of 585, 595, 1,064, 1,20, 1,450, and 1,540 nm as well as intense pulsed light and RF alone and in combination with each other []. Select nonablative optical lasers and other RF devices include the long-pulsed Nd:YAG (1,064 nm), 1,20 nm (CoolTouch; CoolTouch Inc., Roseville, CA, USA), RF (Thermage), Fraxel (Reliant Technologies, Mountainview, CA, USA) [1], and bipolar devices such as the Aurora and Polaris (Syneron Medical Ltd., Yokneam, Israel) [28]. It is apparent that each method has its benefits. Some devices are better at removing brown spots, whereas others may be better at treating accompanying vessels or erythema, and still others may be more effective at improving wrinkles, scars, or even acne. For this reason, the use of a single device may not provide optimal treatment, and combined nonablative rejuvenation techniques can be used for an individual with several concerns []. Unfortunately, although patients are in fact treated with multiple methods
286 Aesth Plast Surg (2009) :28 294 when undergoing nonablative treatment, studies have not investigated the use of various nonablative methods in combination []. Biophysics of Thermal Collagen Remodeling The ability to contract collagen with heat energy is not new in clinical medicine. Thermally induced contraction of collagen has been obtained favorably in sports medicine, altering the elongated shoulder ligaments responsible for shoulder instability [4, 5]. This concept with minimal or even no epidermal damage is extremely appealing. Immediate collagen contraction can be induced for aesthetic rejuvenation, treating skin laxity or other signs of aging on the face or body [15]. Collagen fibers are composed of a triple helix of protein chains, with interchain bonds creating a crystalline structure [15]. Studies indicate that collagen fibrils, when heated to the correct temperature over time, will contract due to breakage of intramolecular hydrogen bonds and may induce immediate tissue tightening [14, 6]. The crystalline triple helical structure transforms to an amorphous, random-coil structure [15]. The chains fold and assume a more stable configuration, creating thickening and shortening of the collagen fibers [15]. Exceeding the critical heat threshold, however, causes the collagen fibrils to denature completely [14, 6]. Too little heat will give rise to no effect, whereas too much heat can cause widespread cell death and protein denaturation, leading to scarring. Mild injury, on the other hand, appears to give rise to the overall production of new dermal ground substance [14, 7, 8]. Over time, remodeling of the photodamaged skin can be seen to give an improved histologic and clinical result [14, 7]. It is postulated that heated fibroblasts may be stimulated to produce collagen [9]. Dermal remodeling is thought to occur through increased collagen 1 deposition, with collagen reorganization into parallel arrays of compact fibrils. Such an effect might occur with both nonablative and ablative systems [4]. A temperature of 57 to 61 C often is quoted as the shrinkage temperature of collagen [15]. However, in fact, for every 5 C decrease in temperature, a 10-fold increase in time is needed to achieve a similar amount of collagen contraction [15]. Thus, no single shrinkage temperature exists, and the amount of contraction is determined by a combination of time and temperature. Studies suggest that for millisecond domain exposures, the shrinkage temperature is above 85 C, whereas for relatively long exposures of several seconds, the shrinkage temperature is in the range of 60 to 65 C [15]. A desired optimal combination of time and temperature can thus be chosen allowing maximal epidermal protection through continuous contact cooling [2, 15]. Unfortunately, it currently is still completely unclear whether controlled collagen denaturation/thermocontraction can be made to occur before significant cellular damage occurs [15]. Moreover, although no definitive study has shown the ideal depth for the treatment of skin laxity through collagen contraction, heating to a depth of 1 to 2 mm seems to target the dermal collagen fibers [15]. Nonablative Skin Remodeling The mechanisms of NSR are multifactorial and still controversial. It is not known specifically what element of NSR stimulates rejuvenation. Most devices use the principles of photothermolysis, either selective or nonselective, whereby thermal destruction of targets produces collagen stimulation [17]. Newer devices use the principles of photomodulation, in which matrix metalloproteinase reduction may produce an upregulation in dermal collagen biosynthesis [17]. Although cellular and molecular dermal responses achieved with nonablative laser treatments are currently not fully elucidated [40], two hypotheses as to how optical nonablative devices work are being proposed. (1) The light energy is absorbed by water, and perhaps by collagen, to cause a direct thermal effect on the dermal ground substance. (2) The light energy is absorbed by hemoglobin, melanin, or both, triggering the cutaneous vessels or adnexal structures to produce cellular mediators and growth factors that may stimulate a wound-healing response. It would also give rise to indirect heating of the dermis, causing a response similar to that of the first proposed mechanism [14]. Most frequently cited is the idea that heating of the dermis through absorption of optical laser energy may cause a dermal wound-healing response involving fibroblast activation and new collagen deposition [40, 41]. In addition, some researchers believe that certain types of laser energy, when absorbed by the dermal microvasculature, may lead to cytokine-mediated responses that induce collagen remodeling. Currently, the relative contributions of these and other potential mechanisms of action are not clear and may differ depending on the laser used [40]. Although responses vary greatly among patients, nonablative laser therapy may result in significant increases in type 1 procollagen messenger RNA expression and quantifiable alterations in molecules associated with remodeling of the dermal matrix [40]. Dermal collagen remodeling has been demonstrated by histopathologic examination of scars treated with a 585-nm pulsed dye laser [4, 42]. Radiofrequency devices generate heat with a mechanism somewhat different from that of the photothermal effect
Aesth Plast Surg (2009) :28 294 287 produced by optical lasers [4]. Heat is generated due to the natural resistance of tissue to the movement of electrons within an RF field (Ohm s law). This resistance, called impedance, creates heat relative to the amount of current (amps) and time (seconds) [4, 4]. Heat is produced when the tissue s inherent resistance (impedance) converts the electrical current to thermal energy. This reaction is dictated by the following formula: Energy ðþ¼i J 2 R T; ð1þ where I is current, R is tissue impedance, and T is time of application [28]. With RF, not only must the depth of energy penetration be considered, but also the fact that soft tissue is made up in multiple layers, including dermis, fat, muscle, and fibrous tissue, all with varying resistance to the movement of RF energy [4]. Impedance is of paramount importance in the understanding of why heat can reach a larger volume of tissue than through the planar heating obtained by nonablative optical lasers [4]. Structures with higher impedance are more susceptible to heating and thus to wounding [7]. Radiofrequency s mechanism of action is twofold in nature: an initial immediate collagen contraction and a secondary wound-healing response, which involves collagen deposition and remodeling with tightening over time. A sparse pattern of collagen denaturation contributes to the immediate skin contraction, while leaving enough healthy tissue to ensure healthy wound healing [4]. A pilot study using the Therma-Cool TC RF device to treat bovine tendon and human abdominal skin clearly demonstrated this double response [14]. The most dramatic changes induced by the novel RF device are detected with electron microscopy, and it seems that the breakage of intramolecular bonds in the collagen fibril appears after the tissue reaches a certain threshold of heating [14]. The morphologic alterations of collagen fibrils include increased diameter and loss of distinct edges, with small areas of focal changes scattered throughout the dermis [14]. Nonablative Optical Lasers and Radiofrequency Nonablative lasers are designed to produce a beneficial change in the dermis with minimal or no epidermal damage, sparing the patient posttreatment morbidity and a prolonged recovery time. Nevertheless, lasers, being light, are governed by optical laws. They get reflected, diffracted, or scattered. As a result, only a small fraction of the energy emitted by the machine actually reaches the intended target. In this manner, the effects are proportionally reduced [4]. Although dermal remodeling as a result of this treatment method is well documented [22, 4], the dermis in fact cannot be heated enough to cause a significant dermal injury without causing an epidermal burn [4]. Radiofrequency and microwave radiation, a subset of RF radiation, are electromagnetic radiation in the frequency range of khz to 00 GHz. Radiofrequency/ microwave radiations are nonionizing in that they possess low levels of energy (less than 10 ev) insufficient to ionize biologically important atoms. The primary effects of RF/ microwave energy on living tissues are considered to be thermal [2]. Because RF energy is produced by an electric current rather than a light source (as are most dermatologic lasers), it is not subject to diminution by tissue scattering or absorption by epidermal melanin. As such, patients of different skin phototypes can be treated with RF-based systems, and significant thermal energies can be generated safely within the deeper tissue layers to effect collagen contraction and new collagen formation [28]. Cooling devices of RF systems appear to be effective in protecting the epidermis from thermal injury [14]. Energy applied through a new infrared light device in multisecond pulse width and low fluences, contrary to the Thermage system, is virtually painless and reported to produce immediate demonstrable changes [15]. The tissue target for infrared light (1,100 1,800 nm) is water [7]. Energy is delivered through a handpiece with epidermal cooling [7]. A tailored spectrum by attenuation of the strongly absorbed wavelengths in the range from 1,400 to 1,500 nm allows a penetration depth of 1 to 2 mm. This is ideal for targeting the reticular dermis [15] and results in nonspecific thermal damage to collagen, effecting immediate collagen contraction and longer-term collagen remodeling [7]. Why lower fluences (20 40 J/cm 2 ) are more effective than higher fluences is not clear. One explanation is that heating of the dermis at these energy levels approaches the point of collagen contraction, which is 57 to 61 C. Heating the collagen to a higher temperature may liquefy collagen beyond any possible immediate contraction. The denatured collagen must then be removed by a wound-healing process that subsequently would cause delayed tissue contraction. A longer pulse also accounts for much less pain during treatment [15]. Unfortunately, the mechanism by which low to mid settings and multiple passes produce dermal retraction also has not been established. It might be speculated that there is a thermal stimulation on fibroblasts rather than obliteration by high settings. Perhaps there is no dermal wounding per se, but rather initiation of the healing mechanism and repair cascade by the intense heat [4]. It is speculated also that deeper heat penetration would cause damage to adipose tissue [2]. In fact, fat tissue may
288 Aesth Plast Surg (2009) :28 294 be heated more readily than dermis due to its inherent high electrical resistance. It is estimated that its temperature can rise to sevenfold that of the dermis when heated by an RF source [44]. Fat atrophy has been cited as one of the most disturbing complications after Thermage treatment [45 47]. Unfortunately, in some patients, it appears that the fat atrophy progresses with time [46]. Nonablative Radiofrequency The new concept of NARF is claimed to be the first method successfully applied for noninvasive collagen denaturation to produce tissue shrinkage and tightening of lax skin [1, 15, 17, 4, 8]. Radiofrequency is color blind and not directed toward specific dermal targets. Instead, it produces controlled volumetric heating of the deep dermis [17] and makes use of relative differences between tissue targets in their resistance to electrical energy [7]. Achieving the appropriate temperature changes in the dermis in a controlled fashion while sparing the epidermis is an essential feature of this method [4, 8, 48]. The RF system heats tissue to between 65 and 75 C, the critical temperature at which collagen denaturation and, ultimately, tissue shrinkage occur [8]. Radiofrequency technology may be monopolar or bipolar [7], and both have been used for cutaneous applications [28]. Monopolar systems deliver through a capacitive coupled electrode (Therma-Cool TC) at a single contact point, a high-frequency current at a wavelength of 6 MHz. A disposable membrane tip encompassing a treatment area of either 1.0 or 1.5 cm 2 is used, and an accompanying disposable adhesive grounding pad serves as a low-resistance path for current flow to complete the electrical circuit [7, 28, 48]. Monopolar electrodes concentrate most of their energy near the point of contact, and energy rapidly diminishes as the current flows toward the grounding electrode [28]. Monopolar RF application produces nonablative tissue tightening of skin by volumetric heating of the deep dermis. It focuses RF energy on dermal collagen while using cryogen application (precooling, parallel cooling, and postcooling of the skin) to minimize any thermal effects on the epidermis [2, 4, 48]. By cooling the epidermis before administration of energy, the Thermage system theoretically allows for a zone of heat production in excess of 65 C in the dermis, with temperatures ranging 5 to 45 C in the epidermis [45]. The device creates an electrical field underneath the electrode that is alternated rapidly from positive to negative, causing charged molecules to move with the electrical field. Heat is generated by the resistance of the target tissue to the passage of electrical energy [48]. The Thermage system is different from previous RF devices in that it uses capacitive coupling rather than conductive coupling to deliver the therapeutic energy. Conductive coupling is based on energy concentrated at the tip of an electrode being delivered to a target. This results in heat production at the skin surface in contact with the electrode, which can produce epidermal injury. Capacitive coupling disperses energy across a surface to create a zone of temperature increase [45]. The combination of intense heat and intense cold permits RF to be nonablative [4]. High fluences (70 150 J/cm 2 ) delivered in a short fixed pulse (B2. s) are typical NARF Therma-Cool system treatment parameters. The pain, however, is significant even at the lowest possible fluence capabilities of that machine because heat is delivered in an extremely short pulse (flash heating) [15]. Histologic evaluation of skin immediately after application of high fluences with a 1-cm electrode tip did not show any evidence of tissue necrosis or incipient inflammation [9]. The device is reported to produce an immediate tightening of the skin as well as collagen deposition and remodeling over time. The majority of patients are reported to see improvement within 4 to 12 weeks after treatment. [45]. Bipolar devices pass electrical current only between two positioned electrodes applied to the skin. No grounding pad is necessary with these systems because no current flows throughout the remainder of the body [28]. It is claimed, however, that bipolar RF cannot produce a uniform volumetric heating comparable at all with monopolar RF. Furthermore, the bipolar RF devices frequently are combined with other light-based technologies, making it difficult to assess what role, if any, bipolar RF plays in treatment outcomes [4]. The most widely studied bipolar RF devices use electrooptical synergy with broadband light (Syneron Aurora) or with a diode laser (Syneron Polaris) (Syneron Medical Ltd., Yokneam Elite, Israel) [17]. The theory is that the combination of optical and bipolar RF energies allow for lower energies with both methods to achieve target heating, thereby increasing safety and reducing discomfort and complications [7, 17, 28]. Photothermolysis is used to preheat a target tissue. In doing so, the impedance of the target is altered and its susceptibility to a subsequent pulse of RF is increased. This has been called electro-optical synergy (ELOSTM; Syneron Medical Ltd). Theoretically, RF elicits deeper tissue heating to induce collagen formation, whereas the synergistic optical component targets fibroblasts, superficial dyschromias, and blood vessels [7]. The safety and efficacy of a new device that implements an innovative combination of bipolar RF and vacuum using a breakthrough technology termed functional aspiration controlled electrothermal stimulation (FACES) technology [49, 50] also has been investigated. Significant
Aesth Plast Surg (2009) :28 294 289 improvement in the skin s appearance and texture was observed during the treatment course and continued to increase during the follow-up period. The mean elastosis score on the wrinkling and elastosis scale before treatment was 4.5. It was reduced to less than 2.5 by 6 months after treatment, representing a drop of an entire wrinkle class (from 2 to 1) on this scale. The reported pain levels were low, and the subjects expressed their satisfaction with this type of treatment and its outcome [49]. Another new technology uses bipolar RF with a vacuum (Lumenis Aluma: Lumenis Inc., Santa Clara, CA, USA) to refine bipolar RF further and to enhance safety and comfort [17]. The Aluma handpiece uses a vacuum to fold the skin, ensuring contact and positioning the dermis in direct alignment with the path of RF. Vacuum positioning combined with the use of a topical conductive coupling medium concentrates heat deep in the dermis. The result is believed to be predictable, effective, and virtually painless [50, 51]. A device that combines a diode laser (915 nm) and bipolar RF (1 MHz) with a vacuum-pneumatic RF is claimed to achieve a higher satisfaction of nonablative facial rejuvenation, especially recontouring and lifting, by using a vector with less discomfort and fewer side effects [2]. Evidence-Based Efficacy of Nonablative Radiofrequency Monopolar Radiofrequency Thermage was approved for the noninvasive treatment of periorbital rhytides and wrinkles by the FDA in 2002 and for full-face treatment in 2004 [52]. The largest multicenter (institution review board approved) believed by the FDA to demonstrate the clinical efficacy of the Thermage device was performed by Fitzpatrick et al. [28, 48, 5]. The study enrolled 79 women and 7 men with the goal to diminish signs of facial aging in the periorbital area. Investigators evaluated treatment efficacy with the Fitzpatrick Wrinkle Classification System (FWCS), and subjects reported on their overall satisfaction and perceptions at 2, 4, and 6 months. Assessment of wrinkle improvement also included review of a series including baseline and 2-, 4-, and 6-month photographs for each subject. All the photographs were masked to block the investigator name, treatment settings, and treatment time. For each subject, sets of the masked photographs taken from the side angles but at different time points were arranged in random side by side. Blinded photographs then were scored separately with the FWCS by three independent clinicians, including two facial plastic surgeons and a dermatologic surgeon, all in private practice. In addition, 4- and 6-month photographs were compared with baseline photographs using an objective technique to measure eyebrow-lift [5]. The authors concluded that a single treatment with the Thermage RF tissue tightening device produces objective and subjective reductions in periorbital wrinkles, measurable changes in brow position, and acceptable epidermal safety. These changes were indicative of a thermally induced early tissue-tightening effect followed by additional tightening over a time course consistent with a thermal wound-healing response [5]. The evidence offered by this study is at best level. The value of blinding photographs is of doubtful significance because this was not a comparative study, and the reviewers were aware anyway that all the patients had received RF treatment. Evaluation of the results was mainly subjective and even for what the authors qualify as objective measurement of brow elevation, they have admitted that many photographs were substandard for scientific measurements [5, 54]. One of the authors used Adobe PhotoShop to make controlled reference lines to measure brow-lifting. It is unclear whether the evaluated images were measured in the same dimensions, but if so, these images were far from standardized [54]. A study that makes such a bold statement for browlifting as little as 5 mm with nonablative treatment should have impeccable photographic standards. At a minimum, a head positioning device should have been used, and an incremental measurement grid standardized to photographic distortion would have been optimal [54]. Bassichis et al. [45] also addressed the effect of the Thermage device on brow elevation in a prospective study of 24 patients [48]. The patients had pretreatment photos, in-office procedure, and follow-up photos. Brow elevation measurements were used to gauge efficacy of the procedure. These results were compared with those for an untreated control group of 12 patients [45]. The authors concluded that the posttreatment measurements were improved (p \ 0.05) compared with the control group. The posttreatment measurements also were improved from the pretreatment baseline (p \ 0.05). The subjective results obtained from patient satisfaction questionnaires did not, however, correlate with the objective data. The data also showed that improvement in brow elevation was not uniform in each patient and that the majority of the study patients did not perceive benefit from the procedure [45]. More positive results were reported by Nahm et al. [55], who prospectively treated one side of the face for 10 volunteers [48, 55]. Measurements regarding brow position were made using standardized digital photographic images taken 1, 2, and months after treatment. Morphologic changes were evaluated using morphologic analysis with computer imaging software. The application of RF to the
290 Aesth Plast Surg (2009) :28 294 face provided quantifiable objective changes. Gradual improvement was noted in all the patients over the -month interval. At that point, a statistically significant average elevation of the midbrow (4. mm average increase) and lateral brow at the lateral canthus (2.4 mm average increase) on the treated side was observed. The authors also noted a statistically significant increase in the level of the palpebral crease (1.9 mm average increase). The jowl area also was diminished in area by 22.6% on the treated side [48, 55]. Ruiz-Esparza and Gomez [9] evaluated a series of 15 volunteer patients who underwent treatment isolated to the preauricular skin [48]. Standardized photographs with a high-resolution digital camera were taken before the procedure, immediately postoperatively, 1 week afterward, and monthly thereafter for at least 4 months and for as long as 14 months [9]. Four dermatologic surgeons independent to the study were asked to evaluate the results by examination of the photographs. Gradual changes, no down time, and minimal risk were demonstrated subjectively. The surgeons stated that treating the preauricular areas rather than the entire surface of the skin of the cheeks or over the skin of the nasolabial folds makes a significant difference. It was theorized that the preauricular area served as an anchoring point for stretching the skin distally to it [9]. Alster and Tanzi [10] treated 50 patients with a variety of skin types [48]. Photographic documentation of clinical improvement in treatment areas taken using identical camera settings, lighting, and patient positioning was independently evaluated by three masked assessors. Patient satisfaction surveys also were obtained at each follow-up visit using a scale of 1 to 10. Although the authors stated that skin-tightening effects after a single RF procedure were modest, they claimed significant improvement in cheek and neck skin laxity for the majority of their patients. The patient satisfaction scores in their series paralleled the claimed clinical improvements [10]. Skin tightening after RF application to the face has been demonstrated in a few preliminary reports. Subjective improvements according to a grading scale have been used to demonstrate changes in the nasolabial fold, mandibular line, cheek contour, and marionette lines [9, 55]. Effectiveness at shrinking eyelid skin also was tested and shown to be mild to moderate at best in one report [11]. Several other reports [2, 18, 56 59] demonstrated equivocal results, some showing more significant improvements than others. Most of these reports are about nonrandomized, noncomparative s with subjective evaluation of results and thus cannot be considered as strong evidence either way. Even if the clinically favorable reports are taken at face value, many questions remain about optimal treatment parameters [2]. The safety and efficacy of multiple RF passes during a single treatment session have not been well documented. Whether additional passes are more efficacious is not known [2], despite claims that multiple passes with monopolar RF using lower fluence has given positive results, especially for nasolabial folds, sagging cheek fat pads, and a sagging submental region [10, 1]. It is reported that multiple passes over a small area will eventually produce edema, giving the transient illusion of improvement [15]. However, targeting such change as an end point of the procedure, in addition to being short lived, may prove risky regarding late-appearing complications such as fat necrosis and subcutaneous scarring [15]. On the other hand, when immediate contraction is obtained, it is claimed that the degree of patient satisfaction is remarkable [15]. Another important question concerns the consistency of results seen after a single treatment. The ideal energy levels for treatment also are not known [2]. Although it has been suggested that lower fluences may work as well as higher fluences, if not better [15], direct comparisons have not been reported [2]. How do results vary according to treatment area? Should we base our energy level on patient perceived pain, or do protocols exist that will work consistently for most patients? [2] All these are still unanswered questions. Conclusion The quest for a method of nonsurgical skin tightening has been the Holy Grail for nonsurgeons not trained to perform face-lifts [9]. As plastic surgeons, our first choice for treating skin laxity is standard aesthetic surgery techniques. However, for patients who do not want to undergo surgery and cannot or will not tolerate any downtime, MRF, the first nonsurgical nonablative treatment to address soft tissue redundancy and the most widely studied and documented technology, may be an alternative [4, 17, 4]. Many patients currently seek the least invasive treatments possible for aesthetic improvement [1]. It is unfortunate that some physicians have misled the public by presenting Thermage RF rejuvenation as a nonsurgical face-lift. This position is false, misleading, and strongly opposed by the manufacturing company itself [4]. Although dermal remodeling may occur with both nonablative and ablative optical and RF systems [4], patients and physicians expecting nonablative results to be similar to those seen after surgical or even ablative techniques may be disappointed [20]. It is important to bear in mind that none of the nonablative technologies can replace the ablative procedures [1]. Neither nonablative nor fractional resurfacing produces results comparable with ablative skin resurfacing [, 9, 56,
Aesth Plast Surg (2009) :28 294 291 60]. Because the degree of collagen remodeling is not expected to be as great as that seen with more destructive approaches, the nonablative technique is meant for individuals who do not wish to take time away from their daily activities [4] and who want to minimize treatment discomfort and downtime [4, 19]. The technique also is not meant for individuals with extensive solar-induced epidermal pigmentary changes [4]. Although observed changes often are more subtle than those seen with ablative techniques [4], both nonablative and fractional resurfacing technologies have become much more popular than the latter because the risks of treatment are limited in the face of rather acceptable improvement []. With the expanding variety of therapies and emerging technologies available for rejuvenation, it often is difficult to determine which specific treatment would benefit an individual patient [61]. Physicians must appreciate the indications, complications, benefits, and limitations of each technique [62]. The key to success remains primarily patient selection and management of patient expectations as well as understanding of what areas in particular need to be improved. It can then be determined whether nonablative rejuvenation is likely to provide these results [19, 4]. Monopolar RF nonablative skin rejuvenation is a promising new procedure that may be used to tighten and contour nonsurgically mild to moderate laxity of the skin without significant underlying structural ptosis. In selected patients and others who wish to avoid surgical treatment methods, MRF treatment offers a valuable option [61]. Good candidates for the technique tend to be youth with minimal facial sagging [19]. However, patients should understand that skin texture will improve, and fine lines will be softened but not eradicated. Cumulative aesthetic benefits will occur gradually and less dramatically than those seen with ablative resurfacing [19]. Patients must understand also that nonablative Thermage technology does not produce the same clinical changes as a surgical rhytidectomy [4]. Although 80% to 85% will see some improvement after Thermage RF treatment, improvement may be subtle. A 5% to 20% improvement in tightening can be expected. A lucky few may show more improvement, and an unfortunate few may see no appreciable tightening at all [7, 4, 4]. The results are the most variable for pure nonablative devices targeting water and for RF technologies [17]. In fact, the results of nonablative RF treatment are neither very predictable nor remarkable [, 11, 18, 8, 4, 45, 6], yet many authors have reported high patient satisfaction [2, 11, 45, 59]. This sheds serious doubts about the validity and subjective nature of these reports and the value of the evidence presented, which is mainly subjective and at best mostly level (Table 1). Nevertheless, realistic expectations of improvement in skin quality, tone, and texture can be fulfilled using what is becoming the fastest growing area of cutaneous cosmetic rejuvenation [20]. Rapid changes in technology have become a constant in our practice of aesthetic surgery [64]. Nonablative technology currently is at the forefront of skin rejuvenation [20]. Although many peer-reviewed publications have supported improvement with Thermage in almost all skin parameters measured including the lifting effect, few have analyzed histologically the skin of the patients treated [14, 4, 44]. However, it must be kept in mind that histologic dermal remodeling, no matter how extensive, may not translate into marked morphologic changes, and improvement in aging features that for most patients are more than simply skin deep. Unfortunately, RF technology is fairly new. Long-term data must await several more years of accumulated clinical treatment and experience [20]. Much information about nonablative skin rejuvenation systems has bypassed the traditional study phase [20]. Manufacturer marketing and media blitzes have progressed at a significantly faster pace than clinical research studies [20]. We all are faced with the difficult task of evaluating new devices and attempting to determine whether they will live up to their promise. Far too often, we purchase expensive new technology that is obsolete within 1 or 2 years. Another dilemma is how we present this technology to our patients. If we embrace a new device early before there is extensive clinical experience, we run the risk of misleading, or worse, injuring our patients [64]. Evidence-based medicine aims to apply evidence gained from the scientific method to certain parts of medical practice. It seeks to assess the quality of evidence relevant to the risks and benefits of treatments (including lack of treatment) [65]. Critics of evidence-based medicine say lack of evidence and lack of benefit are not the same [65]. This perfectly applies to our current assessment of Thermage skin rejuvenation. Although solid evidence about its clinical effectiveness is largely lacking, anecdotal reports and subjective evaluations claim the contrary [66]. Subjective data are very important because an objectively measurable result does not mean that the patient will see an improvement in appearance [45]. The necessity of asking subjects for their evaluation of their personal response to an aesthetic treatment is becoming more and more appreciated [11, 67]. Yet, patient satisfaction does not mean objectively measured positive outcome. In one report, we can read that patients were pleased with the convenience of this noninvasive procedure, but the majority did not perceive a cosmetic benefit [45]. Although RF skin rejuvenation does not improve laxity to the same degree as surgery, it does have the advantage of avoiding surgery-associated recovery time and potential complications [8]. It lies in a shady area of our surgical
292 Aesth Plast Surg (2009) :28 294 Table 1 Levels of evidence in most relevant reported clinical studies Authors Type of study Results Level of evidence Fitzpatrick et al. [5] Bassichis et al. [45] Nahm et al. [55] Ruiz-Esparza et al. [9] Alster and Tanzi [10] Kushikata et al. [57] Multicenter nonrandomized Comparative nonrandomized nonblinded Comparative controlled nonrandomized nonblinded. Each patient acted as own control Thermage RF device produces objective and subjective reductions in periorbital wrinkles Improvement in brow elevation was not uniform in each patient, and majority of the study patients did not perceive benefit from the procedure Objectively measured gradual improvement was noted in all patients over the -month interval Subjective gradual improvement was noted Subjective improvement was noted Relatively good improvement months after treatment, and even better improvement after 6 months following RF treatment. Fritz et al. [56] Noncontrolled nonrandomized 11 patients received a single RF treatment, and 9 patients underwent 2 treatments. Two RF treatments yielded significantly better improvement than a single treatment. Modest overall improvements Finzi et al. [2] Jacobson et al. [58] Yu et al. [59] Hsu et al. [18] Carruthers et al. [11] Nonrandomized Monopolar radiofrequency using a multipass vector (mpave) treatment was safely tolerated with good patient satisfaction. 96% of patients showed some clinical improvement 17 of 24 patients demonstrated visible improvement following RF subjective assessment The combination of broadband infrared light and bipolar radiofrequency produces mild improvement of facial laxity in Asians with no serious adverse sequelae Photographic analysis did not yield statistically significant results Minimal to modest but safe tightening of lids RF radiofrequency Level 1: Evidence obtained from at least one properly designed randomized controlled trial Level 2 1: Evidence obtained from well-designed controlled trials without randomization Level 2 2: Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group Level 2 : Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence Level : Opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees [66] 2 1 2 1 practice, offering a service highly in demand, further amplified by competition and market pressures. Thermage may be useful for the clinician who wants to offer a fullservice practice to patients who absolutely refuse surgery and have realistic expectations about this treatment. It also may play a role for postsurgical patients who want no further surgery but welcome additional nonsurgical tightening [4]. However, for the surgeon with a more conservative approach, Thermage may not offer enough benefit to warrant its use [4]. In the final analysis, the value of nonablative RF skin rejuvenation rests on how ethically we present this new technology to our patients. If it is presented as the only magic bullet that will solve their problems, this certainly would be deceptive and an inexcusable abuse of the patients trust. Nonablative RF must be presented as one option in a full range of treatment methods with a full understanding of the benefits and shortcomings of each. Only then can a patient give his or her full informed consent to proceed with one treatment option or the other. A professional, honest, and friendly interaction between physician and patient greatly improves the possibility for recognized positive outcomes [1]. In the meanwhile, further work clearly is needed to determine appropriate energy levels that allow for maximal