Dermatologic Clinics
Volume 23 • Number 2 • April 2005
Copyright © 2005 W. B. Saunders Company



Using Light in Dermatology: An Update on Lasers, Ultraviolet Phototherapy, and Photodynamic Therapy


Iltefat Hamzavi, MD a, *
Harvey Lui, MD, FRCPC b
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a Department of Dermatology, Wayne State University, 4201 St. Antoine, Suite 5F, Detroit, MI 48201, USA
b Division of Dermatology, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
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* Corresponding author. Department of Dermatology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202
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E-mail address: ihamzavi@med.wayne.edu




PII S0733-8635(04)00115-9
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Indications for light-based treatments, such as lasers, UV phototherapy, and photodynamic therapy, are rapidly increasing within the arena of skin disorders. Physicians can remain current in their understanding of these modalities if they understand a few basic principles outlined in this article. Once these concepts are understood, all the rapid advances can be kept in perspective and physicians can apply the most appropriate technology to the care of their patients while informing them about the limitations of overmarketed but poorly proved strategies.
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It was just over a century ago that Niels Finsen was awarded the 1903 Nobel Prize in Medicine for establishing the scientific basis for using light to treat skin disease [1]. Despite the medical use of light in dermatology throughout the twentieth century, the fundamental mechanisms of action for its therapeutic effects have been systematically explored and clinically exploited only in the last couple of decades. This article highlights some of the most important advances in therapeutic photomedicine over the last decade with a focus on lasers, intense pulsed light (IPL), ultraviolet light (UV) phototherapy, and photodynamic therapy (PDT). Although these treatment modalities have each evolved quite independently of the others, there has been a convergence of interests among clinical practitioners and investigators who use light to treat diseased skin. For example, two very different photonic approaches have been introduced into clinical practice based on the concept that selective wavelengths within the UV light B (UVB) region are more effective for treating psoriasis: narrowband fluorescent lamps and pulsed excimer lasers. What unifies these two examples, and any other dermatologic light sources, is the fact that in essence all they really do is deliver external energy to the skin for therapeutic purposes. Regardless of the device or dermatologic indication, specific biophysical laws govern how all light affects the skin.
The key to developing and refining any type of light-based therapy is to understand how to deliver this energy to cutaneous structures efficiently and effectively in a highly targeted fashion so as to limit collateral light-induced damage to normal tissue. Treating the skin with light can be considered in two stages: understanding how selectively to deliver photons to specific structural targets in the skin (ie, tissue optics), and understanding the biologic processes that occur after a skin target absorbs light photons (ie, photobiologic reactions). Most refinements to phototherapeutic devices exploit either one or both of these two aspects, and the advances highlighted in this article are discussed using this mechanistic perspective.

UNDERSTANDING TISSUE OPTICS AND PHOTOBIOLOGIC REACTIONS
A detailed explanation of tissue optics and photobiologic reactions is beyond the scope of this article, but certain basic biophysical principles warrant a brief summary. The interaction of light with tissue is governed by three basic processes that can occur when a photon of light reaches the skin: (1) reflection, (2) scattering, and (3) absorption. Light that is reflected from the skin and perceived by the human visual system provides the means for diagnosing skin disease, but reflected light does not itself result in any direct therapeutic effect. In the absence of an absorption event (see later), the forward propagation of light deeper within the skin is influenced by the degree to which its direction of travel has been scattered by tissue structures. Tissue scattering of UV, visible, and near infrared light is wavelength-dependent, and in general longer wavelength light penetrates the skin more deeply. Targets that are deeper in the skin require the use of devices that can deliver longer wavelength light.
Absorption is an important biophysical event that involves the transfer of energy from light to tissue. Without photon absorption, energy is not taken up by the skin and no biologic or therapeutic effect occurs. The absorption of photons by specific molecules within the skin also influences light penetration because any photon that is absorbed is no longer capable of propagating through the skin, because that particular photon no longer exists. Like scattering, absorption is wavelength-dependent, but in a somewhat more complicated manner because it depends on the absorption profile or “spectrum” of the light-absorbing molecule, which in this context is usually referred to as the “chromophore.” With the possible exception of UVB phototherapy the specific chromophores for most light-based therapies are precisely known and include hemoglobin; melanin; water; exogenous dyes (ie, tattoo pigment); and photosensitizing drugs (ie, psoralens and PDT photosensitizers). It is ironic that although UVB light is the oldest and most widely used form of phototherapy, the precise chromophore and subsequent biologic tissue reactions for this modality remain unclear at this time.
In summary, both scattering and absorption determine the depth to which light penetrates the skin, but only absorption can lead to photobiologic and phototherapeutic effects. All phototherapeutic applications must by definition be mediated by chromophores present in the skin. For a given photon to have a clinical effect it must actually reach the target structure within the skin and then be absorbed by a specific chromophore within that target. Whether or not these events occur and the degree to which they occur is dependent on the wavelength of light used, the structure of the skin, the presence and location of chromophores, and the preferential ability of diseased tissue to absorb light more efficiently than normal unaffected skin. In clinical parlance, there is often an undue preoccupation with the technical specifications for a given light device rather than a well-grounded understanding of the desired underlying photobiologic and phototherapeutic end points. The reality is that for any clinical indication a multiplicity of possible photonic devices are often available. This simply reflects the fact that from the point of view of the tissue and its chromophores, the exact source of the photons (eg, laser versus IPL versus light-emitting diode versus fluorescent lamp) matters far less than whether the photons are of the appropriate wavelength and delivered to the target in sufficient quantity to cause irreversible tissue changes. As with any therapeutic modality, the ultimate arbiters for the bewildering array of competing light-based therapies and devices are well-designed and rigorously executed controlled clinical studies.
Once the photon is absorbed by the chromophore, the source's light energy is transferred to the skin either to generate heat or drive photochemical reactions. The former scenario encompasses most lasers and IPLs in dermatology, all of which in essence involve the selective and irreversible alteration of tissue using heat [2]. In contrast, UV phototherapy and PDT do not primarily involve the use of light to generate heat, but rather rely on photon absorption to energize photochemistry. In the case of UV therapy it is now generally accepted that the therapeutically useful photochemical reactions culminate in cutaneous immunosuppression, although the exact sequence of reactions is less clear. In PDT the first two photochemical reactions are very clearly defined. The energy of the excited chromophore is first transferred to molecular oxygen to form singlet oxygen, which then reacts with a diverse range of biomolecules. The everexpanding indications for PDT partly mirrors the multiple ways by which singlet oxygen generated by light can affect the skin.

USING LASERS AND INTENSE PULSED LIGHT TO HEAT THE SKIN
Because most lasers in dermatology are used precisely to heat the skin, the advances for these applications are related to increasing the selectivity of these devices by fine tuning the wavelength and pulse duration (ie, the time over which the laser energy is delivered) [3], and simultaneously cooling the skin during light exposure. These modifications have increased the safety and efficacy for photothermal lasers in dermatology, particularly for targeting larger or deeper skin structures, such as larger blood vessels and hair follicles. Another driving force in the evolution of lasers and IPL has been the need to minimize downtime from postprocedure purpura and elaborate wound care protocols.

EXTENDING THE THERAPEUTIC RANGE OF VASCULAR LASERS
Although the principle for treating vascular lesions, such as port wine stains, with yellow 577- or 585-nm light was originally based on hemoglobin's absorption spectrum, red to infrared light seems to target blood vessels better that are situated more deeply. In addition, vascular laser pulse durations have been extended from the submicrosecond to millisecond domain for two reasons. A longer duration of exposure heats a greater tissue volume, which is necessary for larger-caliber vessels. Second, longer pulses conduct heat more gradually within blood vessels resulting in a lesser tendency to immediate purpura, which although temporary, patients find very disfiguring. The long-pulsed neodymium:yttrium–aluminum–garnet (Nd:YAG) and later-model pulsed dye lasers both expand the range of blood vessels that can be treated by incorporating these parameter changes. The longer penetration of the long-pulsed 1064-nm Nd:YAG laser facilitates its use for leg veins including blue veins up to 3 mm in diameter [4]. Not unexpectedly, these lasers are often less effective for finer red telangiectasias presumably because of a mismatch between the vessel's thermal relaxation time and the laser's pulsewidth [3]. Despite these advances, lasers have not yet supplanted conventional sclerotherapy for managing leg veins [5]. The deeper penetration of the recently developed 595-nm, long-pulse (up to 40 milliseconds) dye laser allows the operator to obtain clearance for some port wine stains that is equivalent to the original 585 nm, 450-μs pulsed dye laser results with fewer side effects, such as prolonged purpura and crusting [6]. It may also be helpful for red telangiectasias on the legs [7].

COOLING THE SKIN TO PROTECT THE EPIDERMIS AND SUPERFICIAL DERMIS
Although the judicious selection of wavelength, pulse duration, and fluence allows lasers and IPL sources to generate heat at specific targets within the skin, collateral heat damage can still be sustained by surrounding structures, particularly the epidermis, which contains melanin, a broad-spectrum chromophore. Unwanted epidermal thermal damage becomes even more problematic when treating darker skin types or when using higher fluences as may be the case when treating deeper targets, such as hair follicles. Cooling the skin surface during laser exposures serves to protect the epidermis and superficial dermis from unintended photothermal effects. Skin cooling techniques include chilled probes held in contact with the skin, timed cryogen sprays directed to the skin surface, and forced cold air fans directed at the treatment site. All forms of cooling aim to prevent the superficial layers of the skin from reaching the threshold temperature for thermal damage during laser exposure, and they all differ in terms of reliability and the cost of consumables, such as cryogen. An additional benefit of skin cooling beyond the reduction of superficial crusting and dyschromia [8] is intraoperative pain relief.

INTENSE PULSED LIGHT
IPL sources are now very popular in medicine and have been heavily marketed to the public, dermatologists, other physicians, and nonmedical practitioners. IPL devices are not lasers, but like most cutaneous lasers, produce their desired effect by generating heat. The core technology is relatively simple and involves the use of polychromatic broadband flashlamps equipped with optical filters that allow preselected visible to infrared wavebands (500–1200 nm) to reach the skin [9]. Because multiple wavelengths are delivered, several different chromophores including hemoglobin, melanin, and perhaps even water, can be targeted with the same light exposure. Photorejuvenation is a somewhat broad imprecisely defined concept whose aim is to improve the appearance of the skin by eliminating lentigines and dyspigmentation, telangiectasia, and fine wrinkles. Lasers and IPLs can achieve these effects to some extent, but the main purported advantage with IPLs is that these features can be treated simultaneously with one device [10], whereas with lasers several different devices may be required. There are few controlled clinical trials to confirm these claims for IPL, but nevertheless the systems have become quite popular [11]. In practical terms, multiple IPL treatment sessions are often required, and because of the complexity of selecting the appropriate wavelength cutoff filter, fluence, and pulse duration there is a risk for developing side effects secondary to nonspecific thermal damage. These side effects include crusting, pigmentary changes, and paradoxical increases in hair growth [12]. Another potential area of concern with IPL relates in part to the multiplicity of repeat treatments that are often advocated for both the initial treatment and subsequent maintenance sessions. Because IPL includes infrared radiation, it may be theoretically possible to sustain deleterious cutaneous effects from chronic infrared exposure. The versatility and effective marketing of these devices is a driving force behind their popularity but it remains to be seen if well-designed trials can confirm their efficacy.

FROM LASER RESURFACING TO NONABLATIVE DERMAL REMODELING
Within the span of less than a decade the use of carbon dioxide lasers (λ = 10,600 nm) for ablating rhytides and superficial scarring peaked and then abruptly declined. The controlled ablation of superficial skin layers with the carbon dioxide laser by tissue water as the chromophore improves the skin's texture and appearance, but carries with it significant risks for dyspigmentation and scarring, especially when performed by less experienced operators [13], [14]. Ablative skin resurfacing is still relatively safe and effective in skilled hands when used for treating fine to medium rhytides and elastosis, and may be the gold standard for facial rejuvenation. This procedure is demanding on patients and practitioners, however, because success also requires meticulous and elaborate postoperative wound care and a willingness to accept weeks to months of facial erythema that can often be very conspicuous. More often than not, patients opt for less invasive procedures even if the improvement is less dramatic, and this preference has been fulfilled by the introduction of devices and techniques that replicate the clinical effects of the carbon dioxide laser while minimizing patient inconvenience and downtime.
The erbium (Er):YAG was initially believed to provide a wider safety margin for resurfacing as compared with the carbon dioxide laser because its shorter wavelength (2940 nm) and pulse width resulted in a more attenuated optical path length within tissue. The Er:YAG laser does indeed cause a narrower zone of ablation and residual tissue necrosis, but the tissue effects are probably too shallow to achieve the desired clinical effect. Intraoperatively, Er:YAG-based resurfacing is time consuming because more laser passes are required to ablate a given thickness of tissue. Furthermore, hemostasis is problematic because of this laser's inability coagulatively to seal off blood vessels, which is directly related to its attenuated tissue penetration. In terms of clinical results a controlled study showed that although the Er:YAG laser reduced healing times and side effects it did not produce the same degree of improvement in rhytides as the carbon dioxide laser [15].
To treat abnormal skin texture induced by photoaging effectively, photons must be delivered to the level of the dermis where collagen and elastin reside. Hence, the use of infrared wavelengths, such as with the carbon dioxide and Er:YAG lasers. Because the side effects associated with these two lasers are primarily the result of ablating and wounding the epidermis and superficial dermis, nonablative or subsurface dermal remodeling has been proposed as a preferred technique. Two methods are currently being used to spare the skin's surface when delivering infrared laser energy to the skin: using alternate infrared wavelengths and concurrent skin cooling during treatment. Lasers at 1320 nm Nd:YAG and 1450 nm (diode) seem to penetrate to the level of the dermis without affecting the skin surface, particularly when used in combination with dynamic skin cooling [16]. Commercial Food and Drug Administration (FDA) approval for these devices has established a foothold for nonablative resurfacing in the treatment of acne scars and rhytides [13], [16]. Nonablative techniques require multiple treatments, however, and although histologic effects can be demonstrated, a corresponding clinical response may often be hard to discern [13].

REMOVING HAIR WITH LIGHT
The use of lasers and IPL systems for hair removal has expanded tremendously over the past decade. In fact, in many jurisdictions most treatments are now no longer performed through physician offices. The main advance in this application is the use of longer wavelengths and pulse durations to minimize side effects in darker-skinned patients [17].
The addition of radiofrequency pulses is suggested to remove blonde and gray hairs but there is scant published information to support that claim [11]. As hair removal technology has become more widespread unexpected side effects have been noted, such as the paradoxical stimulation of hair growth. This has been reported with IPL [12] and the long-pulsed alexandrite laser [18]. A striking reticulate erythema ab igne–type reaction has also been reported as being caused by infrared diode laser hair removal [19].

A NEED FOR WELL-DESIGNED TRIALS
The widespread use of lasers and IPL has not necessarily been paralleled by an abundance of adequately powered controlled clinical trials with objective and reproducible end points that are assessed in a blinded fashion. This is partly related to the North American regulatory system for photonic devices, which is very different from the pharmaceutical approval process. Medical devices, such as light sources, can be approved primarily on the basis of technical equivalence to existing technologies without the need for multicenter, controlled trials. In many instances, controlled trials have not been able to confirm a significant advantage for lasers in the treatment of acne [20], warts [21], asymptomatic hemangiomas [22], scars [23], [24], leg veins [5], and periorbital wrinkles [25]. Although promising “proof of concept” studies, clinical experience, marketing, and patient demand may indicate that a laser can be used for a given indication, good-quality controlled studies [26] are best for determining whether that laser should in fact be used.

ULTRAVIOLET LIGHT AS AN IMMUNOMODULATOR
Recent advances in UV phototherapy include a better mechanistic understanding of its biologic effects, more rational dosimetry approaches, and the deployment of several novel UV sources. The basic science for UV phototherapy is characterized best for psoriasis, wherein the induction of T-cell apoptosis has been demonstrated for broadband [27] and narrowband UVB [28] and psoralen plus UV light A (UVA) [29]. Myriad other cutaneous immunologic reactions also occur with UV, but the T-cell–depleting effects are likely pivotal for clearing inflammatory dermatoses and cutaneous T-cell lymphoma. These cytolytic effects on activated immune cells may also explain why UV therapy can be considered a remittive form of psoriasis treatment. The fundamental shift in concept of UV phototherapy as a means of inducing localized cutaneous immunosuppression has provided a far more logical rationale for its general efficacy in a broad range of dermatoses.
In conventional UV phototherapy both diseased and normal skin are simultaneously exposed to light. Although the primary goal of treating inflammatory dermatoses, such as psoriasis, is to clear skin lesions using light, the current approach to UV dosimetry is limited by the need to avoid burning the unaffected skin. Very-high-dose UV exposures (as high as several multiples of the baseline minimal erythema [UVB [30]] or phototoxic [psoralen plus UVA [31]] dose) can indeed clear psoriasis fairly efficiently, but using such fluences on a whole-body basis at the outset of therapy causes severe burning of unaffected skin. With repetitive exposures, normal human skin gradually photoadapts or acquires tolerance to UV light, and the rate at which this develops in normal skin has been established empirically through clinical practice. The concept of UV [32] tolerance guides any course of phototherapy, and detailed insights into its biologic basis and kinetics are still under active systematic study [32].

NARROW-BAND ULTRAVIOLET LIGHT B
Although action spectrum studies of psoriasis from 1981 showed a clear therapeutic benefit for longer versus shorter wavelength UVB [33], the technology for exploiting this advantage became widely available only over the last decade. The development of the Tl-01 narrowband fluorescent UVB (NB-UVB) lamp by Philips Electronics (Utrecht, The Netherlands) probably represents the most significant advance in how phototherapy is now delivered. NB-UVB is the first widely available light source that confirmed the benefit of using selective wavelengths of UVB. The increasing popularity of NB-UVB contrasts with the abrupt decline in the use of systemic psoralen plus UVA, which clearly accelerates photoaging and causes skin cancer [34]. NB-UVB has been shown to be as effective as psoralen plus UVA without as many short-term side effects [35]. In hairless mice exposed to UVB, NB-UVB was shown to be more carcinogenic than broadband UVB [36], but NB-UVB has not been associated with an increased risk of skin cancer when used therapeutically [37]. The latter study evaluated patients who had received a relatively low cumulative NB-UVB number of exposures (mean of 44 treatments), and it is premature to conclude that NB-UVB will not be carcinogenic when used for phototherapy in humans.
Beyond psoriasis, NB-UVB has also been shown to be effective in controlled studies for the treatment of vitiligo, although the response is incomplete [38]. Using quantitative scales to measure depigmentation, Hamzavi et al [38] reported that narrowband phototherapy, even after 6 months of treatment, only repigments the skin by approximately 42%. Targeted phototherapy using the 308-nm excimer laser also treats vitiligo. It may work faster than whole-body NB-UVB but no head-to-head studies are available [39]. According to the British Photodermatology Group, there is good evidence to support the use of NB-UVB for chronic atopic dermatitis, and fair evidence for cutaneous T-cell lymphoma [40].

NOVEL ULTRAVIOLET LIGHT SOURCES
Unlike selective photothermolysis with lasers, which is critically dependent on the rate and number (ie, irradiance and fluence, respectively) of photons delivered to the skin, the effects of UV phototherapy are primarily determined by the total number of photons that reach the skin. Depending on the specific light source, psoriasis can be cleared with UV light exposures ranging from several minutes (conventional fluorescent or incandescent lamps) to fractions of a second (lasers and IPL). UV lasers and IPL sources aim to clear psoriasis more efficiently than conventional broadband UVB in three ways. First, these sources emit relatively longer wavelength UVB; second, they can be targeted to expose only the affected areas while sparing normal skin, thereby allowing much higher fluences to be used safely; and finally, they operate at much higher irradiances so that exposure times are much shorter than with fluorescent lamps. There are now at least three commercial devices that can provide targeted phototherapy: (1) the 308-nm excimer laser, (2) broadband IPL, and (3) the broadband mercury lamp with dual UVB and UVA output. There are a few published controlled clinical studies to show that psoriasis responds to the excimer laser, whereas systematic studies for the other two systems are ongoing [30], [41], [42]. The disadvantages to targeted phototherapy are the higher cost and the relatively time-consuming aspect of covering broad plaques on the body with a series of relatively small spot-size exposures. Parenthetically, non-UV lasers have been used successfully for psoriasis [43], [44], but these techniques have not been widely adapted in dermatology, presumably because of practical limitations.
As with UVB, UVA is also heterogeneous with respect to the clinical effects of specific wavelengths. For example, devices that deliver high-intensity UVA-1 light (ie, 340–400 nm) are effective for treating pruritic disorders, such as atopic dermatitis and mastocytosis [45]. The mechanism of action may hinge on the ability of this UVA waveband to reduce cellular IgE binding sites [46] and induce apoptosis by two different pathways while reducing IgE binding sites [47]. UVA-1 is also effective for sclerosing disorders [48]. Because of limited controlled and comparative data, long treatment times, and high costs, UVA-1 units have not been widely adapted in North America, with most units being installed at select university centers.

THE ARRIVAL OF PHOTODYNAMIC THERAPY
Following its approval by the FDA in 1999 for treating actinic keratoses, PDT was initially slow to catch on in dermatology, and this was largely caused by the low reimbursement for dermatologic PDT in the United States by third-party payers. The concept of PDT is a century old, and its dependence on oxygen-related photochemistry has been well known for most of that time. In clinical practice, the treatment involves the administration of a photosensitizer followed by exposing the skin to light. The drug-activating photons can come from lasers or noncoherent light sources. The photosensitizer, incubation period, and wavelength used to activate the photosensitizer allow the nonthermal selective destruction of neoplastic keratinocytes, sebaceous glands, and hair follicles to be fine-tuned. Indications for PDT can include oncologic uses and destruction of appendigeal structures.
The efficacy of topical PDT using 20% aminolevulinic acid (ALA) and a blue light has been documented in the treatment of actinic keratosis [49]. The procedure as approved by the FDA is painful, however, and requires two visits on separate days [50]. A few studies where the incubation period was reduced to a few hours and a pulsed dye laser or IPL used to activate the photodynamic reactions [50], [51] reduced the pain and overall patient treatment time. An experimental protocol used in mice showed that broad area application of the 20% ALA solution can treat subclinical neoplastic lesions, possibly preventing carcinogenesis [52]. In addition, the methylation of ALA to allow for deeper drug penetration has allowed for more effective treatment of superficial basal cell carcinomas in Europe [53]. This treatment was recently approved by the FDA for treatment of actinic keratosis when activated by a red light [54]. Systemic PDT has shown some promise using a systemic photosensitizer and a noncoherent red light diode array, but further confirmatory studies are needed [55].
The response of actinic keratoses to ALA PDT caused some investigators to evaluate the use of this treatment for the treatment of photoaging. Topical PDT has also been used to treat photoaging of the skin in a few case series with good results [51]. Studies on the long-term follow-up for this indication are lacking, although the procedure seems to be heavily promoted as an off-label cosmetic application.
The use of PDT to ablate appendigeal structures is an area of active investigation. There has been one case series on the use of topical 20% ALA to treat truncal acne with good results. Significant postinflammatory pigmentation and pain, however, were reported [56]. Recently, this technique has been modified by decreasing the incubation period and activating the photosensitizer by a laser. This has been shown to be less painful and may induce a clinical remission of moderate acne [57]. To date, no controlled trials have been published.
Studies are ongoing but the evidence for the use of PDT for acne is limited. This would be a welcome addition to the few effective but safe treatment options for severe acne. The use of PDT for acne has increased significantly in the past year and it is likely that the use of PDT for acne has outpaced its FDA-approved use for actinic keratoses. This is as much a function of reimbursement as efficacy. The third-party payments for PDT for actinic keratosis in the United States have been poor as compared with lower-cost treatments, such as liquid nitrogen.
There are other forms of PDT that have entered the clinical arena for the treatment of acne. There are reports that certain wavelengths of light (blue and red) induce a PDT reaction in endogenous photosensitizers produced by Propionibacterium acnes bacteria resident in the skin. These treatments do not require an exogenous photosensitizer, such as ALA. Both lasers and noncoherent light sources have been reported to be effective [58]. The noncoherent light sources include red and blue wavelengths. They seem to reduce lesions initially with a gradual recurrence of the inflammatory papules and pustules over 3 to 12 months [11], [59].

SUMMARY
It is no longer possible to practice dermatology without drawing on the healing power of light. As compared with drugs, light therapy is in general vastly more versatile with an equal or better safety profile. The range of indications for using light in dermatology cuts across all areas including chronic inflammatory dermatoses, pigmentary disorders, cancer, infections, and cosmetic applications. Physicians can remain up-to-date in their understanding of current and evolving modalities by mastering the basic biophysical principles outlined in this article. Once these concepts are understood all the advances can be kept in perspective. Physicians can then apply the most appropriate technology to the care of their patients while informing patients and themselves about the potential limitations and pitfalls of overmarketed but inadequately proved strategies.
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Adnan Alabdulkarim, MD