REvrEW DERMATOLOGIC LASERS: THREE DECADES OF PROGRESS TrNA S. AI.STER, M.D., ANIl SlEVEN 1960, Theodore Mairnan at Hughes Aircraft Research Laboratories actually developed the first laser, a ruby laser.:' Many other types of lasers have subsequently been developed, but Maimari's original ruby laser manifested all the important properties we associate with today's lasers; it emitted light in a narrow, tightly concentrated beam (collimated), all the light was the same wavelength (monochromatic), and the light waves were all aligned with each other (coherent). In 1963, Leon Goldman and co-workers" performed the initial experiments demonstrating the effects of lasers on human skin, using the only available laser at the time, the ruby laser. Initially, normal white and black skin was irradiated, with and without the addition of various superficial black substances." Subsequently, laser treatment of seborrheic keratoses and hemangiomas was arrernpred.' While it became evident that the damage inflicted was nonspecific thermal destruction of the irradiated site, laser treatment had one major advantage over other destructive treatment methods, the ability to focus high intensity energy onto very small sites. This precision did not enhance target selectivity, but it was inferred from these initial experiments that more damage was induced by equivalent laser pulses in darker lesions. This observation was important to the future development of lasers specifically designed to treat certain cutaneous lesions. Thirty years have passed since the creation of the first laser. Although significant applications for lasers were forecast immediately, many subsequent developments in their diagnostic and therapeutic uses in medicine took decades to be realized. Laser technology has improved, and will continue to improve, health care delivery, diminishing the time, cost, and invasion of many procedures. This review of the use of lasers in dermatology will survey past and present developments and will outline and preview the possibilities of laser techniques. HISTORY OF LASERS The word laser was coined as an acronym for Light Amplification "by the Stimulated Emission of Radiation. While ordinary light is emitted spontaneously by excited atoms or molecules, laser light occurs when an atom or molecule retains excess energy until it is "stimulated" to emit it. Albert Einstein was the first to suggest the existence of stimulated emission.' Scientists believed that atoms and molecules were more likely to emit light sponraneously, and that stimulated emission would be much weaker. After World War II, however, physicists attempted to make stimulated emission dominate, seeking ways for one atom or molecule to stimulate many others to emit light, amplifying it to much higher powers. The first to succeed was Charles H. Townes, who instead of working with light, worked with microwaves, which have a much longer wavelength. Townes built a device he called a "maser," which stood for Microwave Amplification by the Stimulated Emission of Radiation. Together with Arthur Schawlow, Townes outlined the key concepts of stimulated emission in 1958.2 In LASER I'RINCII'LES AND LASER-TISSUE INTERACTION Fundamental to the diverse applications of laser light are its unique properties; (1) coherence, (2) monochromaticity, (3) high intensity, (4) "compressibility" into ultra-short pulses, and (5) runabiliry. Light waves are said to be coherent if they are each in phase with the other (the peaks and valleys of the light waves are aligned). Monochromaticity involves emission of a single wavelength of light. Most known energy sources emit radiation that consists of many different wavelengths. Lasers are also capable of emitting radiation of extremely high intensity, thereby providing a high concentration of light energy in the substance being irradiated. The ability to compress the light energy into ultra-short pulses allows for the excitation of high-energy levels in the molecules specifically being irradiated, while tunability of the wavelength in the range from infrared ro ultraviolet permits selective excitation From the Departments of Dermatology and Pediatrics, Yale University School of Medicine, New Haven, Connecticut, Georgetown University School of Medicine, Washingron DC, and Columbia UniversityCollege of Physiciansand Surgeons, New York, New York. Address for correspondence: Tina S. Alstcr, R. I<OHN, M.D. M.D., Georgetown University Medical Center, Washingtol' Institute of Dcrmato- logicLaser Surgery,23] 1 M Street, N.\XI., Suite 504, Washington, DC 20037. 601 hucrnational Journal of Dermatology Vol. 31, No.9, September 1992 eral, the longer the wavelength of laser light, the deeper the penetration into tissue. More recently, it has been shown that spot size is also an important parameter to consider when monitoring laser-tissue interacrion.":" Regardless of what tissue is absorbing the laser energy, once [his energy is converted to heat, it will spread throughout the surrounding tissue. If the energy source continues for roo long, damage {O normal stroma may occur from heat dissipation, and the relative optical absorptive advantage gained by choosing the appropriate wavelength and spor size will be lost. This can be prevented by consideration of a target's thermal relaxation time. The thermal relaxation time is defined as the rime required for a target to cool from the temperature achieved immediately after laser irradiation to half that temperature.' For example, the time that it takes for an organelle to cool is in the order of a microsecond, whereas cell layers will cool in a millisecond, and large abnormal vessels in portwine stains may take tens of milliseconds. If the exposure duration is long compared with the time required for diffusion of heat to surrounding structures, thermal damage will be extensive and nonspecific regardless of how specifically the laser light is absorbed and heats a target srructure.l" Confining the pulse duration of the laser to the thermal relaxation time of the target tissue limits the extent of thermal damage and demonstrates the advantage of pulsed lasers (with short exposure time) over continuous wave lasers (with longer exposure times). of certain molecular species depending on the absorption spectrum of that molecule. A single laser can provide a combination of several of the above properties ro suit a particular application. The concept of "selective phororherrnolysis" was born from the idea that special properties inherent in laser radiation could be adjusted and selected to confine thermal damage to a few pathologic lesions while minimizing the destruction of normal rissue.? One control of laser-tissue interaction involves marching the wavelength of laser light to the absorption spectrum peak of the target tissue. The absorbing molecules (or chrornophores) within the skin include hemoglobin, melanin, carotenoid, and bilirubin." While no cutaneous lesions contain primarily carotenoid or bilirubin, there are pathologic lesions that are composed primarily of hemoglobin/ or melanin. The naturally occurring optical absorptive advantage of certain tissues, therefore, can be used to optimize laser-tissue interaction. For instance, the beta 577 nm peak of oxyhemoglobin has been shown to correspond most closely to the wavelength demonstrating the best clinical and histologic respon e in the treatment of vascular lesions9-IO because the absorption of melanin weakens toward the longer visible wavelengths (Fig. 1). In those cases where a pathologic lesion does not have a naturally occurring optical absorptive advantage over normal tissue, an exogenous chromophore (i.e., hematoporphyrin) can be administered that is preferentially taken up by the pathologic lesion, thereby simulating an absorptive advanrage.l+'! Exogenous chromophore administration in the treatment of various dermatologic conditions, particularly tumors, is still experimental, but has great potential. Another aspect of tissue optics that must be taken into account when trying to optimize laser parameters is the depth of penetration of light into the skin. In gen- f.. .• E s 10' 0 :£ HbO, ~ o The argon laser emits visible blue-green light with wavelength peaks at 488 and 514 nm. It is a continuous wave system, although there are now "pulsed" systems available, which use a mechanical or optical shuttering device to break up a steady output beam. Absorption of the blue-green light is achieved by chromophores of its complementary colors, such as hemoglobin. The argon laser has been u ed primarily in the treatmenr of vascular lesions, including portwinc stains (Figs. 2 and 3),'-25 telangiectasia, 17.18.2H7 spider varicosiries.l - 0 pyogenic granulornas.!? cherry angiomas, 17 venous lakes.!" angiokeraromas.l! and Kaposi's sarcoma.1I Theoretically, there should be selective absorption of the light by hemoglobin within the blood vessels ,, ~ , (, 10 I I , \ ......\ e- ~ \ •. ;g ;: v , I I I I I , '; I I 0 <.> . \ .ge \M"" 111"' :i w 100 ,'-"\ ,, \ ...•... ~-.. I ..~ '0 10~' ;: Argon Laser : l ,, ,, , ~ o e Lasers can be categorized into one of three major groups based on their active medium: solid, liquid, or gas (Table 1). Each laser has predominant wavelength and specific chromophore interaction capabilities. Several different lasers have been used for a wide array of derrnarologic conditions. Each will be briefly summarized, but without detailing the laser mechanics involved. ...f ; ~ : Mel.nin 10' LASER TYPES 20<1 Figure 1. Absorption (Hb02) and melanin. 30<1 400 500 coefficient 700 1000 spectrum 2000 A (nm1 of hemoglobin 602 Derrnmologic Losers Al\It'T and Kohn Table 1. Characteristics of Lasers Laser Medium Wavelength Chromophore Lesions Treated Argon G~~ 488 nm, 5]4 om Hemoglobin Melanin Vascular Pigrnenred Dye Liquid Variable. depends on dye Variable Vascular Pigmented Ruby Solid 694 nrn Melanin T arroo pigment Pigmented Tartoo Nd:YAG Solid 1060 nrn CO! Gas 10, 00 nrn Vascular Epidermal Dermal Excision Water comprising the lesion; however, several histologic studiesU-J5 have cast doubt on the specificity of the damage showing the argon laser effects possibly due to nonspecific thermal destruction of skin. It ha been shown that the exposure intervals used are too long and exceed the thermal relaxation time of the target tissues, thereby increasing the risk of scarring and dyspigmentarion.Is Several clinicians have, nevertheless, reported excellent results with lesion reg res ion and minimal scarring, .fspecially in those protocols using very low energies.F With the advent of newer, more vascu- Figure 2. Porrwine stains on the nose and medial canthus of a 21-year-old female with prior argon laser test site (mid-nose). lar-specific systems (pulsed dye lasers), however, the argon laser is falling out of favor as the laser of choice for treatment of vascular lesions." 0 Because the wavelength of light is well absorbed by melanin, the argon laser has been used to treat pigrncnred lesions such as lentigo maligna and benign nevi,41-43 "cafe-au-lait" pots," nevus of Ora,17 and chloasma.!? Tattoos success,25,44 bur there have also been treated with some have been reports of significant postoperative scarring. Nonpigmented lesions reported to be uccessfully removed by argon laser have included granuloma faciale;'" and lymphocytoma cutis;'? both having a reddish-purple hue that may selectively ab orb the blue-green light. :,-':iOjP ·H!.:'j" Tunable Dye Laser The tunable dye lasers contain fluore cent dyes (of variOllS composition) that absorb light at one wavelength and then emit laser light at another. The output wavelength of these systems may be varied or tuned by the operator by adjusting the dye used (ranging from approximately 400 to 1000 nm). They may be powered by a number of systems such as a flash lamp or another la er [i.e., argon). The continuous wave dye laser sys- Figure 3. Porrwine stain of same patient (Fig. 2) 8 weeks after three pulsed dye laser treatments. which corresponds to the third absorption peak of oxyhemoglobin. When a very brief pulse duration (400 us) is delivered, precise and localized vascular injury occurs, with a histologic appearance resembling vasculitis.32.4 '-52 More recently, it has been demonstrated that a laser emitting dye laser system provides in the treatment of va cular anornalie va cular injury and continued vascular of light, while the pulsed inrerrnirrenr pulses of lighr. The dye laser sy .rern ha ve been ;1 pplicd to the treatment of vascular lesions, since the damage is highly specific to blood vessels, with paring of adjacent tissue clemenrs.J9.4b.47 The tunable dye laser, utilizing the yellow dye rhodamine 6G, c,\n emit at 5 nm, 5 ar formation at 585 nrn is tems provide a ready output and pigment alteration, seen with the use of the argon ed when pulsed the combination dye laser system , with deeper specificity.52.swhich has been la er, has been eliminat- of laser i even more effective used.l2•49 parameters 10 the Inlernnll<)nal Journal of n.rmnll.lo!\! V,,1. 11. Nu. 9. Seprcrubcr 1992 The portwine tain40.46.47 IS the most common va cu- lar lesion treated giomas,H-16 fa with the pul ed dye laser, but hernania l telangiectasias (Figs. 4 and 5),5- poikilodermav" lymphangioma circurnscr iprurn, ~q Ka- spider va ricositic of the legs with the pul ed dye la5er."~-~~ bur hyperpigmentation [borh persistent and transient) plication. posi's sarcoma.f" and blue rubber bleb nevi" have also been treated succe: sfull)' using this la er system. One of have rhe most important seen on histologic advances in the treatment of port- wine stains is the fact that rhe pulsed dye laser can be safely used without scar formation in chiidrenY·62.6J Recently, there has been renewed interest in treating treatment remains a common lesions such as "cafe-au-lair" following Pigmented been treated with a dye laser tuned length of 504 nrn, comspots to a wave- with selective melanocyte examination of laser-treated damage skin."? The cominuou tunable dye laser ha been used in photodynamic therapy. This procedure involves the systemic administration of a phororoxic agent (usually hematoporphyrin derivative), which is electively taken up and retained by malignant cell, followed by delivery of laser light, resulting in a toxic reaction that kills the malignant cell population. The hematoporphyrin derivative is photoacrive when exposed to 630 nm light, which is most often derived from a tunable dye laser, although a non laser source may be used. Its antitumor effect is thought to result from singlet oxygen production with sub. equent necrosis of the irradiated rumor." .69 Basal cell carcinoma has been reported to re pond to photodynamic rherapy,70-73 but prolonged photo cnsitivity reactions following phoroactivarion of the h maroporphyrin derivative have been encountered." limiting its practicality a a treatment modality. Ruby Laser Figure 4. Telangiectasias on the nose of a 60-year-old man. The ruby laser emits a visible red light with a wavelength of 694 nrn. The red light can be delivered via a longpul e system or a Q- witched (shorr pulse) system and is preferentially absorbed by blue or black pigments. On histologic examination, melanosomal disruption with alteration of both epidermal and dermal pigment has been observed when the ruby laser is u ed-'5.76 The ruby laser ha , therefore, been u ed successfully in the treatment of lentigines," nevoccllular nevi," nevus of Ora,77 and tattoos (Figs. 6 and 7).7N-82 Although initially used in the treatment of vascular Iesions,19,34 ir i no longer indicated for uch lesions becau e of exces ive scar formation. This is due to minimal ab orption by both oxyhemoglobin and deoxyhemoglobin at 694 nrn.6.7 Neodynium The Yttrium Aluminum Nd:YAG laser emirs Garnet ( d:YAG) Laser in the invisible near-infrared portion of the spectrum at 1060 nm. It is a continuous wave laser system without color specificity in its absorption. It rends to be a high energy system with deep tissue penetration, leading to a large amount of nonselecrive thermal destruction. Despite its nonselectiviry, the d:YAC laser has found its way into dermatology. Large cavernous hemangiomas of the skin and mucosal surfaces have been treated uccess fully,KH7 as have dark nodular porrwine stains.S~.8~ In addition, the Nd:YA • Figure 5. Same patient (Fig. 4) 6 weeks after single pulsed dye laser treatment. la cr has been used for tattoo rernoval.f" Even with the recent development of a frequency-doubled variant of this system in which a crystal placed in the beam path Dcrmarologic Lasers AISler and Kuhn Figure 6. Previously untreated professional tattoo on arm of a 21-year-old woman (photo courtesy of R. Rox Anderson, M.D.). Figure 7. Tattoo 1 month after sixth ruby laser treatment (see Fig. 6) (photo courtesy of R. Rox Anderson, M.D.). halves the wavelength the argon laser output (giving a green color similar to and, thus, slightly better absorp- tion by hemoglobin), there remains a significant amount of nonspecific tissue destruction, with possible resultant scarring.t" Perhaps the most interesting future application of the Nd:YAG laser in dermatology closure by laser welding. Laser in diameter and the ability to seal nerve endings, allow for better hemostasis and less postoperative pain and edema will be that of wound welded wounds have Carbon Dioxide and/or foreign (C02) than with conventional The C02 laser techniques. is best suited to treat body reaction."! laser Laser rem. The laser laser, emitting is the most system commonly is usually far-infrared wave such as balanitis portion xerorica of the spectrum at 10,600 nm. The energy from the C02 laser is delivered to tissue through sealed tubes with excellent cosmetic and tive swelling and angled mirrors because it cannot Queyrat.l"? be delivered and bowenoid through optical fibers. The energy emitted by a C02 laser is nonselectively absorbed by both intracellular and extracellular water, and, because soft tissue is 80 changes to 90% water, ed with the C02 handy ablate mentary properties, in these obliterans.l'" papulosis'!" erythroplasia lesions because are confined of has been achieved results and minimal morbidity laser. Hypertrophic loss are common is used in the removal sion of keloidal which it is used. Whether the laser is used in either a defocused mode to vaporize tissue or a focused mode unique with postopera- the pathologic to the squamous epithelium of the epidermis (Figs. 8 and 9). Tattoos!!!·!12 and keloidsll3-!!8 have also been treat- total absorption of the C02 laser is a tool because it enables the surgeon to incise or tissue, the outcome depending on the mode in to incise tissue, its other ha ve been treated the C02 laser. Successful C02 laser treatment of actinic cheilitis,!OS,!06 lentigines.l'" and superficial penile lesions, used laser sys- a continuous light at the invisible le- dermal lesions, including syringomas," adenoma sebaceum,95-98 epidermal nevi,93,99 xanthelasma, !OOtrichoepitheliomas/3,!O! apocrine hidrocystomas, !02 myxoid cysts,103 and neurofibromasl'" The C02 epidermal sions, because it works by tissue vaporization. The most common dermatologic conditions treated by the C02 laser arc verruca vulgaris and condyloma acuminatum, especially when they are large and/or recalcitrant to other forms of treatment.92,93 A variety of epidermal and been shown to heal similarly (by tensile strength measurements) to conventionally sutured wounds, with less tissue manipulation and without introduction of foreign material into the wound, thus decreasing the risk of infection up to 1.5 mm ability to seal blood vessels and lymphatics 605 complications of tartoos. tissue showed subsequent reports with same patients have shown such as the scarring when this laser While C02 promising and piglaser exci- initial results, longrerrn follow-up of these high recurrence rares.!19,120 International Journal of Dermatology Vol. 3), Nn. 9, September Figure B. Periungal warts prior to treatment tesy of Jerome Garden, M.D.). (photo cour- Figure 9. Periungual warts after CO2 laser treatment Fig. 8) (photo courtesy of Jerome Garden, M.D.). The combination of vaporization and excision using the CO2 laser in the defocused and focused modes, respectively, is useful in the treatment of rhinophyma 111.122 mechanism by which the CO2 laser works in these conditions is through conduction of heat from the hot epidermis to the upper dermal blood vessels, producing full-thickness epidermal damage. This has been shown to result in hypertrophic scarring.128.129 Those clinicians who favor the use of the C02 laser now reserve its use for debulking large hypertrophic port wine stains and hemangiomas. Utilizing laser technology, many cutaneous disorders are being treated more effectively and with less morbid- Table 2. Specific Dermarologic Lesions Treated with Laser Surgery ity than with conventional therapies. When determining the appropriate laser for use in a particular condition, it is best to categorize the lesion into one of the following groups: vascular, pigmented, tattoo, epidermal process, or dermal process. The laser chosen should correspond to the predominant chromophore or absorbant tissue in the lesion being treated (Table 2). Lesions Lasers Used Vascular Porrwine stains Tela ngiectasias Dye (585 nm) Argon (488, 514 nm) Hemangiomas Blue rubber bleb nevi angiomas Spider veins Cherry Pigmented Lentigines "Cafe-au-lair" Nevocellular spots Tattoos CO2 (10,600 nm) Ruby (694 nm) Epidermal Verrucae Linear epidermal nevi CO2 (10,600 nm) Actinic cheilitis Rhinophyma 2.8 to 4.2% of procedures.U" Hyperis the most frequently reported compli- Nail plate abnormalities Dermal Keloids Appendages] tumors cation, while infection carries a low occurrence rate, estimated at 0.2 to 0.6%. Reports of unintentional 606 Dye (504 rim) Argon (488, 514 nm) Ruby (694 nm) nevi OF LASER SURGERY Lasers are versatile instruments that are associated with an acceptable risk profile. A survey of complications encountered wirh cutaneous laser surgery found the rate to average trophic scarring (see burns to personnel or patients have also been rare. Perhaps the 1110st worrisome disadvantage of laser use is the unknown risk of inhalation of laser smoke. "Lungdamaging dust" consisting of particles with diameters between 0.1 and 1.0 urn has been found in laser plume and can penetrate into distal lung branches.I' 1 In addition, intact human papillornavirus DI'A 132.111 and HIVvirusJ34 have been isolated in laser smoke, and standard surgical masks do not filter out particles of the size seen in the laser plume of irradiated tissue, raising the obvious concern of infectivity of laser vapor. us Smoke evacuation systems are necessary during laser therapy, especially when using the C02 laser, because copious amounts of vaporized material are generated.l " and acne scars. The surface remodeling using the defocused lower irradiance vaporization technique is akin to a superficial dermabrasion and yields excellent cosmetic results. In addition, cosmetic and functional improvement of nail plate abnormalities may be seen when the C02 laser is used in a focused mode to modify the nail rnarrix.P:' The C02 laser has also been used in the treatment of portwine stainsI24.125 and hernangiomas.t-v'<" The COMPLICATIONS J9l1Z D~rl1l.allJlog:it.: UStTS Alsrer and Kohn 12. FUTURE USES OF LASERS IN DERMATOLOGY Nelson JS, Sun CHC, Berns MW. Study of the tn uiuo and capabilities of uroporphyrin 1 compared to photofrin II. Lasers Surg Med 1986; 6; 131-136. ill vitro photosensitizing While laser surgery of dermatologic conditions has been based primarily on [he principles of selective phororherrnolysis, there are other areas of intellectual intrigue that may further the use of lasers both in treat- 13. Berns M, Hammer-Wilson M, Walter R], et aL Uptake and localization of HpD and active fraction in tissue culture and in serially biopsied human tumors. Ad" Exp Mcd Bioi 1983; 170:501-520. 14. Tan OT, Motemedi M, Welch AJ, et al, Spotsize effects on guinea pig skin following pulsed irradiation. J Invest Dermatol1988; 90:877-881. 15. Morernedi M, Welch A], Cheong WF, er al. Thermal lensing in biologic media. IEEE Quantum Electronics ) 988; 24:696-699. ) 6. Anderson RR, Parrish JA. Microvasculature can be selectively damaged using dye lasers: a basic theory and experimental evidence in human skin. Lasers Surg Med 1981; 1:263-276. 17. Apfelberg DB, Maser MR, Lash H, er al. The argon laser for cutaneous lesions. JAMA 1981; 245:2073-2075. 18. Apfelberg DB, Maser MR, Lash H. Argon laser treatment of cutaneous vascular abnormalities. Ann Plasr Surg 1978; 1:14-18. ) 9. Goldman L, T rcHer R. Laser treatment of extensive mixed cavernous and port wine stains. Arch Derrnarol 1977; 113:504-505. 20. Cosman B. Experience in the argon laser therapy of porr wine stains. Plast Reconsrr Surg 1980; 65:119-129. 21. Noe JM, Barsky SH, Geer DE, et al. Porrwine stains and the response to argon laser therapy: successful treatment of the predictive role of color, age, and biopsy. Plasr Reconsrr Surg 1980; 65:130-136. rnsnr and diagnosis. The use of low-energy healing, presumably blasts':" or by some other lasers to accelerate by stimulation wound of dermal biostirnulative fibro- process138-J45 is but one area generating much interest in the scientific community. Laser induced photodynamic therapy (PDT) is another expanding area, which is already showing promise as a tool for selective cytotoxicity using newer, less toxic, but more photosensitizing substances.r" ditionally, liposomaJl47-149 or monoclonal antibody Adde- livery systems may with laser-induced release of drugs, aid in the diagnosis and subsequent treatment of neoplastic or proliferative conditions. In conclusion, the future practice of dermatology will be greatly benefited by laser technology. 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