REVIEW
DERMATOLOGIC LASERS: THREE DECADES OE PROGRESS TINA S. ALSTER, M.D., AND STEVEN R. KOHN, M.D.
Thirty years have passed since the creation of the first laser. Although significant applications for lasers were forecast immediately, tnany 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.
1960, Theodore Maiman at Hughes Aircraft Research Laboratories actually developed the first laser, a ruby laser.^ Many other types of lasers have subsequently been developed, but Maiman'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 hght 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 attempted.-' 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.
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 spontaneously, 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.^ In
LASER PRINCIPLES 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) tunability. 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 to ultraviolet permits selective excitation
From the Departments of Dermatology and Pediatrics, Yale University School of Medicine, New Haven, Connecticut, Georgetown University School of Medicine, Washington DC, and Columbia University College of Physicians and Surgeons, New York, New York. Address for correspondence: Tina S. Alster, M.D., Georgetown University Medical Center, Washington Institute of Dermatologic Laser Surgery, 2311 M Street, N.W., Suite 504, Washington, DC 20037. 601
International Journal of Dermatology Vol. 31, No. 9, September 1992
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 to suit a particular application. The concept of "selective photothermolysis" 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 tissue.^ One control of laser-tissue interaction involves matching the wavelength of laser light to the absorption spectrum peak of the target tissue. The absorbing molecules (or chromophores) 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 response in the treatment of vascular lesions'*"'" 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 advantage.'^''•' 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-
^
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 interaction.'"^'^^ Regardless of what tissue is absorbing the laser energy, once this energy is converted to heat, it will spread throughout the surrounding tissue. If the energy source continues for too long, damage to normal stroma may occur from heat dissipation, and the relative optical absorptive advantage gained by choosing the appropriate wavelength and spot 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 time 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 structure."' 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).
LASER TYPES
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 dermatologic conditions. Each will be briefly summarized, but without detailing the laser mechanics involved.
10= -
Argon Laser
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 used primarily in the treatment of vascular lesions, including portwine stains (Figs. 2 and 3),''"^'' telangiectasias,'^'"*'^'"^^ spider varicosities,^**"-^" pyogenic granulomas,'^ cherry angiomas,''' venous lakes,'^ angiokeratomas,^' and Kaposi's sarcoma.'^ Theoretically, there should be selective absorption of the light by hemoglobin within the blood vessels
i, 10 -
*
100
'
200
300 400 500
700
1000
2000 * (nml
Figure 1. Absorption coefficient spectrum of hemoglobin (HbOj) and melanin. 602
Dermatologic Lasers Alster and Kohn
Table 1. Characteristics of Lasers Laser
Medium Wavelength Chromophore
Argon
Gas
Dye
Liquid
Ruby
Solid
Nd:YAG Solid GO2
Gas
Lesions Treated
488 nm. 514 nm Variable, depends on dye 694 nm
Hemoglobin Melanin Variable
Vascular Pigmented Vascular Pigmented
Melanin Tattoo pigment
1060 nm 10,600 nm
—
Pigmented Tattoo Vascular Epidermal Dermal Excision
Water
comprising the lesion; however, several histologic studjgj32-35 i^ayg (-j5[ doubt on the specificity of the damage, showing the argon laser effects possibly due to nonspecific thermal destruction of skin. It has 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 dyspigmentation.^' Several clinicians have, nevertheless, reported excellent results with lesion regression and minimal scarring, especially in those protocols using very low energies.'^ With the advent of newer, more vascular-specific systems (pulsed dye lasers), however, the argon laser is falling out of favor as the laser of choice for treatment of vascular lesions.^*'"^" Because the wavelength of light is well absorbed by melanin, the argon laser has been used to treat pigmented lesions such as lentigo maligna and benign nevi,'""'*^ "cafe-au-lait" spots,'^ nevus of Ota,'^ and chloasma.'^ Tattoos have also been treated with some success,"'•'*'* but there have been reports of significant postoperative scarring. Nonpigmented lesions reported to be successfully removed by argon laser have included granuloma faciale,"*^ and lymphocytoma cutis,'^ both having a reddish-purple hue that may selectively absorb the blue-green light.
Eigure 2. Portwine stains on tlic nose and medial canthus of a 21-year-old female with prior argon laser test site (mid-nose).
Tunable Dye Laser
Figure 3. Portwine stain of same patient (Eig. 2) 8 weeks after three pulsed dye laser treatments.
The tunable dye lasers contain fluorescent dyes (of various 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 laser (i.e., argon). The continuous wave dye laser systems provide a steady output of light, while the pulsed dye laser system provides intermittent pulses of light. The dye laser systems have been applied to the treatment of vascular lesions, since the damage is highly specific to blood vessels, with sparing of adjacent tissue elements.^'•''^'''^ The tunable dye laser, utilizing the yellow dye rhodamine 6G, can emit at 577 nm.
which corresponds to the third absorption peak of oxyhemoglobin. When a very brief pulse duration (400 |is) is delivered, precise and localized vascular injury occurs, with a histologic appearance resembling vasculitis.'^-'"*"-'^ More recently, it has been demonstrated that a laser emitting at 585 nm is even more effective in the treatment of vascular anomalies, with deeper vascular injury and continued vascular specificity."'^^ Scar formation and pigment alteration, which has been seen with the use of the argon laser, has been eliminated when the combination of laser parameters in the pulsed dye laser system is 603
International Journal of Dermatology Vol. 31, No. 9, September 1992
spider varicosities of the legs with the pulsed dye laser,^'*"^'' but hyperpigmentation (both persistent and transient) following treatment remains a common complication. Pigmented lesions such as "cafe-au-lait" spots have been treated with a dye laser tuned to a wavelength of 504 nm, with selective melanocyte damage seen on histologic examination of laser-treated skin.*^ The continuous tunable dye laser has been used in photodynamic therapy. This procedure involves the systemic administration of a phototoxic agent (usually hematoporphyrin derivative), which is selectively taken up and retained by malignant cells, followed by delivery of laser light, resulting in a toxic reaction that kills the malignant cell population. The hematoporphyrin derivative is photoactive when exposed to 630 nm light, which is most often derived from a tunable dye laser, although a nonlaser source may be used. Its antitumor effect is thought to result from singlet oxygen production with subsequent necrosis of the irradiated tumor.'^*-''' Basal cell carcinoma has been reported to respond to photodynamic tberapy,^""^^ but prolonged pbotosensitivity reactions following photoactivation of the hematoporphyrin derivative have been encountered,^"* limiting its practicality as a treatment modality.
The portwine stain'"^'''*'''^ is the most common vascular lesion treated with the pulsed dye laser, but hemangiomas,'''"-'* facial telangiectasias (Figs. 4 and 5),'^ poikiloderma,^** lymphangioma circumscriptum,^' Kaposi's sarcoma,*"" and blue rubber bleb nevi*"' have also been treated successfully using this laser system. One of the most important advances in the treatment of portwine stains is the fact that the pulsed dye laser can be safely used without scar formation in children.'''•"'^-^ Recently, there has been renewed interest in treating
Ruby Laser The ruby laser emits a visible red light with a wavelength of 694 nm. The red light can be delivered via a longpulse system or a Q-switched (short 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 used.^^''''^ The ruby laser has, therefore, been used successfully in the treatment of lentigines,^^ nevocellular nevi,^^ nevus of Ota,^^ and tattoos (Figs. 6 and 7).^'*-'*^ Although initially used in the treatment of vascular lesions,"'^"* it is no longer indicated for such lesions because of excessive scar formation. This is due to minimal absorption by both oxyhemoglobin and deoxyhemoglobin at 694 nm.^'^
Eigure 4. Telangiectasias on the nose of a 60-ycar-old man.
Neodynium Yttrium Aluminum Garnet (Nd:YAG) Laser The Nd:YAG laser emits 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 tends to be a high energy system witb deep tissue penetration, leading to a large amount of nonselective thermal destruction. Despite its nonselectivity, the Nd:YAG laser has found its way into dermatology. Large cavernous hemangiomas of the skin and mucosal surfaces have been treated successfully,**^"^^ as have dark nodular portwine stains.^^'*' In addition, the Nd:YAG laser has been used for tattoo removal.'*'' Even with the recent development of a frequency-doubled variant of this system in which a crystal placed in the beam path
Figure 5. Same patient (Eig. 4) 6 weeks after single pulsed dye laser treatment. 604
Dermatologic Lasers Alster and Kohn
Eigure 6. Previously untreated professional tattoo on arm of a 21-year-old woman (photo courtesy of R. Rox Anderson, M.D.). Eigure 7. Tattoo 1 month after sixth ruby laser treatment (see Eig. 6) (photo courtesy of R. Rox Anderson, M.D.). halves the wavelength (giving a green color similar to the argon laser output and, thus, slightly better absorption by hemoglobin), there remains a significant amount of nonspecific tissue destruction, with possible resultant scarring.'° Perhaps the most interesting future application of the Nd:YAG laser in dermatology will be that of wound closure by laser welding. Laser welded wounds have 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 and/or foreign body reaction."
ability to seal blood vessels and lymphatics up to 1.5 mm in diameter and the ability to seal nerve endings, allow for better hemostasis and less postoperative pain and edema than with conventional techniques. The CO2 laser is best suited to treat epidermal lesions, because it works by tissue vaporization. The most common dermatologic conditions treated by the CO2 laser are verruca vulgaris and condyloma acuminatum, especially when they are large and/or recalcitrant to .other forms of treatment.'-'^' A variety of epidermal and dermal lesions, including syringomas,'"* adenoma sebaceum,'-''"'** epidermal nevi,^^-'' xanthelasma,'"" trichoepitheliomas,"'"" apocrine hidrocystomas,'"- myxoid cysts,'"^ and neurofibromas'"'' have been treated with the CO2 laser. Successful CO2 laser treatment of actinic cheilitis,'"'''"* lentigines,'"^ and superficial penile lesions, such as balanitis xerotica obliterans,'"* erythroplasia of Queyrat,'"^ and bowenoid papulosis"" has been achieved with excellent cosmetic results and minimal postoperative swelling and morbidity because the pathologic changes in these lesions are confined to the squamous epithelium of the epidermis (Figs. 8 and 9).
Carboti Dioxide (CO2) Laser The CO2 laser is the most commonly used laser system. The laser system is usually a continuous wave laser, emitting light at the invisible far-infrared portion of the spectrum at 10,600 nm. The energy from the CO2 laser is delivered to tissue through sealed tubes and angled mirrors because it cannot be delivered through optical fibers. The energy emitted by a CO2 laser is nonselectively absorbed by both intracellular and extracellular water, and, because soft tissue is 80 to 90% water, total absorption of the CO2 laser is a handy tool because it enables the surgeon to incise or ablate tissue, the outcome depending on the mode in which it is used. Whether the laser is used in either a defocused mode to vaporize tissue or a focused mode to incise tissue, its other unique properties, such as the
Tattoos'"'"- and keloids"^""* have also been treated with the CO2 laser. Hypertrophic scarring and pigmentary loss are common complications when this laser is used in the removal of tattoos. While CO2 laser excision of keloidal tissue showed promising initial results, subsequent reports with longterm follow-up of these same patients have shown high recurrence rates."'''^'' 605
International Journal of Dermatology Vol. 31, No. 9, September 1992
Figure 8. Periungal warts prior to treatment (photo courtesy of Jerome Garden, M.D.).
Figure 9. Periungual warts after CO2 laser treatment (see 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^^'-^^^ 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 nai! plate abnormalities may be seen when the CO2 laser is used in a focused mode to modify the nail matrix.'^^ The CO2 laser has also been used in the treatment of portwine stains^^'*''^'' and hemangiomas.'^*'''^^ The 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 hypertrophlc scarring.^^^''^' Those clinicians who favor the use of the CO2 laser now reserve its use for debulking large hypertrophic portwine stains and hemangiomas. Utilizing laser technology, many cutaneous disorders are being treated more effectively and with less morbidity 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).
burns to personnel or patients have also been rare. Perhaps the most 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 ^m has been found in laser plume and can penetrate into distal lung branches.'•'' In addition, intact human papillomavirus DNA'^^'''' and Hivvirus'^'' 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.'^^ Smoke evacuation systems are necessary during laser therapy, especially when using the CO2 laser, because copious amounts of vaporized material are generated.'^"^
Table 2. Specific Dermatologie Lesions Treated with Laser Surgery Lesions
Lasers Used
Vascular Portwine stains Telangiectasias Hemangiomas Blue rubber bleb nevi Cherry angiomas Spider veins
Dye (585 nm) Argon (488, 514 nm)
Pigmented Lentigines "Cafe-au-lait" spots Nevocellular nevi
Dye (504 nm) Argon (488, 514 nm) Ruby (694 nm)
Tattoos
CO2 (10,600 nm) Ruby (694 nm) CO2 (10,600 nm)
COMPLICATIONS OF LASER SURGERY
Epidermal Verrucae Linear epidermal nevi Actinic cheilitis Rhinophyma Nail plate abnormalities Dermal Keloids Appendageal tumors
Lasers are versatile instruments that are associated with an acceptable risk profile. A survey of complications encountered with cutaneous laser surgery found the rate to average 2.8 to 4.2% of procedures.'-"' Hypertrophic scarring is the most frequently reported complication, while infection carries a low occurrence rate, estimated at 0.2 to 0.6%. Reports of unintentional 606
CO2 (10,600 nm)
Dermatologie Lasers Alster and Kohn
FUTURE USES OF LASERS IN DERMATOLOGY
While laser surgery of dermatologie conditions has been based primarily on the principles of selective photothermolysis, there are other areas of intellectual intrigue that may further the use of lasers both in treatment and diagnosis. The use of low-energy lasers to accelerate wound healing, presumably by stimulation of dermal fibroblasts"^ or by some other biostimulative process'^'"'"*' 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.''"^ Additionally, liposomal''*''-''''' or monoclonal antibody delivery systems with laser-induced release of drugs, may aid in the diagnosis and subsequent treatment of neoplastic or proliferative conditions.
12.
Nelson JS, Sun CHC, Berns MW. Study of the in vivo and in vitro photosensitizing capabilities of uroporphyrin I compared to photofrin 11. Lasers Surg Med 1986; 6: 131-136.
13.
Berns M, Hammer-Wilson M, Walter RJ, et al. Uptake and localization of HpD and active fraction in tissue culture and in serially biopsied human tumors. Adv Exp Med Biol 1983; 170:501-520.
14.
Tan OT, Motemedi M, Welch AJ, et al. Spotsize effects on guinea pig skin following pulsed irradiation. J Invest Dermatol 1988; 90:877-88L Motemedi M, Welcb AJ, Cheong WE, et al. Thermal lensing in biologic media. IEEE Quantum Electronics 1988; 24:696-699. 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. Apfelberg DB, Maser MR, Lash H, et al. The argon laser for cutaneous lesions. JAMA 1981; 245:2073-2075. Apfelberg DB, Maser MR, Lash H. Argon laser treatment of cutaneous vascular abnormalities. Ann Plast Surg 1978; 1:14-18. Goldman L, Treffer R. Laser treatment of extensive mixed cavernous and port wine stains. Arch Dermatol 1977; 113:504-505. Cosman B. Experience in the argon laser therapy of port wine stains. Plast Reconstr Surg 1980; 65:119-129. Noe JM, Barsky SH, Geer DE, et al. Portwine stains and the response to argon laser therapy: successful treatment of the predictive role of color, age, and biopsy. Plast Reconstr Surg 1980; 65:130-136. Hobby LW. Treatment of portwine stains and other cutaneous lesions. Contemp Surg 1981; 8:21-45. Arndt K. Treatment technics in argon laser therapy. J Am Acad Dermatol 1984; 11:90-97. Cosman B. Clinical exposure in the laser therapy of portwine stains. Lasers Surg Med 1988; 8:133-152. Apfelberg DB, Maser MR, Lash H. Extended clinical use of the argon laser for cutaneous lesions. Arch Dermatol 1979; 115:719-721. Apfelberg DB, Maser MR, Lash H. Treatment of nevus araneus by means of an argon laser. J Dermatol Surg Oncol 1978; 4:172-174. Arndt KA. Argon laser therapy of small cutaneous vascular lesions. Arch Dermatol 1982; 118:220-224. Apfelberg DB, Maser MR, Lash H, et al. Use of the argon and carbon dioxide lasers for treatment of superficial venous varicosities of the lower extremity. Lasers Surg Med 1984; 4:221-232. Apfelberg DB, Smith T, Maser MR, et ai. Study of three laser systems for treatment of superficial varicosities of the lower extremity. Lasers Surg Med 1987; 7:219-223. Lyons GD, Owens RE, Mouney DF. Argon laser destruction of cutaneous telangiectatic lesions. Laryngoscope 1981; 91:1322-1325. Pasyk KA, Argenta LC, Schelbert EB. Angiokeratoma circumscriptum: successful treatment with the argon laser. Ann Plast Surg 1988; 20:183-190. Tan OT, Carney M, Margolis R, et al. Histologic responses of portwine stains treated by argon, carbon dioxide and dye lasers: a preliminary report. Arch Dermatol 1986; 122:1016-1022.
15.
16.
17. 18.
In conclusion, the future practice of dermatology will be greatly benefited by laser technology. We are just now beginning to manipulate laser effects on tissue in order to maximize desired laser-tissue interactions and design new therapeutics and diagnostics. The benefits of lasers to medicine and mankind in the next 30 years are eagerly anticipated.
19.
20. 21.
REFERENCES 1. 2. 3.
22.
Caruth JAS, McKenzie AL. Medical lasers: science and clinical applications. Bristol, UK: Adam Hilger, 1986. Schawlow AL, Townes CH. Infrared optical masers. Physiol Rev 1958; 112:1940-1949. Maiman TH. Stimulated optical radiation in ruby. Nature 1960; 187:493-494.
23. 24.
4.
Goldman L, Blaney DJ, Kindel DJ, et al. Pathology of the effect of the laser beam on the skin. Nature 1963; 197:912-914.
25.
5.
Goldman L, Blaney DJ, Kindel DJ, et al. Effect of the laser beam on the skin. J Invest Dermatol 1963; 40:121122.
26.
6.
Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science 1983; 220:524-527. Anderson RR, Parrish JA. The optics of human skin. J Invest Dermatol 1981; 77:13-19.
7. 8.
Rosen S. Nature and evolution of portwine stains. In: Arndt K, Noe JM, Rosen S, eds. Cutaneous laser therapy: principles and methods. New York: John Wiley & Sons, 1983: 75.
9.
Tong AKF, Tan OT, Boll J, et al. Ultrastructure: effects of melanin pigment on target specificity using a pulsed dye laser (577 nm). J Invest Dermatol 1987; 88:847-852. Tan OT, Murray S, Kurban AK. Action spectrum of vascular specific injury using pulsed irradiation. J Invest Dermatol 1989; 92:717-720. Sherwood KA, Murray S, Kurban AK, et al. Effect of wavelength on cutaneous pigment using pulsed irradiation. J Invest Dermatol 1989; 92:717-720.
10.
11.
27. 28.
29.
30.
31.
32.
607
International Journal of Dermatology Vol. 31, No. 9, September 1992
33.
34.
35.
36.
37.
38. 39.
40.
41. 42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
Greenwald J, Rosen S, Geer DE, et al. Comparative histological studies of the tunable dye (at 577 nm) laser and argon laser. J Invest Dermatol 1981; 77:305-310. Solomon H, Goldman L, Henderson B, et al. Histopathology of the laser treatment of port-wine lesions. J Invest Dermatol 1968; 50:141-146. Apfelberg DB, Kosek J, Maser MR, et al. Histology of portwine stains following argon laser treatment. Br J Plast Surg 1979; 32:232-287. Dixon J, Huether S, Rotering RH. Hypertrophic scarring in argon laser treatment of portwine stains. Plast Reconstr Surg 1984; 73:771-780. Finley JL, Barsky SH, Geer DE, et al. Healing of portwine stains after argon laser therapy. Arch Dermatol 1981; 117:486-489. Tan OT, Stafford TJ. Treatment of port wine stains at 577 nm. Med Instrument 1987; 21:218-221. Garden JM, Polla LL, Tan OT. The treatment of portwine stains by the pulsed dye laser: analysis of pulse duration and long-term therapy. Arch Dermatol 1988; 124:889-896. Morelli J, Tan OT, Garden J, et al. Tunable dye laser (577 nm) treatment of portwine stains. Lasers Surg Med 1986; 694-699. Arndt KA. Argon laser treatment of lentigo maligna. J Am Acad Dermatol 1984; 10:953-957. Oshiro T, Maruyama Y. The ruby and argon lasers in tbe treatment of naevi. Ann Acad Med Singapore 1983; 12:388-395. Goldman L, Igelman JM, Ricbfield DE. Impact of the laser on nevi and melanomas. Arch Dermatol 1964; 90: 71-75. Apfelberg DB, Druker D, Maser MR, et al. Argon laser treatment of decorative tattoos. Br J Plast Surg 1979; 32:232-237. Apfelberg DB, Druker D, Maser MR, et al. Granuloma faciale treatment witb the argon laser. Arcb Dermatol 1983; 119:573-576. Garden JM, Tan OT, Polla L, et al. Tbe pulsed dye laser as a modality for treating cutaneous small blood vessel disease processes. Laser Surg Med 1986; 6:259. Tan OT, Sherwood KA, Gilchrest BA. Successful treatment of children with portwine stains using the flashlamp pulsed tunable dye laser. N Engl J Med 1989; 320:416-421. Garden JM, Tan OT, Kerschmann R, et al. Effect of dye laser pulse duration on selective cutaneous vascular injury. J Invest Dermatol 1986; 87:653-657. Greenwald J, Rosen S, Anderson RR, et al. Comparative histological studies of the tunable dye (at 577 nm) laser and argon laser: the specific vascular effects of tbe dye laser. J Invest Dermatol 1981; 77:305-310. Tan OT, Whitaker D, Garden JM, et al. Pulsed dye laser (577 nm) treatment of portwine stains: ultrastructural evidence of neovascularization and mast cell degranulation in healed lesions. J Invest Dermatol 1988; 90:395-398. Nakagawa H, Tan OT, Parrisb JA. Ultrastructural changes in human skin after exposure to a pulsed laser. J Invest Dermatol 1985; 84:396-400. Tan OT, Murray S, Kurban AK. Action spectrum of vascular specific injury using pulsed irradiation. J Invest Dermatol 1989; 92:868-871.
53.
54.
55.
56.
57.
58. 59.
60.
61. 62.
63.
64.
65.
66.
67.
68.
69.
70. 71,
72.
608
Kurban AK, Sherwood KA, Tan OT. What are the optimal wavelengths for selective vascular injury? Lasers Surg Med 1988; 8:189. Ashinoff R, Geronemus R. Capillary hemangiomas and treatment with the flash lamp-pumped pulsed dye laser. Arcb Dermatol 1991; 127:202-205. Sherwood KA, Tan OT. Treatment of a capillary hemangioma with the flasblamp pulsed dye laser at 585 nm. J' Am Acad Dermatol 1990; 22:136-137. Glassberg E, Lask G, Rabinowitz LG, et al. Capillary hemangiomas: case study of a novel laser treatment and a review of therapeutic options. J Dermatol Surg Oneol 1989; 15:1214-1223. Lowe NJ, Behr KL, et al. Flash-lamp pumped dye laser for rosacea-associated telangiectasia and erythema. J Dermatol Surg Oncol 1991; 17:522-525. Geronemus RG. Poikiloderma. Arch Dermatol 1990; 26:547-548. Weingold D, White P, Burton CS. Treatment of lymphangioma circumscriptum with tunable dye laser. Cutis 1990; 45:365-366. Moritz DL, Lynch WS. Kaposi's sarcoma treated with tbe Candela flash-lamp pulsed dye laser. Am Soc Derm Surg 1990 (abstract). Olsen TG, Milroy SK, Goldman L, et al. Laser surgery for blue rubber bleb nevus. Arcb Dermatol 1979; 115:81-82. Reyes BA, Geronemus R. Treatment of port wine stains during childhood with the flashlamp-pumped dye laser. J Am Acad Dermatol 1990; 23:1142. Ashinoff R, Geronemus R. Elashlamp-pumped pulsed dye laser for port-wine stains in infancy: earlier versus later treatment. J Am Acad Dermatol 1991; 24:467-472. Polla LL, Tan OT, Garden JM, et al. Tunable dye laser for the treatment of benign cutaneous vascular ectasia. Dermatologica 1987; 174:11-17. Goldman MP, Martin DE, Eitzpatrick RE, et al. Pulse dye laser treatment of telangiectasia with and without subtherapeutic sclerotherapy: clinical and histologic examination in the rabbit ear vein mode). J Am Aead Dermatol (in press). Goldman MP, Fitzpatrick RE. Pulsed-dye laser treatment of leg telangiectasia: witb and without simultaneous sclerotherapy. ] Dermatol Surg Oncol 1990; 16: 338-344. Sherwood KA, Kurban AK, Tan OT. Selective melanocyte damage using pulsed irradiation over a variety of wavelengths. Lasers Surg Med 1988; 8:190. Riesz P, Krishna CM. Phthalocyanines and their sulfonated derivatives as photosensitizers in photodynamic therapy. Proe Soc Photo-Optic Instrum Eng 1987; 847:15-28. Sonoda M, Krishna CM, Riesz P. The role of singlet oxygen in tbe photobemolysis of red blood eells sensitized by pbthalocyanine sulfonates. Photochem Photobio( 1987; 46:625-631. Dougherty TJ. Pbotodynamic therapy (PDT) of malignant tumors. Crit Rev Oncol/Hematol 1984; 2:83-116. Tomio L, Calzavara F, Zorat PL, et al. Photoradiation therapy for cutaneous and subcutaneous malignant tumors using bematoporphyrin. Prog Clin Biol Res 1984; 170:829-840. McCaugban JS Jr, Guy JT, Hicks W, et al. Photodynamic therapy for cutaneous and subcutaneous malignant neoplasms. Arch Surg 1989; 124:211-216.
Dermatologie Lasers Alster and Kohn
73. 74.
75.
76.
77. 78.
79.
80.
81.
82.
83.
84.
Berns MW, McCuUough JL. Porphyrin sensitized phototherapy. Arch Dermatol 1986; 122:871-874. Zalar GL, Poh-Fitzpatrick M, Krobn DL, et al. Induction of drug photosensitization in man after parenteral exposure to hematoporphyrin. Arch Dermatol 1977; 113:1392-1397. Polla LL, Margolis RJ, Dover JS, et al. Melanosomes are a primary target of Q-switched ruby laser irradiation in guinea pig skin. J Invest Dermatol 1987; 89:281-286. Dover JS, Margolis RJ, Polla LL, et al. Pigmented guinea pig skin irradiated with Q-switched ruby laser pulses. Arch Dermatol 1989; 125:43-49.
93.
Bailin PL. Use of the CO2 laser for non-PWS cutaneous lesions. In: Arndt KA, Noe JM, Rosen S, eds. Cutaneous laser therapy: principles and methods. New York: John Wiley & Sons, 1983:187.
94.
Wheeland RG, Bailin PL, Reynolds O, et al. Carbon dioxide (CO2) laser vaporization of multiple facial syringomas. J Dermatol Surg Oncol 1986; 12:223-228. Wheeland RG, Bailin PL, Kantor G, et al. Treatment of adenoma sebaceum with carbon dioxide laser vaporization. J Dermatol Surg Oncol 1985; 11:861-864. Janniger CK, Goldberg DJ. Angiofibromas in tuberous sclerosis: comparison of treatment by earbon dioxide and argon laser. J Dermatol Surg Oncol 1990; 16: 317-320. Weston J, Apfelberg DB, Maser MR, et al. Carbon dioxide laserbrasion for treatment of adenoma sebaceum in tuberous sclerosis. Ann Plast Surg 1985; 15:132-137. Spenler CW, Achauer BM, VanderKam VM. Treatment of extensive adenoma sebaceum with a carbon dioxide laser. Ann Plast Surg 1988; 20:586-589. Ratz JL, Bailin PL, Lakeland RF. Carbon dioxide laser treatment of epidermal nevi. J Dermatol Surg Oncol 1986; 12:567-570. Apfelberg DB, Maser MR, Lash H, et al. Treatment of xanthelasma palpebrarum with the carbon dioxide laser. J Dermatol Surg Oncol 1987; 13:149-151. Wheeland RG, Bailin PL, Kronberg E. Carbon dioxide (CO2) laser vaporization for tbe treatment of trichoepitheliomata. J Dermatol Surg Oncol 1984; 10:470^74. Bickley LK, Goldberg DJ. Multiple apocrine hidroeystomas treated by CO2 laser. J Dermatol Surg Oncol 1989; 15:599-602. Huener CJ, Whelland RL, Bailin PL, et al. Lasers: treatment of myxoid cysts with carbon dioxide laser vaporization. J Dermatol Surg Oncol 1988; 29:357-369. Roenigk RK, Ratz JL. CO2 laser treatment of cutaneous neurofibromas. J Dermatol Surg Oncol 1987; 13:187190. David LM. Laser vermilion ablation for actinic cheilitis. J Dermatol Surg Oncol 1985; 11:605-608. Stanley RJ, Roenigk RK. Actinie cheilitis: treatment with the carbon dioxide laser. Mayo Clin Proc 1988; 63: 230-235.
95.
96.
Ahshiro T, Maruyama Y. The ruby and argon lasers in the treatment of naevi. Ann Acad Med 1983; 12: 388-395. Reid WH, McLeod PJ, Ritchie A, et al. Q-switched ruby laser treatment of black tattoos. Br J Plast Surg 1983; 36455-459. Vance CA, McLeod PJ, Reid WH, et al. Q-switched ruby laser treatment of tattoos: a further study. Lasers Surg Med 1985; 5:179. Taylor CR, Anderson RR, Dover JS, et al. Selective photothermolysis of dermal pigmentation: light and electron microscopic analysis of black tattoos treated witb Q-switched ruby laser (abstract). J Invest Dermatol 1989; 92:530.
97.
98.
99.
100.
Reid WH, Miller ID, Murphy MJ, et al. Q-switched ruby laser treatment of tattoos: a 9-year experience. Br J Plast Surg 1990; 43:663-669.
101.
Taylor CR, Gange RW, Dover JS, et al. Treatment of tattoos by Q-switched ruby laser: a dose response study. Areh Dermatol 1990 (in press). Apfelberg DB, Maser MR, White DN, et al. A preliminary study of the combined effect in neodynium: YAG laser photocoagulation and direct steroid instillation in the treatment of capillary cavernous hemangiomas of infancy. Ann Plast Surg 1989; 22:94-104. Landthaler M, Haina D, Brunner R, et al. NeodyniumYAG laser therapy for vascular lesions. J Am Acad Dermatol 1986; 14:107-117.
102.
103.
104.
105.
85.
Shapshay SM, David LM, Zeitels S. Neodynium-YAG laser photoeoagulation of hemangiomas of tbe head and neck. Laryngoscope 1987; 97:323-330. 86. Apfelberg DB, Smith T, Lash H, et al. Preliminary report on tbe use of the neodynium-YAG laser in plastic surgery. Lasers Surg Med 1987; 7:189-198. 87. Rosenfeld H, Sherman R. Treatment of cutaneous and deep vascular lesions with the Nd:YAG laser. Lasers Surg Med 1986; 6:20-23. 88. Goldman L, Nath G, Schindler G. High-power neodynium-YAG laser surgery. Acta Derm Venereol (Stockh) 1973; 53:45-49. 89. Dixon JA, Gilbertson JJ. Argon and neodynium-YAG laser therapy of dark nodular port wine stains in older patients. Lasers Surg Med 1986; 6:5-11. 90. Apfelberg DB, Bailin P, Rosenberg H. Preliminary investigation of KTP/532 laser light in the treatment of hemangiomas and tattoos. Lasers Surg Med 1986; 6:38-42. 91. Abergel RP, Lyons RF, White RA, et al. Skin closure by Nd:YAG laser welding. J Am Acad Dermatol 1986; 14:810-814. 92. McBurney El, Rosen DA. Carbon dioxide laser treatment of verruca vulgaris. J Dermatol Surg Oncol 1984; . 10:45-48.
106. •
107. Dover JS, SmoUer BR, Stern RS, et al. Low-fluence carbon dioxide laser irradiation of lentigines. Arch Dermatol 1988; 124:1219-1224. 108. Ratz JL, Carbon dioxide laser treatment of balanitis xerotica obliterans. J Am Aead Dermatol 1984; 10: 925-928. 109. Greenbaum S, Glogau R, Stegman S, et al. Carbon dioxide laser treatment of erythroplasia of Queyrat. J Dermatol Surg Oncol 1989; 15:747-754. 110. Landthaler M, Haina D, Brunner R, et al. Laser therapy of bowenoid papulosis and Bowen's disease. J Dermatol Surg Oncol 1986; 12:1253-1257. 111. Apfelberg DB, Maser MR, Lash H, et al. Comparison of argon and carbon dioxide laser treatment of decorative tattoos: a preliminary report. Ann Plast Surg 1985; 14:6-15. 112. Bailin PL, Ratz JL, Levine HL. Removal of tattoos by CO2 laser. J Dermatol Surg Oncol 1980; 6:997-1001. 113. Kantor GR, Wheeland RG, Bailin PL, et al. Treatment of earlobe keloids with carbon dioxide laser excision: a 609
Internation.!] Journal of Dermatology Vol. 31, No. 9, September 1992
report of 16 cases. J Dermatol Surg Oncol 1985; 11: 1063-1067.
132. Gardon JM, O'Banion MK, Shelnitz LS, et al. Papillomavirus in the vapor of carbon dioxide laser-treated verrucae. JAMA 1988; 259:1199-1202. 133. Sawcbuk WS, Weber PJ, Lowy DR, et al. Infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or eleetrocoagulation: detection and protection. J Am Acad Dermatol 1989; 20:41-49.
114. Wheeland RG. Excisional surgery performed with the carbon dioxide laser. In: Wheeland RG, ed. Lasers in skin disease. New York: Thieme Medical Publishers, 1988:105. 115. Bailin PL. Use of the CO2 laser for non-PWS cutaneous lesions. In: Arndt KA, Noe JM, Rosen S, eds. Cutaneous laser therapy: principles and methods. Chicester, UK: John Wiley and Sons, 1983:187. 116. Bailin PL, Ratz JL. Use of the carbon dioxide laser in dermatoiogic surgery. In: Ratz JL, ed. Lasers in eutaneous medicine and surgery. Chicago: Year Book Medical Publishers, 1986:73. 117. Ratz JL. Laser applications in dermatology and plastic surgery. In: Dixon J, ed. Surgical applications of lasers. Chicago: Year Book Medical Publishers, 1987:160. 118. Kantor GR, Ratz JL, Wheeland RG. Treatment of acne keloidalis nuehae with carbon dioxide laser. J Am Acad Dermatol 1986; 14:263-267. 119. Apfelberg DB, Maser MR, Lash H, et al. Preliminary results of argon and carbon dioxide laser treatment of keloid scars. Lasers Surg Med 1984; 4:283-290. 120. Apfelberg DB, Maser MR, Wbite DN, et al. Failure of carbon dioxide laser excision of keloids. Lasers Surg Med 1989; 9:382-388. 121. Bobigegian RK, Shapshay DR, Hybey RL. Management of rhinophyma with earbon dioxide laser: Lahey Clinie experience. Lasers Surg Med 1988; 8:397-401. 122. Haas A, Wheeland RG. Treatment of massive rhinopbyma with the carbon dioxide laser. J Dermatol Surg Oncol 1990; 16:645-649. 123. Leshin B, Whitaker DL. Carbon dioxide laser matriectomy. J Dermatol Surg Oncol 1988; 14:608-611. 124. Ratz J, Bailin P, Levine H. CO2 laser treatment of port wine stains: a preliminary report. J Dermatol Surg Oncol 1982; 8:1039-1044.
134. Baggish MS, Polesz BJ, Joret D, et al. Presence of human immunodeficiency virus DNA in laser smoke. Lasers Surg Med 1991; 11:197-203. 135. Nezhat C, Winer WK, Nezhat F, et al. Smoke from laser surgery: is there a health hazard.' Lasers Surg Med 1987; 7:376-382. 136. Garden JM. Tbe hazards of laser plume: a mid-year committee report. Am Soc Laser Med Surg 1989; 3:6. 137. Basford JR, Hallman HO. Does low energy HeNe laser irradiation alter "in vitro" replication of human fibroblasts? Lasers Surg Med 1988; 8:125-129. 138. Mester E, Mester AF, Mester A. The biomedical effects of laser application. Lasers Surg Med 1985; 5:31-39. 139. Lyons RF, Abergel RP, White RA, et al. Biostimulation of wound healing in vivo by a helium-neon laser. Ann Plast Surg 1987; 18:47-50. 140. Kana JS, Hutschenreiter G, Haina D, et al. Effects of low-power density laser radiation on healing of open skin wounds in rats. Arch Surg 1981; 116:293-296. 141. Basford JR, Hallman HO, Sheffield CG, et al. Comparison of cold-quartz ultraviolet, low-energy laser, and ocelusion in wound healing in a swine model. Arch Phys Med Rehabil 1986; 67:151-154. 142. Saperia D, Glassberg E, Lyons RE, et al. Demonstration of elevated type I and type III procollagen mRNA levels in cutaneous wounds treated witb helium-neon laser: proposed mechanism for enhanced wound healing. Biocbem Biophys Res Commun 1986; 138:1123-1128. 143. Braverman B, McCarthy RJ, Ivankovicb AD, et al. Effect of helium-neon and infrared laser irradiation on wound healing in rabbits. Lasers Surg Med 1989; 9:50-58. 144. Hunter J, Leonard L, Wilson R, et al. Effects of low energy laser on wound bealing in a porcine model. Lasers Surg Med 1984; 3:285-290.
125. Bailin PL. Treatment of port wine stains with the CO2 laser: early results. In: Arndt KA, Noe JM, Rosen S, eds. Cutaneous laser therapy: principles and methods. New York: John Wiley & Sons, 1983:129-136. 126. Apfelberg DB, Maser MR, Lash H. Review and usage of argon and carbon dioxide lasers for pediatric hemangiomas. Ann Plast Surg 1984; 12:353-359. 127. Apfelberg DB, Maser MR, Lash H, et al. Benefits of the CO2 laser in oral hemangioma excision. Plast Reconstr Surg 1985; 75:46-50. 128. Buecker JW, Ratz JL, Richfield DF. Histology of port wine stain treated with carbon dioxide laser. J Am Acad Dermatol 1984; 10:1014-1019. 129. Van Gemert MJC, Welch AJ, Tan OT, et al. Limitations of carbon dioxide lasers for treatment of portwine stains. Arch Dermatol 1987; 123:71-73. 130. Olbricbt SM, Stern RS, Tang SV, et al. Complieations of cutaneous laser surgery: a survey. Arch Dermatol 1987; 123:345-349. 131. Wentzell JM, Robinson JK, Wentzell JR JR, et al. Physical properties of aerosols produced by dermabrasion. Arch Dermatol 1989; 125:1637-1643.
145. Surinehak JS, Alago ML, Bellamy RE, et al. Effect of low-level energy lasers on tbe healing of full-thickness skin defects. Lasers Surg Med 1983; 2:267-274. 146. Glassberg E, Lewandowski L, Lask G, et al. Laser-induced photodynamic therapy with aluminum phythalocynine tetrasulfonate as the photosensitizer: differential pbototoxicity in normal and malignant human cells in vitro. J Invest Dermatol 1990; 94:604-610. 147. Khoobehi B, Char CA, Peyman GA. Assessment of laser-induced release of drugs from liposomes: an in vitro study. Lasers Surg Med 1990; 10:60-65. 148. Zeimer RC, Khoobebi B, Niesman MR, et al. A potential method for local drug and dye delivery in the ocular vasculature. Invest Ophthalmol Vis Sci 1988; 29:1179-1183. 149. Weinstein J. Liposomes in tbe diagnosis and treatment of cancer. In: Ostro MJ, ed. Liposomes from biopbysics to therapeutics. New York: Marcel Dekker, 1987:277.
610
DERMATOLOGIC LASERS: THREE DECADES OE PROGRESS TINA S. ALSTER, M.D., AND STEVEN R. KOHN, M.D.
Thirty years have passed since the creation of the first laser. Although significant applications for lasers were forecast immediately, tnany 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.
1960, Theodore Maiman at Hughes Aircraft Research Laboratories actually developed the first laser, a ruby laser.^ Many other types of lasers have subsequently been developed, but Maiman'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 hght 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 attempted.-' 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.
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 spontaneously, 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.^ In
LASER PRINCIPLES 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) tunability. 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 to ultraviolet permits selective excitation
From the Departments of Dermatology and Pediatrics, Yale University School of Medicine, New Haven, Connecticut, Georgetown University School of Medicine, Washington DC, and Columbia University College of Physicians and Surgeons, New York, New York. Address for correspondence: Tina S. Alster, M.D., Georgetown University Medical Center, Washington Institute of Dermatologic Laser Surgery, 2311 M Street, N.W., Suite 504, Washington, DC 20037. 601
International Journal of Dermatology Vol. 31, No. 9, September 1992
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 to suit a particular application. The concept of "selective photothermolysis" 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 tissue.^ One control of laser-tissue interaction involves matching the wavelength of laser light to the absorption spectrum peak of the target tissue. The absorbing molecules (or chromophores) 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 response in the treatment of vascular lesions'*"'" 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 advantage.'^''•' 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-
^
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 interaction.'"^'^^ Regardless of what tissue is absorbing the laser energy, once this energy is converted to heat, it will spread throughout the surrounding tissue. If the energy source continues for too long, damage to normal stroma may occur from heat dissipation, and the relative optical absorptive advantage gained by choosing the appropriate wavelength and spot 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 time 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 structure."' 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).
LASER TYPES
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 dermatologic conditions. Each will be briefly summarized, but without detailing the laser mechanics involved.
10= -
Argon Laser
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 used primarily in the treatment of vascular lesions, including portwine stains (Figs. 2 and 3),''"^'' telangiectasias,'^'"*'^'"^^ spider varicosities,^**"-^" pyogenic granulomas,'^ cherry angiomas,''' venous lakes,'^ angiokeratomas,^' and Kaposi's sarcoma.'^ Theoretically, there should be selective absorption of the light by hemoglobin within the blood vessels
i, 10 -
*
100
'
200
300 400 500
700
1000
2000 * (nml
Figure 1. Absorption coefficient spectrum of hemoglobin (HbOj) and melanin. 602
Dermatologic Lasers Alster and Kohn
Table 1. Characteristics of Lasers Laser
Medium Wavelength Chromophore
Argon
Gas
Dye
Liquid
Ruby
Solid
Nd:YAG Solid GO2
Gas
Lesions Treated
488 nm. 514 nm Variable, depends on dye 694 nm
Hemoglobin Melanin Variable
Vascular Pigmented Vascular Pigmented
Melanin Tattoo pigment
1060 nm 10,600 nm
—
Pigmented Tattoo Vascular Epidermal Dermal Excision
Water
comprising the lesion; however, several histologic studjgj32-35 i^ayg (-j5[ doubt on the specificity of the damage, showing the argon laser effects possibly due to nonspecific thermal destruction of skin. It has 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 dyspigmentation.^' Several clinicians have, nevertheless, reported excellent results with lesion regression and minimal scarring, especially in those protocols using very low energies.'^ With the advent of newer, more vascular-specific systems (pulsed dye lasers), however, the argon laser is falling out of favor as the laser of choice for treatment of vascular lesions.^*'"^" Because the wavelength of light is well absorbed by melanin, the argon laser has been used to treat pigmented lesions such as lentigo maligna and benign nevi,'""'*^ "cafe-au-lait" spots,'^ nevus of Ota,'^ and chloasma.'^ Tattoos have also been treated with some success,"'•'*'* but there have been reports of significant postoperative scarring. Nonpigmented lesions reported to be successfully removed by argon laser have included granuloma faciale,"*^ and lymphocytoma cutis,'^ both having a reddish-purple hue that may selectively absorb the blue-green light.
Eigure 2. Portwine stains on tlic nose and medial canthus of a 21-year-old female with prior argon laser test site (mid-nose).
Tunable Dye Laser
Figure 3. Portwine stain of same patient (Eig. 2) 8 weeks after three pulsed dye laser treatments.
The tunable dye lasers contain fluorescent dyes (of various 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 laser (i.e., argon). The continuous wave dye laser systems provide a steady output of light, while the pulsed dye laser system provides intermittent pulses of light. The dye laser systems have been applied to the treatment of vascular lesions, since the damage is highly specific to blood vessels, with sparing of adjacent tissue elements.^'•''^'''^ The tunable dye laser, utilizing the yellow dye rhodamine 6G, can emit at 577 nm.
which corresponds to the third absorption peak of oxyhemoglobin. When a very brief pulse duration (400 |is) is delivered, precise and localized vascular injury occurs, with a histologic appearance resembling vasculitis.'^-'"*"-'^ More recently, it has been demonstrated that a laser emitting at 585 nm is even more effective in the treatment of vascular anomalies, with deeper vascular injury and continued vascular specificity."'^^ Scar formation and pigment alteration, which has been seen with the use of the argon laser, has been eliminated when the combination of laser parameters in the pulsed dye laser system is 603
International Journal of Dermatology Vol. 31, No. 9, September 1992
spider varicosities of the legs with the pulsed dye laser,^'*"^'' but hyperpigmentation (both persistent and transient) following treatment remains a common complication. Pigmented lesions such as "cafe-au-lait" spots have been treated with a dye laser tuned to a wavelength of 504 nm, with selective melanocyte damage seen on histologic examination of laser-treated skin.*^ The continuous tunable dye laser has been used in photodynamic therapy. This procedure involves the systemic administration of a phototoxic agent (usually hematoporphyrin derivative), which is selectively taken up and retained by malignant cells, followed by delivery of laser light, resulting in a toxic reaction that kills the malignant cell population. The hematoporphyrin derivative is photoactive when exposed to 630 nm light, which is most often derived from a tunable dye laser, although a nonlaser source may be used. Its antitumor effect is thought to result from singlet oxygen production with subsequent necrosis of the irradiated tumor.'^*-''' Basal cell carcinoma has been reported to respond to photodynamic tberapy,^""^^ but prolonged pbotosensitivity reactions following photoactivation of the hematoporphyrin derivative have been encountered,^"* limiting its practicality as a treatment modality.
The portwine stain'"^'''*'''^ is the most common vascular lesion treated with the pulsed dye laser, but hemangiomas,'''"-'* facial telangiectasias (Figs. 4 and 5),'^ poikiloderma,^** lymphangioma circumscriptum,^' Kaposi's sarcoma,*"" and blue rubber bleb nevi*"' have also been treated successfully using this laser system. One of the most important advances in the treatment of portwine stains is the fact that the pulsed dye laser can be safely used without scar formation in children.'''•"'^-^ Recently, there has been renewed interest in treating
Ruby Laser The ruby laser emits a visible red light with a wavelength of 694 nm. The red light can be delivered via a longpulse system or a Q-switched (short 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 used.^^''''^ The ruby laser has, therefore, been used successfully in the treatment of lentigines,^^ nevocellular nevi,^^ nevus of Ota,^^ and tattoos (Figs. 6 and 7).^'*-'*^ Although initially used in the treatment of vascular lesions,"'^"* it is no longer indicated for such lesions because of excessive scar formation. This is due to minimal absorption by both oxyhemoglobin and deoxyhemoglobin at 694 nm.^'^
Eigure 4. Telangiectasias on the nose of a 60-ycar-old man.
Neodynium Yttrium Aluminum Garnet (Nd:YAG) Laser The Nd:YAG laser emits 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 tends to be a high energy system witb deep tissue penetration, leading to a large amount of nonselective thermal destruction. Despite its nonselectivity, the Nd:YAG laser has found its way into dermatology. Large cavernous hemangiomas of the skin and mucosal surfaces have been treated successfully,**^"^^ as have dark nodular portwine stains.^^'*' In addition, the Nd:YAG laser has been used for tattoo removal.'*'' Even with the recent development of a frequency-doubled variant of this system in which a crystal placed in the beam path
Figure 5. Same patient (Eig. 4) 6 weeks after single pulsed dye laser treatment. 604
Dermatologic Lasers Alster and Kohn
Eigure 6. Previously untreated professional tattoo on arm of a 21-year-old woman (photo courtesy of R. Rox Anderson, M.D.). Eigure 7. Tattoo 1 month after sixth ruby laser treatment (see Eig. 6) (photo courtesy of R. Rox Anderson, M.D.). halves the wavelength (giving a green color similar to the argon laser output and, thus, slightly better absorption by hemoglobin), there remains a significant amount of nonspecific tissue destruction, with possible resultant scarring.'° Perhaps the most interesting future application of the Nd:YAG laser in dermatology will be that of wound closure by laser welding. Laser welded wounds have 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 and/or foreign body reaction."
ability to seal blood vessels and lymphatics up to 1.5 mm in diameter and the ability to seal nerve endings, allow for better hemostasis and less postoperative pain and edema than with conventional techniques. The CO2 laser is best suited to treat epidermal lesions, because it works by tissue vaporization. The most common dermatologic conditions treated by the CO2 laser are verruca vulgaris and condyloma acuminatum, especially when they are large and/or recalcitrant to .other forms of treatment.'-'^' A variety of epidermal and dermal lesions, including syringomas,'"* adenoma sebaceum,'-''"'** epidermal nevi,^^-'' xanthelasma,'"" trichoepitheliomas,"'"" apocrine hidrocystomas,'"- myxoid cysts,'"^ and neurofibromas'"'' have been treated with the CO2 laser. Successful CO2 laser treatment of actinic cheilitis,'"'''"* lentigines,'"^ and superficial penile lesions, such as balanitis xerotica obliterans,'"* erythroplasia of Queyrat,'"^ and bowenoid papulosis"" has been achieved with excellent cosmetic results and minimal postoperative swelling and morbidity because the pathologic changes in these lesions are confined to the squamous epithelium of the epidermis (Figs. 8 and 9).
Carboti Dioxide (CO2) Laser The CO2 laser is the most commonly used laser system. The laser system is usually a continuous wave laser, emitting light at the invisible far-infrared portion of the spectrum at 10,600 nm. The energy from the CO2 laser is delivered to tissue through sealed tubes and angled mirrors because it cannot be delivered through optical fibers. The energy emitted by a CO2 laser is nonselectively absorbed by both intracellular and extracellular water, and, because soft tissue is 80 to 90% water, total absorption of the CO2 laser is a handy tool because it enables the surgeon to incise or ablate tissue, the outcome depending on the mode in which it is used. Whether the laser is used in either a defocused mode to vaporize tissue or a focused mode to incise tissue, its other unique properties, such as the
Tattoos'"'"- and keloids"^""* have also been treated with the CO2 laser. Hypertrophic scarring and pigmentary loss are common complications when this laser is used in the removal of tattoos. While CO2 laser excision of keloidal tissue showed promising initial results, subsequent reports with longterm follow-up of these same patients have shown high recurrence rates."'''^'' 605
International Journal of Dermatology Vol. 31, No. 9, September 1992
Figure 8. Periungal warts prior to treatment (photo courtesy of Jerome Garden, M.D.).
Figure 9. Periungual warts after CO2 laser treatment (see 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^^'-^^^ 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 nai! plate abnormalities may be seen when the CO2 laser is used in a focused mode to modify the nail matrix.'^^ The CO2 laser has also been used in the treatment of portwine stains^^'*''^'' and hemangiomas.'^*'''^^ The 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 hypertrophlc scarring.^^^''^' Those clinicians who favor the use of the CO2 laser now reserve its use for debulking large hypertrophic portwine stains and hemangiomas. Utilizing laser technology, many cutaneous disorders are being treated more effectively and with less morbidity 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).
burns to personnel or patients have also been rare. Perhaps the most 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 ^m has been found in laser plume and can penetrate into distal lung branches.'•'' In addition, intact human papillomavirus DNA'^^'''' and Hivvirus'^'' 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.'^^ Smoke evacuation systems are necessary during laser therapy, especially when using the CO2 laser, because copious amounts of vaporized material are generated.'^"^
Table 2. Specific Dermatologie Lesions Treated with Laser Surgery Lesions
Lasers Used
Vascular Portwine stains Telangiectasias Hemangiomas Blue rubber bleb nevi Cherry angiomas Spider veins
Dye (585 nm) Argon (488, 514 nm)
Pigmented Lentigines "Cafe-au-lait" spots Nevocellular nevi
Dye (504 nm) Argon (488, 514 nm) Ruby (694 nm)
Tattoos
CO2 (10,600 nm) Ruby (694 nm) CO2 (10,600 nm)
COMPLICATIONS OF LASER SURGERY
Epidermal Verrucae Linear epidermal nevi Actinic cheilitis Rhinophyma Nail plate abnormalities Dermal Keloids Appendageal tumors
Lasers are versatile instruments that are associated with an acceptable risk profile. A survey of complications encountered with cutaneous laser surgery found the rate to average 2.8 to 4.2% of procedures.'-"' Hypertrophic scarring is the most frequently reported complication, while infection carries a low occurrence rate, estimated at 0.2 to 0.6%. Reports of unintentional 606
CO2 (10,600 nm)
Dermatologie Lasers Alster and Kohn
FUTURE USES OF LASERS IN DERMATOLOGY
While laser surgery of dermatologie conditions has been based primarily on the principles of selective photothermolysis, there are other areas of intellectual intrigue that may further the use of lasers both in treatment and diagnosis. The use of low-energy lasers to accelerate wound healing, presumably by stimulation of dermal fibroblasts"^ or by some other biostimulative process'^'"'"*' 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.''"^ Additionally, liposomal''*''-''''' or monoclonal antibody delivery systems with laser-induced release of drugs, may aid in the diagnosis and subsequent treatment of neoplastic or proliferative conditions.
12.
Nelson JS, Sun CHC, Berns MW. Study of the in vivo and in vitro photosensitizing capabilities of uroporphyrin I compared to photofrin 11. Lasers Surg Med 1986; 6: 131-136.
13.
Berns M, Hammer-Wilson M, Walter RJ, et al. Uptake and localization of HpD and active fraction in tissue culture and in serially biopsied human tumors. Adv Exp Med Biol 1983; 170:501-520.
14.
Tan OT, Motemedi M, Welch AJ, et al. Spotsize effects on guinea pig skin following pulsed irradiation. J Invest Dermatol 1988; 90:877-88L Motemedi M, Welcb AJ, Cheong WE, et al. Thermal lensing in biologic media. IEEE Quantum Electronics 1988; 24:696-699. 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. Apfelberg DB, Maser MR, Lash H, et al. The argon laser for cutaneous lesions. JAMA 1981; 245:2073-2075. Apfelberg DB, Maser MR, Lash H. Argon laser treatment of cutaneous vascular abnormalities. Ann Plast Surg 1978; 1:14-18. Goldman L, Treffer R. Laser treatment of extensive mixed cavernous and port wine stains. Arch Dermatol 1977; 113:504-505. Cosman B. Experience in the argon laser therapy of port wine stains. Plast Reconstr Surg 1980; 65:119-129. Noe JM, Barsky SH, Geer DE, et al. Portwine stains and the response to argon laser therapy: successful treatment of the predictive role of color, age, and biopsy. Plast Reconstr Surg 1980; 65:130-136. Hobby LW. Treatment of portwine stains and other cutaneous lesions. Contemp Surg 1981; 8:21-45. Arndt K. Treatment technics in argon laser therapy. J Am Acad Dermatol 1984; 11:90-97. Cosman B. Clinical exposure in the laser therapy of portwine stains. Lasers Surg Med 1988; 8:133-152. Apfelberg DB, Maser MR, Lash H. Extended clinical use of the argon laser for cutaneous lesions. Arch Dermatol 1979; 115:719-721. Apfelberg DB, Maser MR, Lash H. Treatment of nevus araneus by means of an argon laser. J Dermatol Surg Oncol 1978; 4:172-174. Arndt KA. Argon laser therapy of small cutaneous vascular lesions. Arch Dermatol 1982; 118:220-224. Apfelberg DB, Maser MR, Lash H, et al. Use of the argon and carbon dioxide lasers for treatment of superficial venous varicosities of the lower extremity. Lasers Surg Med 1984; 4:221-232. Apfelberg DB, Smith T, Maser MR, et ai. Study of three laser systems for treatment of superficial varicosities of the lower extremity. Lasers Surg Med 1987; 7:219-223. Lyons GD, Owens RE, Mouney DF. Argon laser destruction of cutaneous telangiectatic lesions. Laryngoscope 1981; 91:1322-1325. Pasyk KA, Argenta LC, Schelbert EB. Angiokeratoma circumscriptum: successful treatment with the argon laser. Ann Plast Surg 1988; 20:183-190. Tan OT, Carney M, Margolis R, et al. Histologic responses of portwine stains treated by argon, carbon dioxide and dye lasers: a preliminary report. Arch Dermatol 1986; 122:1016-1022.
15.
16.
17. 18.
In conclusion, the future practice of dermatology will be greatly benefited by laser technology. We are just now beginning to manipulate laser effects on tissue in order to maximize desired laser-tissue interactions and design new therapeutics and diagnostics. The benefits of lasers to medicine and mankind in the next 30 years are eagerly anticipated.
19.
20. 21.
REFERENCES 1. 2. 3.
22.
Caruth JAS, McKenzie AL. Medical lasers: science and clinical applications. Bristol, UK: Adam Hilger, 1986. Schawlow AL, Townes CH. Infrared optical masers. Physiol Rev 1958; 112:1940-1949. Maiman TH. Stimulated optical radiation in ruby. Nature 1960; 187:493-494.
23. 24.
4.
Goldman L, Blaney DJ, Kindel DJ, et al. Pathology of the effect of the laser beam on the skin. Nature 1963; 197:912-914.
25.
5.
Goldman L, Blaney DJ, Kindel DJ, et al. Effect of the laser beam on the skin. J Invest Dermatol 1963; 40:121122.
26.
6.
Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science 1983; 220:524-527. Anderson RR, Parrish JA. The optics of human skin. J Invest Dermatol 1981; 77:13-19.
7. 8.
Rosen S. Nature and evolution of portwine stains. In: Arndt K, Noe JM, Rosen S, eds. Cutaneous laser therapy: principles and methods. New York: John Wiley & Sons, 1983: 75.
9.
Tong AKF, Tan OT, Boll J, et al. Ultrastructure: effects of melanin pigment on target specificity using a pulsed dye laser (577 nm). J Invest Dermatol 1987; 88:847-852. Tan OT, Murray S, Kurban AK. Action spectrum of vascular specific injury using pulsed irradiation. J Invest Dermatol 1989; 92:717-720. Sherwood KA, Murray S, Kurban AK, et al. Effect of wavelength on cutaneous pigment using pulsed irradiation. J Invest Dermatol 1989; 92:717-720.
10.
11.
27. 28.
29.
30.
31.
32.
607
International Journal of Dermatology Vol. 31, No. 9, September 1992
33.
34.
35.
36.
37.
38. 39.
40.
41. 42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
Greenwald J, Rosen S, Geer DE, et al. Comparative histological studies of the tunable dye (at 577 nm) laser and argon laser. J Invest Dermatol 1981; 77:305-310. Solomon H, Goldman L, Henderson B, et al. Histopathology of the laser treatment of port-wine lesions. J Invest Dermatol 1968; 50:141-146. Apfelberg DB, Kosek J, Maser MR, et al. Histology of portwine stains following argon laser treatment. Br J Plast Surg 1979; 32:232-287. Dixon J, Huether S, Rotering RH. Hypertrophic scarring in argon laser treatment of portwine stains. Plast Reconstr Surg 1984; 73:771-780. Finley JL, Barsky SH, Geer DE, et al. Healing of portwine stains after argon laser therapy. Arch Dermatol 1981; 117:486-489. Tan OT, Stafford TJ. Treatment of port wine stains at 577 nm. Med Instrument 1987; 21:218-221. Garden JM, Polla LL, Tan OT. The treatment of portwine stains by the pulsed dye laser: analysis of pulse duration and long-term therapy. Arch Dermatol 1988; 124:889-896. Morelli J, Tan OT, Garden J, et al. Tunable dye laser (577 nm) treatment of portwine stains. Lasers Surg Med 1986; 694-699. Arndt KA. Argon laser treatment of lentigo maligna. J Am Acad Dermatol 1984; 10:953-957. Oshiro T, Maruyama Y. The ruby and argon lasers in tbe treatment of naevi. Ann Acad Med Singapore 1983; 12:388-395. Goldman L, Igelman JM, Ricbfield DE. Impact of the laser on nevi and melanomas. Arch Dermatol 1964; 90: 71-75. Apfelberg DB, Druker D, Maser MR, et al. Argon laser treatment of decorative tattoos. Br J Plast Surg 1979; 32:232-237. Apfelberg DB, Druker D, Maser MR, et al. Granuloma faciale treatment witb the argon laser. Arcb Dermatol 1983; 119:573-576. Garden JM, Tan OT, Polla L, et al. Tbe pulsed dye laser as a modality for treating cutaneous small blood vessel disease processes. Laser Surg Med 1986; 6:259. Tan OT, Sherwood KA, Gilchrest BA. Successful treatment of children with portwine stains using the flashlamp pulsed tunable dye laser. N Engl J Med 1989; 320:416-421. Garden JM, Tan OT, Kerschmann R, et al. Effect of dye laser pulse duration on selective cutaneous vascular injury. J Invest Dermatol 1986; 87:653-657. Greenwald J, Rosen S, Anderson RR, et al. Comparative histological studies of the tunable dye (at 577 nm) laser and argon laser: the specific vascular effects of tbe dye laser. J Invest Dermatol 1981; 77:305-310. Tan OT, Whitaker D, Garden JM, et al. Pulsed dye laser (577 nm) treatment of portwine stains: ultrastructural evidence of neovascularization and mast cell degranulation in healed lesions. J Invest Dermatol 1988; 90:395-398. Nakagawa H, Tan OT, Parrisb JA. Ultrastructural changes in human skin after exposure to a pulsed laser. J Invest Dermatol 1985; 84:396-400. Tan OT, Murray S, Kurban AK. Action spectrum of vascular specific injury using pulsed irradiation. J Invest Dermatol 1989; 92:868-871.
53.
54.
55.
56.
57.
58. 59.
60.
61. 62.
63.
64.
65.
66.
67.
68.
69.
70. 71,
72.
608
Kurban AK, Sherwood KA, Tan OT. What are the optimal wavelengths for selective vascular injury? Lasers Surg Med 1988; 8:189. Ashinoff R, Geronemus R. Capillary hemangiomas and treatment with the flash lamp-pumped pulsed dye laser. Arcb Dermatol 1991; 127:202-205. Sherwood KA, Tan OT. Treatment of a capillary hemangioma with the flasblamp pulsed dye laser at 585 nm. J' Am Acad Dermatol 1990; 22:136-137. Glassberg E, Lask G, Rabinowitz LG, et al. Capillary hemangiomas: case study of a novel laser treatment and a review of therapeutic options. J Dermatol Surg Oneol 1989; 15:1214-1223. Lowe NJ, Behr KL, et al. Flash-lamp pumped dye laser for rosacea-associated telangiectasia and erythema. J Dermatol Surg Oncol 1991; 17:522-525. Geronemus RG. Poikiloderma. Arch Dermatol 1990; 26:547-548. Weingold D, White P, Burton CS. Treatment of lymphangioma circumscriptum with tunable dye laser. Cutis 1990; 45:365-366. Moritz DL, Lynch WS. Kaposi's sarcoma treated with tbe Candela flash-lamp pulsed dye laser. Am Soc Derm Surg 1990 (abstract). Olsen TG, Milroy SK, Goldman L, et al. Laser surgery for blue rubber bleb nevus. Arcb Dermatol 1979; 115:81-82. Reyes BA, Geronemus R. Treatment of port wine stains during childhood with the flashlamp-pumped dye laser. J Am Acad Dermatol 1990; 23:1142. Ashinoff R, Geronemus R. Elashlamp-pumped pulsed dye laser for port-wine stains in infancy: earlier versus later treatment. J Am Acad Dermatol 1991; 24:467-472. Polla LL, Tan OT, Garden JM, et al. Tunable dye laser for the treatment of benign cutaneous vascular ectasia. Dermatologica 1987; 174:11-17. Goldman MP, Martin DE, Eitzpatrick RE, et al. Pulse dye laser treatment of telangiectasia with and without subtherapeutic sclerotherapy: clinical and histologic examination in the rabbit ear vein mode). J Am Aead Dermatol (in press). Goldman MP, Fitzpatrick RE. Pulsed-dye laser treatment of leg telangiectasia: witb and without simultaneous sclerotherapy. ] Dermatol Surg Oncol 1990; 16: 338-344. Sherwood KA, Kurban AK, Tan OT. Selective melanocyte damage using pulsed irradiation over a variety of wavelengths. Lasers Surg Med 1988; 8:190. Riesz P, Krishna CM. Phthalocyanines and their sulfonated derivatives as photosensitizers in photodynamic therapy. Proe Soc Photo-Optic Instrum Eng 1987; 847:15-28. Sonoda M, Krishna CM, Riesz P. The role of singlet oxygen in tbe photobemolysis of red blood eells sensitized by pbthalocyanine sulfonates. Photochem Photobio( 1987; 46:625-631. Dougherty TJ. Pbotodynamic therapy (PDT) of malignant tumors. Crit Rev Oncol/Hematol 1984; 2:83-116. Tomio L, Calzavara F, Zorat PL, et al. Photoradiation therapy for cutaneous and subcutaneous malignant tumors using bematoporphyrin. Prog Clin Biol Res 1984; 170:829-840. McCaugban JS Jr, Guy JT, Hicks W, et al. Photodynamic therapy for cutaneous and subcutaneous malignant neoplasms. Arch Surg 1989; 124:211-216.
Dermatologie Lasers Alster and Kohn
73. 74.
75.
76.
77. 78.
79.
80.
81.
82.
83.
84.
Berns MW, McCuUough JL. Porphyrin sensitized phototherapy. Arch Dermatol 1986; 122:871-874. Zalar GL, Poh-Fitzpatrick M, Krobn DL, et al. Induction of drug photosensitization in man after parenteral exposure to hematoporphyrin. Arch Dermatol 1977; 113:1392-1397. Polla LL, Margolis RJ, Dover JS, et al. Melanosomes are a primary target of Q-switched ruby laser irradiation in guinea pig skin. J Invest Dermatol 1987; 89:281-286. Dover JS, Margolis RJ, Polla LL, et al. Pigmented guinea pig skin irradiated with Q-switched ruby laser pulses. Arch Dermatol 1989; 125:43-49.
93.
Bailin PL. Use of the CO2 laser for non-PWS cutaneous lesions. In: Arndt KA, Noe JM, Rosen S, eds. Cutaneous laser therapy: principles and methods. New York: John Wiley & Sons, 1983:187.
94.
Wheeland RG, Bailin PL, Reynolds O, et al. Carbon dioxide (CO2) laser vaporization of multiple facial syringomas. J Dermatol Surg Oncol 1986; 12:223-228. Wheeland RG, Bailin PL, Kantor G, et al. Treatment of adenoma sebaceum with carbon dioxide laser vaporization. J Dermatol Surg Oncol 1985; 11:861-864. Janniger CK, Goldberg DJ. Angiofibromas in tuberous sclerosis: comparison of treatment by earbon dioxide and argon laser. J Dermatol Surg Oncol 1990; 16: 317-320. Weston J, Apfelberg DB, Maser MR, et al. Carbon dioxide laserbrasion for treatment of adenoma sebaceum in tuberous sclerosis. Ann Plast Surg 1985; 15:132-137. Spenler CW, Achauer BM, VanderKam VM. Treatment of extensive adenoma sebaceum with a carbon dioxide laser. Ann Plast Surg 1988; 20:586-589. Ratz JL, Bailin PL, Lakeland RF. Carbon dioxide laser treatment of epidermal nevi. J Dermatol Surg Oncol 1986; 12:567-570. Apfelberg DB, Maser MR, Lash H, et al. Treatment of xanthelasma palpebrarum with the carbon dioxide laser. J Dermatol Surg Oncol 1987; 13:149-151. Wheeland RG, Bailin PL, Kronberg E. Carbon dioxide (CO2) laser vaporization for tbe treatment of trichoepitheliomata. J Dermatol Surg Oncol 1984; 10:470^74. Bickley LK, Goldberg DJ. Multiple apocrine hidroeystomas treated by CO2 laser. J Dermatol Surg Oncol 1989; 15:599-602. Huener CJ, Whelland RL, Bailin PL, et al. Lasers: treatment of myxoid cysts with carbon dioxide laser vaporization. J Dermatol Surg Oncol 1988; 29:357-369. Roenigk RK, Ratz JL. CO2 laser treatment of cutaneous neurofibromas. J Dermatol Surg Oncol 1987; 13:187190. David LM. Laser vermilion ablation for actinic cheilitis. J Dermatol Surg Oncol 1985; 11:605-608. Stanley RJ, Roenigk RK. Actinie cheilitis: treatment with the carbon dioxide laser. Mayo Clin Proc 1988; 63: 230-235.
95.
96.
Ahshiro T, Maruyama Y. The ruby and argon lasers in the treatment of naevi. Ann Acad Med 1983; 12: 388-395. Reid WH, McLeod PJ, Ritchie A, et al. Q-switched ruby laser treatment of black tattoos. Br J Plast Surg 1983; 36455-459. Vance CA, McLeod PJ, Reid WH, et al. Q-switched ruby laser treatment of tattoos: a further study. Lasers Surg Med 1985; 5:179. Taylor CR, Anderson RR, Dover JS, et al. Selective photothermolysis of dermal pigmentation: light and electron microscopic analysis of black tattoos treated witb Q-switched ruby laser (abstract). J Invest Dermatol 1989; 92:530.
97.
98.
99.
100.
Reid WH, Miller ID, Murphy MJ, et al. Q-switched ruby laser treatment of tattoos: a 9-year experience. Br J Plast Surg 1990; 43:663-669.
101.
Taylor CR, Gange RW, Dover JS, et al. Treatment of tattoos by Q-switched ruby laser: a dose response study. Areh Dermatol 1990 (in press). Apfelberg DB, Maser MR, White DN, et al. A preliminary study of the combined effect in neodynium: YAG laser photocoagulation and direct steroid instillation in the treatment of capillary cavernous hemangiomas of infancy. Ann Plast Surg 1989; 22:94-104. Landthaler M, Haina D, Brunner R, et al. NeodyniumYAG laser therapy for vascular lesions. J Am Acad Dermatol 1986; 14:107-117.
102.
103.
104.
105.
85.
Shapshay SM, David LM, Zeitels S. Neodynium-YAG laser photoeoagulation of hemangiomas of tbe head and neck. Laryngoscope 1987; 97:323-330. 86. Apfelberg DB, Smith T, Lash H, et al. Preliminary report on tbe use of the neodynium-YAG laser in plastic surgery. Lasers Surg Med 1987; 7:189-198. 87. Rosenfeld H, Sherman R. Treatment of cutaneous and deep vascular lesions with the Nd:YAG laser. Lasers Surg Med 1986; 6:20-23. 88. Goldman L, Nath G, Schindler G. High-power neodynium-YAG laser surgery. Acta Derm Venereol (Stockh) 1973; 53:45-49. 89. Dixon JA, Gilbertson JJ. Argon and neodynium-YAG laser therapy of dark nodular port wine stains in older patients. Lasers Surg Med 1986; 6:5-11. 90. Apfelberg DB, Bailin P, Rosenberg H. Preliminary investigation of KTP/532 laser light in the treatment of hemangiomas and tattoos. Lasers Surg Med 1986; 6:38-42. 91. Abergel RP, Lyons RF, White RA, et al. Skin closure by Nd:YAG laser welding. J Am Acad Dermatol 1986; 14:810-814. 92. McBurney El, Rosen DA. Carbon dioxide laser treatment of verruca vulgaris. J Dermatol Surg Oncol 1984; . 10:45-48.
106. •
107. Dover JS, SmoUer BR, Stern RS, et al. Low-fluence carbon dioxide laser irradiation of lentigines. Arch Dermatol 1988; 124:1219-1224. 108. Ratz JL, Carbon dioxide laser treatment of balanitis xerotica obliterans. J Am Aead Dermatol 1984; 10: 925-928. 109. Greenbaum S, Glogau R, Stegman S, et al. Carbon dioxide laser treatment of erythroplasia of Queyrat. J Dermatol Surg Oncol 1989; 15:747-754. 110. Landthaler M, Haina D, Brunner R, et al. Laser therapy of bowenoid papulosis and Bowen's disease. J Dermatol Surg Oncol 1986; 12:1253-1257. 111. Apfelberg DB, Maser MR, Lash H, et al. Comparison of argon and carbon dioxide laser treatment of decorative tattoos: a preliminary report. Ann Plast Surg 1985; 14:6-15. 112. Bailin PL, Ratz JL, Levine HL. Removal of tattoos by CO2 laser. J Dermatol Surg Oncol 1980; 6:997-1001. 113. Kantor GR, Wheeland RG, Bailin PL, et al. Treatment of earlobe keloids with carbon dioxide laser excision: a 609
Internation.!] Journal of Dermatology Vol. 31, No. 9, September 1992
report of 16 cases. J Dermatol Surg Oncol 1985; 11: 1063-1067.
132. Gardon JM, O'Banion MK, Shelnitz LS, et al. Papillomavirus in the vapor of carbon dioxide laser-treated verrucae. JAMA 1988; 259:1199-1202. 133. Sawcbuk WS, Weber PJ, Lowy DR, et al. Infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or eleetrocoagulation: detection and protection. J Am Acad Dermatol 1989; 20:41-49.
114. Wheeland RG. Excisional surgery performed with the carbon dioxide laser. In: Wheeland RG, ed. Lasers in skin disease. New York: Thieme Medical Publishers, 1988:105. 115. Bailin PL. Use of the CO2 laser for non-PWS cutaneous lesions. In: Arndt KA, Noe JM, Rosen S, eds. Cutaneous laser therapy: principles and methods. Chicester, UK: John Wiley and Sons, 1983:187. 116. Bailin PL, Ratz JL. Use of the carbon dioxide laser in dermatoiogic surgery. In: Ratz JL, ed. Lasers in eutaneous medicine and surgery. Chicago: Year Book Medical Publishers, 1986:73. 117. Ratz JL. Laser applications in dermatology and plastic surgery. In: Dixon J, ed. Surgical applications of lasers. Chicago: Year Book Medical Publishers, 1987:160. 118. Kantor GR, Ratz JL, Wheeland RG. Treatment of acne keloidalis nuehae with carbon dioxide laser. J Am Acad Dermatol 1986; 14:263-267. 119. Apfelberg DB, Maser MR, Lash H, et al. Preliminary results of argon and carbon dioxide laser treatment of keloid scars. Lasers Surg Med 1984; 4:283-290. 120. Apfelberg DB, Maser MR, Wbite DN, et al. Failure of carbon dioxide laser excision of keloids. Lasers Surg Med 1989; 9:382-388. 121. Bobigegian RK, Shapshay DR, Hybey RL. Management of rhinophyma with earbon dioxide laser: Lahey Clinie experience. Lasers Surg Med 1988; 8:397-401. 122. Haas A, Wheeland RG. Treatment of massive rhinopbyma with the carbon dioxide laser. J Dermatol Surg Oncol 1990; 16:645-649. 123. Leshin B, Whitaker DL. Carbon dioxide laser matriectomy. J Dermatol Surg Oncol 1988; 14:608-611. 124. Ratz J, Bailin P, Levine H. CO2 laser treatment of port wine stains: a preliminary report. J Dermatol Surg Oncol 1982; 8:1039-1044.
134. Baggish MS, Polesz BJ, Joret D, et al. Presence of human immunodeficiency virus DNA in laser smoke. Lasers Surg Med 1991; 11:197-203. 135. Nezhat C, Winer WK, Nezhat F, et al. Smoke from laser surgery: is there a health hazard.' Lasers Surg Med 1987; 7:376-382. 136. Garden JM. Tbe hazards of laser plume: a mid-year committee report. Am Soc Laser Med Surg 1989; 3:6. 137. Basford JR, Hallman HO. Does low energy HeNe laser irradiation alter "in vitro" replication of human fibroblasts? Lasers Surg Med 1988; 8:125-129. 138. Mester E, Mester AF, Mester A. The biomedical effects of laser application. Lasers Surg Med 1985; 5:31-39. 139. Lyons RF, Abergel RP, White RA, et al. Biostimulation of wound healing in vivo by a helium-neon laser. Ann Plast Surg 1987; 18:47-50. 140. Kana JS, Hutschenreiter G, Haina D, et al. Effects of low-power density laser radiation on healing of open skin wounds in rats. Arch Surg 1981; 116:293-296. 141. Basford JR, Hallman HO, Sheffield CG, et al. Comparison of cold-quartz ultraviolet, low-energy laser, and ocelusion in wound healing in a swine model. Arch Phys Med Rehabil 1986; 67:151-154. 142. Saperia D, Glassberg E, Lyons RE, et al. Demonstration of elevated type I and type III procollagen mRNA levels in cutaneous wounds treated witb helium-neon laser: proposed mechanism for enhanced wound healing. Biocbem Biophys Res Commun 1986; 138:1123-1128. 143. Braverman B, McCarthy RJ, Ivankovicb AD, et al. Effect of helium-neon and infrared laser irradiation on wound healing in rabbits. Lasers Surg Med 1989; 9:50-58. 144. Hunter J, Leonard L, Wilson R, et al. Effects of low energy laser on wound bealing in a porcine model. Lasers Surg Med 1984; 3:285-290.
125. Bailin PL. Treatment of port wine stains with the CO2 laser: early results. In: Arndt KA, Noe JM, Rosen S, eds. Cutaneous laser therapy: principles and methods. New York: John Wiley & Sons, 1983:129-136. 126. Apfelberg DB, Maser MR, Lash H. Review and usage of argon and carbon dioxide lasers for pediatric hemangiomas. Ann Plast Surg 1984; 12:353-359. 127. Apfelberg DB, Maser MR, Lash H, et al. Benefits of the CO2 laser in oral hemangioma excision. Plast Reconstr Surg 1985; 75:46-50. 128. Buecker JW, Ratz JL, Richfield DF. Histology of port wine stain treated with carbon dioxide laser. J Am Acad Dermatol 1984; 10:1014-1019. 129. Van Gemert MJC, Welch AJ, Tan OT, et al. Limitations of carbon dioxide lasers for treatment of portwine stains. Arch Dermatol 1987; 123:71-73. 130. Olbricbt SM, Stern RS, Tang SV, et al. Complieations of cutaneous laser surgery: a survey. Arch Dermatol 1987; 123:345-349. 131. Wentzell JM, Robinson JK, Wentzell JR JR, et al. Physical properties of aerosols produced by dermabrasion. Arch Dermatol 1989; 125:1637-1643.
145. Surinehak JS, Alago ML, Bellamy RE, et al. Effect of low-level energy lasers on tbe healing of full-thickness skin defects. Lasers Surg Med 1983; 2:267-274. 146. Glassberg E, Lewandowski L, Lask G, et al. Laser-induced photodynamic therapy with aluminum phythalocynine tetrasulfonate as the photosensitizer: differential pbototoxicity in normal and malignant human cells in vitro. J Invest Dermatol 1990; 94:604-610. 147. Khoobehi B, Char CA, Peyman GA. Assessment of laser-induced release of drugs from liposomes: an in vitro study. Lasers Surg Med 1990; 10:60-65. 148. Zeimer RC, Khoobebi B, Niesman MR, et al. A potential method for local drug and dye delivery in the ocular vasculature. Invest Ophthalmol Vis Sci 1988; 29:1179-1183. 149. Weinstein J. Liposomes in tbe diagnosis and treatment of cancer. In: Ostro MJ, ed. Liposomes from biopbysics to therapeutics. New York: Marcel Dekker, 1987:277.
610
