CLINICAL USE OF THE EPILASER SYSTEM R. Rox Anderson, M.D. Harvard Medical School March, 1998 reprinted with permission LASER HAIR REMOVAL- INTRODUCTION Unwanted, pigmented hair is a common cosmetic problem for both sexes. Until recently, the only long-lasting method of hair removal was electrolysis, which requires tedious insertion of an electrode into each hair follicle. The late Leon Goldman first described ruby laser injury to pigmented hair follicles. Over 20 years ago, Ohshiro noted hair loss from nev; after treatment with a ruby laser. At fluences affecting hair follicles, however, the epidermis was severely damaged. A detailed understanding of "selective photothermolysis" (1) later emerged, and is widely applied for vascular, pigmented lesions, tattoos, and now hair removal. The first quantitative, controlled clinical study of laser hair removal in normal human skin was reported by Grossman, et al (2). Ruby laser pulses were delivered through a cold sapphire handpiece held in contact to protect the epidermis. This pilot study showed two significant responses of dark, terminal (coarse) hair follicles, reported by the investigators in two peer-reviewed journals: Temporary hair removal for 1-3 months in all subjects, at all fluences (2). Permanent reduction* of hair at fluences >30 J/CM2, for at least two years after a single treatment (3). Hair loss was greater in sites that were shaved (vs. wax-epilated) before treatment. "Permanent" is defined as significant and stable loss of hair for a period longer than the complete natural hair growth cycle (about one year). *FDA clearance for claim of permanent hair reduction pending Through a cooperative license and research agreement with Massachusetts General Hospital, Palomar supported basic and clinical research by R. Anderson and colleagues, leading to FDA clearance of the first ruby laser system for hair removal, the EpiLaser. A confusing array of other ruby, alexandrite, and xenon flashlamp devices now exists for hair removal-along with speculations about actual performance. In partnership with Coherent, Palomar has established its leadership position with a ruby laser specifically optimized for long-term removal of pigmented hair. This is the EpiLaser System. OPTIMAL TARGETING OF HAIR FOLLICLES The natural target pigment for laser hair removal is melanin (eumelanin, pheomelanin). A ruby laser was chosen over others, because the 694 nm wavelength offers the highest selectivity for deep melanin absorption, about 30% stronger than alexandrite laser wavelengths, with equivalent penetration into the living dermis. Laser energy, pulse duration, micropulse structure, repetition rate, spot size, and the unique skin-cooling handpiece device have been systematically optimized for safety, efficacy, and speed of treatment. Effective laser hair removal requires damage to those parts of the living hair follicle responsible for production and regeneration of a hair shaft. Anatomically, there are two main target structures: the "'bulge," a region of epithelial stem cells located 1-1.5 mm below the skin surface the "bulb," a deep, heavily-pigmented, proliferating part of anagen follicles. The bulge is usually devoid of melanin, but is in close proximity to the pigmented hair shaft. Plucking or wax-epilation of hair shafts prior to laser treatment significantly reduces effectiveness for long-term hair loss, but does not affect temporary hair loss (2). All hairs go through a cycle of active growth (anagen), transition (catagen), and resting (telogen) phases. The length of hair at different body sites is governed by the duration of anagen. Duration of telogen also varies with body site, and may be as long as a year on the leg. Temporary loss of hair can therefore be achieved simply by inducing telogen. This is the mechanism for the reliable, nearly complete loss of pigmented hair for several months after each treatment with the EpiLaser and several other lasers. It is important to realize however, that temporary hair loss does not predict permanent hair loss which is what most patients seek. Reliable, controlled, quantitative, long-term clinical results are the only way to be sure of performance. The EpiLaser System and its unique handpiece are optimized specifically for the goal of permanent reduction of unwanted hair. This was accomplished by a combination of high pulse energy, stretched laser pulsewidth, large spot size, convergent beam optics, aggressive skin cooling and physical compression during delivery of each laser pulse. Human studies (summarized below) show three distinct responses to high-fluence, large-spot-size treatment using the unique handpiece, which account for the apparently permanent (3) reduction of pigmented, coarse hair: miniaturization of hair follicles (dominant mechanism for EpiLaser) decreased pigmentation of regrowing hair degeneration of hair follicles with replacement by fibrosis CLINICAL TRIALS - EFFICACY Studies were performed at Massachusetts General Hospital and the Laser and Skin Cancer Center of New York. Large test sites on the back or thighs of 100 consecutive patients with skin type I-IV (fair to olive-skinned) and any hair color, were shaved and treated with a range of fluences using the EpiLaser System. Baseline and subsequent regrowing terminal hair counts were taken from high-quality digital images of each site. Adjacent, untreated control sites were also counted. Results from one and two treatments given one month apart (later determined to be too close), were compared in each patient at each fluence. Treatment at any body site elected by the patient was also given. Efficacy is best appreciated as the percentage of terminal hair which regrows over time, shown below for different fluences: Figure 1. Hair regrowth followed for one year after 1 and 2 treatments, at a fluence of 40J/CM2. First Data Set: - 1 Treatment only, at 40 J/cm2 Second Data Set - 2 Treatments, both at 40 J/cm2 Third Data Set - Shaved Control - no treatments   The data in Figure 1 is not "best cases"-it is from all, consecutive patients treated under identical conditions. The study showed: 100% of patients have complete or nearly-complete, temporary hair loss for 1-3 months after each treatment, at all laser fluences. Apparently-permanent reduction of hair occurred in the majority of patients. Hair shaft diameter and pigmentation were both significantly smaller after treatment, suggesting miniaturization of follicles. Histology (not shown) was also consistent with miniaturization of hair follicles as the dominant mechanism for loss of terminal hairs. About 75% of patients with black, brown, auburn, or red hair had apparently permanent hair reduction, whereas only about 20% of patients with blonde hair had apparently-permanent hair reduction. The degree of apparently-permanent hair reduction was fluence-dependent. SIDE EFFECTS No scarring has been observed, but it is wise to warn patients that this might occur rarely after any skin treatment. The most common side-effect, seen in about 1 patient in 3, is transient hyper- or hypo-pigmentation, which clears in 1-6 months. Pigmented lesions such as lentigines and freckles are frequently and permanently removed. These pigmentary changes are fluence- and skin type-dependent; the ideal patient for laser hair removal has dark hair and fair skin. Moderate pain, perifollicular erythema and edema occur commonly and resolved within a few days after each treatment. Local blisters occur at high fluences in dark-skinned patients (less than 10% incidence in this study). OTHER STUDIES A multicenter treatment study in about 150 patients is being conducted, in which up to 6 treatments are given over a 1-year period. Study investigators are listed below (5). Preliminary results are consistent with efficacy and safety described above, but final results testing permanent hair reduction are not yet available. A clinical study comparing different spot size-fluence combinations has been performed, which showed larger spot sizes are far more effective at a given fluence. Other studies have confirmed that the cooling handpiece provides deep follicle targeting while reducing epidermal injury. TREATMENT GUIDELINES Skin color Tolerated fluence is set by epidermal pigmentation. Fair-skinned patients are most easily treated. For patients presenting with a "tan" or with dark skin type, pretreatment with topical 4% hydroquinone (or other bleaching agents), sunscreen and sun avoidance for 6 weeks, should be considered prior to laser treatment. Hair color Temporary (1-3 month) hair loss almost always occurs after each laser treatment, regardless of hair color. However, the effectiveness for permanent hair reduction is strongly correlated with hair color. Blonde or white-haired patients are unlikely to experience permanent reduction in hair. Hair loss in these patients can be maintained if desired, by treatment at approximately three month intervals. Anesthesia: EpiLaser's cold handpiece greatly reduces pain during treatment. Although less-sensitive areas (back, legs, axillae) can frequently be treated without any anesthesia, topical anesthesia is generally used, e.g. EMLA'. Technique: Patients should not epilate or pluck hair for several weeks before treatment. Hair is shaved, usually before application of anesthetic, prior to laser treatment. After removal of anesthetic cream (if used), laser pulses at the desired fluence and spot size, are delivered with the handpiece pressed firmly against the skin. The handpiece is then picked up and placed firmly on an adjacent site, until the desired area is covered. Because of active cooling, overlapping pulses to one skin site are not harmful. Over-cooling or under-cooling of the skin is prevented by the unique EpiLaser handpiece. Immediate responses The ideal immediate response, is vaporization of the hair shaft with no other apparent effect. After a few minutes, there is perifollicular erythema and edema. if there is confluent edema or a positive Nikolski sign (epidermal separation forced by lateral pressure on the skin), fluence should be reduced. Body site All body sites except the eye can be safely treated. Safety This high-energy laser system is specifically designed for deep tissue penetration, and strong absorption by melanin. it is capable of causing severe retinal injury when applied near the surface of a patient's eye. Do not use this laser or similar hair-removal devices on or near the surface of a patient's eve. Use anywhere inside the skeletal orbit may potentially cause direct eye injury. Proper eye protection must also be worn by patient and operating personnel to prevent inadvertent exposure to the eyes. A SMART HANDPIECE The EpiLaser contact-cooling handpiece (US patent #5,595,568) is unique. By strongly converging the light beam as it enters skin, the highest light intensity actually occurs well below the skin surface. By allowing firm compression of the dermis, hair follicles are laid out for easier targeting. The EpiLaser handpiece is truly optimized for protective, fast, efficient hair removal. A SMART LASER SYSTEM Ruby lasers have about 30% stronger absorption in human hair follicles, compared with alexandrite lasers. But all ruby lasers are not alike. Efficacy for long-term hair removal increases with both fluence and spot size. High pulse energy is therefore required, regardless of how rapidly pulses are delivered. The EpiLaser's stretched pulse (3 ms) enhances epidermal protection by allowing extra time for heat conduction into the handpiece not just before, but also during each laser pulse. Another hazard is the energy carried by "micropulses" inherent in ruby and alexandrite lasers. If any one micropulse carries more than about 0.4 J/CM2, epidermal damage occurs. Micropulses in the EpiLaser laser have been specifically suppressed below this level. REFERENCES CITED Anderson RR, Parrish JA "Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation" Science 220: 524-527, 1983 Grossman MC, Dierickx CC, Farinelli WA, Flotte TJ, Anderson RR "Damage to hair follicles by normal-mode ruby laser pulses" J Amer. Acad. Dermatol 35: 889-894, 1996 Dierickx CC, Anderson RR "Permanent hair removal by normal-mode ruby laser" Arch Dermatol. 1998 (in press) Anderson RR, Parrish JA "Optics of human skin" J. Invest. Dermatol. 77:13-19, 1981 The Palomar Multicenter Study Group consists of: Joop Grevelink, MD Boston, MA David Goldberg, MD Westwood, NJ Melanie Grossman, MD New York, NY Jerome Garden, MD Chicago, IL George Hruza, MD St. Louis, MO Jay Burns, MD Dallas, TX Suzanne Kilmer, MD Sacramento, CA Sharyn Laughlin, MD Ottawa, Ont. Canada Harvey Lui, MD Vancouver, BC, Canada