Key words: laser; tattoo; Nd:YAG; KTP; removal

Lasers in Surgery and Medicine 45:621 627 (2013) A Continuously Variable Beam-Diameter, High-Fluence, Q-Switched Nd:YAG Laser for Tattoo Removal: Comparison of the Maximum Beam Diameter to a Standard 4-mm-Diameter Treatment Beam Eric F. Bernstein, MD, MSE 1 and Jennifer M. Civiok, BS 2 1 Main Line Center for Laser Surgery, 32 Parking Plaza, Suite 200, Ardmore, Pennsylvania 19003 2 Cynosure, Inc., 5 Carlisle Road, Westford, Massachusetts 01886 Background: Laser beam diameter affects the depth of laser penetration. Q-switched lasers tend to have smaller maximum spot sizes than other dermatologic lasers, making beam diameter a potentially more significant factor in treatment outcomes. Objective: To compare the clinical effect of using the maximum-size treatment beam available for each delivered fluence during laser tattoo removal to a standard 4-mm-diameter treatment beam. Method: Thirteen tattoos were treated in 12 subjects using a Q-switched Nd:YAG laser equipped with a treatment beam diameter that was adjustable in 1 mm increments and a setting that would enable the maximally achievable diameter ( MAX-ON setting) with any fluence. Tattoos were randomly bisected and treated on one side with the MAX-ON setting and on the contralateral side with a standard 4-mm-diameter spot ( MAX-OFF setting). Photographs were taken 8 weeks following each treatment and each half-tattoo was evaluated for clearance on a 10-point scale by physicians blinded to the treatment conditions. Results: Tattoo clearance was greater on the side treated with the MAX-ON setting in a statistically significant manner following the 1st through 4th treatments, with the MAX-OFF treatment site approaching the clearance of the MAX-ON treatment site after the 5th and 6th treatments. Conclusions: This high-energy, Q-switched Nd:YAG laser with a continuously variable spot-size safely and effectively removes tattoos, with greater removal when using a larger spot-size. Lasers Surg. Med. 45:621 627, 2013. ß 2013 Wiley Periodicals, Inc. yttrium-aluminum-garnet (Nd:YAG) laser incorporating a potassium-titanyl-phosphate (KTP) frequency-doubling crystal [4,9,14,19 24]. These lasers fracture the tattoo ink, which is aggregated in cutaneous macrophages, and then stimulates an inflammatory response that helps carry the fractured ink away. The combination of fracturing tattoo granules and stimulating inflammation, results in removal of tattoo ink via the lymphatics [13,21]. Q-switched lasers used for tattoo removal are limited in the amount of total energy they can deliver, as are all lasers. However, with Q- switched lasers used for tattoo removal, the beam diameters available to deliver clinically meaningful fluences are more limited than other lasers, such as those used for laser hair removal or treatment of vascular lesions. This means that the beam diameters available for laser tattoo removal can affect the depth of penetration of laser energy in a clinically meaningful way, potentially depositing variable amounts of laser energy superficially, above the targeted ink particles, resulting in greater side-effects and decreased efficacy [9,10,25,26]. A study from Yonsei University showed increased laser penetration in skin with increasing beam diameter, as well as with increasing fluence; and the benefits of using skin compression to decrease blood as a competing chromophore and decrease the effective depth of targets within the skin, and a hyperosmotic chemical agent to reduce scattering [27]. In our current study we study the effect of beam diameter on the clinical endpoint of tattoo clearance, by using a standard 4-mm-diameter treatment beam to treat 1/2 of a tattoo, and a maximum-diameter treatment beam to treat the contralateral side of the same tattoo, at a selected Key words: laser; tattoo; Nd:YAG; KTP; removal BACKGROUND Using Q-switched lasers for tattoo removal was first reported as early as 1965 when reports were published demonstrating tattoo removal with a Q-switched ruby laser [1,2]. Since that time, three types of Q-switched lasers have been developed for tattoo removal: the ruby [1 7], alexandrite [8 18], and the neodymium-doped, Dr. Bernstein received a research grant from Cynosure, Inc. Jennifer Civiok works for Cynosure, Inc. Contract grant sponsor: Cynosure, Inc.. Correspondence to: Eric F. Bernstein, MD, MSE, Main Line Center for Laser Surgery, The Times Building, 32 Parking Plaza, Suite 200, Ardmore, PA 19003. E-mail: dermguy@dermguy.com Accepted 28 October 2013 Published online 20 November 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/lsm.22203 ß 2013 Wiley Periodicals, Inc.

622 BERNSTEIN AND CIVIOK treatment fluence, using a high-energy, Q-switched, Nd: YAG laser. MATERIALS AND METHODS Subjects Twelve adult volunteers were enrolled in this study, which was approved by an independent Institutional Review Board (Allendale Institutional Review Board, Old Lyme, CT) for treatment of human subjects. Subjects were recruited as they presented to a dermatologic laser center for laser tattoo removal. Subjects were included if they had untreated decorative tattoos not involving the face or neck. Five subjects were male (42%) and seven were female (58%). Subjects ranged in age from 20 to 54, averaging 32 years old. The study was open to all Fitzpatrick skin types. One of the subjects had Fitzpatrick skin type I, six had type II, four had type III, and one had Fitzpatrick skin type IV. No patients with skin types V or VI presented for inclusion into the current study. Every subject was treated to a single tattoo with the exception of one subject who was treated to 2, for a total of 13 tattoos in 12 subjects enrolled in the current study. Seven of the tattoos contained only black ink, while the other six contained a variety of colors including: red, yellow, purple, pink, orange, green, and blue. Tattoos ranged in size from 5 to 270 cm 2, averaging 68 cm 2. The average duration of tattoos on the skin ranged from 3 to 33 years, averaging 15 years since they were first placed. Patients who were actively tan in the treatment site, who had taken isotretinoin within the past 6 months, who had a history of psoriasis or vitiligo, had taken parenteral gold therapy ever in their lifetime, had clinical evidence of an allergic tattoo reaction, or had a history a keloid formation, were excluded from the study. Laser The device used in the current study was a high-energy, Q-switched, variable spot-size, Nd:YAG laser, incorporating a KTP doubling crystal, delivering 1,064 and 532-nm laser energy (Con-Bio RevLite SI, Cynosure, Inc., Westford, MA). At 1,064 nm the laser generates a total energy of 1.6 J with a maximum fluence of 12.0 J/cm 2 using a 3.7- mm-diameter circular treatment beam. This laser enables delivery of continuously variable spot sizes, increasing in 0.1 mm increments. The MAX-ON setting automatically selects the maximum available fluence for any choice of beam diameter, adjustable in 0.1 mm increments, and can be continuously adjusted to various spot sizes from 2.0 to 8.5 mm at 1,064 nm, and from 1.0 to 6.0 mm at 532 nm, and immediately displays the maximum available fluence at every available beam diameter. The optimal fluence is determined by the treating physician before treatment begins, using the maximally available spot size (MAX-ON setting). When a spot size is changed, the system automatically adjusts the fluence to operate at the laser s maximum fluence for that given spot size. The repetition rate varies from a single pulse to 1, 2, 5, and 10 Hz. The laser employs a unique dispersion of maximum energy that delivers very narrow pulse widths at high power and with large spot sizes. Laser Treatment Tattoos were injected prior to treatment with 1% buffered lidocaine with 1:100,000 epinephrine, and once complete hemostasis was achieved, were covered with a clear hydrogel dressing (Vigilon; CR Bard, Inc., Covington, GA) to protect the epidermis and prevent aerosolizing skin and blood during treatment. Less than 10% loss of the incident treatment beam results from use of the hydrogel dressing [7]. Tattoos were randomly divided into two equal halves, and one-half was randomly selected to be treated with the optimal fluence as determined by the treating physician using a 4-mm spot (MAX-OFF setting), while the contralateral side was treated with the identical fluence using the maximally available spot size at that same fluence (MAX-ON setting). The fluence was selected for the first treatment by the treating physician based upon the intensity of the tattoo and the subject s Fitzpatrick skin type, and adjusted based upon the clinical response of the tattoo to laser test-spots. The desired endpoint to ensure optimal fluence selection for each tattoo was immediate, intense tattoo whitening without pinpoint bleeding. The selection of the wavelength was based on ink color, with red, orange, or yellow being treated with 532-nm laser energy, and other colors such as black, blue, green or purple being treated with 1,064-nm laser energy. Every tattoo contained some black ink, and three contained some green ink, two some blue ink, two some purple ink, five some red ink, one pink ink (usually made by mixing white with red ink), and two contained yellow ink. In total, six tattoos contained red, yellow, pink, or orange ink and were treated with both the 532- and 1,064-nm wavelengths; while the remaining seven tattoos that did not contain these colors were only treated with the 1,064-nm wavelength. The fluences used at 1,064 nm ranged from 4.2 to 9.2 J/cm 2, with treatment beam diameters ranging from 6.2 to 4.2 mm in diameter with the MAX-ON setting and a fixed 4-mm-diameter spot for the MAX-OFF setting. Fluences increased with each subsequent treatment, and to achieve these higher fluences were delivered with smaller spot sizes when using the MAX-ON setting (Table 1 and Fig. 1). Fluences used at the 532-nm wavelength ranged from 1.8 to 2.6 J/cm 2, and treatment beam diameters ranged from 5.7 to 4.4 mm for the MAX-ON setting, and were fixed at 4 mm in diameter for the MAX-OFF setting (Table 2). Treatments were performed at 2-month intervals, and for a total of six treatments, with final photographs being taken 3 months following the 6th and final treatment. Blinded Evaluation of Digital Photographs Cross-polarized digital photographs (D80, Nikon Corporation, Melville, NY) were taken by the treating physician before treatment, prior to each subsequent treatment, and 3 months following the final treatment. Photographs were

SPOT SIZE AND TATTOO REMOVAL 623 TABLE 1. Spot Sizes and Fluences Used for Each Treatment With the 1,064-nm Wavelength Fluence (J/cm 2, 1,064 nm only) MAX ON, spot diam. mm Treatment # Average Min Max MAX OFF, spot diam. mm Average Min Max 1 6.6 4.2 7.6 4.0 5.0 4.7 6.2 2 7.4 5.5 8.0 4.0 4.7 4.5 5.4 3 7.9 6.2 8.3 4.0 4.5 4.3 5.1 4 8.4 6.7 9.2 4.0 4.4 4.2 4.9 5 8.5 7.0 8.7 4.0 4.4 4.3 4.8 6 8.9 7.6 9.2 4.0 4.3 4.2 4.6 evaluated in randomized pairs (before/after), in a blinded fashion, by two physicians not involved in the study. Blinded physician evaluators rated the photographs for degree of clearance relative to the photograph selected as the pre-treatment or baseline photograph. Each half of every tattoo was rated separately from the other, and photographs had a dotted line bisecting the tattoo into two halves inserted into each photograph, the half treated using the MAX-ON setting and that treated with the MAX- OFF setting, and evaluators were blinded as to which half was which. The blinded evaluators estimated the percentage clearance of each half of every tattoo in 5% increments from 0% (no improvement) to 100% (complete clearance) representing a 20-point scale. If the assessor incorrectly identified the baseline photograph, then the assessor s rating would be changed to a negative score (i.e., a 30% improvement score would be assigned a 30% score). Clearance on the MAX-ON side was compared to the MAX- OFF side using a Student s t-test. Side Effects Pain of treatment was evaluated by the subjects themselves using a 10-point scale with a score of 0-representing no pain and a score of 10 representing maximal pain. Hyper- and hypo-pigmentation and scarring were evaluated by the treating physician before each treatment and at the final 3-month post-treatment assessment. RESULTS Blinded Evaluation of Digital Photographs Tattoo clearance was recorded for each post-treatment photograph comparing each half of a tattoo to pretreatment baseline photographs, 2 months following the first five treatments and 3 months following the final treatment, for a total of six treatments (Table 3). The progression in clearance can be easily seen when comparing serial cross-polarized digital photographs (Fig. 2). Average clearance following the first treatment was 51% versus 46% increasing to 87% versus 86% following the 6th treatment for the side treated with the MAX-ON and MAX-OFF settings, respectively. Improvement was greater on the side treated with the MAX-ON setting in a statistically significant manner following the 1st through 4th treatments, with the MAX-OFF treatment site approaching the clearance in the MAX-ON treatment Fig. 1. Beam diameter (spot size) for various fluences at 1,064 nm using the MAX-ON setting, which delivers the maximum available spots size for each fluence.

624 BERNSTEIN AND CIVIOK TABLE 2. Spot Sizes and Fluences Used for Each Treatment With the 532-nm Wavelength Fluence (J/cm 2, 532 nm only) MAX ON, spot diam. mm Treatment # Average Min Max MAX OFF, spot diam. mm Average Min Max 1 1.8 1.6 2.0 4.0 5.7 5.4 6.0 2 2.1 2.0 2.2 4.0 5.2 5.1 5.4 3 2.4 2.3 2.4 4.0 4.8 4.4 5.0 4 2.6 2.6 2.6 4.0 4.4 4.4 4.4 5 2.0 2.0 2.0 4.0 5.4 5.4 5.4 6 2.0 2.0 2.0 4.0 5.4 5.4 5.4 site after the 5th and 6th treatments (Fig. 3). No physician evaluators incorrectly identified the pre-treatment photograph in any paired samples. Side Effects Pain of treatment was rated as an average of 2.0 on a 0 (min) to 10 (max) scale, but it must be noted that subjects received buffered lidocaine with epinephrine prior to treatment. No hyper- or hypo-pigmentation or scarring was present prior to any treatment, or 3 months following the 6th and final treatment. DISCUSSION This study demonstrates that the high-energy, variable spot-size, Q-switched Nd:YAG laser is highly effective and safe for removing decorative tattoos, and that the larger spot sizes are more effective than a 4-mm-diameter spot delivering identical fluences. The average clearance as evaluated by blinded observers after the first 1,064-nm laser treatment was 51% on the half of the tattoo treated with the MAX-ON setting, which utilized an average treatment beam diameter of 5.5 mm, as compared to an average of 46% on the half treated using a 4-mm-diameter treatment beam. This difference was highly statistically significant demonstrating the importance of beam diameter in clinical outcomes when treating tattoos with currently available Q-switched lasers, which traditionally utilize beam diameters ranging from 2 to 6 mm in diameter. The statistically significant greater clearance persisted through the first four treatments, favoring the side treated using the MAX-ON setting, which utilized the largest possible beam diameter with each delivered fluence. The average difference in clearance between the MAX-ON and MAX-OFF (4 mm) settings used in the current study was 5%, 5%, 4%, 5%, 2%, and 1% after the 1st, 2nd, 3rd, 4th, 5th, and 6th treatment, respectively. Beam diameters achieved with the MAX-ON setting approached the 4-mm-diameter beam used on the contralateral side as the fluence increased with each subsequent treatment, differing by only an average of 10% by the 6th and final treatment. This is presumably the reason that the clearance rates for each half-tattoo were not statistically different after the final two treatments. In the current study, tattoos responded quite well to the high-energy, Q-switched Nd:YAG laser using either the variable or fixed 4-mm-diameter treatment beam. Approximately 50% of the tattoo ink was removed after the first treatment, with 87% being removed, on average, after the 6th and final treatment. These results are consistent with an earlier study that demonstrated greater than 75% of ink removal in 77% of black tattoos using fluences of 10 12 J/ cm 2, after four treatments [28]. Because that study was done over 2 decades ago, the spot sized used in that study was only 2.5 mm in diameter [28]. In the current study, averaging all tattoos including multi-colored tattoos, an TABLE 3. Improvement of Tattoos Following Treatment on the Side Treated With the MAX-ON Versus MAX-OFF Setting Student s paired t-test, MAX-ON vs. MAX-OFF Percent improvement, MAX-ON Percent improvement, MAX-OFF P-value n ¼ 13 Tx1 51 46 0.000467 n ¼ 13 Tx2 61 56 0.029747 n ¼ 12 Tx3 77 73 0.019065 n ¼ 10 Tx4 79 74 0.013184 n ¼ 10 Tx5 81 79 0.464158 n ¼ 10 Tx6 87 86 0.726314 Statistical significance, P < 0.05.

SPOT SIZE AND TATTOO REMOVAL 625 Fig. 2. Tattoos pre-treatment, and after each of six treatments demonstrating progressive clearance. Black and red ink respond much more effectively than blue or yellow ink as would be expected when using a Q-switched Nd:YAG laser. Fig. 3. Difference in clearance as evaluated by blinded physician observers comparing the side treated with the MAX-ON setting (red), which utilized the maximum beam diameter available for each selected fluence, as compared to the MAX-OFF setting (red) in which a 4-mm-diameter treatment beam was used. average improvement of 76% was measured after four treatments using a lower average fluence of 7.6 J/cm2, with greater improvement noted in the current study at lower fluences, possibly due to the larger-diameter treatment beams used in the current study. In a study using the Qswitched Nd:YAG laser to treat 15 tattoos in subjects with Fitzpatrick skin type VI, more than 1/2 of the tattoos improved 75 95% after 3 4 treatments. Fluences ranged from 3.2 to 5.5 J/cm2 for the first treatments, increasing up to 8.3 J/cm2 for subsequent treatments, all using a 3-mmdiameter treatment beam [22]. Some skin lightening from laser treatment was seen in two subjects, and no scarring was noted [22]. Since more darkly pigmented skin is more at risk of epidermal injury from even the long 1,064-nm wavelength delivered by the Nd:YAG laser, and scattering is greater with smaller beam diameters resulting in more superficial deposition of laser energy, patients with skin of color may benefit the most from the laser used in the

626 BERNSTEIN AND CIVIOK current study receiving increased efficacy and decreased side-effects as compared to other Q-switched Nd:YAG lasers. Few side-effects were seen in the current study, as would be expected when using a high-energy, Q-switched, Nd: YAG laser to treat tattoos. Pain was, of course, mitigated by the use of intradermal lidocaine, thus the 2/10 pain score was no surprise. However, injection of intradermal lidocaine with epinephrine is not painless, and thus the pain associated with injection should have been recorded and would have undoubtedly resulted in a much higher pain scores in the current study. The absence of hypo- or hyper-pigmentation, or scarring, was due to a number of factors. First, although the study was open to all skin types, all subjects had Fitzpatrick skin types I IV, reducing the likelihood of pigmentary alterations, which would be more common in subjects with skin types V or VI. In addition, treatments were administered through a hydrogel dressing to protect the epidermis, presumably limiting side-effects, and the 1,064-nm wavelength is the least absorbed by epidermal melanin pigment of any currently available Q-switched laser, further limiting sideeffects. This laser has an extremely favorable side-effect profile, even when used with a significantly smaller beam diameter [4,14,22,28,29], or in darker skin types [22]. In addition, in the current study operator experience may have played a role in limiting side-effects, along with the use of relatively large beam diameters which enable adequate penetration of laser energy into the dermis. This difference in efficacy between the MAX-ON setting and a 4-mm-diameter spot decreases dramatically with increasing fluence, because the size of the spot when using the MAX-ON setting becomes progressively smaller as the fluence is increased with each treatment, approaching the size of the 4-mm-diameter treatment beam used as a control. For example, the diameter of the treatment beam using the MAX-ON setting with a fluence of 4.2 J/cm 2 is 6.2 mm, decreasing to 5.2 mm at 6 J/cm 2, to 4.2 mm at 9.2 J/ cm 2, and 3.7 mm at 12 J/cm 2. Because tattoo ink fades with each treatment, increasing fluences are necessary to achieve optimal tattoo removal with each subsequent treatment. If too high a fluence is used, especially with the initial treatments when the tattoo is darkest, injury to the skin with scarring can occur. As higher fluences were required with subsequent treatments to obtain an adequate treatment response in the current study, the difference in beam diameter between the 4-mm spot and the MAX-ON setting decreased significantly. In this study a 4-mm-diameter spot was chosen as the control spot size, as it is a standard with many of the higher-powered Q- switched lasers. However, a significant number of Q- switched lasers must use 2- to 3-mm-diameter spots to achieve fluences as high as 12 J/cm 2 at 1,064 nm, if they can achieve fluences this high at all. If this current study had used a 2- to 3-mm-diameter spot as the control, the difference between the MAX-ON setting and the control spot would likely have been greater and persisted until the final study treatments. Lower treatment fluences than were used in the current study are often used to spare the epidermis when treating tattoos in patients with skin of color. The laser used in the current study could deliver these lower fluences with even larger-diameter treatment beams than were used in the current study. This would likely enable greater clearance with fewer side effects than devices using smaller beam diameters to deliver the same fluence. Future studies of tattoo removal in skin of color using the laser studied here could further explore the potential advantages of the MAX-ON setting, thus opening the possibility to more effective treatment for patients with skin of color where lower fluences are typically used. REFERENCES 1. Yules RB, Laub DR, Honey R, Vassiliadis A, Crowley L. The effect of Q-switched ruby laser radiation on dermal tattoo pigment in man. Arch Surg 1967;95(2):179 180. 2. Goldman L, Wilson RG, Hornby P, Meyer RG. Radiation from a Q-switched ruby laser. Effect of repeated impacts of power output of 10 megawatts on a tattoo of man. J Invest Dermatol 1965;44:69 71. 3. Weiss ET, Geronemus RG. Combining fractional resurfacing and Q-switched ruby laser for tattoo removal. Dermatol Surg 2011;37(1):97 99. 4. Levine VJ, Geronemus RG. Tattoo removal with the Q- switched ruby laser and the Q-switched Nd:YAGlaser: A comparative study. Cutis 1995;55(5):291 296. 5. Wheeland RG. Tattoo removal using the ruby laser. West J Med 1992;156(2):190. 6. Laub DR, Yules RB, Arras M, Murray DE, Crowley L, Chase RA. Preliminary histopathological observation of Q-switched ruby laser radiation on dermal tattoo pigment in man. J Surg Res 1968;8(5):220 224. 7. Bernstein EF. The new-generation, high-energy, 595 nm, long pulse-duration, pulsed-dye laser effectively removes spider veins of the lower extremity. Lasers Surg Med 2007;39 (3):218 224. 8. Brauer JA, Reddy KK, Anolik R, Weiss ET, Karen JK, Hale EK, Brightman LA, Bernstein L, Geronemus RG. Successful and rapid treatment of blue and green tattoo pigment with a novel picosecond laser. Arch Dermatol 2012;148(7):820 823. 9. Bernstein EF, Bhawalkar J, Clifford J, Hsia J. Treatment of tattoos with a 755-nm Q-switched alexandrite laser and novel 1064 nm and 532 nm Nd:YAG laser handpieces pumped by the alexandrite treatment beam. J Drugs Dermatol 2010;9(11): 1333 1339. 10. Bernstein EF. Laser tattoo removal. Semin Plast Surg 2007;21(3):175 192. 11. Wang HW, Wang JB, Liu YH, Zuo YG, Jin HZ, Jiang GT, Li HC, Ma DL. [Clinical efficacy of Q-switched Alexandrite laser for pigmentary skin diseases in 4656 patients]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2006;28(2):202 205. 12. Bukhari IA. Removal of amateur blue-black tattoos in Arabic women of skin type (III-IV) with Q-switched alexandrite laser. J Cosmet Dermatol 2005;4(2):107 110. 13. Herd RM, Alora MB, Smoller B, Arndt KA, Dover JS. A clinical and histologic prospective controlled comparative study of the picosecond titanium:sapphire (795 nm) laser versus the Q-switched alexandrite (752 nm) laser for removing tattoo pigment. J Am Acad Dermatol 1999;40(4):603 606. 14. Leuenberger ML, Mulas MW, Hata TR, Goldman MP, Fitzpatrick RE, Grevelink JM. Comparison of the Q-switched alexandrite, Nd:YAG, and ruby lasers in treating blue-black tattoos. Dermatol Surg 1999;25(1):10 14. 15. Garcia C, Clark RE. Tattoo removal using the Alexandrite laser. NC Med J 1995;56(7):336 338. 16. Stafford TJ, Lizek R, Tan OT. Role of the Alexandrite laser for removal of tattoos. Lasers Surg Med 1995;17(1):32 38. 17. Alster TS. Q-switched alexandrite laser treatment (755 nm) of professional, amateur tattoos. J Am Acad Dermatol 1995; 33(1):69 73. 18. Fitzpatrick RE, Goldman MP. Tattoo removal using the alexandrite laser. Arch Dermatol 1994;130(12):1508 1514.

SPOT SIZE AND TATTOO REMOVAL 627 19. Adrian RM, Griffin L. Laser tattoo removal. Clin Plast Surg 2000;27(2):181 192. 20. Werner S, Drosner M, Raulin C. [Tattoo removal Q-switched ruby laser (694 nm) and the Q-switched Nd:YAG laser (532 and 1064 nm). A retrospective study]. Hautarzt 1999;50: 174 180. 21. Ferguson JE, Andrew SM, Jones CJ, August PJ. The Q- switched neodymium:yag laser and tattoos: A microscopic analysis of laser-tattoo interactions. Br J Dermatol 1997;137 (3):405 410. 22. Jones A, Roddey P, Orengo I, Rosen T. The Q-switched ND: YAG laser effectively treats tattoos in darkly pigmented skin. Dermatol Surg 1996;22(12):999 1001. 23. Zelickson BD, Mehregan DA, Zarrin AA, Coles C, Hartwig P, Olson S, Leaf-Davis J. Clinical, histologic, and ultrastructural evaluation of tattoos treated with three laser systems. Lasers Surg Med 1994;15(4):364 372. 24. Kilmer SL, Anderson RR. Clinical use of the Q-switched ruby and the Q-switched Nd:YAG (1064 nm and 532 nm) lasers for treatment of tattoos. J Dermatol Surg Oncol 1993;19(4): 330 338. 25. Bernstein EF. Laser treatment of tattoos. Clin Dermatol 2006;24(1):43 55. 26. Bernstein EF, Kornbluth S, Brown DB, Black J. Treatment of spider veins using a 10 millisecond pulse-duration frequencydoubled neodymium YAG laser. Dermatol Surg 1999;25 (4):316 320. 27. Kwon K, Son T, Lee KJ, Jung B. Enhancement of light propagation depth in skin: Cross-validation of mathematical modeling methods. Lasers Med Sci 2009;24(4):605 615. 28. Kilmer SL, Lee MS, Grevelink JM, Flotte TJ, Anderson RR. The Q-switched Nd:YAG laser effectively treats tattoos. A controlled, dose-response study. Arch Dermatol 1993;129 (8):971 978. 29. Lin T, Jia G, Rong H, Li J, Zhou Z. Comparison of a single treatment with Q-switched ruby laser and Q-switched Nd: YAG laser in removing black-blue Chinese tattoos. J Cosmet Laser Ther 2009;11(4):236 239.