Considerations For Evaluating Picosecond Laser Systems

Clinical White Paper Considerations for Evaluating Picosecond Laser Systems Xiaoming Shang, PhD, Vice President, Laser Technology Research and Distinguished Fellow Candela Corporation Introduction persisted.2 These issues are of particular concern in patients with skin of color (ie, Fitzpatrick skin types IV-VI), Selective elimination of pigment in the skin, without where nanosecond lasers have been shown to cause causing damage to the surrounding tissues requires scarring and carry a ~25% risk of post-inflammatory selective thermolysis of the pigment (chromophore). hyperpigmentation.3-5 Restricted use of lasers for Clinicians can ensure selective thermolysis is achieved by tattoo removal and aesthetic management of pigment making sure that a chromophore is heated using energy irregularities in skin of color is problematic, as patients that targets only that pigment. To specifically target a with skin of color represent an increasing proportion of pigment, a laser treatment should use a wavelength patients in the aesthetic practice.6 Picosecond technology preferentially absorbed by the chromophore, provide is the latest evolution in lasers that minimizes thermal energy that is sufficient to cause damage, and have a impact to surrounding tissues across skin types, thereby pulse duration shorter than the thermal relaxation time of reducing risk.2,5,7 Multiple clinical studies support positive the chromophore.1 results in tattoo removal, in particular for patients with skin of color, and the success of picosecond technology Though the earliest millisecond lasers introduced in in this area has led to wider use in other skin conditions the 1960s represented an improvement over chemical involving dyspigmentation, as well as in other aesthetic and surgical procedures, they were not highly selective, uses including acne scars and wrinkle reduction.8-11 and carried a significant risk of scarring and thermal damage (Figure 1).2 In an effort to improve selectivity and minimize thermal damage to surrounding tissues, Q-switched lasers were introduced in the 1990s. These nanosecond pulse systems were associated with less collateral damage, however the risk of hypopigmentation, hyperpigmentation, and scarring/textural changes 1960s 1990s 2016 Future CO2 lasers Q-switch lasers Picosecond ? millisecond domain nanosecond domain picosecond domain Scarring, thermal damage1 Reduced colateral damage, but still had Minimal risk of hypopigmentation hypopigmentation, hyperpigmentation, and scarring1,2 and scarring1,2 Figure 1. Timeline of laser development

The increased interest in picosecond technology raises FDA-Cleared Indications and the question of how to differentiate between available Specialized Handpieces systems (Figure 2). The design of a picosecond system is integral to its performance, as system design governs Picosecond technologies were first adopted for tattoo not only the technical capabilities of the machine, but also removal, and globally picosecond systems are most its versatility and functionality in the aesthetic practice. In frequently indicated for this purpose. However, advanced this white paper, the following elements of system design systems may also have regulatory approval for multiple will be discussed: Pulse generation, pulse amplification, indications, including acne scars, wrinkles, and/or benign number of wavelengths, and practical considerations pigmented lesions. The indications for the PicoWay such as ease of use and efficacy. Overall, the ideal system system are shown in Figure 3. For tattoo removal, there will have a range of useful picosecond wavelengths are four pure picosecond wavelengths, which can be used FDA-cleared for use in multiple indications, the ability to across 3 specialized handpieces, allowing for targeted consistently generate an ultra-short high-energy pulse, treatment of different ink colors. Further, the PicoWay and a design that supports ease of use (e.g., ergonomics, laser is also indicated for treatment of benign pigmented noise, and heat generation). lesions, wrinkles, and acne scars (Figure 3).13 Important picosecond system design elements Multiple indications for treatment flexibility Wavelengths Number and power of wavelengths 1064 nm 785 nm 730 nm 532 nm Pulse Generation Pulse width and pulse characterisitcs 343 ps 283 ps 250 ps 288 ps Pulse Amplification Energy stability and accuracy Tattoo removal Tattoo removal Tattoo removal Tattoo removal Benign Benign Benign Benign Practical Considerations Ease of use and efficiency Pigmented Pigmented Pigmented Pigmented Figure 2. Considerations for differentiating picosecond systems Lesions Lesions Lesions Lesions Wrinkles Wrinkles Available Picosecond Wavelengths Acne scars The number of picosecond wavelengths generated by a system can vary and is a feature that must be closely Figure 3. FDA-cleared indications of PicoWay by wavelength 2 evaluated. While some manufacturers may claim that they have multiple picosecond wavelengths on their device, pulses may be generated by older nanosecond technology, and many “picosecond” pulses may have lower power and wider pulse width than claimed by the manufacturer. The use of nanosecond technology in intermediate wavelengths (585 nm and 650 nm) is of particular concern, as each carries a well-established risk of hyper/hypopigmentation and scarring. The PicoWay system has four true picosecond wavelengths, 1064, 785, 730, and 532 nm.12 At each of these wavelengths, the PicoWay system delivers consistent, high-energy, single-peak pulses. The availability of multiple wavelengths is important not only for removal of multiple tattoo ink colors, but for treatment of other skin dyspigmentations and concerns.

Pulse Generation Efficient, Single-Stage Amplification Design of the PicoWay System Across devices, the method of pulse generation dictates the pulse width and characteristics (i.e., single pulse KW Alexandrite Pump or multiple sub-pulses, pulse stability). Unlike other systems that have been adapted to include picosecond High Energy Single Stage pulses, the PicoWay system was intentionally designed μ-Cavity Seed Power Ampli er to optimize picosecond pulse delivery. Because the efficacy and safety of picosecond treatment is tied to both Laser selective thermolysis and a pulse duration shorter than or comparable to the stress confinement time of the target Figure 5. The PicoWay system’s single-pulse system chromophore, the delivery of consistent, high-energy, ultra- with single amplifier is simple and designed to short pulses is integral to treatment outcome as it results efficiently generate picosecond wavelengths. in a primarily photoacoustic effect. Different technologies have varying capacities to consistently generate ultra-short Complex, regenerative amplification design pulses (Figure 4). These differences are important because ultra-short pulses lead to a primarily photoacoustic, rather High-speed Electronic Timing Control than thermal effect and delivery of high-energy picosecond pulses allow for more efficient clearance of pigment. Diode Flashlamps Pump The PicoWay system is highly efficient, and uses a KW alexandrite laser to power both a high-energy micro Low Energy Regenerative cavity seed (which easily generates pulses shorter than Seed Laser Power Ampli er 500 picoseconds) and single-stage power amplifier, which increases the picosecond pulse power to generate Figure 6. A low-energy seed and Q-switched sufficient pulse energy (Figure 5). The system’s closed loop regenerative amplification system is more complex feedback delivers highly accurate, stable energy output and results in variable output. with minimal timing and energy fluctuation, allowing for consistent generation of pulses. The automatic optical synchronization circumvents the need for complex electronics, a configuration that allows for better system control of output. The PicoWay system is capable of generating an ultra-short pulse There are several ways to generate picosecond pulses. Low energy diode Product Technology Capability to Generate pumped seed lasers typically require Picoway Ultrashort (<500 ps) complex and larger amplification system High energy μ-cavity seed Pulse* to sufficiently increase energy. Some Others Q-switched mode locking + cavity Capable examples are a regenerative amplification dumping system (Figure 6) or multi-stage amplifier. Diode pumped seed Limited In either case, the system for controlling High output Q-switched laser + pulse output is complex, and high-speed slicing module Limited electronics are required to synchronize the low-energy seed and amplifier(s), Poor potentially leading to inconsistent pulse output. The cavity dumped Q-switched Figure 4. The ability of various systems to deliver ultra-short pulses. mode locking technique involves generation of low-power pulses at

755 nm that are derived from a Q-switched cavity PicoWay system expected vs. delivered energy without further downstream amplification. The use of 450 complicated switching electronics for controlling the timing of Pockels Cells may lead to unstable output -0.5% energy. For tattoo-removal and pigment in particular, 400 this approach is problematic, as the resulting 1064 and 532 nm wavelengths are low power, limiting the utility 400 398 of the system. Finally, in a high output Q-switched laser with pulse slicing modules the picosecond pulse 350 may be sliced from a nanosecond pulse, giving rise to a shorter pulse, but without increased peak power. Pulse width (ps) 300 Because the peak power is directly related to the energy delivered to the chromophore, lower peak 250 +2% power is likely to give rise to an insufficient pulse. 200 Across all adapted systems, the ability to generate 200 204 a short (<500 ps) pulse is limited and precise timing control for synchronization remains an issue. 150 4% 4% 100 Pulse and Energy Consistency 100 104 100 104 50 The PicoWay system was designed to deliver high- energy picosecond pulses at all system wavelengths 0 532 nm 785 nm 730 nm (1064, 532, 785, and 730 nm). In order to compare the output laser characteristics for picosecond 1064 nm systems, data were collected comparing pulse energy and pulse width across several picosecond Expected Delivered systems.13 While the PicoWay system maintained a single, stable pulse with high peak power across all Figure 7. At maximum energy settings, the PicoWay system four wavelengths, other systems generated pulses consistently delivers high-energy with multiple peaks and durations that varied over time, lacking consistency and stable pulse delivery. Consistent PicoWay system pulse width 500 The pulse energy at each PicoWay system wavelength is consistently high, with tightly controlled 450 variation ranging from 0.5 to 4.0% (Figure 7). In contrast, the difference between expected and 450 delivered energy in competing systems varies by up to 40%. In addition to consistently delivering pulse 400 -23% -6% energy, the PicoWay system also consistently delivers 350 -24% 375 an ultra-short pulse (range 250-450ps) across all wavelengths (Figure 8). The PicoWay system delivers Pulse width (ps) 300 343 288 300 -9% as expected, with pulses at or even shorter than 250 283 published specifications, with a pulse width variation 275 of between 9 and 24%. In contrast, competing 250 systems had pulse width variation of up to 194%.13 200 150 100 50 0 532 nm 785 nm 730 nm 1064 nm Speci cation Delivered Figure 8. The PicoWay system consistently delivers picosec- ond width pulses across all wavelengths. Having determined that the variability in pulse width and pulse energy is minimal for the PicoWay system, additional data were collected via fast oscilloscope to better characterize the shape of the delivered pulse for these systems.13 Consistent with earlier findings, the PicoWay system was found to deliver high-power, single-peak pulses at both 1064 and 532 nm (Figure 9). In contrast, the pulses generated by other systems have low pulse energy, multi- subpulse structure, and/or longer, nanosecond pulses. The range of pulse configurations at 1064 nm is shown

in (Figure 10), however similar patterns with multiple peaks were also observed at 532nm. The wide variation observed for other devices is cause for concern, as pulse width, peak power, and delivery of the specified wavelength are drivers of treatment outcome.1 Overall, these findings indicate that systems designed as true picosecond systems have more reliable output across wavelengths and are more likely to deliver the pulse energy, peak power, and pulse width claimed by the manufacturer. PicoWay system delivers a single, consistent pulse A 343 ps B 288 ps Figure 9. The PicoWay system consistently delivers high-power, single-peak pulses at both 1064 nm (A) and 532 nm (B) Variable and longer pulses generated by other systems A 960 ps B Subpulse: 634 ps Effective: 1.06 ns C Subpulse: 421 ps D Subpulse: 1.761 ns Effective: 965 ps Effective: 4.091 ns Figure 10. Systems adapted to provide picosecond pulses may provide pulses of longer pulse duration (A), multiple peaks (B-D) and overall inconsistent performance (Measures at 1064 nm)

System Design clinical versatility and utility. Combined with the ability of the PicoWay system to produce picosecond pulses at all The fundamental differences between the PicoWay system wavelengths, usability and economy make the PicoWay and its competitor systems give rise to differences in system well-suited for use across a broad range of usability. In many picosecond systems, the flash lamp runs indications in the aesthetic practice. constantly at 10Hz (or even at maximum energy), making noise, heating up the treatment room, shortening flashlamp Conclusion lifetime, and increasing service costs. The aggressive cooling required to run these systems can significantly When researching picosecond systems, it is important diminish both patient and physician comfort. The flashlamps to evaluate system features beyond the level of available in the PicoWay system light only when the system is fired, wavelengths and price. The value afforded by true making the system quiet. The PicoWay system runs cool, picosecond pulses at all wavelengths is clear when conserves energy, and is designed to extend flashlamp one considers the importance of offering low downtime service life. treatments with minimal risk of hyper/hypopigmentation across multiple aesthetic indications. While there System design also affects ease of use. The handpieces is no perfect system, systems with simple designs for the PicoWay system are simple, lightweight, and that minimize laser fluctuations and optimize pulse ergonomic. While some systems have multiple handpieces consistency should be considered. For the PicoWay that need to be switched out to deliver different beam sizes system, consistent delivery of high-power picosecond and shapes, the PicoWay system uses single handpieces pulses translates into clinical benefit, highlighting the with a wide range of beam sizes. Physician control of importance of clinical evidence with differentiating wavelength, fluence, repetition rate, and spot size allows between devices.5,8,14-17 In addition to the performance for highly customizable treatments, and the versatility of the of the device itself, the reputation of the company behind handpieces means that there is no compromise of spot size the brand is an important consideration. The PicoWay for fluence. To change spot size, a dial on the handpiece system software was designed to be easily upgraded and is adjusted, eliminating the need to change hand pieces open architecture facilitates future upgrades without the for each spot size. The Zoom 532/1064nm handpiece need for complete system overhaul. Service is always an (range 2-10 mm) operates with both wavelengths but no important factor when looking at lasers and the PicoWay manual handpiece changes are needed to change the system is well-supported by Candela. Taken together, wavelength. Rather the wavelength change is made through the features of the PicoWay system make it a versatile, the software by pressing a single button. In addition, the efficient, and economic addition to the aesthetic practice. PicoWay Resolve handpieces (1064 nm and 532 nm) are able to deliver identical split-beams with same energy in a 6mm x 6mm profile. These features, along with those listed in Figure 11, illustrate how system design can translate into PicoWay System Economy Fast warm-up time Pulse on demand (footswitch activates pulse) No frequent costly ashlamp replacement Uses only 10% of it’s capable energy No consumables Figure 11. The PicoWay system is versatile and efficient. The features above make the PicoWay system an economic choice.

References 10. Levin MK, Ng E, Bae YS, Brauer JA, Geronemus RG. Treatment of pigmentary disorders in patients with skin 1. Anderson RR, Parrish JA. Selective photothermolysis: of color with a novel 755 nm picosecond, Q-switched precise microsurgery by selective absorption of pulsed ra- ruby, and Q-switched Nd:YAG nanosecond lasers: A diation. Science. 1983;220(4596):524–527. retrospective photographic review. Lasers Surg Med. 2016;48(2):181–187. 2. Adatto MA, Amir R, Bhawalkar J, et al. New and Ad- vanced Picosecond Lasers for Tattoo Removal. Curr Probl 11. Torbeck RL, Schilling L, Khorasani H, Dover JS, Arndt Dermatol. 2017;52:113–123. KA, Saedi N. Evolution of the Picosecond Laser: A Review of Literature. Dermatol Surg. 2019;45(2):183–194. 3. Agbai O, Hamzavi I, Jagdeo J. Laser Treatments for Postinflammatory Hyperpigmentation: A Systematic Re- 12. PicoWay 510(k) clearance, (K191685), Sept. 2019. view. JAMA Dermatol. 2017;153(2):199–206. 13. Candela, data on file, 2018. 4. Alexis AF. Lasers and light-based therapies in ethnic skin: treatment options and recommendations for Fitzpat- 14. Ross V, Naseef G, Lin G, et al. Comparison of respons- rick skin types V and VI. Br J Dermatol. 2013;169 Suppl es of tattoos to picosecond and nanosecond Q-switched 3:91–97. neodymium:YAG lasers. Arch Dermatol. 1998;134(2):167- 171. 5. Wang CC, Sue YM, Yang CH, Chen CK. A comparison of Q-switched alexandrite laser and intense pulsed light for 15. Izikson L, Farinelli W, Sakamoto F, Tannous Z, Ander- the treatment of freckles and lentigines in Asian persons: son RR. Safety and effectiveness of black tattoo clearance a randomized, physician-blinded, split-face comparative in a pig model after a single treatment with a novel 758nm trial. J Am Acad Dermatol. 2006;54(5):804-810. 500 picosecond laser: a pilot study. Lasers Surg Med. 2010;42(7):640-646. 6. The Aesthetic Society. Procedural statistics. The Aes- thetic Society website. https://www.surgery.org/media/ 16. Herd RM, Alora MB, Smoller B, Arndt KA, Dover JS. A statistics. Updated 2018. Accessed April 20, 2020. clinical and histologic prospective controlled comparative study of the picosecond titanium:sapphire (795nm) laser 7. Bernstein EF, Schomacker K, Paranjape A, Jones versus the Q-switched alexandrite (752nm) laser for remov- CJ. Pulsed dye laser treatment of rosacea using a nov- ing tattoo pigment. J Am Acad Dermatol. 1999;40(4):603- el 15 mm diameter treatment beam. Lasers Surg Med. 606. 2018;50(8):808–812. 17. Negishi K, Akita H, Matsunaga Y. Prospective study 8. Artzi O, Mehrabi JN, Koren A, Niv R, Lapidoth M, Levi of removing solar lentigines in Asians using a novel du- A. Picosecond 532-nm neodymium-doped yttrium alu- al-wavelength and dual-pulse width picosecond laser. La- minium garnet laser-a novel and promising modality for sers Surg Med. 2018;50(8):851-858. the treatment of café-au-lait macules. Lasers Med Sci. 2018;33(4):693–697. 9. Koren A, Niv R, Cohen S, Artzi O. A 1064-nm Neodymi- um-doped Yttrium Aluminum Garnet Picosecond Laser for the Treatment of Hyperpigmented Scars. Dermatol Surg. 2019;45(5):725–729. © 2020 Candela Corporation. This material contains registered and unregistered trademarks, trade-names, service marks and brand names of Candela Corporation and its affiliates. All other trademarks are the property of their respective owners. All rights reserved. PU07680EN-NA, Rev. A