Fractional CO2 laser resurfacing of photoaged facial and non
Transcription
Fractional CO2 laser resurfacing of photoaged facial and non
Journal of Cosmetic and Laser Therapy, 2009; 11: 190–201 ORIGINAL ARTICLE Fractional CO2 laser resurfacing of photoaged facial and non-facial skin: Histologic and clinical results and side effects GORDON H. SASAKI, HEATHER M. TRAVIS & BARBARA TUCKER J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. Sasaki Advanced Aesthetic Medical Center, Pasadena, Ana Tevez, California, USA and Loma Linda University, Medical Center, Loma Linda, Ana Tevez, California, USA Abstract Background: CO2 fractional ablation offers the potential for facial and non-facial skin resurfacing with minimal downtime and rapid recovery. Objectives: The purpose of this study was (i) to document the average depths and density of adnexal structures in non-lasered facial and non-facial body skin; (ii) to determine injury in ex vivo human thigh skin with varying fractional laser modes; and (iii) to evaluate the clinical safety and efficacy of treatments. Methods: Histologies were obtained from non-lasered facial and non-facial skin from 121 patients and from 14 samples of excised lasered thigh skin. Seventy-one patients were evaluated after varying energy (mJ) and density settings by superficial ablation, deeper penetration, and combined treatment. Results: Skin thickness and adnexal density in non-lasered skin exhibited variable ranges: epidermis (47–105 μm); papillary dermis (61–105 μm); reticular dermis (983–1986 μm); hair follicles (2–14/ HPF); sebaceous glands (2–23/HPF); sweat glands (2–7/HPF). Histological studies of samples from human thigh skin demonstrated that increased fluencies in the superficial, deep and combined mode resulted in predictable deeper levels of ablations and thermal injury. An increase in density settings results in total ablation of the epidermis. Clinical improvement of rhytids and pigmentations in facial and non-facial skin was proportional to increasing energy and density settings. Patient assessments and clinical gradings by the Wilcoxon’s test of outcomes correlated with more aggressive settings. Conclusions: Prior knowledge of normal skin depths and adnexal densities, as well as ex vivo skin laser-injury profiles at varying fluencies and densities, improve the safety and efficiency of fractional CO2 for photorejuvenation of facial and non-facial skin. Key Words: Adnexal densities, carbon dioxide fractional laser, facial and body skin ablation, skin depths Introduction Adhering to the principles of selective photothermolysis (1), fractional photothermolysis (2–9) creates a pattern of spatially precise micro- or macroscopic epidermal and/or dermal zones of thermal injury that spares a larger reservoir of surrounding photodamaged skin, resulting in greater safety, predictable treatment of superficial pigmentations and rhytids, and a smoother recovery period. In contrast, complete ablative lasering of photodamaged skin by carbon dioxide and erbium: YAG lasers, which produce an open wound, are often associated with a protracted uncomfortable healing period and higher rates of complications, including prolonged erythema, dyschromic changes, demarcation lines, scarring, milia and infection (10–13). The first phase of this paper entails a histologic study of punch biopsies from discarded normal human skin, obtained during routine aesthetic or reconstructive procedures, in order to record their average epidermal/dermal depths and average number of adnexal structures/high-powered microscopic field. The second phase of this study documents the ablative depths and collateral thermal profiles, produced by CO2 fractionated laser on ex vivo human thigh skin, removed from a thighplasty. These histologic findings were used to adjust the selections of laser parameters in 72 patients, studied in phase three, to remove superficial lesions, deeper lesions, or more complex lesions by combining deep and superficial injuries for more effective and safer outcomes. Correspondence: Gordon H. Sasaki, Sasaki Advanced Aesthetic Medical Center, 800 S. Fairmount Ave, Suite 319, Pasadena, CA 91105, USA. Fax: 1 626 796 3373. E-mail: [email protected] (Received 2 April 2009; accepted 13 August 2009) ISSN 1476-4172 print/ISSN 1476-4180 online © 2009 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS) DOI: 10.3109/14764170903356465 Fractional CO2 laser resurfacing of photoaged skin Materials and methods J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. Device description A unique ActiveFX™ scanner and DeepFX™ scanner were used in conjunction with the UltraPulse® CO2 Laser System (Lumenis Inc., Santa Clara, CA, USA) to deliver laser energy in fractional modes by controlling the laser power, beam shape and size, number of pulses and density. The UltraPulse® CO2 beam profile is a ‘flat top’shaped pulse that delivers four times more energy per pulse than a super-pulse-shaped beam, which produces at the beginning of the pulse a burst of energy that tails off throughout the duration of the pulse. The UltraPulse® system is also capable of delivering a power density of 240 W/cm2 that, in turn, provides the needed optimal fluence up to 18.6 J/cm2 with a pulse duration of less than l.0 ms. All of these parameters ensure selective photothermolytic ablation, while using either a large spot size of 1.3 mm with the ActiveFX™ scanner or a smaller spot size of 0.12 mm with the DeepFX™ scanner. In the ActiveFX™ mode, pulses of 1.3 mm are delivered in a non-sequential, non-adjacent scan sequence (CoolScan™) of about 30 microthermal zones (MTZ) per centimeter to allow heat dissipation from adjacent pulses within the scan, thereby reducing a thermal dwelling effect. In the DeepFX™ mode, pulses are delivered in circular patterns from the periphery to the center of the pattern’s shape. Currently, ActiveFX™ is usually selected for the treatment of fine rhytids and superficial pigmentations. DeepFX™ is used for the management of moderate/deep rhytids, deeper pigmentations and scars. For lesions that are mixed in depth, a combined TotalFX™ treatment first with DeepFX™, followed immediately by ActiveFX™, provides the potential for optimal results. Histologic studies Phase 1 From 1998 to 2008, 121 patients (24 males, 97 females; age range 43–77 years) consented to have their discarded normal skin from a variety of aesthetic 191 and reconstructive procedures studied for both skin thickness and density of adnexal structures. Each patient signed an informed consent that adhered to the standard of the IRB Public Health Service, bill of rights for medical subjects, the Health Insurance Portability and Accountability Act (HIPAA), and photography release forms. Six millimeter punch biopsies from ex vivo human skin were used to characterize the normal skin profile independently by a pathologist. Samples were fixed in formalin for serial sectioning and staining with hematoxylin and eosin in preparation for histologic examination. Phase 2 Because fluence and density primarily determine the nature of ablative thermal effects on target tissues, an investigation was designed to assess the effects that different levels of energy and degrees of spot overlap in the ActiveFX™, DeepFX™, and TotalFX™ would produce on a strip of ex vivo human thigh skin. Table I summarizes the treatment parameters at each of the 14 designated sites with a constant frequency setting of 125 Hz. Each 5 × 5 mm treated sample site was excised, fixed in formalin, and evaluated independently by a pathologist from serial sectioning and staining with hematoxylin and eosin. Clinical procedures Subjects, treatment sites and parameters The clinical experience was divided into two groups and is summarized in Table II. In Group 1 (November 2006 to December 2007), 22 patients (19 females, three males) were treated only in the ActiveFX™ mode either for wrinkles and superficial pigmentations of photoaging or for moderate acne scarring. Fitzpatrick skin types ranged from I to II (18 Caucasian) and III to IV (four Latin extraction); mean age was 58.4 years (range 40–83 years). Table III lists the treatment areas, number of sites, and the mean fluences, densities, and frequencies delivered to the involved skin. The DeepFX™ scanner and handpiece were unavailable for clinical use until January 2008. Table I. Settings for ActiveFX™, DeepFX™ and TotalFX™ on 14 samples of human thigh skin. ActiveFX™ treatments Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 100 mJ Density 1 125 mJ Density 1 150 mJ Density 1 100 mJ Density 2 100 mJ Density 3 100 mJ Density 6 Sample 7 15 mJ Density 1 Sample 8 20 mJ Density 1 Sample 9 15 mJ Density 2 Sample 10 20 mJ Density 2 Sample 11 15 mJ Density 1 100 mJ Density 1 Sample 12 20 mJ Density 1 100 mJ Density 1 Sample 13 15 mJ Density 2 100 mJ Density 1 Sample 14 20 mJ Density 2 100 mJ Density 1 DeepFX™ treatments TotalFX™ treatments DeepFX™ ActiveFX™ 192 G. H. Sasaki et al. Table II. Clinical experience with TotalFX™, ActiveFX™, and DeepFX™. Treatment mode Group 1 (22 patients) J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. Group 2 (50 patients) Total number of patients ActiveFX™ ActiveFX™ ActiveFX™ ActiveFX™ TotalFX™ TotalFX™ ActiveFX™ ActiveFX™ 16 9 4 3 35 7 7 29 DeepFX™ 3 Indications and sites (no. of patients/site) Wrinkles/pigmentations on forehead, eyelids, nose, face, lips and chin Wrinkles/pigmentations on neck Wrinkles/pigmentations on décolletage Acne scars Wrinkles/pigmentations on forehead, eyelids, nose, face, lips and chin Acne and traumatic scars (5), tattoo (1), café-au-lait macule (1) Wrinkles/pigmentations on forehead, eyelids, nose, face, lips and chin Wrinkles/pigmentations on neck (21), décolletage (15), shoulder (8), upper arm (9), forearm (12), hands (12), lower extremity (4) Syringoma (1), sebaceous adenoma (1), facial scar (1) In Group 2 (January 2008 to January 2009), a total of 50 patients (46 females, four males) received TotalFX™, ActiveFX™, and DeepFX™ treatments for a variety of lesions including fine and moderate wrinkles, superficial pigmentations, acne and traumatic scars, syringomas, sebaceous adenomas, caféau-lait macules, and remnants of red pigmentation in a tattoo previously treated twice with a Q-switched Nd:YAG 532 nm laser. Fitzpatrick skin types extended from I to II (47 Caucasians) and III to IV (one Latina, one Asian); mean age was 56.9 years (range 18–84 years). Table IV summarizes the treatment areas and settings (energies, densities, and frequencies) dispensed at each site. Treatment protocol Each patient received a complete evaluation and examination of the areas, including an explanation of the various available options and a discussion of expectations. Conditions that should be considered for contraindicating laser treatment include pregnancy, use of isotretinoin, recent Accutane exposure, collagen vascular and connective tissue diseases, keloidal disorders, vitiligo history, radiation dermatitis, and skin malignancies. If fractional lasering was selected, the patient was advised about the potential side effects and complica- Table III. Group 1: ActiveFX™ parameters for treatment sites (2006–2007). Parameter settings (mean and range) Area Forehead Eyelids/ periorbital Face/nose Lips and chin Neck Décolletage Acne scars mJ Density Frequency (Hz) 70.7 (50–100) 60.3 (50–70) 1.2 (1–2) 1.0 (1–2) 55.7 (40–75) 55.7 (40–75) 70.2 (50–100) 80.5 (75–100) 1.4 (1–2) 2.0 55.7 (40–75) 75.5 (60–100) 65.3 (50–75) 63.7 (50–75) 87.5 (75–100) 1.2 (1–2) 1.3 (1–2) 2.0 55.7 (40–75) 55.7 (40–75) 87.5 (75–100) tions including erythema, infection acne eruption, contact dermatitis, post-inflammatory hyperpigmentation, hypopigmentation, permanent textural changes and scarring. At the preoperative visit, consents and standardized photographs with a high-quality color D70 Nikon digital camera were obtained. An assessment score (0–9) for wrinkle depth and distribution was assigned to each patient. An estimate of the depth of skin pigmentation (superficial, deep, mixed levels) was made by Wood’s lamp analyses. Prophylactic medications were prescribed that included an antibiotic, antiviral medication, and a mild analgesic. An aftercare sheet was provided stressing the avoidance of direct sun exposure, the need for daily tepid showering, and the frequent application of Aquaphor® at least four times per day until re-epithelialization occurs. On the procedure day, the skin was cleansed of surface oils, debris and makeup. A topical anesthetic gel (lidocaine/tetracaine 23%/7%) was applied without occlusion for about an hour to one treatment site. The anesthetic gel was wiped away carefully with damp gauzes immediately before treatment was begun on a dry skin surface. For other sites to be treated, the topical anesthetic gel was applied and then removed in a serial fashion in order to reduce the chances of significant transcutaneous absorption that can lead to pharmacologic side effects. The patient’s eyes were protected with corneal shields. The staff implemented complete laser precautions during the entire procedure, including the use of protective eye goggles and antiviral masks. Some patients benefited from nerve blocks to the forehead, lower lids and mouth. Subjects in Group 1 received ActiveFX™ treatments to the forehead, eyelids, nose, face, lips and chin, neck and décolletage areas, using average settings: 60–80 mJ, densities 1–2, 55–75 Hz, shape 3 and size 6 mm (as summarized in Table III). On the thinner skin of the eyelids, neck and décolletage, the parameters were modified to lower settings. In thicker skin, containing increased concentrations of adnexal structures (forehead, face and nose), the settings were increased. Treatment parameters were set at the Fractional CO2 laser resurfacing of photoaged skin 193 Table IV. Group 2: TotalFX™, and ActiveFX™ and Deep FX™ parameters for treatment sites (2008–2009). TotalFX™ parameter settings (mean and range) DeepFX™ Area (no. of sites) Forehead Eyelid/periorbital Face/nose Lips and chin Scars, tattoo and café-au-lait macule mJ 18.4 15.3 19.2 20.1 20.1 ActiveFX™ Density (12.5–20) (12.5–17.5) (17.5–20) (17.5–20) (17.5–20) 1.9 1.3 2.0 2.0 2.06 (1–2) (1–2) (1–2) (1.2) (1–2) mJ 125 80 125 125 125 Density 2 1 2–3 3.0 3.0 Frequency (Hz) 125 125 125 125 125 ActiveFX™ parameter setting (mean and range) J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. ActiveFX™ Neck Décolletage Shoulders/upper arms Forearms Hands Lower extremities mJ Density 90–100 90–100 90–100 90–100 90–100 90–100 1 1 1 1 1 1 Frequency (Hz) 125 125 125 125 125 125 DeepFX™ Syringomas Sebaceous adenomas Facial scar mJ Density 17.05 17.5 20.0 3 3 3 highest levels around the lips and chin to improve the radial lip lines and for acne scars. All patients were treated with a single pass, utilizing the CoolScan mode and repeat delays between 0.5 and 1.0 s. An adjustable forced continuous chilling airflow was used to reduce thermal injury and provide pain management during the entire treatment. Patients in Group 2, who received TotalFX™, were treated first with the DeepFX™ to the forehead, eyelids, nose, face, lips and chin, using average energy settings of 15.5–20.0mJ, densities between 1 and 3, shape 2 and size 6-7 mm (as summarized in Table IV). Density 3 was selected for treatment of the nose and lip lines, depending on the severity of the lines or irregularities. Higher average settings were selected to treat the thicker and more adnexal-concentrated skin of the forehead, face/nose, and lips/chin areas while lower average settings were used over the thinner skin of the lateral cheek and eyelids. Immediately thereafter, superficial ablative ActiveFX™ treatments completed the total treatment with higher average settings than used in 2006–2007: 80–125 mJ, densities 1–2, frequency 125 Hz, shape 3 and size 6–7 mm. Only ActiveFX™ treatments (90–100 mJ, density 1, 125 Hz, shape 3, size 7 mm) were used on the neck, décolletage, shoulders/upper arms, forearms, hands and lower extremities. Only DeepFX™ (17 mJ, density 2) treatments were employed for the treatment of syringomas, sebaceous adenomas, and facial scars. Evaluation Prior to treatment, all proposed areas of treatment were evaluated by the senior author (GHS) and an independent member of the office for degrees of wrinkle lines and pigmentations using a 9-point scale (0 = none, 1–3 = mild, 4–6 = moderate, and 7–9 = severe) from standardized photographs. After 3 months, the effectiveness of treatment of the same wrinkle lines and pigmentation was assessed from the post-treatment photographs, utilizing the same scale system. Clinical scores were then compared using the signed-rank statistical Wilcoxon’s test. Subjects were asked to quantify the amount of pain produced during treatments on a 0–9-point scale, in which 0 = no pain and 9 = intolerable pain. Patients also rated their perception of global improvement at least 3 months after treatment on a quartile grading scale: 0–25% (no or minimal improvement); 26–50% (fair improvement); 51–75% (good improvement); and 76–100% (excellent improvement). Results Normal histology findings (Table V) In Group A, skin from the forehead, nose, medial and lateral cheeks, lips and chin averaged a mean total depth of 2196 μm, comprised of the epidermis (105 μm), papillary dermis (105 μm), and reticular dermis (1986 μm). The adnexal density calculated from each of these sites averaged high numbers of hair follicles (14/HPF), sebaceous gland units (23/ HPF), and sweat glands (7/HPF), compared with those counted from specimens in Groups B and C. In general, 90% of adnexal structures were observed in the upper two-thirds of the dermis in all three groups. 62 μma (45–80 μmb) 75 μma (55–95 μmb) 57 μma (40–75 μmb) 117 μma (105–130 μmb) 50 μma (40–60 μmb) 72 μm 115 μma (98–130 μmb) 75 μma (64–85 μmb) 70 μma (58–83 μmb) 25 μma (20–30 μmb) 40 μma (30–50 μmb) 47 μm 120 μma (110–130 μmb) 110 μma (100–120 μmb) 125 μma (115–135 μmb) 120 μma (110–130 μmb) 131 μma (120–141 μmb) 97 μma (85–110 μmb) 126 μma (117–135 μmb) 105 μm Epidermis 60 μma (50–70 μmb) 82 μma (45–120 μmb) 85 μma (60–110 μmb) 122 μma (110–135 μmb) 82 μma (90–110 μmb) 86 μm 115 μma (110–120 μmb) 71 μma (57–85 μmb) 60 μma (40–80 μmb) 40 μma (30–50 μmb) 45 μma (30–60 μmb) 61 μm 95 μma (70–120 μmb) 75 μma (50–100 μmb) 135 μma (120–150 μmb) 97 μma (75–120 μmb) 110 μma (85–140 μmb) 112 μma (90–125 μmb) 110 μma (90–130 μmb) 105 μm Papillary dermis 1100 μma (700–1500 μmb) 800 μma (600–1000 μmb) 725 μma (500–950 μmb) 1900 μma (1700–2100 μmb) 1175 μma (1050–1300 μmb) 1140 μm 1460 μma (1120–1800 μmb) 1407 μma (1115–1700 μmb) 1200 μma (900–1500 μmb) 437 μma (375–500 μmb) 412 μma (300–525 μmb) 983 μm 1700 μma (1500–200 μmb) 2000 μma (1700–2500 μmb) 2100 μma (1500–2700 μmb) 2000 μma (1500–2500 μmb) 2000 μma (1500–2200 μmb) 2000 μma (1500–2300 μmb) 2100 μma (1500–2500 μmb) 1986 μm Reticular dermis aAverage 1298 μm 1307 μm 2139 μm 867 μm 957 μm 1222 μm 1091 μm 2/HPF 3 1 0 4 3/HPFc 4/HPF 2 3 502 μm 497 μm 2 5 7/HPFc 14/HPF 15 16 14 14 8 22 10/HPFc Hair follicles 1330 μm 1552 μm 1690 μm 2209 μm 2336 μm 2209 μm 2241 μm 2217 μm 2360 μm 2185 μm 1915 μm Total average skin thickness HPF = high-powered field. mean; baverage range; caverage number/HPF (three samplings at 10 × magnification). Average Lower extremity (7) Abdomen (7) Dorsal hand (5) Dorsal forearm (9) Group C Brachium (5) Average Lower eyelid (17) Low neck / décolletage (12) Upper eyelid (19) Mid-neck (9) Group B Upper neck (3) Average Chin (7) Lower lip (6) Upper lip (11) Lat. cheek (13) Med. cheek (19) Nose (14) Group A Forehead (13) Skin site (no. of patients) Table V. Variation in skin depth and density of adnexal structures/HPF in 121 patients. 2/HPF 0 0 0 0 1/HPF 2/HPF 2 1 1 3 5/HPF 23/HPF 31 27 24 11 19 35 11/HPF Sebaceous glands J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. 2/HPF 0 0 4 2 6/HPF 2/HPF 0 0 0 2 7/HPF 7/HPF 31 5 3 1 5 1 5/HPF Sweat glands 260–1680 μm 275–1300 μm 320–2100 μm 300–800 μm 400–900 μm 275–1200 μm 245–1070 μm 275–500 μm 250–500 μm 250–1250 μm 150–1500 μm 300–1600 μm 386–1321 μm 400–1700 μm 450–1100 μm 400–1300 μm 450–1100 μm 300–1200 μm 300–1750 μm 400–1100 μm Depth of 90% adnexal structures 194 G. H. Sasaki et al. J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. Fractional CO2 laser resurfacing of photoaged skin In Group B, thinner skin from three levels of the neck and eyelids exhibited an average mean total depth of 1091 μm, consisting of the epidermis (47 μm), papillary dermis (61 μm), and the reticulardermis (983 μm). In contrast to the findings in Group A, the density of adnexal structures per high-power field was lower, consisting of hair follicles (4/HPF), sebaceous glands (2/HPF) and sweat glands (2/HPF). In Group C, skin from the brachium, dorsal forearm, dorsal hand, abdomen and lower extremities demonstrated an average mean total depth of 1298 microns, with contributions from the epidermis (72 μm), papillary dermis (61 μm) and reticular dermis (86 μm). The density of adnexal structures per high-power field was similar to that enumerated in Group B previously, with low counts of hair follicles (2/HPF), sebaceous glands (2/HPF), and sweat glands (2/HPF). Histology in ex vivo human thigh skin Figure 1 depicts typical histologic changes obtained after ActiveFX™ lasering of excised thigh skin. Samples 1, 2 and 3 were treated with fluences that increased from 100 mJ, to 125 mJ and to 150mJ. Other parameters of density 1 and frequency 125 Hz were kept constant in order to evaluate the effects of energy alone on the specimens. At a setting of 100 mJ, a total penetration depth of 145 μm was observed (ablation of 70 μm, 75 μm of thermal injury). When the setting was increased to 125 mJ, the total penetration depth increased to 210 μm (ablation of 100 μm, 110 μm of thermal injury). At the highest setting of 150 mJ, the total depth of penetration was measured at 450 μm (ablation of 150 μm, 300 μm of thermal coagulation). Figure 2 illustrates a representative finding observed after ActiveFX™ treatment. Samples 1, 4, 5 195 and 6 were treated with the density settings incrementally advanced from 1 to 6. Since the energy (100 mJ) and frequency (125 Hz) were kept constant, the total penetration depth (level of ablation and coagulative injury) was confined to the papillary dermis. The interval distances between ablative spots narrowed as the density increased from 1 to density 3. At density 4 (not shown) and above, injury resulted in a loss of the ablative columns, simulating findings observed after full-surface ablative CO2 procedures. Figure 3 shows characteristic changes seen after DeepFX™ treatment. Samples 7 and 8 were treated in the DeepFX™ mode with an increase in fluence from 15 mJ to 20 mJ, keeping the density at 1. At 15 mJ, the total penetration depth was measured at 700 μm (420 μm of ablation, 280 μm of thermal injury). The interval distances between ablative spots were equally spaced apart. At 20 mJ, the total penetration depth increased to about 1100 μm (660 μm of ablation, 440 μm of thermal injury). Figure 4 presents typical examples of microscopic changes in samples 7 and 9, after both received treatments at 15 mJ in the DeepFX™ mode, but at a density of either 1 or 2. Although the total penetration depth remained constant between 660 and 750 μm (420–450 μm of ablation, 240–300 μm of thermal injury), the interval distances between ablative spots narrowed as the density was increased from 1 to 2. When the fluence levels were increased from 15 mJ to 20 mJ, as performed in samples 8 and 10 (not depicted), the total penetration depth increased from 700–750 μm to 900–1000 μm (540–720 μm of ablation, 360–480 μm of thermal injury). As the density changed from 1 (sample 8) to 2 (sample 10), the interval distances between ablative spots narrowed, but did not approach complete surface ablation, observed at densities between 4 and 6. Figure 1. Fluence changes in ablative, thermal, and total micron depths in ex vivo thigh skin after ActiveFX™ treatments (100 mJ, 125 mJ, and 150 mJ of energy) at density 1 and 125 Hz frequency. 196 G. H. Sasaki et al. J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. Figure 2. Density changes in ex vivo thigh skin after ActiveFX™ treatments (density 1, 2, 3, and 6) at 100 mJ and 125 Hz frequency. Figure 5 demonstrates the typical histologic changes that were observed in samples 11 and 12 after TotalFX™ treatment. Sample 11 was treated initially with DeepFX™ at a fluence of 15 mJ and at density 1, followed thereafter by ActiveFX™ at 100 mJ, 125 Hz and density 1. Sample 12 was treated at a higher fluence with the DeepFX™ of 20 mJ, density 1, and then followed with the Active FX™ at 100 mJ, 125 Hz and density 1. In sample 11, the total penetration depth in the DeepFX™ mode was calculated to be at 800 μm (480 μm of ablation, 320 μm of thermal injury), while the total depth of penetration in ActiveFX™ was about 300 μm (125 μm of ablation, 175 μm of thermal injury). When the DeepFX™ fluence was increased from 15 mJ to 20 mJ, as in sample 12, the total penetration depth was about 1150 μm (690 μm of ablation, 460 μm of thermal injury), while the identical ActiveFX™ parameters resulted in a total penetration depth of 275 μm (125 μm of ablation, 150 μm of thermal injury) within the papillary dermis. In sample 13 at 15 mJ (not shown), the total penetration depths in the DeepFX™ mode (825 μm) and in the ActiveFX™ mode (250 μm) were similar to those observed in sample 11 (15 mJ) because of identical fluencies. The only observable difference Figure 3. Fluence changes in ablative, thermal and total micron depths in ex vivo thigh skin after DeepFX™ treatments (15 mJ, 20 mJ) at density 1. J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. Fractional CO2 laser resurfacing of photoaged skin 197 Figure 4. Density changes in ex vivo thigh skin after DeepFX™ treatments (density 1 and 2) at 15 mJ. was the effect of density changes that produced closer impact spots at density 2 than found at density l. In samples 12 and 14 (not shown), the total penetration depths for the DeepFX™ modes at 20 mJ were similar and ranged between 900 and 1000 μm, as were the total penetration depths (200– 240 μm) in the ActiveFX™ mode because of identical fluencies. As anticipated, interval distances between ablative spots narrowed as the density of 1 (sample 12) was increased to a density of 2 (sample 14). Clinical findings Twenty-two patients in Group 1 received only ActiveFX™ treatments with a single pass that averaged lower fluencies (60–80 mJ), frequencies (55–75 Hz) and densities (1–2) to all areas of the visible face, neck and décolletage than did patients in Group 2. The average mean score for pain (0–9) during treatment was 3.2, which was reduced to a score of 1.5 1 hour after the end of the procedure. Patients reported taking a mild analgesic, such as Tylenol or Motrin for a few days until mild desquamation Figure 5. Fluence changes in ablative, thermal and total micron depths in ex vivo thigh skin after DeepFX™ (15 mJ, 20 mJ) followed by identical ActiveFXTM exposures at 100 mJ, 125 Hz frequency and density 1. J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. 198 G. H. Sasaki et al. and re-epithelialization were completed by the fourth day. Minimal swelling and punctate crusting disappeared within a week. No scarring, demarcation lines, infections or hypo-hyperpigmentation were observed during the 3-month evaluation period. After 3 months, the score for photoaging of facial fine–moderate wrinkles and superficial pigmentations improved from 6.4 ± 0.3 at baseline to 4.2 ± 0.4, statistically significant by the Wilcoxon’s test. In contrast, severe wrinkles in the periorbital and perioral areas, mature acne scars, and deep pigmentations in facial skin responded minimally to ActiveFX™ treatments (7.5 ± 0.5 baseline; 6.5 ± 0.2 at 3 months), and accounted for the majority of fair grading (26–50%) on the Quartile Grading Scale by the patients for global improvement. Although patients rated their response to ActiveFX™ treatments of fine crêpey lines and superficial pigmentations in the skin of their necks and décolletage areas as fair–moderate in global improvement, the evaluators determined a lower score of improvement from photographic analyses (5.6 ± 0.3 baseline; 3.7 ± 0.6 at 3 months). Fifty patients in Group 2 were treated with (i) TotalFX™ facial wrinkles and mixed levels of pigmentations (35 patients), acne and traumatic scars, ankle tattoo, and shoulder café-au-lait macule (seven patients); (ii) ActiveFX™ for wrinkles and superficial pigmentations in the face (seven patients), neck (21 patients), décolletage (15 patients), shoulder (eight patients), upper arm (9 patients), forearm (12 patients), hands (12 patients) and lower extremity (four patients); or (iii) DeepFX™ for syringomas (one patient) and sebaceous adenomas (one patient), and a facial scar (one patient). The average facial DeepFX™ settings selected in TotalFX™ were 15–20 mJ and densities 2–3 with the exception of lower treatment parameters for the thinner eyelid skin (12.5–15 mJ, density 1). The average facial ActiveFX™ settings in the TotalFX™ mode were higher (125 mJ, densities 2–3, 125 Hz) than those selected in patients from Group 1. During combined treatment, the average pain score was 2–3 during DeepFX™ treatment, but increased to levels of 3–4 with ActiveFX™ treatments superimposed on the DeepFX™-ablated sites. Patients reported taking stronger analgesics for 3–5 days until desquamation and epithelialization ended by post-treatment days 9–12. In spite of the more aggressive combined treatments, no scarring, demarcation lines, hypo-hyperpigmentations or infections occurred during the 3-month evaluation period. At the end of 3 months, scores for improvement of fine–moderate wrinkle lines and superficial–moderately deep pigmentations improved from a baseline of 6.7 ± 0.3 to 2.3 ± 0.5, which was statistically significant by the Wilcoxon’s test. The majority of patients’ global assessment on the Quartile Grading Scale rated their results as good to excellent (Figure 6). The use of TotalFX™ treatment at settings of 20 mJ, 125 Hz, and density 2–3 for acne and traumatic Figure 6. (A) Pre- and (B) 3 months post-treatment of photoaging with TotalFX™: DeepFX™ (20 mJ, density 2–3) followed by ActiveFX™ (100 mJ, 125 Hz, density 2) with improvements in skin texture, wrinkles and pigmentations. scarring was assessed to have a favorable outcome by the evaluators ‘s score (7.0 ± 0.6 baseline; 3.3 ± 0.4 at 3 months) and the patient’s global evaluation of good results (Figure 7). The level of pain experienced during treatment was not significantly different from those expressed by patients treated for photoaging in the TotalFX™ mode. In contrast, TotalFX™ had no demonstrable effect in modifying the appearance of the remnants of red pigments with the tattoo, nor of reducing the pigmentation of the café-au-lait macule. ActiveFX™ The ActiveFX™ treatments in Group 2 differed in two respects from those treated in Group 1. First, the parameter settings were increased to higher treatment levels for almost identical degrees of facial wrinkles and pigmentations. Second, ActiveFX™ was made available to treat off-facial skin that extended from the neck, décolletage, and upper and lower extremities. Despite the more aggressive settings, the average pain score during treatment was assessed to be about 2.0–2.5 and reduced to 0–1 an hour after completion of the procedure. Patients reported a transient heating sensation that responded favorably to the application of cool wet towels over the treated sites, aided by the continuous chilling air-flow device. Most patients reported taking no analgesics during their healing phase of 3–5 days. Significantly, no scarring, demarcation lines, hypohyperpigmentation or infections were observed during the entire 3-month post-treatment period. The more aggressive treatment settings resulted in improved outcomes both in facial and off-facial skin by the evaluators (6.5 ± 0.3 baseline; 2.0 ± 0.4 at 3 months) and by the patients’ global assessment on the Quartile Grading Scale of good to excellent (Figures 8–10). DeepFX™ Only three patients were treated only with the DeepFX™ for elimination of syringomas, sebaceous adenomas and facial scars at a fluence of 17.5–20 mJ and density of 3. J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. Fractional CO2 laser resurfacing of photoaged skin 199 Figure 7. (A, B) Pre- and (C, D) 5 months post-treatment of acne scarring with TotalFX™: DeepFX™ (20 mJ, density 2–3) followed by ActiveFX™ (100–125 mJ, 125 Hz, density 2–3). Scar softening, textural changes, and pigmentation blending were observed after 3 months. Improvement in smoothing out facial scars was observed at these higher settings. There was no beneficial effect noted on the syringomas or sebaceous adenomas. Discussion In 2004, Manstein and colleagues (2) introduced the concept of fractional photothermolysis that was rapidly incorporated into new laser resurfacing devices and bundled with previous advancements such as pulsed technology and computerized pattern generator (CPG) scanning. The fractional CO2 UltraPulse® laser represents one of the new innovative devices (14–17) and differs from its original predecessor in many significant aspects. The handpieces, software of the CPG, and scan patterns have been changed to provide both superficial resurfacing with ActiveFX™ and deeper thermal injury with DeepFX™, while maintaining the capabilities of complete ablation (MaxFX™) and of surgical functions with the first UltraPulse® device. When the effects of ActiveFX™ are combined with the micro-ablative features and coagulative columns of DeepFX™, not only is minimal cumulative injury documented at the epidermal-papillary levels, but also skin tightening is observed from a combination of tissue collapse and collagen shortening. The study not only confirms that this novel laser system effectively resurfaces a variety of skin conditions such as rhytids, superficial pigmentations and scars, but also extends its safety profile in order to reduce complications and hasten the recovery period. In contrast, the indications and parameters for successful treatment of melasmas, café-au-lait macules, tattoos, striae, cellulite, syringomas, and sebaceous adenomas have yet to be defined. Conclusion The nature of the fractionated wound and variation of penetration depths produced by the ablative and G. H. Sasaki et al. J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. 200 Figure 8. (A) Pre- and (B) 5 months post-treatment with ActiveFX™ (100–125 mJ, 125 Hz, density 2) with improvement on Visia™ photoanalysis of photoaging (C: spots; D: wrinkles; E: pores; F: texture; G: porphyrin). thermal injuries by the UltraPulse® CO2 laser, not only guide patient selection, but also determine facial or non-facial skin usage, number of passes during a single treatment period, and the need for multiple treatments. Non-sequential fractional resurfacing by the superficial, deep and combined modes can result in improvements in photodamaged skin and scars. Histologic and clinical evidence demonstrated the safety and efficacy of fractional resurfacing of facial and non-facial skin. Further refinements in patient selection, laser settings, multiple passes, stacking pulses, and directional patterns of injury may open new avenues to improve the safety and efficacy of this versatile fractional laser system. Acknowledgements Margaret Gaston is acknowledged for her excellence in standardizing and analyzing the photographs in the study. Fractional CO2 laser resurfacing of photoaged skin 201 Disclosure Dr Sasaki is a consultant with Lumenis, Inc. The cost of histologic examinations and interpretations of thigh specimens in phase 2 of this study by pathologist Susan Murakami MD was funded by Lumenis, Inc. J Cosmet Laser Ther Downloaded from informahealthcare.com by Emily Hu on 06/16/10 For personal use only. References Figure 9. (A) Pre- and (B) 3 months post-treatment with ActiveFX™ (100 mJ, 125 Hz, density 2) demonstrating improvement in skin texture, pigmentations and crêpey lines. Figure 10. 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