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A side-by-side comparison of carbon dioxide resurfacing lasers for the treatment of rhytides
CLINICAL AND LABORATORY STUDIES A side-by-side comparison of carbon dioxide resurfacing lasers for the treatment of rhytides Edward A. Gross, MD, and Gary S. Rogers, MD Boston, Massachusetts Background: The use of cutaneous resurfacing lasers to treat rhytides is widely accepted. Several carbon dioxide lasers, many using fundamentally different technologies, are available. Objective: The purpose of this study was to compare the results obtained and side effects after treating rhytides with 3 different carbon dioxide resurfacing lasers. Methods: We performed a randomized, blinded, prospective study wherein 16 subjects had either periorbital or perioral rhytides resurfaced with 1 of 3 carbon dioxide lasers on either side of the face. Results: We were unable to demonstrate any significant differences in improvement in rhytides, patient satisfaction, posttreatment erythema, or other side effects. Conclusion: Our results suggest that operator technique and patient selection are more important factors than laser type with respect to outcome. (J Am Acad Dermatol 1998;39:547-53.)
The use of lasers for cutaneous resurfacing, including the treatment of rhytides and acne scars, has become widely accepted.1-4 Several lasers are available. Most use carbon dioxide (CO2) as a lasing material to emit energy at a wavelength of 10,600 nm. Furthermore, most CO2 resurfacing lasers, in adherence to the principles of selective photothermolysis established by Anderson and Parrish,5 expose the treated surface of the skin to approximately 5 J or more of energy in less than 1 ms.1,5-9 In this manner, tissue is vaporized without enough residual thermal damage to cause scarring. However, lasers vary markedly in the method by which this is achieved. Few studies have been published comparing the results of treatment with different lasers in the same subjects.10 This study compares 3 different CO2 resurfacing lasers side by side in the same subjects. Each laser uses a different technology to deliver energy to the skin. The Coherent Ultrapulse (Coherent Lasers, Inc, Palo Alto, Calif) laser delivers single From the Dermatologic Surgery Unit, Department of Surgery, Boston University School of Medicine. Supported by a grant from the Luxar Corporation, Bothell, Wash. Accepted for publication June 15, 1998. Reprint requests: Edward A. Gross, MD, 88 E Newton St, Boston, MA 02118. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/1/92425
submillisecond pulses of energy.1,3 The Sharplan SilkLaser (Sharplan Lasers Inc, Allendale, NJ) uses a continuous wave of energy that is scanned across the surface of the skin in such a way that any individual point along the treated area is only exposed to the laser energy for less than 1 ms.1,2 The Luxar Novapulse (Luxar Corp, Bothell, Wash) laser uses rapid superpulses of extremely short duration that are clustered together into a burst the total duration of which is less than 1 ms. METHODS
Subjects Subjects were recruited for the study from the healthy adult population within the community. Subjects were aged 18 to 75 years, had Fitzpatrick skin type I to III, and had bilaterally symmetric rhytides around the mouth or eyes. Subjects were excluded if they had a history of previous skin resurfacing, cosmetic surgery, or radiation treatment in the area being considered for laser treatment. Additional exclusion criteria included a clinically significant history of acute or chronic illness, any clinically significant acute or chronic skin disease, cutaneous malignancies of the face, any active acute illness within 4 weeks, use of tobacco within 6 weeks, evidence of active substance or alcohol abuse, participation in a study of another investigational device or drug within 4 weeks, active herpes simplex of the mouth, use of isotretinoin within 12 months, and pregnancy.
547
548 Gross and Rogers Study design This was a prospective, randomized, blinded study with each subject serving as his/her own control. A total of 16 subjects were enrolled. Informed consent was obtained from all subjects. Subjects pretreated the face for 2 weeks before laser treatment with sunscreen cream (skin protection factor 15 or greater) each morning and tretinoin (Retin-A) cream 0.025% each evening. Subjects with skin type III or with a history of postinflammatory hyperpigmentation also pretreated the face with hydroquinone cream 4% each morning. All subjects initiated treatment with acyclovir 400 mg by mouth 3 times daily beginning 24 hours before the treatment.11,12 The 16 subjects were divided into 2 treatment groups of 8 subjects each. In 1 group, subjects were treated with the Luxar Novapulse laser with a Novascan scanner to one side of the face and the Coherent Ultrapulse 5000 laser with a computerized pattern generator to the other side of the face. The other half of the subjects were treated with the Luxar laser and scanner to one side of the face and the Sharplan SilkLaser with a Feathertouch scanner to the other side of the face. In each group, subjects were further randomized as to which side of the face was treated with each laser. In addition, a biopsy specimen (from 1 patient in each group) was obtained from postauricular skin after laser treatment. Baseline assessments of skin texture included clinical evaluation, 35-mm color-slide photographs, and digital images. Anesthesia was accomplished with local and/or regional infiltration of lidocaine 0.5% with 1:200,000 epinephrine. Treatment was performed according to the randomization scheme. Each area was treated sufficiently to assure that, in the investigators’ opinion, the rhytides had been effaced or that ablation to the depth of superficial dermis had been reached, as indicated by the clinical appearance. Between passes, debris was removed with saline solution and gauze. All treatment factors including laser settings, technique, and number of treatment passes were recorded. The Coherent laser was used with the computerized pattern generator with pattern sizes ranging from 3 to 7 mm, density settings of 3 to 7, and fluences of 250 to 350 mJ. The Sharplan laser was used in the Feathertouch mode with pattern sizes ranging from 3 to 9 mm and power settings of 30 to 38 W. The Luxar laser was used with the Novapulse scanner generating 3-mm pattern sizes and power settings of 4 to 6 W. For each laser treatment site, 2 to 4 passes were required to efface the rhytides. If the patient had consented to biopsy, two 3-mm diameter regions of skin on each postauricular surface were treated with 1 and 2 passes, respectively, of the laser used to treat the ipsilateral side of the face, with an energy setting equivalent to 300 mJ. Each 3-mm site
Journal of the American Academy of Dermatology October 1998
was then removed with a punch biopsy and sent for pathologic examination. After the laser treatment, the areas were cleansed with water and petrolatum was applied liberally. An additional set of images was obtained immediately after the laser treatment. The subjects were given cephalexin 250 mg by mouth 4 times daily for 7 days. Subjects with sensitivity to cephalosporins received erythromycin 333 mg by mouth 3 times daily for 7 days. In addition, subjects continued their acyclovir at 400 mg by mouth 3 times daily for a total of 1 week. Posttreatment instructions included frequent washings with lukewarm tap water and applications of petrolatum. All subjects were seen at 48 hours (± 7 hours), 1 week (± 1 day), 2 weeks (± 2 days), 1 month (± 5 days), 2 months (± 9 days), 3 months (± 13 days), and 6 months (± 27 days). At each time point, the clinical response to therapy was clinically measured by an observer blinded as to laser type and laterality. Hyperpigmentation, erythema, crusting, infection, scarring, and patient’s subjective reporting of pain were all assessed with a 4-point scale: 1 = none; 2 = mild; 3 = moderate; 4 = severe. At the 2-week, 1-month, 2-month, 3-month, and 6-month visits, the rhytides were evaluated with a 5-point scale: 1 = worse; 2 = no change (0%10%); 3 = slightly improved (10%-40%); 4 = moderately improved (40%-80%); 5 = greatly improved (80%-100%). In addition, the evaluator and patient completed a subjective assessment survey at the 2week, 1-month, 2-month, 3-month, and 6-month visits. Patient satisfaction was measured with a scale ranging from 1 (not at all satisfied) to 5 (very satisfied). At each follow-up visit, 35-mm slides and digital images were taken of the treated areas. For each subject, erythema was scored clinically and by digital image analysis. Digital images were captured with a Hi-8 camcorder and then captured as 24-bit 320 × 240 pixel jpeg images with a video capture card attached to a personal computer. Each picture contained a color calibration card in the field of view. Then, using Adobe Photoshop version 4.0 (Adobe Systems Inc, San Jose, Calif), the images were converted to the L*a*b* color scheme. The “a” channel was then isolated, and histogram functions were measured for each picture in the area of laser treatment (value “a”). A second value was measured in an untreated area of normal skin (value “an”). A third value was measured over the color calibration card (value “ac”). The erythema score is expressed as the difference between the measured erythema of the treated area and the untreated area, corrected by the measurement of the color calibration card: ([a-an]·[ac/183]), where 183 is the average measured value of the color calibration card. Speed of treatment was evaluated by use of a chronometer during the procedure; the measurement
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Gross and Rogers 549
Table I. Improvement in rhytides and patient satisfaction at end of study (6 months) Improvement in rhytides (blinded observer)* Patient No.
Area treated
L
7 12 5 10 4 14 16 3
Periorbital Periorbital Periorbital Perioral Periorbital Perioral Periorbital Periorbital
4 3 5 5 3 3 4 3
9 13 1 6 8 15 11 2
Perioral Perioral Periorbital Periorbital Periorbital Periorbital Periorbital Perioral
4 3 5 4 4 4 4 4
S
Improvement in rhytides (patient assessment)* C
L
5 4 4 5 3 3 4 3
5 3 5 5 5 4 5 5
P = .56 5 4 4 4 5 4 3 5 P = .42
4 3 5 4 4 5 3 4
S
P = .16 4 4 5 4 5 5 3 4 P = .16
Patient satisfaction with results† C
L
5 3 4 5 5 4 4 5
5 3 5 5 5 4 5 5 4 3 5 5 4 5 3 4
S
C
5 3 5 5 5 4 4 5 P = .32 4 4 5 5 5 5 3 4 P = .16
C, Coherent; L, Luxar; S, Sharplan. *5-Point scale: 1 = worse, 5 = greatly improved (see text for details). †5-Point scale: 1 = not at all satisfied, 5 = very satisfied.
reflects only the period of time beginning when the laser was first discharged until it was placed back into stand-by mode at the end of the procedure. Ease of use for each laser was analyzed by assessments of the investigators. For subjects from whom biopsy specimens were obtained, depth of necrosis was measured on the histologic specimens with an ocular micrometer. Subjects resumed tretinoin cream to the face 4 weeks after the laser treatment. Subjects with evidence of hyperpigmentation began treatment to the face with hydroquinone cream 4% and sunscreen (skin protection factor 15 or greater) each morning. Statistical significance of the data was calculated with the Wilcoxon signed-rank test to determine the differences between values obtained regarding improvement in rhytides and patient satisfaction. The paired t test was used for comparison of the duration of erythema, measured erythema levels, and treatment times. RESULTS
Improvement in rhytides and patient satisfaction with results Overall improvement in rhytides as measured on a clinical scale by a blinded observer and by the subjects and patient satisfaction are presented in Table I. Overall, most subjects had significant
improvement in rhytides. Across all treatment groups, moderate or great improvement was seen in 72% of treatment sites according to a blinded observer and 84% of treatment sites according to subjects. In the Luxar-Coherent comparison group, the average improvement grades, as judged by a blinded observer, were 3.75 and 3.88 for the Luxar and Coherent lasers, respectively. In the other group, the average grades were 4.00 for the Luxar and 4.25 for the Sharplan laser. The average improvement grades as judged by the patient were 4.63 for the Luxar and 4.38 for the Coherent in the Luxar-Coherent group. The averages for the Luxar-Sharplan group were 4.00 and 4.25 for the Luxar and Sharplan lasers, respectively. None of these differences was statistically significant. Fig 1 demonstrates the symmetric results that were typical of most subjects. In addition, most subjects were satisfied with the treatment results. Across all treatment groups and all treatment sites, subjects scored a 4 or 5 on the 5-point satisfaction scale 84% of the time. In the Luxar-Coherent comparison group, the average satisfaction grades were 4.63 and 4.50 for the Luxar and Coherent lasers, respectively. In the
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550 Gross and Rogers
A
B
Fig 1. Baseline (A) and 6-month follow-up (B) photographs after treatment with Luxar Novapulse (left side of face) and Coherent Ultrapulse (right side of face) lasers. Excellent improvement is noted symmetrically.
Table II. Duration of posttreatment erythema Duration (wk) of moderate to severe erythema (≥3)* Comparison group
Luxar vs Coherent Luxar Coherent Luxar vs Sharplan Luxar Sharplan *4-Point
No.
Mean
P
8 8
2.0 3.5
.34
8 8
3.5 3.1
.38
Table III. Quantification of erythema at 2 weeks Erythema value*
Duration (wk) of mild erythema (≥2)* Mean
P
5.0 7.5
.25
8.1 8.1
>.90
Comparison group
Luxar vs Coherent Luxar Coherent Luxar vs Sharplan Luxar Sharplan *([a-a ]·[a /183]): n c
scale: 1 = none, 2 = mild, 3 = moderate, 4 = severe.
other group, the average grades were 4.13 for the Luxar and 4.38 for the Sharplan laser. The differences were not statistically significant. Postprocedure erythema The duration of erythema as assessed by a blinded observer is presented in Table II. Erythema was scored as moderate or severe for an average of 2.0 and 3.5 weeks for the Luxar and Coherent lasers, respectively, in the Luxar-Coherent group and 3.5 and 3.1 weeks for the Luxar and Sharplan Lasers in the Luxar-Sharplan group. The median values were 1.5 and 2 weeks for the Luxar and Coherent lasers in the Luxar-Coherent group and 2 weeks each for the Luxar and Sharplan lasers in the Luxar-Sharplan group. The difference between the mean and median values is explained in large part by 1 outlier in each group of the study (sub-
No.
Mean
P
8 8
6.6 7.9
.32
7 7
7.9 7.2
.30
see text for details.
jects 11 and 16) with moderate erythema that persisted or reappeared up to 12 weeks. Typical results demonstrating equivalent erythema during the postoperative period are shown in Fig 2. The level of erythema as measured by digital image analysis at 2 weeks is presented in Table III. Erythema values were 6.6 and 7.9 for the Luxar and Coherent lasers, respectively, in the LuxarCoherent group, and 7.9 and 7.2 weeks for the Luxar and Sharplan Lasers in the Luxar-Sharplan group. The data from 1 patient in the LuxarSharplan group were unable to be evaluated. These differences were not statistically significant. Ease of use by laser The average times required to complete the procedure are presented in Table IV. These were not significantly different. Physicians operating the lasers were questioned regarding their preferences. All 3 lasers were felt to be satisfactory with regard to ease of use. Advantages reported included the large pattern sizes of the Coherent and Sharplan lasers, the aiming beams of the Coherent and
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Gross and Rogers 551
A
B
C
D
Fig 2. Posttreatment erythema at 48 hours (A), 1 week (B), 4 weeks (C), and 2 months (D) after treatment with Sharplan SilkLaser (left side of face) and Luxar Novapulse (right side of face) lasers. Little difference can be seen between lasers.
Sharplan lasers, and the small physical size of the Sharplan and Luxar Lasers. Hyperpigmentation Hyperpigmentation was deemed to be significant if at least mild hyperpigmentation was noted on more than 1 follow-up visit. In the CoherentLuxar group, 1 of 8 subjects experienced hyperpigmentation on the Coherent-treated side, and 2 of 8 subjects experienced hyperpigmentation on the Luxar-treated side. In the Sharplan-Luxar group, 2 of 8 subjects experienced hyperpigmentation with each laser. All cases of hyperpigmentation resolved completely within 3 months. Other side effects Only 1 patient reported more than mild pain at the 48-hour visit; this patient reported moderate pain on both the Luxar- and Sharplan-treated sides. No significant pain was reported beyond 48 hours. Only 2 subjects experienced more than mild crusting: 1 patient had moderate crusting on the Luxar-treated side at 1 week with mild crusting on the Sharplan-treated side, and the other patient had moderate crusting on both the Luxarand Coherent-treated sides at 48 hours. No sub-
Table IV. Time to complete procedure Time to complete procedure (min) Comparison group
Luxar vs Coherent Luxar Coherent Luxar vs Sharplan Luxar Sharplan
No.
Mean
P
8 8
5.8 5.9
>.90
8 8
5.6 5.2
.54
jects in the study experienced any scarring or infection. Histologic data The results of the 2 subjects from whom biopsy specimens were taken are presented in Table V. After 2 passes, all specimens demonstrated necrosis down to the mid or deep papillary dermis. DISCUSSION
This study attempted to make a direct comparison of the treatment of rhytides with 3 technologi-
Journal of the American Academy of Dermatology October 1998
552 Gross and Rogers
Fig 3. Comparison of posttreatment erythema and hyperpigmentation within and between 2 patients treated with same 2 lasers at same settings: at 48 hours (top row), at 2 weeks (middle row), and at 4 weeks (bottom row). There is notably more difference between patients than between lasers. Images in columns 2 and 4 have been right-left reversed to facilitate comparison.
Table V. Histology of laser-treated sites 1 Pass Comparison group
Depth*
2 Passes Depth*
Description
Description
Luxar vs Coherent Luxar Coherent
0.06 0.04
Superficial papillary dermis Deep epidermis to superficial papillary dermis
0.13 0.10
Deep papillary dermis Mid to deep papillary dermis
Luxar vs Sharplan Luxar Sharplan
0.07 0.05
Superficial papillary dermis Superficial papillary dermis
0.15 0.18
Mid to deep papillary dermis Deep papillary dermis
*Average
depth of necrosis (in millimeters) measured at 3 random points in specimen with an ocular micrometer. Each laser was set to 300 mJ with a spot size of 3 mm.
cally different CO2 resurfacing lasers. By treating symmetric halves of the face with different lasers, it was possible to control for intersubject variability.10 Our results showed that there were not significant differences between lasers with respect to improvement in rhytides, posttreatment erythema, patient satisfaction, treatment times, and other side effects. This is not to say that the 3 lasers are interchangeable. As with any complex surgical instrument, there is a learning period associated with each. We were able to become familiar with the idiosyncrasies of each laser before this study. We also caution that we have only examined 3 of the
many CO2 lasers that are currently marketed for facial resurfacing; our failure to find significant differences may not translate to all CO2 lasers. There are 3 important variables associated with CO2 laser resurfacing: the laser, the operator, and the patient. This study was designed to examine the first of these while controlling for the second and third. As already discussed, we found that the choice of these 3 lasers did not contribute significantly to outcome. With regard to operator differences, we have little comment because all of the subjects were treated by the same 2 surgeons at the same time with essentially identical technique.
Journal of the American Academy of Dermatology Volume 39, Number 4, Part 1
However, with regard to the third variable, differences between subjects were readily apparent. For example, we were impressed that subjects, compared with each other, had sometimes dramatically different degrees of erythema at a given postoperative visit. Fig 3 demonstrates notably different results between 2 patients who were treated with the same laser at the same settings at the same follow-up intervals. Similarly, some subjects had better overall improvement of their rhytides than others. However, within a given subject, there was almost always symmetric improvement between the 2 sides of the face. This experience has led us to the conclusion that patient selection is the most important factor in laser resurfacing. With regard to treatment times, the data presented represent the time to treat limited areas of the face. Differences might have become more significant if resurfacing of the entire face were performed. In addition, it should be noted that the Luxar Novascan scanner produces a significantly smaller spot size than either the Computerized Pattern Generator of the Coherent laser or the Feathertouch scanner of the Sharplan laser. However, the Luxar laser is fired at a more rapid rate (typically 8 times per second in this study) than the Coherent or Sharplan lasers (typically about 1 time per second). Thus a period of time is required to develop the skill necessary to lay down successive exposures of the Novascan precisely and evenly. Although limited, our histologic data demonstrating ablation to the deep epidermis or superficial papillary dermis after 1 pass and to the mid or deep papillary dermis after 2 passes were similar to that already reported.7,13,14 We used a novel method to quantify erythema. The L*a*b* system divides the spectrum of all possible colors (ie, the color space) into a 3dimensional set of coordinates. This system is intended to be homologous to the manner in which the human eye and brain perceive color: the “L” correlates to the lightness versus darkness of a color, the “a” correlates to the red versus green of a color, and the “b” correlates to the blue versus yellow. Takiwaki et al15-17 have used narrow-band reflectance spectrophotometry or tristimulus colorimetry to assess erythema directly on the skin. These authors used the a* channel as the “erythema index” to quantify erythema. We have applied
Gross and Rogers 553 the same principles to digitally captured photographs of skin. This technique allows investigators to analyze color retrospectively on stored data. In addition, investigators can quickly analyze average values over multiple points of measurement. REFERENCES 1. Spicer MS, Goldberg DJ. Lasers in dermatology. J Am Acad Dermatol 1996;34:1-25. 2. Waldorf HA, Kauvar AN, Geronemus RG. Skin resurfacing of fine to deep rhytides using a char-free carbon dioxide laser in 47 subjects. Dermatol Surg 1995;21:940-6. 3. Lowe NJ, Lask G, Griffin ME, et al. Skin resurfacing with the UltraPulse Carbon Dioxide Laser. Dermatol Surg 1995;21:1025-9. 4. Alster TS, West TB. Resurfacing of atrophic facial acne scars with a high-energy, pulsed carbon dioxide laser. Dermatol Surg 1996;22:151-5. 5. Anderson RR, Parish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science 1983;220:524-7. 6. Walsh JT Jr, Flotte TJ, Anderson RR, Deutsch TF. Pulsed CO2 laser tissue ablation: effect of tissue type and pulse duration on thermal damage. Lasers Surg Med 1988;8: 108-18. 7. Kauvar AB, Waldorf HA, Geronemus RG. A histopathological comparison of “char-free” carbon dioxide lasers. Dermatol Surg 1996;22:343-8. 8. Green HA, Domankevitz Y, Nishioka NS. Pulsed carbon dioxide laser ablation of burned skin: in vitro and in vivo analysis. Lasers Surg Med 1990;10:476-84. 9. Walsh JT Jr, Deutsch TF. Pulsed CO2 laser tissue ablation: measurement of the ablation rate. Lasers Surg Med 1988;8:264-75. 10. Alster TS. Comparison of two high-energy, pulsed carbon dioxide lasers in the treatment of periorbital rhytides. Dermatol Surg 1996;22:541-5. 11. Lowe NJ, Lask G, Griffin ME. Laser skin resurfacing: pre- and posttreatment guidelines. Dermatol Surg 1995; 21:1017-9. 12. Ho C, Nguyen Q, Lowe NJ, Griffin ME, Lask G. Laser resurfacing in pigmented skin. Dermatol Surg 1995;21: 1035-7. 13. Alster TS, Kauvar AN, Geronemus RG. Histology of high-energy pulsed CO2 laser resurfacing. Semin Cutan Med Surg 1996;15:189-93. 14. Cotton J, Hood AF, Gonin R, Beesen WH, Hanke CW. Histologic evaluation of preauricular and postauricular human skin after high-energy, short-pulse carbon dioxide laser. Arch Dermatol 1996;132:425-8. 15. Takiwaki H, Serup J. Variation in color and blood flow of the forearm skin during orthostatic maneuver. Skin Pharmacol 1994;7:226-30. 16. Takiwaki H, Overgaard L, Serup J. Comparison of narrow-band reflectance spectrophotometric and tristimulus colorimetric measurements of skin color: twenty-three anatomical sites evaluated by the Dermaspectrometer and the Chroma Meter CR-200. Skin Pharmacol 1994;7:217-25. 17. Takiwaki H, Serup J. Measurement of color parameters of psoriatic plaques by narrow-band reflectance spectrophotometry and tristimulus colorimetry. Skin Pharmacol 1994;7:145-50.
The use of lasers for cutaneous resurfacing, including the treatment of rhytides and acne scars, has become widely accepted.1-4 Several lasers are available. Most use carbon dioxide (CO2) as a lasing material to emit energy at a wavelength of 10,600 nm. Furthermore, most CO2 resurfacing lasers, in adherence to the principles of selective photothermolysis established by Anderson and Parrish,5 expose the treated surface of the skin to approximately 5 J or more of energy in less than 1 ms.1,5-9 In this manner, tissue is vaporized without enough residual thermal damage to cause scarring. However, lasers vary markedly in the method by which this is achieved. Few studies have been published comparing the results of treatment with different lasers in the same subjects.10 This study compares 3 different CO2 resurfacing lasers side by side in the same subjects. Each laser uses a different technology to deliver energy to the skin. The Coherent Ultrapulse (Coherent Lasers, Inc, Palo Alto, Calif) laser delivers single From the Dermatologic Surgery Unit, Department of Surgery, Boston University School of Medicine. Supported by a grant from the Luxar Corporation, Bothell, Wash. Accepted for publication June 15, 1998. Reprint requests: Edward A. Gross, MD, 88 E Newton St, Boston, MA 02118. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/1/92425
submillisecond pulses of energy.1,3 The Sharplan SilkLaser (Sharplan Lasers Inc, Allendale, NJ) uses a continuous wave of energy that is scanned across the surface of the skin in such a way that any individual point along the treated area is only exposed to the laser energy for less than 1 ms.1,2 The Luxar Novapulse (Luxar Corp, Bothell, Wash) laser uses rapid superpulses of extremely short duration that are clustered together into a burst the total duration of which is less than 1 ms. METHODS
Subjects Subjects were recruited for the study from the healthy adult population within the community. Subjects were aged 18 to 75 years, had Fitzpatrick skin type I to III, and had bilaterally symmetric rhytides around the mouth or eyes. Subjects were excluded if they had a history of previous skin resurfacing, cosmetic surgery, or radiation treatment in the area being considered for laser treatment. Additional exclusion criteria included a clinically significant history of acute or chronic illness, any clinically significant acute or chronic skin disease, cutaneous malignancies of the face, any active acute illness within 4 weeks, use of tobacco within 6 weeks, evidence of active substance or alcohol abuse, participation in a study of another investigational device or drug within 4 weeks, active herpes simplex of the mouth, use of isotretinoin within 12 months, and pregnancy.
547
548 Gross and Rogers Study design This was a prospective, randomized, blinded study with each subject serving as his/her own control. A total of 16 subjects were enrolled. Informed consent was obtained from all subjects. Subjects pretreated the face for 2 weeks before laser treatment with sunscreen cream (skin protection factor 15 or greater) each morning and tretinoin (Retin-A) cream 0.025% each evening. Subjects with skin type III or with a history of postinflammatory hyperpigmentation also pretreated the face with hydroquinone cream 4% each morning. All subjects initiated treatment with acyclovir 400 mg by mouth 3 times daily beginning 24 hours before the treatment.11,12 The 16 subjects were divided into 2 treatment groups of 8 subjects each. In 1 group, subjects were treated with the Luxar Novapulse laser with a Novascan scanner to one side of the face and the Coherent Ultrapulse 5000 laser with a computerized pattern generator to the other side of the face. The other half of the subjects were treated with the Luxar laser and scanner to one side of the face and the Sharplan SilkLaser with a Feathertouch scanner to the other side of the face. In each group, subjects were further randomized as to which side of the face was treated with each laser. In addition, a biopsy specimen (from 1 patient in each group) was obtained from postauricular skin after laser treatment. Baseline assessments of skin texture included clinical evaluation, 35-mm color-slide photographs, and digital images. Anesthesia was accomplished with local and/or regional infiltration of lidocaine 0.5% with 1:200,000 epinephrine. Treatment was performed according to the randomization scheme. Each area was treated sufficiently to assure that, in the investigators’ opinion, the rhytides had been effaced or that ablation to the depth of superficial dermis had been reached, as indicated by the clinical appearance. Between passes, debris was removed with saline solution and gauze. All treatment factors including laser settings, technique, and number of treatment passes were recorded. The Coherent laser was used with the computerized pattern generator with pattern sizes ranging from 3 to 7 mm, density settings of 3 to 7, and fluences of 250 to 350 mJ. The Sharplan laser was used in the Feathertouch mode with pattern sizes ranging from 3 to 9 mm and power settings of 30 to 38 W. The Luxar laser was used with the Novapulse scanner generating 3-mm pattern sizes and power settings of 4 to 6 W. For each laser treatment site, 2 to 4 passes were required to efface the rhytides. If the patient had consented to biopsy, two 3-mm diameter regions of skin on each postauricular surface were treated with 1 and 2 passes, respectively, of the laser used to treat the ipsilateral side of the face, with an energy setting equivalent to 300 mJ. Each 3-mm site
Journal of the American Academy of Dermatology October 1998
was then removed with a punch biopsy and sent for pathologic examination. After the laser treatment, the areas were cleansed with water and petrolatum was applied liberally. An additional set of images was obtained immediately after the laser treatment. The subjects were given cephalexin 250 mg by mouth 4 times daily for 7 days. Subjects with sensitivity to cephalosporins received erythromycin 333 mg by mouth 3 times daily for 7 days. In addition, subjects continued their acyclovir at 400 mg by mouth 3 times daily for a total of 1 week. Posttreatment instructions included frequent washings with lukewarm tap water and applications of petrolatum. All subjects were seen at 48 hours (± 7 hours), 1 week (± 1 day), 2 weeks (± 2 days), 1 month (± 5 days), 2 months (± 9 days), 3 months (± 13 days), and 6 months (± 27 days). At each time point, the clinical response to therapy was clinically measured by an observer blinded as to laser type and laterality. Hyperpigmentation, erythema, crusting, infection, scarring, and patient’s subjective reporting of pain were all assessed with a 4-point scale: 1 = none; 2 = mild; 3 = moderate; 4 = severe. At the 2-week, 1-month, 2-month, 3-month, and 6-month visits, the rhytides were evaluated with a 5-point scale: 1 = worse; 2 = no change (0%10%); 3 = slightly improved (10%-40%); 4 = moderately improved (40%-80%); 5 = greatly improved (80%-100%). In addition, the evaluator and patient completed a subjective assessment survey at the 2week, 1-month, 2-month, 3-month, and 6-month visits. Patient satisfaction was measured with a scale ranging from 1 (not at all satisfied) to 5 (very satisfied). At each follow-up visit, 35-mm slides and digital images were taken of the treated areas. For each subject, erythema was scored clinically and by digital image analysis. Digital images were captured with a Hi-8 camcorder and then captured as 24-bit 320 × 240 pixel jpeg images with a video capture card attached to a personal computer. Each picture contained a color calibration card in the field of view. Then, using Adobe Photoshop version 4.0 (Adobe Systems Inc, San Jose, Calif), the images were converted to the L*a*b* color scheme. The “a” channel was then isolated, and histogram functions were measured for each picture in the area of laser treatment (value “a”). A second value was measured in an untreated area of normal skin (value “an”). A third value was measured over the color calibration card (value “ac”). The erythema score is expressed as the difference between the measured erythema of the treated area and the untreated area, corrected by the measurement of the color calibration card: ([a-an]·[ac/183]), where 183 is the average measured value of the color calibration card. Speed of treatment was evaluated by use of a chronometer during the procedure; the measurement
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Gross and Rogers 549
Table I. Improvement in rhytides and patient satisfaction at end of study (6 months) Improvement in rhytides (blinded observer)* Patient No.
Area treated
L
7 12 5 10 4 14 16 3
Periorbital Periorbital Periorbital Perioral Periorbital Perioral Periorbital Periorbital
4 3 5 5 3 3 4 3
9 13 1 6 8 15 11 2
Perioral Perioral Periorbital Periorbital Periorbital Periorbital Periorbital Perioral
4 3 5 4 4 4 4 4
S
Improvement in rhytides (patient assessment)* C
L
5 4 4 5 3 3 4 3
5 3 5 5 5 4 5 5
P = .56 5 4 4 4 5 4 3 5 P = .42
4 3 5 4 4 5 3 4
S
P = .16 4 4 5 4 5 5 3 4 P = .16
Patient satisfaction with results† C
L
5 3 4 5 5 4 4 5
5 3 5 5 5 4 5 5 4 3 5 5 4 5 3 4
S
C
5 3 5 5 5 4 4 5 P = .32 4 4 5 5 5 5 3 4 P = .16
C, Coherent; L, Luxar; S, Sharplan. *5-Point scale: 1 = worse, 5 = greatly improved (see text for details). †5-Point scale: 1 = not at all satisfied, 5 = very satisfied.
reflects only the period of time beginning when the laser was first discharged until it was placed back into stand-by mode at the end of the procedure. Ease of use for each laser was analyzed by assessments of the investigators. For subjects from whom biopsy specimens were obtained, depth of necrosis was measured on the histologic specimens with an ocular micrometer. Subjects resumed tretinoin cream to the face 4 weeks after the laser treatment. Subjects with evidence of hyperpigmentation began treatment to the face with hydroquinone cream 4% and sunscreen (skin protection factor 15 or greater) each morning. Statistical significance of the data was calculated with the Wilcoxon signed-rank test to determine the differences between values obtained regarding improvement in rhytides and patient satisfaction. The paired t test was used for comparison of the duration of erythema, measured erythema levels, and treatment times. RESULTS
Improvement in rhytides and patient satisfaction with results Overall improvement in rhytides as measured on a clinical scale by a blinded observer and by the subjects and patient satisfaction are presented in Table I. Overall, most subjects had significant
improvement in rhytides. Across all treatment groups, moderate or great improvement was seen in 72% of treatment sites according to a blinded observer and 84% of treatment sites according to subjects. In the Luxar-Coherent comparison group, the average improvement grades, as judged by a blinded observer, were 3.75 and 3.88 for the Luxar and Coherent lasers, respectively. In the other group, the average grades were 4.00 for the Luxar and 4.25 for the Sharplan laser. The average improvement grades as judged by the patient were 4.63 for the Luxar and 4.38 for the Coherent in the Luxar-Coherent group. The averages for the Luxar-Sharplan group were 4.00 and 4.25 for the Luxar and Sharplan lasers, respectively. None of these differences was statistically significant. Fig 1 demonstrates the symmetric results that were typical of most subjects. In addition, most subjects were satisfied with the treatment results. Across all treatment groups and all treatment sites, subjects scored a 4 or 5 on the 5-point satisfaction scale 84% of the time. In the Luxar-Coherent comparison group, the average satisfaction grades were 4.63 and 4.50 for the Luxar and Coherent lasers, respectively. In the
Journal of the American Academy of Dermatology October 1998
550 Gross and Rogers
A
B
Fig 1. Baseline (A) and 6-month follow-up (B) photographs after treatment with Luxar Novapulse (left side of face) and Coherent Ultrapulse (right side of face) lasers. Excellent improvement is noted symmetrically.
Table II. Duration of posttreatment erythema Duration (wk) of moderate to severe erythema (≥3)* Comparison group
Luxar vs Coherent Luxar Coherent Luxar vs Sharplan Luxar Sharplan *4-Point
No.
Mean
P
8 8
2.0 3.5
.34
8 8
3.5 3.1
.38
Table III. Quantification of erythema at 2 weeks Erythema value*
Duration (wk) of mild erythema (≥2)* Mean
P
5.0 7.5
.25
8.1 8.1
>.90
Comparison group
Luxar vs Coherent Luxar Coherent Luxar vs Sharplan Luxar Sharplan *([a-a ]·[a /183]): n c
scale: 1 = none, 2 = mild, 3 = moderate, 4 = severe.
other group, the average grades were 4.13 for the Luxar and 4.38 for the Sharplan laser. The differences were not statistically significant. Postprocedure erythema The duration of erythema as assessed by a blinded observer is presented in Table II. Erythema was scored as moderate or severe for an average of 2.0 and 3.5 weeks for the Luxar and Coherent lasers, respectively, in the Luxar-Coherent group and 3.5 and 3.1 weeks for the Luxar and Sharplan Lasers in the Luxar-Sharplan group. The median values were 1.5 and 2 weeks for the Luxar and Coherent lasers in the Luxar-Coherent group and 2 weeks each for the Luxar and Sharplan lasers in the Luxar-Sharplan group. The difference between the mean and median values is explained in large part by 1 outlier in each group of the study (sub-
No.
Mean
P
8 8
6.6 7.9
.32
7 7
7.9 7.2
.30
see text for details.
jects 11 and 16) with moderate erythema that persisted or reappeared up to 12 weeks. Typical results demonstrating equivalent erythema during the postoperative period are shown in Fig 2. The level of erythema as measured by digital image analysis at 2 weeks is presented in Table III. Erythema values were 6.6 and 7.9 for the Luxar and Coherent lasers, respectively, in the LuxarCoherent group, and 7.9 and 7.2 weeks for the Luxar and Sharplan Lasers in the Luxar-Sharplan group. The data from 1 patient in the LuxarSharplan group were unable to be evaluated. These differences were not statistically significant. Ease of use by laser The average times required to complete the procedure are presented in Table IV. These were not significantly different. Physicians operating the lasers were questioned regarding their preferences. All 3 lasers were felt to be satisfactory with regard to ease of use. Advantages reported included the large pattern sizes of the Coherent and Sharplan lasers, the aiming beams of the Coherent and
Journal of the American Academy of Dermatology Volume 39, Number 4, Part 1
Gross and Rogers 551
A
B
C
D
Fig 2. Posttreatment erythema at 48 hours (A), 1 week (B), 4 weeks (C), and 2 months (D) after treatment with Sharplan SilkLaser (left side of face) and Luxar Novapulse (right side of face) lasers. Little difference can be seen between lasers.
Sharplan lasers, and the small physical size of the Sharplan and Luxar Lasers. Hyperpigmentation Hyperpigmentation was deemed to be significant if at least mild hyperpigmentation was noted on more than 1 follow-up visit. In the CoherentLuxar group, 1 of 8 subjects experienced hyperpigmentation on the Coherent-treated side, and 2 of 8 subjects experienced hyperpigmentation on the Luxar-treated side. In the Sharplan-Luxar group, 2 of 8 subjects experienced hyperpigmentation with each laser. All cases of hyperpigmentation resolved completely within 3 months. Other side effects Only 1 patient reported more than mild pain at the 48-hour visit; this patient reported moderate pain on both the Luxar- and Sharplan-treated sides. No significant pain was reported beyond 48 hours. Only 2 subjects experienced more than mild crusting: 1 patient had moderate crusting on the Luxar-treated side at 1 week with mild crusting on the Sharplan-treated side, and the other patient had moderate crusting on both the Luxarand Coherent-treated sides at 48 hours. No sub-
Table IV. Time to complete procedure Time to complete procedure (min) Comparison group
Luxar vs Coherent Luxar Coherent Luxar vs Sharplan Luxar Sharplan
No.
Mean
P
8 8
5.8 5.9
>.90
8 8
5.6 5.2
.54
jects in the study experienced any scarring or infection. Histologic data The results of the 2 subjects from whom biopsy specimens were taken are presented in Table V. After 2 passes, all specimens demonstrated necrosis down to the mid or deep papillary dermis. DISCUSSION
This study attempted to make a direct comparison of the treatment of rhytides with 3 technologi-
Journal of the American Academy of Dermatology October 1998
552 Gross and Rogers
Fig 3. Comparison of posttreatment erythema and hyperpigmentation within and between 2 patients treated with same 2 lasers at same settings: at 48 hours (top row), at 2 weeks (middle row), and at 4 weeks (bottom row). There is notably more difference between patients than between lasers. Images in columns 2 and 4 have been right-left reversed to facilitate comparison.
Table V. Histology of laser-treated sites 1 Pass Comparison group
Depth*
2 Passes Depth*
Description
Description
Luxar vs Coherent Luxar Coherent
0.06 0.04
Superficial papillary dermis Deep epidermis to superficial papillary dermis
0.13 0.10
Deep papillary dermis Mid to deep papillary dermis
Luxar vs Sharplan Luxar Sharplan
0.07 0.05
Superficial papillary dermis Superficial papillary dermis
0.15 0.18
Mid to deep papillary dermis Deep papillary dermis
*Average
depth of necrosis (in millimeters) measured at 3 random points in specimen with an ocular micrometer. Each laser was set to 300 mJ with a spot size of 3 mm.
cally different CO2 resurfacing lasers. By treating symmetric halves of the face with different lasers, it was possible to control for intersubject variability.10 Our results showed that there were not significant differences between lasers with respect to improvement in rhytides, posttreatment erythema, patient satisfaction, treatment times, and other side effects. This is not to say that the 3 lasers are interchangeable. As with any complex surgical instrument, there is a learning period associated with each. We were able to become familiar with the idiosyncrasies of each laser before this study. We also caution that we have only examined 3 of the
many CO2 lasers that are currently marketed for facial resurfacing; our failure to find significant differences may not translate to all CO2 lasers. There are 3 important variables associated with CO2 laser resurfacing: the laser, the operator, and the patient. This study was designed to examine the first of these while controlling for the second and third. As already discussed, we found that the choice of these 3 lasers did not contribute significantly to outcome. With regard to operator differences, we have little comment because all of the subjects were treated by the same 2 surgeons at the same time with essentially identical technique.
Journal of the American Academy of Dermatology Volume 39, Number 4, Part 1
However, with regard to the third variable, differences between subjects were readily apparent. For example, we were impressed that subjects, compared with each other, had sometimes dramatically different degrees of erythema at a given postoperative visit. Fig 3 demonstrates notably different results between 2 patients who were treated with the same laser at the same settings at the same follow-up intervals. Similarly, some subjects had better overall improvement of their rhytides than others. However, within a given subject, there was almost always symmetric improvement between the 2 sides of the face. This experience has led us to the conclusion that patient selection is the most important factor in laser resurfacing. With regard to treatment times, the data presented represent the time to treat limited areas of the face. Differences might have become more significant if resurfacing of the entire face were performed. In addition, it should be noted that the Luxar Novascan scanner produces a significantly smaller spot size than either the Computerized Pattern Generator of the Coherent laser or the Feathertouch scanner of the Sharplan laser. However, the Luxar laser is fired at a more rapid rate (typically 8 times per second in this study) than the Coherent or Sharplan lasers (typically about 1 time per second). Thus a period of time is required to develop the skill necessary to lay down successive exposures of the Novascan precisely and evenly. Although limited, our histologic data demonstrating ablation to the deep epidermis or superficial papillary dermis after 1 pass and to the mid or deep papillary dermis after 2 passes were similar to that already reported.7,13,14 We used a novel method to quantify erythema. The L*a*b* system divides the spectrum of all possible colors (ie, the color space) into a 3dimensional set of coordinates. This system is intended to be homologous to the manner in which the human eye and brain perceive color: the “L” correlates to the lightness versus darkness of a color, the “a” correlates to the red versus green of a color, and the “b” correlates to the blue versus yellow. Takiwaki et al15-17 have used narrow-band reflectance spectrophotometry or tristimulus colorimetry to assess erythema directly on the skin. These authors used the a* channel as the “erythema index” to quantify erythema. We have applied
Gross and Rogers 553 the same principles to digitally captured photographs of skin. This technique allows investigators to analyze color retrospectively on stored data. In addition, investigators can quickly analyze average values over multiple points of measurement. REFERENCES 1. Spicer MS, Goldberg DJ. Lasers in dermatology. J Am Acad Dermatol 1996;34:1-25. 2. Waldorf HA, Kauvar AN, Geronemus RG. Skin resurfacing of fine to deep rhytides using a char-free carbon dioxide laser in 47 subjects. Dermatol Surg 1995;21:940-6. 3. Lowe NJ, Lask G, Griffin ME, et al. Skin resurfacing with the UltraPulse Carbon Dioxide Laser. Dermatol Surg 1995;21:1025-9. 4. Alster TS, West TB. Resurfacing of atrophic facial acne scars with a high-energy, pulsed carbon dioxide laser. Dermatol Surg 1996;22:151-5. 5. Anderson RR, Parish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science 1983;220:524-7. 6. Walsh JT Jr, Flotte TJ, Anderson RR, Deutsch TF. Pulsed CO2 laser tissue ablation: effect of tissue type and pulse duration on thermal damage. Lasers Surg Med 1988;8: 108-18. 7. Kauvar AB, Waldorf HA, Geronemus RG. A histopathological comparison of “char-free” carbon dioxide lasers. Dermatol Surg 1996;22:343-8. 8. Green HA, Domankevitz Y, Nishioka NS. Pulsed carbon dioxide laser ablation of burned skin: in vitro and in vivo analysis. Lasers Surg Med 1990;10:476-84. 9. Walsh JT Jr, Deutsch TF. Pulsed CO2 laser tissue ablation: measurement of the ablation rate. Lasers Surg Med 1988;8:264-75. 10. Alster TS. Comparison of two high-energy, pulsed carbon dioxide lasers in the treatment of periorbital rhytides. Dermatol Surg 1996;22:541-5. 11. Lowe NJ, Lask G, Griffin ME. Laser skin resurfacing: pre- and posttreatment guidelines. Dermatol Surg 1995; 21:1017-9. 12. Ho C, Nguyen Q, Lowe NJ, Griffin ME, Lask G. Laser resurfacing in pigmented skin. Dermatol Surg 1995;21: 1035-7. 13. Alster TS, Kauvar AN, Geronemus RG. Histology of high-energy pulsed CO2 laser resurfacing. Semin Cutan Med Surg 1996;15:189-93. 14. Cotton J, Hood AF, Gonin R, Beesen WH, Hanke CW. Histologic evaluation of preauricular and postauricular human skin after high-energy, short-pulse carbon dioxide laser. Arch Dermatol 1996;132:425-8. 15. Takiwaki H, Serup J. Variation in color and blood flow of the forearm skin during orthostatic maneuver. Skin Pharmacol 1994;7:226-30. 16. Takiwaki H, Overgaard L, Serup J. Comparison of narrow-band reflectance spectrophotometric and tristimulus colorimetric measurements of skin color: twenty-three anatomical sites evaluated by the Dermaspectrometer and the Chroma Meter CR-200. Skin Pharmacol 1994;7:217-25. 17. Takiwaki H, Serup J. Measurement of color parameters of psoriatic plaques by narrow-band reflectance spectrophotometry and tristimulus colorimetry. Skin Pharmacol 1994;7:145-50.