Review of Khatri KA et. al. Efficacy and safety of a 0.65 millisecond pulsed portable ND:YAG laser for hair removal.

March 1, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19199118

 

J Cosmet Laser Ther. 2009 Feb 6:1-6
 

Efficacy and safety of a 0.65 millisecond pulsed portable ND:YAG laser for hair removal.
 

Khatri KA, Lee RA, Goldberg LJ, Khatri B, Garcia V.
 

Skin & Laser Surgery Center of New England, MA and Nashua, NH, USA.
 

In this 6 patient study, Khatri et. al. evaluate the AeroLase portable Nd:YAG laser for laser hair removal (LHR).  While the results appear promising, the conclusion that this device is “as effective and safe as other devices for LHR” is simply not supported.  The main study flaws include a very small number of patients treated, poorly performed hair counts, and a complete lack of statistical analysis.  The authors even neglected to report the variances around mean hair count reductions.
 
A strength of the study is the use of an internal control site, as half the axilla was treated and half was untreated.  The treated half (either upper or lower) was alternated among consecutive patients.  Two treatment regimes (high and low fluence) were studied, one on the left side and one on the right, again alternated among patients. In both cases, randomization would normally be preferred to alternation; however, randomization in such a small number of patients might have resulted in unequal groups. The treatment protocol consisted of a series of four monthly treatments, followed by a one-month and four-month follow up visits.   A single, presumably unblinded, individual counted hairs in treated and control sites, pre-treatment and at both follow-up visits.

 

At the four month follow up, which is a meaningful period for evaluation of permanent hair reduction, the study showed mean reductions in hair counts at both the treated sites (76%) and the control sites (36%).  The authors attribute the reduction at the control sites to “diffusion of energy from the treatment side to the control side.”  In most other studies, a standard (e.g. 1cm2) area within each of the control and treatment sites is chosen for the hair count, with sufficient spacing to eliminate any potential energy diffusion.  In this study, unfortunately, the authors do not disclose how the hair counts were performed, or how the same areas were counted at each of the time points in the study.  Therefore, it is difficult to compare these results to other studies.  Further, the authors do not describe the variance around the mean hair reductions, or the number of patients who achieved greater hair reduction at the treated site than at the control site.  Consequently, it cannot be determined whether the different results in the treated and control sites are statistically significant.

 

The six patients self-reported satisfaction, resulting in 1 patient dissatisfied, 2 patients satisfied and 3 very satisfied. Patient satisfaction is often unrelated to clinical outcomes, as patients may be satisfied that they particpated in a treatment, even if no objective improvement was measured.  So, satisfaction data must be taken with a grain of salt.  The patients were not asked to evaluate improvement of treated sites versus control sites, which might have provided more meaningful data. 

 

Unsurprisingly, histology from treatment site biopsies showed qualitiative changes similar to those described in other articles about light-based hair removal devices.  No conclusions of effectiveness could be drawn however, as quantitative histological analysis was precluded by the limited sample size (two patients) and lack of biopsies of control sites.

 

Contrary to the authors’ conclusions, for a given number of treatments, the Aerolase device is not likely to achieve comparable results to a higher fluence, larger spot laser with integrated skin cooling.  Skin cooling clearly increases the margin between an effective treatment fluence and over-treatment, higher fluences clearly increase the effectiveness of hair reduction, and larger spot sizes (10mm or greater radius) increase the depth of optical penetration, further enhancing results.

 

Nevertheless, to provide effective results, the Aerolase may simply require more treatment sessions than the higher-fluence, integrated cooling devices.  A significantly larger study, with improved hair-count measurement methods, is required to fully elucidate the capabilities of this device.
 

 

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Review of Faurschou A, Pulsed dye laser vs. intense pulsed light for port-wine stains

February 22, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19120324

Br J Dermatol. 2008 Dec 11.

 

Pulsed dye laser vs. intense pulsed light for port-wine stains: a randomized side-by-side trial with blinded response evaluation.

 

Faurschou A, Togsverd-Bo K, Zachariae C, Hædersdal M.

 

Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark.

 

This study is from the same Denmark group that recently compared the pulse dye laser (LPDL) to the intense pulsed light (IPL) for the treatment of photoaging.  In this study, Annesofie Faurschou reports another head-to-head study comparing these two device types, this time for the treatment of portwine stains.  The study was supported by the laser manufacturer and the local sales agent for the IPL, but neither sponsor participated in the conduct or analysis of the study.  In particular, this study compared the Candela VBeam Perfecta (long pulse 595nm dye laser) with the Palomar StarLux IPL with a Lux G handpiece.

The study was adequately, though not optimally, designed to demonstrate the differences with each type of treatment.  First, each study participant received one split-lesion treatment, with the one half of the lesion randomized to each device type, which properly controls for non-study effects (e.g. additional sun exposure).  The use of a split-face design also appropriately controls for patient variability.  However, the use of a series of multiple treatments would have magnified any possible outcome differences, and would better reflect clinical practice.   Second, one evaluation was performed photographically by a blinded assessor.  Blinding appropriately prevents bias, but the introduction of photographic artifact may obscure outcome differences.  Third, a second evaluation was performed with a skin reflectance meter, also performed by a assessor blinded to device-types used on each half.  Blinding appropriately prevents bias, but this meter has been validated for the use of evaluating erythema and pigmentation rather than portwine stains.

In this study, while both devices achieved measurable PWS lightening and no adverse events were found, the pulsed dye laser showed superior efficacy, both by blinded photographic evaluation and by blinded skin photometer.  The difference in lightening was both statistically and clinically significant (i.e. the difference in lightening was visually apparent to the blinded reviewer and the patient), even though only one treatment was performed.  As far as patient preference, 18 of 20 patients preferred to have subsequent treatments with the LPDL, while 2 preferred the IPL.

The superior results of the pulse dye laser may not be considered definitive based solely on this study, as there was no-pre-defined study hypothesis to be proven.  However, the authors refer to several other studies to underline their proposal that the LPDL be considered the first choice modality for PWS treatment, with the IPL reserved for poor-LPDL-responders.  This is an appropriate guideline.


Review of Lach E, Reduction of subcutaneous fat and improvement in cellulite appearance by dual-wavelength, low-level laser energy combined with vacuum and massage

February 15, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19093288

 

J Cosmet Laser Ther. 2008 Dec;10(4):202-9.

 

Reduction of subcutaneous fat and improvement in cellulite appearance by dual-wavelength, low-level laser energy combined with vacuum and massage.

 

Lach E.

 

Boston Surgical Group, Southborough, MA 01772, USA.

 

 

In this article, Elliot Lach MD presents the first publication of the clinical results achieved with the new SmoothShapes cellulite treatment device.  Note that Lach is the inventor of the technology and a shareholder in Eleme, the company which makes the device.

 

In this study of 102 female patients, one thigh was randomized to treatment with the SmoothShapes device and one thigh to massage-alone.  Patients received an average of 14.3 treatments over 4 to 6 weeks.  MRI measurements, thigh circumference measurements and photographs were taken of each patient.  A patient satisfaction questionnaire was completed at the end of the study.  In SmoothShapes treated legs, MRI showed an average decrease in fat thickness of 1.19cm2 from a baseline average of 136.57cm2, which is less than 1% change.  In the control legs, MRI showed an average increase in fat thickness of 3.82cm2 from a baseline average of 133.98 cm2, about a 2% change.  The thigh circumference measurements showed no significant difference between the two SmoothShapes treatment and the control.  While photographs were taken, no grading of the photographs for severity of cellulite was presented.

 

While the MRI results are statistically significant, a <1% decrease in fat thickness cannot be considered clinically significant.  The increased fat thickness in the massage-only group remains unexplained.  No covariance analysis of weight gain or reduction was provided.  While the title of the article refers to “improvement in cellulite,” no evidence of any improvement in the appearance of cellulite was presented.  While patient satisfaction was reported at 72.6%, a placebo effect cannot be ruled out.  Alternatively, a quantifiable evaluation of cellulite appearance should have been easy to perform, by asking the blinded patient and/or a blinded observer to identify the leg that was treated versus the leg receiving massage only (50% correct responses would result from chance, while 100% correct responses would indicate meaningful improvement in all cases).

 

In summary, this study failed to show clinically significant reductions in subcutaneous fat or body circumference, nor was improvement in cellulite appearance shown.  One is left to wonder whether the device has any effect at all.

 


Review of Manstein D, et. al. Selective cryolysis: a novel method of non-invasive fat removal

February 9, 2009

http://www.ncbi.nlm.nih.gov/pubmed/18951424

Lasers Surg Med. 2008 Nov;40(9):595-604

Selective cryolysis: a novel method of non-invasive fat removal.

Manstein D, Laubach H, Watanabe K, Farinelli W, Zurakowski D, Anderson RR.

Department of Dermatology, Wellman Center for Photomedicine , Massachusetts General Hospital , Harvard Medical School , Boston , Massachusetts , USA .

Manstein et. al. present the first animal study results with prototype  Zeltiq devices for non-invasive cold-induced fat destruction.   Note that Manstein is the inventor of the technology and receives royalties from Zeltiq. This report provides critical insight into the device-tissue interaction, the rationale for device parameter selection, and the mechanism of tissue response to the procedure.

Non- invasive surface cooling lowers the temperature of epidermis, dermis and subcutaneous fat via thermal conduction.  Because fat cells are more easily damaged by cold temperatures than are skin cells, this approach attempts to cool the subcutaneous fat below its damage threshold, while keeping the epidermis and dermis above their dermal damage thresholds.  Because cold is delivered from the surface through the dermal layers to the fat, the challenge is to make the dermis cold enough (for long enough) to adequately cool the fat, while keeping the dermal layers from frostbite.

Three animal studies (female black yucatan pigs, age 2-3, ca. 100 lb.) are presented in this paper.  All treatments were performed with the animals under general anesthesia, so treatment pain (e.g. signs of distress) could not be evaluated.

In the first study, a lab prototype was applied to eleven locations (abdomen, flank, buttock) on one animal.  This prototype provided contact cooling of the skin surface to -7C, and attempted to apply sufficient pressure to inhibit blood flow in the skin (which would warm the subcutaneous fat and thus prevent fat cooling below the damage threshold).  Durations varied from 5 to 21 minutes.  This pig was observed for 3.5 months, and except for some slight hyperpigmentation, no apparent skin injury was seen.  The highest degree of fat loss was seen as an easily visible indentation in the skin corresponding to the shape of the applicator.  This occurred at a buttock location with a cooling duration of 10 minutes, and where dermal blood flow was felt to be well inhibited.  By histology, 40% of the total fat layer thickness was removed in this area.  This n=1 experiment demonstrated initial feasibility of this approach.

In the second study, two prototype Zeltiq devices were applied to a total of 60 locations on 4 animals, to test the effect of various device temperature settings and the need for blood-flow suppression.   The first device was a flat cold applicator that could be held against the skin surface (“flat” applicator) but would not inhibit blood flow.  The second device clamped a fold of skin between two cold plates (“fold” applicator), enabling compression of the skin fold, effective suppression of blood flow within the fold and an improved cooling geometry.  Ten control sites were treated with applicators set to skin temperature (20C).  At some treatment sites, thermocouples were used to measure in vivo tissue temperatures during the procedure, demonstrating that significantly colder fat temperatures were achieved with the “fold” applicator, even at the same temperature as the “flat” applicator.  In this study, no clinical or histological evidence of damage to the epidermis or dermis was found, thus demonstrating that it is possible to provide cooling to the fat without damaging the overlying skin layers.  By histology, fat damage was significantly greater at lower applicator temperatures, with the lowest temperature applicator (-7C) achieving the best results.  At 1 month post treatment, most of the “fold” applicator sites showed obvious visible skin indentation (up to 3mm reduction in fat thickness), while none of the “flat” applicator sites showed such indentations.  It is not known if 3mm reduction could be routinely obtained.

This study also provided data regarding the biological mechanism of fat destruction.  At one day post treatment, no damage was seen on histology at either control or treatment sites.  At two days, inflammation (clusters of neutrophils around the fat cells) was seen in the top 3-4 mm of the subcutaneous fat.  At 14 days, fat cell size was reduced, inflammation was more intense and occasional macrophages were observed.  At 30 days, fat cell size was further reduced, and multinucleated giant macrophage cells could be seen.  As mentioned above, no histological damage to overlying skin layers was seen.

The purpose of the third study, in six pigs, was to monitor blood lipids at six time points (1 hour, 1 day, 1 week, and 1, 2, and 3 months) following treatment of a very large portion (approximately 15%) of the body area. This treatment varied from prior studies in three ways.  First, the applicator was flat, had a more efficient cooling plate, and was weighted to apply 38mm Hg pressure to the skin (surface temperatures varied from -5C to -8C).  Second, ultrasound gel was applied to the skin beneath the applicator to enhance thermal conduction.   Third, a 1-minute vibrating massage was performed immediately after the cold exposure.   No significant changes in serum lipids associated with this treatment were seen, indicating the safety of the procedure despite the very large dose.  However, in this study, about 30% of the treatment sites suffered skin freezing, resulting in epidermal necrosis, transient hypopigmentation, but no scarring or ulceration.  It is unknown which of the three changes to the treatment above might have caused this freezing.

Together, these three studies showed that in pigs, it is possible to selectively cool fat below its damage threshold without damaging overlying skin.  While it is not surprising that lower applicator temperatures and effective blood flow suppression provide more cooling of fat and more effective fat destruction, it should be noted that these parameters also bring dermal temperatures closer to their damage thresholds.  The authors note that pig fat may be more sensitive to cold than human fat, because pigs have higher concentration of saturated fatty acids which may enable fat damage.

Because the approach appears to be operating close to the margin of skin damage, it may make sense to consider a study of multiple applications using a slightly lower cold dose (less likely to freeze overlying skin and slightly less damage to the fat).  Multiple applications of cold are likely to do additive damage to fat cells, while the overlying skin should be unharmed by each application.  The applications could be separated by just a few minutes, long enough for the treatment area to return to normal temperature, so that multiple applications could be applied in one treatment session.

If a 3mm fat thickness reduction could be routinely obtained, and the applicator was applied uniformly around the circumference of a body area, a circumference reduction of approximately a 2cm would be achieved.  These results would be considered clinically significant.  Of course, clinical techniques (e.g. layering) would need to be developed to provide cosmetically pleasing results.  No one wants a series of indentations in their skin.  Here again, multiple overlapping lower-dose applications may prove useful.

The need for 10-minute exposures may result in relatively long treatment times.  This would be increased if multiple applications of the device were needed in a single session.  The level of pain associated with this technique and the need for pain management techniques is also unknown.  While the prospect of holding a large piece of ice against the skin for 10 minutes may seem painful, simultaneous pressure on the skin is known to have analgesic effects.

While there are still many unknowns, this report provides critical insight into the device-tissue interaction, the rationale for device parameter selection, and the mechanism of tissue response to the procedure.  Aesthetic device users should demand analogous animal studies for every device that claims to have a novel tissue effect.  Subsequent to the performance of the studies in this paper, Zeltiq has carried out further device modifications and has begun two human clinical studies.

http://clinicaltrials.gov/ct2/show/NCT00762437

http://clinicaltrials.gov/ct2/show/NCT00762307


Review of Jørgensen GF, et.al. Long-pulsed dye laser versus intense pulsed light for photodamaged skin

January 30, 2009

http://www.ncbi.nlm.nih.gov/pubmed/18563775

Lasers Surg Med. 2008 Jul;40(5):293-9.

Long-pulsed dye laser versus intense pulsed light for photodamaged skin: a randomized split-face trial with blinded response evaluation.

Jørgensen GF, Hedelund L, Haedersdal M.

Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.

 

 

In this paper, Gitte Jørgensen reports a rarely seen type of study in the aesthetic space – a randomied comparison of two competing device technologies.  The study was co-sponsored by both device manufacturers, but neither manufacturer participated in the conduct or analysis of the study.  Most aesthetic device studies compare a device treatment to an untreated control, to show that the treatment causes some effect.  In contrast, this study compared the Candela VBeam Perfecta (long pulse 595nm dye laser) with the Ellipse Flex (Intense Pulsed Light) for the treatment of photodamaged skin, to see if the treatments caused different outcomes

The study was well-designed to demonstrate the differences with each type of treatment.  First, the patient population was homogenous (light skin females).  Reduction of patient variability reduces confounding of outcomes and enables smaller sample sizes.  Second, each study participant received a series of 3 split-face treatments with the one side randomized to each device type, which properly controls for non-study effects (e.g. additional sun exposure).  The use of the series of 3 treatments would magnify outcome differences, if there were any.  Third, the evaluation was performed on-site by a blinded, independent physician, to prevent bias and to prevent the introduction of photographic artifact.  Although blinding adequately prevents bias, agreement from multiple blinded observers would be useful to reduce individual subjectivity in the assessment of improvement.

While both devices demonstrated improved outcomes in this study, the long pulse 595nm dye laser achieved overall superior results, due to superior performance on vascular lesions.  Fourteen of 20 patients obtained better clearing of telangiectasias with the pulsed dye laser and the remainder saw no difference.  The difference in lightening was both statistically and clinically significant (i.e. the difference in lightening was visually apparent to the blinded reviewer and the patient). Both devices achieved similar improvements for irregular pigmentation and skin texture.  Neither device showed any improvement in wrinkles/rhytids.  Eighteen of 20 patients preferred the pulsed dye laser, both because of improved vascular clearance and because there was less treatment-related pain.

Despite an excellent study design, there are some limitations to the study conclusions.  The superior results of the pulse dye laser should not be considered definitive, as there was no-pre-defined study hypothesis to be proven.  The study was too small to determine whether there was a significant difference in the rates of adverse effects between the two devices.  Because both devices demonstrated improvement in outcomes, practitioners may be able to achieve pulsed-dye-laser results by simply performing additional IPL treatments.  Possibly, other IPL systems may perform better than the Ellipse product used in this study.


Welcome!

January 29, 2009

Welcome to Aesthetic Device Review, an occasional review of notable articles on aesthetic devices from peer-reviewed publications.