Review of Boulos PR et. al. In the eye of the beholder–skin rejuvenation using a light-emitting diode photomodulation device

April 12, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19215260

Dermatol Surg. 2009 Feb;35(2):229-39.

In the eye of the beholder–skin rejuvenation using a light-emitting diode photomodulation device

Boulos PR, Kelley JM, Falcão MF, Tremblay JF, Davis RB, Hatton MP, Rubin PA

Review copyright 2009 https://aestheticdevicereview.wordpress.com

In an unusual article, Boulos and colleagues present compelling evidence that the GentleWaves LED device simply does not work, and that patient satisfaction is simply the result of a placebo effect.

In this study, 36 patients were treated with the GentleWaves device weekly for 8 weeks, as suggested by several other researchers.  Standardized photography was performed pre-treatment, immediately post-treatment, and 1 month post-treatment.  The unblinded investigator also performed clinical assessments at the same time points.

Thirty raters were asked to select the “after” photo from a randomly ordered before/after pair, looking at one of five aspects of the treatment – redness, wrinkles, dark spots, skin roughness, and general appearance.  Unfortunately, the results were not different from chance.

The data were re-evaluated by using a consensus of three raters for each aspect.  Still, the results were no different from chance.

Next, statistical power was increased by using raters’ confidence in their own judgements to weight the data.  In other words, this analysis more highly weighted the decisions that the raters felt sure about, and underweighted the decisions where the raters felt unsure.  Nevertheless, results again were not different from chance.

Finally, the unblinded investigator’s clinical assessments showed that “there was essentially no effect, or if anything, a negative effect.”

Despite the lack of any objective evidence of improvement whatsoever, patients were quite pleased with the results.  The authors conclude that the treatment is a classic placebo, where patients feel better because they believe that the treatment will work, even though it does nothing.  At AestheticDeviceReview, we would like to see more devices subjected to this type of study.


Review of Hantash BM et. al. Two articles on the Primaeva Bipolar Microneedle Radiofrequency Device

March 29, 2009

1: http://www.ncbi.nlm.nih.gov/pubmed/19226570

Lasers Surg Med. 2009 Feb;41(2):87-95.

Pilot clinical study of a novel minimally invasive bipolar microneedle radiofrequency device.

Hantash BM, Renton B, Berkowitz RL, Stridde BC, Newman J.

2: http://www.ncbi.nlm.nih.gov/pubmed/19143021

Lasers Surg Med. 2009 Jan;41(1):1-9.

Bipolar fractional radiofrequency treatment induces neoelastogenesis and neocollagenesis.

Hantash BM, Ubeid AA, Chang H, Kafi R, Renton B.

Review copyright 2009 https://aestheticdevicereview.wordpress.com

In a pair of articles published a month apart, Hantash and colleagues present the first descriptions of the histological and immunohistochemical effects of the bipolar radiofrequency needle device from Primaeva. Several of the authors are affiliated with Primaeva, and the study was funded by Primaeva. AestheticDeviceReview takes a closer look at these two papers.

Three studies were performed on human abdominoplasty or face-lift patients prior to surgery. In the first study of five patients, a broad range of dosages were applied by varying tissue temperature and duration. Histological results from this group were used to select a narrower range of dosages for examination in a 10-patient second study. Finally, in the third study, a single dosage of 72C for 4 seconds was applied to 22 patients, and both histological and immunohistochemical testing was performed.

Briefly, the radiofrequency device consists of an RF generator attached to a handpiece, which includes a single-patient-use array of 10 needles arranged in 5 pairs. The 250-micron needles are spaced 1.25mm apart, and each needle-pair is independently powered by the generator. Each needle is 6mm long, with the top 3mm insulated and the bottom 3mm exposed to allow electrical current flow. The needles are inserted at a shallow 20 degree angle to the epidermis, such that when properly placed, the tip of the needle is 2mm from the epidermis. Insertion is done by spring-loaded injection. When properly inserted, the exposed portion of the needle is positioned nearly parallel to the skin surface, at 1mm to 2mm below the surface. Each needle pair has a temperature sensor, which is used to control the power so that constant temperature can be maintained. An impedence measurement from each needle-pair also provides feedback on the depth of needle insertion. In this study, a separate skin cooling device is held against the skin after the needles are inserted, maintaining 15C to protect the epidermis from conducted heat from the RF needles. In this prototype configuration, this cooling device requires a 2nd operator, and makes the technique somewhat more difficult to apply.

Because current flows between the two needles in each pair, we expect the RF energy to create five damage zones (one between each pair), and if the heat is applied long enough, temperature conduction should expand the damage zone in all directions, resulting in one contiguous zone of damage. The surface cooling device should prevent the conducted heat from damaging the epidermis. This is exactly what the authors show. In the example shown in the paper, by setting the device at 70C for 1 sec, five zones of about 2mm by 1.25mm x 2.5mm were created. At 70C for 4 seconds, one contiguous zone of damage of about 12mm x 1.5mm x 2.75mm was created. Unfortunately, while many patients were studied, the authors did not present quantitative data on the mean and variation of the size of the damage-zones, so we are left to wonder about intra-patient variation and inter-patient variation.

This description makes it clear that the device does not provide a fractional treatment, which would be characterized by 50 or more micro-thermal-zones of damage per square centimeter. Instead this device creates one to five milli-thermal-zones of damage per square centimeter, so the term “fractional” should not be used. AestheticDeviceReview believes that the relatively large volume of RF-needle-created tissue coagulation may even turn out to offer a clinical benefit compared to fractional treatments, so the fractional label may be unwise as well as unwarranted.

Interestingly, while large amounts of tissue were coagulated, the authors show that important dermal structures such as blood vessels, hair follicles, sebaceous glands, and sweat glands were undamaged by the treatment. Men getting wrinkles treated will not have to worry about bald patches in their beards. Similarly, needles placed into the subcutaneous fat did not cause fat damage, as electrical energy appeared to flow through the interstitial collagen (fibrous septae?). AestheticDeviceReview sees some potential for this technology as a treatment for cellulite.

In the immunohistochemical study, the authors nicely show that the tissue damage is not necrosis, but a zone of thermal coagulation that proceeds through a wound healing response over several weeks, consisting of sequential phases of inflammation, proliferation and ultimately remodelling. Again this should come as no surprise, as this response is similar to that seen with several other radiofrequency devices that have been developed for shrinking collagen-rich soft tissue. For example, temperature-controlled RF needle technology is used to shrink soft palate tissue as a treatment for snoring. See company white paper at: http://www.somnus.com/abstracts/absomnus2.htm

Unlike non-ablative fractional laser treatments, all patients experienced swelling and focal edema which resolved in 48 hours following treatment. Despite the use of skin cooling, erythema appeared on the surface above each thermal damage zone, and this resolved within 8 hours of treatment. Several patients experienced purpura as well, which resolved in less than 7 days. So, overall “downtime” is greater than non-ablative fractional and less than ablative fractional laser treatments.

Is the downtime worth the result? Here, the authors leave us hanging. No data is presented on tissue shrinkage. Why didn’t the authors place tattoos prior to treatment, and measure the effect of treatment on tattoo distance? No data is presented on any change in dermal thickness. Why were so many patients studied, if quantitative histological analysis was not going to be performed? We at AestheticDeviceReview can only wait – perhaps we will see another study next month.


Review of Hruza et. al. Skin Rejuvenation and Wrinkle Reduction Using a Fractional Radiofrequency System

March 22, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19271373

J Drugs Dermatol. 2009 Mar;8(3):259-65.

Skin Rejuvenation and Wrinkle Reduction Using a Fractional Radiofrequency System

Hruza G, Taub AF, Collier SL, Mulholland SR.

Review copyright 2009 aestheticdevicereview.wordpress.com

In this paper, Hruza et. al. present the first report on Syneron’s MatrixRF technology, including both clinical and histological results.  While the inclusion of histological findings is welcome and helpful, both the clinical and histology studies have significant methodological flaws which diminish the value of the report.

The MatrixRF is available with two different “tips”, one with 64 “pins” in an 8×8 arrangement and one with 144 pins (12×12).  The description of each array is unclear, it appears that each pin is an electrode with a width of 200 microns.  The inter-pin spacing on the 64-pin tip is 1.5mm while the denser 144-pin tip has an inter-pin spacing of 1mm, and RF energy is apparently conducted though tissue between adjacent pins. The 64-pin tip is described as providing 5% coverage, and the 144-pin tip is described as 10%.  Delivered energy may be varied by the user.

The histology study should tell us about immediate tissue effects as a function of tip and energy, as well as the uniformity of tissue effect across each tip array and the variations across patients.  In this report, the authors show that the electrodes ablate and coagulate tissue, and that greater energy-per-pin (either fewer pins for a given energy, or more energy) generally results in a deeper ablation. Histological images show that the maximum ablation depth for the highest energy-per pin reaches just into the dermis, and that more typical settings limit the effect to the epidermal layer.  Unfortunately, the uniformity across the array and the variation across patients is not adequately addressed.  The authors tell us that 7 patients were studied with “different combinations of electrode-pins aray densities and energies,” at 7 time points (ranging from immediate to 30 days).  The authors do not tell us which energies were applied to each patient, and in what arrangement.  Worse yet, data on all patients and all time points is never presented.  Instead, the authors provide a table of which presents the “average of maximal depth” of tissue effect, for broad and overlapping ranges of energy delivered.  For example, for the range of 6 to 16 J of energy delivered, with the 64-pin tip, the depth of tissue effect is listed as 250 microns.  We do not know whether this represents one pin in one subject, multiple pins in one subject, or multiple pins in multiple subjects.  Further, this energy range varies by almost a factor of 3. Are we to expect the same results at 6 J as at 16J?  Will every subject have the same response?  The authors also claim, in the paper’s discussion, that depth of tissue effect depends on inter-pin spacing, which is different between the two tips.  However, for a given energy, the 64-pin array has both a wider spacing and a higher energy-per-pin than the 144-pin array.  There is no analysis which tells us whether the increased damage with the 64-pin array is due to the wider spacing or the higher energy-per-pin.

Post-treatment, the histology study should tell us how the body responds to the injury.  Here the authors present a brief, three sentence, qualitative description of tissue healing from the ablative and thermal injury, stating that the epidermis begins to re-epithelialize immediately and that full healing occurs within 2 days.  Given that readers are already very familiar with this type of tissue effect, and the body’s response, perhaps a fuller description of results is unnecessary.

In the 35 patient clinical study, each patient received a series of 3 facial treatments separated by 3 to 4 week intervals, and returned for a one-month follow-up evaluation.  No rationale for the interval was provided, as the histological study showed full recovery at 2 days.  Treatment settings (tip type and energy level) were left to the discretion of the treating physician, and were not reported.  Subjects were evaluated via clinical assessment, photographic assessment, and the usual self-reported-patient-satisfaction survey.

Importantly, the study lacked adequate control.  No untreated facial areas were used to control for any non-treatment-related, concurrent changes to the skin, such as changes in patient hydration or sun exposure.  Consequently, it cannot be determined whether clinical changes were due to the treatment or to other factors.  Further, outcomes were evaluated by comparing the post-treatment clinical evaluation to the pre-treatment photographic record.  In addition to being unblinded, these readings are highly influenced by the quality of the photography.  Thus they cannot be considered reliable.  Self-reported patient surveys are also known to be unreliable, and while these results appeared to be similar to the clinician evaluations, no correlations were reported.  The analysis of this experiment included an interesting result: about half of the patients saw a 40% or greater improvement in clinician-evaluated brightness, tightness, and wrinkling.  If at least a 40% improvement is needed, for a patient to be considered a success, then even using these uncontrolled, unblinded results, about half the patients were not successful.

This type study design is unfortunately all-too-common in the aesthetic device literature.  How could it have been improved?  First, a randomized split-face design should have been used.  As it was unknown prior to the study whether the treatment would have results that differed from doing nothing, an untreated control was appropriate.  (A post-study cross-over could have been offered if patients desired.)  Second, at each study visit, three blinded clinicians should have evaluated the left versus right side of the face, using a standardized procedure.  Intra-observer agreement could be analyzed to determine whether these evaluations were reliable, and in cases where the clinicians did not agree, the data would be discarded.  Third, in the analysis, the difference between the treated and untreated sides would be evaluated for each of the pre-treatment visit, treatment visits, and follow-up visits.  The analysis would measure how this difference changed over time.  This is the proper analysis of an internal control.  Fourth, a minimum improvement in the difference between treated and control sides would be pre-specified as a rule to consider a patient successful.  The study should be sized to show that an appropriate percentage (e.g. 75%) of patients could achieve success.

While the study design and analysis left much to be desired, sufficient data was presented to indicate that the MatrixRF probably provides a fractional version of a light peel.  However, a disclaimer may need to be given to each patient: “actual results may vary.”

~ AestheticDeviceReview


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.