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

March 22, 2009

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

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



January 29, 2009

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