Report of a Novel Fractional Ablative Laser for Tissue Tightening

Skin laxity has been difficult to address through non-invasive modalities. We postulated that use of an ablative fractional resurfacing laser could result in well-controlled tightening through ablation and micro-excavation, while reducing the down-time associated with traditional ablative modalities. We report the first study demonstrating the use of a 10,600nm fractional laser intended for ablative resurfacing and tissue tightening.

Figure 1. Comparative schematic depicting traditional resurfacing, non-ablative fractional resurfacing (NFR™ treatment) and ablative fractional resurfacing (AFR™ treatment), left to right.

Twenty-four healthy subjects between 27 and 72 years of age with Fitzpatrick skin types I-IV were enrolled in an FDA and IRB-approved study (Western Institutional Review Board, Olympia, WA). The primary aim of this investigation was the characterization of the clinical and histological effects of AFR™ treatment for tissue tightening. Each subject was assigned to one of four study sub-groups, in order to support the dose-response analysis of clinical response following treatment across a range of laser parameters.

Four 1.5 x 1.0 cm² test treatment sites, spaced at least 2 mm apart, were identified on the inner forearm of each subject, linearly positioned to be parallel with respect to the radius/ulna. In addition, one comparable test site was designated as the control site for each subject. Topical anesthetic was applied and occluded for 60 minutes prior to treatment. No adjunctive pain management was required.

Treatments were performed within the four designated test sites at laser settings ranging from 5 - 40mJ/MTZ and 100 – 400 MTZ/cm². Laser settings were selected for each test site according to sub-group assignments. Immediately following treatment within each test site, pain was assessed according to a 10-mm visual analog scale.

The safety and efficacy of AFR treatment for tissue tightening was evaluated by subject, study investigator and independent investigator immediately, 48 hours, 1 week, 1 month, and 3 months post-treatment. Clinical appearance and severity of post-treatment responses, including erythema, edema, the presence of petechiae, hypo/hyper-pigmentation and any additional side effects, were evaluated using a 0-3 severity scale at each study follow-up visit. Ex-vivo analysis of human skin was performed in parallel to characterize the extent of tissue shrinkage.

Treatments were well-tolerated over the range of laser settings tested, with no scarring or other adverse events noted. The dose response test protocol resulted in a total of ninety-one test treatment sites, with each subject receiving up to four test treatments. Table 1 lists the number of treatment sites administered for each energy setting tested.

Table 1. Number of test treatment sites for each treatment energy setting (mJ/MTZ)

Treatment Energy (mJ/MTZ)	5 mJ	10 mJ	20 mJ	25 mJ	30 mJ	40 mJ*	All Energies
Number of Treatment Sites	24	27	24	3	17	6	91

*All exposures were performed at a treatment density of 400 MTZ/cm², with the exception of three 40 mJ treatment sites with a density of 100 MTZ/cm².

Subjects developed mild to moderate erythema and edema within all ninety-one test treatment sites immediately after exposures. For moderate energy treatment sites (≤20 mJ), mild to moderate erythema and edema was also observed 48 hours and 1 week post-treatment. This response resolved for the majority of subjects by one month post-treatment. Higher energy treatment sites exhibited complete resolution of all post-treatment responses by 3 months post-treatment.

Additional post-treatment responses, such as edema and petechial bleeding, resolved without adverse sequelae. Post-treatment edema was completely resolved among 87% of subjects within 1 week post-treatment with the remaining subjects presenting with only minor edema at that visit. Very slight petechial bleeding was noted in approximately 20% of subjects immediately post-treatment and 48 hours post-treatment. No post-inflammatory hyper-pigmentation or hypo-pigmentation was observed.

Hematoxylin and Eosin staining was performed on biopsies taken at various intervals post-treatment, ranging from immediately post-treatment to 3 months post-treatment. Lesion dimensions ranged from 125-300 µm in width and 300-1200 µm in depth, for pulse energies of 5 mJ to 40 mJ, respectively. For all treatment energies, histological analyses confirmed the presence of zones of thermal coagulation surrounding ablated voids. The thin eschar layer lining each ablated zone served to indicate a hemostatic response. Ex-vivo histological analyses revealed reproducible shrinkage of human tissue, consistent with the significant volume of tissue ablation demonstrated in vivo.

Figure 2. In-vivo histology showing the wound healing process following 20 mJ AFR™ treatment, with biopsies taken (A) Immediately, (B) 48-hours, (C) 1-wk, (D) 1 month, and (E) 3 months post-treatment . The images show the invagination of the epidermis into the ablated zone at 48 hours (B), and complete re-epithelialization by 1 week (C). By 1 month post treatment, the invagination has regressed, while a sustained coagulation zone is still visible (D). At 3 months, new collagen has replaced the lesion in the dermis (E).

Figure 3. 30, 20 and 10 mJ/MTZ test treatment sites (right to left) one month (left) and 3 months (right) following AFR™ treatment

Figure 4. 10, 20, 30 mJ/MTZ test treatment sites (right to left) one month (left) and 3 months (right) following AFR™ treatment

*As indicated above, the second test treatment sites included biopsy.

This investigation demonstrated the ability of a novel ablative fractional resurfacing laser device to safely remove epidermal and dermal tissue. Tissue ablation penetrated up to 1200 µm in depth with 40 mJ pulse energy settings. In addition, in contrast to traditional ablative resurfacing, treatments were well tolerated with no adverse effects observed.

Given that AFR™ treatment was well-tolerated, even for resurfacing of non-facial treatment areas, it may offer significant safety advantages as compared to traditional ablative resurfacing devices. The treatment modality shows promise for dermatological applications requiring removal of dermal material, such skin resurfacing and treatment of skin laxity. Further studies are needed to elucidate optimal treatment parameters and to characterize the utility of this technology.

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