Biological Effects of Fractional Photothermolysis

Interesting histological changes ensue after mid-infrared fractional photothermolysis. Columns of epidermal and dermal cell necrosis are seen immediately after treatment, with
preservation of the stratum corneum (Fig. 11.2) . Each of the microscopic columns of thermal injury is surrounded by a heat-shock zone that releases cell mediators to signal the wound-healing cascade [13]. Specifically, heat-shock protein (hsp) 70 expression is increased, most prominently within the epidermis in areas that underlie necrotic debris, and in dermal tissues that surround the MTZs [2]. Hsp 70 causes up-regulation of transforming growth factor (TGF)-beta which increases collagen production, thereby stimulating dermal remodeling [2,9 , 10]. Evidence of increased dermal collagen III production is seen after one week [2].

Within an hour of treatment, keratinocytes begin to move to the deep and lateral margins of the epidermal wound [11,13]. By 12 hours, viable cells surround the necrotic debris and begin to form a plug containing this microscopic epidermal necrotic debris (also known as MENDs) [13]. This compact material ranges from 50 to 200 pm in diameter [9,10], and has been found to contain both melanin and elastin [10].

By 24 hours, MENDs are found within the epidermis above each area of the dermal injury with intact stratum corneum [2,13]. Stem cells located in the basal layer appear to be tem­porarily activated and begin to replace the epidermal tissues [10,21]. At this time, the

continuity of the epidermal basal cell layer is also restored. By 48-72 hours posttreat­ment, the epidermis has re-epithelialized, with partial restoration of the basement mem­brane [2].

By seven days there is a complete epidermal regeneration, and exfoliation of coagulated MENDs also starts to occur. This corresponds to a bronze color that patients develop, which disappears with subsequent desquamation.

Three months after treatment, thermal damage columns are completely resolved and replaced with new collagen. Increased undulating rete ridge patterns are also observed [2,9].

Recently, ablative fractional resurfacing has been introduced to overcome extensive epi­dermal and dermal thermal damage associated with traditional ablative devices. Similar to mid-infrared fractional photothermolysis, microscopic zones are created, but instead are composed of ablated, coagulated tissue (Fig. 11.3). This results in changes that are slightly different histologically. Initial studies examined far-infrared (10600 nm) ablative fractional treatment of forearms in subjects with pulse energies ranging from 5-40 mJ with a single

pass. Spot densities of 400 MTZ/cm2, which created an interlesional distance of approxi­mately 500 pm, were used for pulse energies of 5-30 mJ. Densities of 100 MTZ/cm2 were used for 40 mJ [22].

Histological examination showed an immediate ablation of the epidermis and dermis after treatment. Ablative zones, lined by a thin layer of eschar, ranged from 71 to 121 pm in width, and 210 to 659 pm in depth for pulse energies of 5-30 mJ. The total lesion size (including the surrounding thin, coagulation zone) ranged from 138 to 270 pm in width, and 298 to 993 pm in depth. These lesions ended in a tapered manner, unlike traditional CO2 which result in broad, rectangular-shaped thermal coagulation zones parallel to the skin surface. Tapered lesions are beneficial because they allow for deeper dermal ablation while maintaining interlesional tissue viability [22].

Greater increases in depth than width were generally seen with increasing energies. Therefore, the depth-to-width ratio increased with increasing pulse energies [22], unlike nonablative fractional resurfacing which maintains a relatively constant depth-to-width ratio of 5 [20]. This may allow for deeper removal of unwanted dermal material through the transepidermal elimination pathway [11].

By 48 hours, the ablative zone was completely replaced by invaginating epidermal cells. The basement membrane remained partially disrupted, but was completely restored by day 7. Upregulation of hsp 72 was also seen. Microscopic epidermal necrotic debris were also found in the stratum corneum, and were exfoliated by 7 days posttreatment. Increased numbers of spindle cells that were likely to be consistent with fibroblast activity and ongo­ing dermal remodeling, were also noted this time [22].

By one month, the epidermal invagination had considerably regressed, and this space was replaced by newly synthesized collagen. The coagulation zone surrounding the abla­tive zone was also diminished, but was still present. Collagen in both of these zones appeared haphazard with abundant spindle cells still present [22].

Three months posttreatment, scattered areas in the dermis mildly resembled residual lesions. Hsp 72 activity decreased significantly while hsp 47 expression increased, consis­tent with ongoing collagen synthesis and dermal remodeling [22].

Most of the histological studies reported to date have been completed with Fraxel lasers (Reliant Technologies, Inc.). Further studies examining the biological effects with all com­mercial devices available are warranted.