PDL treatment of photoaged skin stemmed from the clinical and histologic collagen changes observed in PDL-treated hypertrophic scars, striae distensae, and acne scars [45-52]. The 585 nm pulsed dye laser (N-lite) at 350 ps and subpurpuric fluences was the first to be studied for photorejuvenation [53]. An early study reported that a single PDL treatment (585 nm, 4504 s) demonstrated a clinical improvement in 75-90% of mild to moderate wrinkles, and 40% in moderate to severe rhytides [54]. Histologic examination showed increased amounts of normal staining in elastin and collagen fibers in the superficial dermis, with increased cellularity and mucin deposition. The LP PDL at 595 nm was then studied for the treatment of photoaging, with an 18% reported improvement in clinical grading [55]. These findings were attributed to the LP PDL’s ability to target facial telangiectasia associated with photodamage [56]. The LP PDL achieved FDA approval for treating photodamage; however, only modest results have been observed, presumably due to predominantly vascular targeting and superficial penetration to the papillary dermis. The application of ALA prior to LP PDL or PDL irradiation thus augments the dermal changes by targeting epidermal photoaging as well. The mechanism of this effect appears to be the activation by the LP PDL at 595 nm of the photosensitizer PplX which preferentially accumulates in photodamaged cells, resulting in their destruction either by apoptosis or an immune-mediated response [1,2].
Clinical studies have shown that the application of the precursor photosensitizer topical ALA prior to illumination with LP PDL has enhanced the ability of this laser to treat photodamage [23]. Photodynamic therapy mediated by LP PDL is effective in the removal of actinic keratoses, actinic cheilitis, lentigines, fine rhytides, and textural changes due to photodamage [23,57]. In a study of 41 patients with AK, the safety and efficacy of LP PDL (595 nm) was assessed following 3 hours versus 14-18 hours incubation with topical 20% 5-ALA for the treatment of AK [23]. The patient mean percent head AK lesions cleared was approximately 90% at an eight-month follow-up, which was comparable to other treatment modalities such as topical fluorouracil or PDT with blue light [23]. This approach achieved rapid full-face treatment times with minimal discomfort; and minimal posttreatment erythema, which resolved within five days and was the first clinical study to demonstrate that short incubation (3 h) ALA was as effective as long (14-18 h) [23]. It was also significant that no crusting, purpura or dyspigmentation was observed; and erythema was minimal, making it appealing as a cosmetic procedure. PDT employing ALA and LP PDL for full-face treatments of diffuse AK demonstrated improvements in photoaging. Since then, treatment of photoaging with topical ALA and LP PDL has been reported with improvements in texture, fine rhytides, and lentigines [58].