Skin aging is a process that can present itself relatively early on in life, sometimes even as soon as 20-30 years of age. Common signs and symptoms associated with skin aging include skin wrinkling, skin dyspigmentation, telangiectasia, and reduced tissue elasticity. At the histological and molecular level, common noticeable features include a reduction in collagen content, fragmentation of collagen fibers, elastotic degeneration of elastic fibers, the appearance of dilated and tortuous dermal vessels, disorientation and atrophy of the epidermis, and up-regulation of matrix metalloproteinases (MMPs), especially MMP-1 and MMP-2 (Kligman, 1989; Takema et al., 1994).
Skin aging can be influenced by both time (normal aging), as well as environmental factors, but the single most influential factor responsible for accelerated skin aging is believed to be ultraviolet (UV) radiation-induced photodamage (Takema et al., 1994).
A wide range of therapeutic modalities has been developed to address the aesthetically undesirable effects associated with skin aging. Most therapeutic modalities depend on some form of controlled epidermal removal and skin wounding to promote collagen biosynthesis, and dermal matrix remodeling; serving as a preliminary means to address the problems associated with skin aging.
These limitations have facilitated the development of technologies such as non-ablative laser resurfacing, which can transcend the restrictions of conventional modalities, and provide safe and efficacious treatment (Hardaway and Ross, 2002; Sachdev et al., 2011; Weiss et al., 2003).
Unlike ablative laser resurfacing, non-ablative laser resurfacing technologies provide aesthetic improvement of aged skin without inducing epidermal destruction; requiring little to no downtime, thus, providing a suitable alternative to traditional therapeutic modalities (Hardaway and Ross, 2002; Weiss et al., 2003).
Low-level light therapy (LLLT) is a novel treatment option available for non-thermal and non-ablative skin rejuvenation, which has been shown to be effective for improving skin conditions such as wrinkles and skin laxity (Barolet et al., 2009; Bhat et al., 2005; Dierickx and Anderson, 2005; Russell et al., 2005; Weiss et al., 2004, 2005). A wide range of different light sources have been used to deliver light for these treatments, particularly to the face, and some are shown in Figure 1. LLLT provides increased rates of wound healing, while also reducing post-operative pain, edema and several types of inflammation, making it a highly desirable modality (Calderhead et al., 2008; Kim and Calderhead, 2011).
Early studies have reported increases in the production of pro-collagen, collagen, basic fibroblast growth factor (bFGF), and proliferation of fibroblasts, following low-energy laser irradiation in different settings (Abergel et al., 1987; Yu et al., 1994). The use of LLLT sources of wavelengths of 633 nm/830 nm is most common in cases of clinical applications involving wound healing and skin rejuvenation. LLLT is now also used for the treatment of chronic, non-healing wounds via the restoration of imbalances in collagenesis/collagenase, which allows for rapid and enhanced wound healing in general (Kim and Calderhead, 2011).
A study conducted by Lee et al. (2007a) investigated the histological and ultrastructural alterations that followed a series of light treatments, utilizing light emitting diodes (LEDs) with parameters of: 830 nm, 55 mW/cm2, 66 J/ cm2 and 633 nm, 105 mW/ cm2, 126 J/ cm2. Alterations in the levels of MMPs and tissue inhibitors of metalloproteinases (TIMPs) were reported. Increased mRNA levels of interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), intercellular adhesion molecule 1 (ICAM-1), and connexin 43 (Cx43) were also reported following LED phototherapy whereas, IL-6 levels were reported to be decreased.
Additionally, a well-marked increase in the amount of collagen was reported in the post-treatment specimens. In fractional-laser resurfacing, the deliberate development of microscopic, photothermally-induced wounds is believed to be responsible for the recruitment of pro-inflammatory cytokines IL-1ß and TNF-α to the site of injury, which contributes to tissue repair. The generation of such a wound healing cascade, thus, contributes to new collagen synthesis.
A clinical study by Weiss et al. demonstrated the benefits of LLLT over traditional thermal-based rejuvenation modalities. A group of 300 patients was administered LLLT (590 nm, 0.10 J/cm2) alone, and another group of 600 patients received LLLT in association with a thermal-based photorejuvenation procedure. Of the patients who received solely light treatment, 90% reported an observable softening of skin textures, as well as a reduction in skin coarseness, and fine lines (Weiss et al., 2005b).
It was observed that, patients who received some form of LLLT (n = 152) reported a noticeable reduction in post-treatment erythema, and an overall impression of increased efficacy, when compared to the patients that received treatment via a thermal photorejuvenation laser or light source lacking any form of LLLT photomodulation (Kucuk et al., 2010; Weiss et al., 2005b).
The reduction in post-treatment erythema can most likely be attributed to the anti-inflammatory effects of LLLT (Barolet et al., 2009). Using various pulse sequence parameters, a multicenter clinical trial was conducted, wherein 90 patients received 8 LLLT treatments over 4 weeks (Geronemus et al., 2003; McDaniel et al., 2003; Weiss et al., 2004, 2005a). The study displayed good overall results, with more than 90% of patients improving by at least one Fitzpatrick photoaging category, and 65% of the patients displaying global improvements in facial texture, fine lines, background erythema and pigmentation with results peaking at 4 to 6 months, following the 8 treatments.
A noticeable increase in papillary dermal collagen and a reduction in MMP-1 were generally observed. A study conducted by Barolet et al. also supported the aforementioned results. The study used a 3-D model of tissue-engineered Human Reconstructed Skin (HRS) to investigate the potential of LLLT (660 nm, 50 mW/cm2, 4 J/cm2) for collagen and MMP-1 modulation.
The results showed an up-regulation of collagen and down-regulation of MMP-1 in vitro. A split-face, single-blinded clinical study was then carried out to assess the results of this treatment on skin texture, and the appearance of individuals with aged/photoaged skin.
Profilometric quantification demonstrated that, more than 90% of individuals had a reduction in rhytid depth and surface roughness, and 87% of individuals reported a reduction in the Fitzpatrick wrinkling severity score, following 12 LLLT treatments (Barolet et al., 2009).