Introduction

With the advancement of laser and non-laser light sources, the focus of skin rejuvenation is optimizing efficacy while minimizing recovery times. The gold standard for rejuvenation, at least for fine wrinkles, has been ablative modalities. Although ablative tools can achieve predictable cosmetic enhancement, the risks of scarring, infection, dyspigmentation, and prolonged recovery time make these modalities less attractive. Patients increasingly try to balance efficacy of skin rejuvenation within the context of downtime. Non-ablative skin rejuvenation normally mitigates the need for advanced anesthesia and can often be performed with only topical anesthesia. Thus, non-ablative modalities have enjoyed a greater role in skin rejuvenation.

A clear definition of non-ablative skin rejuvenation is important as the term is sometimes used haphazardly. In its most pure form, non-ablative rejuvenation improves skin quality without physical removal or vaporization of the skin. Ablative modalities, via vaporization, remove a portion, or all, of the epidermis and sometimes may remove parts of the dermis. This chapter focuses exclusively on non-fractional methods of non-ablative skin rejuvenation.

The dermis (and / or deeper epidermis) can be selectively damaged by two basic approaches:

Treatment of photodamage can be divided into various categories, and treatment protocols are based on a logical approach founded on the laser–tissue interactions delineated above. The goal should be to maximize skin rejuvenation, from reducing telangiectasias and lentigines to enhancing dermal remodeling.

The laser and non-laser systems used for non-ablative rejuvenation are a heterogeneous group of devices that emit wavelengths in the visible (400–760 nm), near-infrared (760–1400 nm), or mid-infrared (1.4–3 µm) ranges, radiofrequency (RF) devices, intense pulsed light (IPL) devices, as well as light-emitting diode (LED) devices (Box 5.1). Each of these modalities can induce dermal remodeling, as well as target other components, without epidermal ablation. Most investigators believe that photothermal heating of the dermis: (1) increases collagen production by fibroblasts and (2) induces dermal matrix remodeling by altering glycosaminoglycans as well as other components of the dermal matrix. Others believe that the laser / light interaction with molecular cellular components alters the cellular function of enzymes as well as cellular structural components. Altering the different components of cells, from enzymes to cellular wall constituents to nucleic acids, may then alter the environment and productivity of a given cell.

Photodynamic therapy (PDT) with aminolevulinic acid (ALA) has been show to augment the effects of laser or other light sources. Multiple laser and light sources have been used for photoactivation of protoporphyrin IX, leading to improved skin rejuvenation (Fig. 5.1).

Figure 5.1 Protoporphyrin IX absorption: due to the multiple absorption peaks of protoporphyrin IX, multiple lasers and light sources can be used to augment the effects following application of porphyrin precursors to the skin.

Non-ablative skin rejuvenation is commonly used to reverse photoaging in the dermis. This damage is directly correlated with the patient’s age and extent of ultraviolet exposure. Ultraviolet B (UVB) light alters nucleic acids as it interacts with epidermal keratinocytes, inducing cellular atypia. Over time, longer-wavelength ultraviolet A (UVA) light causes increases in oxygen radical formation, inducing alterations in the normal homeostasis of vessel formation, apoptosis, pigment generation by melanocytes, immune cell dysregulation, cytokine dysregulation, alteration of dermal matrix composition, and disruption in the transcription, translation, and replication of the cellular genetic code. Histological changes that accompany the clinical findings of photoaging include an atrophic epidermis, loss of the rete pattern, elastic fiber clumping in the papillary dermis, haphazard and reduced collagen production, and increased vasculature. These UV-induced changes correlate with the clinical appearance of photoaged skin, including skin laxity, atrophy and fragility, increased rhytid formation, telangiectasia, and alteration in the overall color, texture, and consistency of the skin. Thus the goal of rejuvenation is to replace damaged epidermal or dermal constituents with more robust, newly created ones. Physicians attempt to alter the quality of the keratinocytes and the pigment production of melanocytes, two key components of epidermal photodamage. Dermal photodamage rejuvenation typically has concentrated on improving the quality and inhibiting the degeneration of fibroblasts. Studies have shown an increase in antioxidant capacity and collagen synthesis after millisecond and nanosecond 532 nm and 1064 nm laser irradiation in fibroblast cell cultures.

Richard Glogau, MD developed a classification scale to chart the progression of clinical photoaging (Table 5.1). One can follow a patient from an early age, with relatively strong homogeneity of skin coloration and minimal wrinkles, to a more aged patient, with wrinkles at rest and a more heterogeneous skin coloration.

As one would expect, treating a Glogau grade I patient with current non-ablative modalities will achieve a higher percentage of photoaging correction versus more severely photodamaged patients. While ablative skin rejuvenation may achieve superior restoration of normal skin structures, especially for the Glogau grade III or IV patient (see Table 5.1), the downtime and potential risks are prohibitive for many patients. Nevertheless, as non-ablative technologies evolve, restoration of young, healthy skin with diminished risks and negligible recovery times is increasingly possible. The remainder of the chapter will focus on patient selection for non-ablative skin rejuvenation and discussion of the different devices.

Patient selection

Patient selection for non-ablative skin rejuvenation begins with an assessment of the degree and type of photoaging (see Table 5.1). The ideal patient is Glogau grade II or III with mild to moderate photodamage. Non-ablative therapies initiate new collagen formation (collagen I and collagen III) and might be appropriate in a Glogau grade I patient to prevent photodamage progression. Alternatively, a patient and / or a physician expecting dramatic change following a non-ablative rejuvenation procedure in a Glogau grade IV patient may be disappointed.

Sadick divides patients in a different manner, where cosmetic deficiencies are based on the histological location of solar damage. His selection process takes into account epidermal (type I) damage (Fig. 5.2) and dermal / subcutaneous (type II) damage (Fig. 5.3), and subsequently treatment is tailored to laser selectivity of the damage.

Figure 5.2 (A–C):Type I photoaging indications.

Republished with permission. Sadick NS 2003 Update on non-ablative light therapy for rejuvenation: a review. Lasers in Surgery and Medicine 32:120-128.

Figure 5.3 Type II Photoaging indications.

Republished with permission. Sadick NS 2003 Update on non-ablative light therapy for rejuvenation: a review. Lasers in Surgery and Medicine 32:120-128.

Another important factor in patient selection is the patient’s Fitzpatrick skin type. Fitzpatrick IV, V, and VI skin types may not be optimal candidates for particular non-ablative rejuvenation modalities that selectively heat melanin. The most common adverse result for non-ablative rejuvenation in darker skin patients is hyperpigmentation, a condition that usually resolves after 4–8 weeks (but can persist longer in some circumstances) with appropriate application of suppressors of melanin synthesis. Mid-infrared lasers, which minimize direct melanin targeting, can be used in patients with darker skin types. However, higher fluences in these patients may result in thermal damage and bulk heating, which can also result in dyspigmentation. Non-cryogen cooling devices can minimize bulk heating, whereas cooling devices that employ cryogen spray may induce pigmentary alterations similar to liquid nitrogen. See Chapter 10 for a detailed discussion of laser and non-laser light sources for the treatment of darker skin types.

Beyond skin type and amount of photodamage, there are some patients who might be excluded from non-ablative lasers and light sources based on medical criteria (Box 5.2). Oral retinoid use, recent rejuvenation procedures, infection, and active dermatitides are reasons to consider deferring a non-ablative rejuvenation procedure. Most likely oral retinoids will not affect the outcome, but no controlled study has investigated their effect on non-ablative skin resurfacing. Many texts advocate waiting a period of 6–12 months, most likely representing an extrapolation from ablative resurfacing wait times. Some cutaneous laser experts have used non-ablative devices 1 month following retinoid use without adverse outcomes.

Physicians must also consider the wavelength of the device. For example, devices that utilize visible light (i.e. LED devices, etc.) may exacerbate a phototoxicity / photosensitivity or a systemic condition that is photosensitive, like cutaneous lupus (although in a recent study only 7% of SLE patients reacted to visible light) (Fig. 5.4). On the other hand, some lasers may confer a protective quality. There is increasing evidence that IPL can activate fibroblasts as well as confer protection from future UV-induced skin damage.

Figure 5.4 Photosensitivity reaction following photodynamic therapy. The patient is shown 6 days after photodynamic therapy. Reaction resolved after 3 weeks.

Fillers and neurotoxins most likely are not affected by non-ablative modalities and can be administered in the same session. However, the non-ablative resurfacing should be performed last. This order will minimize the risk of neurotoxin diffusion, which should cease by 1 hour after the injection, and will reduce the possibility of edema obscuring endpoints in optimal filler placement.

Visible light and near-infrared / vascular lasers (Table 5.2)

Visible light lasers and near-infrared lasers are commonly used to treat vascular and pigmented lesions. Treatment of vascular lesions with visible light lasers can achieve histological correction of dyspigmentation, overall skin texture, dermal matrix abnormalities, and solar elastosis. Clinical improvement of solar lentigines, scars, including keloids and hypertrophic scars, and photoaging have all been observed. Orringer et al have reported increases in type I procollagen messenger RNA and subsequent dermal matrix remodeling following one treatment with a pulsed dye laser. Whether this is secondary to thermal alterations of cellular milieu or to vascular-injury-induced cytokines, the result is dermal remodeling, reversal of photoaging, and partial rhytid correction.

The first laser designed to exploit the principle of selective photothermolysis was the flashlamp-pumped pulsed dye laser (PDL). The laser was optimized to treat port-wine stains. As the understanding of treatment of vascular lesions has progressed, so has the configuration of the PDL, in both composition of the dye (rhodamine) and wavelength. In its approximate 30-year existence, the PDL has moved beyond its original 577 nm wavelength, which corresponds to a hemoglobin absorption peak, and its original 0.45 millisecond pulse duration. Now, commercially available PDLs emit wavelengths between 585 nm and 595 nm, which penetrate deeper into the dermis and into deeper vessels. Newer PDLs have greater pulse duration ranges, most generating pulse trains of up to 40 milliseconds, which avoid intravascular thrombosis in very small vessels and subsequent purpura. Other than direct vascular heating and a resulting increase in dermal temperature, vessel targeting can also create an inflammatory cascade that results in new collagen formation. Bjerring showed a 148% increase in type II collagen 2 weeks after low-fluence PDL treatment and only a 32% increase with IPL; however, the authors conceded that the IPL settings (4–7 J/cm²) were lower than those used in conventional application for red- brown dyschromias.

Other wavelengths that target hemoglobin in blood vessels have been shown to rejuvenate skin. The long-pulsed 755 nm alexandrite laser (Case study 1), the 810 nm diode, and the 1064 Nd : YAG lasers are used for deeper and larger-caliber vessels. The subsequent ‘coincidental’ dermal remodeling correlates to the depth of penetration of each respective laser. Weng et al have demonstrated that collagen synthesis by fibroblasts and antioxidant enzymes were significantly increased following irradiation with the 532 nm, 1064 nm Q-switched Nd : YAG, and 1064 nm long-pulse Nd : YAG lasers. The 1064 nm Nd : YAG laser induces deeper remodeling than the 532 nm laser due to its lower degree of dermal scattering and chromophore absorption at 1064 nm. Thus, some physicians use multiple lasers, such as the 532 nm laser to treat dyschromia and telangiectasia, and following it with a pass with the 1064 nm laser to obtain some deeper remodeling in the same treatment session.

Case Study 1

A Caucasian female in her early 60s presents for total facial rejuvenation with request to focus on lentigenes, telangiectasias, and overall facial rejuvenation (Fig. 5.5A). The long-pulsed alexandrite 755 nm laser was used at a fluence of 36 J/cm² using an 8 mm spot size and a 3 ms pulse duration to treat the patient’s forehead, cheeks, nose, and chin. At 6 weeks following her treatment, significant improvement in hyperpigmented macules, telangiectasias, and an overall more youthful appearance is appreciated (Fig. 5.5B).

Figure 5.5 Patient treated with long-pulsed alexandrite laser for photorejuvenation: (A) pre-treatment, and (B) post-treatment.

Mid-infrared lasers (Table 5.3)

Clinical and histological evidence of non-ablative skin rejuvenation has been observed after use of mid-infrared lasers. The 1320 nm Nd : YAG laser was the first commonly used non-ablative mid-infrared laser to rejuvenate skin. When combined with surface cooling, collagen remodeling is achieved without epidermal damage. With water as the chromophore, the non-specific dermal thermal injury creates edema, vascular changes, and alterations in fibroblast assembly of dermal matrix constituents. The healing sequence can result in mild rhytid correction. The 1450 nm diode laser has been used for non-ablative rejuvenation in the same way as the 1320 nm Nd : YAG.

The 1540 nm erbium : glass laser similarly induces tissue water heating, thermal injury, and neocollagenesis. This laser penetrates to a depth intermediate between 1320 nm (deepest) and 1450 nm (shallowest) among this wavelength range. In planning strategies with all the mid-infrared wavelengths, the depth of penetration should coincide with the depth of solar elastosis.

Each of the non-fractional mid-infrared lasers uses a cooling system to minimize epidermal damage and pigmentary alteration. The 1320 nm Nd : YAG uses either a pre- or post-laser spray, while the 1450 nm diode laser applies cryogen before, during, and after the laser pulse. These combinations of longer wavelengths and surface cooling make these lasers favorable for Fitzpatrick IV, V, and VI skin types. However, particularly in the case of the 1450 nm system, where the total spray time is delivered over a long period (up to 220 ms), there is a risk of cryoinjury. The shorter spray times with the 1320 nm laser and the 5°C sapphire lens incorporated into the 1540 nm erbium : glass laser have not been associated with cryoinjury.

The side effect profile of each of these lasers has a direct correlation with the fluences applied in the treatment of rhytides or acne scars. Although the efficacy of these devices has proven modest in most cases, providers must be cautious to avoid pigmentary changes and the rare case of scarring, which is typically secondary to treating using a fluence that is too high.

Intense pulsed light

IPL devices emit a broad spectrum of wavelengths between 400 and 1200 nm to target multiple structures. These devices, although not emitting monochromatic, collimated, or coherent light, still use selective photothermolysis. IPL can be used to target specific chromophores while avoiding others by using available filters to select certain wavelengths within the 400–1200 nm range. Shorter wavelengths can be used to treat lighter-skinned patients or the spectrum can be ‘red shifted’ through filters or through electronic modulation to minimize melanin absorption in darker-skinned patients. Peaks of hemoglobin absorption can be selectively used to target vascular structures. Finally, for purposes of non-ablative skin rejuvenation, dermal water can be targeted to induce photothermal initiation of neocollagenesis.

The utility and potential risks of the IPL are associated with its diversity. An IPL can be configured to treat the most clinically relevant chromophores (water, melanin, hemoglobin), and thereby multiple dermatologic conditions. There are many available IPL units with a wide array of designs and treatment parameters. Even though newer systems have improved user friendly pre-programmed settings, one should become comfortable with one or two IPL systems as each has different interfaces, wavelength spectrums, filters, power outputs, pulse profiles, cooling systems, and spot sizes. Some of the parameter sets do not allow different IPL systems to be compared easily. For example, there are some IPL devices that calculate their fluences based partly on theoretical modeling and photon recycling whereas others determine fluence based solely on an actual output at the sapphire or quartz window on the handpiece tip. Thus, moving from one IPL device to another does not mean that you will get the same outcome with the same settings on the display panel. A spectrophotometer (color meter) is provided with one new IPL (Icon, Palomar Medical Technologies, Burlington, MA). The meter transmits the patient pigment level directly to the IPL via Bluetooth™ technology. The graphic user interface then shows suggested test spot settings for that particular skin region.

Finally, although the utility of IPL devices allows for treatment of a wide variety of conditions, the addition of radiofrequency has been utilized to supplement and improve outcomes with use of IPL devices (Elos, Syneron). Bipolar radiofrequency exhibits a preference for warmer tissue. This technology takes this property into consideration by utilizing the IPL system to heat the target chromophore and then using the radiofrequency technology to target the now ‘warmer’ tissue target. Contact cooling helps avoid epidermal damage and keep the tissue heat in the dermis. This synergistic technology has proven efficacy in treatment of photoaging, helping reduce wrinkles, lentigenes, and telangiectasias.

Light-emitting diodes

LEDs for photoaging consist of a panel(s) of numerous small lamps that emit low-intensity light. Some companies have miniaturized these devices to handheld units that are used at home, while most professionals are using panels that can treat the entire face in one treatment session. One advantage of LED devices is that they are well tolerated by patients. With no pain, large surface areas of skin can be treated simultaneously.

Typically, LED devices emit a range of wavelengths. These devices are available in various wavelengths from blue to infrared. Depending on the wavelength and treatment parameters, LEDs emit milliwatt light in a small range around a peak wavelength. Thus, for example, if one were to select a LED with a dominant wavelength of 500 nm, the device will likely emit light from approximately 480 to 520 nm.

The interaction of LED devices with the skin are unclear, though most believe that photomodulation of cell receptors, cell organelles, or existing protein products is partially responsible. Unlike many of the devices discussed above, non-thermal interactions with the extracellular matrix and fibroblasts remodel existing collagen, increase collagen production by fibroblasts, inhibit collagenase activity, and result in rhytid reduction.

One of the most popular LED systems is the Gentle Waves^® device (Light BioScience, LLC, Virginia Beach, VA). The system generates 588 nm yellow light pulses with an on-time of 250 ms and off-times of 10 ms for a total of 100 pulses resulting in a total light dose of 0.1 J/cm². Although some trials showed significant improvement in pore size, skin tone, and texture, the most comprehensive controlled clinical trial showed no significant skin changes in objective outcomes after a series of treatments. Boulos found that there was a strong placebo effect with the 588 nm Gentle Waves^® system, and that little objective improvement was observed by blinded raters. Despite the subjective improvement in two trials, objective improvement in blinded studies is unproven.

In a study of 633 nm and 830 nm LED biostimulation, two treatments per week over 4 weeks showed increases in collagen production and mild wrinkle improvement. In a study using a reconstructed skin substitute irradiated with 633 nm LED panels, increases in collagen production were also observed. Additionally, in the clinical arm of the study, patients receiving treatment 3 times a week for 4 weeks (12 treatments) were found to get mild to moderate wrinkle improvement compared with sham treatment.

Photodynamic therapy

Over the past 20 years, photosensitizing agents have enjoyed an increasing role in medical and cosmetic dermatology. Twenty percent 5-aminolevulenic acid (5-ALA, a ‘prodrug’) is absorbed by rapidly proliferating epidermal and dermal cells and converted into photoreactive products of the hemoglobin pathway, most notably protoporphyrin IX (see Fig. 5.1). Protoporphyrin IX is subsequently activated by certain wavelengths of light, as highlighted by the absorption peaks in Figure 5.1, resulting in singlet oxygen production and resultant cellular destruction.

Many light sources have been used for PDT (Box 5.3). This variety is possible owing to multiple absorption peaks by protoporphyrin IX. The largest peaks are at 417, 540, 570, and 630 nm. The PDL, IPL, and LED devices have all been used to activate protoporphyrin IX. There are many variables that affect the immediate PDT response, among them the ALA incubation time, pre-ALA skin preparation regimen, degree of skin photodamage, anatomical region, light dose, wavelength range, and power density. Overall, lower power densities (i.e. continuous wave light sources) create more singlet oxygen than pulsed light. Also, we have found that applying numbing creams simultaneously with the ALA solution can accelerate ALA absorption and thereby accelerate protoporphyrin formation, leading to a much more robust response.

Data from Gold MH 2005 Skin and Aging 13(2):Feb.

^* Device used by author: other settings from colleagues.

(Reproduced with permission of the publisher. Chart appeared in Skin & Aging 13(2):49, 2005.)

Overview of treatment strategy

Patient selection is important to obtain the best expectation–outcome match. Patients may present for treatment of wrinkles and not the other characteristics of photoaging, even though telangiectasia or lentigines may be present. The modality of treatment is also important as each light device offers unique advantages. For example, if the patient presents with a concern of excessive telangiectasia, use of the 532 nm potassium titanyl phosphate (KTP), a PDL, or an IPL device may be warranted. If the goal is to obtain deeper dermal remodeling, one could consider longer-wavelength modalities such as the mid-infrared devices. Due to the widespread use and versatility of IPLs, many dermatologists are treating multiple photoaging characteristics simultaneously, including hyperpigmentation, telangiectasia, rhytides, and skin texture abnormalities. If the patient presents with actinic keratoses, PDT can be performed either at the same appointment or before or after visible pulsed light treatment for red and brown dyschromias. Often a patient presents with multiple telangiectasias and actinic keratoses. If one uses only a vascular laser or IPL, the actinic damage and the associated telangiectasias within the actinic keratoses will persist or relapse; accordingly, either pre-treatment with 5% fluorouracil cream or PDT will enhance the total rejuvenation effect and decrease the likelihood of an incomplete response (Case study 3).

Case Study 3

A 51-year-old white male presents with hyperpigmented patches along bilateral cheeks as well as multiple actinic keratoses on his cheeks and forehead (Fig. 5.7A). Treatment was initiated by the application of Levulan^® (DUSA Pharmaceuticals, Inc.), a 2-hour incubation period, and photodynamic therapy illumination. He was subsequently treated with the V-Beam Perfecta^® (Candela Corporation, Wayland, MA) using a 10 mm spot size, 8 J/cm², a 10 ms pulse duration, with 3 bars of cooling to bilateral cheeks. At 6-week follow-up, there was significant reduction in actinic keratoses, solar lentigenes, telangiectasias, and overall facial rejuvenation (Fig. 5.7B).

Figure 5.7 Patient treated with combination therapy ALA / PDT and pulsed dye laser with marked improvement in actinic damage, lentigines, telangiectasias, and overall skin quality: (A) pre-treatment, and (B) post-treatment.

Conclusion

Non-ablative rejuvenation remodels photodamaged dermal constituents without inducing an epidermal wound. Minimal recovery times make this approach appealing to physicians and patients alike. Reversal of dyschromias (pigment and vascular) are reasonably predictable. Unfortunately, at this point, in the eyes of many clinicians, objective clinical and histologic outcomes with nonablative technologies do not correlate with clinician expectations, with the exception of novel fractional lasers and visible light technologies that target pigmented and vascular lesions.