Lasers for Dermatology and Skin Biology

Popular media initially portrayed lasers, the brightest light sources in the known universe, as a ‘‘death ray’’. Instead, lasers became minimally destructive, precise, versatile surgical tools that also enabled a revolution in biological sciences through live-tissue microscopy. How did that happen, and what might come next? It turns out that laser capabilities—impressive optical power density, collimation, coherence, well-defined wavelength, and impressively brief pulses—are better suited for gentle precision than for wanton destruction. This trend has been going strong for 30 years and shows no signs of slowing down. The need for a better treatment of port wine stains (PWS) led us to hatch the concept of ‘‘selective photothermolysis’’ (SP) (Anderson and Parrish, 1983), which became the basis for many new therapeutic lasers. Light passes harmlessly through space and matter until it is absorbed. It stands to reason that heating (and other events caused by light) begins when and where the light is absorbed. Skin contains specific structures with a high concentration of light-absorbing molecules (chromophores), such as the abnormal blood vessels of PWS. Intense pulses of light at wavelengths preferentially absorbed in these ‘‘target’’ structures can cause selective thermal damage. We showed this for microvessels in skin using yellow light pulses and for melanin-pigmented cells using UV light pulses. For the best selectivity, heat should be confined to the target during the light pulse. In other words, pulse duration should be about equal to the time it takes for cooling the target. Thermal relaxation time turns out to vary with the square of target size. For targets ranging from subcellular particles (nm scale) to multicellular structures (mm scale), thermal relaxation time varies a million-fold, from nanoseconds to milliseconds. These simple ideas led to a burst of new applications for nonscarring, pulsed lasers over a wide range of pulse duration and wavelength, including lasers that did not previously exist. Millisecond pulsed dye lasers (PDLs) for treating microvascular malformations are the first example of any laser specifically invented for a medical need, and they remain the treatment of choice for neonatal and childhood PWS (Chapas et al., 2007). The latest generation of PDLs has variable pulse duration to match various target vessel sizes, and uses dynamic cryogen spray cooling for epidermal protection in pigmented skin. However, PWS treatment remains challenging because a residual vascular lesion almost always persists. Three reasons are hypothesized to account for persistence of PWS—(a) angiogenesis produces new PWS vessels after each laser treatment, (b) insufficient depth of PDL treatment, and (c) an intrinsic lack of sympathetic innervation. These might be overcome. The first report of combined PDL plus the angiogenesis inhibitor drug rapamycin (Nelson et al., 2011)—and for adults with hypertrophic PWS, the use of deeply penetrating nearinfrared wavelengths—is highly effective (Izikson et al., 2009). PWS being microvenous lesions, in theory a source could be made that targets de-oxyhemoglobin, sparing the arterial circulation (Rubin et al., 2012). Other indications for PDLs and their cousin technologies include rosacea, scars, ulcerated infantile hemangioma, warts, and laryngeal lesions including carcinomas. The precision with which very short (nanosecond 10 9 s, or shorter) pulses can target individual pigmented cells or organelles is impressive. In our initial investigation of SP, we found that even Langerhans cells adjacent to pigmented epidermal cells were unaffected. Ophthalmology subsequently developed this as a successful treatment for early-stage glaucoma, targeting pigmented cells in the trabecular meshwork (Latina et al., 1998). In dermatology, Q-switched red and near-infrared lasers proved to be excellent for treating some melanocytoses such as nevus of Ota, useful for cafeau-lait macules and lentigines, but generally a failure for other conditions such as Becker’s nevi. As one might expect, the biology of particular pigmented skin lesions critically affects their response to laser treatment. The pigmented, well-differentiated dermal melanocytes of nevus of Ota are easily removed by Q-switched ruby, alexandrite, or Nd:YAG laser treatment (Taylor et al., 1991). In contrast, congenital melanocytic nevi include both pigmented and nonpigmented melanocytes at various levels of differentiation. Surgical excision is the preferred treatment, and lasers offer a useful alternative only in some cases. Other fascinating aspects of laser targeting of melanocytes have never been developed. For example, sublethal fluences from these Q-switched lasers stimulate melanogenesis and tanning of the skin. Tattoos are a poorly regulated form of ancient nanotechnology. Insoluble,