In 2005, Americans spent more than $300 million on almost 800,000 laser hair removal treatments, according to the American Society of Plastic Surgeons. Lasers also can be used to alter skin pigmentation or to remove unwanted wrinkles, scars and tattoos. However, skin scatters light, and optical energy must penetrate below its top layer for effective dermatological treatment. It also must be focused on the treatment area to avoid damaging surrounding tissue. Optical clearing agents can cause the skin to have a more uniform refractive index, thus reducing light scatter, but they must permeate the skin to be effective. It is possible to use an erbium laser to remove the top layer of skin before applying optical clearing agents, to help them reach the underlying layers, but this results in an open wound. Therefore, Ilya V. Yaroslavsky and his colleagues at Palomar Medical Technologies Inc. in Burlington, Mass., and at Saratov State University in Russia tested the effectiveness of another technique to enhance the ability of optical agents to penetrate the skin without significantly compromising their protective function. They applied a pattern of small, light-absorbing carbon dots — aligned in rows and columns — to the skin and illuminated its surface with intense pulsed light from a flashlamp. The procedure formed a “lattice of islands of thermal damage” that served as routes for the agent to penetrate without disturbing the tissue between the islands. The scientists placed carbon dots in a lattice formation on the skin of healthy human volunteers and on human and pig ex vivo skin samples, followed by topical application of an optical clearing agent and illumination with intense light pulses. As a result, light transmittance through the skin increased by an average of three to 10 times. The researchers used fresh rat, farm pig and Yucatan pig skin samples (in order of increasing similarity to human skin and decreasing cost and availability), followed by tests on healthy human volunteers. Yaroslavsky said that they used various optical clearing agents, including glycerol, propylene glycol and glucose, because there is a lack of agreement in the literature as to which one works best. The carbon dots were approximately 75 to 120 μm in diameter and were spaced about 450 to 500 μm apart. Those measurements were empirically determined to result in the best compromise between skin penetration and safety. The total area of the lattice matched that of the flashlamp window. They employed two flashlamp systems, the EsteLux and MediLux from Palomar. On the volunteers’ skin, the researchers applied a blue dye. After using the flashlamp with a 20-ms pulsewidth and a fluence of 14 J/cm2, they observed that the dye entered the skin, demonstrating increased permeability. On the farm pig sample, they applied Lux lotion from Palomar and a 40 percent glucose solution. After operating the flashlamp with a fluence of 36 J/cm2 and a 20-ms pulsewidth, they saw maximal optical clearing 60 minutes after topical application of the optical clearing agent, which was assessed by the visual appearance of blue wires in the specimen. For 20 J/cm2 and a 10-ms pulsewidth, they saw less optical clearing. They also placed sheets of paper with the printed word “clearing” or the letter “O” under rat skin, and the writing appeared after treatment. Coating the rat skin with glycerol and using the flashlamp with the same pulsewidth and fluence resulted in maximal optical clearing after 60 minutes, but using 40 percent glucose had a less noticeable effect. Overall, glycerol was the most effective optical clearing agent. The researchers then employed a BioSpec holographic-grating spectrophotometer to measure the intensity of light that passed through the skin. For Yucatan pig, farm pig and human skin samples, the relative transmittance (the ratio of intensity after treatment to that before treatment) increased by an average of three to 10 times when the lattice of islands of damage was used. The scientists said that these results demonstrate the effectiveness of the technique, but they believe that further research is necessary for its optimization. Lasers in Surgery and Medicine, October 2006, pp. 824-836.