I. Introduction
Optical clearing based on the introduction of hyperosmotic chemicals or optical clearing agents (OCAs) has been inferred to reduce random scattering within tissue primarily by better refractive index matching, a dehydration action, and collagen dissociation [1]–[4]. Experimental studies on optical clearing of normal and pathological skin and its components (epidermis and dermis) have been carried out using glycerol (G), glucose, propylene glycol, dimethyl sulfoxide (DMSO), cosmetic lotions, gels, and pharmaceutical products [5]–[12]. Current challenges to skin optical clearing include epidermal penetration by clearing agents. The efficiency and efficacy of optical clearing with topically applied OCA are often suboptimal because the permeation of OCA such as glycerol, propylene glycol, glucose, etc. into the skin is slow due to the resistance of the outermost layer of the skin, the stratum corneum (SC) [1]. The SC acts as a barrier to outside invaders entering the human body; it is, hence, responsible for the poor permeability of skin and the poor optical clearing effect of skin with most topically applied clearing agents. Slow diffusion of the index matching agent through the skin barrier makes practical implementation of the approach difficult. To reduce barrier function of the skin during optical clearing, a number of different chemical and physical methods were proposed. Chemical penetration enhancers such as polyurethane prepolymers, oleic acid, and azone (epsilon-Laurocapram) into the transdermal formulation have shown to accelerate the skin permeability of OCA [13]–[15]. For physical methods, a diode laser was applied to enhance transdermal skin clearing agent delivery due to thermal effect [16]. Recently, Tuchin et al. proposed a method of accelerating penetration of the OCA by enhancing epidermal permeability via creating a lattice of microzones (islets) of limited photothermal damage in the SC [17].