## 1 Introduction  
Optical Coherence Tomography (OCT) is a non-ionizing technique that provides real-time cross-sectional images of living tissues. It is based on low-coherence interferometry with micron-scale spatial resolution and millimeter-scale penetration depth within the optical window of 0.65-1.3 \(\upmu\)m [1]. The interferometric measurement of backscattered photons that have preserved their coherence within the imaging volume, enables OCT to record the amplitude and phase of the light signal along with depth information in a 2D image of the scattering medium. Due to the micron resolution and adequate penetration depth, OCT can be employed to display subsurface structural features of tissue sheaths. In clinical settings, OCT finds wide applications in the field of ophthalmology. However, it is still less established as a non-invasive diagnostic method in dermatology where, in contrast to the eye, strong scattering limits the light penetration in the skin. As light absorption is wavelength-dependent, skin imaging is determined by the presence of skin chromophores and OCT devices of 1.3 \(\upmu\)m wavelength are typically chosen where absorption remains low [2]. Alterations in tissue morphology trigger changes in the optical properties of the skin tissue in the near-infrared wavelength range. Hence, the main application of OCT skin imaging is nonmelanoma skin cancers (NMSC) and especially basal cell carcinoma (BCC) due to its distinct spatial localization [3].  
Although the interferometric procedure reduces the effect of multiple backscattering, OCT images are inherently noisy and suffer from image artifacts due to intensity and morphological distortions that stem from the different refractive index (RI) of the multiple scatterers lying within coherence distance in the skin tissue [4]. Human tissues have heterogenous composition consisting mainly of interstitial fluid (ISF) and the cytoplasm. The RI of these components, which are largely composed of water, is lower than that of cell scatterers and as result, strong light scattering occurs. This substantial light scattering hinders the effective use of optical technologies in clinical practice despite the superior resolution of techniques that rely on bio-photonics. As a result, it remains a challenging task to overcome scattering effects and attain adequate imaging depth for in vivo studies. To that end, the tissue optical clearing technique can provide reduced scattering in biological tissues utilizing high RI chemical moieties which are termed optical clearing agents (OCA) [5]. Tissue transparency is increased by effectively raising the RI of the ISF to match the RI of the scatterers. For in vivo skin studies, the so-called physical methods are typically preferred given the non-toxicity prerequisite. These are based on a RI matching process to diminish the optical inhomogeneities using an organic and/or aqueous solution [6]. OCAs are selected with a similar to tissue RI and with the ability to diffuse into a tissue specimen substituting water in order to achieve the RI matching. Typically, these agents are in the form of hyperosmotic liquids and cause tissue dehydration and index matching [7; 8]. Non-reactive chemical agents, such as sugars (glucose), alcohols (glycerol, diols, etc.) and glycol-based polymers (PEG), have previously demonstrated their ability to reduce OCT optical scattering [7; 9; 10; 11; 12; 13]. The aim of this study was to assess the impact of four OCAs (Propylenglycol, Propylenglycol combined with Oleic Acid, Vaseline and Liquid Vaseline) on skin optical permeability. The most suitable OCA was determined by the variations of OCT attenuation coefficient (\(\mu_{\text{OCT}}\)) and epidermal thickness which were assessed through OCT image analysis of non-treated skin, measured at two different but clinically relevant time points.