OCT imaging of noninvasive treatment modalities has recently been investigated while OCT imaging in connection with invasive treatments like simple excisions and Mohs surgery has been more extensively studied [12, 14–17]. Cryosurgery of premalignant lesions like AK is traditionally guided clinically by freeze-thaw time and lateral extent of freezing, and therefore, real-time OCT monitoring of cryo treatment has been thought to potentially improve accuracy and efficacy of the procedure. Unfortunately, the immediate effects of cryotherapy impair OCT imaging of the tissue. Cryotherapy induces an opaque iceball in the tissue, which completely prevents visualization of the treated lesion and the freezing depth [18] (Fig. 15.2a–d). The reason for the opacity is that at the OCT wavelength of 1,300 nm, ice is around ten times more absorbing than liquid water. When the tissue freezes the created ice absorbs all of the OCT laser light, and therefore, OCT images of cryotherapy-treated skin only show an impervious frosty white line at the skin surface. Normal OCT imaging depth and resolution reappears in time with the thawing of the tissue. In cryosurgery-treated grade 1 and 2 AK lesions, OCT imaging has showed vesicle formation in the lesions within twenty minutes after treatment [18]. The vesicles were primarily located along the dermoepidermal junction and appeared as dark areas with a maximum height of 0.47 mm (Fig. 15.2a–d). The vesicles were subclinical by the time of the post-cryosurgery imaging and could thus only be identified using OCT. A vesiculobullous reaction after superficial cryogen application is an indication of successful treatment of superficial epidermal lesions because the separation of epidermis and dermis enables the shedding of the diseased skin [19].