Contemplated methods and compositions use selected agents to clarify biological tissues, and particularly tissues in vivo. In especially preferred aspects, the clarification agent is topically applied to clarify a plurality of layers, wherein the dermal layer that includes a target object remains unclarified. Light energy is then applied to the skin in an amount and under a protocol effective to destroy or alter the target object such that all skin layers avoid thermal damage. For example, hair follicles, collagen, and/or tattoo pigments located in the dermal reticular layer of skin are irradiated under a protocol in which the dermal papillary layer and all epidermal layers are clarified while the dermal reticular layer remains unclarified. Remarkably, such protocol significantly reduces thermal damage in the dermis, epidermis, and hypodermis.