Monitoring Intracellular Cavitation During Selective Laser Targeting of the Retinal

Selective destruction of the retinal pigment epithelium (RPE) has important applications in the treatment of a range of macular diseases such as diabetic retinopathy, diabetic macular edema or central serous retinopathy. Laser photocoagulation is the established therapeutic modality for treating these disorders. However, heat diffusion during the long exposure times results in an extended zone of thermal damage that includes the photoreceptors, the RPE, and the choroid layers. Shorter laser pulses can minimize heat diffusion to surrounding tissue by ensuring that the laser energy is thermally confined within the absorbing RPE cells. Our project aims to develop an in vivo irradiation system that employs high-speed scanning of a continuous wave laser beam, corresponding to equivalent ps exposure times, for selective RPE targeting with minimal damage to the overlying photoreceptors. In order to achieve selectivity in a clinical application, the laser dosage must be precisely determined, since selective RPE lesions are not clinically visible. Rapidly heating the melanosomes creates microscopic bubbles within the RPE cells. This phenomenon, known as cavitation, has been proposed as the mechanism for laser-induced cell damage, and therefore determining the threshold for bubble formation in vivo will be critical. This work focuses on developing a probe system to monitor cavitation, by detecting the backscattered signal of the irradiation laser pulse to obtain information on bubble formation by the melanin microparticles. Laser pulse duration was varied between 3 ps to 50 ps. The fluence threshold for cell death was found to increase with increasing pulse duration (3 -> 50 ps) and coincided with the threshold for bubble formation in the RPE for laser pulses up to 20 ps. The proposed technique of selective laser targeting will be useful for treating RPE-related diseases without incurring the extensive damage associated with the application of conventional laser photocoagulation. Thesis Supervisor: Peter T. So Title: Associate Professor of Mechanical Engineering