Methods and apparatus for automatically aligning a confocal aperture utilize a confocal imaging system and a computer controlled optimization algorithm such as the Nelder-Mead algorithm for imaging an in-vivo eye having chromatic aberration. When using a confocal aperture of 3.4 Airy disks in diameter, images were obtained using retinal radiant exposures of less than 2.44 J/cm2, which is ˜22 times below the current ANSI maximum permissible exposure. The embodied method can be used, e.g., to study RPE morphology in AMD and other diseases, providing a powerful tool for understanding disease pathogenesis and progression, and offering a new means to assess the efficacy of treatments designed to restore RPE health.
