Before getting into the clinical utility of adaptive optics imaging technology, it is prudent to first review the basic principles of imaging with adaptive optics. With conventional optical imaging, the major factor limiting the achievable resolution is the eye's monochromatic aberrations, which are due to imperfections in the optics of the eye. These wavefront aberrations can be separated mathematically into shapes described by low order polynomials (defocus and astigmatism) and higher order polynomials (e.g. coma and trefoil). Although lower order aberrations can be effectively corrected using spectacles or contact lenses, the higher order aberrations cannot over a large field of view. Their effect on visual function is not typically severe; however, higher order aberrations interfere with high-resolution retinal imaging. Ophthalmic adaptive optics systems are designed to measure and correct for these higher-order aberrations, and can provide image resolution that is limited only by the pupil diameter of the eye, the axial length of the eye, and the wavelength of light. As shown in Figure 1, ophthalmic adaptive optics imaging systems have three main components-a wavefront sensor (typically a Shack-Hartmann design, for measuring the eye's aberrations), a corrective element (typically a deformable mirror, for correcting the aberrations), and an imaging device (typically a charge-coupled device [CCD] or photomultiplier tube). These design principles are not absolute, and alternative approaches that do not use a wavefront sensor 1 or that use multiple corrective elements 2,3 have been demonstrated. Nevertheless, the unifying feature of adaptive optics imaging systems is mitigation of the eye's aberrations to achieve nearly diffraction-limited imaging. These imaging systems have so far taken the form of an adaptive optics fundus camera, 4,5 an adaptive optics scanning laser ophthalmoscope, 6 or an adaptive optics optical coherence tomograph (OCT).
7-9Current imaging systems are able to noninvasively resolve numerous structural features of the living human retina. As demonstrated by multiple groups, it is now possible to image both rod and cone photoreceptors, including foveal cones, which are the smallest photoreceptor cells in the retina (see Figure 2). 10-13 Much work has also been done on characterizing the normal photoreceptor mosaic, 10,11,[14][15][16][17][18] although larger databases and convergence on image analysis metrics is needed. While much of the clinical efforts have been directed at imaging the photoreceptors, the ability to resolve other features of the retina is likely to be useful in studying diseases such as glaucoma (lamina cribrosa, nerve fiber layer, ganglion cells), age-related macular degeneration (retinal pigment epithelium[RPE]), and diabetic retinopathy (retinal vasculature). There have been a handful of reports on visualizing RPE cells in the normal human retina using intrinsic autofluorescence in the normal retina 19 or reflectance in some patients with photoreceptor degeneration. 20...