Adaptive optics was originally proposed to remove the blur due to the turbulence in the earth's atmosphere from telescope images. The key to this technology is to use an optical element that can change so as to deviate the light rays to focus light as needed. In most cases, this element is a deformable mirror with tens or even hundreds of moving parts called actuators. Remarkably, applying the same technology to compensate for the optical imperfections (monochromatic aberrations) of the living eye enables non-invasive visualization of the microscopic structures of the retina.
The basic principle of adaptive optics is depicted in the schematic on the right. A beam of light is shined into the eye, and a small amount is reflected back out of the eye and into the optical system. Reflected light is split between a wavefront sensor (which measures the monochromatic aberrations) and the imaging device (can be thought of as a camera or a microscope). The control system sends a signal to the deformable mirror, whose surface changes shape in order to minimize the monochromatic aberrations as seen by the wavefront sensor.
Of course, in practice, adaptive optics systems are rather complex. Shown below is a photograph of one of the adaptive optics scanning light ophthalmoscopes (AOSLO) housed within the Advanced Ocular Imaging Program. The AOSLO is effectively a confocal microscope, allowing the visualization of individual layers of the retina depending on the specific eye condition being studied.
Left, photograph of an AOSLO system, the red camera near the bottom is the wavefront sensor camera. On the right is a diagram depicting the optical design of the system. While the optical elements appear in a single flat plane, they are actually folded in 3 dimensions, which is one of the design features that enables such high-resolution imaging.
We have combined adaptive optics with advanced optical design methods to develop ophthalmoscopes that allow us to study the living retina with unprecedented resolution. Shown below is an example of the increase in resolution afforded by the use of adaptive optics. It is possible to visualize individual photoreceptors and examine disease on a cellular level in a way that isn't possible with conventional imaging tools.
Left, clinical fundus image obtained from a line-scanning ophthalmoscope. Middle panel shows the digital zoom of the black outlined area, while the right panel is the corresponding AO image of the same retinal area.
One of the strengths of our program is the engaged clinical faculty who help drive our research questions towards the most pressing clinical questions. As a result, we have made a number of important discoveries related to the understanding of eye disease and that illustrate the utility of adaptive optics retinal imaging. Some examples are:
The discovery that the amount of light reflected by individual rod photoreceptor cells changes over time, a feature that may be linked to the overall health of the cell. This could provide a non-invasive optical probe of function, similar to techniques like the electrocardiogram or electroretinogram. See the paper by Cooper et al here.
The demonstration that retinal damage was detected with our adaptive optics tools, but could not be detected with conventional tools available to clinicians and researchers. See the paper by Stepien et al here.
The discovery in achromatopsia that despite the near absence of cone function, there is actually significant cone structure remaining. This provides significant hope for the translation of gene therapy approaches from animal studies to eventual human trials. See the paper by Genead et al here.
The discovery that the retinal pigment epithelial cell mosaic can be visualized in the fovea using dark-field imaging enhanced with adaptive optics. The ability to study these cells in vivo will allow us to improve the understanding of age-related macular degeneration, diabetic retinopathy and retinitis pigmentosa among other conditions that affect vision. See the paper by Scoles et al here.
To see more examples from our adaptive optics imaging efforts, please visit our Image Gallery.