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Clinical applications for adaptive optics in retinal imaging emerging
Combining adaptive optics with confocal imaging or OCT is in development.
In the coming years, clinicians should have at their fingertips a variety of adaptive optics configurations that will allow for earlier detection of retinal disease, which could eventually lead to earlier intervention and better outcomes.
Adaptive optics (AO) allows for the observation of subtle changes in the retina, more so than that which can be seen with conventional imaging, according to David R. Williams, PhD, director of the Center for Visual Science at the University of Rochester, N.Y.
“You can see the losses of single photoreceptors in the retina. Therefore, you can track the progress of retinal disease or the efficacy of therapy much more effectively and on shorter time scales,” Williams said.
Correcting aberrations
In 1997, Williams was the first to demonstrate AO techniques correcting for higher-order aberrations; in 2012, Williams was recognized with the Champalimaud Vision Research Award for his pioneering work in AO and career-long contributions to the field.
Combining adaptive optics with optical coherence tomography yields volumetric reconstruction of the retina at a microscopic scale, according to David R. Williams, PhD.
Image: Nale P, OSN
“His techniques neutralize the many complex aberrations that distort light rays transiting the ocular structures on their way to illuminating the retina and on their way back to the equipment recording the retina’s appearance,” Alfred Sommer, MD, MHS, of the Champalimaud Foundation, said of Williams during the 2013 Association for Research and Vision in Ophthalmology Champalimaud Award Lecture.
One of the chief limitations in the development of therapies for the eye is the insensitivity of retinal function measurements, according to Williams.
“Visual acuity, for example, is notoriously poor at detecting the progression of certain diseases like glaucoma,” he said. “With glaucoma, you may have normal visual acuity but devastation of the retina.”
Citing a patient with normal visual acuity but 30% loss of photoreceptors, Williams said, “Conventional clinical measure of visual performance would show nothing, but with AO you can see that this patient has lost a large number of photoreceptors.”
Within the next few years, better AO instruments will be available commercially, according to Williams.
Combined imaging
“One of the wonderful features of AO is that it is compatible with almost any other modality,” Williams said. “For example, Canon is a company that is making an AO system that also comes equipped with confocal imaging — a scanning laser ophthalmoscope. For years, thanks to the work of Austin Roorda, PhD, when he was at the University of Houston, we’ve been using this combination of technologies in the laboratory for better overall performance.”
Likewise, devices in development that combine AO with optical coherence tomography provide axial resolution that is “comparable to the best OCT systems and with the additional transverse resolution benefits of AO,” Williams said. Whereas OCT can achieve resolution on the order of 3 µm in depth axially in the retina, AO takes the other two spatial dimensions (x and y) for 2-µm resolution for both of those dimensions, Williams said.
“As Donald T. Miller, PhD, of Indiana University, and others have shown, combining AO with OCT, you have a 3-µm resolution or less in all three spatial dimensions of the retina, thus allowing volumetric reconstruction of the retina at a microscopic scale,” Williams said.
Stephen A. Burns, PhD, also of Indiana University, has demonstrated the benefits of combining AO with dark-field imaging, according to Williams.
“This will provide better ways of visualizing, for example, blood flow,” he said.
Williams and colleague Jennifer J. Hunter, PhD, are developing fluorescence imaging, both single- and double-photon, in combination with AO.
“We are in the middle of a revolution in our ability to monitor activity in single cells using fluorescent markers,” he said. “Ultimately, we are going to be able to insert these fluorescent probes in any cell in the retina that we desire. We are going to be able to monitor the health and activity of specific biochemical pathways in those cells using these fluorophores.”
Two-photon imaging, which allows examination of the behavior of molecules that fluoresce in the ultraviolet spectral region, is inaccessible with normal fluorescence imaging or normal retinal imaging of any kind, according to Williams.
“This opens up a whole new range of compounds in the eye that we can monitor,” he said.
Of all pending imaging technologies, Williams is most excited about fluorescence imaging because it allows the study of both structure and function in diseased eyes, Williams said.
“However, it is going to take us some time. We do not have approval yet to use these fluorophores in the human eye,” he said.
Genetic engineering is just one method to introduce fluorescent compounds into cells. Williams said he and colleague William H. Merigan, PhD, are currently using fluorescence techniques to monitor the electrical activity of cells in nonhuman primates.
“This offers the opportunity to identify what parts of the retina are healthy and what parts are not,” Williams said. “I think eventually we will figure out how to do that safely in humans.”
The engineering challenge for manufacturers is to ensure that all these AO systems are turnkey operations for clinician ease of use. Williams believes that patients will embrace the new technology.
“Right now, it requires a long session to obtain a good set of images, but I think we will find ways of shortening that time period,” he said. – by Bob Kronemyer