Enhanced Imaging Technique May Help Identify Clinical Trial Participants

August 07, 2014

Just because a photoreceptor has stopped working due to the effects of a retinal degenerative disease doesn’t mean it’s forever lost. In fact, as the Foundation reported previously, José Sahel, M.D., a researcher at the Institut de la Vision in Paris, is developing a treatment to reactivate cones which have lost their light-sensing, antenna-like projections known as outer segments, but still retain their cell bodies, or inner segments.

While moving this type of therapy into a human study, it’s essential to identify patients who have retained these inner segments. But finding such patients presents an imaging challenge that is difficult to overcome. For the past few years, researchers have been able to capture images of cone outer segments using adaptive optics scanning laser ophthalmoscopy (AOSLO). It’s the same technique used by astronomers to correct aberrations in the Earth’s atmosphere while looking at planets and stars. The technology is now being used to correct visual aberrations caused by the lens and cornea when looking through the eye to observe the retina. But capturing inner-segment images has been elusive.

However, a Foundation-funded research group known as the Advanced Ocular Imaging Program at the Medical College of Wisconsin, co-directed by Alfredo Dubra, Ph.D., and Joseph Carroll, Ph.D., appears to have found a solution to the problem, using a technique called “non-confocal split-detector” AOSLO. Led by Drew Scoles a graduate student at the University of Rochester, the Medical College of Wisconsin, the team was able to capture images of inner segments in individuals with normal vision as well as patients with achromatopsia, a condition that affects cones, causing day blindness and loss of central vision. Results of the research study were reported in the journal Investigative Ophthalmology & Visual Science.

“Conventional adaptive optics imaging of photoreceptors requires that the cells are structurally intact. The outer segments behave like tiny optical fibers, guiding a focused light signal towards the pupil for imaging,” explains Dr. Carroll. “However, when the outer segments are gone, this wave-guided signal is diminshed. Thus, we see dark areas. Until now, there was no way to know what, if anything, occupies the dark space.”

By modifying AOSLO to capture scattered light from different areas of the photoreceptor, using non-confocal split detection, the researchers were able to identify inner segments in the achromatopsia patients. The approach should work for any retinal disease where inner segments persist, including retinitis pigmentosa.

“The implications are huge,” says Dr. Dubra. “Whether for evaluating the therapeutic potential in a given retina or monitoring treatment response, the ability to see cells that are structurally compromised dramatically expands the patients that can benefit from adaptive optics imaging.”

“Finding the right types of patients for clinical trials is as important as developing the potential treatments,” says Stephen Rose, Ph.D., chief research officer at the Foundation. “We have been aggressively funding high-tech imaging technologies because they characterize the patients’ retinas so well. Advances like split-detection AOSLO greatly increase our chances for success in human studies because they help us characterize those people who are most likely to respond to treatments.”