Imaging Technique Visualizes Individual Retinal Ganglion Cells

A new imaging technique that modifies confocal adaptive optics scanning light ophthalmoscopy (AOSLO) could revolutionize how eye health and disease are assessed.

Using their new, noninvasive imaging technique, researchers at the University of Rochester Medical Center are able to make out individual cells at the back of the eye that are implicated in vision loss in diseases like glaucoma. They hope their new technique will prevent vision loss via earlier diagnosis and treatment for these diseases.

Through experimentation, the researchers were able to distinguish individual retinal ganglion cells (RGCs), which bear most of the responsibility of relaying visual information to the brain.

There has been a longstanding interest in imaging RGCs because their death causes vision loss in glaucoma, the second leading cause of acquired blindness worldwide. Despite great efforts, no one has successfully captured images of individual RGCs, in part because they are nearly perfectly transparent.

Instead of imaging RGCs directly, glaucoma is currently diagnosed by assessing the thickness of the nerve fibers projecting from the RGCs to the brain. David Williams, dean for research in arts, sciences, and engineering and the William G. Allyn Chair for Medical Optics at the University of Rochester, said by the time retinal nerve fiber thickness has changed detectably, a patient may have lost 100,000 RGCs or more.

"You only have 1.2 million RGCs in the whole eye, so a loss of 100,000 is significant," said Williams. "The sooner we can catch the loss, the better our chances of halting disease and preventing vision loss."

Williams and his team collected multiple images, varying the size and location of the detector they used to gather light scattered out of the retina for each image, and then combined those images. The technique, called multi-offset detection, was performed at the University of Rochester Medical Center in animals as well as volunteers with normal vision and patients with age-related macular degeneration.

Not only did this technique allow the group to visualize individual RGCs, but structures within the cells, like nuclei, could also be distinguished in animals. The hope is that if they can achieve that level of resolution in humans, they will be able to assess glaucoma before the retinal nerve fiber thins — and even before any RGCs die — by detecting size and structure changes in RGC cell bodies.

While RGCs were the main focus of the investigations, they are just one type of cell that can be imaged using this new technique. Using their multi-offset technique in age-related macular degeneration patients, the University of Rochester Medical Center team was able to assess the health of cones near Drusen and in areas where the retina had been damaged, said Ethan Rossi, assistant professor of Ophthalmology at the University of Pittsburgh School of Medicine.

"This technique offers the opportunity to evaluate many cell classes that have previously remained inaccessible to imaging in the living eye," said Rossi. "Not only RGCs, but potentially other translucent cell classes and cellular structures."

More studies will be needed to improve the robustness of the technique and ensure the results are reproducible before it can be widely used in a clinic.