Novel Imaging Technique Provides Potential Improvement for AMD

Johnny Tam, PhD

A new imaging technique that combines adaptive optics and angiography has allowed researchers at the National Eye Institute (NEI) to observe detailed functioning of the neurons, epithelial cells, and blood vessels in the outermost region of the retina.

With access to such unprecedented detail of the tissues and cells in the outermost region of the retina, the diagnosis and treatment of diseases like age-related macular degeneration (AMD) may be improved.

“There are many diseases where we don’t quite understand how or why an eye progresses,” Johnny Tam, PhD, lead author of the study and Stadtman Investigator in the Clinical and Translational Imaging Unit at NEI told MD Magazine®. “We show that there is a unique interaction of indocyanine green with the retinal pigment epithelium as it travels through the choriocapillaris. This interaction provides an opportunity to unravel the cellular changes that trigger disease progression.”

Researchers have long used imaging techniques to explore biopsies or tissue from patients postmortem in an effort to understand how diseases like AMD or even Alzheimer’s disease affect the eye, but these techniques couldn’t be used in a patient’s functioning eye. Prior techniques that could be used in a patient were hindered by the fact that light gets distorted as it passes through different areas of the eye. Previously, it wasn’t possible to simultaneously see multiple cell types interacting within the eye, which is key to understanding diseases that impact the organ.

Tam and his team used adaptive optics, which are techniques that became common in ophthalmology in the 1990s for correcting distortions while observing how indocyanine green dye—an FDA-approved dye commonly used to image blood vessels in the eye and other body parts—travels through the eye. The dye has been used to visualize larger blood vessels in the eye, but certain areas with smaller blood vessels, such as the outer layer of the retina, remained difficult to see.

When the team first injected the dye, they were surprised by how quickly the dye was taken into the retinal pigment epithelial cells and obstructed their view of the choriocapillaris. This reaction ended up being key to the new technique.

“It wasn’t possible to directly image the choriocapillaris blood vessels using indocyanine green dye since they were rapidly obscured by the dye that was taken up by the overlying retinal pigment epithelial cells,” Tam said. “Using high-resolution adaptive optics imaging, we showed that we could subtract out the signal from the retinal pigment epithelial cells. That enabled visualization of the choriocapillaris.”

Twenty-three patients had their eyes examined using the 2 techniques, including 1 with retinitis pigmentosa. In that patient, the team was able to see that retinal pigment epithelial cells and blood vessels seemed to be preserved, while photoreceptors had died.

“This novel combination provides a tremendous opportunity to unravel the cell by cell changes that lead to disease onset and progression,” said Tam.

The study, “Combining multimodal adaptive optics imaging and angiography improves visualization of human eyes with cellular-level resolution,” was published in online Communications Biology.