It is often said that the eyes are the windows to the soul. But now, researchers at a hospital in Israel say the eyes could be a window to the brain. They are using advanced imaging techniques and a new medical device to track changes in pupil size that they hope could lead to the early detection of Alzheimer’s disease.

Israeli eye expert Dr. Yigal Rotenstreich, a retinal researcher, says his team at Ramat Gan’s Sheba Medical Center may have found a way to determine if people will develop Alzheimer’s disease by scanning their retinas for warning signs of the dreaded illness. The retina, with direct access to the brain, is easily accessible for noninvasive imaging and could potentially enable early detection of the disease where clinical symptoms are not yet apparent, the researchers believe.

Alzheimer’s is a type of dementia that causes memory, thought and behavior problems. Symptoms usually develop gradually over a number of years. According to an Alzheimer’s Association 2017 report, more than 5 million Americans are living with Alzheimer’s and this number could rise as high as 16 million by 2050, with US medical costs ballooning to $1.1 trillion from $259 billion this year.

The Sheba team includes Prof. Michal Beeri and Dr. Ramit Ravona-Springer from the Joseph Sagol Neuroscience Center. They use advanced noninvasive imaging techniques to determine the relationship between abnormalities in the retina, such as the volume and the size of its blood vessels and traces of beta-amyloid deposits, and changes in cognitive function and brain structure that are common in people known to be at risk for Alzheimer’s. Beta-amyloid plaques are commonly found in the brains of Alzheimer patients.

Dr.Yigal Rotenstreich of Israel's Sheba Medical Center (Courtesy)

Dr.Yigal Rotenstreich of Israel’s Sheba Medical Center (Courtesy)

A combination of technologies — such as magnetic resonance imaging (MRI) and optical coherence tomography (OCT) — takes 3D images of the eye to measure the parameters of the blood vessels, and a special camera-device, developed by the team, measures the amount of pupil constriction in reaction to various visual stimulations.

“We have developed a unique multi-focal device that measures the amount of pupil constriction when it is exposed to red or blue light. This allows us to test the adequate or inadequate functionality of the visual pathways in different locations of the retina,” Rotenstreich said in an interview with The Times of Israel.

In preliminary studies using the new device, Rotenstreich’s team discovered that there were “aberrant pupil responses” to red and blue light, which suggested a loss of function of retinal neuronal cells in elderly patients who had a “very mild cognitive impairment,” Rotenstreich said.

The hospital now plans to tap into its registry of some 430 subjects, who are the offspring of Alzheimer’s patients of the hospital, to conduct a clinical trial to see if they can identify those same aberrant pupil responses and loss of retinal functionality among those who are at high risk of developing the disease.

“For the first time ever, we are looking for a comprehensive analysis of changes in the function and structure in the retinal blood vessels and studying their relationship with structural, functional and vascular brain biomarkers in the offspring of existing Alzheimer’s patients, who are at a high risk to develop the disease as well,” Rotenstreich said.

Potential treatments for Alzheimer’s have consistently failed in clinical trials “because parts of the brain were already overwhelmed by pathology which begins decades before the actual clinical symptoms become explicit in sufferers of the disease,” Rotenstreich said. “The new set of tests we have developed are noninvasive, reliable, objective and can be done repeatedly with a high reliability. If we are able to use these tests to find Alzheimer’s earlier then we will be able to use treatments earlier with hopefully better efficacy.”

The study, which has already enrolled 50 patients, will look at a number of parameters in different locations in the eye to identify aberrations that could be associated with the disease, Rotenstreich said.

If successful, the findings “could lead to the identification of unique, treatable, noninvasive, low-cost bio-markers for preclinical Alzheimer’s disease,” Rotenstreich said. “This could be the foundation for ongoing clinical assessment and monitoring of treatments for Alzheimer’s. And that would be a tremendous breakthrough.”

Rotenstreich established the Retinal Research Laboratory at Sheba Medical Center’s Goldschleger Eye Institute, where he and his staff conduct clinical studies aimed at developing new treatments and diagnostic tools to solve unmet needs in retinal and macular diseases.