The “Dem Bones” spiritual that says, “your backbone connected from your hip bone” needs another verse that says “your eyes are connected to the brain bone.”

It turns out that the eyes may present the possibility of the early diagnosis of Alzheimer’s, and now a new spate of neuropsychological conditions. It’s particularly exciting because the diagnoses can be made with existing tests and, with some modification, diagnostic devices.

For instance, the thickness of a person’s retina and its response to light could provide early signs of the disease.

The retina is essentially a proxy for what’s happening in the brain”
Steven Silverstein, clinical psychiatrist at Rutgers University in Piscataway, NJ

The links between eye function and disease are expanding as researchers can now identify brain injuries and concussion, and other disorders that correlate with changes in vision.

The significance of vision changes

Vision requires the use of about half of the brain’s neural pathways, explains Laura Balcer, a neuro-ophthalmologist at New York University Langone Health in New York City. Anything that affects a person’s brain, whether it’s a disease or a blow to the head has a strong chance of affecting their sight. Researchers have known for a while that neurological disorders can bring about changes in vision and eye motion.

Multiple Sclerosis

Much of the work to assess neurological conditions through the eye has been done in the context of multiple sclerosis, which causes the immune system to disrupt the nervous system by attacking myelin, the protective layer around nerves involved in pathways for vision.

In the early 2000s, Balcer and her collaborator Steven Galetta, also a neuro-ophthalmologist at Langone Health, helped to develop a test that uses the Sloan low-contrast letter-acuity chart, which is more difficult for people with MS, because they require greater levels of contrast than people without the condition. The test is now a leading tool for monitoring the progression of MS.

More MS tests have evolved, too. The King-Devick test (Devick Technologies), assesses the brain pathways that control eye movement by asking the patient to quickly read a list of numbers. The King-Devick test is now used by NASCAR and other sports to detect concussion.

Ocular Coherence Tomography and Alzheimer’s

The 3D image of the retina OCT has now become a tool to study, monitor and potentially diagnosing neurological disorders.

In MS, for example, the thinning of the retina leads to optic neuritis. By defining a relationship between OCT observations with results from low-contrast vision tests, researchers have correlated a thinning retina with the vision degradation found in MS.

Though OCT is not yet incorporated into the diagnostic criteria, it has significant advantages over using magnetic resonance imaging (MRI) for diagnosing optic-nerve lesions: Its resolution is more than 1,000 times the MRI, and OCT doesn’t have the problem presented by eye movement.

OCT is also helping to uncover the early signs of Parkinson’s disease and Alzheimer’s disease, which could enable treatment before symptoms develop.

In November 2019, U.S, researchers combined OCT with angiography to image blood vessels. By comparing healthy retinas with those of people who had elevated levels of amyloid-β — a peptide linked to Alzheimer’s disease —they found that the foveal avascular zone, a region of the retina that lacks blood vessels, was about one-third larger, on average, in people with elevated amyloid-β

Diagnoses of Neuropsychiatric Disease

Researchers are also finding early biomarkers neuropsychiatric disease, which may allow clinicians to intervene before their onset or progression. For instance, there is evidence that in people with schizophrenia, the small veins, or venules, of the retina are wider and the retina is thinner.

Using electroretinography to diagnose schizophrenia

Electroretinography measures the retina’s electrical response to light, and researchers at Laval University in Quebec City, Canada, are using it to identify how the response of rods and cones changes in people at risk of or diagnosed with neuropsychiatric conditions such as schizophrenia and major depressive disorder. The researchers found that the rods of young people with a high genetic risk of developing schizophrenia responded more weakly to light than those of young people without that risk.

Soon, clinicians may use the technique to distinguish between neuropsychiatric disorders and for distinguishing between mental disorders, for example, schizophrenia and bipolar disorder. These new tools and the ethical consideration that surround their use will continue to evolve, and perhaps become standard tools for use by the ophthalmologist.