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Out of sight

By Alex Piazza

Ten million Americans are blind or visually impaired.

Each year, 75,000 more Americans will succumb to vision problems, according to the National Federation of the Blind.

Globally, 160 million people suffer. And Medicare data shows that almost every one of us will have at least one eye disease in our lifetime.

Researchers at the University of Michigan W.K. Kellogg Eye Center see a brighter future.

There, scientists invented a device to detect age-related vision problems before people begin losing their sight. U-M surgeons were the first to implant a bionic eye so that patients could see objects, light and people standing before them.

U-M researchers also led one of the largest studies of an eye condition that causes serious progressive nearsightedness at a young age—work that recently led the U.S. Food and Drug Administration to approve a new treatment for the disease.

Efforts to treat and, someday, cure and prevent eye disease have cemented the Kellogg Eye Center's reputation as a global leader in vision care, research and training.

“Our work here at the Kellogg Eye Center truly epitomizes translational research,” said Dr. Thomas Gardner, Professor of Ophthalmology and Visual Sciences, who is an expert on how diabetes impacts sight. “Diabetes is a major cause of vision impairment, but why that is remains uncertain, which presents us with yet another fascinating biological challenge. This work has important implications for the entire U.S. economy because, as we know, the costs of diabetes and its complications are staggering.”

Below are two examples of how U-M researchers at the Kellogg Eye Center are working on ways to improve sight.

Common mutations

The overall survival time is only three years after diagnosis and no standardized treatments exist.

Though rare, vitreoretinal lymphoma bears some grim statistics, especially when incidence of this eye cancer has tripled over the last 15 years.

But U-M researchers are using next-generation sequencing techniques to identify a targeted treatment for the deadly disease that also can cause blindness.

“We are dealing with a disease where, for starters, there are no drugs that directly target the genetic changes unique to these tumors,” said Dr. Rajesh Rao, Assistant Professor of Ophthalmology and Visual Sciences at U-M. “And furthermore, the survival rate is low, with a 25 percent survival rate five years after being diagnosed.”

Radiation and chemotherapy often are used to treat the tumor, but both treatments are frequently ineffective and can cause severe side effects.

Rao, along with U-M Assistant Professor of Pathology and Urology Dr. Scott Tomlins, recently analyzed tissue samples from four patients with vitreoretinal lymphoma to help identify a more targeted approach to treat this disease.

“One of the biggest problems we face with vitreoretinal lymphoma is trying to diagnose it,” said Rao, also an assistant professor of pathology. “This condition can look like inflammation and smolder for years. The eye biopsy may not detect the cancer cells, so this cancer often is not diagnosed until it involves the brain. When diagnosed at this stage, the prognosis is awful,”

Using an approach developed by U-M scientists, a surgeon starts by taking a tiny sample of the clear gel that fills the space between a patient’s lens and retina, known as the vitreous. Researchers used a kit to isolate DNA from the clear gel.

They then tested the samples against a panel that identifies alterations in more than 125 cancer-related genes. Unlike other sequencing techniques that require a fresh biopsy sample, the panel can be used with archived tissue samples—even those that are decades old. This allows researchers to obtain enough samples rapidly—no easy task for a rare disease.

The panel targets alterations in genes for which targeted treatments have already been approved or are being tested in clinical trials.

Since their test can detect tumor DNA in very small quantities, researchers may be able to detect vitreoretinal lymphoma in the eye even if it goes undetected in conventional biopsies. Rao and Tomlins hope to expand their study to confirm their initial results.

“Our ultimate goal is to figure out what mutations are common with this disease, and then identify whether drugs already exist that could potentially treat it,” he said. “This precision medicine strategy could be used to nominate novel, targeted therapies in lymphomas and other blinding and deadly eye diseases for which few treatments exist.”

Economic barriers

To see, your brain and eyes have to work together.

But when one eye fails to work properly with your brain, you can experience a form of vision impairment called lazy eye, which often results in the inability of one eye to focus as well as the other.

Lazy eye, or amblyopia, affects two out of every 100 children, making it the most common cause of visual impairment among kids, according to the National Eye Institute.

Early identification and treatment can help children avoid irreversible lifelong vision impairment, but U-M research suggests economic barriers prevent many children from obtaining the necessary eye care services to check for this problem.

Using claims data for nearly 900,000 U.S. children with health insurance, U-M researchers led by Dr. Joshua Stein followed a cohort for up to 14 years from birth to assess whether household net worth affects rates of eye doctor visits.

Researchers found considerably lower use of eye care services among children in less affluent families than those in more affluent ones. This disparity led to an estimated 13,000 missed diagnoses of misaligned eyes, or strabismus, which affects an estimated 4 percent of the U.S. population, and 5,000 missed diagnoses of lazy eye over a ten-year period.

“When sight-threatening eye diseases such as misaligned eyes and lazy eye go undetected early in life, the eventual diagnoses often come too late to reverse the damage done by these diseases, and the patient is saddled with suboptimal vision for life,” said Stein, Edward T. and Ellen K. Dryer Career Development Professor of Ophthalmology and Visual Sciences. “Since children in families who have no health insurance are likely to have even worse access to care than the children in our sample did, the extent to which cases are going undetected may be even greater than our study indicates.”

Children in the highest category of net worth had a 55 percent increased cumulative incidence of diagnosed lazy eye, compared with kids in the lowest category of net worth—a statistic that illustrates the disparity between the rates of eye care visits based on household net worth.

This research also emphasizes the importance of early identification and treatment of visual impairment among all children, regardless of their family’s economic situation.

“Given how important good eyesight is to strong academic performance and future employment prospects, policymakers should support mandatory preschool eye examinations as a sure way to make a positive difference in children’s lives,” Stein said.


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