The State of Genetic Testing for Glaucoma

Newswise — When Dr. Janey Wiggs gave a presentation on Genetics and Glaucoma at last summer’s Glaucoma Foundation (TGF) Symposium, she spoke about genetics as a tool we should be using hand in hand with all our other clinical tools. “Glaucoma is actually one of the most heritable of all human conditions,” she explained. “The genetics are so strong for the disease that we can capitalize on this association.”

Dr. Wiggs is a physician-scientist at the Massachusetts Eye and Ear Infirmary and Harvard Medical School. She is currently the Paul Austin Chandler Professor of Ophthalmology at Harvard Medical School.

ln September, in a TGF webinar, Dr. Wiggs spoke further about the state of genetic testing for glaucoma. “We want to find the genes we can use for genetic testing so that we can identify people who are at high risk for glaucoma early,” she said. “It’s really important to know what the disease is before it becomes manifest because nothing can be done about bringing back vision that is lost.”

Dr. Wiggs spoke about both early and adult-onset glaucoma. There are currently 12 genes that are known to cause early-onset conditions, like congenital glaucoma, which is usually present in children and caused by rare mutations in genes that have very large effects.  As a result, those mutations are transmitted in families and testing can be very important because everyone in the family who has this mutation can be identified and treatment can begin at very early stages of the disease.

Adult-onset glaucoma, the most common form, has a more complex inheritance. While more than 100 genetic variants are known, there are many more.

Testing for a single mutation doesn’t give much information. “Instead, we test a number of variants and then just calculate how many variants an individual has to determine their risk score,” Dr. Wiggs explained.

Some people are going to have a lot of those variants and they’re going to be in the 90th percentile.  Others are going to have just a few and they are going to be in the bottom of that distribution. A lot of people are in the middle.

And according to Dr. Wiggs, people with the most risk variants are the ones with the highest risk for the disease, as compared to those in the lowest distribution.

Dr. Wiggs and Dr. Louis Pasquale at Mt. Sinai in New York came up with an idea to evaluate the impact of these scores for POAG – the most common form of glaucoma–among a very large number of people from the Mass General and Brigham Biobank and also from Mt. Sinai. “We identified the people who were in the top risk and bottom risk tiers and invited them into the clinic at both hospitals for a comprehensive exam,” said Dr. Wiggs.

The striking result was that people in the high polygenic risk group were 35 percent more likely to have glaucoma compared to 10 percent in the lowest risk group.

Most exciting and important, she noted, was that 50 percent of these individuals from the high-risk group diagnosed with glaucoma were previously undiagnosed.

“It’s been extremely exciting to have this kind of progress in the last 5 or 10 years,“ says Dr. Wiggs. “For example, the fact we can identify carriers of high-impact mutations in early-onset glaucoma allows for early surveillance and treatment.  But there is still so much work to do to be able to offer comprehensive genetic testing for all of our patients.”

What is the availability of genetic testing for glaucoma?  Dr. Wiggs suggests that early-onset glaucoma patients under the age of 40 be tested. But genetic testing to ascertain high polygenic risk scores is really just coming into the clinical space. At this time “23 and Me” has a polygenic risk score test available for a fee.

She adds that the glaucoma service at Mass Eye and Ear is developing a new genetic test for its glaucoma patients that will test for the early-onset glaucoma genes and the polygenic risk score at the same time. This will eventually become part of its glaucoma service.