“I’ve worn glasses ever since I can remember. I’d only take them off if I was playing softball or hockey,” recalls Danny Barrett. “But I had to stop playing team sports when I was 12 or 13 because my vision got too bad. That was a big change in my life and it came at a time when it was developmentally hard, being a teenager.”

Danny Barrett, a participant in the Retinitis Pigmentosa study

Vision loss at a young age is often the reality for those afflicted with Retinitis Pigmentosa (RP), a rare degenerative eye disease that can be passed down through families. Characterized by a loss of cells in the retina – the light sensitive tissue that lines the back of the eye – symptoms typically include difficulty seeing at night and a loss of peripheral (side) vision.

People with RP tend to lose their vision slowly over time, but the type and speed of vision loss varies from person to person. It also depends on the form of the condition they have.

While some might not show symptoms until their early teens, many will say they’ve been night blind since they can remember, could never see stars in the sky, could never play spotlight. In some cases, their poor vision affected their education and their ability to reach their full potential. Some are significantly visually challenged.

Only on “The Rock”

Newfoundland and Labrador is unique because of the isolated population which results in mutations (changes in genes which everyone has) being clustered geographically. This means that genetic conditions such as RP, which are caused by mutations, are clustered in certain communities. Even in NL there are many different types of RP caused by different gene mutations.

This is where ophthalmologist and Eastern Health retina surgeon, Dr. James Whelan, comes in. He and geneticist, Dr. Jane Green, are at the helm of a natural history study that’s tracking the progress of participants who have a specific form of Retinitis Pigmentosa.

Dr. James Whelan, ophthalmologist and retina surgeon

“I was always fascinated by gene therapy, how it might be possible to switch out a defective gene with a normal gene and potentially cure someone,” says Dr. Whelan. “When I came back home in 2000 and started working with patients, other general ophthalmologists around me said they’d seen some RP patients and wondered if their condition genetically differed from that of others – and whether gene therapy could help. I thought it could.”

Several years later, Dr. Whelan saw a research paper from Sweden about a study involving patients with specific RP mutations. The retina images published in the article looked very similar to those of some of his own patients. He decided to reach out to geneticist Dr. Jane Green to see if there was any basis to his suspicion that some NL families had the same mutation, and to set up his own study.

Dr. Green had been compiling pedigrees on families in which there was a hereditary loss of sight since the 70’s and was instrumental in providing study participants.

In 1978, she had partnered with ophthalmologist Dr. Gordon Johnson, who in his own practice had noted that RP often seemed to run in families. Together, they set up a weekly ocular genetics clinic at Health Sciences Centre, or the General Hospital as it was called then. They wanted to understand what conditions caused blindness in so many Newfoundland families.

Geneticist Dr. Jane Green

Sometimes patients would tell them about family members still living in rural communities who had the same issue, so they’d hold outreach clinics in those areas. Over time, they identified groups of people who shared the same symptoms.

The clinic ran until 1986, however little was known about the gene or genes that caused Retinitis Pigmentosa, let alone potential mutations. It wasn’t until 2001 that the RLBP1 gene was identified as causing one type of RP in Sweden and also in one area of Newfoundland and Labrador.

In some cases, patients are diagnosed when they are toddlers. “At such a young age, it’s sometimes difficult for parents to realize there is an issue,” says Dr. Green. “Parents have said to me, ‘I thought she was afraid of the dark,’ or ‘he always walked with his hand on the wall,’ never realizing it was due to vision loss.”

Danny was one of those toddlers and was diagnosed when he was three, more than 45 years ago. “In my case, the first sign was night blindness. My mother told me I’d get up in the night and take off running like little kids do, and I’d run right into the wall.”

Future Plans

When Danny heard about the natural history study, he wanted in. “I’ve always loved cars and motorcycles. When I was younger and heard talk of a cure, I’d say, ‘I’m getting myself this. I’m getting myself that.’ Now it’s more about if they could find a cure, it would create independence for me. I’d just like to be able to do the little things in life that most people take for granted – like taking a moonlit walk with my wife.”

And that’s the aim of this natural history study – to garner enough evidence to follow-up with a treatment study – with the ultimate goal of providing gene therapy replacement as a potential cure for this disease.

To do that, questions about the study participants need to be answered, such as: How big a disability do they have? How progressive is the disease? What specific factors of their visual function does it affect? What is it about their disease that is changing and how can we influence that?

“We need to have measurable variables,” stresses Dr. Whelan, “which means we do extensive testing on these patients to see what changes they experience and how fast those changes occur.”

Involvement in the study is a serious commitment. Participants undergo four days of testing per year, which is broken down to two days, twice a year, not including travel time and time away from jobs, home and family.

“Testing can be quite intense,” says Nurse Coordinator Krista Rideout. “For one test in particular, patients must patch their good eye at least 12 hours before their visit, and then sit in a dark room for hours while we a perform a test that measures how the eye adjusts during low levels of illumination.”

Nurse Krista Rideout standing next to colour dome she uses during dark adaptation day testing

Through this testing, one of the things discovered about the mutation that is unique, is that these individuals have very abnormal dark adaptation. “They can’t go from light to dark,” says Dr. Whelan. “So if they’re in a bright environment for a long time, they can’t adjust to a darkened environment – it washes out their vision – which means they are essentially blinded. Even if our gene therapy just changed that for them, it would be very beneficial.”

Right now, ophthalmology, especially retinal diseases is at the forefront of gene therapy. Once they prove that gene replacement therapy works, the concept could be applied to other diseases.

“Imagine if we could identify shortly after someone is born that they have this genetic defect; that we can intervene; that we might not only prevent damage from occurring, but may be able to cure the disease,” Dr. Whelan adds. “It’s potentially life-changing.”

Despite it all, Danny never let RP get him down, or stop him from doing what he wanted to do, and that includes taking part in the study. “If I could prevent some young man or woman from going through what I’ve gone through, that would be great.” ■

This story was written by Robyn Lush, a communications specialist with Eastern Health.