When Connor Gronsdahl was just over three weeks old, his parents, Peggy and Kevin, noticed one of his pupils looked white under certain lighting. So they asked their family doctor about it. He took a quick look at the eye, said there was nothing to worry about.

Not long after, the couple from Assiniboia, Saskatchewan, noticed the whiteness became even more pronounced. The family’s doctor still didn’t think anything was wrong, but Peggy and Kevin called an optometrist who agreed something was odd, and said the baby needed to see a doctor. The family doctor still didn’t think anything was wrong.

The optometrist pushed and got an appointment at a hospital in Saskatoon, 330 km north of their home, but the ophthalmic resident there didn’t detect anything wrong either, Peggy Gronsdahl says. Then, Connor suddenly became quite ill, with vomiting. This triggered another visit to the hospital. This time, doctors paid attention because the baby’s cornea had clouded over, and his eye was swelling. The family travelled to Regina, where a CT scan revealed Connor had retinoblastoma (RB).

That’s when an urgent referral to the Hospital for Sick Children in Toronto happened, one of only half a dozen centres in all of Canada where there is expertise to treat these cancers, says Gronsdahl, who is also member of the Canadian Retinoblastoma Society’s board. Connor’s affected eye was removed, but he was considered at-risk for recurrence, leading to numerous trips to Toronto and more than $30,000 in out-of-pocket expenses for flights and hotels over the next nine years.

“It was obvious from the get-go that he was going to have to lose the eye. He was diagnosed June 11 [2000], we were in Toronto at the docs on the thirteenth, and he had his eye removed on the sixteenth,” Gronsdahl says.

What is retinoblastoma?

Because retinoblastoma is a rare cancer affecting about one in every 15,000 births, the Gronsdahl’s trouble getting a diagnosis isn’t uncommon. Most physicians simply aren’t familiar with the condition. But one thing eyecare specialists and doctors alike need to be alert to is parents saying “my child has this funny white look in his eye,” says Dr. Brenda Gallie from the Hospital for Sick Children. Dr. Gallie is one of the country’s few retinoblastoma specialists.

The cancer is “one-hundred percent curable,” as long as it is caught early and the tumour has not spread beyond the eye, Dr. Gallie says. Treatments can range from enucleation, to chemotherapy, to radiotherapy. There is also a variety of experimental treatments in the medical research pipeline.

As for who is at risk, she notes 50 percent of affected children have a mutated gene making them susceptible to retinoblastoma. This sometimes is inherited, and any infant who has family members with a history of retinoblastoma should be screened carefully.

Genetic testing can even be done prior to birth, so that infants with the mutation can be delivered early to treat the tumours while they are still tiny.

How do you check for retinoblastoma?

The Canadian Association of Optometrists recommends that all babies have their first eye exam before the age of six months, says Dr. Susan Leat, PhD, professor of optometry at the University of Waterloo. Screening is not just for retinoblastoma, but for a variety of eye conditions. Optometrists play an important role in detecting the disease, since they are often the first eyecare professional a baby will see.

A red flag for possible retinoblastoma is parents coming in saying they’ve noticed a white reflection in one eye in a photograph on their digital camera, instead of red eye. Retinoblastoma tends to be visible in photographs taken with a flash, but with the red-eye reduction setting turned off.

“Sometimes this ‘white eye’ can be seem without a camera and might be described as a ‘cat’s eye’ pupil. They might be concerned and bring the child in,” Dr. Leat says. Not all cases of digital-camera white eye have retinoblastoma—there can be other serious causes, so an eye examination is always warranted. Some patients are brought in because of concerns about strabismus, another possible presentation of retinoblastoma, but this presentation doesn’t happen in every case.

Optometrists are often involved in working with retinoblastoma patients after they have undergone treatment. Many have vision impairment and need low-vision rehabilitation, and need devices ranging from special spectacles, to magnifying devices, to electronic devices to optimize their remaining vision, Dr. Leat says.

New retinoblastoma treatments in the works

A variety of new approaches to treating retinoblastoma is in the research pipeline, though not yet available clinically. Researchers at the Washington University School of Medicine are testing the effectiveness of implanting a small radioactive disc or plaque into the affected eye of retinoblastoma patients. The plaque contains radioactive “seeds” on one side, and it is positioned so that the seeds beam or deliver radiation directly to the tumours.

The idea isn’t new, and has been used to treat people with ocular melanoma. For retinoblastoma, according the researchers, the idea is that the plaque would be used to treat remaining tumour cells after the main one has been removed. It would be for patients who have remaining tumour cells that have resisted chemotherapy and other treatments.

Last summer, researchers from Children’s Hospital Los Angeles announced they’d developed a new way to deliver drugs to the eye, in the form of a small silicone cup which is sealed to the outer surface of the eyeball (episclera). It is inserted under the conjunctiva to the sclera and delivers drugs slowly through passive diffusion through the sclera. It reportedly would not hinder vision.

The episcleral drug reservoir can allow continuous delivery of drugs over several weeks or months, and could be used for a variety of eye conditions. Because the drugs are administered directly to the eye, for retinoblastoma it could mean lower chemotherapy dosages, researchers say. It is, however, still a work in progress.

Another approached being tested by at researchers at Jefferson Medical College, in Philadelphia, is intra-arterial chemotherapy. Here, high doses of chemotherapy are delivery directly into the artery that leads to the affected eye. The technique was initially developed by researchers in Japan more than a decade ago. However, good-quality clinical trials demonstrating safety and efficacy have not been done, Dr. Gallie cautions.

First-ever retinoblastoma treatment guidelines

The National Retinoblastoma Strategy Canadian Guidelines for Care were published in the Canadian Journal of Ophthalmology last November. These are “the first guidelines ever in the world for the care of retinoblastoma,” says Dr. Gallie, who was on the guidelines steering committee.

The 92-page guidelines cover everything from diagnosis to treatments, genetics, risk, the role of ophthalmologists, optometrists, oncologists and other health professionals, communication between involved health professionals, as well as public awareness and information on how families should be directed to getting care, social services and support groups. (The guidelines are available on the Canadian Ophthalmological Society’s website.)

Not long after Connor was diagnosed, Gronsdahl became active with the Canadian Retinoblastoma Society, an organization that helps parents, families, retinoblastoma survivors and health professionals get information relating to the disease. It was a mix of parents and survivors talking about disparities in the healthcare system when it came to retinoblastoma that spurred on the developed of medical guidelines for the cancer, Gronsdahl says.

“We had a meeting in 2006, which brought together about 30 people, 25 percent of whom were survivors or parents of retinoblastoma children...also represented was every treatment centre, oncology, ophthalmology, genetic councillors, nurses, all the specialists involved in the care of retinoblastoma,” Gronsdahl says.

Families identified shortcomings in the system, or areas where there could be improvement by standarding of care to best practices, as well as what physicians need to do to ensure proper referral, she said. Experts who developed the guidelines included ophthalmologists, oncologists, researchers, geneticists, social works and optometrists.

“Patients and the doctors really worked collaboratively. You don’t really see that very often,” Gronsdahl says.

Dr. Gallie notes "the guidelines are already being adopted by other countries.” •