Thousands of retinal-disease patients in British Columbia are being exposed to an “increased risk of severe glaucoma and peripheral blindness” because toxins may be leaching into an injectable medication that is widely used in that province, a group of top eye doctors is warning.
The B.C. Society of Eye Physicians and Surgeons (BCSEPS) has taken the unusual step of hiring a lawyer to press its demand that the provincial government halt use of the injections, whose potential dangers were flagged by glaucoma specialists in an e-mail in February.
“We have given the government a deadline of May 24, 2019, to adequately address this practice, which is dangerously affecting thousands of patients on a daily basis,” the BCSEPS executive wrote in a May 16 e-mail to ophthalmologists that was obtained by The Globe and Mail.
But the B.C. government strongly disagrees with the eye doctors’ conclusion, saying provincial officials and University of British Columbia researchers spent more than a year conducting a quality review before determining the injections were safe.
“This is a really important program that is providing vision-saving treatments to 20,000 patients a year across British Columbia," said Maureen O’Donnell, the executive vice-president of clinical policy, planning and partnerships at the Provincial Health Services Authority. "It’s important that it does proceed.”
At the centre of the controversy is a drug called Avastin, one of a handful of anti-vascular endothelial growth factor, or anti-VEGF, eye injections that have revolutionized the treatment of wet, age-related macular degeneration, or WMD, once a common cause of irreversible blindness.
Avastin, however, is not Health Canada-approved to treat WMD or any other retinal disease; it is a cancer drug that is very similar to Lucentis, an approved WMD treatment that is 10 times more expensive than Avastin.
Doctors regularly prescribe Avastin, or bevacizumab, off-label for WMD because rigorous clinical trials have shown it to be as safe and effective as its pricier cousin. The main concern is that Avastin – which is sold in large vials geared toward oncology patients – has to be split, or compounded, at a pharmacy into smaller doses for eye injections, creating a risk for contamination.
“New and growing evidence suggests that a toxin is leaching from syringes containing medication that has been compounded prior to injection (compared to non-compounded anti-VEGF medication that are not left to sit in a syringe for prolonged periods after compounding)," the BCSEPS e-mail said.
The co-presidents of BCSEPS declined, through a spokeswoman, to answer any questions about the e-mail.
Catherine Birt, an ophthalmologist with Toronto’s Sunnybrook Health Sciences Centre and the president of the Canadian Glaucoma Society, said glaucoma specialists in B.C. recently began noticing an unexpected spike in severe glaucoma cases among patients treated with anti-VEGF injections.
The national group surveyed its members informally and found the problem appeared isolated to B.C., where a preliminary poll of glaucoma specialists found that between 20 per cent and 30 per cent of recent surgical glaucoma cases were among patients being treated with anti-VEGF drugs.
“Many of these glaucoma cases are advanced in nature and have resulted in surgical intervention. Even more concerning is that a significant number of cases have resulted in blindness,” a group of B.C. glaucoma specialists wrote in a Feb. 11 e-mail to the province, also obtained by The Globe.
Glaucoma specialists in Toronto, Calgary and Edmonton reported very few such cases, while their colleagues in Kingston and Halifax reported none, the e-mail said.
Dr. Birt of the Canadian Glaucoma Society said the anomalies in B.C. “cry out” for a deeper investigation.
“I don’t think it’s been proven with adequate scientific rigour yet, but the most common theory that’s coming up is that silicone particles are being released into the medication through the use of certain types of syringes, especially if [the medication] is left to sit in the syringe for a while," Dr. Birt said.
Dr. O’Donnell of B.C.'s Provincial Health Services Authority said the government conducted a thorough supply-chain review as part of its internal probe and found no evidence of silicone or other toxins leaching into compounded anti-VEGF drugs.
Over all, Dr. O’Donnell said, the province concluded that among patients who received anti-VEGF injections in B.C., the rate of glaucoma requiring surgery was up to 2.1 per cent, an acceptable risk considering anti-VEGF drugs can prevent or reverse severe vision loss.
“We’re balancing this risk of glaucoma, which would then need to be treated, with a potential loss of vision if patients didn’t receive the retinal treatment,” she said.
Nonetheless, BCSEPS in its e-mail advised ophthalmologists to prescribe the non-compounded – and substantially more expensive – alternatives to Avastin wherever possible.
That would mean a sea change: About 85 per cent of all anti-VEGF injections performed in B.C. are done using Avastin, Dr. O’Donnell said. The remaining injections are performed with another anti-VEGF drug called Eylea (14 per cent) and Lucentis (1 per cent), both of which are approved to treat WMD and come packaged in the correct dose for eye injections.
Some other provinces, including Nova Scotia, New Brunswick, Manitoba and Alberta, also cover Avastin for retinal conditions, according to the Canadian Agency for Drugs and Technologies in Health, which concluded in a 2016 review that Avastin, Lucentis and Eylea were all safe and effective for treating WMD and other retinal conditions.
But Avastin was dramatically cheaper: $3,397 for two years of injections compared with $19,364 for two years of treatment of Eylea and $39,360 for two years of treatment with Lucentis.