Metagenomics test saves woman’s sight after mystery infection

A 29-year-old doctor from Bristol has had her eyesight saved after a “game-changing” test identified a mystery infection that had plagued her health for five years.

Ellie Irwin suffered persistent inflammation in her right eye resulting in blurred vision and underwent intensive treatment to no avail. At one point she even considered having her eye removed.

It was only after Ellie was offered a “last resort” analysis called metagenomics, that she was diagnosed with a rare bacterial infection which was cured with antibiotics.

“It’s been transformative,” Ellie told the BBC. “I feel so fortunate.”

Professor Carlos Pavesio, consultant ophthalmologist at Moorfields Eye Hospital in London, says Ellie’s case is a “breakthrough in the diagnosis of infectious diseases”.

“There are many patients we treat with chronic infections for years, but despite multiple tests we cannot identify the bug responsible,” he says.

In 2019, while still at medical school, Ellie began suffering from inflammation in her right eye. All tests for infection came back negative and it was assumed she had an autoimmune condition.

Ellie was prescribed steroid eye drops and immunosuppressants, some of which needed to be given by intravenous infusion.

“It was completely dominating my life,” Ellie says. “I needed eye drops every single hour and it was difficult to balance that alongside starting work as a junior doctor. My vision was really variable, and I would have some bad days.

“I was on so much medication and going to so many appointments, yet I didn’t feel I was getting any better.”

The treatment and inflammation led to Ellie developing a cataract that had to be surgically removed, just after she graduated from medical school.

Ellie says she eventually reached “breaking point”, and even began considering having her affected eye removed.

“Whilst losing sight in one eye is terrifying,” she says, “my biggest fear was that it might spread to my left eye.”

It was one of Ellie’s doctors at Southmead Hospital in Bristol who suggested metagenomics – a last resort test not generally available to patients and only used where standard diagnostic tools have failed to identify or rule out infection.

Metagenomics technology uses cutting-edge genomic sequencing, which can identify all bacteria, funghi or parasites present in a sample by comparing them against a database of millions of pathogens.

A team at Moorfields Eye Hospital arranged for a sample of fluid to be taken from inside Ellie’s eye and sent to the metagenomics labs at Great Ormond Street Hospital (GOSH) – the only lab in the UK officially recognised to carry out these diagnostic tests for patients, and one of only a few in the world.

Currently, the standard method for detecting bacterial infections is by trying to grow a sample of it in a Petri dish.

For viruses, the most common diagnostic tool is a PCR test. These will be familiar to many from the pandemic, when millions sent off swabs in the post to confirm whether they had Covid.

However, Dr Julianne Brown, principal clinical scientist at the GOSH metagenomics service, says PCR has some drawbacks.

“The trouble with PCR is that you have to think of the viruses that might be causing an infection and do a separate test for each and every one,” she says. “So if you’ve got an infection with something that’s unexpected, rare or not previously known, you won’t find it.”

Dr Brown says metagenomics is “an enormous step up – it’s a complete game-changer”.

In Ellie’s case, metagenomics diagnosed a rare strain of the bacterial infection leptospirosis found in South America.

It is now presumed Ellie picked up the bug swimming in the Amazon river in 2018, while on a trip to Ecuador and Colombia.

Ellie says it was an emotional moment when she was given the results of the test.

“I broke down – I just had to cry. I never imagined that it would come back positive and be for something that was treatable,” she says.

“I was given three weeks of antibiotics and within days my vision was clearer and the inflammation subsided.”

A single metagenomics test costs around £1,300, which is far more than standard diagnostics. However, as the technology is developed that price is likely to fall rapidly.

Virologist Professor Judy Breuer, who has been developing metagenomics at GOSH and University College London (UCL) for more than a decade, says her team currently receives three or four samples a week from hospitals around the UK for metagenomic testing in addition to those it carries out on its own patients.

These are often samples from parts of the body that are normally sterile sites, where bacteria are not usually found such as the brain, central nervous system, liver and eye.

“In the future, we think metagenomics will become a first line test and be able to diagnose infection in any sample, probably within the same day,” she says.

It’s also likely to become faster, cheaper and easier to do, explains Dr Brown, meaning it will become available to more patients rather than just a small number who are severely unwell.

Resolving her eye problems has allowed Ellie to concentrate on her training as a GP and arrange her wedding.

Ellie was married in Newcastle on 29 March, the same day the city celebrated Newcastle United’s win in the Carabao Cup.

She says: “We got a shout-out from Ant and Dec and went up on a scissor lift above the Newcastle United fans, which was incredible.”

Prof Breuer says she is thrilled with how the treatment is changing lives.

“It is amazing to see the impact it is having for patients like Ellie.”