Metagenomics solves uveitis mystery

A UK patient’s debilitating case of uveitis, whose cause had baffled doctors for four years, was finally resolved using metagenomics – the study of all genetic material from all organisms in a sample.

Ellie Irwin first noted symptoms of uveitis in one eye in 2019, but by 2020 her condition had worsened and she was referred to Moorfields Eye Hospital. “I was on increasing amounts of medications to dampen down my immune system; however, the inflammation persisted. From 2022 I was on hourly steroid drops, among many other oral medications, and a monthly infusion; I was increasingly losing hope.”

By the end of 2023, Irwin said she was at the point of asking to have her eye removed. “All that was stopping me was the fear that it could start affecting my other eye. My condition occupied my thoughts almost every waking hour and it felt truly inescapable.”

Although the unilateral nature of the infection led Moorfields’ ophthalmologist Professor Carlos Pavesio to strongly suspect an infection, all available tests for this had returned negative. His colleague, Dr Colin Chu, suggested they try Great Ormond Street Hospital (GOSH)’s new metagenomics service, which uses cutting-edge genomic sequencing to identify all the bacteria and viruses present in a patient’s sample. It had never been used before in the UK for ophthalmology but, working with the GOSH team, Prof Pavesio identified the cause of Irwin’s symptoms as bacterial leptospirosis – specifically a strain endemic to South America, where Irwin had been travelling in 2019.

Within a month of antibiotic treatment, Irwin was free of symptoms. “I am now off my infusion and all my oral medications, needing only one eye drop a day, which has completely changed my life,” she said. “I got married a few weeks ago and was able to enjoy the day without thinking about my eye, something I never imagined possible just a few months before.”