The Effect of Metagenomic Sequencing on Patient Clinical Outcomes for Intraocular Infections: A Multicenter Randomized Controlled Trial.

Abstract

To determine whether the addition of an unbiased test, metagenomic sequencing of intraocular fluid, compared to standard-of-care diagnostics alone, leads to better patient outcomes in presumed infectious intraocular inflammatory eye diseases. A randomized controlled trial was conducted from May 2022 through February 2024. Eligible participants had intraocular inflammation concerning for an infectious etiology, were 18 years or older, and had vision better than no light perception (NLP). This study enrolled participants at 6 tertiary referral eye centers in the United States (5 sites) and Thailand (1 site). Participants were randomized to have their physician have access to deep sequencing results or not. The main outcomes were (1) clinical improvement on examination at 4 weeks after randomization and (2) appropriate therapy administered by the treating physician as determined by an independent expert panel. Among the 100 participants enrolled (median [IQR] age, 62.0 [47.5-71.0] years; 57 [57.0%] were women), 92 participants completed the study. Forty-one (41.0%) participants had resolution of inflammation at their 2-week follow-up and 23 (23.0%) participants had a pathogen identified with routine diagnostics and exited the study. Twenty-one (21.0%) participants met the criteria for randomization. At the primary endpoint, 8 (88.9%) patients in the metagenomic sequencing group had clinical improvement compared to 7 (63.6%) patients in the no metagenomic sequencing group (risk difference, 30% [95% CI: 0.6%-59.1%]; relative risk [RR] = 1.35 [95% CI: 1.01-1.81]; P = 0.045). Eight (88.9%) patients were considered to receive the appropriate therapy in the metagenomic sequencing group compared to 11 (100%) patients in the no metagenomic sequencing group (risk difference, -12.0% [95% CI: -38.0%-14.0%]; RR = 0.89 [95% CI: 0.68-1.15]; P = .37). There were 3 nonstudy related adverse events. Having access to metagenomic sequencing results modestly improved clinical outcomes in a subset of patients with suspected intraocular infections. Larger studies are needed to determine the long-term impact on management and clinical outcomes. https://clinicaltrials.gov/ct2/show/NCT05286203.