TY - JOUR KW - Uveitis KW - clinical outcomes KW - deep sequencing AU - Jessica Shantha AU - Kareem Moussa AU - Wipada Laovirojjanakul AU - Steven Yeh AU - Edmund Tsui AU - Judy Chen AU - Albert Vitale AU - Akbar Shakoor AU - Marissa Larochelle AU - Katherine Niemeyer AU - Akshay Mentreddy AU - Itamar Livnat AU - Myra Safo AU - Wendy Ao AU - Charlene Choo AU - Daisy Yan AU - Lina Zhong AU - Cindi Chen AU - Kirsten Da Silva AU - Amit Reddy AU - Jennifer Lee AU - Amol Sura AU - Eric Crowell AU - Ying Qian AU - Yael Sharon AU - Armin Hinterwirth AU - Travis Porco AU - Benjamin Arnold AU - John Gonzales AU - Nisha Acharya AU - Thomas Lietman AU - Thuy Doan AU - OPTICS Group AB -

OBJECTIVE: 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.

DESIGN: A randomized controlled trial was conducted from May 2022 through February 2024.

PARTICIPANTS: 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).

INTERVENTIONS: Participants were randomized to have their physicians have access to deep sequencing results or not.

MAIN OUTCOMES AND MEASURES: 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.

RESULTS: 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% to 59.1%]; relative risk (RR)=1.35 [95% CI: 1.01 to 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% to 14.0%]; RR= 0.89 [95% CI: 0.68 to 1.15]; P=0.37). There were 3 non-study related adverse events.

CONCLUSIONS: 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.

TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT05286203.

BT - American journal of ophthalmology C1 - https://www.ncbi.nlm.nih.gov/pubmed/40653257 DA - 07/2025 DO - 10.1016/j.ajo.2025.07.003 J2 - Am J Ophthalmol LA - eng N2 -

OBJECTIVE: 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.

DESIGN: A randomized controlled trial was conducted from May 2022 through February 2024.

PARTICIPANTS: 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).

INTERVENTIONS: Participants were randomized to have their physicians have access to deep sequencing results or not.

MAIN OUTCOMES AND MEASURES: 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.

RESULTS: 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% to 59.1%]; relative risk (RR)=1.35 [95% CI: 1.01 to 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% to 14.0%]; RR= 0.89 [95% CI: 0.68 to 1.15]; P=0.37). There were 3 non-study related adverse events.

CONCLUSIONS: 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.

TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT05286203.

PY - 2025 T2 - American journal of ophthalmology TI - The Effect of Metagenomic Sequencing on Patient Clinical Outcomes for Intraocular Infections: A Multicenter Randomized Controlled Trial. SN - 1879-1891 ER -