| Title: | Plasma metabolomic associations with incident rhegmatogenous retinal detachment in UK Biobank |
| Journal: | Ophthalmology Science |
| Published: | 1 Apr 2026 |
| DOI: | https://doi.org/10.1016/j.xops.2026.101195 |
| URL: | https://www.ophthalmologyscience.org/article/S2666-9145(26)00133-8/pdf |
Publication 18132
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Objective To investigate the associations of plasma metabolites with incident rhegmatogenous retinal detachment (RRD). Design Prospective cohort study. Subjects 213,173 UK Biobank participants. Methods Plasma metabolomics were quantified using the Nightingale Health platform based on proton nuclear magnetic resonance (1H-NMR) spectroscopy, covering 251 metabolites. Associations with incident RRD were assessed using Cox proportional hazards models and restricted cubic splines. Two-sample Mendelian randomization (MR) analyses were conducted to assess whether genetically predicted metabolite levels showed patterns consistent with the observational associations. A metabolomic risk score (MRS) was constructed based on significant metabolites to evaluate their combined effects on RRD. Principal component analysis (PCA) was used to test whether the metabolite profiles improved RRD risk prediction. Main Outcome Measures Incident RRD, defined as the first recorded diagnosis during follow-up. Results Over a median follow-up of 11.10 years, 1,111 participants developed RRD. Seventeen metabolites were significantly associated with RRD after false discovery rate correction (P FDR < 0.05), including eleven HDL-associated metabolites, four fatty acids, one VLDL-associated metabolite, and creatinine. Among them, omega-3, docosahexaenoic acid (DHA), and 11 HDL-associated metabolites were inversely associated with RRD, whereas monounsaturated fatty acids to total fatty acids, creatinine, and free cholesterol to total lipids in large VLDL showed positive associations. MR analyses provided supportive genetic evidence consistent with the inverse associations for omega-3, DHA, phospholipids in very large HDL, and total lipids in large HDL. Compared with participants in the low MRS group, those with high MRS had a significantly higher risk (HR = 1.608, 95% CI: 1.187-2.178, P = 0.002). However, the RRD-associated metabolites did not materially improve model discrimination (C-index 0.694-0.697 across models). Conclusions This study identified 17 plasma metabolites associated with RRD risk, particularly omega-3 and HDL-related lipids. Although metabolomics did not improve risk prediction, these findings provide exploratory evidence of systemic metabolic patterns associated with RRD risk.</p>
11 Authors
- Yuelan Gao
- Jianming Xu
- Jun Yu
- Yuzhou Zhang
- Mary Ho
- Ka Wai Kam
- Alvin L. Young
- Chi Pui Pang
- Clement C. Tham
- Jason C. Yam
- Li Jia Chen
1 Application
| Application ID | Title |
|---|---|
| 91320 | Effect of diet and diet-gene on ocular diseases |
Enabling scientific discoveries that improve human health