Association between Circulating Ketone Bodies and Primary Open-Angle Glaucoma and Related Ocular Parameters
In brief
Higher blood ketones nearly double glaucoma risk in large UK cohort
In the UK Biobank, participants with elevated circulating ketone bodies had almost twice the risk of developing primary open-angle glaucoma (hazard ratio ≈ 1.9) over follow-up, and they also showed higher intraocular pressure and thinner ganglion cell layers, partly independent of pressure. These findings suggest ketone levels could flag metabolic susceptibility, but causal links remain uncertain.
- Journal
- Ophthalmology science (Q1)
- Published
- 6 July 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Jianqi Chen, Zhirong Wang, Shuifeng Deng, Zhidong Li, Xiaohong Chen, Jingying Liang, et al.
- PMID
- 42568854
- DOI
- 10.1016/j.xops.2026.101313
Why clinicians should know about it
- Picked for Ophthalmology (paper of the day, 11 August 2026): Prospective cohort, ketone bodies linked to POAG risk
Abstract
OBJECTIVE: Ketone bodies are key metabolic intermediates with both neuroprotective and pro-oxidative properties; however, their role in glaucoma remains unclear. This study aimed to investigate associations between circulating ketone bodies and the incidence of primary open-angle glaucoma (POAG), as well as related ocular parameters, in the UK Biobank. DESIGN: Combined cross-sectional analysis and prospective cohort study. PARTICIPANTS: A total of 456 499 participants were included in the cohort analysis; 104 225 were included in the baseline intraocular pressure (IOP) analysis, 41 495 in the baseline ganglion cell complex (GCC) thickness analysis, and 39 498 in the IOP-adjusted GCC thickness analysis. METHODS: Circulating ketone bodies were quantified using nuclear magnetic resonance-based metabolomics. Cox proportional hazards models were used to estimate hazard ratios for POAG incidence. Linear regression models assessed associations with baseline IOP and GCC thickness. Restricted cubic spline models were applied to evaluate dose-response relationships, and subgroup analyses were conducted to explore potential effect modification. MAIN OUTCOME MEASURES: Incidence of POAG. RESULTS: During follow-up, 2330 participants developed POAG. Higher circulating ketone body levels were associated with an increased incidence of POAG after full adjustment (hazard ratio: 1.93, 95% confidence interval [CI]: 1.25-2.99, P = 0.003). Elevated ketone body levels were also associated with higher baseline IOP (β = 1.84, 95% CI: 1.57-2.10, P < 0.001) and thinner GCC both before (β = -1.62, 95% CI: -2.66 to -0.57, P = 0.002) and after IOP adjustment (β = -1.48, 95% CI: -2.53 to -0.42, P = 0.006), suggesting associations that are partially IOP-independent. CONCLUSIONS: Elevated circulating ketone body levels were associated with a higher incidence of POAG and related ocular phenotypes. Circulating ketone body levels may serve as a potential biomarker of systemic metabolic dysregulation associated with increased POAG susceptibility.Financial Disclosure(s)Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Abstract as published, via PubMed.
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