Study Finds Ketone Body Levels a Potential Biomarker for POAG Incidence

This graph from the study shows levels of circulating ketone bodies in relation to GCC thickness. While the observed differences in thickness were modest in absolute magnitude and may have limited clinical significance at the individual patient level, the researchers noted that they may nevertheless reflect subtle neurodegenerative changes of significance at the population level. Photo: Chen J, et al. Ophthalmol Sci. July 6, 2026. Click image to enlarge. Ketone bodies have attracted increasing attention from researchers as key intermediates of systemic metabolism. Ketones are increasingly recognized not only as alternative energy substrates but also as signaling metabolites involved in cellular regulation. Many studies are currently investigating these metabolites’ levels for neuroprotective properties in ocular conditions like glaucoma; nevertheless, evidence linking ketone metabolism to primary open-angle glaucoma (POAG) remains inconsistent.In a study recently published in Ophthalmology Science, researchers from China carried out a large population-based cohort study from the UK Biobank and found that higher circulating ketone body levels were associated with an increased POAG incidence. Elevated ketone body levels were also associated with higher baseline intraocular pressure (IOP) and lower ganglion cell complex (GCC) thickness. This association with GCC thickness remained significant after additional adjustment for IOP, which suggests that circulating ketone body levels may serve as a biomarker of biological processes related to retinal neurodegeneration beyond IOP-related pathways.“Given that POAG represents a downstream clinical endpoint that develops following cumulative structural and functional changes, whereas elevated IOP and GCC thinning are earlier disease-related phenotypes, these findings may indicate that circulating ketone body levels are more directly associated with early glaucoma-related alterations than with clinically detectable POAG itself,” the study authors wrote in their paper.A total of 456,499 participants were included in the cohort analysis; 104,225 were included in the baseline IOP analysis, 41,495 in the baseline GCC thickness analysis and 39,498 in the IOP-adjusted GCC thickness analysis. During follow-up, 2,330 participants developed POAG.Higher circulating ketone body levels were associated with an increased incidence of POAG after full adjustment (hazard ratio: 1.93). Elevated ketone body levels were also associated with higher baseline IOP and thinner GCC both before and after IOP adjustment, which suggested that associations that were partially IOP-independent.The UK Biobank data did not allow the researchers to distinguish the underlying causes of these associations in detail. Consequently, their observations should be interpreted as relating to circulating ketone body levels themselves rather than to any specific source of ketosis. Furthermore, elevated circulating ketone body levels may, at least in part, reflect broader systemic metabolic dysregulation rather than an isolated biological exposure. Therefore, the present findings should be interpreted as evidence of an epidemiological association rather than proof of a causal role of ketone body metabolism in POAG development.“Consequently, we were unable to evaluate within-individual changes in ketone body levels over time or examine whether longitudinal variations in ketone body levels are associated with subsequent POAG incidence,” the research team concluded. “Future research with repeated assessments of ketone bodies will be important to determine whether temporal patterns of ketone metabolism provide additional value for risk prediction.”Click here for the journal source. Chen J, Wang Z, Deng S, et al. Association between circulating ketone bodies and primary open-angle glaucoma and related ocular parameters. Ophthalmol Sci. July 6, 2026. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.