Aqueous Humor Metabolomics May Help Identify Glaucoma

Checking for glaucoma
Researchers believe the aqueous humor metabolics may offer a sign of disease.

Analyzing the metabolic profile of aqueous humor using nuclear magnetic resonance (NMR) spectroscopy distinguished glaucoma patients from controls with “high accuracy” in a cross-sectional study published in Experimental Eye Research.

The researchers examined if aqueous humor could be a potential molecular biomarker for glaucoma neuropathy that would offer additional options for glaucoma classification beyond intraocular pressure. They hypothesized that they’d find differences between glaucoma types, as well as in glaucoma patients and control patients, using NMR spectroscopy.

The investigators recruited 90 people and segmented them into 3 groups of 30, primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and a healthy control group. Patients were recruited when trabeculectomy, cataract surgery or a drainage implant for glaucoma patients, or cataract surgery for control patients, was proposed. Diagnosis was determined by typical glaucomatous damage on structural and functional examinations.

Researchers determined discriminant spectral regions and possible contributing metabolites between the groups. They used a 400 MHz spectrometer to achieve a 1H NMR spectra. They applied principle component analysis (PCA), machine learning algorithms, and descriptive statistics to find metabolic variance between groups and to identify the spectral regions and potential metabolites that could be glaucoma biomarkers. Using PCA, researchers found 14 regions of the NMR spectra significant in metabolic variance in the glaucoma and control groups; however, they found no differences between the POAG and NTG groups. 

The glaucoma groups had higher content in regions typical for betaine and taurine, possibly linked to neuroprotective mechanisms, and also a higher content in regions that are typical for glutamate, which can indicate damaged neurons and oxidative stress. Glutamate can be toxic to the optic nerve, although the pathophysiology behind this damage is not well understood, according to the researchers. However, the study shows, it seems to be released by damaged neurons, mediating retinal ganglion cell death by apoptosis.

“These results show how aqueous humor metabolomics based on NMR spectroscopy can distinguish glaucoma patients from controls with a high accuracy. Further studies are needed to validate these results in order to incorporate them in clinical practice,” study authors said.


Breda J, Sava A, Himmelreich U, et al. Metabolomic profiling of aqueous humor from glaucoma patients – The metabolomics in surgical ophthalmological patients (MISO) study. 2020;30(11):108268. doi: 10.1016/j.exer.2020.108268.