Move Out of the Tunnel… and into the Light!

I believe metabolomics has the potential to shed light into the pathophysiology behind glaucomatous damage, as well as providing potential biomarkers for early glaucoma detection. Metabolomics is the detailed study of metabolites created by the cellular processes in an organism. Influenced by both genetic and environmental factors, the metabolite profile gives us a “fingerprint” of the health status of the organism at the time of sampling. But aside from disease mechanisms and biomarkers, this technology has also been increasingly used for drug target discovery and the prediction of drug effects – and it can help move medical care towards a more personalized approach.

For all of these reasons, metabolomics is becoming widely used across different fields, from cancer research to obstetrics and, of course, ophthalmology – where it keeps proving its value. A recent paper has shown the potential of metabolomics for the diagnosis of age-related macular degeneration (AMD); both the presence and stages of the disease could be distinguished by identifying differences in metabolic profiles in controls and patients with AMD (1). Glaucoma (the leading world cause of irreversible blindness [2]) is also a good candidate for metabolomic analysis, which has the potential to break knowledge barriers, driving us towards new treatments and personalized care. Our research group, led by Ingeborg Stalmans, recently reviewed results that have already been delivered by metabolomics in terms of understanding the pathophysiological processes of glaucoma in a clinical setting (3). Only one metabolome-wide study for glaucoma has been published to date; it identified significant metabolic differences in blood plasma samples from patients with primary open-angle glaucoma (POAG) and samples from healthy controls (4).

We feel that we can push this research a step further, so we are collecting blood, urine and aqueous humor samples from patients with POAG who are undergoing surgery (MISO Study; NCT03098316). All samples will be analyzed using two complementary metabolomics techniques (mass spectrometry and nuclear magnetic resonance spectroscopy) and compared with control samples (from patients with cataract and no other eye disease). As metabolomics provides an overview of whole body metabolism, we are also including a study group of patients with normal-tension glaucoma (NTG), since systemic vascular dysregulation is thought to play an important role in the pathogenesis in this group of patients. In my view, metabolomics will help bring glaucoma care into a new era by reducing the numbers of patients arriving in our office already at an advanced stage of disease, and by revealing new research paths that can be used to develop new drugs and improve ophthalmic care.