Metabolomics in glaucoma: A systematic review

Author: Wang Y, Hou XW, Liang G, Pan CW.

Geographical coverage: United States of America (USA), China, France, Japan, Italy, Belgium, Australia, Spain, and the Netherlands.

Sector: Service delivery

Sub–sector: Screening, diagnosis, detection

Equity focus:  Not reported

Study population: Patients with glaucoma

Review type: Effectiveness review

Quantitative synthesis method: Pathway enrichment analysis

Qualitative synthesis method: Not applicable

Background 

Glaucoma is a leading cause of irreversible blindness, accounting for about 12 % of cases worldwide. It affects an estimated 3.54 % of adults aged 40–80 years, and prevalence is projected to reach 111.8 million by 2040. Because the disease is usually asymptomatic until the late stages, early diagnosis is challenging. Metabolomics – the study of small‑molecule metabolic by‑products – could help to identify early biomarkers and therapeutic targets, but published studies are limited by small samples, lack of validation and heterogeneous analytical techniques.

Objectives 

To summarise metabolic profiles reported in glaucoma and to identify metabolites and biochemical pathways consistently associated with the disease.

Main findings

Metabolomics shows promise for identifying biomarkers and clarifying metabolic pathways in open‑angle glaucoma (OAG).

The search retrieved 698 records, of which 18 case–control studies (sample sizes 19–506) met the inclusion criteria. Seven amino‑acid metabolites (arginine, glycine, alanine, lysine, methionine, phenylalanine, tyrosine), two phosphatidylcholines (PC aa C34:2, PC aa C36:4) and eight complementary metabolites (acetyl‑carnitine, propionyl‑carnitine, butyryl‑carnitine, carnitine, glutamine, hypoxanthine, spermine, spermidine) were repeatedly linked to OAG. Pathway‑enrichment analysis highlighted amino‑acid metabolism as central to disease pathophysiology and revealed sample‑dependent metabolic signatures.

Methodology 

PubMed and Web of Science were searched to 11 November 2020 for English‑language metabolomic studies that assessed glaucoma biomarkers using mass‑spectrometry‑ or nuclear‑magnetic‑resonance‑based approaches. Reference lists were scanned for additional studies. Two reviewers independently screened records, extracted data and assessed quality using the QUADOMICS tool (an adaptation of the Quality Assessment of Diagnostic Accuracy Studies tool for ‘omics’ research). Findings were synthesised descriptively, and pathway‑enrichment and topology analyses provided an overview of metabolic signatures.

Applicability / external validity

Interpretation is limited by variability in metabolite‑identification methods, a focus on OAG (with little evidence on other glaucoma types) and the absence of quantitative validation. Larger prospective studies covering diverse glaucoma subtypes are required.

Geographic focus

The included were conducted in the United States of America, China, France, Japan, Italy, Belgium, Australia, Spain, and the Netherlands.

Summary of quality assessment 

The authors did not contact study investigators, supply a list of excluded studies or state how many reviewers extracted data, and several sections used biased language.