Aqueous humour biomarker profiles in angle-closure glaucoma: systematic review and meta-analysis

To evaluate aqueous humour biomarker concentrations in patients with angle-closure glaucoma (ACG) compared to cataract controls.

A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A comprehensive literature search was conducted using Ovid MEDLINE, Embase, and the Cochrane Library from January 2000 to August 2024 to identify comparative studies assessing aqueous humour biomarkers in adult patients with ACG versus cataract controls. Biomarkers analyzed included cytokines, chemokines, growth factors, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs), among others. The primary analysis compared biomarker levels between ACG and cataract controls. Meta-analyses were performed using a random-effects model, with heterogeneity evaluated using the I² statistic.

Seventeen observational studies involving 919 eyes (500 ACG [54.4%] and 419 cataract controls [45.6%]) were included. ACG eyes had significantly elevated levels of VEGF (standard mean difference [SMD] = 2.73; 95% CI = 0.61-4.86]; p = 0.01), IL-8 (SMD = 2.87, 95% CI = 0.03-5.70; p = 0.05), MMP-2 (SMD = 1.14, 95% CI = 0.53-1.75; p = 0.0002), monocyte chemoattractant protein-1 (SMD = 1.00, 95% CI = 0.52-1.49; p < 0.0001), and TIMP-1 (SMD = 1.75, 95% CI = 0.72-2.78; p = 0.0009). Subgroup analysis revealed significantly higher tumour necrosis factor-α (SMD = 3.41, 95% CI = 0.58, 6.23; p = 0.02) and IL-6 (SMD = 2.43, 95% CI = [0.00, 4.85]; p = 0.05) levels in patients with acute primary angle closure compared to controls.

Several biomarkers were elevated in the aqueous humour of patients with ACG compared to cataract controls, providing insights into the molecular mechanisms of angle closure and elevated intraocular pressure. Future studies should focus on the potential for biomarker-driven diagnostics and longitudinal designs to further advance personalized management strategies.