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Background <p>Glaucoma is a leading cause of irreversible blindness worldwide. Current diagnostic methods often fail to detect disease at early stages. MicroRNAs (miRNAs), owing to their regulatory role in gene expression, have been investigated as potential biomarkers, although their diagnostic utility and clinical feasibility remain under evaluation.</p> Objectives <p>The aim of this work is to systematically review and synthesize evidence on the diagnostic significance of microRNAs and related genetic markers in glaucoma and its subtypes.</p> Methods <p>A systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including 16 studies with 17,300 participants. Odds ratios (ORs) and log ORs with 95% confidence intervals (CIs) were pooled using fixed-effects models. Subgroup analyses were performed by sample type, glaucoma subtype, and molecular pathway.</p> Results <p>Specific miRNAs (e.g., miR-143-3p, miR-182) were significantly associated with glaucoma (OR 6.32, 95% CI 5.31–7.54, <i>p</i> &lt; 0.001). Stronger correlations were observed in aqueous humor samples (OR 13.79, 95% CI 6.81–27.94, <i>p</i> &lt; 0.001). Dysregulation of miRNAs was linked to increased retinal ganglion cell apoptosis and altered aqueous humor osmolality. Genetic analysis showed that common alleles in <i>ATOH7</i> (OR 1.55, 95% CI 1.40–1.72) and <i>CDKN2B</i> (OR 1.66, 95% CI 1.55–1.78) significantly increased glaucoma risk, while miR182 variants also showed strong associations. The autotaxin (ATX)–lysophosphatidic acid (LPA) pathway was consistently implicated (OR 3.94, 95% CI 2.46–6.32).</p> Conclusions <p>MiRNAs, particularly in blood samples, show promise as feasible biomarkers for early glaucoma detection, while aqueous-humor-based testing remains clinically limited owing to invasiveness. Genetic variants such as <i>ATOH7</i>, <i>CDKN2B</i>, and miR182 modestly but consistently contribute to glaucoma susceptibility. Large-scale longitudinal studies are warranted to validate these findings and translate them into routine clinical practice.</p>

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Can MicroRNAs Serve as Diagnostic Biomarkers for Glaucoma? A Systematic Review and Meta-analysis of Their Diagnostic Significance

  • 期刊论文

  • 发表日期：

    2025年12月26日

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  • Kai-Yang Chen,
  • Hoi-Chun Chan,
  • Chi-Ming Chan

摘要

Background

Glaucoma is a leading cause of irreversible blindness worldwide. Current diagnostic methods often fail to detect disease at early stages. MicroRNAs (miRNAs), owing to their regulatory role in gene expression, have been investigated as potential biomarkers, although their diagnostic utility and clinical feasibility remain under evaluation.

Objectives

The aim of this work is to systematically review and synthesize evidence on the diagnostic significance of microRNAs and related genetic markers in glaucoma and its subtypes.

Methods

A systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including 16 studies with 17,300 participants. Odds ratios (ORs) and log ORs with 95% confidence intervals (CIs) were pooled using fixed-effects models. Subgroup analyses were performed by sample type, glaucoma subtype, and molecular pathway.

Results

Specific miRNAs (e.g., miR-143-3p, miR-182) were significantly associated with glaucoma (OR 6.32, 95% CI 5.31–7.54, p < 0.001). Stronger correlations were observed in aqueous humor samples (OR 13.79, 95% CI 6.81–27.94, p < 0.001). Dysregulation of miRNAs was linked to increased retinal ganglion cell apoptosis and altered aqueous humor osmolality. Genetic analysis showed that common alleles in ATOH7 (OR 1.55, 95% CI 1.40–1.72) and CDKN2B (OR 1.66, 95% CI 1.55–1.78) significantly increased glaucoma risk, while miR182 variants also showed strong associations. The autotaxin (ATX)–lysophosphatidic acid (LPA) pathway was consistently implicated (OR 3.94, 95% CI 2.46–6.32).

Conclusions

MiRNAs, particularly in blood samples, show promise as feasible biomarkers for early glaucoma detection, while aqueous-humor-based testing remains clinically limited owing to invasiveness. Genetic variants such as ATOH7, CDKN2B, and miR182 modestly but consistently contribute to glaucoma susceptibility. Large-scale longitudinal studies are warranted to validate these findings and translate them into routine clinical practice.