Ocular and Systemic Risk Factors and Biomarkers for Primary Glaucoma: An Umbrella Review of Systematic Reviews With Meta-Analyses.

Purpose: To synthesize and evaluate the quality of evidence from existing meta-analyses on ocular and systemic factors and biomarkers associated with primary glaucoma. Methods: Systematic reviews with meta-analysis evaluating ocular and systemic factors or biomarkers of glaucoma were included. Searches of PubMed, Embase, and Cochrane Library were conducted from inception to June 25, 2023, without language restrictions. Two researchers independently conducted screening, data extraction, and quality appraisal. The summary effect size, 95% confidence interval, and 95% prediction interval were estimated by random-effect models. The between-study heterogeneity (I2), evidence of small-study effects, and evidence of excess significance bias were reported. The equivalent standardized mean differences or odds ratios were calculated from original study estimates. Results: Thirty-six systematic reviews and meta-analyses were included, examining 87 factors related to ocular biometrics, lifestyle habits, diets, ocular and systemic disorders, and biomarkers from ocular imaging, serum, plasma, and aqueous humor. Three ocular factors (intraocular pressure, myopia, and corneal hysteresis) and one peripheral biomarker (total antioxidant status) were graded as highly suggestive evidence. Among the 41 factors, 8 (20%) were classified as suggestive evidence, while 3 (7%) of the 46 biomarkers received the same classification. Additionally, 29 of 54 (54%) factors and 18 of 33 (55%) biomarkers were graded as weak evidence. Conclusions: This umbrella review highlights the evidence hierarchy of various ocular and systemic risk factors and biomarkers associated with glaucoma. Further high-quality studies are essential to strengthen the evidence base.