The Multifaceted Nongenetic Risk Factors for Primary Open-angle Glaucoma: An Overview of Systematic Reviews.

Topic: A synthesis of the current knowledge on risk factors for primary open-angle glaucoma (POAG).

Clinical Relevance: This review advances understanding, guides future research, and informs strategies for preventing and treating POAG.

Method: We conducted a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant systematic reviews (SRs) published in English after 2012. The inclusion criteria focused on SRs investigating risk factors for POAG. We registered the study prospectively in the PROSPERO database (CRD42022351372) and used Covidence and the Risk of Bias in Systematic Reviews tool to manage article selection and assess the risk of bias in the included SRs. Data was extracted independently by 2 authors.

Results: After removing duplicate SRs, we assessed 2542 SRs. Of these, 2396 were determined to be irrelevant, leaving 138 for a full-text review. Following this, 78 were excluded with reasons, resulting in 60 SRs. Of these, 30 had a low risk of bias. In our bias assessment, SRs categorized as high risk of bias were characterized by 1) lack of sufficient detail in the bias assessment of the SR and 2) insufficient information or missing calculations of heterogeneity among the included studies. In our study, we identified 22 risk factors associated with POAG. The SRs covered a wide range of risk factors for POAG. Among these, the strongest associations with POAG, based on effect size, were observed in 2 SRs related to obstructive sleep apnea (OSA), with a pooled odds ratio (OR) of 3.66 (95% confidence interval [CI]: 1.70-7.90) and an adjusted OR of 2.46 (95% CI: 1.32-4.59). Similarly, 2 SRs investigating Helicobacter pylori (H. pylori) infections showed significant associations, with pooled ORs of 2.08 (95% CI: 1.48-2.93) and 2.08 (95% CI: 1.42-3.04), respectively.

Conclusion: This article summarizes the current knowledge on risk factors for POAG from published SRs. Our findings highlight the complexity of the disease and the nature of the factors that may affect various populations. Among the reported associations with low risk of bias, we found the highest effect estimates for OSA and H. pylori infections in relation to POAG. Our review helps advance understanding, guide future research, and inform strategies for the prevention and treatment of POAG.

Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.