Nonocular Influencing Factors for Primary Glaucoma: An Umbrella Review of Meta-Analysis.

Introduction: Glaucoma is the main cause of irreversible blindness worldwide. Still, little is known about nonocular risk factors. We use an umbrella review to examine the meta-analytic evidence of the correlation between nonocular factors and glaucoma.

Method: We searched PubMed and Embase databases up to July 24, 2020. Eligible meta-analyses (MAs) included cohort, case-control, and randomized controlled study designs. Two authors independently extracted the data and evaluated the methodological quality of the MAs. AMSTAR 2 was used to assess the methodological quality of each included MA.

Results: This umbrella review contains 22 MAs with 22 unique nonocular factors in total. We identified 11 factors that increase the risk of glaucoma: hyperlipidemia, nocturnal dip in blood pressure, infection with Helicobacter pylori, myopia, obstructive sleep apnea syndrome, corneal properties, diabetes, hypertension, hypothyroidism, migraine, and plasma homocysteine. We identified 3 factors that reduce the risk of glaucoma: dietary intake of vitamin A, dietary intake of vitamin C, and short-term statin use. We identified 8 factors that had no association with glaucoma: dietary intake of vitamin B, dietary intake of vitamin E, cigarette smoking, Alzheimer's disease, serum folic acid, serum vitamin B6, serum vitamin B12, and serum vitamin D.

Conclusions: In this umbrella review of MAs, evidence was found for associations of various nonocular factors with glaucoma to different degrees. However, risk factors were only mildly associated, suggesting low impact of systemic risk factors. Additional higher quality studies are needed to provide robust evidence.