Association between glaucoma and risk of stroke: A systematic review and meta-analysis

Author: Wang M, Chen N, Sun BC, Guo CB, Zhang S, Huang MJ, Zhou BG, Wang XY, Huang Z.

Geographical coverage: Taiwan, Korea, and Spain.

Sector: Risk factors

Sub-sector: Stroke

Equity focus: Not explicitly stated

Study population: Patients with glaucoma

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background

Glaucoma, a major cause of irreversible blindness globally, is chronic optic neuropathy characterised by progressive retinal ganglion cell loss, optic nerve damage, and visual field deterioration. In 2020, approximately 21 million people in China had glaucoma, with a 2.93% prevalence among middle-aged and elderly populations in Europe. Due to the ageing global population, the number of glaucoma patients is expected to rise to 111.8 million by 2040. Besides its ocular effects, glaucoma has been linked to systemic conditions including vascular, endocrine, and neurological disorders. Furthermore, stroke, a leading cause of disability and mortality, is influenced by factors such as hypertension, genetic predisposition, and lifestyle choices. Recent studies have investigated the potential connection between glaucoma and stroke, but results remain inconsistent.

Objectives

To explore the association of glaucoma with the risk of stroke.

Main findings

Overall, authors found that glaucoma was associated with an increased risk of stroke.

The review included seven studies with a total of 362,267 participants. Four of these seven included studies were retrospective cohort studies, two were cross-sectional, and one was a case-control study. The studies were published between 2004 and 2017 and included a sample size ranging from 100 to 306,692 individuals. The studies were conducted in Asia (n=6) and Europe (n=1). The glaucoma subtypes studied included open-angle glaucoma (open‑angle glaucoma (OAG), n=5), normal-tension glaucoma (normal‑tension glaucoma (NTG), n=1), and neovascular glaucoma (neovascular glaucoma (NVG), n=1). Five studies were of high quality and the remaining two were of moderate quality.

The meta-analysis showed that glaucoma was associated with an increased risk of stroke (odds ratio, odds ratio (OR)=1.94, 95% confidence interval (CI): 1.45 to 2.59). Subgroup analyses by glaucoma type revealed that OAG was associated with a significant increase in stroke risk (n=5, OR=1.43, 95% CI: 1.27 to 1.61, p<0.00001). Normal-tension glaucoma exhibited the highest association (n=1, OR = 6.34, 95% CI: 4.80–8.38, p<0.00001), while neovascular glaucoma was also linked to a higher stroke risk (n=1, OR=2.07; 95% CI: 1.42 to 3.02; p=0.0002). Subgroup analyses stratified by type of stroke showed a significant positive association between glaucoma and unspecific stroke (n=5, OR=1.88; 95% CI: 1.34 to 2.66; p = 0.0003) and ischemic stroke (n=2, OR=2.20; 95% CI: 1.67 to 2.89; p<0.00001); however, no significance was observed for study with haemorrhagic stroke (n=1, OR=1.15; 95% CI: 0.35 to 3.78; p=0.82).

Methodology

Observational studies (cross-sectional, cohort study, case–control study) examining the association between glaucoma and stroke risk were included in the review authors if they reported unadjusted or adjusted effect estimates (OR, relative risk (RR), hazard ratio (HR), with 95% CI) or provided raw data for calculation, along with a clearly defined time period. Authors searched in PubMed, EMBASE, and Web of Science databases from inception to February 2022. Reference lists of the relevant articles were scanned to identify additional relevant publications. No language limits were applied. Two reviewers independently screened the potentially relevant articles against the eligibility criteria, extracted data of included studies, and assessed the study quality using the Newcastle–Ottawa Scale (NOS) for cohort and case–control studies, and the Agency for Healthcare Research and Quality (AHRQ) checklist for cross-sectional studies. Data was analysed using a random-effects model meta-analysis. Heterogeneity was assessed using the Cochrane’s Q test and I² statistic (I²). Subgroup analyses were performed according to the study design, adjustment for confounders, type of glaucoma, and stroke. The sensitivity analysis was performed by deleting each study individually to assess the quality and consistency of the results.

Applicability/external validity

Authors note that due to a lack of data on different types of glaucoma in included studies the findings should be interpreted with caution.

Geographic focus

Included studies were conducted in Taiwan, Korea, and Spain.

Summary of quality assessment

Overall, there is high confidence in the conclusions about the effects of this study.