Evidence of stroke in glaucoma patients

Author: Malvankar-Mehta MS, Rahman M, Suri A, Hutnik CM.

Geographical coverage: Not reported

Sector: Glaucoma

Sub–sector: Stroke

Equity focus: Not explicitly stated

Study population: Patients with mild to moderate glaucoma

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background

Glaucoma is a progressive optic neuropathy and the second leading cause of vision loss worldwide. It affected an estimated 67 million people in 2010 and its prevalence rose to about 80 million by 2020, with numbers continuing to climb. The economic burden is considerable; in the United States alone, direct medical costs for glaucoma management exceed US$2.9 billion each year. Although available treatments can slow disease progression, glaucoma often still leads to sight loss because it is frequently diagnosed late and public awareness remains low. Beyond its ocular consequences, glaucoma has been linked to systemic vascular conditions, particularly cardiovascular disease and stroke. Some studies suggest that shared mechanisms of vascular dysregulation mean people with glaucoma may be at greater risk of stroke. However, individual study findings have been inconsistent, varying in sample size, methodology and reported outcomes. This review therefore sought to clarify the evidence on the association between glaucoma and the risk of stroke.

Objectives

To evaluate whether adults with glaucoma are at increased risk of stroke compared with those without glaucoma, by synthesising the available quantitative evidence.

Main findings

Nine studies involving 376 650 participants met the inclusion criteria: seven cohort studies and two cross‑sectional studies. Eight were judged to be of fair methodological quality and one of poor quality. Meta‑analysis showed a statistically significant increase in the hazard of stroke for several glaucoma sub‑types: open‑angle glaucoma—hazard ratio (HR) 1.36 (95 % confidence interval, CI 1.08 to 1.71); normal‑tension glaucoma—HR 6.34 (95 % CI 4.80 to 8.38); and neovascular glaucoma—HR 2.07 (95 % CI 1.41 to 3.03). Overall, people with glaucoma had more than twice the hazard of stroke (pooled HR 2.19, 95 % CI 1.28 to 3.86). Pooled estimates also indicated increased odds of stroke—odds ratio (OR) 1.37 (95 % CI 1.32 to 1.43)—and an elevated relative risk (RR) 2.10 (95 % CI 1.64 to 2.68).

Methodology

Eligible studies enrolled adults with mild to moderate glaucoma and included randomised controlled trials, clinical or comparative studies, multicentre studies, observational designs, systematic reviews, meta‑analyses and case series published in English. MEDLINE In‑Process & Other Non‑Indexed Citations, MEDLINE Daily, MEDLINE, Embase and the Cochrane Library were searched from inception to 30 June 2023, with monthly auto‑alerts to capture new records. Supplementary searches covered the Health Economic Evaluation Database, Web of Science, ProQuest Dissertations and Theses, the Canadian Health Research Collection and conference abstracts from major ophthalmology societies. Grey literature and reference lists of included articles were hand‑searched, and subject experts were contacted for additional studies. Two reviewers independently screened records, extracted data and assessed methodological quality using the modified Downs and Black checklist; disagreements were resolved by discussion or adjudication by a third reviewer. Random‑effects meta‑analysis was performed. Heterogeneity was explored using the χ² test, the I² statistic and Z‑values, and publication bias was assessed visually with a funnel plot.

Applicability / external validity

Included studies were conducted in varied healthcare settings and populations, and definitions of glaucoma, study methods and participant characteristics differed. These factors limit the direct generalisability of the pooled estimates, but the findings are likely to be applicable to regions with similar healthcare systems and patient demographics.

Geographic focus

The geographic origin of the included studies was not reported.

Summary of quality assessment

Confidence in the pooled effect estimates is limited by several methodological concerns. The search was restricted to English‑language publications and no list of excluded studies was provided, raising the possibility of publication bias. Although two reviewers independently carried out study selection, data extraction and quality appraisal using a validated checklist, the authors did not present results stratified by risk of bias. Variation in study design, outcome definitions and glaucoma classification contributed to substantial heterogeneity (I² values were high for several analyses). These issues mean that, overall, the strength of evidence is considered low and the true effect may differ from the pooled estimates.