Associations of statin use with the onset and progression of open-angle glaucoma: A systematic review and meta-analysis

Author: Yuan Y, Xiong R, Wu Y, Ha J, Wang W, Han X, He M.

Geographical coverage: The United States, Netherlands and China.

Sector: Biomedical

Sub-sector: Risk

Equity focus:  Not reported

Study population: Patients with glaucoma

Review type: Epidemiology (risk association) review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background

Glaucoma, the leading cause of irreversible blindness worldwide, is projected to rise to 111.8 million cases by 2040. Open-angle glaucoma (OAG) accounts for 60 %–90 % of cases; vascular dysfunction and neuro‑inflammation may influence its onset and progression. Statins, routinely prescribed for cardiovascular disease prevention, have attracted interest as potential neuro‑protective agents in glaucoma. Earlier studies suggested that statin use reduced the risk of OAG, but recent findings are inconsistent.

Objectives 

To assess the association between statin use and OAG onset and progression.

Main findings

Statin use is associated with a small reduction in the risk of OAG onset, but evidence for an effect on disease progression is inconclusive.

The search identified 610 articles; 14 studies were included in the review and eight in the meta‑analysis. Ten studies (515 788 participants; mean age 68.7 years; 62.3 % female) examined OAG onset, and seven (26 347 participants; mean age 67.3 years; 52.2 % female) examined progression. Twelve studies showed potential selection and confounding bias.

Meta‑analysis of eight studies (515 600 participants) found a significantly lower risk of OAG onset in statin users (pooled relative risk [RR] 0.95, 95 % confidence interval [CI] 0.93–0.98). Sensitivity analyses confirmed this inverse association. Among hyper‑lipidaemic patients, statin use remained protective (pooled RR 0.95, 95 % CI 0.93–0.98), but the association was not significant when healthy participants were included (pooled RR 0.92, 95 % CI 0.82–1.02). Findings on OAG progression were inconsistent.

Methodology 

PubMed, Embase and Web of Science were searched to 3 February 2021 for English‑language studies reporting associations between statin use and OAG onset or progression in humans. Two reviewers independently screened records, extracted data and assessed quality with the Newcastle–Ottawa Scale; disagreements were resolved by a senior reviewer. Random‑effects meta‑analysis produced pooled estimates. Trim‑and‑fill, subgroup and sensitivity analyses were undertaken. Heterogeneity was evaluated with the Q statistic and I², and publication bias with Begg and Egger tests.

Applicability / external validity

Evidence is limited and potentially confounded; well‑designed, adequately powered studies are needed to inform clinical guidance.

Geographic focus

Included studies were conducted in the United States of America, Netherlands, and China.

Summary of quality assessment

Medium confidence in the conclusions: investigators and experts were not contacted, excluded studies were not listed and results were not stratified by risk of bias.