Methodological quality of the review: High confidence

Author: Akbari M, Akbari S, Pasquale LR

Geographical coverage: Not reported

Sector: Glaucoma

Sub-sector: Mortality

Equity focus: None specified

Review type: Other review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background: Primary open angle glaucoma (POAG) is a multifactorial, chronic, progressive disease that results in damaged structural integrity of the optic nerve and diminished visual function. Understanding the relationship between POAG and mortality is critical, with an estimated 44.7 million people affected worldwide by the year 2010. If true mortality rates in patients with POAG differ from those of the general population, this information may provide insight into the underlying disease etiology.

Objectives: To conduct a meta-analysis to estimate the relationship between primary open angle glaucoma (POAG) and mortality.

Main findings: A total of nine studies were included in the review. One study was a population-based, annual, cross-sectional study, while the others were prospective cohorts. The mean time follow-up ranged from 4.5 to 16 years. Collectively, the sample size was 146,848, with 2811 classified as having POAG. Criteria used for POAG and mortality assessment varied between studies.

A significant risk was not detected in the final pooled analysis (RR, 1.13; 95% confidence interval [CI], 0.97-1.31) for all-cause mortality. A meta-regression across mean follow-up time, age, and sex was not significant. A meta-regression across diabetes status in three of the nine studies did not demonstrate significant results (P=.94). Sub-group analysis on cardiovascular mortality from four of the nine studies was marginally significant (RR, 1.20; 95% CI, 1.00-1.43; P=.05), but insignificant after removal of a study in which POAG was ascertained by self and proxy report (RR, 1.12; 95% CI, 0.87-1.46).

Authors note that this meta-analysis does not demonstrate an association between POAG and all-cause or cardiovascular mortality. A Q test for heterogeneity was significant in the primary analysis (P= .04), but insignificant for the secondary analysis (P= .41). The I² statistic failed to show significant heterogeneity in both primary and secondary analyses.

Methodology: Studies were included if they:

(a) Reported POAG or IOP status

(b) Excluded secondary glaucoma

(c) Reported all-cause mortality relative risks (RR) with 95% confidence intervals (CI)

(d) Included a control group

(e) Were written in English

Two authors independently conducted searches on the PUBMED, EMBASE and Web of Science databases without date restrictions. A combination of text words and Medical Subject Headings of the National Library of Medicine or subject headings was used in the database search. The titles of all articles were read and the relevant abstracts evaluated. The bibliographies were reviewed, manual searches were conducted and authors were contacted for further potentially relevant studies.

Study quality was assessed using the suggested framework from another publication. Variables examined included adequate explanation of study sampling and diagnostic criteria for POAG, outcome results for high proportion of the population, and appropriate statistical adjustment of the outcome. Two reviewers independently extracted data on included studies including: study reference details, methods and patient characteristics.

Authors used the Q test to evaluate study heterogeneity and the I² statistic to estimate the proportion of total variability of the pooled estimate due to between-study variation. Pooled estimates used a random-effects model. Additionally, authors performed a meta-regression to assess heterogeneity in the length of follow-up age, sex, age and diabetes status across studies. In a sub-group analysis, authors assessed the relationship between POAG and cardiovascular mortality using four studies in which data were available. A sensitivity analysis was performed to assess the robustness of the pooled estimates of all-cause and cardiovascular mortality.

Applicability/external validity: Authors note excluding studies limited to non-generalizable patients and including studies reporting an adequate explanation of study sampling. Studies included in the meta-analysis were conducted in a population of African descendent, Asians and European descendants.

Geographic focus: Authors did not report the geographical location of studies included in the review.

Summary of quality assessment: Overall, there is high confidence in the conclusions about the effects of this review. Authors used appropriate methods to pool data for analyses and appropriately discussed and acknowledged heterogeneity across included studies. However, minor limitations were identified. Authors excluded studies written in languages other than English, however it was noted that abstracts were not available to determine its eligibility for inclusion. Authors appropriately discussed limitations of the review and did not draw strong policy conclusions.