Intraocular pressure fluctuation and the risk of glaucomatous damage deterioration: a Meta-analysis

Author: Guo ZZ., Chang K, Wei X.

Geographical coverage: Japan, United States (US), Sweden, Korea.

Sector: Glaucoma treatment

Sub-sector: Intraocular pressure

Equity focus: Not reported

Study population: Patients with open-angle glaucoma

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background

Glaucoma remains a leading cause of irreversible vision loss across the globe. While intraocular pressure (IOP)-lowering treatments can help delay disease progression, some individuals still experience deterioration in visual function even when their IOP appears normal. This inconsistency has prompted research into whether IOP fluctuations themselves contribute to glaucoma progression. Although some studies support the hypothesis that IOP variability is harmful, others have not confirmed this association. This meta-analysis was undertaken to address these conflicting results and provide clearer evidence on the topic.

Objectives

The primary aim of this study was to determine whether increased fluctuation in intraocular pressure is a risk factor for progression in patients with open-angle glaucoma.

Main findings

A total of fifteen longitudinal studies involving 2,637 patients and 2,211 eyes were included in the meta-analysis. The studies had follow-up durations ranging from three to eight and a half years. The pooled hazard ratio (HR) for the association between IOP fluctuation and glaucoma progression was 1.23, with a 95 percent confidence interval (CI) of 1.04 to 1.46 (p=0.02), indicating that greater IOP variability is associated with increased risk of disease progression.

Subgroup analysis showed that short-term IOP fluctuations (defined as fluctuations over 24 hours or less) were not significantly associated with glaucoma progression (HR = 0.98, 95% CI: 0.78–1.24, p = 0.89). In contrast, long-term fluctuations (greater than 24 hours) demonstrated a significant relationship with disease progression (HR = 1.43, 95% CI: 1.13–1.82, p = 0.003). A sensitivity analysis conducted by removing statistical outliers still showed a significant association, with a pooled HR of 1.10 (95% CI: 1.03–1.18, p = 0.004).

Methodology

The literature search was conducted in August 2017 using PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). No language restrictions were applied. Eligible studies included those involving patients with open-angle glaucoma that reported an association between IOP fluctuation and disease progression. Two reviewers independently screened studies against inclusion criteria and extracted relevant data, although the report did not specify the number of reviewers performing each task.

The methodological quality of included studies was assessed based on the methods used for measuring and calculating IOP fluctuation and for defining glaucoma progression, along with attention to study design, confounding control, and statistical techniques. However, the review did not use a standardised risk-of-bias tool such as the Cochrane Risk of Bias or the Newcastle-Ottawa Scale. Statistical synthesis was conducted using a random-effects meta-analysis to pool hazard ratios. Heterogeneity across studies was evaluated using the Q test and I² statistic. Publication bias was assessed using funnel plots. Subgroup analyses compared short- versus long-term IOP fluctuations, and sensitivity analysis was used to test the robustness of results by excluding outliers.

Applicability/external validity

The review’s findings suggest that long-term IOP fluctuation is an important risk factor for disease progression in open-angle glaucoma. These results underscore the need for clinicians to monitor IOP variability in addition to mean IOP. The authors also recommend future studies to further explore the effects of IOP fluctuation in both glaucoma patients and individuals without the condition.

Geographic focus

The included studies were conducted in Japan, the US, Sweden, and Korea, representing a range of healthcare systems and populations.

Summary of quality assessment

Confidence in the conclusions of the review is rated as low. The literature search, while systematic, was limited to three databases and did not include grey literature or other sources that could provide additional relevant studies. Although the authors assessed the quality of included studies, they did not use a formal risk-of-bias tool, nor did they stratify or report results based on risk-of-bias categories. The number of reviewers involved in study screening and data extraction was not clearly reported. These limitations suggest caution in interpreting the pooled results, although the consistency of findings related to long-term IOP fluctuation lends support to the observed association.