Quantifying the effect of intraocular pressure reduction on the occurrence of glaucoma
Methodological quality of the review: High confidence
Author: Peeters A, Webers CA, Prins MH, Zeegers MP, Hendrikse F, Schouten JS.
Geographical coverage: Not reported
Sector: Glaucoma
Sub-sector: Glaucoma treatment
Equity focus: Not specified.
Review type: Effectiveness review
Quantitative synthesis method: Meta-analysis
Qualitative synthesis method: Not applicable
Background: High intraocular pressure (IOP) is an important risk factor for glaucoma progression in patients with ocular hypertension (OH) and is a prognostic factor in patients with primary open-angle glaucoma (POAG). There are three ways to reduce IOP (medication, laser treatment and surgery). Therefore, it is of interest to investigate to what extent a larger IOP reduction in OH patients influences the risk of conversion to glaucoma.
Objectives: To estimate the effect of reducing IOP on: (i) the incidence of POAG in patients with OH, and (ii) the progression of glaucoma.
Main findings: One line summary: The results showed that OH therapy reduces the risk of conversion to glaucoma. This risk reduction increases with greater IOP reduction
In this review, nine OH and one POAG trials were identified. As only one trial was identified for POAG, a meta-analysis was not performed. Results from the OH trials were pooled in a meta-analysis. Five OH trials had a score above 10 on quality assessment (maximum score was 16). Authors noted that there was no indication of significant heterogeneity or publication bias within the review. Review authors stated that all studies on OH showed a positive effect of IOP reduction by glaucoma medication on reduction of the incidence of glaucoma. The meta-analysis of OH trials gave a pooled RR of 0.61 [95% confidence interval (CI) 0.45–0.83]. Meta-regression showed a decrease of the RR of glaucoma conversion by 14% with each mmHg extra IOP reduction (P = 0.045). Authors noted that the inclusion of a hypothetical study showing no treatment effect in the meta-analysis did not change its conclusions. Overall, authors concluded that the results showed that OH therapy reduces the risk of conversion to glaucoma. This risk reduction increases with greater IOP reduction.
Methodology: The following databases were used Medline and Embase and the Cochrane Register of Controlled Trials to identify trials with: a randomized comparison of IOP-lowering intervention versus placebo or no treatment; visual field loss or optic disc changes as outcome; and follow-up >6 months. Studies written in languages other than English, French, Dutch and German were excluded. Subsequently, the reference lists of the selected articles and of two meta-analysis articles were consulted until no further studies were identified. Two authors independently screened studies for inclusion against criteria, assessed methodological quality of studies. Methodological quality of included studies was evaluated using criteria recommended by Delphi list, Cochrane Collaboration, as well as criteria added by the authors. It is not clear from the review if two authors independently extracted data of included studies.
A meta-analysis of relevant randomized controlled trials (RCTs) was conducted. A pooled relative risk (RR) was calculated by a random effects model. Risk reduction of glaucoma conversion per mmHg of IOP reduction was quantified in a meta-regression model. Heterogeneity was assessed by judging the forest plot and by the Q-test and I2 statistic. To examine publication bias, authors used Egger’s measure of publication bias. In addition, authors conducted a sensitivity analysis to examine the robustness of the findings to different assumptions, and also examined the impact of the exclusion of poorer quality on the outcome of the meta-analysis.
Applicability/external validity: Authors noted that findings from this review as well as the literature search are consistent to on other meta-analysis published recently at the time. In addition, authors mentioned that the trial interventions were limited to the use of topical medication. As expected, surgery or laser treatment was not included in any of the trials because it is not a primary treatment option for OH.
Geographic focus: It is not clear from the review countries included in the review.
Summary of quality assessment: There was high confidence in conclusions about the effects of this review as a minor limitation was identified. Although authors restricted language to English, French, German and Dutch, this systematic review was based on comprehensive searches. Methods used to screen studies for eligibility, extract data and quality assess included studies were appropriately conducted, minimizing risk of bias.
