Methodological quality of the review: Low confidence

Author: Aguinaga Ontoso I, Guillen Grima F, Aguinaga Ontoso E, Fernandez Fernandez LR

Geographical coverage: Not reported

Sector: Glaucoma

Sub-sector: Treatment

Equity focus: None specified

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background: Glaucoma is a serious disease that may cause a decrease in peripheral vision as well as blindness. Treatment of extreme levels of high intra-ocular pressure (IOP) reduces the risk of glaucoma, but the effect of treatment of mild and moderate IOP to prevent the onset of glaucoma is unknown.

Objectives: The objective of this review was to study the effect of treatment with timolol in patients with mild IOP in the prevention of glaucoma.

Main findings: In the first phase, 13 studies were selected. In most of the studies, 53% used eyes as the study unit (masked 61.5% and controls 84.6%). Timolol was the drug most frequently used. The combined effect size of all the studies of the first step was –7.55% and the weighted effect size was –11.34%.

The treatments in papers selected in the first step were not the same – some of the studies used timolol, others epinephrine, others a combination that included timolol. In the second phase, only five studies which used timolol have used randomisation were selected. The combined effect size was –6.25%, and the weighted effect size was –6.45%.

The pooled effect was computed Z by two methods: adding Zs and adding weighted Zs. The Z obtained by adding Zs had a value of 2.31120 (p = 0.017 one tail). Using the method of adding weighted Zs a value of 2.4201 (p = 0.0082 one tail) was obtained. Based on these findings, authors concluded that results show that the treatment of patients with mild and moderate IOP with timolol may help to prevent the onset of glaucoma. In addition, authors noted that longer-term studies are required to provide a better understanding of the preventative effect of timolol.

Methodology: The MEDLINE CD-ROM system in the library of the Universidad Pública de Navarra was used to search for keywords ‘glaucoma suspects’ or ‘glaucoma prevention’ from 1967 to 1995. Gray literatures were also searched for relevant articles, and abstracts of Ophthalmology Congress were also reviewed. The search was done in two phases.  Only studies to assess the effect of pharmacological treatment (non-surgical) in the prevention of glaucoma were used, and persons included in the study had an IOP lower than 30 mm Hg.

Effect size was computed for all the selected papers using the formula ES = Pt – Pc where Pt and Pc are the proportions in the treatment and control groups. In the meta-analysis, papers which used randomisation – and in which there was not a big bias and in which timolol was used – were chosen. Combined-effect size estimations and weighted combined-effect estimation were computed, as well as the pooled Z by two methods: the Stouffer’s methods of adding Zs and adding weighted Zs. In order to determine if some publication bias existed, a graphic of effect size by number of studies was drawn.

Applicability/external validity: No methods were used either to assess the applicability/external validity of the results or to discuss how generalizable the results are.

Geographic: This study focuses on all countries, though it is not clear if results from low/middle-income settings were found. However, the findings can be applicable to all settings.

Summary of quality assessment: Authors conducted a meta-analysis of the findings and appropriately reported inclusion/exclusion criteria used for study selection. However, this review had some important limitations. The authors did not avoid publication and language bias. Authors did not report methods used to select studies and to extract data of included studies, nor did they discuss the quality and risk of bias of included studies. Therefore, there is low confidence in the conclusions about the effects of this study.