Medical interventions for primary open angle glaucoma and ocular hypertension

Ocular hypertension (OHT) is a condition with raised intraocular pressure (IOP) without visual field changes or discernible pathology of the optic nerve head. Ocular hypertension with IOP above 21 mmHg untreated is a major risk factor for development of primary open angle glaucoma, which is progressive nerve fibre loss and damage to the optic disc so that the visual field develops characteristic defects. Topical medications are given to reduce the IOP as a way of preventing the onset or progression of damage and associated visual field loss. These medications may have local and systemic side effects that may be severe enough for the treatment to be stopped and include local irritation, drowsiness, shortage of breath and cardiovascular side effects, particularly in the elderly. The results of this review support the current practice of topical medication to lower IOP and clearly demonstrate a visual field protective effect. The review authors identified a total of 26 controlled trials that randomised 4979 people with OHT or open angle glaucoma to receive topical medication or a placebo, another topical medication or no treatment for at least a year. Meta-analysis of 10 trials testing different topical medications against placebo or untreated controls showed reduced incidence of glaucomatous visual field defects with treatment for people with OHT. The odds ratio (OR) was 0.62 (range 0.5 to 0.8). The class of beta-blockers (including timolol) had positive but weak evidence for a beneficial effect in protecting against visual field defects (OR 0.7, range 0.5 to 1.0). No single drug showed significant visual field protection in OHT with the evidence available. Medications included beta-blockers, dorzolamide, brimonidine, pilocarpine and epinephrine. From the reports, the majority of trials were of low methodological quality. Local and systemic side effects leading to treatment being stopped were often poorly reported and did not appear to differ between treatment groups. Drop-outs due to side effects occurred with similar frequency in people treated with beta-blocker or placebo and appeared to be less with timolol compared to brimonidine, in three trials.

Authors' conclusions: 

The results of this review support the current practice of IOP lowering treatment of OHT. A visual field protective effect has been clearly demonstrated for medical IOP lowering treatment. Positive but weak evidence for a beneficial effect of the class of beta-blockers has been shown.

Direct comparisons of prostaglandins or brimonidine to placebo are not available and the comparison of dorzolamide to placebo failed to demonstrate a protective effect. However, absence of data or failure to prove effectiveness should not be interpreted as proof of absence of any effect. The decision to treat a patient or not, as well as the decision regarding the drug with which to start treatment, should remain individualised, taking in to account the amount of damage, the level of IOP, age and other patient characteristics.

Read the full abstract...

Primary open angle glaucoma (POAG) is a progressive optic neuropathy with an elevated intraocular pressure (IOP), where the optic nerve head becomes pathologically excavated and the visual field (VF) is characteristically altered. Ocular hypertension (OHT) is a condition with elevated IOP but without discernible pathology of the optic nerve head or the VF. It is a major risk factor for development of POAG.


To assess and compare the effectiveness of topical pharmacological treatment for POAG or OHT to prevent progression or onset of glaucomatous optic neuropathy.

Search strategy: 

We searched CENTRAL, MEDLINE and EMBASE in May 2007. We searched the bibliographies of identified articles and contacted experts, investigators and pharmaceutical companies for additional published and unpublished studies.

Selection criteria: 

Randomised controlled trials comparing topical pharmacological treatment to placebo, no treatment or other treatment for specified endpoints which included people with POAG or OHT, and with duration of treatment of at least one year.

Data collection and analysis: 

Two authors independently extracted data and assessed trial quality. Where appropriate, we summarised data using Peto odds ratio and mean difference after testing for heterogeneity between studies.

Main results: 

We included 26 trials, which randomised 4979 participants, in this review. Meta-analysis of 10 trials clearly demonstrated reduction of onset of VF defects in treated OHT (OR 0.62, 95% CI 0.47 to 0.81). No single drug showed a significant VF protection compared to placebo or untreated controls. We did identify some border line evidence for a positive influence of treatment on VF prognosis (OR 0.67, 95% CI 0.45 to 1.00) for the beta-blockers .

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