Primary prevention of glaucomatous visual field defects in patients with ocular hypertension by using topical pressure lowering agents seems to be effective, as shown in this meta-analysis of five methodologically adequate trials. The overall positive effect, as seen in the ocular hypertension treatment study9
remained robust, even when combined with all the other non-significant trials to date.
In comparison, a 1993 meta-analysis of randomised controlled trials by Rossetti et al5
identified only three appropriate randomised controlled trials out of a total of 102 trials.6,7,20
Although the pooled treatment effect showed a reduced risk for progression to glaucoma (odds ratio 0.75), the 95% confidence interval was wide (0.42 to 1.35), indicating that worsening of visual field defects could not be excluded in the intervention group.
The recent ocular hypertension treatment study had to exclude 1692 of 3328 patients screened for inclusion in the study for various reasons.9
The overall effectiveness of treatment may therefore be different in real practice. Moreover, the effectiveness of the investigators' treatment strategy in patients with mildly raised intraocular pressure (above 21 mm Hg, but below 24 mm Hg) remains unanswered.
Until now, only few adequate trials have been completed to address the issue of effective secondary prevention of visual field deterioration with pressure lowering treatment in patients with manifest primary open angle glaucoma, most probably because of ethical concerns of including an untreated control group. However, the results of our meta-analysis, as well as the early manifest glaucoma trial,11,12
show that reducing the intraocular pressure in patients with open angle glaucoma leads to a significant delay of visual field loss, particularly for those patients with increased intraocular pressure, as seen in the subgroup analysis of these patients.
In normal tension glaucoma, lowering the intraocular pressure may be beneficial as seen in the normal tension glaucoma study,13
but this has to be confirmed by larger trials and newer treatment modalities, because in this study, the development of excess cases of cataracts may have offset the treatment effect. In addition, we were not able to show a significant treatment effect convincingly when combining the data for patients with normal tension glaucoma in our subgroup analysis. This was mainly due to low power because of the small number of patients with normal tension glaucoma enrolled in these two studies.
Our analysis may have some limitations. Firstly, we cannot fully exclude publication bias; we did not perform a statistical test for the detection of publication bias, since these tests have very low power in meta-analysis of only five trials. However, we did not impose restrictions by language or year of publication, and the search results were complemented by hand searching of relevant journals, yielding more than 1000 reports that we assessed for inclusion in this review. Secondly, since our meta-analysis would lose significance (confidence interval 0.47 to 1.01) by excluding the ocular hypertension treatment study,9
the overall beneficial effect can only be safely assumed in patients with intraocular pressure of 24 mm Hg or more. Four of five included studies on ocular hypertension had high dropout rates, and therefore the magnitude of effect may have been biased.
Although the more recent trials discussed in our report seem methodologically sound, some general questions remain. In particular, it is not entirely clear why some patients may experience disease progression much faster than others (with and without treatment), even if they do not differ in terms of their risk factor profile: The results of the early manifest glaucoma trial11,12
showed that the visual fields of many treated patients deteriorated and those of many untreated patients did not. Therefore, more research is needed to identify subgroups that may be particularly susceptible to pressure reduction strategies. Conversely, some patients, especially those with only borderline elevated intraocular pressure or particular genetic traits, may or may not need immediate intervention.
Although lowering the intraocular pressure in patients with ocular hypertension of 24 mm Hg or more to prevent progression to primary open angle glaucoma seems to be beneficial, uncertainty prevails about the optimal treatment for patients with slightly raised intraocular pressure of 22 mm Hg or 23 mm Hg. In general, patients with manifest open angle glaucoma showed a significant delay in progression of visual field deterioration when treated with a pressure lowering strategy. More research is needed in the subgroup of patients without increased intraocular pressure to determine which patients with normal tension glaucoma will benefit most, since our analysis was unable to show a consistent beneficial effect in these patients.
What is already known on this topic
Primary open angle glaucoma is a leading cause of blindness in industrialised countries
Lowering intraocular pressure is generally used to prevent and to treat primary open angle glaucoma, although a meta-analysis of trials on ocular hypertension did not show a significant preventive treatment effect
What this study adds
Medical reduction of ocular pressure seems to be beneficial for the primary prevention of glaucomatous visual field defects
Only one adequate trial has shown effective secondary prevention of visual field deterioration with topical treatment or surgery in patients with manifest primary open angle glaucoma
A meta-analysis summarising data on normal tension glaucoma was inconclusive