Results of the European Glaucoma Prevention Study. Results of the betaxolol versus placebo treatment trial in ocular hypertension. Influence of carteolol and timolol on IOP an visual fields in glaucoma: a multi-center, double-masked, prospective study. Long-term effects of timolol therapy in ocular hypertension: a double-masked, randomised trial. A 7 year prospective comparative study of three topical beta blockers in the management of primary open angle glaucoma. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Effect of timolol versus pilocarpine on visual field progression in patients with primary open-angle glaucoma. Longterm effect of topical beta-blockers on intraocular pressure and visual field sensitivity in ocular hypertension and chronic open-angle glaucoma. Comparison of latanoprost monotherapy and combined therapy of 0.5% timolol and 1% dorzolamide in chronic primary angle-closure glaucoma (CACG) in Japanese patients.
The European Glaucoma Prevention Study (EGPS) seeks to evaluate the efficacy of reduction of intraocular pressure (IOP) by dorzolamide in preventing or delaying primary open-angle glaucoma (POAG) in patients affected by ocular hypertension (OHT).
                Randomized, double-masked, controlled clinical trial.
                One thousand eighty-one patients (age, > or =30 years) were enrolled by 18 European centers. The patients fulfilled a series of inclusion criteria, including: IOP 22 to 29 mmHg; 2 normal and reliable visual fields (on the basis of mean deviation and corrected pattern standard deviation or corrected loss variance of standard 30/II Humphrey or Octopus perimetry); normal optic disc as determined by the Optic Disc Reading Center.
                Patients were randomized to treatment with dorzolamide or placebo (the vehicle of dorzolamide).
                Efficacy end points were visual field, optic disc changes, or both. A visual field change during follow-up had to be confirmed by 2 further positive tests. Optic disc change was defined on the basis of the agreement of 2 of 3 independent observers evaluating optic disc stereo slides. The safety end point was an IOP of more than 35 mmHg on 2 consecutive examinations.
                During the course of the study, the mean percent reduction in IOP in the dorzolamide group was 15% after 6 months and 22% after 5 years. Mean IOP declined by 9% after 6 months and by 19% after 5 years in the placebo group. At 60 months, the cumulative probability of converting to an efficacy end point was 13.4% in the dorzolamide group and 14.1% in the placebo group (hazard ratio, 0.86; 95% confidence interval [CI], 0.58-1.26; P = 0.45). The cumulative probability of developing an efficacy or a safety end point was 13.7% in the dorzolamide group and 16.4% in the placebo group (hazard ratio, 0.73; 95% CI, 0.51-1.06; P = 0.1).
                Dorzolamide reduced IOP by 15% to 22% throughout the 5 years of the trial. However, the EGPS failed to detect a statistically significant difference between medical therapy and placebo in reducing the incidence of POAG among a large population of OHT patients at moderate risk for developing POAG, because placebo also significantly and consistently lowered IOP. To determine whether treatment with betaxolol can delay or prevent the conversion from ocular hypertension to early glaucoma on the basis of visual field criteria, by means of a prospective, randomised, placebo-controlled trial.
                Three hundred and fifty-six ocular hypertensives were randomized to treatment with either betaxolol drops or placebo drops during the period 1992-1996. Each patient was followed prospectively with 4-monthly visits. Examination at each visit included visual field testing, intra-ocular pressure (IOP) measurement and optic disc imaging. Conversion to early glaucoma was defined on the basis of visual field change by AGIS criteria. An intent-to-treat analysis compared visual field conversion after 3 years in the treatment and placebo arms. Normal visual field survival analysis was also performed. The IOP characteristics of the two treatment groups were compared.
                Two hundred and fifty-five patients completed the study, which ended in 1998, with a range of follow-up of 2-6 years. Sixteen (13.2%) of 121 patients in the placebo group converted to glaucoma, compared with 12 (9.0%) of 134 patients in the betaxolol group. The intent-to-treat analysis demonstrated no evidence of any difference in conversion rates between the betaxolol and placebo groups after 3 years. Visual field survival analysis demonstrated no significant difference between the betaxolol and placebo groups. The betaxolol-treated group had significantly lower post-treatment IOP values. Converters had significantly higher pre- and post-treatment IOP values than non-converters.
                Betaxolol significantly lowered the IOP level compared with placebo. Conversion to glaucoma was found to be related to both the baseline and post-treatment IOP levels. However the intent-to-treat analysis did not demonstrate a statistically significant reduction in the conversion rate in the betaxolol-treated group. The influences of Carteolol and Timolol eye drops on intraocular pressure (IOP) and visual fields were compared in a multi-center, double-masked, prospective study. Two-hundred and forty eyes of 120 patients were initially included in the study, and 142 eyes of 72 patients fulfilled all the criteria for final statistical analysis. Both drugs significantly reduced IOP. The visual fields in both treatment groups did not change during one year of treatment. In both groups some patients improved slightly, and others deteriorated slightly. This indicates that locally applied beta-blockers may efficiently stop further progression of visual field defects in cases with increased IOP and early visual field damage. There was no difference between Carteolol and Timolol in this regard. The side effects were minimal, and there were no differences in their frequency or intensity in the two treatment groups. Increased intraocular pressure (IOP) has been shown to be one of the most important risk factors for developing glaucoma. Yet it has not been clearly demonstrated that IOP-lowering treatment can reduce the incidence of glaucoma damage in patients with ocular hypertension. The aim of the current paper was to report the results of a long-term study addressing this very problem.
                We conducted a randomised, double-masked study comparing timolol and placebo treatment in 90 patients with ocular hypertension plus some additional risk factor. Patients were followed at 3-month intervals prospectively for 10 years or until glaucomatous field loss could be demonstrated with computerised perimetry. A post-study analysis was performed including all available data, thus extending maximum follow-up to 17 years.
                After 5 years of follow-up eight patients in the placebo group and five patients in the timolol group had developed glaucomatous field loss (NS); the corresponding figures after 10 years were 15 patients in the placebo group and seven patients in the timolol group. Survival analysis showed a tendency but no statistically significant difference between treatment groups (P = 0.07). Study attrition was large. Eighteen patients in each group had developed glaucomatous field loss when also post-study data were included. IOP reduction was greater in eyes passing the 10-year visit without field loss (5.7 mmHg), than in those that reached an end-point (2.3 mmHg; P = 0.0002).
                In this long-term study we found a tendency but failed to prove a beneficial effect of topical timolol treatment in patients with elevated IOP, normal visual fields and some additional risk factor. The intent-to-treat analysis showed no difference between treatment groups. The high attrition shows the difficulties associated with very long follow-up. To determine the long term efficacy of monotherapy with topically applied beta blocking agents and to determine whether selective beta blockers were able to preserve the visual field more effectively than non-selective agents.
                A prospective randomised, open, comparative study of three topically applied beta blockers-timolol, betaxolol, and carteolol-was carried out on 153 patients (280 eyes) with newly diagnosed open angle glaucoma. Those patients who were not withdrawn were followed by the same observers for a minimum of 2 years and a maximum of 7 years, with clinical observations, Goldmann tonometry and 24.2 Humphrey visual field analysis.
                All three drugs lowered the IOP significantly from untreated levels but betaxolol took up to 12 months in some instances to reach the maximum pressure reduction. After 7 years only 43% of the eyes begun on timolol, 34% of those started on carteolol, and 29% of those on betaxolol were still being treated with these medications alone. Visual fields were analysed throughout the trial by CPSD and MD and at the end by linear regression analysis (PROGRESSOR). The visual fields remained the same without apparent improvement or deterioration throughout the period of follow up. Eight patients (11 eyes) were withdrawn because of continuing field loss in spite of reduction in IOP (six using carteolol and five using betaxolol).
                Analysis shows that less than half the eyes initially treated with topical beta blockers might be expected to still be being treated with their original medication after 5 years. The rest required either additional medication or trabeculectomy. There was no statistically significant improvement or deterioration in the visual fields over a 7 year period. On the evidence of this trial there are no particular advantages in using selective beta blockers. Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study.
                To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of POAG.
                A total of 1636 participants with no evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24 mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye were randomized to either observation or treatment with commercially available topical ocular hypotensive medication. The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less.
                The primary outcome was the development of reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG. Abnormalities were determined by masked certified readers at the reading centers, and attribution to POAG was decided by the masked Endpoint Committee.
                During the course of the study, the mean +/- SD reduction in IOP in the medication group was 22.5% +/- 9.9%. The IOP declined by 4.0% +/- 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P<.0001). There was little evidence of increased systemic or ocular risk associated with ocular hypotensive medication.
                Topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG. Relatively few studies have been conducted linking decreasing intraocular pressure (IOP) to preservation of visual field. This investigation was conducted to determine if this link could be made and to compare the long-term effect of two ocular hypotensive agents on preservation of visual field.
                In an observer-masked study, 189 patients with primary open-angle glaucoma received either timolol or pilocarpine by random allocation. The dose of antiglaucoma agent was increased from 0.25% to 0.5% twice daily for timolol or from 2% to 4% four times daily for pilocarpine if the initial IOP response was inadequate. After an on-treatment baseline, visual fields were followed every 4 months for 2 years using the Octopus program 32.
                Compared with timolol, significantly more patients receiving pilocarpine discontinued use because of inadequate IOP control (P < or = 0.01). By comparing the mean visual field scores, it can be seen that the pilocarpine group had a significantly worse score at all timepoints from month 4 to month 24. The pilocarpine group also had a greater mean number of test loci with decreased sensitivity of 5 or more decibels (dB) at all timepoints. The mean within-patient regression slope for timolol was 0.01 dB/month and for pilocarpine was -0.06 dB/month (P < 0.01). The study has shown that over a 2-year period, patients treated with pilocarpine 2% or 4% four times daily experienced a significantly greater visual field deterioration than that seen in patients receiving either 0.25% or 0.5% timolol twice daily.
                Although these data do not support a link between lowering of IOP and visual field preservation, treatment with timolol was associated with significantly less visual field loss than treatment with pilocarpine. In a prospective, randomized study, nineteen patients with ocular hypertension (n = 14) or chronic open-angle glaucoma (n = 5) were treated with either betaxolol 0.5% or timolol 0.5% in both eyes twice daily. Visual field sensitivity and intraocular pressure were assessed with the Octopus perimeter (program G1) and applanation tonometry, respectively, at 3, 6, 12, 24, 36, and 48 months during treatment. Four of the nineteen patients (two timolol-treated and two betaxolol-treated) were lost to follow-up after the 36-month examination. Whereas both drugs reduced the intraocular pressure, the decrease in the timolol-treated group was statistically more pronounced than in the betaxolol-treated group at month 3, 6, and 48 (p < 0.03). In both treatment groups, the visual field mean sensitivity (MS) index decreased slightly during the first six months of treatment, but remained so only in the timolol-treated group at all subsequent examinations. In the betaxolol-treated group, there was a statistically significant increase in MS at the 12, 24, 36, and 48 month visits (p < 0.01). These findings suggest that factors other than IOP alone may determine visual field outcome. To compare the efficacy, adverse effects, and patient compliance of latanoprost monotherapy with unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of chronic primary angle-closure glaucoma (CACG), 36 Japanese patients with CACG following laser iridotomy (LPI) were treated for 12 weeks with instillation of latanoprost alone or with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. After 12 weeks of treatment, latanoprost reduced intraocular pressure (IOP) from 22.2 +/- 2.0 mmHg to 14.8 +/- 1.9 mmHg (33% reduction); timolol maleate and dorzolamide hydrochloride also reduced IOP from 22.5 +/- 2.2 mmHg to 17.1 +/- 2.7 mmHg (24% reduction). Latanoprost monotherapy significantly lowered IOP compared with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. Furthermore, a systemic adverse effect of bradycardia was not observed in the latanoprost monotherapy group. Concerning compliance, no significant difference was observed between the two groups. Thus, latanoprost monotherapy is more effective than unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of CACG following relief of pupillary block in Japanese patients.
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.