Twelve-month results of an ongoing randomized trial comparing brimonidine tartrate 0.2% and timolol 0.5% given twice daily in patients with glaucoma or ocular hypertension. Brimonidine Study Group 2. Effect of timolol versus pilocarpine on visual field progression in patients with primary open-angle glaucoma. Timolol treatment prevents or delays glaucomatous visual field loss in individuals with ocular hypertension: a five-year, randomized, double-masked, clinical trial. Long-term effect of ophthalmic beta-adrenoceptor antagonists on intraocular pressure and retinal sensitivity in 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. Influence of carteolol and timolol on IOP an visual fields in glaucoma: a multi-center, double-masked, prospective study. A long-term clinical trial of timolol therapy versus no treatment in the management of glaucoma suspects. A 1-year study of brimonidine twice daily in glaucoma and ocular hypertension. A controlled, randomized, multicenter clinical trial. Chronic Brimonidine Study Group. Long-term effects of timolol therapy in ocular hypertension: a double-masked, randomised trial. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. A comparison of treated and untreated glaucoma suspects. Levobunolol compared with timolol: a four-year study. Results of the betaxolol versus placebo treatment trial in ocular hypertension. Levobunolol. A four-year study of efficacy and safety in glaucoma treatment. The Levobunolol Study Group. Results of the European Glaucoma Prevention Study. Comparison of the effects of brimonidine 0.2% and timolol 0.5% on retinal nerve fiber layer thickness in ocular hypertensive patients: a prospective, unmasked study. A comparative evaluation of timolol maleate and pilocarpine in the treatment of chronic open angle glaucoma. A comparison of the effects of betaxolol, timolol, and pilocarpine on visual function in patients with open-angle glaucoma. Decrease of optic disc cupping and pallor of ocular hypertensives with timolol therapy. Longterm visual field follow-up of glaucoma patients treated with beta-blockers. Ocular hypertension: correlation of anterior chamber angle width and risk of progression to glaucoma. A 7 year prospective comparative study of three topical beta blockers in the management of primary open angle glaucoma. A clinical trial of timolol and epinephrine in the treatment of primary open-angle glaucoma.
To compare the long-term safety and ocular-hypotensive efficacy of brimonidine tartrate 0.2% with timolol maleate 0.5% administered twice daily in patients with glaucoma or ocular hypertension.
                A double-masked, parallel-group, active-controlled, multicenter clinical trial of 12 months' duration.
                Four hundred eighty-three patients with glaucoma or ocular hypertension were enrolled. Of these, 463 were evaluated according to the protocol criteria (280 in the brimonidine tartrate group and 183 in the timolol group).
                Brimonidine tartrate 0.2% or timolol maleate 0.5% was administered twice daily.
                The primary efficacy variable was intraocular pressure (IOP).
                Brimonidine and timolol produced significant (P < 0.001) and sustained mean reductions in IOP throughout the 1-year follow-up when measured at hour 0 (trough) and at hour 2 (peak). At weeks 1 and 2 and month 12, significantly greater mean decreases in IOP measured at peak (P < or = 0.007) were observed in patients treated with brimonidine as compared to timolol, whereas the mean decreases in IOP measured at trough was significantly greater in patients treated with timolol as compared to brimonidine (P < 0.001) at all follow-up visits. Both drugs were well-tolerated. The incidence of adverse events was similar in both treatment groups, except for ocular allergy, oral dryness, and conjunctival follicles, which occurred more frequently in the brimonidine group, and burning-stinging, which occurred more frequently in the timolol group. Patients receiving timolol experienced significant decreases in heart rate at all follow-up visits.
                Topically applied twice daily for 12 months, brimonidine tartrate 0.2% was safe and effective in lowering IOP in patients with glaucoma or ocular hypertension. 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. A 5-year, randomized, double-masked, clinical trial was conducted to determine whether treatment with topical timolol maleate was effective in preventing or delaying the onset of glaucomatous visual field loss in subjects with ocular hypertension. Sixty-five individuals considered to be at moderate risk for developing open-angle glaucoma were recruited for the study. In each patient, one eye was chosen randomly to receive timolol twice-daily while the fellow eye received diluent (placebo). Timolol administration reduced IOP from baseline in the treated eyes over the course of the study by a mean +/- SD of 4.9 +/- 3.4 mm Hg. Timolol administration also produced a mean +/- SD contralateral reduction of IOP from baseline in the untreated fellow eyes of 2.9 +/- 3.1 mm Hg. The mean +/- SD difference in IOP between the treated and untreated eyes during the study was 2.3 +/- 2.6 mm Hg. Over the course of the study reproducible visual field loss developed in 4 timolol treated eyes and 10 placebo treated eyes (P = .039, McNemar test). Clinical progressive optic disc cupping was noted in four treated and eight untreated eyes (P = .11, McNemar test). In the 42 subjects who completed a minimum 4-year follow-up, baseline and final optic disc photographs were analyzed using a computer image analysis system to determine changes in the area of disc pallor. The mean +/- SD increase in optic disc pallor was 0.86% +/- 2.4% in the timolol treated eyes and 1.80% +/- 3.6% in the placebo treated eyes. This difference was statistically significant (P = .04, paired t-test). This study provides evidence that medical treatment prevents or delays the onset of glaucomatous visual field loss and optic disc damage in individuals with ocular hypertension. The magnitude of the protective effect of timolol was partially obscured by the contralateral reduction of IOP in the placebo treated fellow eyes. Timolol (TIM) and betaxolol (BET) were evaluated for their effects on both intraocular pressure and retinal sensitivity as determined from visual fields in a randomized two-year parallel study in 20 patients with primary open-angle glaucoma. All treatments were twice-daily in both eyes. TIM was more effective than BET as an ocular hypotensive agent throughout the two year period. With regard to retinal sensitivity as measured by automated visual fields, there was a decrease in retinal sensitivity in the first six months in the TIM and BET treatment groups by 0.5-0.6 dB, and 0.2-0.3 dB, respectively. However, at the one and two year visits, retinal sensitivity increased 0.8-0.9 dB in the BET treatment group only. It appears that ocular hypotensive efficacy may not relate to retinal sensitivity within a period of two years or less in patients with mildly to moderately elevated intraocular pressure. Further work may reveal the reliability of this observation, and its clinical relevance. 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. 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. One hundred seven patients with intraocular pressures (IOPs) between 22 and 28 mmHg with normal visual fields on Goldmann perimetry and without evidence of optic nerve damage were randomly assigned to either a timolol treatment (TT) or a no treatment (NT) arm in a prospective clinical trial. The patients were followed for an average of 56 and 51 months, respectively. Criteria for failure were a confirmed IOP of greater than 32 mmHg, stereophotographically documented optic nerve progression, or development of glaucomatous visual field loss by Goldmann or Octopus perimetry. Nine patients failed in the TT group and 17 in the NT group (P = 0.07). Of the nine TT group failures, six had discontinued timolol before failure (4 for greater than 6 months). In a Cox proportional hazards analysis controlling for confounding variables, timolol was found to be significantly protective with an adjusted risk ratio of 0.38 (95% confidence interval = 0.16-0.89, P = 0.03). When only field and disc failure criteria were considered, timolol treatment was found to be significantly protective in an analysis considering patients who stopped timolol as being lost to follow-up (P = 0.05). A higher tonographic facility of outflow was protective in all analyses. A trend toward a substantial loss of effectiveness of timolol on IOP was not observed. Seasonal fluctuations in IOP were observed (P = 0.0007), with higher IOP occurring in the winter. The results demonstrate a favorable influence of timolol therapy on the clinical course of patients with mildly elevated IOP.(ABSTRACT TRUNCATED AT 250 WORDS) Brimonidin tartrate is a highly selective alpha 2-agonist. This study investigates the safety and efficacy of 0.2% brimonidine administered twice daily for 1 year in patients with glaucoma or ocular hypertension.
                The study design was a multicenter, double-masked, randomized, parallel-group, active-controlled comparison clinical trial. Subjects instilled 0.2% brimonidine or 0.5% timolol maleate twice daily for 12 months. Subjects were examined at baseline, week 1, and months 1, 2, 3, 6, 9, and 12. A subset of subjects was examined at week 2.
                Of 443 subjects enrolled in this study, 374 met the entry criteria; 186 received brimonidine and 188 received timolol. Brimonidine-treated subjects showed an overall mean peak reduction in intraocular pressure (IOP) of 6.5 mm Hg; timolol-treated subjects had a mean peak reduction in IOP of 6.1 mm Hg. Brimonidine lowered mean peak IOP significantly more than timolol at week 2 and month 3 (P < .03); no significant difference was observed between the groups for this variable at other visits throughout the 1-year course of the study. No evidence of tachyphylaxis was seen in either group. Allergy was seen in 9% of subjects treated with brimonidine. Dry mouth was more common in the brimonidine-treated group than in the timolol-treated group (33.0% vs 19.4%), but complaints of burning and stinging were more common in the timolol-treated group (41.9%) than in the brimonidine-treated patients (28.1%). Headache, fatigue, and drowsiness were similar in the 2 groups. In general, the tolerance to medication was acceptable.
                Brimonidine is safe and effective in lowering IOP in glaucomatous eyes. Brimonidine provides a sustained long-term ocular hypotensive effect, is well tolerated, and has a low rate of allergic response. 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. 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. One hundred forty-three patients with intraocular pressures (IOPs) above 22 mmHg and without visual field defects or any obvious evidence of optic nerve damage were randomly assigned to either a timolol treatment group or no treatment in a 6-year prospective clinical trial. Endpoints were defined as reproducible visual field defects on automatic perimetry, disc hemorrhages, or stereophotographically documented optic nerve head changes. Endpoints developed in 42 patients: 28 visual field defects, 8 changes in disc appearance, and 6 disc hemorrhages. Of the 42 patients, 20 were treated and 22 were not. Survival analysis showed no statistically significant differences in failure time to any endpoints between the two groups. In the untreated group, the time to failure of disc change was related to the mean IOP during the study and also to the changes in the IOP from baseline. A significant correlation was found between initial cup-to-disc ratio and survival time to visual field defects in the untreated group. Fifty-one patients with raised intraocular pressure (IOP) were treated for up to four years with one of three ophthalmic solutions: 0.5% levobunolol, 1% levobunolol, or 0.5% timolol. The study was conducted as a double-masked, randomised trial in which medications were administered twice daily to both eyes. Levobunolol and timolol were equally effective in reducing overall mean IOP; reductions were greater than 8.8 mmHg in all three treatment groups. The study showed levobunolol to be as safe and effective as timolol in the long-term control of raised 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. In a 4-year, double-masked, parallel, multicenter study comparing the efficacy and safety of levobunolol and timolol, 391 patients with open-angle glaucoma or ocular hypertension were randomly assigned to receive masked 0.5% or 1% levobunolol, or 0.5% timolol, twice daily. Mean decreases in intraocular pressure (IOP) over 4 years of therapy were 7.1, 7.2, and 7.0 mmHg for 0.5% levobunolol, 1% levobunolol, or 0.5% timolol, respectively. Little attenuation of ocular hypotensive efficacy occurred. The 4-year efficacy failure rate for the three groups, which did not differ from each other, was approximately 30%. Adverse experiences requiring cessation of therapy occurred in an additional 10% of patients. The vast majority of efficacy failures (79/95) and of adverse events (33/37) requiring removal from the study occurred during the first 2 years. Overall mean decreases in heart rate for the 4 years ranged from 3 to 6 beats per minute for all treatment groups; overall mean decreases in systolic and diastolic blood pressure ranged between 1 and 2 mmHg. The authors concluded that levobunolol is relatively effective and relatively safe for the long-term (4-year) treatment of elevated IOP. 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. The aim of this study was to compare the effects of brimonidine and timolol on retinal nerve fiber layer (RNFL) thickness in ocular hypertensive patients.
                This was a prospective, comparative, and unmasked study. For 12 months, 38 eyes of 19 patients with primary open-angle glaucoma received brimonidine tartrate 0.2%, and 40 eyes of 20 patients received timolol maleate 0.5%. Intraocular pressure (IOP) was measured every 2 months, and RNFL thickness was assessed using Scanning laser polarimetry (GDx) at baseline and at 12 months.
                Mean IOP reduction was similar in both groups. Within each treatment group, the RNFL thickness for ellipse average (P = 0.004), superior (P = 0.035), temporal (P = 0.003), inferior (P < 0.0001), and nasal averages (P = 0.044) were significantly decreased from baseline in timolol at 12 months. However, the RNFL thickness for ellipse average and four quadrants showed no significant change from baseline in brimonidine. The between-group difference in RNFL change showed a significant reduction for ellipse average (P = 0.02), temporal (P = 0.005), and inferior averages (P = 0.016) following timolol therapy, as compared to brimonidine.
                There appear to be less progression for RNFL damage following brimonidine 0.2% therapy compared to timolol 0.5% in ocular hypertensive patients over 1 year. This finding does not correlate with IOP reduction. Ninety-two eyes with newly-diagnosed chronic open angle glaucoma (COAG) were treated in a randomised prospective trial with either timolol or pilocarpine. Their visual field survival was monitored on a 3-monthly basis over 2 years using both Goldmann and Friedmann perimetry. Concomitant tonometric data was derived by applanation. Fields were assessed and quantified using algorithms designed to give the greatest sensitivity for glaucomatous field loss. Microcomputer programmes specifically designed for this purpose were used in the data collection and subsequent analysis. The author compares the effect of betaxolol, timolol, and pilocarpine on visual functions in patients with glaucoma.
                Sixty-eight patients with early glaucoma were randomly allocated to betaxolol, timolol, or pilocarpine treatment and their visual fields, motion detection, and contrast sensitivity were studied over a 24-month period. A subset of the betaxolol and timolol group were also followed with short-wave automated perimetry. One eye of each patient was used in the analysis.
                All three drugs reduced pressure effectively. Pilocarpine and timolol were not significantly different from each other and both produced a more marked pressure reduction than betaxolol. There were no significant differences between the drugs on the visual fields, contrast sensitivity, or motion detection. Betaxolol appeared to have a better impact on the blue-yellow sensitivity of the upper nasal and upper temporal visual field quadrants than timolol.
                In spite of a greater pressure reduction, timolol did not have a more favorable effect on visual function. In the short-wave automated perimetry, the betaxolol did marginally better than timolol. The apparent dissociation between pressure reduction and protection of visual function deserves further study. The purpose of this study was to determine whether timolol drops compared to placebo drops had a significant effect on optic disc cupping and pallor in ocular hypertensives.
                Thirty-seven ocular hypertensives were randomly assigned to placebo or 0.5% timolol drops to both eyes in a double masked clinical trial. Measurements of ocular pressure and photographs of the optic disc for cupping by photogrammetry and pallor by computerized image analysis were made at about 3 month intervals, for 18 to 24 months of follow-up.
                None of the subjects developed visual field loss when tested with the Goldmann perimeter by kinetic and static means at six month intervals. Subjects treated with timolol developed a significant decrease in ocular pressure and a significant decrease in optic disc cupping with a smaller decrease in pallor compared to subject treated with placebo. Multivariate analyses indicated that the decrease of optic disc cupping and pallor was not associated with the ocular pressure on treatment or the decrease in ocular pressure during the trial.
                Timolol treatment was associated with a decrease in optic disc cupping and pallor. The effect of timolol appears to be related to mechanisms other than the decrease in ocular pressure. In a prospective, randomized, double-masked study, 44 patients with primary open-angle glaucoma were treated either with 0.5% betaxolol or 0.5% timolol in both eyes twice daily. Twenty-nine patients could be followed up for 48 months. Seventeen of these patients were treated with betaxolol and 12 with timolol. Each examination included visual field measurements with an Octopus automated perimeter 201 (Program G1), intraocular pressure measurement, funduscopy, as well as pulse and arterial blood pressure measurements. Both drugs lowered in the intraocular pressure. This reduction was slightly but not statistically significantly higher in the timolol-treated group. However, the visual fields improved more in the betaxolol group. Patients treated with betaxolol had significantly smaller averaged mean defects (p < 0.05) and higher averaged mean sensitivities (p < 0.05, Wilcoxon rank score text) than did timolol-treated patients at months 3, 6, 12, and 18. Thereafter, the difference between the two groups was not statistically significant in this relatively small sample size. For betaxolol patients the cumulative area-under-the-curve analysis for the worse eye yielded significantly larger mean sensitivities beyond month 12 (exception: month 30; p < 0.05) and significantly smaller mean defects beyond month 6 (p < 0.05). Twenty five patients with ocular hypertension (OH) and a narrow angle and 34 patients with OH and an open angle were followed for an average of six years. One eye of each patient had been randomly assigned to treatment with topical timolol. A shallow axial anterior chamber depth and a narrow angle (van Herick Grade 2 or less) was associated with the development of angle-closure glaucoma (ACG) in the narrow angle group, but the open angle group developed significantly more visual field loss. Nine patients (36%) in the narrow angle group developed ACG, and nine patients (26.5%) in the open angle group developed glaucomatous discs and field loss. The reduction in intraocular pressure due to topical timolol was equal in the narrow angle and the open angle groups, but topical timolol did not protect against the development of angle-closure glaucoma or visual field loss. 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. Forty-seven patients with chronic open-angle glaucoma who required therapy but who had never been treated previously were enrolled in a prospective randomized, long-term clinical trial comparing the effectiveness of 0.5% timolol maleate and 1% epinephrine. Patients were followed for an average of 33 months. There were 20 failures, 18 of which were because of inadequate intraocular pressure (IOP) control (required 20% reduction in outflow pressure). Twelve failures were in the epinephrine group and eight were in the timolol group. During the first year of therapy, 35% compared with 0% of patients failed in the epinephrine and timolol groups, respectively (P less than 0.01). During the later years of the study, the failure rates in the two groups were similar. The results suggest that timolol is superior to epinephrine during the first year of therapy, and likely as effective as epinephrine in the long-term treatment of glaucoma.
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.