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At least 199 records · Page 11Linked to original sources
PubMed2005

Brimonidine and timolol fixed-combination therapy versus monotherapy: a 3-month randomized trial in patients with glaucoma or ocular hypertension.

PURPOSE: The aim of this study was to compare the safety and intraocular pressure (IOP)- lowering efficacy of a fixed combination of brimonidine 0.2% and timolol 0.5% (fixed brimonidine/ timolol) versus each drug used as monotherapy. METHODS: Patients with glaucoma or ocular hypertension were randomized to receive fixed brimonidine/timolol BID (n = 385), brimonidine 0.2% TID (n = 382), or timolol 0.5% BID (n = 392) in a multicenter, double-masked study. The primary outcome measure was decrease from baseline IOP. RESULTS: Over all follow-up measurements, the mean decrease from baseline IOP ranged from 4.9 to 7.6 mmHg with brimonidine/timolol, from 3.1 to 5.5 mmHg with brimonidine, and from 4.3 to 6.2 mmHg with timolol. Mean IOP reductions from baseline were significantly larger with fixed brimonidine/timolol than with timolol at all follow-up measurements (P < or = 0.026); the difference was greater than 1.5 mmHg at 10 AM (peak effect for each treatment). Mean IOP reductions from baseline were significantly larger with fixed brimonidine/ timolol than with brimonidine at 8 AM, 10 AM, and 3 PM (P < 0.001); the difference was greater than 1.5 mmHg. The rate of discontinuations owing to adverse events was 3.6% in the fixed timolol/brimonidine group. CONCLUSIONS: The fixed combination of brimonidine and timolol was well-tolerated and provided significantly better IOP control compared with either brimonidine or timolol used alone.

Adrenergic alpha-Agonists↗
PubMed2003

Comparison of the effects of topical levobunolol and timolol solution on the human ocular surface.

PURPOSE: To compare the effects of levobunolol hydrochloride and timolol maleate on tear volume, precorneal tear film stability, and corneal epithelial barrier function in normal human eyes. SUBJECTS AND METHODS: The study population consisted of 14 healthy volunteers. To obtain pretreatment baseline values, we determined the radius of the tear meniscus (RTM) by meniscometry; the noninvasive breakup time (NIBUT) of the precorneal tear film with a tear specular microscope; and corneal fluorescein uptake with a fluorophotometer. Levobunolol hydrochloride (0.5%) or timolol maleate solution (0.5%) was instilled twice daily for 4 weeks into 1 eye; the contralateral eye was treated with the other topical drug twice daily for the same period. At the end of the study period, the same tests were performed, and the pre- and posttreatment results were compared. RESULTS: Timolol solution did, and levobunolol did not, significantly reduce NIBUT from the baseline values. RTM was significantly decreased by treatment with either timolol or levobunolol solution. Corneal fluorescein uptake was not significantly changed, although it was higher after treatment with both topical drugs. CONCLUSIONS: Four-week treatment with timolol solution resulted in significant instability of the precorneal tear film. Both timolol and levobunolol solution significantly decreased tear volume on the ocular surface. These results indicate that levobunolol solution applied twice daily has equal effects on the tear volume and corneal epithelial barrier function as does timolol solution applied twice daily and that it affects precorneal tear film stability less than timolol solution.

Adrenergic beta-Antagonists↗
PubMed2000

Clinical success and quality of life with brimonidine 0.2% or timolol 0.5% used twice daily in glaucoma or ocular t hypertension: a randomized clinical trial. Brimonidine Outcomes Study Group I.

PURPOSE: To compare the clinical success rates and quality of life impact of brimonidine 0.2% with timolol 0.5% in newly diagnosed patients naive to glaucoma therapy. METHODS: A prospective, multicenter, randomized, double-masked, clinical effectiveness trial in which the clinical outcomes of twice daily brimonidine tartrate 0.2% were compared with those of timolol maleate 0.5% in patients with glaucoma and' ocular hypertension was conducted. Two hundred nineteen patients were enrolled--111 in the brimonidine group and 108 in the timolol group. Patients instilled their study medications twice daily for 4 months. Factors for determining clinical success were reduction of intraocular pressure (IOP), safety, and adverse events. Quality of life effects were assessed with the SF-36 Health Survey and Glaucoma Disability Index questionnaires. RESULTS: Clinical success was 71% (75/106) with brimonidine and 70% (73/105) with timolol as initial treatment. The overall mean decrease in IOP was 6.5 mm Hg with brimonidine and 6.2 mm Hg with timolol. Few patients reported a specific adverse event and, with the exception of a slightly higher rate of ocular burning and stinging in the brimonidine group, there were no significant between-group differences. No significant chronotropic effects on the heart were seen with brimonidine, while small but significant mean decreases in heart rate were seen at months 1 and 4 with timolol. Mean systolic and diastolic blood pressure remained relatively stable in both groups. Quality of life remained stable, with no significant between-group differences. CONCLUSIONS: As a first-line agent for the treatment of glaucoma and ocular hypertension, brimonidine has clinical effectiveness equivalent to timolol, but with less chronotropic effect on the heart. Brimonidine is a viable alternative to timolol for first-line therapy in glaucoma and ocular hypertension.

Adrenergic alpha-Agonists↗
PubMed2001

Comparison of the additive intraocular pressure-lowering effect of latanoprost and dorzolamide when added to timolol in patients with open-angle glaucoma or ocular hypertension: a randomized, open-label, multicenter study in Greece.

PURPOSE: To compare the intraocular pressure-lowering effect of latanoprost with that of dorzolamide when added to timolol. PATIENTS AND METHODS: This randomized, open-label study with two parallel groups was conducted in five centers in Greece. The study enrolled 148 patients with inadequately controlled open-angle or pseudoexfoliation glaucoma (intraocular pressure of at least 22 mm Hg) or ocular hypertension (intraocular pressure of at least 27 mm Hg) who were receiving monotherapy with a beta-blocker or dual therapy in which one of the agents was a beta-blocker. The patients were switched to timolol 0.5% twice daily for 2 to 4 weeks (run-in period) before the start of the study (baseline). At baseline, the patients were randomized to receive latanoprost 0.005% once daily or dorzolamide 2% twice daily as add-on therapy to timolol. The intraocular pressure was recorded at 9:30 AM, 12:30 PM, and 3:30 PM at baseline and at 3 months. Safety was followed throughout the study. RESULTS: The diurnal intraocular pressure reduction was significant in both groups (P < 0.001). The mean intraocular pressure reduction from baseline was 32% for the latanoprost plus timolol group and 20% for the dorzolamide plus timolol group. The least square estimate of the mean diurnal intraocular pressure reduction after 3 months was -7.06 mm Hg in the latanoprost plus timolol group and -4.44 mm Hg in the dorzolamide plus timolol group (P < 0.001). Drugs administered in both treatment groups were well tolerated. CONCLUSION: This study clearly showed that the additive diurnal intraocular pressure-lowering effect of latanoprost is superior to that of dorzolamide in patients treated with timolol.

Adrenergic beta-Antagonists↗
PubMed2004

Efficacy of bunazosin hydrochloride 0.01% as adjunctive therapy of latanoprost or timolol.

PURPOSE: To evaluate the ocular hypotensive response of bunazosin hydrochloride 0.01% administered as adjunctive therapy in patients with glaucoma who were already receiving latanoprost 0.005% or timolol 0.5%. METHODS: Patients with primary open angle glaucoma who had received latanoprost (n = 60) or timolol (n = 60) for 6 months or longer were enrolled and prospectively randomized to receive additional administration of bunazosin or placebo. One hundred twenty eyes of 120 patients were thus divided into 4 subgroups of 30 patients each. Bunazosin was administered twice daily, and timolol or latanoprost was administered per label. The patients were followed up for 3 months. Responders were defined as having a reduction in intraocular pressure of greater than 2 mm Hg from baseline. RESULTS: Mean baseline intraocular pressure was 22.3 +/- 3.0 mm Hg in the bunazosin subgroup and 22.3 +/- 3.1 mm Hg in the placebo subgroup of the latanoprost arm, and 22.5 +/- 3.5 mm Hg in the bunazosin subgroup and 22.3 +/- 3.0 mm Hg in the placebo subgroup of the timolol arm. In the bunazosin subgroups of both arms, intraocular pressure was significantly reduced compared with baseline measurements (P < 0.05) with mean intraocular pressure measurement reductions of 2.1 +/- 2.4 mm Hg and 2.8 +/- 2.1 mm Hg in the latanoprost arm and 2.6 +/- 2.1 mm Hg and 2.8 +/- 2.1 mm Hg in the timolol arm at 6 and 12 weeks after the start of the follow-up, respectively. In the latanoprost group, bunazosin provided a further reduction of intraocular pressure (7.7%) at 12 weeks from that initially obtained at 2 weeks (P = 0.0377). In the placebo subgroups of the latanoprost and timolol arms, no significant change was found between at baseline and at any visit after the start of the follow-up. In the latanoprost and timolol arms, there was a significant difference in intraocular pressure and its change between the bunazosin subgroup and placebo subgroup at any visit after 4 weeks from the start of the follow-up (P < 0.01). CONCLUSION: Bunazosin hydrochloride 0.01% may provide an additional intraocular pressure reduction in patients already receiving latanoprost or timolol. Since adding bunazosin to eyes treated with latanoprost caused a relatively small hypotensive response at 2 weeks and provided a further reduction from 2 weeks to 12 weeks, longer than 4 weeks may be required to evaluate a clinically meaningful response to treatment. Further investigation on more cases and longer follow-up are needed.

Adrenergic alpha-Antagonists↗
PubMed2004

Effects on aqueous flow of dorzolamide combined with either timolol or acetazolamide.

PURPOSE: To determine the effect on aqueous flow of topical dorzolamide 2%, topical timolol 0.5%, or oral acetazolamide 250 mg when used alone or when dorzolamide is combined with either timolol or acetazolamide. METHODS: In 30 patients with ocular hypertension, aqueous flow and intraocular pressure (IOP) were determined at baseline and on the following combinations of drugs in a crossover design: (1) vehicle alone, (2) dorzolamide alone, (3) acetazolamide alone, (4) timolol alone, (5) dorzolamide + acetazolamide, and (6) dorzolamide + timolol. Treated eyes were compared with control eyes and comparisons were made between treatments. RESULTS: Compared with baseline, significant (P < 0.04) IOP reductions in the order of efficacy were: dorzolamide + timolol > dorzolamide + acetazolamide = acetazolamide = timolol > dorzolamide. Aqueous flow was reduced more by dorzolamide + timolol than by each drug alone (P < 0.04) and more by dorzolamide + acetazolamide than by dorzolamide alone (P < 0.04). CONCLUSION: The combination of dorzolamide and timolol demonstrated significant aqueous flow additivity and had greater IOP efficacy than the combination of dorzolamide and acetazolamide.

Acetazolamide↗
PubMed1981

Effect of timolol on platelet aggregation in coronary heart disease.

The immediate effect of beta-blockers versus placebo in platelet function was studied in ten healthy men one hour after either 40 mg propranolol, 5 mg timolol or placebo was given. Both beta-blockers had similar platelet effects. They increased the ADP-threshold in a platelet aggregation test and reduced the plasma level of beta-thromboglobulin whereas the primary aggregation remained unchanged. Forty-four patients were given timolol 10 mg twice daily or corresponding placebo medication in a secondary prevention trial after a myocardial infarction. At rest and also immediately after a near maximal exercise test the platelet function was similar on timolol and placebo. During exercise a lower ADP-threshold and a higher plasma level of beta-thromboglobulin was observed irrespective of whether the patients received placebo or timolol. Thus, the acute platelet inhibiting effect of timolol observed after a single dose disappeared during chronic timolol treatment. During 24 hours continuous ambulatory ECG monitoring patients on timolol treatment had significantly less arrhythmias than patients on placebo. A general effect on platelets cannot explain this antiarrhythmic effect of timolol during chronic therapy.

Adult↗
PubMed1993

Absorption of ocular timolol: drug concentrations and beta-receptor binding activity in the aqueous humour of the treated and contralateral eye.

We studied the ocular and systemic absorption of 40 microliters of topical 0.5% timolol in 57 patients using radioligand binding techniques. The mean concentration of timolol in aqueous humour of the treated eye was 1.9 +/- 0.8 micrograms/ml 74 minutes after instillation of the drug. About 18 h after drug instillation the aqueous humour concentration of timolol was 105.5 +/- 60.9 ng/ml. Timolol was found in 15 (42%) contralateral eyes. Concentration of timolol in the contralateral eye increased from 0.04 +/- 0.08 ng/ml at 50 min to 0.3 +/- 0.2 ng/ml at 134 min and was 0.2 +/- 0.4 ng/ml at 18 h after instillation. Timolol concentrations in the aqueous humour of the treated eye appeared to be high enough to occupy beta 1- and beta 2-receptors completely (100%) at 74 min and at 18 h after drug instillation. Timolol concentrations in the contralateral eye were high enough to occupy up to 33.0 +/- 24.7% of the beta 2-receptors and up to 51.7 +/- 35.1% of beta 2-receptors. High drug concentrations and complete beta-receptor occupancy in the aqueous humour of the treated eye after topical timolol are in agreement with the long-lasting ocular hypotensive effects. The low drug concentrations and partial receptor occupancy in the contralateral eye may also be of some clinical significance.

Absorption↗
PubMed2001

Meta-analysis of randomised controlled trials comparing latanoprost with timolol in the treatment of patients with open angle glaucoma or ocular hypertension.

AIM: To evaluate the comparative efficacy and tolerance of latanoprost versus timolol through a meta-analysis of randomised controlled trials (RCTs). METHODS: Systematic retrieval of RCTs of latanoprost versus timolol to allow pooling of results from head to head comparison studies. Quality of trials was assessed based on randomisation, masking, and withdrawal. Sensitivity analyses were used to estimate the effects of quality of study on outcomes. The data sources were Medline, Embase, Scientific Citation Index, Merck Glaucoma, and Pharmacia and Upjohn ophthalmology databases. There were 1256 patients with open angle glaucoma or ocular hypertension reported in 11 trials of latanoprost versus timolol. The main outcome measures were (i) percentage intraocular pressure (IOP) reduction for efficacy; (ii) relative risk, risk difference, and number needed to harm for side effects such as hyperaemia, conjunctivitis, increased pigmentation, hypotension, and bradycardia expressed as dichotomous outcomes; and (iii) reduction in systemic blood pressure and heart rate as side effects. RESULTS: Both 0.005% latanoprost once daily and 0.5% timolol twice daily reduced IOP. The percentage reductions in IOP from baseline (mean (SE)) produced by latanoprost and timolol were 30.2 (2.3) and 26.9 (3.4) at 3 months. The difference in IOP reduction between the two treatments were 5.0 (95% confidence intervals 2.8, 7.3). However, latanoprost caused iris pigmentation in more patients than timolol (relative risk = 8.01, 95% confidence intervals 1.87, 34.30). The 2 year risk with latanoprost reached 18% (51/277). Hyperaemia was also more often observed with latanoprost (relative risk =2.20, 95% confidence intervals 1.33, 3.64). Timolol caused a significant reduction in heart rate of 4 beats/minute (95% confidence interval 2, 6). CONCLUSION: This meta-analysis suggests that latanoprost is more effective than timolol in lowering IOP. However, it often causes iris pigmentation. While current evidence suggests that this pigmentation is benign, careful lifetime evaluation of patients is still justified.

Adrenergic beta-Antagonists↗
PubMed2003

A randomised, double masked, multicentre clinical trial comparing bimatoprost and timolol for the treatment of glaucoma and ocular hypertension.

AIM: To evaluate the safety and efficacy of bimatoprost 0.03% once daily or twice daily compared with timolol 0.5% twice daily in patients with glaucoma or ocular hypertension. METHODS: Multicentre, double masked, randomised, parallel group, 3 month trial comparing bimatoprost once daily (n=240), bimatoprost twice daily (n=240), and timolol twice daily (n=122). The primary efficacy end point was diurnal intraocular pressure (IOP) (8 am, 10 am, 4 pm). Safety measures included adverse events, ocular parameters, and systemic variables. RESULTS: Bimatoprost once daily provided significantly lower mean IOP than timolol twice daily at all times and follow up visits (p<0.001). At month 3, mean IOP reductions from baseline at 10 am (peak timolol effect) were bimatoprost once daily, 8.0 mm Hg (32.4%); bimatoprost twice daily, 6.3 mm Hg (25.2%); timolol, 5.5 mm Hg (22.7%). Bimatoprost twice daily was also more effective than timolol, but was not as effective as bimatoprost once daily. A higher percentage of patients achieved low target pressures with bimatoprost once daily than with timolol. The most frequent side effects with bimatoprost were eyelash growth and mild conjunctival hyperaemia. Systemic safety parameters were not affected by bimatoprost. CONCLUSIONS: Bimatoprost 0.03% once daily demonstrated superior efficacy compared with timolol 0.5% twice daily in patients with elevated IOP. Bimatoprost once daily was more effective than twice daily dosing.

Adult↗
PubMedDate not supplied

Comparison of efficacy and tolerability between two gel-forming timolol maleate ophthalmic solutions in patients with glaucoma or ocular hypertension.

PURPOSE: To compare two gel-forming timolol maleate ophthalmic solutions, Timoptol XE and Lizmon TG, in regard to efficacy and tolerability in patients with glaucoma or ocular hypertension by means of a patient-masked prospective randomized crossover study. SUBJECTS AND METHODS: A total of 37 patients with glaucoma or ocular hypertension under treatment with antiglaucoma ophthalmic solutions including 0.5% twice-daily timolol maleate participated in this study. Only timolol maleate was withdrawn and either Timoptol XE or Lizmon TG was randomly allocated. After instillation for 1 month, the other ophthalmic solution was subsequently instilled for another month. Routine ophthalmic examination including slit-lamp examination and intraocular pressure (IOP) monitoring was conducted before instillation of gel-forming ophthalmic solutions and just after completing the instillation of each ophthalmic solution. Patient questionnaire surveys were also performed just after completing the instillation of each ophthalmic solution. RESULTS: Mean IOP, just before the withdrawal of timolol ophthalmic solution, was 16.4 +/- 2.9 mm Hg. At the end of Timoptol XE or Lizmon TG instillation, mean IOPs were 16.3 +/- 2.5 or 16.3 +/- 3.0 mm Hg, respectively. The results of the questionnaire survey showed no significant difference between Timoptol XE and Lizmon TG in regard to all survey items. Twenty-nine patients (78.4%) preferred to use gel-forming timolol solutions rather than twice-daily timolol ophthalmic solution. The presence of concurrently used ophthalmic solutions did not effect the incidences of subjective symptoms. The incidences of objective adverse effects were not significantly different between two gel-forming timolol ophthalmic solutions. CONCLUSION: Both gel-forming timolol ophthalmic solutions could be good choices for glaucoma treatment.

Adult↗
PubMed1987

Beneficial effects of timolol on infarct size and late ventricular tachycardia in patients with acute myocardial infarction.

This investigation was undertaken to study the effects of beta-adrenergic blockade with timolol on infarct size and on the incidence of late ventricular tachycardia in patients with acute myocardial infarction of less than 6 hr of evolution. Patients were assigned randomly either to a placebo-treated group (98 patients) or to a timolol-treated group (102 patients). The patients were treated with 5.5 mg iv timolol (or matched placebo) as a bolus divided into four doses during the first 2 hr followed by 10 mg orally twice daily for 1 month. Cumulative total creatine kinase (CK) release, which reflects the amount of myocardial necrosis was 1677 +/- 132 IU/liter in the placebo group (n = 83) and 1274 +/- 73 IU/liter in the timolol group (n = 81, p less than .01), a 24% reduction. Cumulative release of CK-MB was 138 +/- 8 IU/liter in the placebo group and 106 +/- 8 IU/liter in the timolol group (p less than .01), a 23% reduction. Twenty-four hour Holter electrocardiograms were obtained on days 7, 14, 21, and 28 after the onset of the acute myocardial infarction in 80 patients in the placebo group and 82 patients in the timolol group. The incidence of ventricular tachycardia was lower in the timolol than in the placebo group (7 vs 16 patients, p = .05). We conclude that early administration of intravenous timolol followed by oral treatment in patients with acute myocardial infarction reduces infarct size as assessed by CK and CK-MB serum activity, and decreases the occurrence of late ventricular tachycardia.

Blood Pressure↗
PubMed2006

[Preparation and testing of buffered eye drops containing pilocarpine chloride with timolol maleate].

BACKGROUND/AIM: In glaucoma therapy beta-blocator, timolol-maleate, is the first-line medicine of selection, whereas a miotic, pilocarpine chloride, is one of the oldest medicines used for the treatment of this illness. They are applied as eye drops. In order to achieve a better therapeutic effect and improve life quality of the ill, we produced and tested eye drops formulations based on combining pilocarpinechloride and timolol maleate in buffers of diferent pH values. METHODS: Following the general pharmacopoeial eye drops preparation regulation, we prepared formulations, of solution type, of pilocarpine chloride and timolol maleate combination, of pilocarpine choloride alone and of timolol maleate alone. A modified phosphate buffer according to Sorensen at 7.4, 7.7 and 8.0 pH values was used as a solvent. The quality of the produced formulations was examined using physical and physico-chemical methods and biological tests. Following pharmacopoeial regulations, we examined clarity, pH value and sterilty. Pilocarpine chloride level was determined by means of ion-par (High Performance Liguid Chromatography) RP-HPLC method, whereas UV/VIS absorption spectrophotometry was used for determining the level of both timolol maleate, and timolol. RESULTS: Results showed that monocomponent and combined preparations complied with the regulation demands. With the increase in the pH value of the solution pilocarpine chloride level decreased in relation to its initial content, whereas timolol level showed a tendency of moderate increase. CONCLUSION: Magistrally prepared pilocarpine chloride eye drops with timolol maleate have satisfied all the required conditions for an ophtalmological preparation. A modified phosphate buffer according to Sorensen at 7.4 pH value proved to be the most optimal solvent.

Adrenergic beta-Antagonists↗
PubMed1992

Basal tear turnover and topical timolol in glaucoma patients and healthy controls by fluorophotometry.

To assess the effect of glaucoma and timolol on tear secretion, basal tear turnover was measured with fluorophotometry in 13 open-angle glaucoma patients not using any ophthalmic medication, 24 patients using timolol medication daily, and 41 healthy control subjects. Basal tear turnover is defined as the tear turnover at the lowest level of reflex lacrimation possible under physiologic conditions. Tear turnover was calculated from the decay of the tear fluorescence after instillation of fluorescein. Minimal influence of reflex lacrimation was obtained by instilling 1 microliter of 2% fluorescein without touching the eye and by discarding measurements performed in the first 5 min. Minimization was confirmed by a monophasic decay of tear fluorescence. The values of patients who used timolol and those who did not use timolol were significantly lower than those of healthy control subjects (mean values in percent/minute +/- standard deviation: 10.1 +/- 3.2, 12.3 +/- 4.1, and 15.6 +/- 5.4, respectively; Student's t-test: P < 0.02). The values of patients who used timolol were significantly lower compared to those of patients who did not use timolol (P = 0.03). The tear film break up time values of patients who used timolol were significantly shorter than those of patients who did not use timolol and healthy control subjects (Fisher exact test: P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1983

Effects of l- and d-timolol on cyclic AMP synthesis and intraocular pressure in water-loaded, albino and pigmented rabbits.

Topical 2% l- or d-timolol reduced the elevation of intraocular pressure induced by water-loading in conscious rabbits. This drug effect appeared on the peak elevation (in pigmented eyes) and on the down-phase (in albino and pigmented eyes) of elevated intraocular pressure. The contralateral eye and the treated eye responded similarly. In urethane anesthetized, water-loaded rabbits, a greater inhibitory effect of l-timolol was observed in pigmented eyes than in albino eyes. Two per cent l-timolol caused alterations of heart rate and arterial blood pressure in water-loaded anesthetized rabbits, but time courses of these alterations did not correlate with the inhibitory effect on the elevation of intraocular pressure. The beta-adrenergic antagonistic activity of l-timolol and d-timolol were compared by their ability to inhibit l-isoproterenol-stimulated cyclic AMP synthesis in the rabbit iris-ciliary body preparation in vitro. The I50S for l- and d-timolol differ by about 1.5 log units. In our studies, d-timolol has little of the intraocular pressure lowering and the beta-adrenergic antagonistic activity of l-timolol. Thus, the conscious, water-loaded, pigmented rabbit can be used as a model for studying the effects of beta-adrenergic antagonists on intraocular pressure.

Animals↗
PubMed1996

Serial administration of adrenergic antagonist and agonist ("pulsatile therapy") reduces the incidence of long-term drift to timolol in humans.

PURPOSE: To test whether the incidence of long-term drift to timolol can be reduced by a "pulsatile" treatment (6 months timolol-2 months dipivefrin). METHODS: In a randomized clinical trial, 100 consecutive subjects with ocular hypertension or high-tension primary open-angle glaucoma in at least one eye were randomly assigned to either group A, which was administered timolol 0.5% twice a day (b.i.d.), or to group B, which was administered timolol 0.5% b.i.d. (6 months) alternated with 0.1% dipivefrin b.i.d. (2 months). Diurnal intraocular pressure (IOP) was measured at recruitment, 1 month later during timolol administration ("reference value"), and every 6 months in group A or at the end of each pulse in group B. In bilateral cases, the right eye only was considered for the analysis. Length of follow-up was 54 months. Long-term drift was diagnosed if the IOP on timolol increased by at least 5 mm Hg over the reference value and was followed by a </ = 2mm Hg increase after withdrawing timolol for 2 weeks. RESULTS: Reference values were comparable in both groups (16.4+/-1.2 mm Hg in group A, 15.9+/-1.7 mm Hg in group B). Eleven subjects (four in group A and seven in group B) did not complete follow-up because IOP increased >5 mm Hg in the study eye without detectable drift to the beta-blocker. The actual 54-month incidence of long-term drift was 45% (21/46) in group A versus 7% (3/43) in group B (P<0.01). In group B, IOP was always higher during dipivefrin pulse than on timolol (paired samples t-test, P<0.01). However, dipivefrin proved more effective through follow-up; IOP was 21.1+/-1.2 mm Hg at month 8 (first "pulse") and 18.6+/-0.95 mm Hg at month 48 (last "pulse") (paired samples t-test, P<0.01). CONCLUSIONS: Serial administration of adrenergic antagonist and agonist can reduce the incidence of long-term drift to the beta-blockade in ocular hypertension and primary open angle glaucoma.

Adrenergic Agonists↗
PubMed1999

Timolol effects on aqueous humor dynamics in eyes of anesthetized rats.

Anterior chambers of the eyes of male rats were cannulated under pentobarbital anesthesia for intracameral infusions of balanced salt solution (BSS) and intraocular pressure (IOP) recording. Blood pressure was recorded from a femoral artery. IOP was recorded during a 2-h intracameral infusion composed of a constant component (0.05 microl/min) and a periodic component (0.25 microl/min), cycling at 4 min on and then 4 min off. After a 20-min baseline period, 1 drop of timolol (0.5%) or BSS was applied to the cornea and repeated 1 h later. Intracameral infusions of BSS and 0.05% timolol were also compared. Topical timolol slightly delayed the BSS-induced IOP rise (p <.05). Complex demodulation and the estimated gain parameter of a second-order transfer function fit to the periodic responses revealed that topical timolol also reduced (p <.05) passive outflow resistance. Intracameral timolol markedly delayed the BSS-induced rise in IOP. Initially, timolol decreased both outflow impedance and nonresistive components (p <.05) of IOP, but these effects dissipated by 2 h when IOPs were similar. In all experiments, within-group blood pressure was unchanged. Topical and intracameral timolol have different effects on IOP. The data support the opinion that, in vivo, timolol acts at beta-receptors that control both outflow impedance and nonresistive mechanisms, probably vascular, to lower IOP.

Administration, Topical↗
PubMed2003

Human lens epithelial cell damage and stimulation of their secretion of chemical mediators by benzalkonium chloride rather than latanoprost and timolol.

OBJECTIVE: To investigate the effects of latanoprost, timolol maleate, and benzalkonium chloride on cell damage and induction of the secretion of chemical mediators of stress and wound healing by human lens epithelial cells in culture. METHODS: Cells from a human lens epithelial cell line (SRA01/04) were cultured in Dulbecco minimum essential medium supplemented with 5% fetal bovine serum. The amounts of latanoprost (50 micro g/mL), timolol maleate (5 mg/mL), or benzalkonium chloride (200 micro g/mL) used in eyedrops, and x10 to x1000 dilutions thereof, were added to the medium. After 7 days' culture, cell morphological changes were assessed using phase-contrast microscopy, and cell-free culture supernatants were collected for prostaglandin E2 (PGE2), interleukin 1alpha (IL-1alpha), and interleukin 6 (IL-6) iodine I 125 radioimmunoassay, enzyme-linked immunosorbent assay, and chemiluminescent enzyme immunoassay, respectively. RESULTS: All cells that were cultured with the concentrations of latanoprost, timolol, or benzalkonium chloride used in eyedrops detached from the culture dish and died within 3 days. At a x10 dilution of latanoprost or timolol or a x100 dilution of benzalkonium chloride, no proliferation or elongation of the cells was observed. Secretions of PGE2, IL-1alpha, and IL-6 at x10 dilutions of latanoprost or timolol were 3 to 77 times higher than in controls, whereas they were 190 to 305 times higher at a x180 dilution of benzalkonium chloride. The amounts of these soluble mediators in culture supernatants depended on the dose of latanoprost, timolol, or benzalkonium chloride added. CONCLUSION: Our results indicate that benzalkonium chloride, used as the preservative in eyedrops containing latanoprost or timolol, is the agent most damaging to lens epithelial cells and most strongly stimulates the expression of soluble chemical mediators in these cells.

Antihypertensive Agents↗