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PubMed1987

[Long-term study of chronic glaucoma treated with beta blockers (timolol)].

In the study presented here the authors documented 50 patients with chronic glaucoma, aged between 42 and 86, who were followed up on an outpatient basis for a minimum of 3 and a maximum of 6 years. The results can be summarized as follows: 1) treatment with timolol resulted in an average lowering of intraocular pressure by 6 mm Hg, without any fall-off in effect over several years; 2) there was no deterioration in visual fields or visual acuity during treatment with timolol, and in some cases there was an improvement; 3) in the cases of angle-closure glaucoma the therapy was combined with pilocarpine; this resulted in a greater lowering of pressure than that achieved by treatment with timolol alone in cases of open-angle glaucoma.

Adult↗

PubMed1987

[Effectiveness and tolerance of an active combination of timolol and pilocarpine--a pilot project].

A pilot study was conducted to find out whether it is possible to achieve a further drop in intraocular pressure in eyes with glaucoma, which is about 22 mmHg after treatment with 0.5% timolol, by employing a combination preparation of timolol 0.5% and pilocarpine 2% or timolol 0.5% and pilocarpine 4% respectively, administered as eyedrops. This resulted in an average additional lowering of 1.9 mmHg after 2 hrs and by 2.1 mmHg after 6 hours (TP2) or by 3.0 mmHg after 2 and 3.5 mmHg after 6 and by 2.7 mmHg after 12 hours (TP4), the therapeutically relevant duration of effectivity being 6 (TP2) or 12 (TP4) hours, respectively.

Dose-Response Relationship, Drug↗

PubMed1985

[Pressure lowering effect and side effects of 0.5% and 1.0% levobunolol eyedrops, compared with 0.5% timolol eyedrops in patients with open-angle glaucoma].

Fifty patients with open-angle glaucoma were treated twice daily for one year with topical 0.5% levobunolol, 1% levobunolol, or 0.5% timolol. Both concentrations of levobunolol were as effective as timolol in reducing intraocular pressure over the one-year period. At the concentrations tested, levobunolol and timolol decreased heart rate to a similar extent, suggesting that systemic absorption occurred after topical instillation. In all three treatment groups, clinically insignificant changes in blood pressure were observed sporadically throughout the one-year period. Very few clinically significant toxic ocular reactions were observed.

Dose-Response Relationship, Drug↗

PubMed1982

[Are 0.1% timolol-maleate eyedrops suitable for treating chronic glaucoma? (author's transl)].

On the basis of 47 patients with chronic open-angle glaucoma, the administration of 0.1% timolol-maleate eye-drops was investigated in the form of a controlled long-term study over a period of 56 weeks. It was found that in a remarkable proportion of chronic glaucoma cases, this low concentration had an adequate, long-term effect, reducing IOP by 24-27%. The results obtained give sufficient grounds for the assumption that in the initial stages of glaucoma, the 0.1% solution is just as effective as solutions of a higher concentration, provided that a satisfactory degree of responsiveness to timolol-maleate is present from the outset. The local and systemic side-effects are relatively slight and therefore also fewer than with higher concentrations. Since in over 50% of patients with chronic glaucoma, 0.1% timolol-maleate eye-drops reduce IOP adequately over a considerable period of time, the 0.1% solution is to be recommended at all events for the initial treatment of glaucoma patients.

Chronic Disease↗

PubMed1981

[Timolol in the treatment of glaucoma (author's transl)].

Untolerated or insufficiently effective Therapy in 32 patients (63 eyes) with primary open-angle glaucoma was discontinued and substituted with Timolol, and all patients were followed up over a period of 60 weeks. Timolol was well tolerated in all cases without any local or systemic side effects. Either alone or in combination with other medications Timolol brought about an adequate reduction in intraocular pressure in eyes which hitherto had no longer responded to conventional conservative therapy.

Follow-Up Studies↗

PubMed1981

[Timolol versus Diamox (author's transl)].

Comparisons between tonography results confirm an almost identical action of timolol and diamox: With both, the intraocular pressure and the minute volume of aqueous flow are significantly reduced, while the resistance to the aqueous outflow remains unchanged. In a consecutive tonometric study it was proved that timolol, when fully developed, inhibits the pressure-lowering effect of diamox (500 mg i.v.) when applied two hours before the latter. Thus the action of timolol is not additive but rather substitutive to the action of diamox. Its maximal pressure-lowering effect corresponds to the half of the aqueous outflow-pressure gradient.

Acetazolamide↗

PubMed1980

[Clinical experience in treatment of glaucoma with timolol (author's transl)].

Forty patients with primary and secondary glaucoma were treated with the beta-blocking agent Timolol for six months. We used a 0.25% or 0.5% solution twice a day. In several cases sufficient pressure regulation was achieved by means of Timolol monotherapy. If pilocarpine or acetazolamide therapy was not sufficient we used a combination therapy with Timolol.

Acetazolamide↗

PubMed1980

[Long-term results with timolol].

The results of an 18-month study with Timolol in 36 patients with glaucoma or ocular hypertension are presented. Patients with ocular hypertension were well controlled with Timolol alone, while in the glaucoma group most patients needed combined treatment with a parasympathomimetic drug. Some trends suggest a continuous diminution of the hypotensive effect to Timolol, especially in the glaucoma group. No severe reactions were observed, although slight bradycardia could represent a risk for patients with severe heart conditions. Minor local and systemic side effects are mentioned.

Clinical Trials as Topic↗

PubMed1980

[Experience with timolol in consulting patients (author's transl)].

Experience obtained in the treatment of 78 eyes of patients suffering from open-angle glaucoma with the beta-blocker Timolol 0.25% and 0.5%. Timolol was only given to patients whose intraocular pressure could no longer be adequately regulated by the medications previously employed. A synopsis is given of the medications used over many years. The intraocular pressures of the eyes that responded to Timolol remained below 23 mmHg even after prolonged use, so that a fistulizing operation was initially unnecessary.

Clonidine↗

PubMed2002

A prospective, long-term, randomized study of the efficacy and safety of the drug combination pilocarpine 1% with clonidine 0.06% or clonidine 0.125% versus timolol 0.25%.

The purpose of this prospective, randomized study was to evaluate the efficacy and safety of the drug combinations--pilocarpine 1% with clonidine 0.06% and pilocarpine 1% with clonidine 0.125%, in comparison with timolol 0.25%. 54 patients with bilateral primary open angle glaucoma and comparable IOP were assigned to three study groups: group 1 received the drug combination of pilocarpine 1% and clonidine 0.06%, group 2 received the drug combination pilocarpine 1% and clonidine 0.125% and group 3 only timolol 0.25% drops. In all groups twice-daily medication was used. Mean diurnal IOP as well as ocular and systemic side effects were evaluated at week 1, 2, 4, 8 and 12. Changes in blood pressure, pulse rate, pupil size and patient symptoms were also recorded. At three months all patients had completed the study. Diurnal IOP was significantly reduced from baseline in all groups and consistent IOP reduction was achieved in all three groups at all follow up periods. Mean IOP reduction was 18.40%, 28.45% and 24.64% in group 1, group 2 and group 3, respectively. Flattening of the diurnal fluctuation in IOP was also seen in all patients. On comparing the IOP reduction achieved amongst the three groups, there was a statistically significant difference between group 1 and group 2 as well as between group I and group 3 while the difference between group 2 and group 3 was statistically insignificant. The drug combinations of pilocarpine 1% and clonidine did not produce any statistically significant effect on pupil diameter. No statistically significant difference was noted with respect to patient symptoms, blood pressure and pulse rate. In conclusion, the drug combination of pilocarpine 1% and clonidine 0.125% produces IOP reduction comparable to that achieved with timolol 0.25% drops in twice daily dosage and does not result in any significant ocular and systemic adverse effects.

Adrenergic alpha-Agonists↗

PubMed2002

Tolerability and efficacy of dorzolamide versus acetazolamide added to timolol.

PURPOSE: Evaluate the safety and efficacy of dorzolamide versus acetazolamide when added to once daily 0.5% timolol maleate ophthalmic gel forming solution (timolol gel). METHODS: This was a randomized, double-masked, multicenter, active-controlled, parallel group study of 215 patients with open-angle glaucoma or ocular hypertension. Following a two-week treatment period with timolol gel, patients with IOP > or = 22 mm Hg and who tolerated one week of acetazolamide 250-mg q.i.d. either were randomized to acetazolamide or dorzolamide 2% three times daily for 12 weeks. RESULTS: In 155 randomized patients (dorzolamide, N = 80, acetazolamide, N = 75), compared to the dorzolamide, acetazolamide had a statistically greater number of systemic adverse events (dorzolamide 50%, acetazolamide 75%, p = 0.001), adverse events associated with carbonic anhydrase inhibitor (CAI) therapy (dorzolamide 26%, acetazolamide 53%, p < 0.001) and discontinuations due to CAI adverse experiences (dorzolamide 8%, acetazolamide 24%, p = 0.007). Intent to treat analysis found that changes from baseline in IOP were similar at both troughs (dorzolamide 1.4 +/- 0.46 mm Hg, acetazolamide 0.8 +/- 0.47 mm Hg, p = 0.386). However, per-protocol analysis found statistically improved pressure control with acetazolamide (0.1 +/- 0.42 mm Hg) compared to dorzolamide (1.9 +/- 0.43 mm Hg) (p = 0.009). CONCLUSIONS: This study found a greater incidence of systemic and CAI adverse experiences and discontinuations due to acetazolamide compared to dorzolamide.

Acetazolamide↗

PubMed2003

Effect of changing from concomitant timolol pilocarpine to bimatoprost monotherapy on ocular blood flow and IOP in primary chronic angle closure glaucoma.

The aim of the present prospective masked study was to assess the effect of bimatoprost monotherapy on ocular blood flow and intraocular pressure (IOP) in eyes of primary chronic angle closure glaucoma patients already on concomitant timolol and pilocarpine. Thirty two patients of bilateral primary chronic angle closure glaucoma (PCACG) on topical timolol 0.5% twice a day and pilocarpine 2% three times daily were switched over to bimatoprost 0.03% once daily in both eyes. Intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) were recorded before and after starting bimatoprost and were followed up every four weeks for three months. Bimatoprost had statistically significant (p < 0.05) mean IOP reduction from 19.3 +/- 6.6 to 13.5 +/- 4.5 mmHg (30.5%) and there was improvement from 858 +/- 260 to 1261 +/- 321 microL/min (46.8%) in mean pulsatile ocular blood flow (p < 0.05). Conjunctival hyperemia (32%) was the most common adverse effect of bimatoprost. Bimatoprost 0.03% monotherapy improved ocular blood flow and provided a better diurnal IOP control than concomitant timolol-pilocarpine in eyes with primary chronic angle closure glaucoma and was found to be well tolerated.

Administration, Topical↗

PubMed2003

A six-week, parallel, randomized, double-blind study comparing the efficacy and safety of the 0.5% timolol/2.0% MK-507 combination b.i.d. to the concomitant administration of 0.5% timolol b.i.d. and 2.0% MK-507 b.i.d.

This was a 6-week, parallel, randomized, double-blind study comparing the efficacy and safety of the 0.5% timolol/2.0% MK-507 combination b.i.d. to the concomitant administration of 0.5% timolol b.i.d. and 2.0% MK-507 b.i.d. Patients with ocular hypertension or open-angle glaucoma from 21 to 85 years of age were enrolled in this study. Each of them should have intraocular pressure (IOP) of 20 mmHg or more in the study eye after they completed the wash-out period. The patients enrolled were randomly assigned to either combination (0.5% timolol/2.0% MK-507 b.i.d. and placebo b.i.d.) or concomitant (0.5% timolol b.i.d. and 2.0% MK-507 b.i.d.) treatment. During the study, no systemic or topical medication affecting IOP other than test drugs were allowed. A total of 20 randomized patients were included in the intention-to-treat population for analysis of data. The ten were assigned to the combination treatment and others were assigned to the concomitant treatment. There was no statistically significant difference between the two study treatments in terms of gender distribution, average age, and average IOP at the trough and the peak before starting the test medications. Mean reduction of the IOP from baseline to the final visit at the trough was 5.04 mmHg in the combination treatment and was 2.73 mmHg in the concomitant treatment. Mean reduction of the IOP at the peak was 2.19 mmHg in the combination treatment and was 2.53 mmHg in the concomitant treatment. There were no statistically significant differences in the above analyses between the two treatments. Safety evaluation was carried out, and number of adverse events in each treatment group did not differ substantially. Ocular signs and symptoms were evaluated in each visit, and all of the between-treatment values were not different significantly, either. Laboratory tests were performed, and showed no significant differences between pre- and post-treatment periods. None of these was found to be clinically serious, either. We concluded that the 0.5% timolol/2.0% MK-507 combination b.i.d. is equivalent in the efficacy of lowering IOP as well as safety compared to the concomitant administration of 0.5% timolol b.i.d. and 2.0% MK-507 b.i.d. in patients with ocular hypertension or open-angle glaucoma.

Adult↗

PubMed2004

Binding affinities of ocular hypotensive beta-blockers levobetaxolol, levobunolol, and timolol at endogenous guinea pig beta-adrenoceptors.

The current study determined the relative affinities and selectivities of numerous beta-adrenoceptor antagonists at the endogenous beta(1)- and beta(2)-adrenoceptors in guinea pig heart and lung, respectively, using [(3)H]-CGP12177. Specific binding of [(3)H]-CGP12177 comprised 80 +/- 0.2% (n = 11) and 94 +/- 0.2% (n = 16) of the total binding in washed heart and lung homogenates, respectively. Concentration-dependent displacement of [(3)H]-CGP12177 binding from beta-adrenoceptors in both preparations was observed with nine different beta-adrenoceptor antagonists. Levobetaxolol, betaxolol, CGP-20712A, levobunolol, and timolol yielded bi-phasic (two-site-fit) competition curves in the heart, while CGP-20712A, ICI-118551 and levobunolol produced bi-phasic curves in the lung preparation. The high-affinity component of [(3)H]-CGP12177 binding in the heart and lung reflected binding to beta(1)-receptors and beta(2)-receptors, respectively. The binding inhibition parameters (IC(50)s) for displacement of [(3)H]-CGP12177 from these predominantly high-affinity sites were: levobetaxolol (24.9 +/- 1.6 nM heart, 4810 +/- 367 nM lung), racemic betaxolol (37.9 +/- 8.7 mM heart; 8840 +/- 424 mM lung), CGP-20712A (4.6 +/- 0.9 nM heart; 171,000 +/- 109,000 nM lung), ICI-118551 (9230 +/- 3240 nM heart; 2.9 +/- 0.6 nM lung), levobunolol (42 +/- 15 nM heart, 0.3 +/- 0.2 nM lung), (l)-timolol (3.1 nM heart, 2.9 +/- 1.5 nM lung), ICI-215001 (5840 +/- 114 nM heart; 26100 +/- 3200 nM lung), BRL-37344 (83,300 +/- 2660 nM heart; 13,200 +/- 1250 lung). These data indicated that while levobetaxolol and betaxolol possessed a 193-233-fold selectivity for beta(1)-receptors, levobunolol exhibited a 140-fold beta(2)-receptor selectivity and (l)-timolol was essentially nonselective.

Adrenergic beta-Antagonists↗

PubMed1985

Interaction of timolol and caffeine on intraocular pressure.

The clinical interaction of 0.5% timolol maleate and 400 mg of oral caffeine on the intraocular pressure of 20 normotensive volunteers was studied. Caffeine administration did not significantly alter the reduction in intraocular pressure in timolol treated eyes. An antagonism, however, was observed in the fellow timolol untreated eyes with caffeine. The crossover reduction in intraocular pressure noted in the control group was significantly depressed in the caffeine group. A proposed mechanism for these observations is discussed.

Adult↗

PubMed1986

Influence of pindolol and timolol treatment on the visual fields of glaucoma patients.

In a prospective, multicenter, randomized, double-masked study of glaucoma patients, visual fields, intraocular pressures, blood pressures, and pulse rates were measured after a 4-week wash-out period and after three and six months of treatment with either pindolol 1% or timolol 0.5% twice daily. Both drugs reduced significantly the IOP. The blood pressure was not changed significantly whereas the pulse rate was reduced more in the timolol treated group than in the pindolol treated group. The visual fields of the pindolol group showed on the average a slight tendency towards improvement and in the timolol treated group a very slight tendency for deterioration. The difference between these two trends was statistically significant (p less than 0.05).

Blood Pressure↗

PubMed1996

Ocular mini-tablets for controlled release of timolol: evaluation in rabbits.

Topical delivery of timolol by inserts or similar controlled-release devices may offer distinct advantages over administration by eyedrops. The purpose of this investigation was the evaluation in rabbits of ophthalmic inserts (denominated mini-tablets, MT) for sustained/controlled release of timolol maleate (TiM). The MTs (diameter 3.5 mm, thickness 1.5 mm, average TiM content 0.34 or 0.68 mg) were prepared by compressing appropriate mixtures of powders with a standard tabletting machine. A thin, rate-controlling membrane was applied over the devices by spraying aqueous dispersions of acrylic copolymers. A first series of different (uncoated and coated) MTs were tested for release of TiM to the lacrimal fluid, using commercial eyedrops (Timoptol 0.5%) as a reference standard. Two MTs (one of which was coated) and the same reference solution were then selected for an ocular absorption study. Analysis of TiM in the aqueous humor indicated that the coated MT was capable of maintaining low and steady levels of TiM for at least 19 h, while the other device, identical but uncoated, produced a prolonged-pulse effect lasting about 8 h. The apparent mean residence time (MRT) of TiM in the aqueous humor was 1.3 h for the reference solution, 3.2 h for the uncoated MT, and 5.7 h for the coated one. The present preliminary results point to the potential validity of coated mini-tablets as simple systems for controlled ocular delivery of timolol.

Absorption↗

PubMed1997

The effect of 0.5% timolol maleate on the ocular perfusion of ocular hypertensive patients by scanning laser flowmetry.

To understand the effect of 0.5% timolol maleate on the ocular perfusion of the optic disc and macula in ocular hypertensive patients, we enrolled 10 males and 15 females without any systemic or ocular disease, except intraocular pressure higher than 20 mmHg. Their average age was 33 +/- 13 y/o (range 14-45). Under the randomized, double-masked design, one drop of 0.5% timolol maleate was given in one eye, and placebo in the fellow eye. Heart rate, blood pressure, intraocular pressure, and ocular perfusion were measured at baseline, and then 30 minutes and 2 hours after treatment. Ocular perfusion was measured by Heidelberg Retina Flowmeter (Heidelberg Engineering GmbH, Heidelberg, Germany). We used 10 degrees measurement field and 10 x 10 pixels measurement frame. Four areas were measured, i.e., temporal upper, temporal lower, and nasal parts of the optic disc, and macula. In comparison to the baseline, the treated eyes had a slight reduction of blood flow, volume, and velocity 30 minutes after treatment, but these parameters came back close to the baseline value at 2 hours after treatment. Similar changes were also noted in the control eyes. The results showed that a single drop of 0.5% timolol had minimal effects on the retinal and macular circulation within 2 hours after treatment.

Adolescent↗