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At least 271 records · Page 15Linked to original sources

PubMed2000

Comparison of the intraocular pressure lowering effect of latanoprost and a fixed combination of timolol-pilocarpine eye drops in patients insufficiently controlled with beta adrenergic antagonists. French Latanoprost Study Group, and the Swedish Latanoprost Study Group.

AIMS: To compare the effect on intraocular pressure (IOP) of latanoprost monotherapy and timolol-pilocarpine in patients with glaucoma or ocular hypertension with inadequately controlled IOP on topical beta adrenergic antagonists. METHODS: This was a multicentre, randomised, observer masked, 6 week study performed in France and Sweden. 23 centres enrolled 237 patients with glaucoma or ocular hypertension and an IOP of at least 22 mm Hg on treatment with topical beta adrenergic antagonists, alone or in combination. After a 21 day run in period on timolol 0.5% twice daily, patients were randomised either to latanoprost 0.005% once daily or to a fixed combination of timolol-pilocarpine twice daily. Changes in mean diurnal IOP from the baseline to the 6 week visit were determined with an analysis of covariance. RESULTS: Mean diurnal IOP was statistically significantly decreased from baseline in both groups (p<0.001). Switching to latanoprost treatment reduced mean diurnal IOP by 5.4 (SEM 0.3) mm Hg (ANCOVA -22%) and switching to timolol-pilocarpine treatment reduced mean diurnal IOP by 4.9 (0.4) mm Hg (-20%). Blurred vision, decreased visual acuity, decreased twilight vision, and headache were statistically significantly more frequent in the timolol-pilocarpine group. CONCLUSIONS: Latanoprost monotherapy was at least as effective as fixed combination timolol-pilocarpine twice daily treatment in reducing mean diurnal IOP in patients not adequately controlled on topical beta adrenergic antagonists. Latanoprost was better tolerated than timolol-pilocarpine regarding side effects. These results indicate that a switch to latanoprost monotherapy can be attempted before combination therapy is initiated.

Adult↗

PubMed2003

Unoprostone as adjunctive therapy to timolol: a double masked randomised study versus brimonidine and dorzolamide.

AIMS: To compare the safety and efficacy of unoprostone, brimonidine, and dorzolamide as adjunctive therapy to timolol in patients with primary open angle glaucoma or ocular hypertension. METHODS: This was a randomised, double masked, parallel group, multicentre (14) study. After using timolol maleate 0.5% monotherapy twice a day for 2 weeks, patients (n = 146) with an early morning intraocular pressure (IOP) between 22 and 28 mm Hg, inclusively, received unoprostone isopropyl 0.15% (n = 50), brimonidine tartrate 0.2% (n = 48), or dorzolamide hydrochloride 2.0% (n = 48) twice daily as adjunctive therapy to timolol maleate 0.5% for another 12 weeks. Safety was based on comprehensive ophthalmic examinations, adverse events, and vital signs. Efficacy was based on mean change from baseline in the 8 hour diurnal IOP at week 12. Baseline was defined as values obtained after 2 weeks of timolol monotherapy. RESULTS: Each drug was safe and well tolerated. Burning/stinging was the most common treatment emergent adverse event. No clinically relevant changes from baseline were observed for any ophthalmic examination or vital signs. At week 12, each adjunctive therapy produced statistically significant (p<0.001) reductions from timolol treated baseline in the mean 8 hour diurnal IOP (-2.7 mm Hg, unoprostone; -2.8 mm Hg, brimonidine; -3.1 mm Hg, dorzolamide). The extent of IOP reduction did not differ significantly between unoprostone and either brimonidine (p = 0.154) or dorzolamide (p = 0.101). CONCLUSION: Unoprostone was safe and well tolerated and provided a clinically and statistically significant additional reduction in IOP when added to stable monotherapy with timolol. Furthermore, unoprostone was not significantly different from brimonidine and dorzolamide as adjunctive therapy to timolol.

Adult↗

PubMed2001

Timolol may inhibit aqueous humor secretion by cAMP-independent action on ciliary epithelial cells.

The beta-adrenergic antagonist timolol reduces ciliary epithelial secretion in glaucomatous patients. Whether inhibition is mediated by reducing cAMP is unknown. Elemental composition of rabbit ciliary epithelium was studied by electron probe X-ray microanalysis. Volume of cultured bovine pigmented ciliary epithelial (PE) cells was measured by electronic cell sizing; Ca(2+) activity and pH were monitored with fura 2 and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, respectively. Timolol (10 microM) produced similar K and Cl losses from ciliary epithelia in HCO/CO(2) solution but had no effect in HCO/CO(2)-free solution or in HCO/CO(2) solution containing the carbonic anhydrase inhibitor acetazolamide. Inhibition of Na(+)/H(+) exchange by dimethylamiloride in HCO/CO(2) solution reduced Cl and K comparably to timolol. cAMP did not reverse timolol's effects. Timolol (100 nM, 10 microM) and levobunolol (10 microM) produced cAMP-independent inhibition of the regulatory volume increase (RVI) in PE cells and increased intracellular Ca(2+) and pH. Increasing Ca(2+) with ionomycin also blocked the RVI. The results document a previously unrecognized cAMP-independent transport effect of timolol. Inhibition of Cl(-)/HCO exchange may mediate timolol's inhibition of aqueous humor formation.

Animals↗

PubMed1999

The short-term effect of adding brimonidine 0.2% to timolol treatment in patients with open-angle glaucoma.

Brimonidine, a highly selective alpha(2)-adrenoceptor agonist, was studied to determine its ocular hypotensive effect and side effects in patients with elevated intraocular pressure (IOP) while on continuing therapy with timolol. This was a prospective, randomized, placebo-controlled study in 15 patients with primary open-angle or pseudoexfoliation glaucoma on therapy receiving timolol 0.5% twice daily, with IOP greater than or equal to 22 mm Hg in one eye. IOP measurements, blood pressure and pulse rate were assessed on 2 days at a baseline and 1, 2, 4, 6 and 8 h later. A single drop of brimonidine 0.2% or placebo was added to treatment with timolol. The reductions in IOP at all time intervals observed with brimonidine + timolol were significantly greater than those with timolol + placebo. The maximum mean net decrease in IOP was 19.23 +/- 10.60% at 4 h. Statistically significant decreases in systemic blood pressure and pulse rate without clinical symptoms were observed in the group receiving brimonidine + timolol. This study suggests that a combination of brimonidine and timolol may have potential in the treatment of glaucoma. Further clinical trials with brimonidine are indicated to assess its further role as adjunctive agent.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Changing antiglaucoma therapy from timolol to betaxolol: effect on ocular blood flow.

The aim of the present study was to investigate the effect of a therapy change from timolol to betaxolol on ocular blood flow in patients with open-angle glaucoma. This randomized double-blind study comprised 34 consecutive patients with open-angle glaucoma, already treated with either timolol alone or in combination with other antiglaucoma agents. The patients were randomly allocated to receive either betaxolol (n = 17) or timolol (n = 17) instead of the present timolol drops. Additional antiglaucoma therapy remained unchanged. The retinal blood flow was assessed by scanning laser Doppler flowmetry and the pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. Ocular blood flow measurement as well as systemic hemodynamic and intraocular pressure (IOP) measurements were performed at baseline and 1 week and 1 and 3 months after the therapy change. Visual field testing was performed at baseline and at 3 months. After 3 months of treatment with either timolol or betaxolol, neither the retinal nor the pulsatile choroidal blood flow were significantly altered. The power to detect a 9% change in pulsatile choroidal blood flow and a 20% change in retinal blood flow in the present study was 90%. The IOP was not significantly altered in either group. In contrast, visual fields slightly improved after betaxolol treatment compared to baseline (p = 0.047), but this effect was not significant versus timolol. Changing therapy from timolol to betaxolol has no effect on ocular blood flow in patients with open-angle glaucoma.

Adolescent↗

PubMed1982

Role of the beta-adrenergic receptor-binding agent 'timolol' in the treatment of open-angle glaucoma.

A follow-up study was performed on 54 eyes with chronic open-angle glaucoma treated with timolol maleate. It was carried out as an open clinical trial with a selected group of eyes. During 2 years of application the effect of timolol under normal conditions as well as under stress tests (darkness test, water-, coffee- or tea-drinking test, early morning measurements) was observed. Until now 40% of patients were regulated with 0.25% timolol twice daily. Another 50% obtained good pressure values under 0.5% timolol therapy and the rest with 0.5% timolol and 2% pilocarpine twice daily. Early morning measurement was shown to be the most important indicator of intraocular pressure regulation by beta-blocking agents. While timolol is usually very effective in reducing the intraocular pressure during daytime, several patients showed unattended high morning pressure values. Up to now, no severe side-effects of timolol therapy have been observed.

Adrenergic beta-Antagonists↗

PubMed1982

Timolol-related reduction in mortality and reinfarction in patients ages 65-75 years surviving acute myocardial infarction. Prepared for the Norwegian Multicentre Study Group.

Long-term treatment with timolol in patients ages 65--75 years who survived myocardial infarction was related to a significant reduction, compared with placebo, in overall mortality (p less than 0.05), total cardiac death (p less than 0.01), sudden death (p less than 0.05) and reinfarction (p less than 0.01). The analyses were based on 732 patients (384 taking placebo and 348 timolol) from a cohort of 1884 patients in the Norwegian multicenter timolol study. The dosage of timolol was 10 mg twice daily and the patients were followed for 12--33 months (mean 17 months). There were 83 deaths in the placebo group and 52 deaths in the timolol group, a reduction of 35.5%. There were 69 initial reinfarctions in the placebo group and 38 in the timolol group, a reduction of 39.2%. There was no difference in the reduction of mortality and reinfarction between patients 65--75 years of age and patients less than 65 years of age. The incidence of side effects, the number of withdrawals and the reasons for withdrawal were similar in older and younger patients. We conclude that age should not be a decision-making factor concerning timolol therapy in postinfarct patients.

Adrenergic beta-Antagonists↗

PubMed1987

Increased occurrence of left ventricular thrombi during early treatment with timolol in patients with acute myocardial infarction.

To examine whether early intervention with timolol influences the occurrence of left ventricular thrombi in acute anterior myocardial infarction, 40 patients with acute anterior myocardial infarction admitted to hospital within 6 hr of onset of symptoms were randomly assigned to receive intravenous followed by oral timolol maleate or placebo. Five (25%) of 20 patients in the placebo group and 14 (73.7%) of 19 patients with confirmed infarction in the timolol group developed a left ventricular apical thrombus as detected by two-dimensional echocardiography from 2 to 10 days after inclusion (p less than .005). Patients received anticoagulants only after a left ventricular thrombus had been diagnosed. Only one patient with thrombus suffered peripheral embolization (timolol group). The treatment groups were comparable with respect to location of regional left ventricular dysfunction, electrocardiographic changes, and infarct size estimated by creatine kinase release. However, computer-assisted regional wall motion analysis demonstrated significantly reduced apical wall motion in the timolol group compared with the placebo group (p less than .01). Also, the mean heart rate during the first 10 days after the acute infarction was reduced by 13% in the timolol group (p less than .001). The reduction in heart rate and left ventricular apical wall motion caused by timolol in patients with acute anterior myocardial infarction may increase the occurrence of left ventricular thrombi.

Creatine Kinase↗

PubMedDate not supplied

A pooled-data analysis of three randomized, double-masked, six-month clinical studies comparing the intraocular pressure reducing effect of latanoprost and timolol.

PURPOSE: To compare the intraocular pressure (IOP) reduction by latanoprost and timolol, and to study factors of prognostic value for assessing this reduction. METHODS: We analyzed 829 patients included in three phase 111 studies comparing six months' treatment with 0.005% latanoprost once daily and 0.5% timolol twice daily in patients with open-angle glaucoma or ocular hypertension. Analysis of covariance controlled for differences in baseline IOP and sex was used to assess the IOP reduction. RESULTS: Latanoprost reduced diurnal IOP (average of morning, noon and afternoon assessments) by 7.7 mmHg (31%) and timolol by 6.5 mmHg (26%) after six months of treatment. Thus the diurnal IOP was reduced 1.2 mmHg (18%) more with latanoprost than with timolol (p<0.001). Latanoprost-treated patients showed a further decrease in morning IOP of 0.7 mmHg (9%, p<0.001) from the initial morning IOP reduction obtained at two weeks. No such further decrease in IOP was seen with timolol. Higher baseline diurnal IOP resulted in a larger diurnal reduction during treatment with both drugs (p<0.001). Diurnal IOP in women was reduced 0.7 mmHg (11%) less than males with both drugs (p<0.001). CONCLUSIONS: Latanoprost was more effective than timolol in reducing mean diurnal IOP. The effect after two weeks was maintained for timolol while with latanoprost there was a further, significant IOP reduction from two weeks to six months. Baseline IOP was the only factor of clinical importance found to be of prognostic value for assessing the IOP reduction.

Aged↗

PubMedDate not supplied

Timolol treatment after myocardial infarction in diabetic patients.

In diabetic patients long-term treatment with timolol after myocardial infarction was related to a reduction in overall mortality, total cardiac death, sudden death, and nonfatal reinfarction, compared with patients in a placebo group. The analyses were based on 99 diabetic patients in the Norwegian timolol multicenter study. The dosage of timolol was 10 mg twice daily and the follow-up period was 12-33 mo (mean: 17 mo). When analyzing all randomized patients, there were 14 deaths in the placebo group and 6 deaths in the timolol group, a reduction of 62.8% (P less than 0.05). The number of nonfatal reinfarctions was 10 in the placebo group and 2 in the timolol group, a reduction of 82.7% (P less than 0.05). With regard to inclusion rate, side effects, withdrawals, and timolol-related reduction in mortality and reinfarction, the diabetic patients basically behaved like nondiabetic patients. The data were analyzed retrospectively and should be confirmed by a prospective study. The study also indicates that long-term treatment with timolol may induce slight carbohydrate intolerance.

Adult↗

PubMed1999

Intraocular pressure-lowering effects of latanoprost monotherapy versus latanoprost or pilocarpine in combination with timolol: a randomized, observer-masked multicenter study in patients with open-angle glaucoma. Italian Latanoprost Study Group.

PURPOSE: To compare intraocular pressure (IOP) after adding either latanoprost or pilocarpine to timolol treatment or switching to latanoprost monotherapy in glaucomatous eyes in which IOP was inadequately controlled with timolol. METHODS: This 6-month randomized study comprised 148 patients with primary open-angle or pseudoexfoliation glaucoma, which was inadequately controlled with topical beta-adrenergic antagonists. After a 2- to 4-week run-in period with timolol 0.5% twice daily, patients were assigned in randomized fashion to three study groups: one group received add-on therapy of latanoprost 0.005% once daily, the second group received add-on therapy of pilocarpine 2% three times daily, and the third group switched to latanoprost 0.005% once daily. Mean diurnal IOP was measured at baseline and after 3 and 6 months of treatment. RESULTS: At 6 months, 128 patients had completed the study. Diurnal IOP was significantly reduced from baseline in all groups. Adding latanoprost to timolol treatment reduced diurnal IOP by 6.1+/-0.3 mmHg (-28%), adding pilocarpine to timolol treatment reduced diurnal IOP by 4.2+/-0.3 mmHg (-19%), and switching from timolol to latanoprost monotherapy reduced diurnal IOP by 5.5+/-0.3 mmHg (-25%). CONCLUSION: A significantly greater reduction in diurnal IOP was achieved after addition of latanoprost than after addition of pilocarpine in patients in whom IOP was not adequately controlled with timolol alone. Further, the results of this study indicate that a switch to latanoprost monotherapy can be attempted before combination treatment is initiated.

Adolescent↗

PubMed1976

[The anti-hypertensive effect of timolol maleate (blocadren) in gradated combination with a diuretic].

In a controlled double-blind crossover study followed by an open longterm continuation period, the antihypertensive effect of timolol (Blocadren), a new beta-receptor antagonist, was investigated in 24 ambulatory patients with mild to moderate essential hypertension who were concomitantly receiving Moduretic as baseline diuretic therapy. The addition of timolol to one tablet daily Moduretic resulted in a clinically and statistically significant further reduction of supine and upright systolic and diastolic blood pressures. The average total daily dosage schedule for timolol ranged between 15 and 20 mg, with the same blood pressure lowering effect whether the divided dose was given twice or three times. Significant sinus bradycardia was consistently observed but well tolerated, with only one patient requiring dose reduction. After 48 weeks of treatment (comprising 46 weeks Moduretic and 36 weeks timolol) 20 of 22 patients were normotensive (supine diastolic blood pressure below 90 mm Hg) while in two the hypotensive response proved inadequate. One patient was dropped from the study after 3 days of timolol treatment because of acute bronchial asthma. When specifically questioned, one-third of the patients admitted experiencing cold extremities. One patient exhibited Raynaud's syndrome which was treated symptomatically while continuing in the study. In terms of electrolyte balance, the fixed combination of hydrochlorothiazide and the antikaluretic amiloride (Moduretic) as baseline therapy essentially proved adequate. On occasion, however, two subject revealed hypokalemia requiring short-term oral potassium supplement. During the initial 10 to 16 weeks a steady decline in serum potassium was observed but this stabilized itself thereafter. The concomitant administration of Moduretic and timolol (Blocadren) was shown to be an effective therapeutic regimen in patients with mild to moderate essential hypertension. This combination is particularly suitable for patient compliance in longterm therapy, as timolol can be given twice daily.

Amiloride↗

PubMed1999

The dorzolamide/timolol combination versus timolol plus pilocarpine: patient preference and impact on daily life. United States Patient Preference Study Group. International Patient Preference Study Group.

PURPOSE: To compare the 2.0% dorzolamide/0.5% timolol fixed combination (COSOPT; Merck & Co., Whitehouse Station, NJ) to 0.5% timolol plus 2.0% pilocarpine given concomitantly, and to determine patient preference, tolerability, and impact on daily life in patients with elevated intraocular pressure (IOP). METHODS: Two multi-center, randomized, cross-over, observer masked studies were conducted, one in the United States (97 patients) and one in Europe (93 patients). The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference and perception of side effects and activity limitations resulting from study medications. Intraocular pressure was measured before and 2 hours after the morning dose of study medication (hour 0 and hour 2). RESULTS: In both studies, among patients with a preference, the combination was preterred to timolol plus pilocarpine by a ratio of 4 to 1. The most commonly cited reason for this preference was side effects. Patients in both studies also reported that the combination interfered significantly less with daily life in terms of side effects and activity limitations. They also reported missing significantly fewer doses of study medication while taking the combination and being significantly more satisfied with it. The efficacy of these two treatments was not significantly different, based on IOP measurements at hour 0 and 2 hours after administration. Patients reported significantly more adverse events while receiving timolol plus pilocarpine in both studies, and in the U.S. study, significantly more patients discontinued therapy while receiving timolol plus pilocarpine than while receiving the combination. CONCLUSION: Compared with timolol plus pilocarpine, patients preferred the combination of 2% dorzolamide/0.5% timolol, and reported less interference in daily activities, better tolerability, and better compliance with therapy.

Activities of Daily Living↗

PubMed2000

Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hypertension.

PURPOSE: To compare the around-the-clock intraocular pressure (IOP) reduction induced by timolol 0.5%, latanoprost 0.005%, and dorzolamide in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: In this crossover trial, 20 patients with POAG (n = 10) or OHT (n = 10) were treated with timolol, latanoprost, and dorzolamide for 1 month. The treatment sequence was randomized. All patients underwent measurements for four 24-hour tonometric curves: at baseline and after each 1-month period of treatment. The patients were admitted to the hospital, and IOP was measured by two well-trained evaluators masked to treatment assignment. Measurements were taken at 3, 6, and 9 AM and noon and at 3, 6, and 9 PM and midnight by handheld electronic tonometer (TonoPen XL; Bio-Rad, Glendale, CA) with the patient supine and sitting, and a Goldmann applanation tonometer (Haag-Streit, Bern, Switzerland) with the patient sitting at the slit lamp. Systemic blood pressure was recorded at the same times. The between-group differences were tested for significance by means of parametric analysis of variance. The circadian IOP curve of a small group of untreated healthy young subjects was also recorded using the same procedures. To compare the circadian IOP rhythms in the POAG-OHT and control groups, the acrophases for each subject were calculated. RESULTS: When Goldmann sitting values were considered, all the drugs significantly reduced IOP in comparison with baseline at all times, except for timolol at 3 AM. Latanoprost was more effective in lowering IOP than timolol at 3, 6, and 9 AM (P = 0.03), noon (P = 0.01), 9 PM, and midnight (P = 0.05) and was more effective than dorzolamide at 9 AM, noon (P = 0.03), and 3 and 6 PM (P = 0.04). Timolol was more effective than dorzolamide at 3 PM (P = 0.05), whereas dorzolamide performed better than timolol at midnight and 3 AM (P = 0.05). An ancillary finding of this study was that in the group of healthy subjects, the pattern of IOP curve was different that in patients with eye disease. CONCLUSIONS: Latanoprost seemed to lead to a fairly uniform circadian reduction in IOP, whereas timolol seemed to be less effective during the nighttime hours. Dorzolamide was less effective than latanoprost but led to a significant reduction in nocturnal IOP. The reason for the difference in the pattern of the IOP curve of healthy subjects is currently unknown and deserves further investigation.

Aged↗

PubMed2001

Effect of latanoprost and timolol on the histopathology of the rabbit conjunctiva.

PURPOSE: Long-term medical treatment of glaucoma has an effect on the conjunctiva, possibly affecting the outcome of subsequent filtering surgery. The type and extent of these tissue changes caused by frequently used medications is important. An animal study using rabbits was performed to assess the tissue changes caused by timolol, latanoprost, and a combination of both substances. METHODS: Rabbits were treated with timolol, latanoprost, or a combination of these drugs for 18 months. Conjunctival specimens were examined by light microscopy, quantitative transmission electron microscopy, and immunohistochemistry with antibodies against matrix metalloproteinase (MMP)-3 and tissue inhibitors of metalloproteinase (TIMP)-2. RESULTS: By electron microscopy, the area of subepithelial collagen was significantly larger (P: < 0.03; Mann-Whitney test) in timolol-treated eyes (71.6%) than in control (52.7%) and latanoprost-treated eyes (57.7%). An increase of amorphous material was present in timolol-treated eyes (25.6% versus 7.6% in the controls) as well as a smaller area of empty spaces (2.5% versus 39.4% in control eyes). Latanoprost-treated eyes had no significant increase of empty spaces but showed a marked staining for MMP-3 in the conjunctiva. This staining was not present in control or timolol-treated eyes. Morphologically, degenerative changes of fibrocytes were seen in timolol-treated eyes only. CONCLUSIONS: A significant increase of subepithelial collagen density was present in timolol-treated eyes, whereas this finding was not apparent in latanoprost-treated eyes. Latanoprost-treated eyes showed an upregulation of MMP-3, which may be the reason for reduced extracellular matrix accumulation in such eyes. The morphologic feature of increased subepithelial collagen density and extracellular matrix changes may relate to failure of filtering blebs.

Animals↗

PubMed2002

[Comparison of latanoprost monotherapy with timolol-dorzolamide combination in patients with open-angle glaucoma or ocular hypertension].

PURPOSE: To compare the efficacy and safety of latanoprost monotherapy to dorzolamide combined with timolol from pooled data of five multicenter, randomized, 3-month, observer-masked trials with identical study design. METHODS: Patients who were on a beta-blocker or dual therapy where one agent was a beta-blocker were eligible after a 2- to 4-week run-in period on timolol 0.5%, twice daily. Patients then either discontinued timolol treatment and received latanoprost monotherapy n=345) or continued on timolol and received dorzolamide add-on therapy (n=352). Data from these 697 patients were included in the meta-analysis. RESULTS: From an overall baseline of 22.8mmHg, the mean IOP reduction was 4.8mmHg (21%) in latanoprost-treated patients and 4.1mmHg (18%) in timolol + dorzolamide-treated patients p<0.001). A reduction in diurnal IOP of >=20% was achieved in 54% of the latanoprost-treated patients compared with 44% of the timolol + dorzolamide-treated patients. There was no marked difference between the two groups in the incidence of ocular and systemic events. CONCLUSION: This meta-analysis provides further support that a switch to latanoprost monotherapy can be an alternative to combined treatment with timolol + dorzolamide.

Antihypertensive Agents↗

PubMed1978

[Experimental studies with timolol: a new ocular hypotensive agent (author's transl)].

The present report reviews the animal pharmacology supporting the clinical use of timolol maleate ophthalmic solution in the therapy of glaucoma and elevated intraocular pressure (IOP). The studies have included the effects of timolol upon normal IOP of rabbits and upon elevated IOP in two models of experimental ocular hypertension. Comparisons are made between the latter actions of timolol and those of the reference adrenergic antiglaucoma agent, epinephrine. The interaction of timolol and the beta-adrenergic stimulant, isoproterenol, was also studied to assess the ability of timolol to block beta-adrenergic receptors in the eye. Additionally, the penetration and distribution of timolol in ocular and extraocular tissues and fluids following local application to the eyes of rabbits is described and a resume of the toxicological studies with timolol are presented.

Animals↗

PubMed2005

Comparative analysis of the efficacy and safety of latanoprost, travoprost and the fixed combination timolol-dorzolamide; a prospective, randomized, masked, cross-over design study.

PURPOSE: To analyse comparatively the efficacy and tolerance of latanoprost, travoprost and the fixed combination timolol-dorzolamide in the treatment of primary open angle glaucoma and ocular hypertension. METHOD: Prospective, investigator masked, randomized study that included 38 patients (38 eyes) with primary open angle glaucoma uncontrolled under beta blockers. Each patient received latanoprost, travoprost and the fixed combination timolol-dorzolamide (for 3 months each). The first drug and the order of the next drugs administered were randomized. The follow up period was 9 months. At the baseline and at the end of each therapeutic period (3 months) we determined the IOP (at 8, 10 a.m. and 4 p.m.), visual acuity, C/D ratio, blood pressure, heart rate and local tolerance. We have also photographed the eyelids, lashes, conjunctiva and iris. After each month of treatment we determined the IOP (at 8 and 10 am), visual acuity, blood pressure, heart rate and local tolerance. RESULTS: The mean initial IOP was 25.1 2.89 mmHg and after 9 months of treatment 21.67 4.59 mmHg. Each drug induced a statistically significant IOP decrease (the fixed combination timolol-dorzolamide decreased IOP with 14.33%, travoprost with 18.39% and latanoprost with 22.1%). The IOP lowering was comparable for the prostaglandin derivatives and superior to the fixed combination timolol-dorzolamide. None of these drugs had a negative influence on the visual field, C/D ratio, visual acuity, blood pressure and heart rate. There was good local tolerance. The side effects were more frequent after travoprost (37) and latanoprost (22) than after the fixed combination timolol-dorzolamide (4 cases). The most important adverse events for the prostaglandin derivatives were conjunctival hyperemia, eyelashes pigmentation and growth, iris pigmentation. There was no necessary to stop the medication because of these effects. CONCLUSIONS: Travoprost, latanoprost and the fixed combination timolol-dorzolamide are efficient in the treatment of primary open angle glaucoma. The prostaglandin derivatives determined similar IOP decrease, which was superior to the fixed combination timolol-dorzolamide; the local tolerance was good, the fixed combination causing the fewest side effects.

Aged↗