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PubMed1983

Electrophysiologic effects of intravenous timolol.

We evaluated the electrophysiologic effects and dose response of the long-acting beta-blocking drug timolol given intravenously to 12 patients during intracardiac electrophysiologic study. Electrophysiologic parameters were measured during control and immediately, 30 minutes, and 48 hours following infusion. Significant changes in electrophysiologic parameters were only observed in the five patients (Group B) who received 0.05 mg/kg and not in the seven patients who received 0.02 mg/kg (Group A). In Group B patients immediately after timolol infusion sinus cycle length increased from 840 +/- 254 msec to 1048 +/- 63 msec (P less than 0.01), A-H interval during normal sinus rhythm increased from 94 +/- 42 msec to 101 +/- 45 msec (P less than 0.05), paced cycle length to A-V nodal Wenckebach increased from 370 +/- 45 msec to 430 +/- 76 msec (P less than 0.05), and A-V nodal effective refractory period increased from 284 +/- 63 msec to 360 +/- 83 msec (P less than 0.01). Significant increases in these electrophysiologic parameters were also noted at 30 minutes following timolol infusion. Other conduction times, atrial and ventricular refractory periods, and corrected sinus node recovery. time were unaltered by timolol. All electrophysiologic parameters returned to control in 48 hours. No adverse effects were observed. We conclude that intravenous timolol in doses of 0.05 mg/kg significantly increases sinus cycle length and prolongs A-V nodal conduction and refractoriness, demonstrates peak effects immediately after intravenous administration, and is well tolerated.

Adolescent↗

PubMed2006

Nitric oxide synthase in retina and optic nerve head of rat with increased intraocular pressure and effect of timolol.

We investigated the expression of nitric oxide synthase (NOS) isoforms -1, -2 and -3 in the retina and optic nerve head (ONH) in an experimental rat model of elevated intraocular pressure (IOP) before and after treatment with timolol, to assess whether its neuroprotective action is associated with the activity of these enzymes. Episcleral vein cauterization in unilateral eyes of Wistar rats was performed to produce elevated IOP. Histological sections of retina and ONH from animals with normal IOP, with elevated IOP, and elevated IOP treated with timolol, were studied by immunohistochemistry with antibodies to NOS-1, NOS-2, and NOS-3. In the control rats, NOS-1 was localized to photoreceptor inner segments, amacrine cells and bipolar cells in the retina, and in astrocytes, pericytes and vascular nitrergic terminals in the ONH. NOS-3 immunostaining localized to the endothelial cells. The rats with elevated IOP showed increased expression of NOS-1 in the plexiform layers of the retina and reactive astrocytes in the ONH. These cells also showed NOS-2 positivity. The rats treated with timolol showed reduced expression of NOS-1 in the retina and ONH. NOS-2 was only detected in a few groups of astrocytes in the ONH. NOS-3 was unchanged in both elevated IOP and timolol-treated groups. These results show that excessive levels of NO synthesized by the NOS-1 and -2 isoforms, considered neurotoxic, might contribute to the progressive lesions of retinal ganglion cell axons. Their reduction after treatment suggests a possible neuroprotective effect of timolol in neurons exposed to excessive amounts of NO.

Animals↗

PubMed2006

Nonaqueous capillary electrophoresis method for the enantiomeric purity determination of S-timolol using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin: validation using the accuracy profile strategy and estimation of uncertainty.

Nonaqueous capillary electrophoresis (NACE) was successfully applied to the enantiomeric purity determination of S-timolol maleate using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin (HDMS-beta-CD) as chiral selector. With a background electrolyte made up of a methanolic solution of 0.75 M formic acid, 30 mM potassium camphorsulfonate and containing 30 mM HDMS-beta-CD, the determination of 0.1% of R-timolol in S-timolol could be performed with an enantiomeric resolution of 8.5. Pyridoxine was selected as internal standard. The NACE method was then fully validated by applying a novel strategy using accuracy profiles. It is based on beta-expectation tolerance intervals for the total measurement error which includes trueness and intermediate precision. The uncertainty of measurements derived from beta-expectation tolerance intervals was estimated at each concentration level of the validation standards. To confirm the suitability of the developed and validated method, several real samples of S-timolol maleate containing R-timolol maleate at different concentrations were analysed and the results were compared to those obtained by liquid chromatography.

Antihypertensive Agents↗

PubMed2005

Effects of anti-glaucoma drugs timolol and GLC756, a novel mixed dopamine D2 receptor agonist and D1 receptor antagonist, on endotoxin-induced-uveitis and -arthritis in rats.

Anti-glaucoma drugs exhibiting anti-inflammatory properties are desirable for the long-term treatment of glaucoma since they may reduce the risk for treatment-related inflammatory processes in outer compartments of the eye. The purpose of this study was to evaluate potential anti-inflammatory effects of two topically and systemically applied anti-glaucoma drugs i.e. GLC 756, a novel mixed dopamine D2 receptor agonist and D1 receptor antagonist, and timolol a beta-adrenoceptor antagonist using endotoxin-induced uveitis (EIU) and arthritis in rats as an in vivo model. For EIU, 8-week-old Lewis rats were intravenously injected at 160 microg lipopolysaccharide (LPS) from Salmonella typhimurium. GLC756, timolol, or betamethasone, as a positive control, were either topically (0.4%, 0.5%, and 0.1%, respectively, 16-times 20 microL eye drops during 48 h) or systemically (1mg/kg subcutaneous for 5 days) administered. Cell infiltration in tissue of the eye and knee joint were assessed histopathologically and in special compartments of the eye by confocal microscopy 48 h after LPS-induction. Numerous infiltrating cells were detected in the eyes after LPS-induction and half of the animals showed arthritis. Topical and systemic pre-treatment with GLC756 and timolol resulted in reduced cell infiltration in the eye. In addition, GLC756 reduced, whereas timolol increased the incidence of arthritis. Betamethasone suppressed almost completely the cell infiltration in the eye and the incidence of arthritis. In conclusion, the observations that GLC756 reduced cell infiltration in the eye and the incidence of arthritis after LPS-induction is compatible with anti-inflammatory properties of this drug. By contrast, timolol produced no consistent anti-inflammatory effect since both inhibitory as well as stimulatory effects on inflammatory processes were seen.

Animals↗

PubMed2004

Intraocular pressure-reducing effects and safety of latanoprost versus timolol in patients with chronic angle-closure glaucoma.

OBJECTIVE: To demonstrate that the intraocular pressure (IOP)-reducing effect of latanoprost once daily is at least as good as that of timolol twice daily in patients with chronic angle-closure glaucoma (CACG). DESIGN: Randomized, double-masked, multicenter 12-week study. PARTICIPANTS: In all, 137 patients with unilateral or bilateral CACG were treated with latanoprost, and 138 were treated with timolol. METHODS: Patients received either latanoprost (9 pm) and a placebo (9 am) or timolol (both 9 am and 9 pm). Intraocular pressure was measured at 9 am and 5 pm at baseline and weeks 2, 6, and 12. MAIN OUTCOME MEASURES: The difference between groups in daily IOP (average of 9 am and 5 pm measures) reduction was the primary outcome. Secondary outcomes included differences between groups in IOP reductions at 9 am and 5 pm, and in proportions of patients reaching specified daily IOP levels. RESULTS: Using repeated measures (analysis of covariance: intent to treat), mean changes from baseline in daily IOP levels during 12 weeks were -8.2 mmHg and -5.2 mmHg for latanoprost- and timolol-treated patients, respectively (difference: -3.0 mmHg [95% confidence interval: -4.0, -2.1], P<0.001). Greater reductions in IOP levels at both 9 am and 5 pm were found in latanoprost-treated patients (P<0.001 for both), and greater proportions of patients receiving latanoprost reached prespecified target daily IOP levels (P<0.001 for all 3 target levels tested). Both drugs were well tolerated. CONCLUSION: Latanoprost administered once daily provides significantly greater IOP reduction in CACG patients than does timolol instilled twice daily.

Adult↗

PubMed2005

A 12-week, randomized, double-masked, multicenter study of the fixed combination of latanoprost and timolol in the evening versus the individual components.

PURPOSE: To compare the efficacy and tolerability of fixed-combination latanoprost and timolol applied in the evening with the concomitant use of the individual components. DESIGN: Twelve-week, randomized, double-masked, multicenter study. PARTICIPANTS: Five hundred seventeen randomized patients with ocular hypertension; open-angle, pigmentary, or exfoliation glaucoma; and baseline (after washout) intraocular pressure (IOP) levels between 23 and 33 mmHg. METHODS: Patients received either the fixed combination of latanoprost and timolol once daily in the evening and a placebo in the morning and evening or the unfixed combination of latanoprost once daily in the evening and timolol in the morning and evening. Study visits were at weeks 2, 6, and 12. MAIN OUTCOME MEASURES: The primary efficacy end point was mean change from baseline to week 12 in diurnal IOP (mean IOPs of 8 am, 12 pm, and 4 pm). The fixed combination was considered noninferior to the unfixed combination if the upper limit of the 95% confidence interval (CI) of the difference was <1.5 mmHg (analysis of covariance). Adverse events were recorded at each visit. RESULTS: In all, 502 patients were included in intent-to-treat analyses (fixed combination, n = 255; unfixed combination, n = 247). For the fixed- and unfixed-combination groups, mean baseline diurnal IOP levels were 25.4 mmHg and 25.2 mmHg, respectively, and mean diurnal IOP reductions were 8.7 mmHg and 9.0 mmHg (between-treatment difference, 0.3 mmHg; 95% CI, -0.1 to 0.7 mmHg; P = 0.15). Both treatments were well tolerated. CONCLUSIONS: The fixed combination of latanoprost and timolol administered once daily in the evening is not inferior to the unfixed combination of latanoprost once daily in the evening and timolol twice daily. The fixed combination provides an effective and well-tolerated alternative to multiple instillations.

Adult↗

PubMed2001

Evaluation of travoprost as adjunctive therapy in patients with uncontrolled intraocular pressure while using timolol 0.5%.

PURPOSE: To evaluate the intraocular pressure-lowering efficacy and safety of travoprost 0.0015% and 0.004%, dosed daily in the evening compared with vehicle, in patients with open-angle glaucoma or ocular hypertension, whose intraocular pressure was not adequately controlled on timolol 0.5% twice daily (twice daily). METHODS: Subjects who qualified at screening began a run-in period dosing timolol twice daily for 3 weeks. If the subjects had an intraocular pressure of 24 to 36 mm Hg at 8 AM and 21 to 36 mm Hg at 10 AM and 4 pm in at least one eye on timolol, they were randomized to one of two concentrations of travoprost (0.0015% or 0.004%) or vehicle solution every day and were followed for 6 months. Four hundred twenty-six subjects were randomized. The mean intraocular pressure at 8 AM, 10 AM, and 4 PM in the patient's eye with the higher intraocular pressure was used for the analysis. RESULTS: Mean baseline values (25 mm Hg) for subjects at eligibility (while maintained on timolol) were not significantly different (P <.0001) among the treatment groups. The intraocular pressure was lowered an additional -5.7 to -7.2 mm Hg and -5.1 to -6.7 mm Hg in the travoprost 0.004% and 0.0015% concentrations, respectively. These changes were significantly (P < or =.0001) different from the vehicle group (-1.3 to -2.8 mm Hg). The intraocular pressure range on treatment at all visit times over the 6-month treatment period ranged from 17.9 to 19.2 mm Hg for travoprost 0.004% and 18.3 to 20.1 mm Hg for travoprost 0.0015% compared with 22.4 to 24.1 mm Hg for vehicle. Average hyperemia scores ranged from trace to mild (mean 0.5 on a scale of 0 = none/trace; 1= mild; 2 = moderate; 3 = severe) for all treatment groups. No iris pigmentation changes were observed in any patient during this study. There were no clinically or statistically significant changes from baseline in visual acuity, ocular cells and flare, fundus parameter, cup-to-disk ratio and visual field between the treatment groups. There were no serious adverse events reported for any treatment group. CONCLUSIONS: Travoprost produced clinically relevant and statistically significant additional intraocular pressure reductions from baseline when used adjunctively with timolol in subjects with open-angle glaucoma or ocular hypertension.

Adrenergic beta-Antagonists↗

PubMed1996

A comparative study of the effects of timolol and latanoprost on blood flow velocity of the retrobulbar vessels.

PURPOSE: To examine the effects of topical timolol and latanoprost on retrobulbar vessel blood velocity in patients with glaucoma or ocular hypertension. METHODS: Nine patients with primary open-angle glaucoma and six patients with ocular hypertension were enrolled for this study. All patients were treated topically with 0.5% timolol or 0.005% latanoprost, using a double-masked crossover design with a 3-week washout before administration of each drug. Each patient had a baseline color Doppler imaging ultrasound of the central retinal artery, short posterior ciliary arteries, and ophthalmic artery and two other ultrasound examinations during the 1-week treatment with each drug, performed 12 hours after the first dose of the drug and 12 hours after the last dose, 7 days later. RESULTS: Both topical timolol and topical latanoprost significantly reduced the intraocular pressure. The only significant change observed in the retrobulbar blood velocity with timolol was a reduction of end diastolic velocity in the ophthalmic artery 12 hours after the first dose, accompanied by a trend toward a decrease in the peak systolic velocity and an increase in the resistance index in the same vessel. No change in blood velocity was observed with latanoprost. CONCLUSION: Topical timolol and latanoprost significantly reduced the intraocular pressure in ocular hypertensive and glaucoma patients without creating substantial hemodynamic changes in the retrobulbar vessels.

Administration, Topical↗

PubMed1987

Compliance with topical timolol treatment.

To determine if compliance with timolol treatment was better than compliance with pilocarpine treatment (as reported previously), we measured compliance with timolol treatment in a sample of 110 patients using an unobtrusive eyedrop medication monitor, which recorded electronically the date and time of each drug administration over a four- to six-week period. The patients administered a mean +/- S.D. of 82.7% +/- 19.0% of the prescribed timolol doses (range, 20% to 100%). Forty-five patients were treated concurrently with timolol and pilocarpine. These patients administered a mean +/- S.D. of 84.3% +/- 14.0% of the prescribed timolol doses and 77.7% +/- 18.7% of the prescribed pilocarpine doses (P = .012, van der Waerden test). Our results suggest that while compliance is influenced by the drug regimen, defaulting is not eliminated by prescribing a more convenient medication with fewer side effects.

Adolescent↗

PubMed1999

Comparison of 24-hour intraocular pressure reduction with two dosing regimens of latanoprost and timolol maleate in patients with primary open-angle glaucoma.

PURPOSE: To compare the 24-hour diurnal ocular hypotensive efficacy of two dosing regimens of latanoprost, once daily (8 AM or 10 PM), vs timolol maleate, twice daily. METHODS: We measured six diurnal intraocular pressure curves (6 AM, 10 AM, 2 PM, 6 PM, 10 PM, and 2 AM) in one randomly selected eye of 34 Greek patients newly diagnosed with primary open-angle glaucoma. The first diurnal curve was an untreated baseline. Patients began taking timolol 0.5%, twice daily, for 2 months. Patients were randomly assigned to latanoprost 0.005% given at 8 AM or 10 PM for 1 month and then changed to the other dosing regimen for 1 month. A diurnal curve was performed after each dosing period. RESULTS: The baseline diurnal pressure for all 34 subjects was 23.1 +/- 3.7 mm Hg. The average intraocular pressures at 6 AM for patients who were given latanoprost in the evening (17.9 +/- 2.9 mm Hg) was statistically lower than that in patients given timolol solution (20.1 +/- 2.5 mm Hg, P = .003); however, patients who were given timolol demonstrated a similar diurnal intraocular pressure (19.1 +/- 2.8 mm Hg) to both morning (18.8 +/- 3.7 mm Hg) and evening doses (18.8 +/- 3.6 mm Hg) of latanoprost (P =.329). When the two latanoprost dosages were compared directly, evening administration provided a statistically lower intraocular pressure at 10 AM (P = .0001) and morning administration at 10 PM (P = .0001). This study had an 80% power to exclude a 1.2-mm Hg difference between groups. CONCLUSIONS: This study indicates that in a small population, both latanoprost and timolol are effective in lowering intraocular pressure throughout a 24-hour period; however, latanoprost is most effective in the 12-hour to 24-hour period after administration.

Adrenergic beta-Antagonists↗

PubMed2003

The beta-adrenoceptor antagonists metipranolol and timolol are retinal neuroprotectants: comparison with betaxolol.

beta-adrenoceptor antagonists are used clinically to reduce elevated intraocular pressure in glaucoma which is characterised by a loss of retinal ganglion cells. Previous studies have shown that the beta(1)-selective adrenoceptor antagonist, betaxolol, is additionally able to protect retinal neurones in vitro and ganglion cells in vivo from the detrimental effects of either ischemia-reperfusion or from excitotoxicity, after topical application. The neuroprotective effect of betaxolol is thought not to be elicited through an interaction with beta-adrenoceptors, but by its ability to reduce influx of sodium and calcium through voltage-sensitive calcium and sodium channels. In the present study it is shown that the non-selective beta-adrenoceptor antagonists, metipranolol and timolol behave like betaxolol. When topically applied they all attenuate the detrimental effect of ischemia-reperfusion. Protection of the retina was determined by evaluating changes in the electroretinogram and by assessing the loss of mRNA for Thy-1, which is expressed in retinal ganglion cells. In addition, studies conducted on neurones in mixed retinal cultures demonstrated that metipranolol, betaxolol and timolol were all able to partially counteract anoxia-induced cell loss and viability reduction. The influence of timolol was, however, not significant. Within the confines of these investigations, an order of neuroprotective efficacy was delineated for the three beta-adrenoceptor antagonists: betaxolol>metipranolol>timolol. The ability of the beta-adrenoceptor antagonists to attenuate ligand-induced stimulation of calcium and sodium entry into neuronal preparations showed a similar order of effectiveness. In conclusion, the ability to confer neuroprotection to retinal neurones is a common feature of three ophthalmic beta-adrenoceptor antagonists (betaxolol, metipranolol and timolol). A comparison of the effectiveness of the individual compounds in protecting retinal cells in vivo was not possible in these studies. However, in vitro studies show that the capacity of the individual beta-adrenoceptor antagonists to act as neuroprotectants appears to relate to their capacity to attenuate neuronal calcium and sodium influx.

Adrenergic beta-Antagonists↗

PubMed2002

Quantitative determination of oxprenolol and timolol in urine by capillary zone electrophoresis.

A simple capillary zone electrophoretic method with UV detection has been developed for the quantitative determination of the beta-adrenoreceptor antagonists (beta-blockers) oxprenolol and timolol in human urine, preceded by a solid-phase extraction step. The electrophoretic separation was performed on a 78 cm x 75 microm I.D. fused-silica capillary (effective capillary length: 70 cm). The electrolyte consisted of a Na2B4O7-H3BO3 (50 mM), pH 9. The introduction of the sample was made hydrostatically for 20 s and the running voltage 25 kV at the injector end of the capillary. Photometric detection was used at a wavelength of 229 nm for oxprenolol and 280 nm for timolol. Under these conditions oxprenolol migrated at 4.76+/-0.05 min and timolol at 4.97+/-0.05 min. The solid-phase extraction methods were optimised for each beta-blocker and provided recoveries of 72.8% for timolol and 94.52% for oxprenolol. Good resolution from the endogenous compounds present in the urine matrix were achieved for both compounds. The method was applied to the determination of both beta-blockers in pharmaceutical formulations and urine samples obtained from hypertensive patients after the ingestion of a therapeutic dose (in a 24-h time interval after the ingestion). The quantitative results were compared with results previously obtained at our laboratories by HPLC and were found to be in good agreement. Good reproducibility, linearity, accuracy and quantitation limits (in urine) of 0.19 microg/ml for timolol and 0.20 microg/ml for oxprenolol were obtained, allowing the method to be applied to pharmacokinetic studies of these compounds.

Adrenergic beta-Antagonists↗

PubMed1984

Timolol and postoperative intraocular pressure.

We studied the effect of timolol instillation at surgery on the acute postoperative pressure rise following extracapsular cataract extraction (ECCE) and posterior chamber lens implantation. The intraocular pressure (IOP) was measured daily during the first week following surgery in 85 eyes. Timolol was instilled immediately following surgery in 34 eyes; the remaining 51 served as controls. The mean preoperative IOP was 18.7 mm Hg in the treated and control groups. The mean IOP on the first day following surgery was 20.0 mm Hg in the timolol group and 20.7 mm Hg in the control group. Twenty-six percent of the timolol group had a pressure greater than 23.0 mm Hg (mean 35.6 mm Hg); 33% of the control group had a pressure greater than 23.0 mm Hg (mean 31.0 mm Hg). The IOP in all treated and untreated patients with ocular hypertension on the first day following surgery returned to normal within three days. Timolol, therefore, had no effect on acute postoperative pressure elevation following ECCE and posterior chamber lens implantation.

Cataract Extraction↗

PubMed2000

Ongoing clinical assessment of the safety profile and efficacy of brimonidine compared with timolol: year-three results. Brimonidine Study Group II.

OBJECTIVE: We compared the safety profile and efficacy of brimonidine 0.2% BID with those of timolol 0.5% BID over 3 years in patients with ocular hypertension and glaucoma. METHODS: Ninety-four eligible patients from an ongoing multicenter, interventional, double-masked clinical trial were followed through year 3, 48 receiving brimonidine 0.2% and 46 receiving timolol 0.5%. Study visits occurred at months 24, 27, 30, 33, and 36. The primary efficacy variable was mean reduction from baseline intraocular pressure (IOP) at trough. Visual acuity, visual fields, and safety variables (adverse events, ocular symptoms, heart rate, blood pressure, and laboratory test results) were monitored throughout the study. RESULTS: The 2 treatment groups were well matched, with no significant differences in demographic or clinical characteristics. Both drug regimens caused significant mean reductions from baseline IOP at trough during year 3 (P < 0.001), with no significant differences between groups at any study visit. The overall mean reduction from baseline IOP at trough was 5.02 mm Hg with brimonidine and 5.57 mm Hg with timolol (P = 0.383). Brimonidine caused reductions in IOP at trough that were equivalent to those with timolol at months 30 and 36 (within the 95% CI). Visual fields were unchanged or improved in 95% of patients in both treatment groups. Both drug regimens appeared to be safe and were well tolerated. Ocular allergy occurred in 2 brimonidine-treated patients (4.2%). There were no statistically significant differences in adverse-event reports and no clinically significant effects on any ocular or systemic safety variable in either group. CONCLUSIONS: Brimonidine 0.2% BID continues to appear to be safe, well tolerated, and effective in the long-term management of ocular hypertension and glaucoma. Over 3 years, it provided sustained IOP-lowering efficacy and visual-field preservation equal to those with timolol 0.5% BID.

Adrenergic alpha-Agonists↗

PubMed1978

Long-term experience with timolol ophthalmic solution in patients with open-angle glaucoma.

Timolol was used by 37 glaucoma patients from 1 to 18 months. Of those 37 patients, 31 used timolol for three months or longer and 7 used timolol for over one year. Timolol produced sustained reductions in intraocular pressure with continuous administration and did not induce miosis, accommodative spasm, or other annoying side effects. Systemic absorption produced a mild slowing of resting pulse rate. In some patients, timolol's ocular hypotensive effects are additive to miotics and carbonic anhydrase inhibitors.

Adult↗

PubMed1981

Timolol in uncontrolled childhood glaucomas.

Thirty-four patients with childhood glaucoma who had difficult management problems in spite of conventional glaucoma medications were entered into an investigational protocol designed at a time when timolol was not available commercially. Since controlled studies in adult glaucoma had demonstrated the efficacy of timolol, a trial of the drug in these difficult childhood cases seemed justified. The study was approved by the Human Studies Committees of the Children's Hospital Medical Center and the Massachusetts Eye and Ear Infirmary, Boston, MA. These children have been followed for periods up to 2 1/2 years. In general, timolol was added to the maximum tolerated medical therapy. Definite improvement was noted in 10 patients, modest or equivocal improvement in 11, and in 13 no substantial benefit to their course occurred when timolol was added. youngsters over 5 years of age showed an average reduction in resting pulse rate of 6 beats/minute similar to that previously found in adult patients. Under 5 years of age no change in the resting pulse rate could be detected. One patient was discontinued from timolol for a possible adverse effect. The experience particularly in very young children is still quite limited, but the beneficial effects observed warrant further evaluation.

Adolescent↗

PubMed1988

The effects of withdrawal of timolol in chronically treated glaucoma patients.

The dynamics of aqueous humor were studied before and after discontinuing timolol maleate in chronic users. Nineteen patients (mean length of treatment, 44 months) were studied by measuring their baseline intraocular pressure (IOP) and aqueous humor flow during treatment and 2 days to 6 weeks after discontinuing the drug. Flow did not increase significantly until 4 days after discontinuing timolol, and IOP did not increase significantly until 14 days later. Flow did not revert to its normal rate for 2 to 6 weeks. Intraocular pressure was 15% lower and the flow 24% lower during maintenance treatment than 1 month after discontinuing timolol. This comparison demonstrates the efficacy of chronic treatment. Recovery of aqueous flow is slow after stopping timolol. This finding suggests that lower or less frequent doses than are customarily used might be equally efficacious. If timolol is discontinued before filtration surgery, its effects will remain for 2 to 4 weeks.

Adult↗

PubMed1996

The use of dorzolamide and pilocarpine as adjunctive therapy to timolol in patients with elevated intraocular pressure. The Dorzolamide Additivity Study Group.

PURPOSE: To report the results of two studies on the use of dorzolamide as adjunctive therapy to timolol in patients with elevated intraocular pressure (IOP). In the larger study, the additive effect of dorzolamide administered twice daily also was compared with 2% pilocarpine. METHODS: Both studies were parallel, randomized, double-masked, placebo-controlled comparisons. In the pilot study, 32 patients received 0.5% timolol twice daily plus either 2% dorzolamide twice daily or placebo twice daily for 8 days. In the Pilocarpine Comparison Study, 261 patients received 0.5% timolol twice daily plus 0.7% dorzolamide twice daily, 2% dorzolamide twice daily, 2% pilocarpine four times daily, or placebo (twice daily or 4 times daily) for 2 weeks. Patients then entered a 6-month extension period and received 0.5% timolol twice daily plus either 0.7% dorzolamide twice daily, 2% dorzolamide twice daily, or 2% pilocarpine four times daily. RESULTS: In the pilot study, after 8 days, additional mean percent reductions in IOP for 2% dorzolamide and placebo were 17% and 3% at morning trough and 19% and 2% at peak, respectively. In the Pilocarpine Comparison Study, after 6 months, additional mean percent reductions in IOP (morning trough) were 9%, 13%, and 10% for 0.7% dorzolamide, 2% dorzolamide, and 2% pilocarpine, respectively. Patients receiving 2% pilocarpine had the highest rate of discontinuation due to a clinical adverse experience, and the use of dorzolamide was not associated with systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors. CONCLUSION: Dorzolamide twice daily was effective and well tolerated by the patients in these studies as adjunctive therapy to timolol. The larger study demonstrated that both concentrations of dorzolamide produce similar IOP-lowering effects to 2% pilocarpine.

Adrenergic beta-Antagonists↗