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Plasma timolol concentrations of timolol maleate: timolol gel-forming solution (TIMOPTIC-XE) once daily versus timolol maleate ophthalmic solution twice daily.

PURPOSE: The objective of this study was to compare plasma concentrations of timolol following multiple dosing of the therapeutic regimens of timolol maleate ophthalmic gel-forming solution (Timolol GS; TIMOPTIC-XE) and timolol maleate ophthalmic solution. Timolol maleate ophthalmic gel-forming solution is also referred to as Timolol GS, i.e. gel-forming solution. METHODS: This was a masked observer, two-period crossover study in six normal male subjects randomized to receive either Timolol GS, 0.5% (TIMOPTIC-XE,) once daily (0530 hours) or timolol maleate ophthalmic solution (0.5% TIMOPTIC) twice daily (0530 and 1730 hours) for 8 days, in both eyes. On Day 8, a blood sample was obtained prior to treatment, as well as 1, 2, 4, 8, 10, 12, 13, 14, 16, and 24 hours following the morning instillation. After a 7-day inter-period washout interval, subjects received the opposite treatment. RESULTS: Timolol GS (TIMOPTIC-XE): Plasma concentrations of timolol rarely exceeded 0.375 ng/ml (the lower limit of assay quantification). For all subjects, peak plasma concentrations of timolol averaged <0.3 ng/ml within 4 hours after the last dose. The highest single observation was 0.49 ng/ml in one subject (at hour 2). Timolol solution: For all subjects, peak plasma concentrations of timolol averaged about 0.5 ng/ml and 0.3 ng/ml within 4 hours following the first and second dose, respectively, on Day 8. The highest single observation was 0.95 ng/ml in one subject (at hour 2). CONCLUSIONS: The data suggest that there is less systemic exposure to timolol following once-daily therapy with Timolol GS 0.5% compared with twice daily therapy with timolol maleate ophthalmic solution 0.5%.

Absorption↗

A randomized trial in patients inadequately controlled with timolol alone comparing the dorzolamide-timolol combination to monotherapy with timolol or dorzolamide. Dorzolamide-Timolol Combination Study Group.

OBJECTIVE: To compare the dorzolamide-timolol fixed combination twice daily to its components, timolol maleate and dorzolamide hydrochloride, given in their usual monotherapy regimens in patients whose intraocular pressure (IOP) was not controlled on timolol twice daily alone. DESIGN: Parallel, randomized, double-masked, and active-controlled study. PARTICIPANTS: Enrolled were 253 patients from 22 sites throughout the United States. INTERVENTION: After a 3-week run-in of timolol (TIMOPTIC; Merck & Co., Inc., Whitehouse Station, NJ) twice daily, eligible patients received either the combination (COSOPT; Merck & Co., Inc., Whitehouse Station, NJ) twice daily (plus placebo to ensure masking), timolol twice daily (plus placebo to ensure masking), or dorzolamide (TRUSOPT; Merck & Co. Inc., Whitehouse Station, NJ) three times daily for 3 months. MAIN OUTCOME MEASURES: Intraocular pressure taken at hours 0 (trough) and 2 (peak) after week 2 and months 1, 2, and 3 was compared to baseline within each treatment group and between the combination and each component group. The safety profile of the combination was compared to each component. RESULTS: The combination was numerically superior at all study timepoints and was statistically superior at all timepoints except for month 2, hour 0 for timolol, and month 2, hour 2 for dorzolamide. The safety profile of the combination reflected those of its two components. The number of patients reporting ocular or local adverse experiences was greater for the combination (45%) and dorzolamide (45%) than for timolol (27%), with burning and/or stinging eye being the most frequently reported. CONCLUSION: The dorzolamide-timolol combination provides additional IOP lowering compared to either of its individual components and generally is well-tolerated.

Adrenergic beta-Antagonists↗

[The influence of RS-Timolol in comparison with R-Timolol and S-Timolol on the intraocular pressure in water-loaded rabbits].

PURPOSE: It is assumed that S-timolol can produce more severe systemic adverse reactions than R-timolol. The aim of this study was to estimate the intraocular pressure-lowering effect of RS-timolol in comparison to R-timolol and S-timolol in water-loaded rabbits. MATERIAL AND METHODS: Ocular hypertension was provoked in rabbits by orogastric water loading. Topical administration of one of three timolol solutions: 0.85%, RS-timolol, or 3% R-timolol, or 0.5% S-timolol was performed to the right eyes 40 min before starting the water loading procedure. Left eyes served as a control group. Intraocular pressure was measured before and 30, 60, 90, 120 min after the water loading. RESULTS: Intraocular pressure-lowering effect of all three timolol solutions was comparable. CONCLUSION: RS-timolol can be effective for lowering intraocular pressure in rabbits.

Adrenergic beta-Antagonists↗

A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide. Dorzolamide-Timolol Study Group.

OBJECTIVE: To compare the efficacy and safety of a fixed combination of 2.0% dorzolamide and 0.5% timolol administered twice daily with each of the individual components administered in their usual monotherapy dose regimens in patients who had washed out all ocular hypotensive medications. DESIGN: A 3-month, parallel, randomized, double-masked, active-controlled, multicenter clinical trial. PARTICIPANTS: A total of 335 patients with bilateral ocular hypertension or open-angle glaucoma participated. INTERVENTION: After completing a washout of ocular hypotensive medications, patients were randomized to receive either the dorzolamide-timolol combination twice daily plus placebo once daily, 0.5% timolol twice daily plus placebo once daily, or 2.0% dorzolamide three times daily. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) was measured at morning trough (hour 0) and peak (2 hours postdose) on day 1, week 2, and months 1, 2, and 3. Ocular and systemic safety were evaluated at each study visit. RESULTS: Intraocular pressure reduction was greater on average in the combination group than in the dorzolamide and timolol groups. At morning trough (month 3, hour 0), the mean reduction in IOP from baseline was 27.4% (-7.7 mmHg) for the combination, 15.5% (-4.6 mmHg) for dorzolamide, and 22.2% (-6.4 mmHg) for timolol. At morning peak (month 3, hour 2), the mean IOP reduction from baseline was 32.7% (-9.0 mmHg), 19.8% (-5.4 mmHg), and 22.6% (-6.3 mmHg) for the combination, dorzolamide, and timolol, respectively. Overall, the incidence of clinical adverse experiences was comparable between the combination and each of its components. The proportion of patients who discontinued from the study because of clinical adverse experiences was also comparable between the combination and dorzolamide, although it was significantly greater in the combination group than in the timolol group (7% vs. 1%, P = 0.035). Similarly, comparable numbers of patients in the combination and dorzolamide groups reported ocular symptoms; however, when compared to the timolol group, more patients receiving the combination reported blurred vision, burning eye, stinging eye, and tearing eye. CONCLUSIONS: After a washout of ocular hypotensive therapy, the IOP-lowering effect of the dorzolamide-timolol combination was greater than that of either of its components administered as monotherapy. The combination is generally well-tolerated and provides a convenient alternative to concomitant therapy with its individual components.

Adrenergic beta-Antagonists↗

Timolol maleate 0.5% versus timolol maleate in gel forming solution 0.5% (Timolol GFS) in open angle glaucoma in India. Preliminary safety and efficacy study.

PURPOSE: To compare the efficacy and safety profile of Timolol maleate 0.5% versus Timolol gel forming solution (GFS) 0.5% in open angle glaucoma in Indian eyes. METHODS: In a prospective crossover study 52 patients of open angle glaucoma, well controlled intraocular pressure (IOP) on 0.5% timolol maleate solution were switched over to timolol GFS once a day, after a washout period of one month. A diurnal IOP measurement was done after 6 weeks and compared with patients on timolol maleate 0.5% twice a day. In addition, side effects reported or observed were compared. RESULTS: Statistically significant difference was not observed in ocular hypotensive effect of the two treatment. The side-effects in both the treatment groups were similar except for higher incidence of blurring of vision in patients on timolol GFS. The compliance was better with timolol GFS, but was not statistically significant. CONCLUSION: The results of this study suggest that the more convenient 0.5% timolol in gel forming solution can be offered as an equally efficacious and well-tolerated alternative to twice daily 0.5% timolol solution in open angle glaucoma.

Adrenergic beta-Antagonists↗

A randomized trial in patients inadequately controlled with timolol alone comparing the dorzolamide-timolol combination to monotherapy with timolol or dorzolamide.

OBJECTIVE: To compare the dorzolamide-timolol fixed combination twice daily to its components, timolol maleate and dorzolamide hydrochloride, given in their usual monotherapy regimens in patients whose intraocular pressure (IOP) was not controlled on timolol twice daily alone. DESIGN: Parallel, randomized, double-masked, and active-controlled study. PARTICIPANTS: Enrolled were 253 patients from 22 sites throughout the United States. INTERVENTION: After a 3-week run-in of timolol (TIMOPTIC; Merck & Co., Inc., Whitehouse Station, NJ) twice daily, eligible patients received either the combination (COSOPT; Merck & Co., Inc., Whitehouse Station, NJ) twice daily (plus placebo to ensure masking), timolol twice daily (plus placebo to ensure masking), or dorzolamide (TRUSOPT; Merck & Co. Inc., Whitehouse Station, NJ) three times daily for 3 months. MAIN OUTCOME MEASURES: Intraocular pressure taken at hours 0 (trough) and 2 (peak) after week 2 and months 1, 2, and 3 was compared to baseline within each treatment group and between the combination and each component group. The safety profile of the combination was compared to each component. RESULTS: The combination was numerically superior at all study timepoints and was statistically superior at all timepoints except for month 2, hour 0 for timolol, and month 2, hour 2 for dorzolamide. The safety profile of the combination reflected those of its two components. The number of patients reporting ocular or local adverse experiences was greater for the combination (45%) and dorzolamide (45%) than for timolol (27%), with burning and/or stinging eye being the most frequently reported. CONCLUSION: The dorzolamide-timolol combination provides additional IOP lowering compared to either of its individual components and generally is well-tolerated.

Adrenergic beta-Antagonists↗

Efficacy and tolerability of timolol maleate ophthalmic gel-forming solution versus timolol ophthalmic solution in adults with open-angle glaucoma or ocular hypertension: a six-month, double-masked, multicenter study.

BACKGROUND: Timolol has been formulated in a highly purified gellan gum to improve its duration of action. The efficacy of this formulation in short-term studies using once-daily dosing has been reported. OBJECTIVE: The purpose of this study was to evaluate the efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution (timolol GS) given once daily versus 0.5% timolol solution given twice daily in a long-term trial. METHODS: This was a multicenter, double-masked, 6-month trial. After a washout of ocular hypotensive medication, 286 patients with open-angle glaucoma or ocular hypertension were randomly assigned in a 2:1 ratio to receive 0.5% timolol GS in both eyes once daily or 0.5% timolol solution in both eyes twice daily. All patients received a morning (9 AM) and evening (9 PM) dose. For patients in the timolol GS group, the evening dose consisted of a vehicle only, whereas for patients in the timolol solution group, both doses consisted of active drug. Intraocular pressure (IOP) was measured at trough (before morning instillation) and peak (2 hours after instillation) at follow-up examinations at weeks 2, 4, 8, 12, and 24. Adverse events were monitored using patient reports. RESULTS: Of the 286 patients randomized, 191 received timolol GS and 95 received timolol solution. Ninety-three percent of patients (265/286) completed the study. At the end of the treatment interval (week 24), the mean decrease in IOP at trough ranged from 5.6 to 5.9 mm Hg in the timolol GS group and from 6.3 to 6.6 mm Hg in the timolol solution group. Similar efficacy was observed at 11 AM (peak). At week 24, the difference in mean IOP between treatments was -0.61 mm Hg (95% CI -1.44 to 0.22) at trough and -0.79 mm Hg (95% CI -1.77 to 0.20) at peak, indicating no significant difference between the 2 timolol formulations. The number of reports of blurred vision and tearing was significantly higher in the timolol GS group than in the timolol solution group (P = 0.04), whereas burning/stinging was reported more frequently in the timolol solution group than in the timolol GS group (P = 0.04). At week 12, the decrease in mean heart rate at trough (hour 0) was significantly less for patients in the timolol GS group than for those in the timolol solution group (-1.1 vs -4.2 bpm; P = 0.024). At week 24 (hour 0), the decrease in mean heart rate was less for patients treated with timolol GS by 2.5 bpm (P = 0.051). The heart rate data at peak (hour 2) was similar to that observed at trough at week 12 (-2.7 vs -5.7 bpm; P = 0.006) and week 24 (-3.1 vs -4.7 bpm; P = 0.063). The mean change in blood pressure was not significantly different between treatments. There were no clinically significant differences between the groups in visual acuity, biomicroscopy and ophthalmoscopy results, or visual fields. CONCLUSIONS: Timolol 0.5% GS administered once daily was shown to be as effective in lowering IOP as the equivalent concentration of timolol 0.5% solution administered twice daily in patients with ocular hypertension or open-angle glaucoma.

Adult↗

Improved systemic safety and risk-benefit ratio of topical 0.1% timolol hydrogel compared with 0.5% timolol aqueous solution in the treatment of glaucoma.

PURPOSE: The purpose of the study was to compare the systemic safety and risk-benefit ratio of 0.1% timolol hydrogel and 0.5% aqueous timolol eye drops in the treatment of glaucoma. METHODS: An 8-week randomised, double-blind, cross-over, multicentre study. A total of 25 patients with primary open-angle glaucoma, exfoliation glaucoma, or ocular hypertension was enrolled. After completing a wash-out period, patients were randomly chosen to receive either 0.1% timolol hydrogel once daily or 0.5% aqueous timolol eye drops twice daily. Intraocular pressure and heart rate during rest and exercise, head-up tilt test results, spirometry readings, and plasma concentrations of timolol were recorded. The risk-benefit ratio was determined by calculating the ratio between several heart rate endpoints and the change in intraocular pressure (IOP). RESULTS: The mean drug-induced change in the peak heart rate during exercise was -13.5 beats/min (SD 7.6) in the 0.5% aqueous timolol group and -5.1 beats/min (SD 6.7) in the 0.1% timolol hydrogel group (P<0.001; 95% CI 4.06-12.18). There was no significant difference in the IOP-reducing efficacy between these compounds. The risk-benefit ratio was significantly improved when 0.1% timolol hydrogel was used, compared with 0.5% aqueous timolol in the exercise test. In the head-up tilt test the risk-benefit ratio was significantly improved at rest (P<0.05), at 1 min (P<0.05) and at 5 min (P<0.001) after patients had received 0.1% timolol hydrogel. There were, however, no differences in spirometry readings. After patients had been treated with 0.1% timolol hydrogel, plasma concentrations of timolol were 1/6 (at peak) and 1/50 (at trough) of those of 0.5% aqueous timolol. CONCLUSIONS: Drug-induced changes in the peak heart rate, and head-up tilt test results as well as plasma concentrations of timolol, were significantly more pronounced after treatment with 0.5% aqueous timolol than with 0.1% timolol hydrogel. Because of the statistically similar IOP-reducing efficacy of these formulations the risk-benefit ratio was significantly improved when patients used 0.1% timolol hydrogel instead of 0.5% aqueous timolol.

Administration, Topical↗

Differences in ocular surface irritation between timolol hemihydrate and timolol maleate.

PURPOSE: We evaluated the anterior segment surface reaction findings between timolol hemihydrate and timolol maleate. The only known difference between these preparations is the maleate salt. METHODS: After a baseline examination, we randomized 28 healthy subjects (26 completed) to timolol hemihydrate or timolol maleate given in both eyes twice daily, in a double masked fashion, for 1 week. Subjects then were evaluated at the morning trough (hour 0 examination), dosed, and re-evaluated in 1 hour (hour 1 examination). Subjects were left untreated for 1 week and then switched to the opposite medication for the second study period. RESULTS: Corneal staining (graded 0 to 4) for timolol maleate was worse between baseline (0.9) and hour 0 (1.4; P =.009) and baseline and hour 1 (1.4; P =.011). Also, mean punctate corneal staining for timolol maleate was increased from baseline (22.6) to hour 0 (31.7; P =.033) and showed borderline significance to hour 1 (33.4; P =.058), and for timolol hemihydrate there was a borderline significant elevation from baseline (24.2) to hour 1 (29.8; P =.060). When treatment groups were compared, there was a greater change in corneal staining with timolol maleate than timolol hemihydrate from baseline to hour 0 (P =.020) and greater staining with timolol maleate than timolol hemihydrate at hour 0 (P =.032). Nasal conjunctiva showed increased mean staining with timolol maleate from baseline (23.6, P =.035) to hour 0 (29.5, P =.035) and to hour 1 (31.9 P =.038) but not with timolol hemihydrate. There were increased symptoms of ocular dryness from baseline to hour 0 with timolol maleate (P =.012) but not with timolol hemihydrate. CONCLUSIONS: The study suggests that timolol maleate potentially may have more of an irritant effect than timolol hemihydrate on the corneal and nasal conjunctival epithelium.

Adrenergic beta-Antagonists↗

Effects of D-timolol and L-timolol on ocular blood flow and intraocular pressure.

Effects of D-timolol and L-timolol on IOP were compared with two rabbit models. When the drug solution was injected into vortex vein, 1% D-timolol produced ocular hypotension just like 0.5% L-timolol except D-timolol was less potent than L-timolol to lower the IOP. On the other hand, when 0.5% of D-timolol and L-timolol were instilled into the rabbit eye on IOP recovery model both agents showed equipotency to delayed the IOP recovery. Effects of D-timolol and L-timolol on ocular blood flow were also studied with two rabbit models. D-Timolol at 0.5% did not affect the ocular pulsatile blood flow measured with Langham's pneumatonometer whereas 0.5% L-timolol significantly suppressed it. D-Timolol (0.5%) was found to increase retinal and choroidal blood flows measured with laser Doppler method whereas L-timolol suppressed it. These results indicate that D-timolol though less potent than L-timolol to lower IOP, is superior over L-timolol to improve the blood flow in retina and choroid.

Administration, Topical↗

Twice-daily 0.2% brimonidine-0.5% timolol fixed-combination therapy vs monotherapy with timolol or brimonidine in patients with glaucoma or ocular hypertension: a 12-month randomized trial.

OBJECTIVE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a fixed combination of 0.2% brimonidine tartrate and 0.5% timolol maleate (fixed brimonidine-timolol) compared with the component medications. METHODS: In 2 identical, 12-month, randomized, double-masked multicenter trials, patients with ocular hypertension or glaucoma were treated with fixed brimonidine-timolol twice daily (n = 385), 0.2% brimonidine tartrate 3 times daily (n = 382), or 0.5% timolol maleate twice daily (n = 392). MAIN OUTCOMES MEASURES: Mean change from baseline IOP and incidence of adverse events. RESULTS: The mean decrease from baseline IOP during 12-month follow-up was 4.4 to 7.6 mm Hg with fixed brimonidine-timolol, 2.7 to 5.5 mm Hg with brimonidine, and 3.9 to 6.2 mm Hg with timolol. Mean IOP reductions were significantly greater with fixed brimonidine-timolol compared with timolol at all measurements (P< or =.002) and brimonidine at 8 am, 10 am, and 3 pm (P<.001) but not at 5 pm. The incidence of treatment-related adverse events in the fixed-combination group was lower than that in the brimonidine group (P = .006) but higher than that in the timolol group (P<.001). The rate of discontinuation for adverse events was 14.3% with the fixed combination, 30.6% with brimonidine, and 5.1% with timolol. CONCLUSIONS: Twice-daily fixed brimonidine-timolol therapy provides sustained IOP lowering superior to monotherapy with either thrice-daily brimonidine or twice-daily timolol and is better tolerated than brimonidine but less well tolerated than timolol. APPLICATION TO CLINICAL PRACTICE: Fixed brimonidine-timolol is an effective and convenient IOP-lowering therapy.

Adult↗

The efficacy and safety of the dorzolamide-timolol combination versus the concomitant administration of its components. Dorzolamide-Timolol Study Group.

OBJECTIVE: To evaluate whether a fixed combination of 2% dorzolamide and 0.5% timolol given twice daily showed equivalent efficacy to the concomitant administration of 2% dorzolamide given three times daily and 0.5% timolol given twice daily in patients whose intraocular pressure (IOP) remained elevated during monotherapy with 0.5% timolol twice daily. DESIGN: Multicenter, parallel, randomized, double-masked clinical trial with an open-label extension. PARTICIPANTS AND INTERVENTION: In the masked phase, 242 patients received either the dorzolamide-timolol combination twice daily and placebo three times daily or dorzolamide three times daily and timolol twice daily for up to 3 months. In the open-label extension, 220 patients received the dorzolamide-timolol combination twice daily for up to 9 months. MAIN OUTCOME MEASURES: The criterion for establishing treatment equivalency was a 95% or greater confidence that the absolute difference in the mean change in IOP from baseline was less than 1.5 mmHg between treatments. RESULTS: During 3 months of treatment, the dorzolamide-timolol combination reduced IOP relative to the 0.5% timolol baseline by approximately 14% at hour 0 (just before the morning dose), 20% at hour 2, and 15% at hour 8. The IOP-lowering effect of concomitant therapy with dorzolamide and timolol was approximately 16% at hour 0.20% at hour 2, and 17% at hour 8. At hours 0, 2, and 8, there was greater than 97% confidence that the treatments were equivalent. During the open-label extension, the mean IOP reduction ranged from 14% to 15% at hour 0 and from 20% to 21% at hour 2. The treatment groups were generally comparable in terms of adverse events, symptoms, ocular signs, visual acuity, visual fields, physical examination, and laboratory measures. CONCLUSIONS: The IOP-lowering effect of the dorzolamide-timolol combination is comparable to that of dorzolamide three times daily plus timolol twice daily and is maintained for up to 1 year. The dorzolamide-timolol combination provides clinically important reduction in IOP relative to baseline treatment with timolol alone and is generally well-tolerated for up to 1 year.

Adrenergic beta-Antagonists↗

Cardiovascular effects of ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel.

The objective of this randomized, double-masked, cross-over study was to compare the cardiovascular effects of two glaucoma formulations, ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel. Twenty-four young healthy subjects received for 2 weeks either twice daily 0.5% timolol solution or once daily 0.1% timolol hydrogel. Heart rate (HR), blood pressure, atrio-ventricular conduction (PR interval), corrected QT time (QTc) and heart rate variability (HRV) were measured in supine position and during head-up tilted position. The mean peak concentrations of timolol in plasma were significantly higher after administration of 0.5% aqueous solution than after 0.1% hydrogel. A 0.5% timolol aqueous solution decreased HR on average by 3 bpm in supine position and by 7 bpm in head-up tilted position while no significant effects were observed with 0.1% timolol hydrogel. During tilt test HR was significantly lower after administration of timolol aqueous solution than after timolol hydrogel (mean +/- SD, 77 +/- 11 bpm versus 86 +/- 13 bpm, P < 0.05). Timolol aqueous solution slightly decreased QTc during tilt (5.9 +/- 5.6 ms, P < 0.01). During tilt tests, timolol aqueous solution slightly increased atrio-ventricular conduction (7.2 ms, P = 0.02). No significant differences were found in HRV. These results indicate that in healthy volunteers, ophthalmic 0.5% timolol aqueous solution produces more pronounced cardiac beta-blocking effects than 0.1% timolol hydrogel.

Adult↗

The safety and efficacy of switching timolol maleate 0.5% solution to timolol hemihydrate 0.5% solution given twice daily.

This study was undertaken to evaluate the safety and efficacy of switching patients treated with timolol maleate to timolol hemihydrate. In patients with ocular hypertension or chronic open-angle glaucoma treated with beta-blockers for at least three months, we prescribed timolol maleate solution 0.5% given twice daily for one month. We then switched each patient to timolol hemihydrate solution 0.5% (Betimol, Ciba Vision Ophthalmics) given twice daily for three months. This study found over the first three months in 30 completed subjects, using a worse eye analysis, that the intraocular pressure changed from 18.3+/-2.1 mm Hg on timolol maleate to 18.8+/-2.3 mm Hg on timolol hemihydrate (P=0.10) 12 hours after dosing. There was no difference in the overall incidence of unsolicited anterior segment side effects between timolol maleate (4 cases) versus timolol hemihydrate (3 cases) (P=0.69). One patient exited the study because of pain and burning in both eyes while on timolol maleate. No patient was discontinued due to loss of intraocular pressure control after switching to timolol hemihydrate. It was concluded that switching from timolol maleate to timolol hemihydrate is safe and effective in maintaining control of the intraocular pressure.

Aged↗

Efficacy of latanoprost or fixed-combination latanoprost-timolol in patients switched from a combination of timolol and a nonprostaglandin medication.

PURPOSE: To compare latanoprost with the fixed-combination latanoprost-timolol in glaucoma or ocular hypertension patients switched from a combination glaucoma therapy with timolol and another nonprostaglandin medication. DESIGN: Prospective randomized clinical trial. METHODS: Glaucoma or ocular hypertension patients receiving a combined treatment of timolol 0.5% and another nonprostaglandin medication (pilocarpine 4%, alpha-agonist, or a topical carbonic anhydrase inhibitor) underwent a 30-day washout of their medications. A masked observer then measured their intraocular pressure (IOP). The subjects were randomized to either latanoprost or fixed-combination latanoprost-timolol eyedrops to use once daily at 7 am. The IOP was measured again 30 days after the patients started using one of the study drugs by the same examiner at the same time. MAIN OUTCOME MEASURE: Comparison of the study medications' hypotensive effect. RESULTS: Fifty-three eyes (28 in the latanoprost group and 25 in the latanoprost-timolol group) from 28 patients were included in the study. The IOP reduction was greater in both study groups compared with the previous combination therapy with timolol and another nonprostaglandin medication in millimeters of mercury (7.7+/-2.3 vs. 5.5+/-2.3, P<0.001, for the latanoprost group; 8.5+/-3.5 vs. 6.3+/-2.7, P<0.001, for the latanoprost-timolol group) and percentage (35.8+/-8.2% vs. 25.6+/-8.9%, P<0.001, for the latanoprost group; 38.6+/-8.7% vs. 28.6+/-9.0%, P<0.001, for the latanoprost-timolol group). There was no statistical difference between latanoprost and fixed-combination latanoprost-timolol in reducing IOP, in either millimeters of mercury (P = 0.3) or percentage (P = 0.2). CONCLUSIONS: Both latanoprost and fixed-combination latanoprost-timolol may be viable substitutes for timolol and another nonprostaglandin medication in glaucoma or ocular hypertension patients.

Adult↗

Patient preference, efficacy, and compliance with timolol maleate ophthalmic gel-forming solution versus timolol maleate ophthalmic solution in patients with ocular hypertension or open-angle glaucoma.

This study was designed to compare timolol maleate ophthalmic gel-forming solution 0.5% (timolol gel) once daily with timolol maleate ophthalmic solution 0.5% (timolol solution) twice daily with respect to patient preference, intraocular pressure (IOP)-lowering effect, and tolerability. A total of 202 patients with ocular hypertension or open-angle glaucoma and an IOP > or = 22 mm Hg were enrolled in this 12-week, randomized, observer-masked, two-period crossover study. Significantly more patients preferred timolol gel to timolol solution (P < 0.001). Ninety-two percent of patients preferring timolol gel strongly agreed or agreed that once-daily dosing was a reason for their preference. Those who preferred timolol solution did so because of fewer side effects. The mean IOP-lowering effects of the 2 treatments were similar at both morning trough and peak time points. The incidence of drug-related adverse experiences was similar (timolol gel 11.4% vs timolol solution 10.9%). Because both treatments were well tolerated and effective in lowering IOP, timolol gel, with its once-daily dosing regimen, should be considered in patients who are candidates for therapy with an ophthalmic beta-blocking agent.

Adrenergic beta-Antagonists↗

[Comparison of once-daily nonpreserved timolol and timolol maleate gel-forming solution associated with latanoprost].

AIM: To compare the efficacy and safety of a single daily instillation of nonpreserved timolol to a timolol maleate gel-forming solution in patients with chronic glaucoma or ocular hypertension already treated with latanoprost. PATIENTS AND METHODS: A randomized, prospective, multicenter, open, parallel-group clinical trial was undertaken with 73 patients with chronic glaucoma treated with latanoprost and a timolol maleate gel-forming solution. In 36 patients, the previous regimen was substituted by nonpreserved timolol given instead of timolol maleate gel for 3 months. The changes in intraocular pressure (IOP) were recorded as well as local and systemic tolerance and patient compliance. RESULTS: At 3 months, both regimens were found equivalent in maintaining IOP control between D0 and D84. The difference with baseline was -0.08 +/- 2.22 mmHg and -0.38 +/- 2.41 mmHg in the nonpreserved timolol group and in the timolol maleate gel-forming solution group, respectively (CI 95% [-0.79; 1.38]). After 84 days of treatment, blurred vision (5.9%) and eyelid deposits (5.9%) were reduced in the preservative-free timolol group compared to the other group (respectively, 33.3% and 24.2%). These differences were statistically significant for both signs (blurred vision: p < 0.0001 and for eyelid deposits: p = 0.03). CONCLUSION: This short-term study has demonstrated the equivalence of nonpreserved timolol to timolol maleate gel-forming solution in terms of IOP control. Moreover, the local tolerance of nonpreserved timolol was better.

Aged↗

A comparative analysis of the effects of the fixed combination of timolol and dorzolamide versus latanoprost plus timolol on ocular hemodynamics and visual function in patients with primary open-angle glaucoma.

AIMS: The aim of this study was to assess the effects of fixed combination of timolol and dorzolamide and latanoprost plus timolol on retinal, choroidal, and retrobulbar hemodynamics and visual function in primary open-angle glaucoma (OAG) subjects. METHODS: Sixteen (16) OAG patients (age, 63.5 +/- 10.8 years; 9 male) were evaluated in a randomized, crossover, double-blind study design after 4 weeks of treatment of latanoprost with timolol and fixed combination of timolol and dorzolamide. After randomization, 9 right eyes and 7 left eyes were included in the hemodynamic portion of the study. Measurements included: adverse events check, visual acuity, contrast sensitivity, blood pressure, heart rate, intraocular pressure (IOP), and fundus examination. Ocular blood flow was assessed using confocal scanning laser Doppler flowmetry, color Doppler imaging, and scanning laser ophthalmoscopy. RESULTS: Both therapies were effective at lowering IOP, whereas there was no statistically significant difference between latanoprost plus timolol and the fixed combination of timolol and dorzolamide (13.9% and 12.2% reduction, respectively; P = 0.5533). Fixed combination of timolol and dorzolamide significantly increased central retinal artery end diastolic blood flow velocity (P = 0.0168) and lowered resistance to flow (P = 0.0279). Temporal posterior ciliary artery peak systolic and end diastolic velocities were significantly increased with the fixed combination of timolol and dorzolamide (P = 0.0125 and 0.0238, respectively). Latanoprost plus timolol had no significant effects on ocular blood flow during 4 weeks of treatment. There were no statistically significant differences in adverse events, blood pressure, heart rate, visual acuity, contrast sensitivity scanning laser ophthalmoscopy, or Heidelberg Retinal Flowmeter for any treatment period. CONCLUSIONS: Fixed combination of timolol and dorzolamide therapy might increase blood flow in OAG patients while attaining a similar IOP reduction compared to latanoprost plus timolol. Visual function, however, was not different in this short-term comparison between the two treatments.

Adrenergic beta-Antagonists↗