Timolol Gel Research Articles

24-Hour IOP control with once-daily bimatoprost, timolol gel-forming solution, or latanoprost: a 1-month, randomized, comparative clinical trial

PurposeTo compare the efficacy and safety of once-daily (QD) bimatoprost, latanoprost, and timolol gel-forming solution in providing 24-hour intraocular pressure (IOP) control. DesignThis was a randomized, multicenter, investigator-masked, prospective, parallel-group, clinical trial. ParticipantsPatients with open-angle glaucoma or ocular hypertension. InterventionAfter washout of any previous ocular hypotensive medications, patients were randomly assigned to treatment with bimatoprost 0.03% ophthalmic solution QD (n=38) or latanoprost 0.005% ophthalmic solution QD (n=38) between 7 and 9 pm, or timolol maleate 0.5% gel-forming ophthalmic solution QD (n=39) between 7 and 9 am for 1 month. Main outcome measuresThe primary outcome measure, circadian IOP, was measured at eight time points over the course of 24 hours beginning at 8 am on day 28 and with the last measurement at 8 am on day 29. IOP was also measured at 8 am and 10 am at baseline and at 8 am on day 14. Safety measures included adverse events, biomicroscopy, visual acuity, heart rate, and blood pressure. ResultsAt 10 am (peak drug effect) on day 28, the mean IOP reduction from baseline was significantly greater with bimatoprost (9.3 mm Hg, 40.3%) than with timolol gel (7.1 mm Hg, 31.1%; P=.024, Wilcoxon rank sum test) or latanoprost (7.4 mm Hg, 33.3%). In the overall analysis of IOP measured over the course of 24 hours, mean IOP was significantly lower with bimatoprost or latanoprost than with timolol gel (P<.001; analysis of repeated measures). The analysis of repeated measures also showed a significant difference between bimatoprost and latanoprost (P=.003). In the area-under-the-curve analysis, bimatoprost and latanoprost were superior to timolol gel (P≤.018) but comparable to each other (P≥.223). All treatment regimens were well tolerated, with few discontinuations due to adverse events. There were no significant effects on systemic safety parameters. ConclusionOnce-daily bimatoprost or latanoprost provided significantly better 24-hour IOP control than timolol gel in patients with glaucoma or ocular hypertension. Some measurements suggested a trend for greater efficacy of bimatoprost over latanoprost. All three treatments were well tolerated.

Observed time between prescription refills for newer ocular hypotensive agents: the effect of bottle size

Purpose To describe prescription refill patterns of ocular hypotensive therapies and to measure differences among refill rates across bottle sizes. Design Retrospective, population-based, cohort study. Methods This study included patients dispensed bimatoprost, brimonidine, dorzolamide/timolol, latanoprost, timolol gel (XE) 0.5%, or travoprost between January 1, 1996, and March 30, 2002. The initial fill date was identified for the cohort-defining ocular hypotensive, and the number of days between each subsequent refill was calculated. The analysis was repeated in patients with at least four refills to evaluate potential bias. Descriptive and survival analyses evaluated differences in refill rates across bottle sizes. Results In the 27,387 patients contributing up to four evaluable refill sequences, the amount of drug contained in bottles did not predict the number of days between fills. Patients dispensed larger bottles typically refilled sooner than drop-count studies would predict; results for patients with at least four refills (n = 12,976) confirmed these findings. Survival analysis demonstrated that the bottle size trend held across classes of therapy. Compared with 5.0-ml bottles, patients dispensed 10.0-ml and 15.0-ml bottles returned for refills at approximately 1.5 times the expected rate. When average wholesale prices were applied to refill intervals for selected agents, a 45% excess cost per month was found for the larger bottle sizes (10.0 ml vs 5.0 ml or 5.0 ml vs 2.5 ml). Conclusions Expected refill patterns predicted by bottle size and mean number of drops do not reflect observed refill patterns. Patients dispensed larger bottle sizes return for refills much sooner than expected, regardless of the class of therapy.

The safety and efficacy of timolol 0.5% in xanthan gum versus timolol gel forming solution 0.5%

Purpose. To evaluate the efficacy and safety of timolol maleate 0.5% gel forming solution (TXE, Merck) versus timolol maleate 0.5% gel forming solution (TXG, Falcon) in primary open-angle glaucoma and ocular hypertension patients. Methods. Following a washout period patients were randomly begun on either TXE or TXG each given once each morning for six weeks (Period 1). Patients then were crossed over to the opposite medicine for Period 2. Following each 6-week treatment period the intraocular pressure was obtained at 08:00 trough and +2 and +8 hours post-dosing. Anterior segment staining and photography were performed to assess surface irritation. Results. Thirty-two patients were enrolled in this study; 28 completed. The diurnal intraocular pressure as well as the 08:00 trough and +2 hour post dosing pressures were statistically equal between groups, although a trend to a lower mean pressure was observed in the TXE (17.9 ± 3.2mmHg) compared to the TXG (18.6 ± 3.4mmHg) group. However, eight hours after dosing the pressure was 17.5 ± 3.2mmHg in the TXE group and 18.9 ± 3.3mmHg in the TXG group (P = 0.0019). Safety was similar between groups, including corneal and conjunctival staining, conjunctival hyperemia graded by anterior segment photography and at the slit lamp, and unsolicited and solicited side effects. Vision recovery after instillation was similar between groups. Conclusion. TXE demonstrates a lower intraocular pressure eight hours after dosing than does TXG, but safety appears similar between products.

Latanoprost versus timolol gel to prevent ocular hypertension after phacoemulsification and intraocular lens implantation

PurposeTo evaluate the efficacy of latanoprost and timolol gel in preventing ocular hypertension in the early period after phacoemulsification and posterior chamber intraocular lens (PC IOL) implantation. SettingDepartment of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China. MethodsThis prospective randomized double-masked clinical trial comprised patients with uncomplicated cataract having phacoemulsification with PC IOL implantation. They were randomly assigned to 1 of 3 groups: postoperative application of timolol 0.5% gel-forming solution (Timoptol-XE®) (Group 1), latanoprost 0.005% (Group 2), and control (Group 3). Intraocular pressure (IOP) was measured 2, 4, and 24 hours postoperatively. The anterior chamber was examined for the levels of cells and flare using slitlamp biomicroscopy. ResultsGroup 1 had a significantly greater reduction in mean IOP 2, 4, and 24 hours after phacoemulsification and PC IOL implantation than Group 3 (P < .05). There were no significant differences between Groups 2 and 3 at any interval (P > .05). No excessive postoperative anterior chamber inflammation was observed in any group. ConclusionsA single dose of latanoprost given after phacoemulsification and PC IOL implantation did not produce a significant IOP-lowering effect when compared with a control group in the first 24 hours postoperatively. A single dose of timolol gel produced a significant postoperative IOP decrease as soon as 2 hours and up to 24 hours after surgery. Timolol gel and latanoprost are safe, but timolol is more effective than latanoprost in preventing postoperative ocular hypertension.

Efficacy and safety of timolol solution once daily vs timolol gel added to latanoprost

PURPOSE: To compare the efficacy and safety of timolol hemihydrate 0.5% (Betimol, Ciba Vision Ophthalmics, Duluth, Georgia) vs timolol maleate gel-forming solution 0.5% (Timoptic-XE, Merck, Blue Bell, Pennsylvania), both given every morning added to latanoprost 0.005% given every evening. METHODS: A multicenter, randomized, crossover comparison was performed in patients with primary open-angle glaucoma or ocular hypertension. After at least a 4-week run-in period with latanoprost 0.005% (Xalatan, Pharmacia & Upjohn, Kalamazoo, Michigan), both eyes from 30 patients (60 eyes) were randomly assigned to one of the two adjunctive therapies, timolol hemihydrate or timolol maleate gel for 6 weeks. At the end of the first period, the study medicine was discontinued for a 2-week washout period. Patients then received the opposite medication for the second 6-week period. This study had an 80% power to exclude a 1-mm Hg difference between groups. RESULTS: The baseline intraocular pressure after 1 month of latanoprost treatment only for all 30 subjects was 20.8 ± 2.6 mm Hg. After 6 weeks of timolol hemihydrate, the 24-hour trough intraocular pressure was 17.5 ± 3.4 mm Hg, and for timolol maleate gel, 17.9 ± 3.5 mm Hg ( P = .74). The peak level 2 hours after dosing for timolol hemihydate was 16.4 ± 2.6 mm Hg, and for timolol maleate gel, 16.8 ± 3.8 mm Hg ( P = .84). No patient was discontinued from the study because of lack of efficacy. No differences were observed between treatments in visual acuity, anterior segment findings, or adverse events. CONCLUSIONS: Once-daily β-blocker therapy is an effective ocular hypotensive adjunctive treatment 24 hours after dosing when added to latanoprost, for which timolol hemihydrate 0.5% solution and timolol maleate gel 0.5% appear equally effective and safe.

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 ≥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.

Efficacy and Safety of Timolol Solution Once Daily versus Timolol Gel in Treating Elevated Intraocular Pressure

To evaluate the efficacy and safety of timolol hemihydrate once daily versus timolol maleate gel forming solution once daily in patients with primary open-angle glaucoma or ocular hypertension. We prospectively randomized patients with primary open-angle glaucoma or ocular hypertension to receive either timolol hemihydrate 0.5% solution or timolol maleate gel forming solution 0.5% every morning. The primary efficacy variable was the 8:00 AM trough intraocular pressure (IOP) 24 hours after administration. Three months after initiation of therapy, baseline IOP had decreased from 23.6 +/- 1.9 mmHg to 18.3 +/- 2.8 mmHg in the group taking timolol hemihydrate (n = 22) and from 23.7 +/- 2.2 mmHg to 18.4 +/- 3.1 mmHg in the group receiving timolol maleate gel (n = 21) at the 24-hour trough level. This was not a significant difference between groups at 3 months. Also, no difference was observed between groups in the 2-hour post instillation IOP. Visual acuity was decreased in the group receiving timolol maleate gel compared with those receiving timolol hemihydrate one minute after instillation of study medicine at month 3. Otherwise, ocular and systemic safety were similar between groups. No differences between groups in cardiac pulse or systolic and diastolic blood pressure were observed. Timolol hemihydrate 0.5% solution given once a day appears to be as efficacious and safe in decreasing IOP as timolol maleate gel 0.5% given once a day.

Timolol gel versus acetazolamide in the prophylaxis of ocular hypertension after phacoemulsification

Purpose: To compare postoperative intraocular pressure (IOP) after administration of acetazolamide and timolol following phacoemulsification and intraocular lens implantation.Setting: Ophthalmic Consultants of Long Island, Rockville Centre, New York, USA.Methods: Sixty patients were included in a prospective, randomized, masked trial. The patients received either two doses of oral, sustained-release acetazolamide (Diamox® Sequels®) or a single dose of topical timolol 0.5% gel (Timoptic XE®). Intraocular pressure was measured by Goldmann applanation tonometry preoperatively and 1 day postoperatively.Results: Mean preoperative IOP was 16.4 mm Hg. One day postoperatively, it was 19.5 mm Hg in the oral acetazolamide group and 15.9 mm Hg in the timolol gel group. One patient in the acetazolamide group developed significant adverse reactions.Conclusion: Prophylactic use of topical timolol 0.5% gel for viscoelastic-induced ocular hypertension after cataract extraction appears to offer better IOP control than oral acetazolamide and has potentially fewer adverse systemic effects.

Comparison of Topical Timolol Gel to Oral Acetazolamide in the Prophylaxis of Viscoelastic-Induced Ocular Hypertension After Penetrating Keratoplasty

Viscoelastic-induced ocular hypertension following penetrating keratoplasty (PK) may result in endothelial cell loss and optic nerve damage. In a prospective, randomized, masked trial, two doses of oral sustained-release acetazolamide were compared to a single dose of topical 0.5% timolol gel after 40 PKs. The mean preoperative intraocular pressure (IOP) was 17.4 mm Hg for the oral acetazolamide group and 16.7 mm Hg for the timolol gel group. The mean IOP on the first postoperative day was 17.9 mm Hg with oral acetazolamide and 12.9 mm Hg with timolol gel. One patient developed significant adverse reactions with oral acetazolamide; there were no adverse reactions with timolol gel. Prophylactic use of timolol gel for viscoelastic-induced ocular hypertension after PK appears to offer better IOP control than oral acetazolamide, with potentially fewer adverse systemic effects.

A Double-Masked, Placebo-Controlled Evaluation of Timolol in a Gel Vehicle

We evaluated a topical formulation of timolol in an anionic heteropolysaccharide gellan gum (Gelrite). Fifty-five white patients with ocular hypertension entered a double-masked, placebo-controlled, four-period, incomplete block crossover study. After washout of any ocular hypotensive medications, the intraocular pressure of both eyes of all patients was measured at 0 (09:00 h), 2, 4, 6, 8, 12, and 24 h (diurnal baseline). Patients were then randomized to receive, at 2-week intervals, one drop of each of four of the six treatments in one eye (0.008% timolol gel, 0.1% timolol gel, placebo gel, 0.008% timolol solution, 0.1% timolol solution, and placebo solution). Fellow eyes received the appropriate placebo. As measured by least-squares means, adjusted for the unmedicated baseline diurnal values, there was a clear dose-response, with the 0.1% treatments being more effective ocular hypotensive agents than the 0.008% treatments, which in turn were more effective than the placebo treatments. Within each concentration at several observation points, the gel formulation elicited a 1-2-mm Hg greater efficacy than the solution. Gel-treated subjects had a greater incidence of blurred vision. We conclude that formulation of timolol with a gel may increase efficacy, and thus duration of action. This may possibly allow use of a lower concentration of timolol or a reduced frequency of instillation. Further evaluation in chronic dosing studies is justified.