Timolol Maleate Gel-forming Solution Research Articles

Effect of timolol maleate gel-forming solution on intraocular pressure, pupil diameter, and heart rate in normal and glaucomatous cats.

To determine the effects of once-daily topical treatment with timolol maleate gel-forming solution (GFS) on intraocular pressure (IOP), pupil diameter (PD), and heart rate (HR) in normal cats and cats with feline primary congenital glaucoma (FCG). A single drop of timolol maleate 0.5% GFS was administered topically to one randomly assigned eye of 18 adult cats (8 normal, 10 FCG) at 8 am for 8 days; the opposite eye served as the untreated control. IOP was measured in both eyes (OU) every 2 h (PD and HR were measured every 4 h), for 14 h total, 1 day prior to and on days 1 and 8 of treatment. In a second treatment phase, a single drop of timolol was administered at 8 pm for 3 nights and IOP, PD, and HR were measured, as above, beginning at 8 am on day 4. Slit-lamp examinations were conducted prior to and after treatment phases. Comparisons of mean IOP, PD, and HR were made at each time point and between treated and untreated eyes by repeated-measures ANOVA and Tukey-Kramer post hoc test, with P < 0.05 considered significant. Timolol maleate 0.5% GFS had an inconsistent effect on IOP, with maximum IOP-lowering effect (mean = 5.6 mmHg, 17.4%) observed 6 h post-treatment in FCG. The drug caused significant miosis (from 4 to 8 h post-treatment), but had no effect on HR. Once-daily application of timolol maleate 0.5% GFS may be of limited clinical benefit in the management of feline congenital glaucoma.

Three Cases of Infantile Hemanioma Treated with Topical Timolol

Infantile hemangioma is a common, benign tumor of infancy. Although systemic propranolol was found to be effective in the treatment of infantile hemangioma, its use is often challenging for clinicians owing to its potential side effects. Recent small studies have suggested that the topical use of timolol maleate gel, a non-selective beta-adrenergic antagonist, might be effective for the treatment of superficial infantile hemangioma. Here, we report three cases of infantile hemangioma of different sizes and depths treated with the topical timolol maleate gel-forming solution.

Timolol Maleate 0.5% or 0.1% Gel‐Forming Solution for Infantile Hemangiomas: A Retrospective, Multicenter, Cohort Study

Therapeutic options for superficial infantile hemangiomas (IH) are limited. Recently, timolol maleate gel, a topical nonselective beta-blocker, has been reported as a potentially effective treatment for superficial IH. This study is an extension of a previously published pilot study designed to further investigate the efficacy and safety and to identify predictors of good response of topical 0.5% or 0.1% timolol maleate gel-forming solution. This was a retrospective cohort study including patients enrolled from five centers. Patients were included if they were treated with timolol maleate 0.1% or 0.5% gel-forming solution and had photographic documentation of the IH and at least one follow-up visit. Patients with concomitant active treatment using other IH treatments were excluded. The primary endpoint was change in the appearance of IH as evaluated using a visual analog scale (VAS). Data from 73 subjects were available for final analysis. Timolol maleate gel-forming solution 0.5% was used in 85% (62/73) of patients, the remainder being treated with 0.1%. The median age at treatment initiation was 4.27 months (interquartile range [IQR] 2.63-7.21 mos), and patients were treated for a mean of 3.4 ± 2.7 months. All patients except one improved, with a mean improvement of 45 ± 29.5%. Predictors of better response were superficial type of hemangioma (p = 0.01), 0.5% timolol concentration (p = 0.01), and duration of use longer than 3 months (p = 0.04). Sleeping disturbance was noted in one patient. This study further demonstrates the efficacy and tolerability of topical timolol maleate and gradual improvement with longer treatment in patients with superficial IH.

Contrast Sensitivity and Optical Quality of the Eye after Instillation of Timolol Maleate Gel-Forming Solution and Brinzolamide Ophthalmic Suspension

To investigate the influence of timolol maleate 0.5% gel-forming solution and brinzolamide 1% ophthalmic suspension on contrast sensitivity, ocular higher-order aberration (HOA), and corneal surface light scattering. Prospective, comparative study. Forty normal volunteers were enrolled in this study. We evaluated contrast sensitivity, ocular HOA, and corneal light scattering before and 2, 5, 10, and 15 minutes after instillation of antiglaucoma eyedrops. Contrast sensitivity function was assessed with the CSV-1000RN chart (Vector Vision Co., Greenville, OH). Higher-order aberration was measured for a 4-mm pupil using the Hartmann-Shack aberrometer (KR-9000PW; Topcon, Tokyo, Japan). Corneal surface light scattering was quantitatively evaluated by using the Scheimpflug camera (EAS-1000, Nidek, Aichi, Japan). Time course of changes in contrast sensitivity, ocular HOAs, and corneal light scattering. Both timolol gel-forming solution and brinzolamide significantly decreased contrast sensitivity for at least 5 minutes after instillation (P<0.01). There were no significant differences in contrast sensitivity between the drugs at any time points. Higher-order aberration, such as third- and fourth-order aberrations and total HOAs, significantly increased after instillation of each drug (P<0.001). Timolol gel-forming solution significantly increased HOA up to 5 minutes after instillation (P<0.05), whereas brinzolamide significantly increased HOA for at least 2 minutes after instillation (P<0.001). Corneal surface scattering significantly increased for 5 minutes after instillation of brinzolamide (P<0.01), but not after instillation of timolol gel-forming solution. Both drugs temporarily deteriorate contrast sensitivity function and optical quality of the eye. However, the mechanism underlying contrast sensitivity reduction seems to be different between the drugs. The reduction may be mainly attributed to increased HOA after instillation of timolol gel and increased light scattering after instillation of brinzolamide. The authors have no proprietary or commercial interest in any materials discussed in this article.

Short-term tolerability of once-daily timolol hemihydrate 0.5%, timolol maleate in sorbate 0.5%, and generic timolol maleate gel-forming solution 0.5% in glaucoma and/or ocular hypertension: A prospective, randomized, double-masked, active-controlled, three-period crossover pilot study

Objective: The aim of this study was to compare symptoms and anterior segment tolerability with short-term (3-day) administration of once-daily timolol hemihydrate 0.5%, timolol maleate in sorbate 0.5%, and generic timolol maleate gel-forming solution 0.5% in the treatment of glaucoma and/or ocular hypertension.Methods: In this prospective, randomized, double-masked, active-controlled, 3-period crossover pilot study, eligible patients had primary open-angle, pigmentdispersion, or exfoliation glaucoma, and/or ocular hypertension in ≥1 eye; had a best corrected visual acuity of 1.0 or better in each eye, as measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing chart; were receiving 1 glaucoma medication; and had an untreated intraocular pressure (IOP) of ≤28 mm Hg in both eyes after washout (if required) at visit 2 (day 0). Patients were assigned to receive, in randomized order, timolol hemihydrate 0.5%, timolol in sorbate 0.5%, or generic timolol gelforming solution 0.5%, 1 drop each morning (~8 am) in the qualified eye(s) (washout IOP ≤28 mm Hg) for 3 days. Each treatment period was separated by a 7-day washout period. At all baseline and end-of-treatment study visits, patients completed a solicited symptom survey (used for the assessment of stinging or burning [grade 0 = none to 4 = severe] and blurred or dimmed vision [grade 0 = none to 4 = severe], among other parameters) and underwent ETDRS, Goldmann applanation tonometry, slit-lamp biomicroscopy, anterior segment staining (corneal, conjunctival nasal, and conjunctival temporal staining), conjuncti-val hyperemia assessment, measurement of tear breakup time, and Schirmer's testing with anesthesia. At end-of-treatment assessments, patients were questioned about adverse events.Results: Thirty patients were enrolled (15 men, 15 women; mean [SD] age, 66.3 [8.9] years; white, 19 patients, black, 11; primary open-angle glaucoma, 17; ocular hypertension, 13). Mean (SD) stinging or burning grade was significantly greater with timolol in sorbate compared with timolol hemihydrate and timolol gel-forming solution (0.9 [0.9] vs 0.4 [0.6] and 0.2 [0.6], respectively; P < 0.001). The between-treatment differences on anterior segment staining, conjunctival hyperemia, tear breakup time, and Schirmer's testing with anesthesia were not significant, with the exception of the change from baseline in conjunctival nasal staining by count, which was significantly higher with timolol gel-forming solution compared with timolol hemihydrate and timolol in sorbate (3.1 [13.4] vs −2.9 [10.1] and −3.0 [8.0], respectively; P = 0.04). On the solicited symptom survey, timolol gel-forming solution was associated with a poorer mean score on blurred or dimmed vision compared with timolol hemihydrate and timolol in sorbate (0.3 [0.7] vs 0.1 [0.3] and 0.0 [0.2], respectively; P = 0.02). Mean best corrected ETDRS visual acuity immediately after instillation was significantly lower with timolol gel-forming solution compared with timolol hemihydrate and timolol in sorbate (49.6 [8.4] vs 53.0 [6.1] and 53.1 [6.7], respectively; P = 0.007). The mean 24-hour trough IOP did not differ significantly between the 3 treatments.Conclusions: In this pilot study that compared the symptoms and tolerability of once-daily timolol hemihydrate 0.5%, timolol in sorbate 0.5%, and timolol gel-forming solution 0.5% in these patients with glaucoma and/or ocular hypertension, short-term (3-day) administration of timolol in sorbate was associated with more stinging or burning compared with timolol hemihydrate and timolol gel-forming solution. Timolol gel-forming solution was associated with more postinstillation blurred or dimmed vision compared with timolol hemihydrate and timolol in sorbate.

The Effects of a Timolol Maleate Gel-Forming Solution on Normotensive Beagle Dogs

The effects of a timolol maleate gel-forming solution (TMGS) on intraocular pressure (IOP), blood pressure (BP), and pupil size (PS) were evaluated in normotensive dogs. TMGS was administered once daily to six normotensive beagle dogs. TMGS administration reduced IOP and PS. The hypotensive effect persisted for 24 hr after the administration. The mean reduction in IOP was 5.3 mm Hg (P<0.01). The changes in BP and PS were not significant. These results suggest that TMGS can potentially be used in the treatments of glaucoma and ocular hypertension in dogs.

A Randomized Trial Assessing Dorzolamide in Patients With Glaucoma Who Are Younger Than 6 Years

To evaluate dorzolamide hydrochloride in patients younger than 6 years who have an elevated intraocular pressure or glaucoma. A 3-month, controlled, randomized, double-masked, multicenter, clinical trial. Patients were randomized to 2% dorzolamide 3 times daily or timolol maleate gel-forming solution (0.25% for patients <2 years and 0.5% for patients > or =2 but <6 years) once daily plus placebo twice daily. If the intraocular pressure was not controlled through monotherapy, younger patients received concomitant dorzolamide 3 times daily and 0.25% timolol gel-forming solution once daily and older patients received a fixed combination of 2% dorzolamide and 0.5% timolol twice daily. The primary safety variable was the proportion of patients who discontinued therapy for a drug-related adverse experience. Intraocular pressure reduction was a secondary measure. One younger patient (1.8%) of 56 randomized to dorzolamide discontinued concomitant therapy because of bradycardia. Two older patients (3.0%) of 66 discontinued dorzolamide because of ocular adverse experiences. The most frequent ocular adverse experiences were discharge and ocular hyperemia (younger cohort) and ocular hyperemia and burning/stinging (older cohort). At week 12, the mean change in intraocular pressure for dorzolamide was statistically significant from baseline (-7.3 mm Hg [-20.6%] and -7.1 mm Hg [-23.3%]) in the younger and older cohorts, respectively; P<.001 for both. Dorzolamide was generally well tolerated and demonstrated efficacy for up to 3 months in patients younger than 6 years.

Comparaison du timolol sans conservateur et du timolol à délivrance prolongée donnés une fois par jour en association à du latanoprost

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. 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. 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). 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.

Comparative efficacy of gel-forming and ophthalmic solutions of 0.5% timolol in open-angle glaucoma

We compared the efficacy in lowering intraocular pressure (IOP) of 0.5% timolol maleate gel-forming solution (GFS) once daily with 0.5% timolol maleate ophthalmic solution twice daily in patients with open-angle glaucoma. In both treatment groups (30 eyes each), IOP was measured at baseline and weeks 2, 4, 8, 12, and 24. The mean decrease of IOP at trough ranged from 5.5 to 5.9 mm Hg for timolol GFS and from 6.1 to 6.5 mm Hg for timolol solution.

Long-term intraocular pressure–lowering efficacy and safety of timolol maleate gel-forming solution 0.5% compared with timoptic XE 0.5% in a 12-month study

PURPOSE: To evaluate the long-term intraocular pressure–lowering efficacy and safety of timolol maleate gel-forming solution 0.5% (Timolol GFS 0.5%, Alcon Research Ltd, Fort Worth, Texas) compared with Timoptic XE 0.5% (Merck, Inc, West Point, Pennsylvania) in patients with open-angle glaucoma or ocular hypertension. METHODS: Two hundred forty-one patients with open-angle glaucoma or ocular hypertension, who had intraocular pressure between 22 and 36 mm Hg in at least one eye, were randomly assigned in a 2:1 ratio to receive either Timolol GFS 0.5% once daily or Timoptic XE 0.5% once daily, in a 12-month randomized, multicenter, double-masked, prospective study. The primary efficacy variable was mean trough intraocular pressure measured at 8:00 am, approximately 24 hours after dosing. RESULTS: The Timolol GFS 0.5% group produced significant trough intraocular pressure reductions from a baseline of 4.5 to 5.2 mm Hg ( P = .0001), compared with reductions of 4.1 to 5.3 mm Hg ( P = .0001) in the Timoptic XE 0.5% group. The difference in mean intraocular pressure between the two treatments was 0.9 mm Hg or less, and the upper 95% confidence limit between groups was 0.92 mm Hg or less at all time points, demonstrating both clinical and statistical equivalence. A similar percentage of patients in the Timolol GFS 0.5% group (71%) and Timoptic XE group (72%) had clinically relevant reductions in intraocular pressure. There was no significant difference in the safety profiles of the two treatments. CONCLUSION: Both treatments were clinically effective in lowering intraocular pressure and maintaining the reductions over long-term use. Timolol GFS 0.5% is a safe and effective therapy for open-angle glaucoma or ocular hypertension and is both clinically and statistically equivalent to Timoptic XE 0.5% in reducing intraocular pressure.

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.

Efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD compared with 0.5% levobunolol hydrochloride BID in patients with open-angle glaucoma or ocular hypertension

We compared the efficacy of timolol maleate ophthalmic gel-forming solution 0.5% QD with that of levobunolol hydrochloride 0.5% BID, as measured by change in intraocular pressure (IOP), effect on heart rate, and ocular tolerability. The study had a positive-controlled, double-masked, randomized, multicenter, 12-week, two-period (6 weeks each), crossover design. One hundred fifty-two patients with open-angle glaucoma or ocular hypertension were randomized to receive either timolol maleate gel-forming solution QD or levobunolol BID for 6 weeks, followed by a crossover to the alternate treatment. IOP and heart rate were measured at morning trough and peak during weeks 3, 6, 9, and 12. Timolol maleate gel-forming solution QD was comparable to levobunolol BID in reducing IOP at peak and trough. Although the effects on peak heart rate were similar between the two medications, the effect on trough heart rate of timolol maleate gel-forming solution QD was significantly less than that of levobunolol BID ( P = 0.001). The incidence of ocular burning and stinging was comparable between the two treatments. Patients experienced significantly more blurred vision when using timolol maleate gel-forming solution than when using levobunolol ( P = 0.013). Overall, more patients experienced at least one adverse event when using timolol maleate gel-forming solution. Timolol maleate gel-forming solution QD is as efficacious in reducing IOP as levobunolol BID.

Daily cost of beta-adrenergic blocker therapy.

To evaluate the daily cost of beta-blocker therapy among commercially available products. Ten different beta-adrenergic blocker preparations, each in 10-mL bottles (except Timoptic-XE [Merck brand of timolol maleate gel-forming solution], which was in a 5-mL bottle), were acquired from a local pharmacy. Each of 10 subjects dispensed 10 drops from each bottle onto an analytical scale. The mean drop volume for each preparation was then calculated. The fill volume of each bottle and the amount of each medicine that was wasted upon dispensing also were determined. Additionally, 60 pharmacies in the United States were randomly chosen to determine the average cost of each preparation studied. Based on all data obtained, an average daily cost of each medicine was calculated. The generic formulation of timolol maleate (Falcon) ($0.55) and Betimol (Ciba Vision Ophthalmics brand of timolol hemihydrate) ($0.57) demonstrated the lowest cost per day of therapy. In contrast, Betoptic-S (Alcon brand of betaxolol hydrochloride) ($1.60) and Betagan (Allergan brand of levobunonol hydrochloride) ($1.35) had the highest daily cost of therapy. Ocupress (Otsuka America brand of carteolol hydrochloride) had the smallest drop volume (31 microL) and Timoptic-XE had the highest (49 microL). Most preparations were close to their stated bottle fill volume. The amount of wasted medicine varied and was least with Ocupress (27%) and greatest with Betoptic-S (54%). The mean pharmacy price for a 10-mL bottle was lowest for OptiPranolol (Bausch & Lomb brand of metipranolol) ($25.51) and Betimol ($28.28); Betoptic-S ($44.80) and Betagan ($43.67) were the most expensive. Although all commercially available beta-adrenergic blockers effectively lower intraocular pressure, one differential factor between medicines is cost, which may be influenced by the price at the pharmacy, volume of medication per bottle, drop size, and medicine wastage.