Dorzolamide/timolol Fixed Combination Research Articles

Add-on Effect of Prostaglandin Analogues in Dorzolamide/Timolol Fixed Combination Treated Primary Open Angle Glaucoma Patients

Purpose: To evaluate the additive intraocular pressure (IOP)-lowering effect of three different prostaglandin analogues in dorzolamide/timolol fixed combination (DTFC)-treated primary open angle glaucoma (POAG).Methods: In this retrospective chart review, adjunctive latanoprost, travoprost, or bimatoprost were administered in DTFC-treated POAG patients who required additional IOP-lowering treatment. IOP, mean deviation value, and adverse drug reactions (ADRs) were evaluated.Results: In the latanoprost group, the baseline IOP was 22.1 ± 1.3 mmHg. The mean IOP after 12 months of adjunctive latanoprost was 18.6 ± 1.3 mmHg and the reduction rate was 15.8% (p = 0.000). In the travoprost group, the mean IOP after adjunct travoprost was 18.2 ± 1.5 mmHg and the reduction rate was 16.9% (p = 0.000). In the bimatoprost group, the mean IOP and reduction rate were 18.1 ± 1.5 mmHg and 17.0%, respectively (p = 0.000). There were no significant differences in the additional IOP reduction rate among the three groups (p = 0.687). The most common ADR was conjunctival hyperemia in all three groups. However, there were no serious ADRs causing ocular damage.Conclusions: Latanoprost, travoprost, and bimatoprost showed additional IOP reduction by 15.8-17.0% in DTFC-treated POAG patients.

Use of a Novel Microshunt in Refractory Childhood Glaucoma: Initial Experience in a Compassionate Use/Early Access Cohort

In patients with refractory childhood glaucoma, treatment options include trabeculectomy or large glaucoma drainage devices (GDDs) with attendant short- and long-term risks. A novel polymer-based microshunt is under review by the US Food and Drug Administration (FDA) for use in adults. The device is attractive for children given the long-term stability of the polymer and the small conjunctival incision required for implantation. This early clinical series explores the safety and efficacy of this device in patients with refractory childhood glaucoma who would otherwise undergo trabeculectomy or implantation of a GDD. Prospective single-center case series under FDA compassionate use investigational device exemption. FDA and institutional review board approvals were obtained to treat ≤20 children using this investigational device under the compassionate use pathway. Single eyes in patients with refractory childhood glaucoma were treated surgically with the microshunt. Patients with ≥1 year of follow-up are reported. Twelve eyes of 12 children (15 months to 14 years if age) with mean preoperative intraocular pressure of 22.72 ± 4.8 mm Hg on 3.3 ± 0.65 medications were treated beginning in December 2019. No intraoperative complications occurred. Among eyes with ≥1 year of follow-up (range 12-23 months), 9 were successfully controlled. In this group, preoperative intraocular pressure 21.6 ± 4.9 mm Hg dropped 45% to 11.9 ± 3.8 mm Hg at 1 year; 7 patients were taking no medications at 12 months, and 2 required 2 medications (fixed-combination dorzolamide-timolol). Three eyes failed, requiring additional surgery. These early data suggest that the device is safe and appears effective in patients with refractory childhood glaucoma. A prospective, multicenter pivotal trial is planned.

Morphological changes in the trabecular meshwork and Schlemm\u2019s canal after treatment with topical intraocular pressure-lowering agents

Glaucoma treatment is usually initiated with topical medication that lowers the intraocular pressure (IOP) by reducing the aqueous production, enhancing the aqueous outflow, or both. However, the effect of topical IOP-lowering medications on the microstructures of the aqueous outflow pathway are relatively unknown. In this retrospective, observational study, 56 treatment-naïve patients with primary open-angle glaucoma were enrolled. Images of the nasal and temporal corneoscleral limbus were obtained using anterior segment optical coherence tomography (AS-OCT). The conjunctival vessels and iris anatomy were used as landmarks to select the same limbal area scan, and the trabecular meshwork (TM) width, TM thickness, and Schlemm’s canal (SC) area were measured before and after using the IOP-lowering agents for 3 months. Among the 56 patients enrolled, 33 patients used prostaglandin (PG) analogues, and 23 patients used dorzolamide/timolol fixed combination (DTFC). After 3 months of DTFC usage, the TM width, TM thickness, and SC area did not show significant changes in either the nasal or temporal sectors. Conversely, after prostaglandin analog usage, the TM thickness significantly increased, and the SC area significantly decreased (all P < 0.01). These findings warrant a deeper investigation into their relationship to aqueous outflow through the conventional and unconventional outflow pathways after treatment with PG analogues.

Effect of prostaglandin analogues on anterior scleral thickness and corneal thickness in patients with primary open-angle glaucoma

Prostaglandin (PG) analogues are usually prescribed as a first-line therapy in patients with glaucoma because of its once-daily dosing benefit and effective intraocular pressure (IOP) reduction. However, the mechanism of PG analogues is not completely understood. In this study, we investigated the effect of PG analogues on the anterior scleral thickness (AST) in treatment-naïve eyes with primary open-angle glaucoma using anterior segment optical coherence tomography. The AST was measured at the location of the scleral spur, 1000 μm, and 2000 μm posterior to the scleral spur and was compared before and after using the medications for 3 months and 1 year. Among 54 patients enrolled in this study, 31 patients used prostaglandin analogues and 23 patients used dorzolamide/timolol fixed combination (DTFC) drugs. There was no significant difference in untreated IOP, glaucoma severity, and baseline AST values between the two groups. While there was no significant changes in AST after using the DTFC drugs, the AST at all 3 locations showed a significant reduction in both the nasal and temporal sectors after using PG analogues for 1 year (all, P < 0.05). These findings suggest that the AST reduction after using PG analogues might be related with the increased uveoscleral outflow.

Can dorzolamide/timolol-fixed combination effectively treat primary open-angle glaucoma?: A protocol for systematic review and meta-analysis.

Background:Primary open-angle glaucoma (POAG) is a very common disorder, and it is the second leading cause that results in blindness worldwide after cataracts. Previous studies have reported that dorzolamide/timolol-fixed combination (DTFC) can be used in treating POAG. However, there are still inconsistent results. Thus, this study will systematically investigate the efficacy and safety of DTFC on POAG.Methods:A comprehensive search will be carried out in Cochrane Library, MEDLINE, EMBASE, CINAHI, ACMD, China National Knowledge Infrastructure, and WANGFANG database from origin to the present. There are no limitations related to the language and publication status. Only randomized controlled trials that assessed the efficacy and safety of DTFC for the treatment of POAG will be included. Two researchers will independently undertake record selection, data extraction, and study quality assessment. Any divisions will be solved by discussion with a third researcher. We will perform statistical analysis using RevMan 5.3 softwareResults:This study will summarize the present evidence to identify the efficacy and safety of DTFC in treating POAG through mean intraocular pressure, best corrected visual acuity, contrast sensitivity, bioelectric activity of the retina, rate of progression of glaucoma, quality of life, and adverse events.Conclusions:The results of this study will provide evidence of DTFC for the treatment of POAG.Systematic review registration:INPLASY202040120.

Dorzolamide/Timolol Fixed Combination: Learning from the Past and Looking Toward the Future.

The key clinical attributes of preserved dorzolamide/timolol fixed combination (DTFC) and the emerging potential of preservative-free (PF) DTFC are reviewed with published evidence and clinical experience. The indications and role of DTFC in current glaucoma management are critically discussed. Preserved DTFC became the first intraocular pressure (IOP)-lowering fixed combination (FC) approved by the US Food and Drug Administration (FDA) and remains one of most commonly used medications worldwide. The pharmacological properties of DTFC reflect those of its two time-tested constituents, i.e., the carbonic anhydrase inhibitor dorzolamide and the non-selective beta-blocker timolol. In regulatory studies DTFC lowers IOP on average by 9 mmHg (32.7%) at peak and by 7.7 mmHg (27%) at trough. In trials DTFC shows equivalence to unfixed concomitant therapy, but in real-life practice it may prove superior owing to enhanced convenience, elimination of the washout effect from the second drop, improved tolerability, and better adherence. PF DTFC became the first PF FC approved, first in unit-dose pipettes, and more recently in a multidose format. Cumulative evidence has confirmed that PF DTFC is at least equivalent in efficacy to preserved DTFC and provides a tangible clinical benefit to patients with glaucoma suffering from ocular surface disease by improving tolerability and adherence. Finally, we identify areas that warrant further investigation with preserved and PF DTFC

Comparative Study between the Effect of Dorzolamide/Timolol Fixed Combination and Brimonidine/Timolol Fixed Combination on Corneal Endothelium

Abstract Background: Glaucoma is one of the most important cause of irreversible blindness in the world. Elevated Intraocular Pressure (IOP) remains the main known risk factor for the development and progression of the disease. The main thera-peutic goal is to preserve visual function by reducing the IOP, which is the key modifiable risk factor. Aim of Study: Is to compare the effect and safety of Dorzolamide/Timolol-Fixed Combination (DTFC) and Bri-monidine/Timolol-Fixed Combination (BTFC), on corneal endothelium after 3 months. Patient and Methods: This comparative non-randomized controlled clinical trial study included 57 eyes of 57 patients which was conducted in Damietta Eye Hospital. Their age ranged from 20-70 years old. The study population was divided into two groups: First group receiving DTFC: Included 27 eyes of 27 patients with open angle glaucoma and second group receiving BTFC included 30 eyes of 30 patients with open angle glaucoma. Result: Show that this adjusted difference between group 1 and group 2 through 3 months follow-up had no statistical significance in all variables such as IOP (p=0.172), CCT (p=0.072) and CD (p=0.406). Conclusion: The patients that received two fixed-combination (dorzolamide/timolol) and (brimonidine/timolol) had no statistically significant effect on CCT and ECD after 3 months from using these drugs.

24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.

IntroductionThe aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD).MethodsProspective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period.ResultsForty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001).ConclusionsIn this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy.Trial registrationClinicalTrials.gov (NCT02802137).FundingSanten.

Effects of a dorzolamide/timolol fixed combination on diurnal intraocular pressure, heart rate, blood pressure, and ocular perfusion pressure in normal-tension glaucoma.

The aim of this study was to evaluate the effects of a dorzolamide-timolol fixed combination (DTFC) on intraocular pressure (IOP), heart rate (HR), blood pressure (BP), ocular perfusion pressure (OPP), and diastolic ocular perfusion pressure (DOPP) in patients with normal-tension glaucoma (NTG). A prospective, interventional, single-blind, single-center study was conducted. Newly diagnosed NTG patients that had not been treated with a glaucoma medication in the most recent 4weeks were included. Patients were examined at baseline (without medication) and week 4 (under medication). Baseline IOP, HR, systolic and diastolic BP, OPP, and DOPP were measured at 8am, 12pm, and 4pm. At week 4, IOP, HR, systolic and diastolic BP, OPP, and DOPP were measured at 10am and 8pm as well. After 4weeks of DTFC treatment, IOP was significantly reduced at all time points (1.6-2.6mmHg, P<0.001), and the average IOP reduction was 14.4%. HR and systolic BP showed no statistically significant difference at all time points; however, diastolic BP was decreased significantly at 12pm and 4pm (P=0.004 and 0.001). OPP and DOPP showed no statistical significant difference after DTFC. DTFC has favorable effects on IOP and can be used without concerns of DOPP in patients with NTG.

Comparison of brimonidine-timolol and dorzolamide-timolol in the management of intraocular pressure increase after phacoemulsification.

To compare the effectiveness of brimonidine/timolol fixed combination (BTFC) and dorzolamide/timolol fixed combination (DTFC) in the management of short-term intraocular pressure (IOP) increase after phacoemulsification surgery. Eighty eyes of 80 patients undergoing phacoemulsification and intraocular lens (IOL) implantation were randomly assigned into three groups. Group 1 consisted of 28 eyes and represented the control group. Group 2 consisted of 25 eyes undergoing phacoemulsification surgery and BTFC was instilled at the end of surgery. Group 3 consisted of 27 eyes undergoing phacoemulsification surgery and DTFC was instilled at the end of surgery. IOP was measured preoperatively and 6, 24h and 1wk postoperatively. There was no statistically significant difference in preoperative baseline IOP among the three groups (P=0.84). However, IOP was significantly lower in groups 2 and 3 compared to the control group (P<0.05 for all comparisons) at all postoperative visits. There was no significant difference between groups 2 and 3 at any visit. Eight eyes (28.6%) in the control group, two (8%) in Group 2 and one (3.7%) in Group 3 had IOP >25 mm Hg at 6h after surgery (P=0.008). However, IOP decreased and was >25 mm Hg in only one eye in each group at 24h after surgery. BTFC and DTFC have similar effects in reducing increases in IOP after phacoemulsification surgery and can both be recommended for preventing IOP spikes after such surgery.

Adherence to Preservative-Free Dorzolamide/Timolol Fixed Combination Assessed by Counting the Unused Single-Dose Units

Purpose: To investigate the actual adherence to treatment with preservative-free dorzolamide-timolol fixed combination (DTFC) eyedrops of primary open-angle glaucoma (POAG) patients by counting the number of unused single-dose units of DTFC. Methods: This study included 34 POAG patients newly prescribed with preservative-free DTFC eyedrops (formulated in single-dose units). The enrolled patients were asked to bring the unused DTFC units on their next visit after 2 weeks of treatment with DTFC. On their second visit, they were asked to complete a questionnaire regarding the self-reported adherence and the number of unused DTFC single-dose units was counted. The actual adherence (%) was calculated by dividing the expected number of used DTFC units by the actual number of used DTFC units. The correlation between the self-reported adherence and the measured adherence was assessed. Results: Twenty-nine (93.5%) patients answered they adhered to the medication by more than 90% and 2 (6.5%) answered they instilled the eyedrops at 80-90% of the dosing schedule. However, after counting the unused DTFC single-dose units, 9 (29.0%) patients showed an actual adherence of <90%. Moreover, the actual adherence of 3 (9.7%) patients was <60%. Unexpectedly, 4 (12.9%) patients showed the actual adherence exceeding 100% (196%, 1 patient; 107-132%, 3 patients). Conclusions: We demonstrated a large difference between the self-reported and the actual adherence to treatment by counting the unused single-dose units of eyedrops. Preservative-free topical anti-glaucoma medications (formulated in single-dose units) provide clinicians an opportunity to assess the actual adherence of glaucoma patients by counting the unused units of eyedrops. J Korean Ophthalmol Soc 2015;56(6):906-910

Intraocular Pressure–lowering Efficacy of Dorzolamide/Timolol Fixed Combination in Normal-tension Glaucoma

To investigate the intraocular pressure (IOP)-lowering efficacy and safety of dorzolamide/timolol fixed combination (DTFC) in patients with normal-tension glaucoma (NTG). An open-label, 12-week, 2-center study was conducted. Thirty-seven patients with treatment-naïve NTG received DTFC for 12 weeks to reduce IOP. Primary outcome measures were changes in IOP from baseline to 12 weeks of treatment at a peak drug effect. Secondary outcome measures were changes in IOP from baseline to 12 weeks of treatment a trough drug effect and 8 hours after drug administration. At each visit, IOP was measured at 9 AM and then DTFC was administered by a hospital personnel. IOP was also measured at 11 AM and 5 PM At week 12, the IOP was measured at 1 and 3 PM as well. The IOP at peak drug effect (11 AM) at 12 weeks was significantly reduced to 11.9±2.6 mm Hg from the baseline of 15.6±2.5 mm Hg (23.7%, P<0.0001). Significant reduction in the IOP was also achieved at trough drug effect (9 AM) and at 8 hours after drug administration (5 PM) at 12 weeks (20.5% and 24.4%, respectively, all P<0.0001). Eye irritation (59.5%) was the most frequently reported adverse event followed by ocular hyperemia (16.2%). The majority of eye irritations were mild in intensity. No patients discontinued the DTFC due to an adverse event and no systemic adverse event was considered related to study medication. DTFC is a safe and effective IOP-lowering agent in patients with NTG.

Comparison of Dorzolamide-Timolol Fixed Combination and Latanoprost, Effects on Intraocular Pressure and Ocular Pulse Amplitude

Purpose: To compare dorzolamide-timolol fixed combination (DTFC) and latanoprost with regard to their effects on intraocular pressure (IOP) and ocular pulse amplitude (OPA). Methods: Sixty eyes of 60 patients with open angle glaucoma or glaucoma suspect were included in the present study. Patients were divided into 2 groups, DTFC-treated (n = 30) and latanoprost-treated (n = 30). IOP and OPA were measured with dynamic contour tonometer (DCT) and Goldmann applanation tonometer (GAT), before and at least 1 month after treatment. Results: GAT IOP, DCT IOP and OPA decreased by 2.25 ± 2.23 mm Hg, 1.97 ± 2.06 mm Hg, and 0.14 ± 0.88 mm Hg, respectively in the DTFC-treated group. In the latanoprost-treated group, GAT IOP, DCT IOP and OPA was reduced by 2.74 ± 2.96 mm Hg, 2.06 ± 3.50 mm Hg, and 0.69 ± 1.07 mm Hg, respectively. There was no significant difference (p = 0.311) in the decline of IOP between the 2 groups, but OPA of the DTFC-treated group decreased less than the latanoprost-treated group (p = 0.032). Conclusions: No significant differences were observed in the short-term decline of IOP between the 2 medications. However, the influence of DTFC on OPA appeared negligible in the latanoprost-treated group. J Korean Ophthalmol Soc 2014;55(6):854-859

The Effect of Nebulized Dorzolamide/Timolol Fixed Combination Mist versus Drops on Retrobulbar Blood Flow and Intraocular Pressure in Glaucoma Patients

The aim of this study was to evaluate intraocular pressure (IOP), retrobulbar blood flow (RBF), and ocular side effects after the application of topical dorzolamide/timolol fixed combination (DTFC) drops vs topical nebulized DTFC mist in patients with primary open-angle glaucoma. A total of 15 POAG patients were enrolled in a prospective study. Retrobulbar blood flow was measured in the ophthalmic (OA) and central retinal (CRA) arteries using color Doppler imaging. DTFC mist or drops were applied to the experimental eye, and it was examined after 15 and 60 minutes. DTFC mist was applied 6 times for 30 seconds using a misting device. DTFC mist significantly increased peak-systolic (PSV) and end-diastolic (EDV) velocities after 15 and 60 minutes in both the arteries (OA: increase of 12.5% and 9.6% in PSV, P=0.01; increase of 25.8% and 23.1% in EDV, P=0.03; CRA: increase of 11.5% and 8.7% in PSV, increase of 32% and 21.6% in EDV, respectively, P<0.05). DTFC drops had a similar effect on PSV and EDV in the CRA after 15 and 60 minutes (increase of 8.1% and 9.6% in PSV; increase of 17.1% and 23% in EDV, respectively, P=0.03), but a significant effect on PSV and EDV in the OA was documented only after 15 minutes (increase of 9% and 21.4%, respectively, P=0.02). DTFC mist reduced the resistance index in the CRA after 15 and 60 minutes (decrease of 8.5% and 10.2%, respectively, P=0.04). Both methodologies showed a significant decrease in IOP after 15 and 60 minutes (P<0.05). All patients complained of ocular irritation after drop application, and 1 patient complained of general weakness after mist treatment. Nebulized DTFC mist significantly reduced IOP and increased blood flow in the OA and the CRA, causing no ocular irritation as compared with traditional DTFC drop methodology.

Twenty-four hour efficacy with the dorzolamide/timolol-fixed combination compared with the brimonidine/timolol-fixed combination in primary open-angle glaucoma

The aim of this study is to compare the 24-hour efficacy of dorzolamide/timolol-fixed combination (DTFC) and brimonidine/timolol-fixed combination (BTFC) in primary open-angle glaucoma (POAG). One eye each of 77 POAG patients was included in this prospective, observer-masked, crossover comparison. Following a 2-month timolol run-in period, patients had three intraocular pressure (IOP) measurements at 1000, 1200 and 1400 h while on timolol treatment. Patients showing at least a 20% IOP reduction on timolol were randomised to 3 months of therapy with DTFC or BTFC, and then were crossed over to the opposite therapy. Sixty POAG patients completed the study. The mean 24-hour IOP was significantly reduced with both the fixed combinations compared with the timolol-treated diurnal IOP (P < 0.001). When the two fixed combinations were compared directly, DTFC demonstrated a lower mean 24-hour IOP level as compared with BTFC (mean difference: -0.7 mm Hg, 95% confidence interval (CI): (-1.0, -0.3), P < 0.001). At two individual time points, DTFC significantly reduced IOP more than BTFC: at 1800 h (-1.0 mm Hg, 95% CI (-1.6,-0.5), P = 0.001) and at 0200 (-0.9 mm Hg, 95% CI: (-1.4,-0.5), P = 0.001). No significant difference existed for the other time points. Both the fixed combinations significantly reduce 24-hour IOP in POAG. DTFC provided significantly better 24-hour efficacy.

Safety, tolerability, and efficacy of fixed combination therapy with dorzolamide hydrochloride 2% and timolol maleate 0.5% in glaucoma and ocular hypertension

Glaucoma is a collection of diseases characterized by multifactorial progressive changes leading to visual field loss and optic neuropathy most frequently due to elevated intraocular pressure (IOP). The goal of treatment is the lowering of the IOP to prevent additional optic nerve damage. Treatment usually begins with topical pharmacological agents as monotherapy, progresses to combination therapy with agents from up to 4 different classes of IOP-lowering medications, and then proceeds to laser or incisional surgical modalities for refractory cases. The fixed combination therapy with the carbonic anhydrase inhibitor dorzolamide hydrochloride 2% and the beta blocker timolol maleate 0.5% is now available in a generic formulation for the treatment of patients who have not responded sufficiently to monotherapy with beta adrenergic blockers. In pre- and postmarketing clinical studies, the fixed combination dorzolamide–timolol has been shown to be safe and efficacious, and well tolerated by patients. The fixed combination dorzolamide–timolol is convenient for patients, reduces their dosing regimen with the goal of increasing their compliance, reduces the effects of “washout” when instilling multiple drops, and reduces the preservative burden by reducing the number of drops administered per day.

Considerations in glaucoma therapy: fixed combinations versus their component medications

Fixed combinations of medications that lower intraocular pressure (IOP) are increasingly used in the treatment of glaucoma and ocular hypertension and offer several potential advantages over combined use of the separate component medications including enhanced convenience, improved adherence, reduced exposure to preservatives, and possible cost savings. This review aims to examine the current role of IOP-lowering fixed combinations in disease management. The results of studies that compared the efficacy and safety of IOP-lowering fixed combinations with their component medications are summarized, including those fixed combinations that consist of a prostaglandin analog and timolol. The fixed combinations currently available for use in the United States are fixed-combination dorzolamide/timolol (FCDT) and fixed-combination brimonidine/timolol (FCBT). Both of these fixed combinations reduce IOP more effectively than their component medications used separately as monotherapy. FCBT therapy also demonstrates a more favorable safety profile and reduced ocular allergy compared to monotherapy with brimonidine, a component medication. Few studies have directly compared the efficacy and safety of FCDT and FCBT, but available evidence suggests that FCBT is at least as effective as FCDT in lowering IOP and is more comfortable and better tolerated. Additional studies are needed to further evaluate the comparative efficacy and tolerability of FCDT and FCBT in the management of glaucoma and ocular hypertension.

Three-month, randomized, parallel-group comparison of brimonidine–timolol versus dorzolamide–timolol fixed-combination therapy

ABSTRACTObjective: Fixed combinations of 0.2% brimonidine–0.5% timolol and 2% dorzolamide–0.5% timolol are used to lower intraocular pressure (IOP). The objective of this study was to evaluate the IOP-lowering efficacy and ocular tolerability of brimonidine–timolol compared with dorzolamide–timolol when used as monotherapy or as adjunctive therapy to a prostaglandin analog (PGA) in patients with glaucoma or ocular hypertension.Study design and methods: Pooled data analysis of two randomized, investigator-masked, 3-month, parallel-group studies with identical protocols (ten sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who were in need of lower IOP received topical brimonidine–timolol BID or dorzolamide–timolol BID as monotherapy (n = 101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost, or travoprost) (n = 79).Clinical trial registration: The studies are registered with the identifiers NCT00822081 and NCT00822055 at http://www.clinicaltrials.gov.Main outcome measures: IOP was measured at 10 a.m. (peak effect) at baseline and at months 1 and 3. Tolerability/comfort was evaluated using a patient questionnaire.Results: There were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years. There were also no statistically significant differences between treatment groups in baseline IOP. At month 3, the mean (SD) reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (4.2) mmHg (32.3%) with brimonidine–timolol versus 6.7 (5.0) mmHg (26.1%) with dorzolamide–timolol (p = 0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3%) with brimonidine–timolol versus 5.2 (3.7) mmHg (23.5%) with dorzolamide–timolol (p = 0.213). Patients on brimonidine–timolol reported less burning (p < 0.001), stinging (p < 0.001), and unusual taste (p < 0.001) than patients on dorzolamide–timolol.Conclusions: Fixed-combination brimonidine–timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide–timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine–timolol received higher ratings of ocular comfort than dorzolamide–timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine–timolol and dorzolamide–timolol during long-term treatment.

Success rates for switching to dorzolamide/timolol fixed combination in timolol responders who are insufficiently controlled by latanoprost monotherapy

We aimed to investigate the safety and efficacy of dorzolamide/timolol fixed combination (DTFC) in timolol responders with ocular hypertension or open-angle glaucoma who switched to DTFC because of insufficient control on latanoprost. We carried out a prospective, open-label cohort study with an active-historical control in which qualifying patients must have been treated with latanoprost monotherapy for at least 4 weeks, must have demonstrated insufficiently controlled intraocular pressure (IOP) (> or = 19 mmHg at 08.00 hours), and must have shown a decrease in IOP at 2 hours after timolol instillation of > or = 3 mmHg or > or = 15%. Patients then began DTFC dosed at 08.00 hours and 20.00 hours and discontinued latanoprost. Patients were evaluated again after 4 and 12 weeks. In 57 patients IOP was further reduced by 2.4 +/- 3.3 mmHg at 08.00 hours (p < 0.0001) and by 3.5 +/- 3.3 mmHg at 10.00 hours (p < 0.0001) after switching to DTFC. Responses to the Comparison of Ophthalmic Medications for Tolerability (COMTol) questionnaire showed no difference between DTFC and latanoprost for in terms of overall preference, typical daily activities, limitation of activities, compliance, satisfaction or quality of life (p > 0.05). However, greater frequency in burning and/or stinging (p < 0.0001) and bitter taste (p < 0.0001) were observed with DTFC, whereas unusual taste (p = 0.02) and itchy eyes (p = 0.05) were associated with latanoprost. This study suggests that patients who are insufficiently controlled on latanoprost monotherapy, and who are timolol responders, can generally achieve further IOP reduction and similar tolerance levels when changed to DTFC.

Meta-analysis of 24-Hour Intraocular Pressure Studies Evaluating the Efficacy of Glaucoma Medicines

To evaluate efficacy and safety data of currently available ocular hypotensive medicines derived from 24-hour studies, of similar design, in patients with primary open-angle glaucoma (POAG), exfoliative glaucoma, or ocular hypertension (OH). Meta-analysis of published articles evaluating patients with POAG, exfoliative glaucoma, or OH. We included articles that were randomized, prospective, single- or double-masked, comparative studies of ocular hypotensive therapies over 24 hours. Each article selected contained an untreated baseline, >or=4-week treatment period, >/=20 patients per treatment arm, and >or=6 time points not spaced >5 hours apart and used Goldmann applanation or Tonopen tonometry (supine measurements) to measure intraocular pressure (IOP). Twenty-four-hour IOP efficacy. This analysis included 864 separate 24-hour treatment curves from 386 patients in 28 treatment arms from 11 studies. A statistical difference in the mean diurnal pressure decrease existed between monotherapy treatments for POAG/OH patients, with bimatoprost (29%) and travoprost (27%) showing the greatest 24-hour reduction (P = 0.026). Timolol 0.5% was less effective than latanoprost (24% vs. 19% reduction) but decreased the pressure at each night time point (P = 0.0003). Dorzolamide showed a 19% 24-hour pressure reduction and brimonidine 0.2% a 14% one. In exfoliative glaucoma patients, latanoprost and travoprost showed higher baseline and treatment pressures, although the pressure reductions (29% and 31%, respectively) were greater generally than observed with POAG/OH. An evening-dosed latanoprost/timolol fixed combination reduced the pressure 33%, and the dorzolamide/timolol fixed combination (DTFC), 26%. However, the power to detect a difference for this specific comparison was probably low, due to the limited number of patients (n = 20) in the DTFC group. A statistical difference between evening-dosed (24%) and morning-dosed (18%) latanoprost (P<0.0001) was noted, but not between evening (27%) and morning (26%) travoprost (P = 0.074). The mean reduction of night time points was statistically lower than day time points for latanoprost (P = 0.031), timolol (P = 0.032), and brimonidine (P = 0.050), but not for dorzolamide. Dorzolamide (P = 0.60), travoprost (P = 0.064), and bimatoprost (P = 0.057) did not demonstrate nighttime pressures lower than daytime ones. The mean reduction of night time points was statistically lower than that of day time points for latanoprost (P = 0.031), timolol (P = 0.032), and brimonidine (P = 0.050), but not for dorzolamide (P = 0.60), bimatoprost (P = 0.057), travoprost (P = 0.064). Similar relative efficacies generally exist in various classes of ocular hypotensive agents during night and day hours.