cloprostenol and dorzolamide

To evaluate the intraocular pressure (IOP) reduction achieved by the most frequently prescribed antiglaucoma drugs in patients with normal tension glaucoma (NTG).. Systematic review and meta-analysis.. Fifteen randomized clinical trials reported 25 arms for peak IOP reduction, 16 arms for trough IOP reduction, and 13 arms for diurnal curve IOP reduction.. Pertinent publications were identified through systematic searches of PubMed, EMBASE, and the Cochrane Controlled Trials Register. The patients had to be diagnosed as having NTG. Methodological quality was assessed by the Delphi list on a scale from 0 to 18. The pooled 1-month IOP-lowering effects were calculated using the 2-step DerSimonian and Laird estimate method of the random effects model.. Absolute and relative reductions in IOP from baseline for peak and trough moments.. Quality scores of included studies were generally high, with a mean quality score of 12.7 (range, 9-16). Relative IOP reductions were peak, 15% (12%-18%), and trough, 18% (8%-27%) for timolol; peak, 14% (8%-19%), and trough, 12% (-7% to 31%) for dorzolamide; peak, 24% (17%-31%), and trough, 11% (7%-14%) for brimonidine; peak, 20% (17%-24%), and trough, 20% (18%-23%) for latanoprost; peak, 21% (16%-25%), and trough, 18% (14%-22%) for bimatoprost. The differences in absolute IOP reductions between prostaglandin analogues and timolol varied from 0.9 to 1.0 mmHg at peak and -0.1 to 0.2 mmHg at trough.. Latanoprost, bimatoprost, and timolol are the most effective IOP-lowering agents in patients with NTG.

Topics: Aged; Amides; Antihypertensive Agents; Betaxolol; Bimatoprost; Brimonidine Tartrate; Cloprostenol; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Quinoxalines; Randomized Controlled Trials as Topic; Sulfonamides; Thiazines; Thiophenes; Timolol; Tonometry, Ocular; Travoprost

Fixed combinations represent a combination of two ocular hypotensive agents into one single ophthalmic solution. Current commercially available fixed combinations used in glaucoma treatment include Combigan, Cosopt, Xalcom, Duotrav and Ganfort. Statistically significant superiority of the ocular hipotensive efficacy of the fixed combinations vs monotherapy with the two individual constituents is present connected with Cosopt and Xalcom. It also exists vs timolol ophthalmic solution relative to Combigan, Duotrav and Ganfort but is missing within these fixed combinations vs brimonidine, travatan and bimatoprost respectively. A slight reduction, that is clinically and statistically insignificant relative to fixed combination efficacy vs the nonfixed combinations (e.g. concomitant but separate administration of the two individual components) is acceptable when this is balanced by potential benefits of the fixed combinations therapy (improved tolerability and convenience,increased compliance,cost and time economies,decreased washout effect and reduced exposure to preservatives).

Topics: Amides; Antihypertensive Agents; Bimatoprost; Brimonidine Tartrate; Cloprostenol; Drug Combinations; Drug Therapy, Combination; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Travoprost; Treatment Outcome

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.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Circadian Rhythm; Cloprostenol; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Exfoliation Syndrome; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Single-Blind Method; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Travoprost; Treatment Outcome

Despite treatment, glaucoma patients may still suffer vision loss because of inadequate control of intraocular pressure or late presentation. This article reviews the latest evidence supporting a reappraisal of first-line treatment in the management of glaucoma, including a review of latanoprost, recently approved for first-line treatment of glaucoma and ocular hypertension.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Brimonidine Tartrate; Cloprostenol; Dinoprost; Drug Therapy, Combination; Glaucoma; Humans; Latanoprost; Lipids; Prostaglandins; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Travoprost

Bimatoprost, a prostamide, effectively lowers intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. In clinical trials, bimatoprost has demonstrated superiority to the beta-adrenergic antagonist timolol and has consistently provided approximately 1-2 mmHg greater mean IOP lowering than the prostaglandin latanoprost. Bimatoprost is more effective than either timolol or latanoprost in allowing patients to reach the low target pressures that best protect the visual field. Patients on bimatoprost therapy achieve low pressures throughout the day and night. Moreover, 1-year trials have shown that the efficacy of bimatoprost is sustained with long-term use. The most common side effects have been conjunctival hyperaemia, graded as trace or mild, and eyelash growth. No safety concerns have arisen in postmarketing surveillance. Bimatoprost appears to be a valuable new agent for glaucoma therapy.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amides; Antihypertensive Agents; Benzimidazoles; Bimatoprost; Clinical Trials as Topic; Cloprostenol; Drug Combinations; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Lipids; Omeprazole; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes

Bimatoprost, a synthetic prostamide analogue, is a new ocular hypotensive agent indicated for the second-line treatment of open-angle glaucoma and ocular hypertension. The drug is formulated as a 0.03% ophthalmic solution. Bimatoprost lowers intraocular pressure (IOP) by increasing aqueous humour outflow. When applied topically once daily in patients with ocular hypertension or glaucoma, bimatoprost 0.03% significantly reduced IOP. Mean IOP was reduced by approximately 7.5 to 9.2mm Hg 12 hours after drug administration in randomised clinical trials. The reduction in IOP was maintained throughout the 24-hour dosage interval. Once-daily treatment with bimatoprost 0.03% was found to be significantly more effective than timolol 0.5% (administered twice daily as an ophthalmic solution or once daily as a gel-forming solution) in randomised comparative trials in patients with ocular hypertension and glaucoma. Furthermore, after 1 to 6 months' treatment, the percentage of patients reaching a target IOP of < or =17mm Hg was significantly greater in the bimatoprost-treated groups than in those receiving timolol. Bimatoprost 0.03% ophthalmic solution was found to be at least as effective as topical latanoprost 0.005% administered once daily in two clinical trials. Reductions in IOP 16 and 20 hours postdose were greater in patients treated with bimatoprost, indicating superior control of IOP at timepoints throughout the dosage interval. In patients refractory to beta-blocker therapy, treatment with bimatoprost 0.03% produced greater reductions in diurnal IOP measurements than combination therapy with topical dorzolamide 2%/timolol 0.5%; approximately twice as many bimatoprost 0.03% recipients achieved an IOP of < or =16mm Hg. The most commonly reported adverse effect during clinical trials of once-daily bimatoprost 0.03% was conjunctival hyperaemia which occurred in 42 to 46% of patients treated. However, most cases were mild and only 1 to 4% of patients withdrew from treatment as a result. Overall withdrawal rates as a result of adverse events during clinical trials ranged from 2.6 to 7%. Bimatoprost has been reported to cause changes in the pigmentation of the periorbital skin, eyelashes and iris, and increase eyelash growth. The long-term consequences of these effects are unknown. Cardiopulmonary adverse effects, which have been associated with the use of beta-blockers such as timolol, were not reported in clinical trials of bimatoprost. Thus, in clinical trials o

Topics: Administration, Topical; Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Conjunctival Diseases; Dose-Response Relationship, Drug; Drug Therapy, Combination; Glaucoma, Open-Angle; Intraocular Pressure; Latanoprost; Lipids; Ocular Hypertension; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

Fixed-combination ocular hypotensives have multiple advantages, but triple-therapy dorzolamide/brimonidine/timolol (dorz/brim/tim) is only available in Latin and South America, and information on its relative efficacy is limited. This study compares the efficacy and tolerability of fixed-combination bimatoprost/timolol (bim/tim) and dorz/brim/tim in Mexican patients with primary open-angle glaucoma or ocular hypertension.. In this investigator-masked, crossover study, patients with unmet target intraocular pressure (IOP) on once-daily bim/tim or twice-daily dorz/brim/tim received the opposite medication for 3 months before returning to their pre-baseline medication for 3 months. IOP was evaluated before and after morning instillation at months 2, 3, 5 and 6. Primary endpoints were mean IOP change and Ocular Surface Disease Index© (OSDI) score at each visit. The intent-to-treat population was the a priori analysis population, but due to the number of discontinuations, the per-protocol and intent-to-treat populations were used for the primary efficacy and sensitivity analyses, respectively.. Seventy-eight and 56 patients were included in the intent-to-treat and per-protocol populations, respectively. At month 3, statistically significant IOP reductions from baseline were observed in the bim/tim (P < 0.01) and dorz/brim/tim (P < 0.0001) groups, regardless of assessment time. At month 6, patients returned to bim/tim exhibited no significant IOP increase (regardless of assessment time), but patients returned to dorz/brim/tim exhibited a statistically significant IOP increase (P < 0.001) when assessed before instillation of study treatment. Results were similar in both intent-to-treat and per-protocol analysis populations. In the per-protocol analysis, 70% of patients on bim/tim at month 3 had an IOP <14 mm Hg, which declined to 58% (P = 0.0061) at month 6 (ie, after 3 months of dorz/brim/tim treatment). In patients receiving dorz/brim/tim at month 3, 38% had an IOP <14 mm Hg, which remained comparable after return to bim/tim. OSDI scores and incidence of adverse events were similar in both groups.. In this first direct comparison of the efficacy of dorz/brim/tim and bim/tim, patients switched from dorz/brim/tim to bim/tim demonstrated improved/lower IOP; when returned to dorz/brim/tim, IOP increased to levels seen at study initiation, suggesting that once-daily bim/tim may have greater IOP-lowering efficacy. Both bim/tim and dorz/brim/tim were well tolerated with minimal ocular surface damage.. ClinicalTrials.gov: NCT01737853 (registered October 9, 2012).

Topics: Administration, Topical; Aged; Aged, 80 and over; Amides; Antihypertensive Agents; Bimatoprost; Brimonidine Tartrate; Circadian Rhythm; Cloprostenol; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Treatment Outcome

This prospective, multicenter, single-masked study evaluated the additive effect of dorzolamide hydrochloride 2% on the diurnal intraocular pressure (IOP) curve and retinal and retrobulbar hemodynamics in patients with primary open-angle glaucoma (POAG) treated with morning-dosed bimatoprost 0.03%.. Eighty-nine patients (aged, 60.7 ± 11.8 years, range 33-80; 68 women) with POAG received bimatoprost dosed once in the morning for 1 month, after which dorzolamide was added twice daily for 2 months. IOP (Goldmann) and arterial blood pressure (BP) and diurnal ocular perfusion pressures (OPP) were measured every 2 hr for 24 hr. Heidelberg retina flowmetry of the retinal microcirculation was recorded four times daily in 64 patients and colour Doppler imaging of the ophthalmic and central retinal arteries was recorded five times daily in 25 patients. All measurements were taken after the two phases of treatment and compared using anova analysis with Bonferroni adjustment.. Mean baseline IOP was 16.5 ± 3.4 mmHg. Mean diurnal IOP with dorzolamide adjunctive therapy (12.9 ± 2.1 mmHg) was significantly lower compared to mean IOP with bimatoprost monotherapy (13.6 ± 2.2 mmHg) (p = 0.03). Adjunctive dorzolamide therapy significantly decreased vascular resistance in the ophthalmic artery (p = 0.02). Mean diastolic BP and OPP were significantly lower after adjunctive therapy. There were no changes in retinal microcirculation between the two phases of treatment.. Adjunctive dorzolamide therapy to morning-dosed bimatoprost 0.03% reduced diurnal IOP and vascular resistance in the ophthalmic artery but did not alter retinal circulation in this group of patients with POAG.

Topics: Adult; Aged; Aged, 80 and over; Amides; Antihypertensive Agents; Bimatoprost; Blood Flow Velocity; Blood Pressure; Circadian Rhythm; Cloprostenol; Drug Administration Schedule; Drug Therapy, Combination; Eye; Female; Glaucoma, Open-Angle; Hemodynamics; Humans; Intraocular Pressure; Laser-Doppler Flowmetry; Male; Middle Aged; Ophthalmic Artery; Prospective Studies; Retinal Artery; Single-Blind Method; Sulfonamides; Thiophenes; Tonometry, Ocular; Ultrasonography, Doppler, Color

To assess the additive effect of dorzolamide hydrochloride 2% on the diurnal intraocular pressure (IOP) curve and retrobulbar haemodynamics in patients with primary open-angle glaucoma (POAG) treated with morning-dosed bimatoprost 0.03%.. Twenty-five patients with POAG were evaluated in a prospective, single-masked study. After a 1 week run-in period with bimatoprost all patients were treated with bimatoprost dosed once in the morning for 1 month, after which dorzolamide was added twice daily for 2 months. Goldmann applanation IOP, arterial blood pressure (ABP) and heart rate were measured every 2 h for 24 h and diurnal ocular perfusion pressure (OPP) was calculated. Colour Doppler imaging (CDI) of the ophthalmic artery (OA) and the central retinal artery (CRA) was recorded five times daily. All measurements were taken after the two phases of treatment and were compared.. The mean baseline IOP was 14.8 ± 3.5 mm Hg. Mean IOP following bimatoprost monotherapy (12.8 ± 2.9 mm Hg) and after 2 months of dorzolamide adjunctive therapy (12.2 ± 2.6 mm Hg) were not statistically significantly different (p=0.544). Only at the 4:00 h time point was IOP significantly reduced using the bimatoprost/dorzolamide combined treatment (p=0.013). The 24 h IOP fluctuations were lower when dorzolamide was added (6.0 ± 2.3 mm Hg vs 4.6 ± 1.5 Hg, p=0.0016). Repeated analysis of variance detected a significant decrease of vascular resistance in the OA (p=0.0167) with adjunctive dorzolamide treatment.. The addition of dorzolamide to morning-dosed bimatoprost had an additive hypotensive effect only on the night-time IOP curve at 4:00 h and resulted in a lower IOP fluctuation. Dorzolamide added to bimatoprost may reduce vascular resistance in the OA.

Topics: Adult; Aged; Aged, 80 and over; Amides; Antihypertensive Agents; Bimatoprost; Blood Flow Velocity; Cloprostenol; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Hemodynamics; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Artery; Ophthalmic Solutions; Orbit; Prospective Studies; Single-Blind Method; Sulfonamides; Thiophenes

To compare the efficacy of brimonidine, dorzolamide, and brinzolamide in reducing intraocular pressure (IOP) when used as adjunctive therapy to a prostaglandin analog (PGA).. Randomized, controlled, investigator-masked, single-site, parallel-group clinical trial.. One hundred twenty eyes of 120 patients with open-angle glaucoma or ocular hypertension who had inadequate IOP control after at least 6 weeks of monotherapy with a once-daily PGA (bimatoprost, latanoprost, or travoprost).. Study eyes were assigned randomly to adjunctive treatment with thrice-daily brimonidine tartrate 0.15% (n = 41), dorzolamide hydrochloride 2% (n = 40), or brinzolamide 1% (n = 39) for 4 months.. Efficacy was evaluated by IOP measured at 10 am and 4 pm at baseline, month 1, and month 4.. The mean IOP at each hour at PGA-treated baseline was comparable among treatment groups. After initiation of adjunctive therapy, the mean IOP was lower and the mean change from baseline IOP was greater in the brimonidine group than in either the dorzolamide group or the brinzolamide group at 10 am and 4 pm at months 1 and 4 (P<0.001). After 4 months of adjunctive treatment, the mean IOP reduction from baseline at 10 am and 4 pm was 4.8 mmHg (21%) and 3.8 mmHg (19%) with brimonidine, 3.4 mmHg (16%) and 2.8 mmHg (14%) with dorzolamide, and 3.4 mmHg (16%) and 2.6 mmHg (13%) with brinzolamide (P<0.001 for brimonidine vs. dorzolamide and brinzolamide at each time point). Each of the study drugs was well tolerated, and all patients completed the study.. The addition of brimonidine to a PGA provided greater IOP lowering than the addition of either dorzolamide or brinzolamide. Further studies are needed to evaluate the relative long-term efficacy and tolerability of these medications as adjunctive therapy to a PGA.. Proprietary or commercial disclosure may be found after the references.

Topics: Aged; Aged, 80 and over; Amides; Antihypertensive Agents; Bimatoprost; Brimonidine Tartrate; Cloprostenol; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F, Synthetic; Quinoxalines; Single-Blind Method; Sulfonamides; Thiazines; Thiophenes; Tonometry, Ocular; Travoprost; Treatment Outcome

The aim of this study was to evaluate the intraocular pressure (IOP) efficacy and safety of dorzolamide/timolol in fixed combination (DTFC) versus bimatoprost in open-angle glaucoma (OAG) patients poorly controlled (> or =21 mmHg) on latanoprost.. This was a prospective, double-masked, randomized, controlled, cross-over evaluation. After a 6-week wash-out period, the patients then returned for baseline diurnal curve testing every 2 h (8 AM to 8 PM). Patients with an IOP of 22-29 mmHg inclusive at 8 AMwere randomized to either bimatoprost dosed each evening or DTFC twice-daily. Patients returned in 8 weeks for the Period 1 diurnal curve and were switched to the opposite treatment. Patients again returned in 8 weeks for the Period 2 diurnal curve.. Of the 29 patients, mean untreated baseline IOP (visit 2) was 24.6 +/- 2.6 mmHg and treatment mean IOP was statistically lower with bimatoprost 17.6 +/- 2.0 mmHg than for DTFC 18.8 +/- 2.5 mmHg (P = 0.03), as was the IOP range (P = 0.02) and IOP peak (P = 0.003). No significant differences were found between DTFC and bimatoprost at individual time points after a modified Bonferroni correction (>0.02). DTFC demonstrated a greater incidence of stinging or burning (n = 12) than bimatoprost (n = 0; P = < 0.0001).. This study suggests that OAG patients generally can obtain similar IOP control at individual time points (when a Bonferroni correction is considered) by switching to either DTFC or bimatoprost, but overall diurnal control is statistically better with bimatoprost.

Topics: Aged; Aged, 80 and over; Amides; Bimatoprost; Cloprostenol; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Latanoprost; Male; Middle Aged; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

To compare the ocular hypotensive efficacy and safety of topical bimatoprost and timolol-dorzolamide combination in patients with primary open-angle glaucoma (POAG) or ocular hypertension during 6 months of treatment.. A sample of 65 patients with a diagnosis of POAG or ocular hypertension were randomized to receive either bimatoprost 0.03% once daily or timolol-dorzolamide combination twice daily. Study visits occurred at baseline and after 2 weeks and 1, 3 and 6 months of therapy. Intraocular pressure (IOP) measurements were performed at 12.00 hours at all study visits and also at 08.00 hours and 16.00 hours at baseline and 6-month visits. At each visit, local and systemic side-effects that occurred during the treatment period were recorded. Student's t-test was used to compare the differences between IOP values.. Differences in IOP between the bimatoprost and timolol-dorzolamide groups were statistically insignificant at all study visits (p > 0.05). In the bimatoprost-treated group, the IOP reduction was 6.2 +/- 1.8 mmHg, whereas it was 6.5 +/- 2.3 mmHg in the timolol-dorzolamide group after 6 months of treatment. The difference was not statistically significant (p = 0.48).. The IOP-lowering efficacies of bimatoprost and timolol-dorzolamide combination were similar over a 6-month follow-up. Both bimatoprost and the timolol-dorzolamide combination were well tolerated. Bimatoprost can be used as a longterm monotherapy agent in the treatment of POAG and ocular hypertension.

Topics: Aged; Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Lipids; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Single-Blind Method; Sulfonamides; Thiophenes; Timolol

The purpose of this study was to compare travoprost (TRAV; travoprost 0.004%) and the fixed-combination of dorzolamide/timolol (DTFC; dorzolamide 2.0%/timolol maleate 0.5%) ophthalmic solutions for reducing intraocular pressure (IOP) in patients with primary open-angle glaucoma (OAG) or ocular hypertension (OHT).. This was a randomized single masked, study with parallel controls. The TRAV group (n = 29) dosed once daily at 9:00 PM while the DTFC group (n = 27) dosed twice daily at 9:00 AM and 9:00 PM. IOP was measured at baseline, and following 3 weeks and 6 weeks of treatment at 8:00 AM, 12:00 PM, 4:00 PM, and 8:00 PM.. Mean average IOP reductions from baseline during the course of the day were 7.5 (32.7%) and 7.1 (30.7%) mmHg for TRAV and 4.8 (23.1%) and 4.5 (21.7%) mmHg for DTFC at 3 weeks and 6 weeks, respectively. The greater IOP reduction for patients receiving TRAV was statistically significant at both the 3 and 6 week visits when averaged across all four time points (p < 0.01). The two products were well-tolerated over the course of the 6 week study. Some factors such as taste perversion were reported more often in the DTFC group.. Travoprost monotherapy provided better efficacy in terms of IOP reduction and percentage of IOP reduction compared to dorzolamide 2.0%/timolol maleate 0.5% fixed combination.

Topics: Cloprostenol; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Single-Blind Method; Sulfonamides; Thiophenes; Timolol; Travoprost

Reduced choroidal perfusion is hypothesized to play a role in the pathogenesis of normal tension glaucoma. Thus the impact of antiglaucomatous eye drops on ocular perfusion has been the focus of recent research and the subject of intensive investigations. The present study investigates whether topically applied latanoprost or bimatoprost influence ocular perfusion in patients with normal tension glaucoma and compares these effects with that changes detected after the treatment with dorzolamide.. Ocular hemodynamics were assessed by color Doppler imaging (CDI) shortly before and after a one-month treatment with either latanoprost, bimatoprost or dorzolamide. Primary end-points of the study were peak systolic and end-diastolic blood flow velocities in the short posterior ciliary artery (SPCA) under the new therapy. Intraocular pressure (IOP) and additional perfusion parameters in the SPCA and other retrobulbar vessels were tracked as observational parameters. n = 42 patients with normal tension glaucoma were enrolled in the study.. Systolic and diastolic blood flow velocities in the SPCA showed no significant alteration after the treatment with latanoprost or bimatoprost. Dorzolamide lead to increase of peak systolic velocity. IOP was reduced by all three agents in a range reported in the literature.. Topically applied latanoprost and bimatoprost act in a hemodynamically neutral manner and have the capability to lower IOP even in patients with normal tension glaucoma and low initial IOP level. Dorzolamide accelerates blood flow in systole. None of the tested compounds has a negative impact on hemodynamics in the short posterior ciliary arteries.

Topics: Administration, Topical; Amides; Antihypertensive Agents; Bimatoprost; Blood Flow Velocity; Ciliary Arteries; Cloprostenol; Eye; Glaucoma, Open-Angle; Hemodynamics; Humans; Intraocular Pressure; Latanoprost; Lipids; Ophthalmic Artery; Ophthalmic Solutions; Prospective Studies; Prostaglandins F, Synthetic; Regional Blood Flow; Retinal Artery; Single-Blind Method; Sulfonamides; Thiophenes; Ultrasonography, Doppler, Color

To analyse comparatively the efficacy and tolerance of latanoprost, travoprost and the fixed combination timolol-dorzolamide in the treatment of primary open angle glaucoma and ocular hypertension.. Prospective, investigator masked, randomized study that included 38 patients (38 eyes) with primary open angle glaucoma uncontrolled under beta blockers. Each patient received latanoprost, travoprost and the fixed combination timolol-dorzolamide (for 3 months each). The first drug and the order of the next drugs administered were randomized. The follow up period was 9 months. At the baseline and at the end of each therapeutic period (3 months) we determined the IOP (at 8, 10 a.m. and 4 p.m.), visual acuity, C/D ratio, blood pressure, heart rate and local tolerance. We have also photographed the eyelids, lashes, conjunctiva and iris. After each month of treatment we determined the IOP (at 8 and 10 am), visual acuity, blood pressure, heart rate and local tolerance.. The mean initial IOP was 25.1 2.89 mmHg and after 9 months of treatment 21.67 4.59 mmHg. Each drug induced a statistically significant IOP decrease (the fixed combination timolol-dorzolamide decreased IOP with 14.33%, travoprost with 18.39% and latanoprost with 22.1%). The IOP lowering was comparable for the prostaglandin derivatives and superior to the fixed combination timolol-dorzolamide. None of these drugs had a negative influence on the visual field, C/D ratio, visual acuity, blood pressure and heart rate. There was good local tolerance. The side effects were more frequent after travoprost (37) and latanoprost (22) than after the fixed combination timolol-dorzolamide (4 cases). The most important adverse events for the prostaglandin derivatives were conjunctival hyperemia, eyelashes pigmentation and growth, iris pigmentation. There was no necessary to stop the medication because of these effects.. Travoprost, latanoprost and the fixed combination timolol-dorzolamide are efficient in the treatment of primary open angle glaucoma. The prostaglandin derivatives determined similar IOP decrease, which was superior to the fixed combination timolol-dorzolamide; the local tolerance was good, the fixed combination causing the fewest side effects.

Topics: Aged; Antihypertensive Agents; Cloprostenol; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Latanoprost; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Travoprost; Treatment Outcome

The topical medication represents the first line therapy for the primary open angle glaucoma. The study is aimed at assessing the structural and immunohistochemical changes of conjunctiva induced by topical glaucoma medication.. For this purpose, we carried out a 40 weeks, prospective, experimental, epidemiological-operational and randomized study enrolling 18 patients (36 eyes) with recently primary open angle glaucoma. The eyes were divided into treatment (non-selective beta blockers or selective, prostaglandin analogues, topical carbonic anhydrase inhibitors) in four groups. The assessment was performed by comparison with control group (4 patients) who was instilled with natural tears (with different preservative). Both the cytology and the conjunctival biopsy specimens were investigated by histological exams and immunohistochemistry using different monoclonal antibodies. The study was performed by collaboration with The National Institute of Research and Development in Pathology and Biomedical Sciences-"V. Babes"-Bucharest.. The morphometric analysis of histological sections of conjunctiva showed the following changes: squamous metaplasia (significant increases in the thickness and number of epithelial cell layers), inflammation (increase the number of lymphocytes, macrophages and fibroblasts) and subconjunctival fibrosis. According to the type of medication, we observed the significant increase of subepithelial collagen density and degenerative changes of fibrocytes, the reduction of extracellular matrix and also the up-regulation of antibodies against matrix metalloproteinase and allergic changes. According to structural changes, the immunohistochemistry confirmed the tendency of chronic inflammation.. This study revealed important structural and immunohistochemical changes of conjunctiva after topical glaucoma medication. The category and the intensity of these changes are dependent on the sort of therapy and the topical treatment period. The findings showed that benzalkonium chloride (the most common preservative of antiglaucoma drugs) is a major factor for conjunctival metaplasia.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Antihypertensive Agents; Benzalkonium Compounds; Betaxolol; Carbonic Anhydrase Inhibitors; Cloprostenol; Conjunctiva; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Immunohistochemistry; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prospective Studies; Sulfonamides; Thiophenes; Timolol; Travoprost

Histological changes of, in particular, collagen and extracellular matrix after administration of topical prostaglandin F(2alpha)(PGF (2alpha)) analogues have been reported. In view of this observation, we investigated the influence of PGF(2alpha) analogues on the central corneal thickness.. In a non-randomized, controlled, cross-sectional study, 403 eyes from 208 consecutive patients were examined: 149 eyes (normals/controls) and 79 with ocular hypertension (OHT), 119 eyes with primary open angle glaucoma (POAG) and 56 eyes with normal tension glaucoma (NTG). One experienced ophthalmologist measured the central corneal thickness (CCT) using ultrasound pachymetry (Tomey AL-2000, sequence of 5 measurements with an SD < 3 microm). The central corneal power was measured with the Zeiss keratometer. Depending on the topical treatment, the patients were classified into 4 groups: A) PGF(2alpha) analogues (n = 78), B) carbonic anhydrase inhibitors (n = 26), C) combination of PGF (2)(alpha) analogues and carbonic anhydrase inhibitors (n = 41), D) none of these drugs (n = 258). T tests and multiple linear regression analyses were used for statistical analysis.. CCT was decreased significantly (p < 0.01 each) in eyes treated with PGF(2alpha) analogues (group A: 529 +/- 34 microM), in comparison with the untreated and non-glaucomatous eyes (part of group D: 542 +/- 35 microM, n = 148), untreated glaucomatous/OHT eyes (part of group D: 563 +/- 37 microM, n = 110), eyes treated with carbonic anhydrase inhibitors (group B: 561 +/- 32 microm) and eyes with a topical application of both PGF (2)(alpha) analogues and carbonic anhydrase inhibitors (group C: 555 +/- 48 microM. No correlation was found between CCT and diagnosis (OHT, POAG, NTG, control), gender, central corneal power, and intraocular pressure in a multivariate analysis.. The present findings suggest that the topical application of prostaglandin F(2alpha) analogues onto the cornea reduces the central corneal thickness significantly. These changes might be attributed to effects of PGF(2alpha) analogues on the extracellular matrix of the corneal stroma via upregulation of matrix metalloproteinases. In clinical practice, corneal thinning under local PGF (2)(alpha) analogue treatment could result in underestimation of intraocular pressure levels as measured by applanation tonometry.

Topics: Acetazolamide; Administration, Topical; Adult; Aged; Carbonic Anhydrase Inhibitors; Cloprostenol; Collagen; Cornea; Corneal Topography; Cross-Sectional Studies; Dinoprost; Drug Therapy, Combination; Extracellular Matrix; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Travoprost; Ultrasonography

Examination of the response of the retinal proteome to elevated intraocular pressure (IOP) and to the pharmacological normalization of IOP is crucial, in order to develop drugs with neuroptorective potential. We used a hereditary rat model of ocular hypertension to lower IOP with travaprost and dorzolamide applied topically on the eye surface, and examine changes of the retinal proteome. Our data demonstrate that elevated IOP causes alterations in the retinal protein profile, in particular in high-mobility-group-protein B1 (HMGB1), calmodulin, heat-shock-protein (HSP) 70 and carbonic anhydrase II expression. The changes of the retinal proteome by dorzolamide or travoprost are different and independent of the IOP lowering effect. This fact suggests that the eye drops exert a direct IOP-independent effect on retinal metabolism. Further investigations are required to elucidate the potential neuroprotective mechanisms signaled through changes of HMGB1, calmodulin, HSP70 and carbonic anhydrase II expression in glaucoma. The data may facilitate development of eye drops that exert neuroprotection through direct pharmacological effect.

Topics: Animals; Calmodulin; Carbonic Anhydrase II; Cloprostenol; Disease Models, Animal; Glaucoma; HMGB1 Protein; HSP70 Heat-Shock Proteins; Intraocular Pressure; Ophthalmic Solutions; Peptide Mapping; Proteome; Proteomics; Rats; Retina; Sulfonamides; Thiophenes; Travoprost

Topics: Amides; Antihypertensive Agents; Bimatoprost; Circadian Rhythm; Cloprostenol; Cornea; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Exfoliation Syndrome; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Single-Blind Method; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Travoprost; Treatment Outcome

Topics: Amides; Antihypertensive Agents; Bimatoprost; Circadian Rhythm; Cloprostenol; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Exfoliation Syndrome; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Single-Blind Method; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Travoprost; Treatment Outcome

A retrospective chart review study at a Veterans Affairs hospital evaluated intraocular pressure change after dorzolamide hydrochloride 2% was administered to patients already using travoprost. A literature search found no other study that looked specifically at this combination of drugs.. A chart review of 46 patients at the Veterans Affairs Illiana Health Care System was performed evaluating the intraocular pressures after dorzolamide hydrochloride was added to travoprost. Baseline intraocular pressures were obtained on patients who had been on travoprost at least 4 months. Endpoint intraocular pressures were then obtained from the visit closest to 6 months after the addition of dorzolamide hydrochloride.. An average intraocular pressure reduction of an additional 20.6% was observed after adding only dorzolamide hydrochloride to travoprost.. This study confirmed our clinical observations that dorzolamide hydrochloride added to travoprost is an excellent and safe choice to further lower intraocular pressures.

Topics: Aged; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Cloprostenol; Dose-Response Relationship, Drug; Drug Therapy, Combination; Follow-Up Studies; Glaucoma, Open-Angle; Gonioscopy; Humans; Intraocular Pressure; Middle Aged; Ocular Hypertension; Retrospective Studies; Sulfonamides; Thiophenes; Travoprost; Treatment Outcome; Visual Fields

To investigate the ocular surface inflammatory response to chronic topical treatments in patients with glaucoma by measuring the cytokine level in tears using multiplex bead analysis.. Tear samples were collected from 21 patients with glaucoma and 12 healthy volunteers. Tears were analysed for the presence of 17 cytokines: interleukin (IL)1beta, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL17, granulocyte-colony stimulating factor, granulocyte-macrophage stimulating factor, interferon (INF)gamma, monocyte chemotactic protein (MCP)1, macrophage inflammatory protein 1beta and tumour necrosis factor (TNF)alpha. The cytokines in each sample of tears were measured using multiplex bead analysis with microspheres as solid support for immunoassays.. In the tears of treated patients, proinflammatory cytokines (IL1beta, IL6, IL12, TNFalpha) were significantly increased compared with controls. T helper (Th)1 (INFgamma, IL2) and Th2 (IL5, IL10, IL4) type cytokines were also significantly higher (p<0.05); however, the most marked increase was observed with Th1 cytokines. The expression of chemokine IL8 and MCP1 was also increased in the treated group.. This study shows that pro-inflammatory cytokine secretion by conjunctival cells is increased in response to topical treatments for glaucoma. The characterisation of cytokines in tears was previously limited by the small volume attainable, a limitation that has been overcome by multiplex analysis.

Topics: Administration, Topical; Aged; Amides; Antihypertensive Agents; Bimatoprost; Brimonidine Tartrate; Carteolol; Case-Control Studies; Chemokines; Cloprostenol; Cytokines; Dose-Response Relationship, Immunologic; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Lipids; Male; Prospective Studies; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Tears; Thiophenes; Timolol

To compare the effectiveness and associated costs of travoprost versus a fixed combination of dorzolamide + timolol as first-line therapy for glaucoma according to data collected by the United Kingdom General Practitioner Research Database (UK-GPRD).. Patients with a diagnosis of ocular hypertension, glaucoma, or who had been treated topically by surgery or laser therapy were selected. Patients starting first-line treatment with travoprost or a fixed dorzolamide + timolol combination were included. Times to treatment failure were compared with an adjusted Cox model.. Cost and treatment failure defined as a prescription change (adding or removing a topical treatment, or initiating laser therapy or surgery).. 56 612 patients were extracted from the database and 39 808 patients received at least one topical prescription for IOP-lowering (intraocular pressure) therapy. Of these, 639 were treated with travoprost and 387 with dorzolamide + timolol, as first-line therapies. No significant difference was found between patient characteristics. Patients were aged 70.0 years and 48.5% were male. At 1 year, treatment failure was experienced by 30.4% of patients receiving travoprost and 49.4% receiving dorzolamide + timolol (p < 0.001). The hazard ratio for failure was 0.79 (p < 0.03) less with travoprost, after adjusting on age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management were significantly (p < 0.001) lower with travoprost ( pound198.31) than with dorzolamide + timolol ( pound312.21).. This retrospective costs and consequences analysis study showed that travoprost is more efficient than dorzolamide + timolol as first-line therapy for glaucoma patients. Patients continued longer with first-line treatment when prescribed travoprost at a lower cost.

Topics: Aged; Antihypertensive Agents; Cloprostenol; Cost-Benefit Analysis; Databases, Factual; Drug Combinations; Drug Costs; Female; Glaucoma; Humans; Male; Physicians, Family; Sulfonamides; Thiophenes; Timolol; Travoprost; United Kingdom