dorzolamide and Glaucoma--Open-Angle

Fixed-combination (FC) therapy is used in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients who require more than one medication to reach their target intraocular pressure (IOP). Currently, there are several FC therapies available for the treatment of glaucoma. The FC of latanoprost/timolol (LTFC) is a commonly used FC. Here, we conducted systematic review to compare the IOP-lowering effects of LTFC with other FCs for patients with POAG and OHT.. We searched PubMed, EMBASE, the Cochrane Library, and Web of Science for randomized-controlled clinical trials and cross-over studies. The outcomes were mean IOP and IOP fluctuation after one month of treatment. Meta-analysis was carried out using RevMan (version 5.1) software. After conducting meta-analyses, we rated the quality of each meta-analysis as high, moderate, low, or very low using the "GRADE" system.. We included 16 trials in this meta-analysis. Moderate-quality meta-analysis showed that LTFC had a comparable mean IOP to that of a fixed combination of travoprost and timolol (TTFC) [mean difference (MD): 0.07 mmHg] and a fixed combination of dorzolamide and timolol (DTFC) [MD: -0.31 mmHg], and it also had a comparable IOP-fluctuation effect compared to that of TTFC [MD: 0.13 mm Hg] and DTFC [MD: 0.25 mmHg]. Compared to the fixed combination of bimatoprost and timolol (BiTFC), moderate-quality evidence showed a higher mean IOP in the LTFC group [MD 0.76 mmHg], whereas low-quality meta-analysis showed higher IOP fluctuation [MD 1.09 mmHg] in the LTFC group.. LTFC is as effective as TTFC and DTFC, but worse than BiTFC in controlling mean IOP and IOP fluctuation for POAG or OHT patients. The quality of our meta-analyses was assessed as moderate, with the exception of one low-quality analysis that compared the IOP fluctuation of LTFC and BiTFC.

Topics: Antihypertensive Agents; Bimatoprost; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Sulfonamides; Thiophenes; Timolol; Travoprost; Treatment Outcome

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

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

To estimate the intraocular pressure (IOP)-lowering effect of 2% dorzolamide or 0.005% latanoprost when added to 0.5% timolol.. Meta-analysis of randomized clinical trials.. Seventeen articles reporting on 19 study arms with 5 possible treatment combinations and 4 study arms serving as controls.. Articles written in English, German, French, or Dutch and published up to December 2004 were identified in Medline, Embase, the Cochrane Controlled Trials Register, and references from relevant articles. For the article to be considered, over 85% of the patients had to have primary open-angle glaucoma or ocular hypertension. The pooled 1- to 3-month additional IOP-lowering effect after a run-in phase on timolol was calculated by performing meta-analysis using the random effects model.. Absolute and relative changes in IOP after run-in on timolol for peak moment, trough moment, or mean diurnal curve.. The pooled change from baseline [mean (95% confidence interval)] for 0.5% timolol varied from -0.7 mmHg (-1.2 to -0.2, for the mean diurnal curve) to -2.0 mmHg (-1.3 to -2.7, at peak). Pooled changes for 2% dorzolamide in concomitant use with 0.5% timolol were -4.1 mmHg (-4.4 to -3.8) at trough and -4.9 mmHg (-5.3 to -4.5) at peak. The fixed 2% dorzolamide and 0.5% timolol combination resulted in a pooled change of -3.8 mmHg (-4.2 to -3.4) at trough and -4.9 mmHg (-5.3 to -4.5) at peak. The concomitant use of 0.005% latanoprost and 0.5% timolol gave a pooled change from baseline of -6.0 mmHg (-6.8 to -5.2) at the mean diurnal curve. The fixed combination of 0.005% latanoprost and 0.5% timolol resulted in a mean change of -3.0 mmHg (-3.8 to -2.2) at the mean diurnal curve.. In this meta-analysis of clinical trials, the addition of dorzolamide or latanoprost further lowers IOP in eyes on timolol. This result may not be generalizable because these trials may have included nonresponders to timolol.

Topics: Antihypertensive Agents; Databases, Factual; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Timolol

The primary standard therapy in patients with open-angle glaucoma and ocular hypertension is carried out by means of monotherapy with synthetic prostaglandin analogues. Most of the glaucoma patients need more than one medication for adequate intraocular pressure control. Timolol represents the basic component of these combinations. Timolol topical ophthalmic combinations with dorzolamide (Cosopt), pilocarpine, latanoprost (Xalacom), travoprost and unoprostone are thoroughly described. Most antiglaucoma medications achieve on one side directly baroprotection by decreasing intraocular pressure and on the other side they produce indirectly vasoprotection, that is secondary to intraocular pressure lowering. The Cosopt, due to its Dorzolamide component, makes an exception since it produces directly both baroprotection by aqueous humor flow suppression and vasoprotection by increasing the blood flow within the retina, choroid, optic nerve head and retrobulbar area. Given these considerations as well as the fact that the ocular hypotensive effect of both the Cosopt and the latanoprost are equally potent, a question seems reasonable according to accepted standard i.e. Cosopt or latanoprost as primary glaucoma therapy?

Topics: Administration, Topical; Adrenergic beta-Antagonists; Antihypertensive Agents; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

Almost five years have elapsed since the introduction of latanoprost on several markets and considering the large number of publications dealing with it, the authors felt that it was worth re-evaluating the drug.. The criterion used to select trials for inclusion in the review was: all articles mentioning the drug in common electronic data-bases; these were then screened and considered, on the basis of methodological quality.. Experimental data suggest that latanoprost acts by remodeling the extracellular matrix in the ciliary muscle, thus increasing the flow of aqueous humor through the ciliary muscle bundles of the uveoscleral pathway. POAG: Latanoprost persistently improves the pulsatile ocular blood flow in primary open angle glaucoma (POAG). Recent trials confirmed the greater IOP-lowering efficacy of latanoprost vs. timolol, dorzolamide, brimonidine and unoprostone. Trials lasting up to 24 months showed that latanoprost is effective in long-term treatment of POAG and ocular hypertension (OH), with no signs of loss of efficacy when compared to timolol or dorzolamide. Latanoprost provides better control of circadian IOP. Non-responders to beta-blockers should preferably be switched to latanoprost monotherapy before a combination therapy is started. The possibility of a fixed combination of latanoprost and timolol has been explored, with promising results. NTG: Latanoprost is effective in normal tension glaucoma (NTG), lowering IOP, improving pulsatile ocular blood flow and increasing ocular perfusion pressure. OTHER GLAUCOMAS: Latanoprost may provide effective IOP control in angle-closure glaucoma after iridectomy, in pigmentary glaucoma, glaucoma after cataract extraction and steroid-induced glaucoma. However, latanoprost was effective in only a minority of pediatric cases of glaucoma and is contraindicated in all forms of uveitic glaucoma.. In the articles reviewed, new or duration-related adverse events were reported.

Topics: Antihypertensive Agents; Aqueous Humor; Blood Flow Velocity; Circadian Rhythm; Clinical Trials as Topic; Drug Therapy, Combination; Eye; Glaucoma, Angle-Closure; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prostaglandins F, Synthetic; Safety; Sulfonamides; Thiophenes; Timolol

The presence of a circadian variation of both intraocular pressure (IOP) and aqueous humor flow has been demonstrated in several studies. It must therefore be considered important to monitor IOP and evaluate the efficacy of ocular hypotensive drugs over the 24 hours of the day. The efficacy of latanoprost on IOP during both day and night has been evaluated and the most important results from four such studies are reviewed. The studies reviewed here clearly demonstrate that topical administration of latanoprost 0.005% once daily provided a steady reduction of the IOP during both day and night. Given as a single dose to healthy volunteers, latanoprost resulted in a sustained effect with a significant IOP reduction over 24 hours, and the reduction was still present, however less pronounced, even after 48 hours. Latanoprost administered once daily for 4 weeks to patients with glaucoma or ocular hypertension was more effective in reducing the IOP over 24 hours than timolol gel solution 0.5% once daily, timolol aqueous solution 0.5% twice daily, or dorzolamide 2% three times daily. Latanoprost applied once daily thus provided a better effect on the IOP together with a stable and sustained IOP reduction during both day and night.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Circadian Rhythm; Gels; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Timolol

We reviewed available data comparing latanoprost and combined timolol and dorzolamide and the additive effect of latanoprost in patients receiving timolol and dorzolamide in combination using a literature search through the electronic Medline database and presentations from proceedings of recent glaucoma meetings. Several studies have shown that the intraocular pressure (IOP)-lowering effect of latanoprost once a day is equivalent to timolol 0.5% twice a day and concomitant or combined dorzolamide 2% twice a day. Adding latanoprost to timolol and dorzolamide leads to a further 16% reduction of IOP. We conclude that the effect on IOP reduction of latanoprost is similar to combined timolol and dorzolamide, and the additive effect of latanoprost to a combination of timolol and dorzolamide is clinically relevant. In most cases, the overall safety profile of latanoprost is better than combined timolol and dorzolamide.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Drug Synergism; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

To compare the efficacy and safety of latanoprost monotherapy to dorzolamide combined with timolol from pooled data of five multicenter, randomized, 3-month, observer-masked trials with identical study design.. Patients who were on a beta-blocker or dual therapy where one agent was a beta-blocker were eligible after a 2- to 4-week run-in period on timolol 0.5%, twice daily. Patients then either discontinued timolol treatment and received latanoprost monotherapy n=345) or continued on timolol and received dorzolamide add-on therapy (n=352). Data from these 697 patients were included in the meta-analysis.. From an overall baseline of 22.8mmHg, the mean IOP reduction was 4.8mmHg (21%) in latanoprost-treated patients and 4.1mmHg (18%) in timolol + dorzolamide-treated patients p<0.001). A reduction in diurnal IOP of >=20% was achieved in 54% of the latanoprost-treated patients compared with 44% of the timolol + dorzolamide-treated patients. There was no marked difference between the two groups in the incidence of ocular and systemic events.. This meta-analysis provides further support that a switch to latanoprost monotherapy can be an alternative to combined treatment with timolol + dorzolamide.

Topics: Antihypertensive Agents; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

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

To report a severe case of dorzolamide-induced immune thrombocytopenia, to review the literature on this topic, and to draw attention to the serious potential side effects of this topical sulfonamide.. An 83-year-old man with primary open-angle glaucoma in both eyes who was taking topical dorzolamide therapy for 3.5 years developed a severe thrombocytopenia (10,000 platelets/microL). The amount of platelets was not influenced by prednisone therapy but increased rapidly to 100,000/microL after the withdrawal of dorzolamide.. Although the potential capacity of sulfonamides to induce thrombocytopenia is well known, no case of dorzolamide-induced immune thrombocytopenia was published in the medical literature until July 2000.. Considering the possible severe side effects that can be induced by topical dorzolamide 2%, ophthalmologists should carefully evaluate during the medical history of their patients the risk of sensitivity to sulfonamides.

Topics: Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Glaucoma, Open-Angle; Humans; Male; Platelet Count; Sulfonamides; Thiophenes; Thrombocytopenia

Carbonic anhydrase (CA) plays an important role in the secretion of aqueous humor. The orally administered CA inhibitor acetazolamide lowers the intraocular pressure (IOP) of patients with glaucoma. However, approximately 50% of patients stop treatment with acetazolamide as a consequence of intolerable side effects due to the extraocular inhibition of the enzyme. This prompted attempts to develop a topically active CA inhibitor. Merck Research Laboratories focused on developing a water- and solvent-soluble compound to penetrate the cornea. Dorzolamide hydrochloride is a potent inhibitor of human CA isoenzyme II, with an IC50 value of 0.18 nM in vitro. In contrast, its inhibitory activity against human CA isozyme I is much weaker (IC50 value of 600 nM). Topically administered dorzolamide penetrated the ciliary body, inhibited its CA activity and had a hypotensive effect in rabbits; in contrast, topical administration of acetazolamide or methazolamide did not decrease IOP. In clinical trials, dorzolamide administered 3 times daily was effective in lowering IOP in patients with open-angle glaucoma or ocular hypertension. The hypotensive effect of dorzolamide 0.5% was similar to that of oral CA inhibitors or timolol (0.25%) twice daily. Dorzolamide did not induce the severe systemic adverse events associated with oral CA inhibitors. Dorzolamide was as effective as pilocarpine or dipivefrine as an adjunctive therapy in patients receiving beta-adrenergic antagonists. Dorzolamide also reduced IOP and accelerated retinal arteriovenous passage time in addition to improving visual function in patients with normal-tension glaucoma.

Topics: Animals; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Clinical Trials as Topic; Eye; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Rabbits; Sulfonamides; Thiophenes

The nonselective beta-blocker timolol and the carbonic anhydrase inhibitor dorzolamide both lower intraocular pressure (IOP). Timolol and dorzolamide have different mechanisms of action and their effects are additive when administered together. Therefore, the 2 drugs are frequently used concomitantly to treat patients with open-angle glaucoma who have not adequately responded to first-line therapy. A barrier to good compliance with concomitant therapy is the need to administer 5 or 6 drops of medication on 2 or 4 occasions during the day. Timolol 0.5% and dorzolamide 2.0% have therefore been combined in a single formulation, reducing the number of administrations required to 2 per day. Clinical trials in patients with glaucoma have demonstrated that dorzolamide 2%/timolol 0.5% (dorzolamide/timolol) is superior to monotherapy with the individual components. When dorzolamide/timolol administered twice daily was compared with concomitant treatment with dorzolamide 2% and timolol 0.5%, each administered twice daily for 90 days, both regimens resulted in marked lowering of trough IOP (measured just before the morning dose) compared with baseline (reduction in IOP = 4.2mm Hg). The effect of the 2 regimens on IOP at all time points, both before treatment and at peak effect (2 hours after treatment), were virtually indistinguishable. When the combined formulation was compared with a concomitant regimen that included dorzolamide 2% 3 times daily and timolol 0.5% twice daily the concomitant regimen was slightly more efficacious than the combined regimen at trough after 90 days: IOP was lowered by 3.6mm Hg in the combined group versus 4.1 mm Hg in the concomitant group. Dorzolamide/timolol has been compared with concomitant administration of timolol 0.5% and the IOP lowering miotic drug, pilocarpine 2.0%. This non-blind patient-preference study found that both regimens reduced IOP. However, the dorzolamide/timolol combination was preferred by the patients because of reduced frequency and severity of adverse effects and less frequent administration. Dorzolamide/timolol was well tolerated in clinical trials, the adverse effects reflected those of the individual components, and no additional tolerability issues were identified. However, the potential for timolol to cause cardiorespiratory effects must be considered when prescribing this combination. Furthermore, dorzolamide is a sulfonamide and can cause allergic reactions in those who are hypersensitive to this class. Dorzolamide/timolol is a well tolerated and effective fixed combination for lowering IOP in the treatment of open-angle glaucoma and is likely to be useful in those patients who do not respond adequately to first-line monotherapy. Compared with concomitant therapy with the same 2 drugs the primary advantage is convenience, which may lead to improved compliance. Studies of compliance and comparisons with other currently available combination therapies would be useful to fully define the value of the formulation. Nonetheless, dorzolamide combined with timolol in a single applicator system will be a useful addition to the treatment options for glaucoma, a leading cause of preventable blindness.

Topics: Adrenergic beta-Antagonists; Carbonic Anhydrase Inhibitors; Drug Combinations; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Sulfonamides; Thiophenes; Timolol; Vision, Ocular

Primary open-angle glaucoma is a condition associated with an elevated intraocular pressure (IOP) that is defined as optic degeneration with a slowly progressive deterioration of the visual field that may lead to blindness. More than 1 million Americans are being treated for glaucoma, and 80,000 are legally blind as a result of the disease. Glaucoma has its highest prevalence among the elderly population, with an incidence of approximately 1% in those older than 60 years, 3% in those between the ages of 70 and 80 years, and more than 9% in those older than 80 years. Treatment is directed at lowering high ocular pressures. The initial treatment, in most cases topical therapy with a beta-adrenergic blocking agent, reduces the IOP to help preserve sight. But such topical agents may also have adverse systemic effects on cardiac, pulmonary, central nervous system (CNS), and endocrine functions.

Topics: Adrenergic beta-Antagonists; Brimonidine Tartrate; Cardiovascular System; Central Nervous System; Clonidine; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Neurosecretory Systems; Ophthalmic Solutions; Prostaglandins F, Synthetic; Quinoxalines; Respiratory System; Sulfonamides; Thiophenes

Topics: Adrenergic alpha-Agonists; Carbonic Anhydrase Inhibitors; Clonidine; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Treatment Outcome

Topics: Administration, Topical; Carbonic Anhydrase Inhibitors; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes

This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues.. A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews.. BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation.. As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy.. jRCTs051190125.. Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC–prostaglandin analogue combination therapy.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Cross-Over Studies; Drug Combinations; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ophthalmic Solutions; Prostaglandins, Synthetic; Timolol

To reduce the frequency of dorzolamide eye drop administration and increasing the duration of action.. This study aims to compare the effect of dorzolamide loaded-nanoliposome with marketed dorzolamide HCl eye drop on intraocular pressure in primary open angle glaucoma and ocular hypertension patients.. A randomized study was conducted in a hospital.. Twenty patients with primary open angle glaucoma or ocular hypertension (in both eyes) diagnosis were recruited as participants.. Dorzolamide loaded-nanoliposome was prepared by thin layer hydration method and characterized. Intra ocular pressure were compared between the two groups who received marketed dorzolamide solution or dorzolamide-loaded nanoliposome.. The main outcome measures include intraocular pressure initially (day 0) and on days 14 and 28 and adverse effect of dorzolamide-loaded nanoliposome eye drop.. Based on the results of repeated measure, intra ocular pressure was seen to decrease in both the groups. But these reductions in the intervention group (dorzolamide-loaded eye drop) were significantly higher than those in control group (p < 0.05).. This study confirmed safety and long-lasting efficacy of dorzolamide loaded-nanoliposome eye drop. The highly enhanced permeation through the cornea can be attributed to similarity of phospholipid bilayer of liposomes to the biological membrane and their small particle size and positive zeta potential.

Topics: Antihypertensive Agents; Cornea; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Liposomes; Nanoparticles; Ocular Hypertension; Ophthalmic Solutions; Permeability; Sulfonamides; Thiophenes; Time Factors

To investigate the efficacy and safety of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery.. Children with primary pediatric glaucoma having postsurgical untreated intraocular pressure (IOP) between 22 and 26 mm Hg were eligible. At baseline, patients were administered latanoprost once daily. Depending on IOP reduction, patients were allocated to continuation of latanoprost monotherapy or addition of dorzolamide twice daily, or switch to dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered nonresponders. The primary endpoint was the percentage of responders. Study treatment continued for 3 years or until treatment failure. The present article reports the 1-year analysis results.. A total of 35 patients (57 eyes) were analyzed. The mean age was 4.0 years (SD, 3.8). In total, 51 eyes were included in the efficacy analysis. In total, 43 eyes (84.3%; 95% confidence interval, 74.3-94.3) were considered responders: 29 on latanoprost monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely related to the age at the time of surgery. IOP reduction was 8.7 mm Hg (SD, 2.2) for latanoprost, 7.5 mm Hg (SD, 1.4) for the latanoprost/dorzolamide combination, and 8.7 mm Hg (SD, 2.1) for the dorzolamide monotherapy. Only mild or moderate local adverse events were noted. None of the patients was withdrawn due to adverse events.. Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children postsurgery. Nonresponders were mainly patients with early presentation of the disease.

Topics: Antihypertensive Agents; Child; Child, Preschool; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Italy; Latanoprost; Male; Ocular Hypertension; Prognosis; Prospective Studies; Prostaglandins F, Synthetic; Single-Blind Method; Sulfonamides; Thiophenes; Tonometry, Ocular; Treatment Outcome

To compare the efficiency of brinzolamide/brimonidine fixed combination vs the dorzolamide/timolol fixed combination.. Forty-four eyes of 44 patients were divided in 2 groups treated either with dorzolamide/timolol twice a day (group A) or with brinzolamide/brimonidine twice a day (group B). Complete ophthalmic examination including Goldmann applanation tonometry was performed before treatment administration and 1, 4, 8, and 12 weeks afterwards. The intraocular pressure (IOP) was measured twice a day (morning at 9 AM and afternoon at 4 PM).. At the end of the follow-up period (12 weeks), mean morning IOP reduction was 7.0 ± 2.8 mm Hg in group A and 8.4 ± 1.9 mm Hg in group B. A significant difference was found (p = 0.0343). In contrast, mean afternoon IOP reduction was 8.6 ± 2.7 mm Hg in group A and 7.9 ± 1.6 mm Hg in group B and no significant difference was found (p = 0.3413). No significant adverse effects were observed in either group.. Brinzolamide/brimonidine seems to be an effective and safe alternative β-blocker free fixed combination, especially for patients with comorbidities, having its own antihypertensive profile.

Topics: Aged; Antihypertensive Agents; Double-Blind Method; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Sulfonamides; Thiazines; Thiophenes; Timolol; Tonometry, Ocular; 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

To compare the efficacy and safety of dorzolamide hydrochloride 2%/timolol maleate 0.5% fixed combination (DTFC) with latanoprost 0.005%/timolol maleate 0.5% fixed combination (LTFC) on diurnal intraocular pressure (IOP) in patients with primary open-angle glaucoma.. Thirty-three primary open-angle glaucoma patients with IOP of 22-32 mmHg measured at any time were included. Patients were randomized to either DTFC twice daily or latanoprost 0.005%/timolol maleate 0.5% fixed combination (LTFC) once a day in the evening. After a 6-week treatment period with each combination, IOP were measured every 4 h during 24 h (first diurnal curve) and after 6 weeks of washout period, the patients were switched to the other treatment for 6 weeks of the second diurnal curve.. The mean baseline IOP was 25.09±2.8 mmHg. After the treatment period, mean diurnal IOP was statistically lower with LTFC (16.3 mmHg) than with DTFC (17.3 mmHg), and the peak IOP value was 18.5 mmHg with LTFC and 19.9±2.6 mmHg with DTFC (P<0.05). No significant side effects were reported except stinging and bitter taste with the DTFC group.. Mean diurnal IOP and peak IOP were lower with LTFC than with DTFC in patients with primary open-angle glaucoma.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Carbonic Anhydrase Inhibitors; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Neuroprotective Agents; Optic Disk; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

The purpose of this study was to verify the ocular comfort of a fixed topical combination of brinzolamide 1% plus timolol 0.5% suspension vs. dorzolamide 2% plus timolol 0.5% solution, both preserved with benzalkonium chloride (BAK), in patients with primary open-angle glaucoma (POAG) through subjective and objective methods. BAK is the most commonly used preservative in topical glaucoma medications.. 62 subjects were examined and included in the analysis. Each patient was asked to complete a questionnaire on symptoms (Ocular Surface Disease Index) and then underwent a series of examinations. The Ocular Protection Index evaluated the risk of damage to the ocular surface, and was expressed as the ratio between fluorescein breakup time and blinking interval. These and other analyses were repeated 30 days after instillation of the new eye drop treatment.. The results demonstrated that patients enrolled with the preserved fixed combination of dorzolamide or brinzolamide represented a subgroup of patients in which the discomfort symptoms were supposedly justified by the presence of BAK used chronically in antihypertensive drops. Ocular discomfort scores were significantly higher with dorzolamide/timolol than brinzolamide/timolol (p < 0.0001).. This work shows the better tolerability of brinzolamide 1% plus timolol 0.5% suspension, compared with dorzolamide 2% plus timolol 0.5% solution. Fortunately, some of the adverse reactions induced by preserved eye drop glaucoma medication are reversible after removing the preservatives. Both the potential for added benefit and patient compliance should be considered when selecting ocular hypotensive therapy.

Topics: Administration, Ophthalmic; Aged; Antihypertensive Agents; Benzalkonium Compounds; Carbonic Anhydrase Inhibitors; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Preservatives, Pharmaceutical; Prospective Studies; Single-Blind Method; Sulfonamides; Suspensions; Thiazines; Thiophenes; Time Factors; Timolol

To investigate the ocular hypotensive effect and safety of dorzolamide hydrochloride 1 %/timolol maleate 0.5 % fixed-combination eye drops.. The study cohort comprised 34 patients with either primary open-angle glaucoma or ocular hypertension who were being concomitantly treated with dorzolamide hydrochloride 1 % eye drops and timolol maleate 0.5 % eye drops. The dorzolamide hydrochloride 1 % and timolol maleate 0.5 % eye drops were replaced with dorzolamide hydrochloride 1 %/timolol maleate 0.5 % fixed-combination eye drops without any washout period. The intraocular pressure (IOP) was evaluated both before and 1 and 3 months after the treatment change. The patients were asked to complete a questionnaire on adherence to the treatment protocol 1 month after the change in treatment.. The IOP was 15.5 ± 2.7 mmHg at the time of treatment change, 15.2 ± 2.7 mmHg at 1 month post-change, and 15.5 ± 2.9 mmHg at 3 months post-change, which is consistent with that before the treatment change (p = 0.286). Based on the completed questionnaire, following the treatment change, 50 % of patients felt a stinging sensation following administration of the eye drops and 11.8 % experienced blurred vision. In no case were the eye drops discontinued due to adverse reactions or insufficient IOP decrease.. The replacement of concomitant treatment with dorzolamide hydrochloride 1 % and timolol maleate 0.5 % eye drops with dorzolamide hydrochloride 1 %/timolol maleate 0.5 % fixed-combination eye drops improved protocol adherence and preserved the IOP.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Medication Adherence; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Surveys and Questionnaires; Thiophenes; Timolol; Tonometry, Ocular

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 ocular surface status and tolerability after switching glaucoma patients from dorzolamide/timolol to brinzolamide/timolol fixed combination (FC).. Six-month, multicenter, open-label, prospective study that switched 72 patients from dorzolamide/timolol to brinzolamide/timolol FC. Intraocular pressure (IOP), tear film break-up-time (TF-BUT), fluorescein staining and Glaucoma Symptom Scale (GSS) questionnaire were recorded at baseline and after 6 months.. Median interquartile range (IQR) IOP was 16 (IQR 15 - 18) mmHg at baseline and 16 (15 - 17) mmHg and 6 months. TF-BUT significantly improved (p < 0.0001); the regression analysis found a negative association between TF-BUT changes and age at baseline and at month 6 (r = -0.32; p = 0.0082 and r = -0.31; p = 0.0085). Patients with no corneal fluorescein staining statistically increased after substitution (p = 0.04). Quality of life - as examined by the GSS symptoms (SYMP) score - statistically improved (p < 0.0001), revealing an association between GSS SYMP score and age [coefficient -0.67, 95% confidence interval (CI) -1.13 to -0.21, p = 0.0005), superficial keratitis (coefficient -8.26, 95% CI -15.73 to -0.80, p = 0.031) and TF-BUT (coefficient 4.94, 95% CI 1.71 to 8.17, p = 0.003).. Brinzolamide/timolol FC is associated with reduced topical discomfort and improved signs of ocular surface disease. The good tolerability and comfort of this FC might contribute to good patient adherence.

Topics: Aged; Antihypertensive Agents; Diagnostic Techniques, Ophthalmological; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Quality of Life; Sulfonamides; Surveys and Questionnaires; Thiazines; Thiophenes; Timolol

To investigate the IOP-lowering effect and safety of a combined ophthalmic solution (MK-0507A) of 1% dorzolamide hydrochloride and 0.5% timolol maleate in comparison to 0.5% timolol maleate (timolol), and 1% dorzolamide hydrochloride and 0.5% timolol maleate concomitant therapy (concomitant therapy).. This study was conducted in patients with either primary open angle glaucoma or ocular hypertension. The patients with IOP > or = 18 mmHg following the administration of timolol for 4 weeks during the observation period (474 patients) were randomized to receive either MK-0507A (189 patients), timolol (92 patients) or concomitant therapy (193 patients) during the treatment period and when evaluated for IOP at Week 8. The primary evaluation criteria were change in 2 hour IOP from baseline to Week 8.. The least square means of the changes in hour 2 IOP from baseline to Week 8 were -2.50 mmHg, -1.82 mmHg and -2.78 mmHg in the MK-0507 A group, timolol group and concomitant therapy group, respectively. MK-0507A demonstrated a significant reduction in IOP compared to timolol. Further- more, the 95% confidence interval of the difference between MK-0507A and concomitant groups satisfied the pre-specified criteria for non-inferiority confirming the non-inferiority of MK-0507A relative to the concomitant therapy. In addition, MK-0507A had safety comparable to that of timolol and concomitant therapy.. MK-0507A has a significantly superior IOP-lowering effect relative to timolol. MK-0507A also showed a non-inferior IOP-lowering effect relative to the concomitant therapy. MK-0507A was safe compared to both timolol and concomitant therapy.

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

To assess the effects of adding dorzolamide to timolol monotherapy on ocular haemodynamics and retinal oxygen saturation in patients with primary open-angle glaucoma (POAG).. Twenty-four patients (12 healthy, 12 with POAG) were treated with dorzolamide/timolol combination (DT) versus timolol maleate 0.5% twice daily in a randomized, crossover, double-blind study conducted over a period of 18 months. Patients received each treatment for 8 months then crossed over to the other treatment after a 1-month washout and second baseline. Goldmann applanation tonometry, Heidelberg retinal flowmetry (HRF), colour Doppler imaging (CDI) and retinal photographic oximetry were performed at each visit.. DT significantly reduced intraocular pressure (IOP) in both glaucomatous [right eye (OD) -13.15%, left eye (OS) -14.43%; p < 0.036] and non-glaucomatous (OD -12.4%, OS -13.88%; p < 0.039) patients compared to timolol after 8 months of treatment. DT significantly reduced the number of zero blood flow pixels in the superior (-39.72%; p < 0.014) and inferior (-51.44%; p < 0.008) retina in the non-glaucomatous group and inferior retina in the glaucomatous group (-55.38%, p < 0.006). The continuation of timolol monotherapy from baseline did not change (p < 0.05) any measured parameter and neither treatment had a significant effect (p < 0.05) on retinal oximetry or CDI parameters.. The addition of dorzolamide to timolol monotherapy decreases IOP and increases retinal blood flow in the superficial retinal vasculature in both glaucomatous and healthy patients following 8 months of treatment. The combination of increased retinal blood flow with consistent oxygen saturation may potentially increase oxygen delivery to the retina.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Eye; Glaucoma, Open-Angle; Hemodynamics; Humans; Intraocular Pressure; Laser-Doppler Flowmetry; Middle Aged; Oximetry; Oxygen; Regional Blood Flow; Retina; Retinal Vessels; Sulfonamides; Thiophenes; Timolol; Ultrasonography, Doppler, Color

This study aims to identify progression factors in patients with primary open-angle glaucoma (POAG), including the effects of treatment with dorzolamide 2% or brinzolamide 1%, each added to timolol 0.5%.. A sample of 161 POAG patients were prospectively randomized to receive either dorzolamide 2% (DT) or brinzolamide 1% (BT) b.i.d., each added to timolol 0.5%, during a 60-month, evaluator-masked study. Progression was determined by perimetric criteria. Factors associated with visual field progression were estimated using a conditional Cox hazard model with patient intraclass correlation and were expressed as hazard ratios (HRs) with 95% confidence intervals (95% CIs).. Predictive baseline factors were lower diastolic blood pressure (DBP), lower mean arterial pressure (MAP), antihypertensive treatment, lower end-diastolic velocity (EDV) in the ophthalmic artery (OA) and short posterior ciliary artery (SPCA), and a higher resistivity index (RI) in the OA and SPCA. Progression risk decreased by approximately 30% and 20% with each centimetre per second increase of EDV in the OA and SPCA, respectively, from baseline to the last follow-up visit. Each RI decrease (or increase) of 0.01 unit in the OA or SPCA was associated with an approximate 20% decrease (or increase) in risk for progression. In a multivariate analysis, progression risk was significantly lower in eyes treated with DT (HR=0.65, 95% CI 0.41-0.90) compared with those treated with BT.. Progression increased with lower DBP, lower MAP, antihypertensive medication, lower EDV in the OA and SPCA, and higher RI in the OA and SPCA. The risk for progression in patients treated with DT was half that in patients treated with BT.

Topics: Aged; Antihypertensive Agents; Blood Flow Velocity; Blood Pressure; Carbonic Anhydrase Inhibitors; Ciliary Arteries; Disease Progression; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Artery; Proportional Hazards Models; Prospective Studies; Retinal Artery; Risk Factors; Sulfonamides; Thiazines; Thiophenes; Timolol; Tonometry, Ocular; Ultrasonography, Doppler, Color; Vision Disorders; Visual Fields

The authors have reported previously that a study population, consisting of patients with glaucoma and ocular hypertension, is characterized by an impaired association between ocular blood flow parameters and systemic blood pressure, indicative of abnormal autoregulation. Here they report on the effects of dorzolamide and timolol on ocular pressure/flow relationships to test the hypothesis that these drugs improve autoregulation.. One hundred forty patients with primary open-angle glaucoma or ocular hypertension were included in a clinical trial in a controlled, randomized double-masked study in two parallel groups. Seventy patients were randomly assigned to receive timolol, and 70 patients were randomly assigned to receive dorzolamide for a 6-month period. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude. The association between blood flow parameters and systemic blood pressure was compared before and after the 6-month treatment period.. Before treatment a significant association was observed between ocular blood flow parameters and systemic blood pressure in both parallel groups (r = 0.23-0.42). All regression lines between ocular hemodynamic parameters and systemic blood pressure were less steep after treatment with either dorzolamide or timolol (r = 0.03-0.24).. The present study indicates that intraocular pressure reduction with timolol or dorzolamide is associated with normalization of the ocular pressure/flow relationship. Whether this is related to the beneficial effects of IOP-lowering therapy in glaucoma remains to be established. (ClinicalTrials.gov number, NCT00991822.).

Topics: Aged; Antihypertensive Agents; Blood Flow Velocity; Blood Pressure; Choroid; Cross-Over Studies; Double-Blind Method; Female; Glaucoma, Open-Angle; Hemodynamics; Humans; Interferometry; Intraocular Pressure; Laser-Doppler Flowmetry; Lasers; Male; Middle Aged; Ocular Hypertension; Optic Disk; Optic Nerve Diseases; Regional Blood Flow; Sulfonamides; Thiophenes; Timolol

To compare intraocular pressure (IOP) reductions with fixed-combination (FC) latanoprost/timolol once daily in the evening vsFC dorzolamide/timolol twice daily.. This evaluator-masked, multicentre, controlled clinical trial randomized subjects with primary open-angle glaucoma or ocular hypertension with IOP insufficiently responsive to beta-blocker therapy (screening IOP>21 and <37 mm Hg) to FC latanoprost-timolol (N=135) or FC dorzolamide/timolol (N=135). At screening, baseline, and after 4 and 12 weeks of therapy, IOP was measured three times at 0800, 1200, and 1600 hours. Adverse events were recorded at each visit. The primary efficacy end point was whether either FC could be shown to be inferior to the other with respect to change in mean daytime IOP from baseline to week 12.. Mean daytime IOP levels were similar at baseline. Mean reductions in daytime IOP from baseline to week 12 were -9.7 mm Hg for FC latanoprost-timolol and -9.5 mm Hg for FC dorzolamide/timolol. The difference between FC latanoprost/timolol-FC dorzolamide-timolol was -0.2 mm Hg (95% confidence interval (CI), -0.8 to -0.4 mm Hg). The upper bound of the 95% CI was <1.5 mm Hg, indicating that neither FC is inferior to the other. However, a significantly greater percentage of subjects treated with FC latanoprost/timolol achieved IOP levels

Topics: Aged; Antihypertensive Agents; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Visual Acuity; Visual Fields

To compare brimonidine/timolol fixed combination (BrTFC; Combigan *) with dorzolamide/timolol fixed combination (DTFC; Cosopt dagger) in terms of ability to lower intraocular pressure (IOP) in primary open-angle glaucoma (POAG).. This was a prospective, randomized, double-masked, crossover study. After 6 weeks of therapy with timolol maleate 0.5% twice daily, patients were randomized to BrTFC twice daily or DTFC twice daily for 6 weeks, before being crossed over to the other treatment arm for a further 6 weeks. At all follow-up visits, IOP was measured at 09.00 (pre-instillation) 12.00 and 16.00. The primary outcome measure was change in mean diurnal IOP from baseline at 6 weeks. The secondary outcome was percentage of patients with IOP <18 mmHg at 6 weeks. Data were analyzed from all patients who completed the study.. Twenty-five patients were randomized and 20 completed the study. Mean diurnal IOP (mean +/- standard deviation [SD]) was 20.28 +/- 2.03 mmHg at timolol-treated baseline. After 6 weeks, mean diurnal IOP was 16.28 +/- 2.07 mmHg following BrTFC and 17.23 +/- 2.29 mmHg following DTFC (difference: 0.95 mmHg, 95% CI 0.10-1.80, p = 0.03). Mean IOP at 09.00 was 20.95 +/- 2.31 mmHg at baseline. This was reduced to 15.85 +/- 2.56 mmHg following BrTFC and 17.55 +/- 2.67 mmHg following DTFC (difference: 1.70, 95% CI 0.80-2.60, p = 0.001). For the 12.00 and 16.00 timepoints, the mean changes from baseline in the two arms were comparable. Percentages of patients achieving a target IOP of <18 mmHg were 85% following BrTFC and 60% following DTFC (p = NS [not significant]). No treatment-related adverse events were reported with either therapy. Key limitations include the small size of the study population and the 6-week duration of treatment periods, which prevents drawing conclusions regarding long-term therapy.. Reductions from baseline in mean diurnal IOP and morning IOP were greater with BrTFC than with DTFC.

Topics: Aged; Aged, 80 and over; Algorithms; Antihypertensive Agents; Brimonidine Tartrate; Cross-Over Studies; Dosage Forms; Double-Blind Method; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Quinoxalines; Sulfonamides; Thiophenes; Timolol

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 report the long-term effect of the dorzolamide/timolol (DTFC) and latanoprost/timolol (LTFC) fixed combinations on intraocular pressure (IOP) and visual field defects over time in naïve primary open-angle glaucoma (POAG) patients.. Prospective, 4-year, open-label, interventional study.. high-volume outpatient clinic.. 178 patients were assigned to receive medical treatment with either DTFC or LTFC.. over 4 years, tri-monthly IOP and yearly visual field assessment (Octopus 101, Program G2). outcomes: effect of treatment on IOP, visual field indices mean defect (MD), and visual field indices variance loss (VL) over time.. DTFC and LTFC significantly (p < or = 0.001) reduced mean IOP over time (from 22.6 +/- 3.0 to 13.8 +/- 1.9 mmHg and from 22.3 +/- 4.0 to 14.7 +/- 1.9 mmHg, respectively). In all, 56 patients (70.9%) and 14 (17.9%) showed a significant MD improvement in the DTFC- and LTFC-treated groups, respectively, p = 0.0001. DTFC progressively and significantly decreased mean VL (from 30.21 +/- 23.88 to 8.11 +/- 8.50 dB). Mean sensitivity slopes during follow-up were 1.14 dB/year and -0.34 dB/year for DTFC and LTFC treatment groups, respectively; p = 0.028.. Both treatments significantly reduced IOP as compared with baseline. Additionally, treatment with dorzolamide/timolol fixed combination seem to be effective in preventing glaucomatous visual field progression. This study has some limitations that should be noted, among them its open-label design.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Disease Progression; Dosage Forms; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome; Visual Fields

To compare the effect on the retrobulbar hemodynamics and intraocular pressure (IOP) of dorzolamide 2% and brinzolamide 1%, each added to timolol 0.5% in patients with primary open-angle glaucoma (POAG).. 146 POAG patients were prospectively randomized to receive either dorzolamide 2% or brinzolamide 1% BID, each added to timolol 0.5%, during a 60-month evaluator-masked study. At baseline and every 6 months for 60 months, we measured the retrobulbar hemodynamic parameters in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCA) using color Doppler imaging (CDI), intraocular pressure (IOP), and blood pressure measurements.. Dorzolamide significantly increased the end-diastolic velocity (EDV) in the OA in 1.22 cm/s, 95% confidence interval (95% CI) 0.90-1.56 cm/s, P < 0.001 and reduced the resistivity index (RI) in the OA in 0.04 units, 95% CI 0.03-0.05, P < 0.001. None of the retrobulbar parameters changed significantly on therapy with brinzolamide when the results were analyzed at month 60. Both dorzolamide and brinzolamide significantly decreased IOP (-4.3, 95% CI -4.5 to -4.2 mmHg and -4.3, 95% CI -4.4 to -4.2 mmHg, respectively). Dorzolamide significantly reduced the RI in the OA from 0.74 (0.02) to 0.70 (0.02), CRA from 0.66 (0.02) to 0.62 (0.02), and SPCA from 0.66 (0.02) to 0.62 (0.02), P < 0.001, respectively.. Our results suggest augmented retrobulbar blood flow after 5 years of treatment with dorzolamide but not with brinzolamide, each added to timolol, in POAG patients.

Topics: Administration, Topical; Aged; Antihypertensive Agents; Blood Pressure; Carbonic Anhydrase Inhibitors; Drug Administration Schedule; Drug Combinations; Female; Glaucoma, Open-Angle; Hemodynamics; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Regional Blood Flow; Sulfonamides; Thiazines; Thiophenes; Timolol; Ultrasonography, Doppler, Color

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 evaluate the 24-hour efficacy and tolerability of 2% dorzolamide/0.5% timolol fixed combination (DTFC) solution in open-angle glaucoma and ocular hypertension.. Randomized, parallel, double-masked, multicenter study. Patients with insufficiently controlled intraocular pressure (IOP > or = 22 mmHg) were randomized to DTFC (N = 117) or timolol (N = 115). IOP was measured at baseline, 6 weeks, and 8 weeks, with measurements taken at 6 p.m., 8 p.m., 10 p.m., 2 a.m., 6 a.m., 8 a.m., 10 a.m., and 2 p.m. ClinicalTrials. gov identifier: NCT00108017 MAIN OUTCOME MEASURES: Statistically significant change in IOP from untreated baseline for DTFC at all hours at week 8. Secondary outcome measures included: IOP-lowering at week 6 at all individual time points, change from baseline to 8 weeks in mean daytime IOP (average of 8 a.m., 10 a.m., 2 p.m., 6 p.m., and 8 p.m. IOPs) and night-time IOP (10 p.m., 2 a.m., 6 a.m.), and comparison of DTFC with timolol after 8 weeks.. Patients receiving DTFC had a statistically significant and clinically relevant reduction in IOP at week 8 compared with baseline at all eight time points (p < 0.001). Significant IOP reductions were also seen at all time points at week 6 (p < 0.001). DTFC significantly lowered mean daytime IOP and night-time IOP ( p < 0.001 for both). Timolol alone also significantly reduced IOP from baseline at 8 weeks for all diurnal time points, and mean daytime and night-time IOP ( p < 0.001 for all). Compared with timolol alone, there were significantly greater reductions with DTFC at 10 a. m. (p = 0.003) and 2 p. m. (p = 0.016), and for mean daytime IOP (p = 0.025) at 8 weeks. Significant between-treatment differences were not observed at other time points. Both treatments were well-tolerated, with no differences observed in the safety profiles between the treatment groups.. Both DTFC and timolol provided significant IOP reduction over the entire 24-hour measurement period. Although this study was not designed or powered to compare DTFC and timolol, DTFC exhibited greater IOP-lowering than timolol during the daytime, but not at night.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol

This study assessed the long-term effects of dorzolamide 2% BID added to timolol maleate 0.5% BID on intraocular pressure (IOP), retrobulbar blood flow, and the progression of visual field damage in patients with primary open-angle glaucoma.. This was a prospective, 4-year, open-label intervention study. All consecutive patients with a clinical diagnosis of open-angle glaucoma in both eyes (mean defect greater than -6 dB) who presented for a regular check-up between January and July 2001 at the Instituto Galego de Oftalmoloxía were screened for study eligibility. All participants had been treated with timolol 0.5% BID in both eyes for at least 6 months before the screening visit. Dorzolamide 2% BID was added to timolol 0.5% BID in the eye with the larger visual field defect (study eye), whereas timolol 0.5% BID was continued in the eye with the smaller visual field defect (control eye). Variables evaluated at baseline and every 6 months for 48 months included retrobulbar hemodynamic parameters (using color Doppler imaging), progression of visual field damage, and IOP. Progression of visual field damage was defined according to modified Anderson criteria. Visual field progression-free survival rates for the study and control eyes were plotted using Kaplan-Meier analysis and were compared using a log-rank test.. Forty-five patients met the inclusion criteria, of whom 5 were lost to follow-up. Thus, 80 eyes of 40 patients were included in the analysis. Patients' mean (SD) age was 68.0 (7.1) years; all patients were white and 21 (52.5%) were male. Mean baseline IOP was 19.18 (1.34) and 18.23 (1.64) mm Hg in the study and control eyes, respectively (P=0.006). The combination of dorzolamide and timolol was associated with significant increases from baseline in enddiastolic velocity in the ophthalmic and short posterior ciliary arteries (P<0.001) and significant decreases in the resistivity index in both arteries (P<0.001). Twenty-three of the 80 eyes (28.8%) had progression of visual field damage (7 study eyes and 16 control eyes). On Kaplan-Meier survival analysis, the risk of progression was significantly lower in the eye treated with dorzolamide and timolol compared with the eye treated with timolol alone (hazard ratio=0.41; 95% CI, 0.17 to 0.94; P=0.035). Mean changes in IOP from baseline to month 48 were -1.10 mm Hg in the dorzolamide and timolol group (95% CI, -1.73 to -0.51; P<0.001) and 1.27 mm Hg in the control group (95% CI, -2.74 to 1.72; P=NS).. In this 4-year, open-label study in patients with primary open-angle glaucoma, dorzolamide 2% BID added to timolol 0.5% BID was associated with a significant reduction in IOP and significant increases in retrobulbar hemodynamic parameters in both the ophthalmic and short posterior ciliary arteries. Dorzolamide added to timolol may be effective in preventing progression of glaucomatous visual field damage.

Topics: Aged; Antihypertensive Agents; Disease Progression; Dose-Response Relationship, Drug; Drug Combinations; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ophthalmic Solutions; Orbit; Prospective Studies; Regional Blood Flow; Sulfonamides; Thiophenes; Time Factors; Timolol; Treatment Outcome; Visual Fields

To evaluate open-angle glaucoma patients, who were insufficiently controlled on latanoprost monotherapy, to determine the 24 h intraocular pressure (IOP) efficacy and safety when changing them to dorzolamide/timolol (DTFC) or latanoprost/timolol fixed combination (LTFC) or adding DTFC.. A prospective, observer-masked, placebo-controlled, crossover, comparison. Consecutive adults with primary open-angle or exfoliative glaucoma who exhibit a mean baseline IOP >21 mm Hg on latanoprost monotherapy were randomised for 3 months to: DTFC, LTFC or DTFC and latanoprost. Patients were then crossed over to the next treatment for periods 2 and 3. At the end of the latanoprost run-in and after each 3-month treatment period, patients underwent 24 h IOP monitoring.. 31 patients completed this study. All three adjunctive therapies significantly reduced the IOP at each time point and for the mean 24 h curve, except at 18:00 and 02:00 with DTFC and 02:00 with LTFC. When the three treatments were compared directly, the DTFC and latanoprost therapy demonstrated lower IOPs versus the other treatment groups, including: the mean 24 h pressure, maximum as well as minimum levels and individual time points following a modified Bonferroni correction (p<0.0032).. This study showed DTFC, LTFC and the addition of DTFC to latanoprost significantly decrease the IOP compared with latanoprost alone, but the latter therapy regime yields the greatest IOP reduction.

Topics: Antihypertensive Agents; Cross-Over Studies; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

The aim of this study was to evaluate the ocular discomfort of brinzolamide 1%/timolol 0.5% ophthalmic suspension fixed combination dosed twice-daily compared to dorzolamide 2%/timolol 0.5% ophthalmic solution fixed combination dosed twice-daily.. This was a prospective, double-masked, parallel-group, randomized, clinical trial. Patients had open-angle glaucoma or ocular hypertension and were randomized to twice-daily therapy with either brinzolamide 1%/timolol 0.5% or dorzolamide 2%/timolol 0.5%. Patients completed ocular discomfort assessments (based on burning, stinging, a feeling of heat or warmth, sharp pain, or smarting pain) on their current intraocular pressure-lowering therapy at baseline and on study medication after 1 week of dosing.. In the intent-to-treat analyses, mean ocular discomfort scores at 1 week were significantly lower in eyes receiving brinzolamide 1%/timolol 0.5% than dorzolamide 2%/timolol 0.5% (0.77 vs. 1.53; P = 0.0003). Mean increases from baseline in ocular discomfort scores were statistically significant in both groups but were smaller in eyes receiving brinzolamide 1%/timolol 0.5% (0.49; P = 0.0028) than dorzolamide 2%/timolol 0.5% (1.32; P < 0.0001). Over threefold more patients on brinzolamide 1%/timolol 0.5% (23/47, 49%) than dorzolamide 2%/timolol 0.5% (7/47, 15%) reported no ocular discomfort after 1 week of therapy (P = 0.0004).. Brinzolamide 1%/timolol 0.5% ophthalmic suspension is associated with a statistically significantly less ocular discomfort profile than dorzolamide 2%/timolol 0.5% ophthalmic solution.

Topics: Adult; Aged; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiazines; Thiophenes; Timolol

To compare the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure (IOP) over 8 weeks.. This 8-week, multicentric, interventional, randomized, open-label, parallel group study was conducted at 4 centers in Brazil and 1 center in Argentina. Patients with open-angle glaucoma or ocular hypertension were randomized to receive bilaterally fixed combination of brimonidine/timolol maleate 0.5% or fixed combination of dorzolamide 2%/timolol 0.5% twice daily at 8:00 AM and 8:00 PM. A modified diurnal tension curve (8:00 AM, 10:30 AM, 02:00 PM, and 4:00 PM) followed by the water drinking test (WDT), which estimates IOP peak of diurnal tension curve, were performed in the baseline and week-8 visits. Adverse events data were recorded at each visit.. A total of 210 patients were randomized (brimonidine/timolol, n=111; dorzolamide/timolol, n=99). Mean baseline IOP was 23.43+/-3.22 mm Hg and 23.43+/-4.06 mm Hg in the patients treated with brimonidine/timolol and dorzolamide/timolol, respectively (P=0.993). Mean diurnal IOP reduction after 8 weeks were 7.02+/-3.06 mm Hg and 6.91+/-3.67 mm Hg, respectively (P=0.811). The adjusted difference between groups (analysis of covariance) at week 8 was not statistically significant (P=0.847). Mean baseline WDT peak was 27.79+/-4.29 mm Hg in the brimonidine/timolol group and 27.68+/-5.46 mm Hg in the dorzolamide/timolol group. After 8 weeks of treatment, mean WDT peaks were 20.94+/-3.76 mm Hg (P<0.001) and 20.98+/-4.19 (P<0.001), respectively. The adjusted difference between groups (analysis of covariance) was not statistically significant (P=0.469). No statistical difference in terms of adverse events was found between groups.. Both fixed combinations were capable of significantly reducing the mean diurnal IOP, mean diurnal peak, and mean WDT peak after 8 weeks of treatment. Also, both fixed combinations are well tolerated with few side effects.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Circadian Rhythm; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Treatment Outcome; Young Adult

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.

Topics: Aged; Antihypertensive Agents; Cohort Studies; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Patient Satisfaction; Prospective Studies; Quality of Life; Sulfonamides; Surveys and Questionnaires; Thiophenes; Timolol; Treatment Outcome

To compare the effect of dorzolamide hydrochloride 2%, timolol maleate 0.5%, and their fixed combination on intraocular pressure (IOP)and retinal and optic nerve head haemodynamics in primary open-angle glaucoma patients.. Twenty-eight patients with early moderate glaucomatous damage treated with β-blockers (>6 months) with IOP values ranging from 18 to 22 mmHg at trough participated in this trial. After a 4-week washout period,patients were randomised in two groups: group I started with dorzolamide 2% monotherapy and group II with timolol 0.50% monotherapy for 4 weeks. After this period, both groups switched to dorzolamide/timolol fixed combination for 4 weeks. IOP, ocular diastolic perfusion pressure, heart rate, and Scanning Laser Doppler Flowmetry measurements at the peripapillary retina and neuroretinal rim were taken at T0 (enrolment), T1 (wash out), T2(monotherapy), and T3 (dorzolamide/timolol).Data were compared between different study times. Statistical analysis was conducted using a paired t-test.. Between T1 and T3, IOP decreased significantly in group I (-21.40%) (P<0.001)and in group II (-21.25%) (P<0.001). At the same time intervals, blood flow increased significantly at rim level for group I (+30.03%)(P<0.05) and also when all patients were considered (rim +20.81%) (P<0.05). Between T1 and T3, we also observed a significant increase of ODPP in group I (+7.24%) (P<0.01)and in group II (+6.08%) (P<0.05) and when all patients were considered (+6.71%)(P<0.001) [corrected].. Dorzolamide/timolol fixed combination increased blood flow significantly at the neuroretinal rim showing a combination of hypotensive and haemodynamic effects.

Topics: Aged; Analysis of Variance; Antihypertensive Agents; Drug Combinations; Female; Glaucoma, Open-Angle; Heart Rate; Humans; Intraocular Pressure; Laser-Doppler Flowmetry; Male; Middle Aged; Optic Disk; Regional Blood Flow; Sulfonamides; Thiophenes; Timolol

Efficacy of the latanoprost versus timolol/dorzolamide combination therapy in patients with primary open angle glaucoma. The study was designed as a 6 months randomized, observer-masked study comprising 120 patients with primary open-angle glaucoma in Feiz Hospital, Isfahan, Iran, from 2006 to 2007. The patients were randomized (latanoprost, n = 60; dorzolamide/timolol, n = 60) to treatment with either latanoprost, 0.005% once daily, or the combination of timolol 0.5% twice daily, and dorzolamide 2% 3 times daily. The mean intraocular pressure (IOP) after one, 3, and 6 months of treatment was compared with baseline in the 2 groups.. A total of 120 patients were randomized to 2 equal treatment groups. The mean baseline IOP values were similar between the 2 groups. The mean (standard error of mean [SE]) IOP reductions at months one was 7.2 (0.4), at month 3 was 7.3 (0.4), and at month 6 was 7.1 (0.3) mm Hg for the latanoprost group and 7.5 (0.3), 7.8 (0.3), and 7.4 (0.3) mm Hg for the dorzolamide/timolol group. The 2 therapies were similarly effective.. The latanoprost and dorzolamide/timolol combination were equally effective at lowering IOP compared to untreated baseline.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

Treatment of glaucoma is aimed at reducing intraocular pressure (IOP) to prevent further damage to the optic nerve. For patients who do not respond to monotherapy, combination treatment may be effective in achieving therapeutic reduction or target IOP.. To evaluate the effectiveness and safety of dorzolamide 2% with timolol 0.5% alone or combined with latanoprost in reducing IOP in a real-world setting.. A prospective, open-label, multicenter, nonrandomized interventional study was designed. Three hundred fifty patients with primary open-angle glaucoma or ocular hypertension and uncontrolled IOP after latanoprost monotherapy for 4 or more weeks were treated with combination dorzolamide-timolol twice daily added to their existing latanoprost therapy (D/T-Add-On; n = 280) or dorzolamide-timolol twice daily monotherapy (D/T-Switch; n = 70). The primary effectiveness outcome measure was the change in IOP after 6 and 12 weeks of treatment.. Of the total population, 313 patients completed this trial (248 D/T-Add-On; 65 D/T-Switch). After 12 weeks, the mean +/- SD IOP decrease was -6.3 +/- 3.6 mm Hg (-28.1%) and -5.8 +/- 4.9 mm Hg (-23.5%) in the D/T-Add-On and D/T-Switch groups, respectively (both p < 0.001). Therapeutic response rates (defined as IOP reduction >20%) after 12 weeks of treatment for the D/T-Add-On and the D/T-Switch groups were 66.4% (186/280) and 52.9% (37/70), respectively. There were 116 predominantly mild, nonserious adverse events attributed to the study drugs, reported by 86 (24.6%) patients. The most frequent adverse events were eye irritation (n = 42; 12.0%) and taste perversion (n = 15; 4.3%). No serious adverse events related to the study medications were reported.. In patients with primary open-angle glaucoma or ocular hypertension and elevated IOP while on monotherapy with latanoprost, switching to dorzolamide-timolol or combining dorzolamide-timolol with latanoprost are effective and safe treatment options for reducing IOP and achieving therapeutic response.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Canada; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To assess the effects of brinzolamide and dorzolamide on ocular haemodynamics and retinal oxygen saturation in patients with primary open-angle glaucoma (OAG).. Fifteen patients with OAG were evaluated in a randomised, cross-over, double-blind study. They were treated with either brinzolamide or dorzolamide for 3 months and then crossed-over after a 4-week washout period. They were given timolol during a 4-week run-in period and during washout. The following were performed after run-in, after washout and after each treatment period: adverse events check, measurement of visual acuity, contrast sensitivity, blood pressure, heart rate, and intraocular pressure, and fundus examination. Ocular blood flow was assessed using confocal scanning laser Doppler flowmetry (HRF) and colour Doppler imaging (CDI). Retinal oxygenation levels were determined using a non-invasive measurement of haemoglobin oxygen saturation by digital photographic fundus oximetry.. Both brinzolamide and dorzolamide reduced the number of zero-flow pixels in the retina as measured by HRF, suggesting an increase in retinal blood flow (-6.86 and -0.452 respectively) with brinzolamide treatment resulting in fewer zero-flow pixels than dorzolamide (-6.41) (p = 0.024). Both brinzolamide and dorzolamide increased oxygen saturation in the retina as measured by photographic retinal oximetry in the superior (0.82 (p = 0.002) and 0.87 (p = 0.005)) and inferior (0.88 (p = 0.035) and 0.82 (p = 0.002)) retinal veins. No significant changes were found in CDI measurements of the retrobulbar blood supply during either treatment.. This pilot study suggests that brinzolamide and dorzolamide may increase retinal oxygen saturation in patients with OAG.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Carbonic Anhydrase Inhibitors; Contrast Sensitivity; Cross-Over Studies; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Laser-Doppler Flowmetry; Male; Microcirculation; Middle Aged; Oxygen; Pilot Projects; Retinal Vessels; Sulfonamides; Thiazines; Thiophenes; Visual Acuity

Clinically, dorzolamide (Trusopt(R); Merck & Co Inc, West Point, PA, USA) is often used twice daily (b.i.d.) or three times daily (t.i.d.) as adjunctive therapy with prostaglandins. Our purpose was to determine the effect of dorzolamide on intraocular pressure (IOP) when added to latanoprost (Xalatan(R); Pfizer Inc, New York, NY, USA) baseline treatment, and to evaluate potential efficacy differences between b.i.d. and t.i.d. dosing of dorzolamide.. This was a prospective, randomised, two-period crossover trial in ocular hypertensive or primary open-angle glaucoma patients (29 eyes in 15 patients) with an IOP of > 20 mmHg on latanoprost baseline treatment. Patients were randomly assigned to b.i.d. (08.00 and 20.00) or t.i.d. (08.00, 16.00 and 20.00) dosing of dorzolamide, treated in both eyes for 4 weeks, washed out for 3 weeks, then switched to the opposite dosing frequency for 4 weeks. Diurnal IOP measurements (every 2 hours from 08.00 to 20.00) were performed at baseline and at the end of treatment periods.. The mean baseline IOP was 20.9+/-0.6 mmHg. After b.i.d. and t.i.d. dosing, the mean IOP was 17.7+/-0.6 mmHg (13.5% reduction) and 17.8+/-0.8 mmHg (16.5% reduction), respectively (both P<0.001 compared with baseline IOP). Diurnal IOP control was similar in the two groups, although mean IOP reduction was significantly lower at 18.00 on the t.i.d. regimen (4.7+/-3.3 mmHg) than with the b.i.d. regimen (2.3+/-2.7 mmHg, P=0.038). At other time points, no significant differences between the groups were observed.. Dorzolamide 2% added to latanoprost 0.005% baseline treatment caused a significant decrease in IOP. The b.i.d. versus t.i.d. dosing of dorzolamide did not significantly affect a change in IOP except at one afternoon time point.

Topics: Antihypertensive Agents; Cross-Over Studies; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes

To evaluate the effect of the timolol-dorzolamide fixed combination (TDFC) and latanoprost 0.005% on 24-hour intraocular pressure (IOP), systolic (SBP) and diastolic (DBP) blood pressure, and diastolic ocular perfusion pressure (DOPP) in patients with primary open-angle glaucoma (POAG).. This was an institutional, randomized clinical trial. After a 24-hour assessment without treatment, 27 previously untreated patients with POAG were randomized to 6 weeks' treatment with twice-daily TDFC (8 AM and 8 PM) followed by once-daily latanoprost 0.005% (8 PM), or vice versa. One eye was analyzed per patient. The mean values of IOP, DBP, SBP, and DOPP (difference between DBP and IOP) were recorded at each time point, and the 24-hour data are the mean values of each patient's measurements over the 24-hour period. The differences between the values of the first treatment period and the baseline and the second treatment period and washout were calculated and analyzed by means of an analysis of variance model that tested the effects of sequence and treatment.. Both treatments significantly reduced 24-hour IOP (P < 0.0001), but TDFC led to lower 24-hour pressure (mean +/- SD: 15.4 +/- 1.9 vs. 16.7 +/- 1.7 mm Hg; P = 0.004). Latanoprost did not lead to any significant reduction in mean 24-hour SBP and DBP (SBP: P = 0.952; DBP: P = 0.831), but TDFC did (SBP and DBP: P < 0.0001). Both treatments significantly increased 24-hour DOPP (P < 0.0001), with no difference between the two medications (P = 0.09).. In previously untreated patients with POAG, TDFC, and latanoprost equally enhanced 24-hour DOPP: the former by counteracting the decrease in DBP with a substantial reduction in IOP and the latter by not affecting DBP and significantly reducing IOP. (isrctn.org number, ISRCTN67123277.).

Topics: Antihypertensive Agents; Blood Pressure; Circadian Rhythm; Cross-Over Studies; Diastole; Double-Blind Method; Drug Combinations; Female; Glaucoma, Open-Angle; Gonioscopy; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

To evaluate the predictive factors of open-angle glaucoma (OAG) in patients affected by ocular hypertension enrolled in the European Glaucoma Prevention Study (EGPS).. Randomized, double-masked, controlled clinical trial.. One thousand seventy-seven patients, > or =30 years old, were enrolled at 18 European centers. The patients met inclusion criteria: intraocular pressure, 22 to 29 mmHg; 2 normal and reliable visual fields (VFs) (on the basis of mean deviation and corrected pattern standard deviation [PSD]); and a normal optic disc, as determined by an optic disc reading center.. Treatment with dorzolamide or a placebo (the vehicle of dorzolamide) in one or both eyes.. Efficacy end points were VF and/or optic disc changes. Baseline demographic and clinical data were collected before randomization, except for corneal thickness measurements, which were determined during follow-up. Proportional hazards models were used to identify factors that predicted which participants in the EGPS had developed OAG.. In multivariate analyses, factors that predicted the development of OAG included older age (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.04-1.69), larger vertical cup-to-disc (C/D) ratio (HR, 1.34; 95% CI, 1.14-1.58), larger vertical C/D ratio asymmetry (HR, 1.46; 95% CI, 1.11-1.93), higher PSD (HR, 1.66; 95% CI, 1.15-2.38), and lesser central corneal thickness (HR, 1.32; 95% CI, 1.05-1.67).. Baseline age, vertical C/D ratio, vertical C/D ratio asymmetry, and PSD were good predictors of the onset of OAG in the EGPS. Central corneal thickness was found to be a powerful predictor of the development of OAG. The EGPS results agree with the findings of the Ocular Hypertension Treatment Study and support the need for a thorough evaluation of patients with ocular hypertension.

Topics: Antihypertensive Agents; Disease Progression; Double-Blind Method; Europe; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prognosis; Proportional Hazards Models; Risk Factors; Sulfonamides; Thiophenes; Visual Acuity

To compare the 24-hour efficacy of dorzolamide and timolol maleate administered twice daily to primary open-angle glaucoma patients whose intraocular pressure (IOP) could not be adequately controlled with latanoprost monotherapy.. In this double-blind prospective crossover clinical comparison trial, 36 primary open-angle glaucoma patients with uncontrolled IOP despite treatment with latanoprost applied once daily were administered timolol and dorzolamide twice daily. The treatment sequence was randomized. All patients underwent measurements for four 24-hour tonometric curves: at baseline and after each 4-week period of treatment. The IOP measurements were taken at 06:00, 09:00, 12:00, 15:00, 18:00, 21:00, 24:00 and 03:00 h. The between-group differences were tested for significance by means of parametric analysis of variance at each time point and circadian curve. The peak values within circadian curve were defined. The mean of the exact amount and percentage of additional IOP reductions from baseline were evaluated and success rates (a minimum of 10% reduction) were determined for both drug regimens.. The mean peak/circadian curve IOPs were 23.4 +/- 2.2/21.8 +/- 2.2 mm Hg at dorzolamide baseline, 23.3 +/- 2.2/21.7 +/- 2.1 mm Hg at timolol baseline, and reduced to 20.2 +/- 1.7/18.7 +/- 1.7 mm Hg and 20.7 +/- 2.4/19.4 +/- 1.6 mm Hg, respectively. When added to latanoprost, both dorzolamide and timolol lowered IOP at circadian curve significantly (p < 0.05). Dorzolamide reduced baseline IOP values at each time point. Timolol also significantly reduced baseline IOP values at all time points except at 03:00. The mean of the exact amount and percentage of reduction in IOP at circadian curve and 5 out of 8 time points were significantly greater with dorzolamide add-on treatment (p < 0.05). The successful reduction rates were 86% for the dorzolamide group and 61% for the timolol group (p = 0.016; chi(2) test).. Both of the combinations are effective in lowering IOP, the exact amount and percentage of reduction is greater with the latanoprost + dorzolamide regimen, especially at night-time.

Topics: Antihypertensive Agents; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

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 objective of this study was to compare the effect of the latanoprost/timolol fixed combination (LTFC) and the dorzolamide/timolol fixed combination (DTFC) on the retrobulbar haemodynamic and intraocular pressure (IOP) in patents with open-angle glaucoma (OAG). This was a prospective, examiner masked, randomised and crossover study. Participants were 32 consecutive subjects, who met the inclusion/exclusion criteria, with newly diagnosed OAG. Patients were randomised to either LTFC or DTFC for the first 1-month treatment phase after a 1-month washout period, without medical treatment, patients began with the opposite treatment for the second 1-month treatment period. Colour Doppler parameters in ophthalmic artery (OA) and posterior ciliary arteries (PCA), ocular perfusion pressure, IOP and systemic haemodynamics were assessed at each baseline and at the end of each treatment period. The main outcomes include peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) in OA and PCA. DTFC significantly increased EDV in OA from 7.55 (1.16) to 9.32 (1.22), p<0.0001, and in the PCA from 4.41 (0.70) to 5.36 (0.60), p<0.0001, and significantly decreased RI in OA from 0.775 (0.036) to 0.725 (0.032), p<0.0001, and in the PCA from 0.694 (0.045) to 0.634 (0.034). LTFC significantly decreased the EDV and significantly increased RI in PCA, p=0.0076 and p=0.0009, respectively. There were no statistical significant differences in the IOP lowering effect between both treatments. DTFC seems to have a beneficial vascular effect on retrobulbar vessels in OAG patients.

Topics: Aged; Aged, 80 and over; Blood Flow Velocity; Ciliary Arteries; Cross-Over Studies; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Artery; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

To evaluate the intercurrent factors for the development of open-angle glaucoma (OAG) in ocular hypertensive patients who were enrolled in the European Glaucoma Prevention Study (EGPS).. Randomized, double masked, controlled clinical trial.. setting: Multicenter. study population: A total of 1,077 patients fulfilled a series of inclusion criteria, including intraocular pressure (IOP) 22 to 29 mm Hg, normal and reliable visual fields (VFs) and normal optic disks. intervention: Treatment with dorzolamide or placebo. main outcome measures: Glaucoma-related VF or optic disk changes. Clinical data were collected every six months during a five-year follow-up. Proportional hazards models were used to identify the factors that during follow-up (intercurrent factors) were associated with the development of OAG.. In multivariate analyses, adjusting for treatment arms and baseline predictive factors, mean follow-up IOP reduction (hazard ratio [HR] 0.89, 95% confidence intervals [CI] 0.80 to 0.98), mean follow-up IOP (HR 1.12, 95% CI 1.03 to 1.22), area under the curve of IOP (mm Hg per year) (HR 1.09, 95% CI 1.06 to 1.12), disk hemorrhages (HR 1.97, 95% CI 1.21 to 3.22), and use of systemic diuretics (HR 2.41, 95% CI 1.12 to 5.19) were associated with the development of OAG. Baseline central corneal thickness, vertical cup/disk ratio, vertical cup/disk ratio asymmetry, and pattern standard deviation remained statistically significant.. These results suggest the need for future investigations to better elucidate the role of systemic diuretics in the development of OAG, because IOP and disk hemorrhages have already been shown to be important intercurrent factors in the Ocular Hypertension Treatment Study (OHTS) and Early Manifest Glaucoma Trial (EMGT).

Topics: Antihypertensive Agents; Cardiovascular Diseases; Confidence Intervals; Cornea; Diuretics; Double-Blind Method; Europe; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Optic Disk; Prevalence; Proportional Hazards Models; Retinal Hemorrhage; Retrospective Studies; Risk Factors; Sulfonamides; Thiophenes; Time Factors; Treatment Outcome

Inhibitors of carboanhydrase (ICA) in the form of dorzolamide 2% drops and brinzolamide 1% drops are in use for 8-10 years, with a significant intraocular pressure (IOP) lowering effect. The goal of the present study was to obtain precise data on the efficacy of local ICA in conjunction with timolol 0.5% drops, and to evaluate the incidence of side effects. This was a prospective study that lasted 2 years and included 110 patients. Initial IOP values, before therapy with ICA, amounted to 19 +/- 8.4 mm Hg in group A and 20.5 +/- mm Hg in group B. Although the results obtained demonstrated statistically significant lowering of IOP (in group A by 4.5 +/- 2.4 mm Hg, and in group B by 4.6 +/- 2.1 mm Hg) after therapy with ICA, the difference between the groups was not found. Dorzolamide more frequently caused local side effects like aching, itching and pain in the eye. Aditional lowering of lOP in our patients was somewhat greater than reported before (4.6:4.3). Side effects (itching, aching, pain) were three times more frequent in the group treated with dorzolamide than reported by other authors; this difference could be due to patient age, as our patients were mostly elderly people and the data are subjective. The results of this study suggested the effectiveness of additional local therapy with ICA in patients with open angle glaucoma.

Topics: Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Sulfonamides; Thiazines; Thiophenes; Timolol

To assess the effects of dorzolamide/timolol fixed combination (DTFC) and latanoprost 0.005% on the retrobulbar haemodynamics and intraocular pressure (IOP) of open-angle glaucoma patients.. 22 consecutive subjects with newly diagnosed, open-angle glaucoma were included in this prospective, examiner masked, randomized, crossover study. The patients were randomized into two different arms. Peak systolic velocity (PSV), end-diastolic velocity (EDV), Pourcelot's resistance index (RI) and intraocular pressure (IOP) were determined at baseline and after 1 month of medical treatment with DTFC or latanoprost 0.005% in both groups. A 4-week washout period, without medical treatment, between study arms was carried out. Primary efficacy variables were the PSV, EDV and RI in the ophthalmic artery (OA) and short posterior ciliary artery (SPCA) and intraocular pressure (IOP). Inter- and intra-group comparisons were performed with a one-way ANOVA test and two-tailed paired Student's t-test respectively.. Intraocular pressure (IOP) and colour Doppler imaging (CDI) measurements were similar at baseline. Compared to baseline and washout measurements, only the fixed combination dorzolamide/timolol significantly increased the EDV in the OA and in the SPCA, p = 0.00012 and p = 0.00012, respectively and decreased the resistance index in the ophthalmic and short posterior ciliary arteries, p = 0.00011 and p = 0.00031, respectively. There were no statistically significant differences in the IOP lowering effect of either treatment.. Over a treatment period of 1 month, only the fixed combination dorzolamide/timolol seems to have a vascular effect on retrobulbar vessels. Further research is necessary to confirm these results.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Eye; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Prostaglandins F, Synthetic; Regional Blood Flow; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

The aim of this study was to evaluate the effects of brimonidine 0.2% and dorzolamide 2% on the ocular blood flow velocity in patients with newly diagnosed primary open-angle glaucoma (POAG). Forty-four (44) patients with newly diagnosed POAG were included in a prospective, comparative, randomized clinical study. Twenty-six (26) healthy volunteers, whose age and gender matched, were recruited to compare the baseline hemodynamic characteristics of the patients. After a complete eye examination, baseline blood flow velocity measurements of the retrobulbar vessels were made with color Doppler ultrasonography. Patients were randomly assigned to receive either brimonidine 0.2% or dorzolamide 2% for a 3-month period. Blood flow velocity measurements were repeated after 3 months. Both brimonidine and dorzolamide significantly reduced the intraocular pressure. The baseline ophthalmic artery pulsatility index was higher in patients with POAG than control subjects. Whereas there was a significant increase in peak systolic velocity of the central retinal artery, no significant change was observed in the other vessels with brimonidine and dorzolamide treatment. There was little difference, in terms of ocular blood flow velocity, between newly diagnosed glaucoma patients and control subjects. Both topical brimonidine and dorzolamide significantly reduced the intraocular pressure without altering ocular blood flow velocity in patients with newly diagnosed POAG.

Topics: Antihypertensive Agents; Blood Flow Velocity; Blood Pressure; Brimonidine Tartrate; Eye; Female; Glaucoma, Open-Angle; Heart Rate; Humans; Instillation, Drug; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Quinoxalines; Sulfonamides; Thiophenes; Treatment Outcome; Ultrasonography, Doppler, Color

To investigate the effect of timolol-dorzolamide and timolol-pilocarpine fixed combinations on retrobulbar vessel blood flow.. Prospective, randomized, masked, crossover clinical trial.. Sixteen patients with primary open angle glaucoma, treated with timolol 0.5%, received timolol 0.5%-dorzolamide 2% and timolol 0.5%-pilocarpine 2% for four weeks each. Heart rate, blood pressure, intraocular pressure (IOP), and peak systolic (PSV) and end diastolic velocities (EDV) in ophthalmic, central retinal, and short posterior ciliary arteries were measured before and after each treatment, and resistivity index was calculated.. The IOP was reduced (P < .01) by timolol-dorzolamide and, more effectively, timolol-pilocarpine combinations. In central retinal artery, the end diastolic velocity was increased by the timolol-dorzolamide combination (P < .01), resulting in higher end diastolic velocity and lower resistivity index values (both P < .01) compared with the timolol-pilocarpine combination.. The timolol-dorzolamide combination increases the end diastolic velocity in central retinal artery, despite a lower intraocular pressure decrease, suggesting an effect on retinal circulation.

Topics: Aged; Antihypertensive Agents; Blood Flow Velocity; Blood Pressure; Ciliary Arteries; Cross-Over Studies; Drug Therapy, Combination; Glaucoma, Open-Angle; Heart Rate; Humans; Intraocular Pressure; Middle Aged; Ophthalmic Artery; Pilocarpine; Prospective Studies; Regional Blood Flow; Retinal Artery; Sulfonamides; Thiophenes; Timolol; Ultrasonography, Doppler, Color

To compare the short-term effects of timolol 0.5%, brimonidine 0.2%, dorzolamide 2%, and latanoprost 0.005% on intraocular pressure (IOP), blood pressure (BP), and diastolic ocular perfusion pressure (DOPP), calculated as the difference between the diastolic blood pressure (DBP) and IOP.. According to a 4 x 4 Latin squares design for repeated measures, 27 untreated patients and patients with newly diagnosed primary open-angle glaucoma (POAG) were treated with timolol 0.5% at 8 AM and 8 PM; brimonidine 0.2% at 8 AM and 8 PM; dorzolamide 2% at 8 AM, 2 PM, and 8 PM; and latanoprost 0.005% at 8 PM. The duration of each treatment course was 6-weeks, with a 4-week washout between each treatment. IOP and BP were measured at baseline and at the end of each treatment period. IOP was measured every 2 hours throughout a 24-hour period. Sitting IOP was measured from 8 AM to 10 PM by Goldmann applanation tonometry. Supine IOP was assessed from 12 to 6 AM by means of a handheld electronic tonometer (TonoPen XL; Mentor, Norwell, MA). BP monitoring was performed by means of an automated portable device (TM-2430; A & D Co., Saitama, Japan).. All the drugs tested decreased the IOP significantly at all time points in comparison with baseline pressure. The mean 24-hour IOP after latanoprost administration (16.62+/-0.98 mm Hg) was significantly lower than that after timolol, brimonidine, or dorzolamide (P=0.0001). During the 24-hour period, brimonidine induced a significant decrease in systolic BP (SBP) and DBP at all time points when compared with baseline measurements and with those after administration of the other drugs (P<0.0001). Timolol caused a significant decrease in DBP and SBP at all the 24-hour time points when compared with the baseline and with the dorzolamide- and latanoprost-induced changes (P<0.0001). The mean 24-hour DOPPs were 50.7+/-5.9 mm Hg at baseline, 53+/-5.5 mm Hg with timolol, 46.2+/-5.4 mm Hg with brimonidine, 55.9+/-4.6 mm Hg with dorzolamide, and 56.4+/-4.9 mm Hg with latanoprost. Brimonidine induced a significant decrease in the mean 24-hour DOPP compared with that at baseline (P<0.0001), whereas dorzolamide and latanoprost induced a significant increase (P<0.0001).. Latanoprost seemed to induce a uniform reduction in IOP during the 24-hour period, although timolol was as effective as latanoprost during the daytime, and dorzolamide are as effective as latanoprost at night. SBP and DBP were significantly decreased by either timolol or brimonidine. In this study of patients with newly diagnosed POAG, only dorzolamide and latanoprost significantly increased mean 24-hour DOPP.

Topics: Administration, Topical; Antihypertensive Agents; Blood Pressure; Brimonidine Tartrate; Circadian Rhythm; Diastole; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Perfusion; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

To compare the additive effect of dorzolamide or carteolol to latanoprost on intraocular pressure (IOP) in glaucoma patients.. Prospective open-label randomized crossover clinical study.. A total of 64 patients with primary open-angle glaucoma were treated with latanoprost 0.005% once daily for 3 months then randomized to receive latanoprost plus dorzolamide 1% 3 times daily (dorzolamide preceding group; n=32) or carteolol hydrochloride 2% twice daily (carteolol preceding group; n=32) for a further 3 months. Then, all patients were crossed over to the opposite treatment arm for a further 3 months. IOP was recorded each month at around the time same as on the baseline day.. Sixty-one patients (95%) completed this trial. In the dorzolamide preceding group, mean (+/-SD) IOP was 19.0+/-2.1 mm Hg at baseline and 16.0+/-2.1 mm Hg at the end of latanoprost monotherapy (P<0.01). Addition of dorzolamide reduced IOP to 15.0+/-1.3 mm Hg and this was not changed by switching to carteolol (15.1+/-1.7 mm Hg). In the carteolol preceding group, IOP was 19.1+/-1.9 mm Hg at baseline and 16.2+/-1.2 mm Hg at the end of latanoprost monotherapy (P<0.01). Addition of carteolol reduced IOP to 14.9+/-1.5 mm Hg, and after switching to dorzolamide IOP was 15.2+/-1.5 mm Hg. Mean additional IOP reduction was 0.9+/-1.2 mm Hg (5.6%) for the latanoprost-dorzolamide combination and 1.1+/-1.5 mm Hg (6.8%) for the latanoprost-carteolol combination. Hence, IOP reduction by carteolol and dorzolamide additionally to latanoprost was not different.. Both dorzolamide and carteolol reduce IOP additively when used in combination with latanoprost, and the additive effect of these drugs is equal.

Topics: Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Carteolol; Cross-Over Studies; Drug Synergism; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Treatment Outcome

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

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

Topics: Adrenergic beta-Antagonists; Aged; Blood Pressure; Cross-Over Studies; Double-Blind Method; Eye; Female; Glaucoma, Open-Angle; Heart Rate; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Regional Blood Flow; Sulfonamides; Thiophenes; Timolol; Visual Acuity

We compared latanoprost monotherapy therapy with timolol/ dorzolamide in patients with primary open-angle glaucoma to evaluate the effects on intraocular pressure (IOP) and occurrence of adverse events. IOP and topical side effects were evaluated at the beginning, first, and third months. Mean IOP was decreased at the third month. The most common side effect was hyperemia (43.6%). We concluded that latanoprost reduces IOP better than fixed combination and its topical side effects are tolerable.

Topics: Adult; Aged; Aged, 80 and over; Drug Therapy, Combination; Eye Color; Eyelashes; Female; Glaucoma, Open-Angle; Humans; Hyperemia; Intraocular Pressure; Latanoprost; Male; Middle Aged; Pain; Prostaglandins F, Synthetic; Pruritus; Sulfonamides; Thiophenes; Timolol

To compare the additive intraocular pressure (IOP)-lowering effects of latanoprost 0.005% and brimonidine 0.2% in primary open-angle glaucoma (POAG) patients uncontrolled on fixed combination of timolol 0.5% and dorzolamide 2% (TDC) alone.. In all, 80 eyes of 80 POAG patients with IOP inadequately controlled by TDC were randomly assigned to receive either latanoprost 0.005% or brimonidine 0.2%. IOP measurements were recorded at 1000 (peak effect) and 1600 (trough effect) on day 0 (baseline) and at 1 and 3 months. At each stage and time point, the mean IOP reductions from baseline were evaluated for both groups, and success rates (minimum 15% reduction) were determined.. At baseline, the mean peak/trough IOPs with TDC were 20.2/21.6 and 19.9/21.4 mmHg in latanoprost and brimonidine groups, respectively. Latanoprost+TDC reduced the mean peak/trough IOP by 4.4/3.4 and 5.2/3.5 mmHg at 1 and 3 months. The corresponding values for brimonidine+TDC were 3.9/2.9 and 4.6/2.9 mmHg. Each of these results represented a significant reduction from baseline (P<0.001 for all); however, the groups' peak/trough reductions from baseline did not differ at any time point (P>0.05 for all). With the latanoprost+TDC combination, the peak/trough success rates at 1 and 3 months were 76.3%/42.1% and 77.1%/40%. The corresponding values with the brimonidine+TDC combination were 71.8%/41% and 77.7%/41.7%. There were no significant differences in the groups' success rates at any time point (P>0.05 for all).. Addition of latanoprost 0.005% or brimonidine 0.2% to TDC reduces peak/trough IOPs significantly and the effects of these combinations are comparable.

Topics: Adult; Aged; Antihypertensive Agents; Brimonidine Tartrate; Drug Combinations; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Latanoprost; Male; Middle Aged; Prospective Studies; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To determine the ocular hypotensive efficacy and safety of dorzolamide when added to brimonidine or timolol in patients with uncontrolled primary open-angle glaucoma (POAG).. This is a 1-year prospective open-label clinical trial of 48 consecutive POAG patients with inadequate intraocular pressure (IOP) control while using brimonidine 0.2% (23 patients) and timolol 0.5% (25 patients), 2 times daily. Patients were assigned to receive dorzolamide 2% as adjunctive therapy, added 3 times daily to brimonidine or timolol. IOP was measured on week 2, and months 3, 6, 9, and 12.. A significant reduction in IOP from the baseline was observed after dorzolamide use in both groups at visits during that year (P < 0.001). Overall, mean IOP reduction was 5.6 +/- 1.9 mmHg with the brimonidine-dorzolamide combination, and 6.8 +/- 1.7 mmHg with timolol-dorzolamide after 1 year of treatment; the difference was significant (P = 0.029). No statistical differences existed between the groups for adverse events (P < 0.05).. The addition of dorzolamide to brimonidine or timolol has significant IOP-lowering efficacy during 1 year in patients with POAG whose IOPs were inadequately controlled with brimonidine or timolol alone. The IOP-lowering effect of the timolol-dorzolamide combination at 1 year was more pronounced than brimonidine-dorzolamide. Both combinations were well-tolerated by the patients.

Topics: Adult; Aged; Antihypertensive Agents; Brimonidine Tartrate; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Prospective Studies; Quinoxalines; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

The European Glaucoma Prevention Study (EGPS) seeks to evaluate the efficacy of reduction of intraocular pressure (IOP) by dorzolamide in preventing or delaying primary open-angle glaucoma (POAG) in patients affected by ocular hypertension (OHT).. Randomized, double-masked, controlled clinical trial.. One thousand eighty-one patients (age, > or =30 years) were enrolled by 18 European centers. The patients fulfilled a series of inclusion criteria, including: IOP 22 to 29 mmHg; 2 normal and reliable visual fields (on the basis of mean deviation and corrected pattern standard deviation or corrected loss variance of standard 30/II Humphrey or Octopus perimetry); normal optic disc as determined by the Optic Disc Reading Center.. Patients were randomized to treatment with dorzolamide or placebo (the vehicle of dorzolamide).. Efficacy end points were visual field, optic disc changes, or both. A visual field change during follow-up had to be confirmed by 2 further positive tests. Optic disc change was defined on the basis of the agreement of 2 of 3 independent observers evaluating optic disc stereo slides. The safety end point was an IOP of more than 35 mmHg on 2 consecutive examinations.. During the course of the study, the mean percent reduction in IOP in the dorzolamide group was 15% after 6 months and 22% after 5 years. Mean IOP declined by 9% after 6 months and by 19% after 5 years in the placebo group. At 60 months, the cumulative probability of converting to an efficacy end point was 13.4% in the dorzolamide group and 14.1% in the placebo group (hazard ratio, 0.86; 95% confidence interval [CI], 0.58-1.26; P = 0.45). The cumulative probability of developing an efficacy or a safety end point was 13.7% in the dorzolamide group and 16.4% in the placebo group (hazard ratio, 0.73; 95% CI, 0.51-1.06; P = 0.1).. Dorzolamide reduced IOP by 15% to 22% throughout the 5 years of the trial. However, the EGPS failed to detect a statistically significant difference between medical therapy and placebo in reducing the incidence of POAG among a large population of OHT patients at moderate risk for developing POAG, because placebo also significantly and consistently lowered IOP.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Disease Progression; Double-Blind Method; Europe; Female; Glaucoma, Open-Angle; Humans; Incidence; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Quality Assurance, Health Care; Safety; Sulfonamides; Thiophenes; Treatment Outcome

To evaluate the 24-hour efficacy of brimonidine purite versus dorzolamide, each added to latanoprost.. Double-masked, 2-center, prospective, crossover comparison.. Primary open-angle glaucoma (POAG) subjects.. Subjects were randomized to brimonidine purite or dorzolamide, each given twice daily, for the first 6-week treatment period after a 6-week latanoprost run-in. Subjects began the opposite treatment for the second 6-week period after a 6-week latanoprost-only treatment between periods. Intraocular pressure (IOP) was measured at 8 am, 12 pm, 4 pm, 8 pm, 12 am, 4 am, and 8 am at each baseline and at the end of each treatment period. This study provided an 80% power that a 1.5-mmHg difference could be excluded between groups if 27 subjects completed the study. A standard deviation (SD) of 2.8 mmHg was assumed.. Twenty-four-hour efficacy of intraocular pressures of brimonidine purite versus dorzolamide, each added to latanoprost.. In 31 completed subjects, the baseline mean diurnal 24-hour IOP (+/- SD) was 19.0+/-1.7 mmHg for brimonidine purite and 19.0+/-1.6 mmHg for dorzolamide (P = 0.52). The 8 am IOP after 6 weeks of therapy was 18.4+/-2.1 mmHg for brimonidine purite and 18.9+/-1.9 mmHg for dorzolamide (P = 0.40). The mean diurnal IOP was 16.9+/-1.5 mmHg for brimonidine purite and 16.8+/-1.5 mmHg for dorzolamide (P = 0.66). Dorzolamide caused a more bitter taste (P = 0.01) than brimonidine purite.. This study suggests that brimonidine purite and dorzolamide, added to latanoprost, have similar efficacy and safety in POAG or ocular hypertensive subjects.

Topics: Aged; Antihypertensive Agents; Brimonidine Tartrate; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Prospective Studies; Prostaglandins F, Synthetic; Quinoxalines; Safety; Sulfonamides; Thiophenes; Visual Acuity

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

The study investigated whether dorzolamide influences the autoregulatory behavior of major retinal arterioles in glaucoma patients via a moderate perfusion pressure reduction.. The study included one eye each of 12 untreated patients with a primary open-angle glaucoma (POAG) (age 60.8 +/- 8.3, IOP 22.3 +/- 6.5 mmHg). Changes in the diameter of a retinal artery segment before (120 s), during (100 s), and after (380 s) artificial IOP elevation to 38 mmHg for 100 s were recorded continuously by means of a Retinal Vessel Analyzer. The measurement was repeated after 4-week treatment with dorzolamide eye drops t.i.d.. Ocular perfusion pressure (mmHg) was reduced by the intraocular pressure (IOP) elevation from 58 (+/- 10) to 41 (+/- 11) in the pretreatment examination and from 60 (+/- 8) to 40 (+/- 8) posttreatment (differences between the examinations n.s.). Before IOP elevation, the arterial diameter was found to be +1.7 +/- 3.5% greater in the posttreated eyes than in the pretreated eyes (p < 0.02). During IOP elevation, the arterial diameter decreased by -1.8% +/- 3.8 in the pretreated eyes, whereas dilatation by +1.4% +/- 2.5 was observed in the posttreated eyes (p = 0.02). At the end of the observation period following IOP elevation, the vessel diameter in the pretreated eyes had increased by +1.8% +/- 4.2, whereas in the posttreated eyes it had decreased by -1.7% +/- 3.0. On average, dorzolamide reduced IOP by -5.6 mmHg (p = 0.001).. The arterial diameter dilatation during IOP elevation in dorzolamide-treated eyes could be an accelerated counter-regulation on the induced elevated IOP and could constitute an additional therapeutic effect.

Topics: Aged; Blood Pressure; Carbonic Anhydrase Inhibitors; Female; Glaucoma, Open-Angle; Homeostasis; Humans; Intraocular Pressure; Male; Middle Aged; Muscle, Smooth, Vascular; Ocular Hypertension; Ophthalmic Solutions; Retinal Artery; Sulfonamides; Thiophenes; Vasodilation

Brinzolamide and dorzolamide are often used as adjunctive therapy to other antiglaucoma agents. The purpose of this study was to compare the efficacy and safety of brinzolamide 1% versus dorzolamide 1% when added to the combination therapy of latanoprost and a beta-blocker in patients with glaucoma.. An 8-week, randomized, open-label comparative study was performed in 52 patients with glaucoma. Brinzolamide 1% (twice a day) or dorzolamide 1% (3 times a day) was randomly administered to the patients who had been treated with both latanoprost and a betablocker.. Intraocular pressure (IOP) were both decreased significantly (P < 0.0001) from 18.6 +/- 2.3 mmHg to 16.7 +/- 2.3 mmHg and from 18.4 +/- 2.6 mmHg to 16.6 +/- 2.5 mmHg, respectively, 8 weeks after the addition of brinzolamide or dorzolamide. However, the difference between the groups was not significant (P = 0.86). The incidence of ocular irritation was significantly higher (P < 0.0001) in the dorzolamide group (74%) than the brinzolamide group (16%), but there was no significant difference in blurred vision between the groups (dorzolamide 37% versus brinzolamide 52%, P = 0.40).. We concluded that the efficacy of brinzolamide 1% was equivalent to dorzolamide 1%; however, the safety of brinzolamide 1% was superior to dorzolamide 1% as adjunctive therapy to the combination with latanoprost and a beta-blocker.

Topics: Adrenergic beta-Antagonists; Aged; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Instillation, Drug; Intraocular Pressure; Latanoprost; Male; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiazines; Thiophenes; Treatment Outcome

There is evidence that perfusion abnormalities of the optic nerve head are involved in the pathogenesis of glaucoma. There is therefore considerable interest in the effects of topical antiglaucoma drugs on ocular blood flow. A study was undertaken to compare the ocular haemodynamic effects of dorzolamide and timolol in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT).. One hundred and forty patients with POAG or OHT were included in a controlled, randomised, double blind study in two parallel groups; 70 were randomised to receive timolol and 70 to receive dorzolamide for a period of 6 months. Subjects whose intraocular pressure (IOP) did not respond to either of the two drugs were switched to the alternative treatment after 2 weeks. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude.. Five patients did not respond to timolol and were changed to the dorzolamide group, and 18 patients changed from dorzolamide treatment to timolol. The effects of both drugs on IOP and ocular perfusion pressure were comparable. Dorzolamide, but not timolol, increased blood flow in the temporal neuroretinal rim (8.5 (1.6)%, p<0.001 versus timolol) and the cup of the optic nerve head (13.5 (2.5)%, p<0.001 versus timolol), and fundus pulsation amplitude (8.9 (1.3)%, p<0.001 versus timolol).. This study indicates augmented blood flow in the optic nerve head and choroid after 6 months of treatment with dorzolamide, but not with timolol. It remains to be established whether this effect can help to reduce visual field loss in patients with glaucoma.

Topics: Aged; Antihypertensive Agents; Choroid; Double-Blind Method; Eye; Female; Glaucoma, Open-Angle; Heart Rate; Hemodynamics; Humans; Intraocular Pressure; Laser-Doppler Flowmetry; Male; Middle Aged; Ocular Hypertension; Optic Disk; Regional Blood Flow; Regression Analysis; Retinal Vessels; Sulfonamides; Thiophenes; Timolol

The aim of this study was evaluate the efficacy and ocular discomfort of substituting brinzolamide for dorzolamide in patients with glaucoma treated by latanoprost, timolol, and dorzolamide.. An 8-week, prospective, randomized, open-label, comparative study was performed in 58 patients with primary open-angle glaucoma treated by latanoprost, timolol, and dorzolamide. These patients were randomly enrolled into two groups: (1) dorzolamide three times daily was substituted with brinzolamide twice-daily (substituting group); and (2) dorzolamide three times daily was continued (control group). Intraocular pressure (IOP) was measured at baseline, 4, and 8 weeks after the enrollment. Subjective ocular discomfort (irritation and blurred vision) at the time of the instillation of the patient was noted with interview.. The IOPs at baseline, 4 and 8 weeks after the enrollment were 17.7 +/- 2.7 mmHg, 17.5 +/- 2.6 mmHg, and 17.4 +/- 2.9 mmHg in the substituting group, and 18.0 +/- 2.5 mmHg, 17.8 +/- 2.5 mmHg, and 17.9 +/- 2.6 mmHg in the control group, respectively. There were no significant differences in IOP changes between the two groups (P = 0.74). In the substituting group, ocular irritation was decreased significantly (P = 0.0014) from 63% to 20%. The slight increase of blurred vision from 27% to 37% that occurred in the substituting group was not significant (P = 0.58). In the control group, neither ocular irritation (P = 0.58, from 68% to 57%) nor blurred vision (P = 0.99, from 25% to 21%) was changed.. Substituting brinzolamide for dorzolamide maintained stable IOP with improvement in ocular comfort in patients with glaucoma.

Topics: Aged; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Sulfonamides; Thiazines; Thiophenes; Timolol; Vision, Ocular

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

To compare ocular tolerability of dorzolamide 2%, brinzolamide 1%, and placebo given three times daily.. A prospective, double-masked, three-centre, crossover comparison in which 25 ocular hypertensive or primary-open angle glaucoma subjects were randomized to receive dorzolamide, brinzolamide, or placebo three times daily for 3 days. Intraocular pressure, visual acuity, a visual analogue scale, and ocular and systemic symptom queries were completed at the end of each period.. After chronic dosing, there was a significant difference in ocular pain on the visual analogue scale among the groups at the 10-s postinstillation time point with dorzolamide having the highest level (22.5+/-28.9) compared to brinzolamide (5.0+/-8.7) or placebo (3.2+/-10.4) (P=0.0006). No differences between groups were observed preinstillation nor following dosing at 3 or 10-min postinstillation. On the initial instillation, the 10-s postinstillation pain was rated as 43.3+/-77.1, which was significantly higher than after chronic dosing (P=0.017). On the ocular symptom query, dorzolamide had the highest incidence of burning/stinging and redness compared to the other groups, but was generally characterized as mild. There were no significant differences in the visual acuity at any time point.. This study suggests that subjects treated with dorzolamide suffer more ocular pain upon instillation compared to brinzolamide or placebo. However, pain symptoms are fewer following chronic dosing and are generally characterized as mild.

Topics: Adult; Aged; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Pain; Pain Measurement; Prospective Studies; Severity of Illness Index; Sulfonamides; Thiazines; Thiophenes

To compare the efficacy and safety of the fixed combination of latanoprost and timolol with those of the fixed combination of dorzolamide and timolol in patients with elevated intraocular pressure (IOP).. Three-month, randomized, parallel group, evaluator-masked, multicenter study.. Patients with primary open-angle glaucoma or ocular hypertension with elevated IOP insufficiently responsive to monotherapy; 253 randomized: 125 to receive a fixed combination of latanoprost 0.005% and timolol 0.5% once daily, and 128 to receive a fixed combination of dorzolamide 2% and timolol 0.5% twice daily.. Visits were at screening (current ocular hypotensive therapy was discontinued), 2 weeks (if needed for an IOP-safety check), baseline (randomization), and after 1 and 3 months of therapy. Intraocular pressure was measured in triplicate at 8 am, 12 pm, and 4 pm at each study visit, and diurnal IOP was calculated as the mean value of these recordings. Adverse events were recorded at each visit.. The difference between treatment groups in the change in mean diurnal IOP from baseline to month 3.. Mean diurnal IOP levels were similar at baseline. Mean (+/- standard error of the mean) reductions in diurnal IOP from baseline to month 3 were 9.4+/-0.27 mmHg in the latanoprost/timolol fixed-combination group, versus 8.4+/-0.26 mmHg in patients receiving the dorzolamide/timolol fixed combination. The mean difference in diurnal IOP reduction between treatments was 1.00 mmHg (95% confidence interval, 0.31-1.69; P = 0.005) in favor of the latanoprost/timolol fixed combination. Both treatments generally were well tolerated.. The fixed combination of latanoprost and timolol was slightly more effective than that of dorzolamide and timolol in reducing mean diurnal IOP, and both treatments were generally well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To compare the intraocular pressure (IOP) lowering effect, tolerability, and patient-reported measures of the dorzolamide/timolol fixed combination and the concomitant administration of brimonidine and timolol after 3 months.. Four hundred ninety-two patients with ocular hypertension, primary open-angle glaucoma, exfoliative glaucoma, or pigmentary glaucoma participated in this randomized, observer-masked, multicenter study. Following 3 weeks of timolol monotherapy, patients with a peak IOP of > or = 2 mm Hg were randomized to receive either fixed combination dorzolamide/timolol twice daily or concomitant brimonidine plus timolol twice daily for 3 months. The IOP-lowering effects at peak and trough, tolerability, and patient-reported convenience and satisfaction were measured at months 1 and 3.. At month 3 peak, the dorzolamide/timolol group had an adjusted mean (SE) change from baseline IOP of -4.30 (0.24) mm Hg versus -5.27 (0.23) mm Hg in the brimonidine-plus-timolol group, with a treatment difference of 0.97 mm Hg (95% CI: 0.40, 1.53). At the month 3 trough timepoint and both month 1 timepoints, the 95% CIs of the treatment differences were within the prespecified comparability boundary of +/- 1.5 mm Hg. The incidence of drug-related adverse experiences was similar between treatment groups. Patient-reported assessments of convenience and satisfaction showed no statistically significant differences between treatment groups.. The IOP-lowering effect of the dorzolamide/timolol fixed combination and concomitant brimonidine plus timolol were comparable at 3 of the 4 timepoints measured. Patient-reported measures and the incidence of adverse experiences in both treatment groups were similar.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Patient Satisfaction; Prospective Studies; Quinoxalines; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To compare the intraocular pressure (IOP) reduction between dorzolamide 2% and brimonidine 0.2% in primary open-angle glaucoma (POAG) or ocular hypertension (OHT).. This study was a prospective, double-masked, randomized, crossover comparison of dorzolamide 2% (Trusopt) and brimonidine 0.2% (Alphagan), three times daily during two six-week study periods. The primary endpoint was mean change from baseline in trough IOP and secondary endpoints were mean change from baseline in IOP one and three hours after dosing. T-tests and a repeated-measures ANOVA were used to statistically evaluate the data.. Of 43 patients enrolled, 41 completed the first treatment and 38 completed both treatments. Baseline IOP for dorzolamide was 24.3 mm Hg and brimonidine, 24.6 mm Hg (P = 0.9). Mean IOP reduction at trough was similar for both agents, 3.0 mm Hg (P = 0.96). Reductions at one and three hours were comparable (P = ns). Both agents were well tolerated with adverse events consistent with the package inserts. Dorzolamide was associated with more frequent stinging (P = 0.017) and burning (P < 0.001), while brimonidine was associated with more frequent dry eye (P = 0.04).. Dorzolamide and brimonidine, as monotherapy, produced equivalent IOP-lowering efficacy at trough and at one and three hours after instillation, and both were well tolerated.

Topics: Adrenergic alpha-Agonists; Antihypertensive Agents; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Cross-Over Studies; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Quinoxalines; Safety; Sulfonamides; Thiophenes; Treatment Outcome

To evaluate the clinical efficiency and tolerability of brimonidine and dorzolamide twice daily as an adjunctive therapy for glaucoma patients with an inadequate response to beta-blockers therapy.. This multicenter prospective analysis included 92 patients (180 eyes) with primary open-angle glaucoma or ocular hypertension on therapy beta-blockers and with intraocular pressure (IOP) greater than or equal to 18mmHg. The patients were randomly treated either with brimonidine 0.2% or dorzolamide 2% added for three months. Efficiency was determined by the reduction in 15% IOP from baseline at the first and the third month.. Mean pre-treatment IOP was 22.37 DE 2.8 mmHg in the brimonidine group and 22.38 DE 2.6 mmHg in the dorzolamide group; mean post-treatment IOP decrease was 4.39 mmHg in the brimonidine group and 3.29 mmHg in the dorzolamide group. Clinical control at the first month was achieved in 78.3% and 71% of cases respectively (p=0.05). No statistical differences existed between groups for systemic adverse events. Four patients on brimonidine discontinued treatment due to local side effects. In the dorzolamide group, two patients left the treatment referring itching and three others left due to ocular allergy.. This study found similar efficiency and safety when treating with brimonidine or dorzolamide as an adjunctive therapy for patients with hypertension or primary open-angle glaucoma.

Topics: Adrenergic beta-Antagonists; Adult; Antihypertensive Agents; Brimonidine Tartrate; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Quality of Life; Quinoxalines; Sulfonamides; Thiophenes; Tonometry, Ocular; Treatment Outcome

To evaluate the efficacy of brimonidine purite versus dorzolamide given twice daily in primary open angle glaucoma or ocular hypertensive subjects.. In this double masked, multicentre, prospective, crossover comparison 33 subjects were randomised to brimonidine purite or dorzolamide for the first 4 week treatment period after a 4 week washout. Subjects began the opposite treatment for the second 4 week period after another 4 week washout. Intraocular pressure (IOP) was measured at 08:00 (trough) and 10:00, 18:00, and 20:00 hours after dosing at each baseline and at the end of each treatment period.. The baseline diurnal IOP was 22.9 (SD 2.8) for brimonidine purite and 22.2 (SD 2.4) mm Hg for dorzolamide. The trough IOP following 4 weeks of therapy was 21.0 (SD 3.7) for brimonidine purite and 21.0 (SD 3.1) mm Hg for dorzolamide (p = 0.90). The mean diurnal IOP was 19.3 (SD 3.1) for brimonidine purite and 19.8 (SD 2.4) mm Hg for dorzolamide (p = 0.46). Dorzolamide caused more ocular stinging upon instillation (n = 8) than brimonidine purite (n = 1) (p = 0.02). No statistical differences existed between groups for systemic adverse events.. This study suggests that brimonidine purite and dorzolamide each given twice daily have similar efficacy in primary open angle glaucoma or ocular hypertensive subjects. However, a trend was observed at 10:00 of greater brimonidine purite efficacy compared with dorzolamide.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Quinoxalines; Sulfonamides; Thiophenes

The diurnal efficacy and safety of the fixed combinations of latanoprost/timolol given once daily vs dorzolamide/timolol given twice daily in primary open-angle glaucoma or ocular hypertensive patients.. A double-masked, two-centre, crossover comparison.. In 33 patients, the mean diurnal IOP (0800-2000, measured every 2 h) for latanoprost/timolol fixed combination was 17.3+/-2.2 mmHg and for dorzolamide/timolol, the fixed combination was 17.0+/-2.0 mmHg (P = 0.36). Additionally, there was no statistical difference for individual time points following a Bonferroni correction. A bitter taste was found more frequently with the dorzolamide/timolol fixed combination (n = 6) than the latanoprost/timolol fixed combination (n = 0) (P = 0.040), while the latanoprost/timolol fixed combination demonstrated more conjunctival hyperaemia (n = 9) than the dorzolamide/timolol fixed combination (n = 2) (P = 0.045). One patient was discontinued early from the dorzolamide/timolol fixed combination due to elevated IOP.. This study suggests that the daytime diurnal IOP is not statistically different between the dorzolamide/timolol fixed combination and latanoprost/timolol fixed combination in primary open-angle glaucoma and ocular hypertensive patients.

Topics: Adult; Aged; Antihypertensive Agents; Chronotherapy; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

The newer ocular hypotensive agents available to treat glaucoma and ocular hypertension (OHT) include latanoprost, a prostaglandin F(2alpha) analogue, and the fixed combination of dorzolamide hydrochloride, a carbonic anhydrase inhibitor, and timolol maleate, a beta-blocker.. The aim of this study was to compare the efficacy and tolerability of latanoprost with that of the fixed combination of dorzolamide and timolol over 8 weeks.. This interventional, 8-week, randomized, open-label, parallel-group study was conducted at 18 centers in 6 Latin American countries. Patients with unilateral or bilateral primary open-angle, pigmentary, or exfoliative glaucoma or OHT were randomized to receive latanoprost, 1 drop in the affected eye QD (evening), or fixed-combination dorzolamide/timolol, 1 drop in the affected eye BID (morning and evening). Medications were self-administered, 1 drop per affected eye. At baseline and week 8, intraocular pressure (IOP) was measured 3 times each at 8:30 am, 10:00 am, 2:00 pm, and 5:00 pm and after the water-drinking test, which estimates the IOP peak of diurnal tension curve, performed following the 5:00 pm IOP assessment. The primary efficacy outcome was change in diurnal IOP (the mean of IOP measurements) from baseline to week 8. Adverse effect (AE) data were recorded at each visit.. A total of 229 patients were randomized (latanoprost, n = 112; dorzolamide/timolol, n = 117). Mean baseline diurnal IOP values were similar between the 2 groups. Mean (SD) diurnal IOP reductions at week 8 before the water-drinking test were 6.9 (3.0) mm Hg for the latanoprost group and 6.4 (3.2) mm Hg for the dorzolamide/timolol group. Mean IOP values were similar at all time points except at 5:00 pm, when levels were significantly lower in latanoprost-treated patients (P = 0.025). After the water-drinking test, the increase in IOP values was similar between groups at baseline but lower in latanoprost-treated patients at week 8 (adjusted difference, 1.08 mm Hg; P = 0.012). Fewer patients treated with latanoprost reported ocular or systemic AEs (P = 0.025 and P < 0.001, respectively).. In this study of patients with unilateral or bilateral primary open-angle, pigmentary, or exfoliative glaucoma or OHT IOP reductions generally were similar between treatment groups, except at 5:00 pm, when the mean IOP level was significantly lower in latanoprost-treated patients. Latanoprost was better tolerated than fixed-combination dorzolamide and timolol.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

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

To establish the efficacy and safety of timolol 0.5%/dorzolamide 2% fixed combination versus timolol 0.5%/pilocarpine 2% fixed combination, each given twice daily, in primary open-angle glaucoma and ocular hypertensive patients.. In this prospective, multicenter, double-masked trial, 37 patients were treated twice daily with timolol for 4 weeks. Then, they were randomized to one of the treatment medications for 6 weeks, after which they were treated with timolol again for 2 weeks before placed on the opposite treatment medication for 6 weeks.. A total of 36 patients completed the trial. The mean baseline intraocular pressure (IOP) was 22.3 +/- 3.7 mmHg. Following 6 weeks of treatment, the mean decrease of IOP was 18.0 +/- 2.2 mmHg for timolol/dorzolamide combination and 17.4 +/- 2.0 for timolol/pilocarpine combination. The mean diurnal curve IOP was 18.1 +/- 2.2 mmHg for timolol/dorzolamide group and 16.7 +/- 1.9 mmHg for timolol/pilocarpine group. These differences were statistically significant. Statistically more patients reported ocular pain and diminished vision during use of the timolol/pilocarpine combination.. This study suggest that timolol 0.5%/pilocarpine 2% fixed combination can provide at least similar efficacious reduction in IOP as timolol 0.5 %/dorzolamide 2% fixed combination in patients with primary open-angle glaucoma and ocular hypertension.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Miotics; Pilocarpine; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To evaluate the effects of dorzolamide/timolol fixed combination (D/T) compared to latanoprost on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in primary open-angle glaucoma (POAG) patients.. Thirty patients with POAG were randomized in an open-label, cross-over study. Intraocular pressure reduction was achieved by 4 weeks medical therapy with D/T twice daily or latanoprost 0.005% dosed once in the evening. During a 4-week run-in and a 4-week wash-out period between study arms, patients ceased use of all other glaucoma medications and used timolol maleate 0.5% twice daily. Primary efficacy variables were IOP and POBF.. There was no difference in baseline IOP and POBF parameters between the two study arms. Both D/T and latanoprost statistically significantly reduced IOP by 4.6 mmHg (p < 0.0001) and 3.75 mmHg (p < 0.0001) and increased POBF by 2.048 microl/second (p = 0.0030) and 2.147 microl/second (p = 0.0009), respectively. Repeated measures anova detected significant changes in POBF with treatment (p = 0.0361). Dorzolamide/timolol fixed combination statistically significantly increased pulse volume by 0.767 microl (p = 0.0087), while latanoprost therapy had no significant effect (p = 0.2407).. Both drugs had similar effects in terms of IOP reduction. Dorzolamide/timolol significantly increased pulse volume while latanoprost had no effect. Further studies are necessary to establish whether the enhancement of choroidal blood flow can prevent glaucoma progression.

Topics: Adult; Aged; Antihypertensive Agents; Blood Flow Velocity; Cross-Over Studies; Drug Therapy, Combination; Eye; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Prostaglandins F, Synthetic; Pulsatile Flow; Regional Blood Flow; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Ultrasonography, Doppler

Cost is an issue when prescribing two drugs with equivalent efficacy. We compared the direct medical costs of topical brinzolamide 1% (twice a day or three times daily) with topical dorzolamide 2% (twice a day or three times daily) in France, Italy, Portugal and Spain in patients with ocular hypertension or primary open-angle glaucoma.. Three double-blind, controlled, randomised trials (with a study duration of 3 months) compared the response rate of brinzolamide twice a day or three times daily versus dorzolamide three times daily, and the response rate of brinzolamide-timolol twice a day versus a dorzolamide-timolol combination twice a day. A fourth double-blind randomised trial (with a duration of 12 months) compared brinzolamide twice a day and three times daily with timolol monotherapy. Local tolerance was compared in two dedicated studies. Rates of switching to a new medication regimen were evaluated through a US health maintenance organisation database. In case of treatment failure, the patients were treated with latanoprost. A model was developed to value direct medical costs over 3 months. The economic perspective was that of the third-party payer and the patient, and included direct medical costs (reimbursed part plus co-payment).. Patients with ocular hypertension and/or primary open-angle glaucoma who had not responded to or could not tolerate beta-blocker therapy.. The daily direct medical costs of therapy with the two drugs.. As monotherapy, brinzolamide twice daily and three times daily was found to be as efficacious as dorzolamide three times a day. Brinzolamide twice daily plus timolol was also as efficacious as a combination of dorzolamide and timolol twice a day. Stinging of the eye upon instillation with brinzolamide was experienced by fewer patients than with dorzolamide (p < 0.0001). The likelihood of patients treated with dorzolamide changing therapy was 1.28 times greater than that for those treated with brinzolamide. The size of the brinzolamide drop is 18.7% smaller than that of dorzolamide allowing seven more therapy days per bottle with brinzolamide twice daily than with dorzolamide monotherapy, and five more days when brinzolamide is used three times a day. The direct medical costs for patients treated with brinzolamide were lower in all four European countries when drop size was taken into account than for those treated with dorzolamide. Sensitivity analyses confirmed the robustness of our findings.. Because brinzolamide can be prescribed twice daily in monotherapy and because fewer patients treated with brinzolamide switch therapy due to local intolerance, our model suggests that brinzolamide is a cost-saving alternative to dorzolamide.

Topics: Administration, Topical; Carbonic Anhydrase Inhibitors; Drug Administration Schedule; Economics, Pharmaceutical; Europe; Glaucoma, Open-Angle; Humans; Ocular Hypertension; Randomized Controlled Trials as Topic; Sulfonamides; Thiazines; Thiophenes

To compare the efficacy and safety of timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily.. Prospective multicenter, randomized, double-masked, crossover comparison study.. Primary open-angle glaucoma or ocular hypertension patients were randomly assigned to one of the treatment groups for a 6-week treatment period and then crossed over to the opposite treatment. Diurnal curve testing was performed at 8:00 AM, 10:00 AM, 4:00 PM, 6:00 PM, and 8:00 PM at baseline and the end of each treatment period. The run-in medicine was timolol twice daily for 28 days.. Thirty-two patients completed this trial. The baseline trough pressure was 24.3 +/- 3.0 mm Hg, and the diurnal curve was 23.4 +/- 3.2 mm Hg. For the fixed combination the treatment trough pressure was 20.8 +/- 4.1 mm Hg and the diurnal curve was 19.6 +/- 3.6 mm Hg, whereas timolol and unoprostone concomitant therapy showed a treatment trough pressure of 20.1 +/- 4.5 mm Hg and a diurnal pressure of 19.8 +/- 4.1 mm Hg. There was no significant difference between treatment groups at any time point, for the diurnal curve, or in the extended reduction from baseline. There was no difference between treatment groups regarding ocular and systemic unsolicited or solicited adverse events. Burning, stinging, and conjunctival hyperemia were the adverse events most noted. There were no serious adverse events during this trial.. This study suggests that both timolol/dorzolamide 2% fixed combination and concomitant timolol maleate 0.5% and unoprostone 0.15% therapy provide similar efficacy and safety throughout the daytime diurnal curve.

Topics: Antihypertensive Agents; Cross-Over Studies; Dinoprost; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome; Visual Acuity

To evaluate the safety and efficacy of the timolol/dorzolamide fixed combination vs latanoprost 0.005% in exfoliation glaucoma patients.. We randomized in an observer-masked fashion 65 newly diagnosed exfoliation glaucoma patients to either the timolol/dorzolamide twice daily or latanoprost daily treatment for 2 months and then crossed these over to the other treatment.. A total of fifty-four patients completed the study. After 2 months of chronic dosing, the morning intraocular pressure (IOP) (10:00) was reduced from a baseline of 31.2+/-6.5 mmHg to 18.1+/-3.0 with the fixed combination and to 18.9+/-4.1 mmHg with latanoprost (P = 0.21). Six patients were discontinued early from both treatment periods owing to inadequate IOP control and two others were discontinued from latanoprost treatment only. The fixed combination showed a significantly greater incidence of taste perversion (P < 0.001) and stinging upon instillation (P = 0.036), while latanoprost showed a trend for increased conjunctival injection (P = 0.056). However, five patients demonstrated either bradycardia or asthmatic symptoms with initiation of the fixed combination therapy. One patient on latanoprost complained of dizziness. Patient preference was generally given to latanoprost (63 vs 20.3%) mainly because of its once daily dosing (P < 0001).. This study suggests that both latanoprost and the timolol/dorzolamide fixed combination are efficacious in the treatment of newly diagnosed exfoliation glaucoma.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Patient Satisfaction; Prostaglandins F, Synthetic; Single-Blind Method; Sulfonamides; Thiophenes; Timolol

To compare the efficacy and tolerability of the 2% dorzolamide/0.5% timolol combination ophthalmic solution twice daily to the concomitant administration of 0.2% brimonidine ophthalmic solution twice daily and 0.5% timolol ophthalmic solution twice daily.. Randomized, multicenter, observer-masked, parallel-group study.. Two hundred ninety-three patients with ocular hypertension or primary open-angle glaucoma participated.. After an open-label 3-week 0.5% timolol run-in period, patients with an hour 2 intraocular pressure (IOP) of > or = 22 mmHg were randomly assigned to receive either the dorzolamide/timolol combination twice daily or the concomitant use of brimonidine twice daily and timolol twice daily (brimonidine + timolol) for 6 months.. The IOP-lowering effects at hour 0 and hour 2 were collected at 1, 3, and 6 months. We hypothesized that both treatment regimens would have comparable hour 2 IOP-lowering effects at month 3. The treatments were considered comparable if the two-sided 95% confidence interval of the treatment difference was within +/- 1.5 mmHg. Tolerability data were also collected at 1, 3, and 6 months.. The primary efficacy analysis was based on the modified intent-to-treat population. At month 3, hour 2, the dorzolamide/timolol group had an adjusted mean (standard error) change in IOP of -5.04 (0.30) mmHg versus -5.41 (0.30) mmHg in the brimonidine + timolol group, with a treatment difference of 0.36 (0.40) mmHg (95% confidence interval [CI] of -0.42-1.14 mmHg). At month 3, hour 0, the dorzolamide/timolol group had a change in IOP of -3.66 (0.29) mmHg versus -4.15 (0.28) mmHg in the brimonidine + timolol group, with a treatment difference of 0.49 (0.39) mmHg (95% CI of -0.27-1.25 mmHg). Likewise, at all other observed time points, the 95% confidence interval of the treatment difference was within +/- 1.5 mmHg. Ninety-three patients (64%) in the dorzolamide/timolol group and 88 patients (60%) in the brimonidine + timolol group had adverse experiences that were deemed drug related by the investigator, for which 7 patients (5%) in the dorzolamide/timolol group and 8 patients (5%) in the brimonidine + timolol group were discontinued from the study.. The efficacy of the dorzolamide/timolol combination and the concomitant administration of brimonidine and timolol were comparable. The incidence of drug-related adverse experiences and the incidence of discontinuations caused by drug-related adverse experiences were similar between groups.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Quinoxalines; Safety; Sulfonamides; Thiophenes; Timolol; Visual Acuity; Visual Fields

To compare the circadian intraocular pressure (IOP) reductions induced by latanoprost, brimonidine tartrate, and a fixed combination of timolol maleate and dorzolamide hydrochloride in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).. In this crossover study, 10 patients with POAG and 10 with OHT were treated with latanoprost once a day, brimonidine twice a day, and a fixed combination of timolol and dorzolamide twice a day for 1 month. Four 24-hour tonometric curves were obtained for each patient. Intraocular pressure (IOP) was measured at 3, 6, and 9 AM, and at noon and at 3, 6, and 9 PM, and at midnight, using a handheld electronic tonometer with the patient in supine and sitting positions and a Goldmann applanation tonometer with the patient sitting at the slitlamp.. Reduction of circadian IOP.. All the drugs significantly reduced IOP compared with the baseline at all times, except for brimonidine at midnight, 3 AM, and 6 AM. Latanoprost was more effective than brimonidine in lowering IOP at 3 and 6 AM and at 3 PM (P=.03), and the combination of timolol and dorzolamide was more effective than brimonidine at 3 and 9 AM (P=.04) and at 3 and 6 PM (P =.05) and more effective than latanoprost at 9 AM (P=.05).. Latanoprost and the fixed combination of timolol and dorzolamide led to similar circadian reductions in IOP, whereas brimonidine was less effective, particularly during the night.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Circadian Rhythm; Cross-Over Studies; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Posture; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

To compare the safety and efficacy of unoprostone, brimonidine, and dorzolamide as adjunctive therapy to timolol in patients with primary open angle glaucoma or ocular hypertension.. This was a randomised, double masked, parallel group, multicentre (14) study. After using timolol maleate 0.5% monotherapy twice a day for 2 weeks, patients (n = 146) with an early morning intraocular pressure (IOP) between 22 and 28 mm Hg, inclusively, received unoprostone isopropyl 0.15% (n = 50), brimonidine tartrate 0.2% (n = 48), or dorzolamide hydrochloride 2.0% (n = 48) twice daily as adjunctive therapy to timolol maleate 0.5% for another 12 weeks. Safety was based on comprehensive ophthalmic examinations, adverse events, and vital signs. Efficacy was based on mean change from baseline in the 8 hour diurnal IOP at week 12. Baseline was defined as values obtained after 2 weeks of timolol monotherapy.. Each drug was safe and well tolerated. Burning/stinging was the most common treatment emergent adverse event. No clinically relevant changes from baseline were observed for any ophthalmic examination or vital signs. At week 12, each adjunctive therapy produced statistically significant (p<0.001) reductions from timolol treated baseline in the mean 8 hour diurnal IOP (-2.7 mm Hg, unoprostone; -2.8 mm Hg, brimonidine; -3.1 mm Hg, dorzolamide). The extent of IOP reduction did not differ significantly between unoprostone and either brimonidine (p = 0.154) or dorzolamide (p = 0.101).. Unoprostone was safe and well tolerated and provided a clinically and statistically significant additional reduction in IOP when added to stable monotherapy with timolol. Furthermore, unoprostone was not significantly different from brimonidine and dorzolamide as adjunctive therapy to timolol.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Chemotherapy, Adjuvant; Dinoprost; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Quinoxalines; Sulfonamides; Thiophenes; Timolol

To establish the efficacy and safety of timolol maleate/dorzolamide fixed combination (TDFC) versus timolol maleate/pilocarpine fixed combination (TPFC), each given twice daily, in primary open-angle glaucoma or ocular hypertensive patients.. In this prospective, multicentred, double-masked trial, 37 patients were treated twice daily with timolol for 4 weeks. They were then randomized to one of the treatment medications for 6 weeks, after which they were treated with timolol again for 2 weeks before being placed on the opposite treatment medication for 6 weeks.. A total of 36 patients completed the trial. Their mean baseline intraocular pressure (IOP) was 22.3 +/- 3.7 mmHg. Following 6 weeks of treatment, the mean trough (08.00 hours) IOP was 18.0 +/- 2.2 mmHg for TDFC and 17.4 +/- 2.0 mmHg for TPFC (p = 0.22). The mean diurnal curve IOP was 18.1 +/- 2.2 mmHg for TDFC and 16.7 +/- 1.9 mmHg for TPFC (p = 0.0007). At the remaining time-points (10.00, 18.00 and 20.00 hours), TPFC IOPs were statistically lower than TDFC IOPs (p < 0.03). There were statistically more unsolicited reports of vision change and ocular pain associated with TPFC (p = 0.04). Six patients were discontinued early from TPFC therapy (17%) versus two from TDFC (6%) (p = 0.13).. This study suggests that TPFC can provide at least a similar efficacious reduction in IOP as TDFC in patients with primary open-angle glaucoma or ocular hypertension.

Topics: Antihypertensive Agents; Double-Blind Method; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Pilocarpine; Prospective Studies; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To evaluate the efficacy and safety of commercially available latanoprost 0.005% given every evening versus timolol 0.5% and dorzolamide 2% fixed combination (TDFC) given twice daily to white Greeks with primary open-angle glaucoma and ocular hypertensive patients.. A single-masked, two-center, crossover comparison with two 6-week treatment periods occurring after at least a 3-week medicine-free period. Diurnal curve intraocular pressures were taken at 2:00 AM, 6:00 AM, 10:00 AM, 2:00 PM, 6:00 PM, and 10:00 PM.. Thirty-four subjects with primary open-angle glaucoma or ocular hypertension were enrolled.. Latanoprost 0.005% given every evening and TDFC twice daily.. The primary efficacy variable was diurnal intraocular pressure.. Thirty-three patients completed the study. On the last day of treatment, the mean diurnal intraocular pressure for latanoprost was 15.9 +/- 2.3 mmHg and for TDFC was 15.3 +/- 2.0 mmHg (P = 0.05). Individual time points for intraocular pressure were not statistically different between groups except at the 10:00 PM time point, when the mean for TDFC was 14.6 +/- 2.7 mmHg and for latanoprost was 16.6 +/- 3.1 mmHg (P < 0.006). Eighteen patients overall preferred latanoprost versus 2 patients for the fixed combination, generally because of the greater convenience of once daily dosing. Adverse events were not significantly different between groups except that a bitter taste was found more frequently with TDFC (n = 9) than with latanoprost (n = 0; P = 0.009). Despite screening to exclude intolerance to beta-blockers, a single patient had to discontinue the TDFC because of new-onset asthma.. This study indicates that the 24-hour diurnal intraocular pressure is lowered more, by a small but statistically significant amount, with TDFC compared with latanoprost in primary open-angle glaucoma and ocular hypertensive patients.

Topics: Adult; Antihypertensive Agents; Circadian Rhythm; Cross-Over Studies; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Safety; Single-Blind Method; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To compare the replacement of every drug with latanoprost 0.005% once a day in glaucomatous eyes with poorly controlled intraocular pressure upon combination therapy, versus addition of latanoprost to the pre-existing treatment.. prospective, investigator-masked, two-center, randomized clinical trial lasting 3 months.. open-angle glaucoma; IOP > or = 21 mm Hg upon the combination of a non-selective beta-blocker with pilocarpine or dorzolamide or both; no previous bulbar surgery; and prior glaucoma therapy lasting at least 2 years. Two treatment arms: (1) addition of latanoprost 0.005% QD to the pre-existing therapy [group A]; (2) substitution with latanoprost alone [group B].. One hundred thirty-six eyes (68 eyes/treatment group) were randomized according to intraocular pressure level and the number of adjunctive medications to beta blocker. Both treatments provided a significant IOP decrease over baseline (from 23.5 +/- 1.4 to 19.7 +/- 1.9 mm Hg in group A, (P < 0.001); from 23.2 +/- 1.3 to 20.1 +/- 2.2 mm Hg in group B (P < 0.001), paired Student t test). At the end of the follow-up period, group A showed a higher number of intraocular readings less than or equal to 18 mm Hg than group B (42.6% vs. 30.8%; Fisher exact test: P = 0.018).. In eyes showing an intraocular pressure greater than 21 mm Hg upon combination therapy, the substitution of the pre-existing treatment with latanoprost can provide a significant IOP decrease. However, adding latanoprost to the pre-existing therapy is more likely to achieve a target intraocular pressure less than or equal to 18 mm Hg.

Topics: Adrenergic beta-Antagonists; Aged; Dose-Response Relationship, Drug; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Pilocarpine; Prostaglandins F, Synthetic; Retreatment; Single-Blind Method; Sulfonamides; Thiophenes

The purpose of this prospective, randomized, cross-over study was to investigate and compare the microcirculatory effects of timolol, dorzolamide and latanoprost in newly diagnosed primary open-angle glaucoma (POAG) patients. Haemodynamics were assessed using fluorescein angiography by means of a scanning laser ophthalmoscope (SLO). Visual function and visual field indices were evaluated during all drug treatment phases.. Fourteen patients with newly diagnosed POAG (age 55 +/- 7 years; 10 male, four female) were recruited for the study. At baseline examination, blood pressure, heart rate, intraocular pressure (IOP), SLO angiograms, and contrast sensitivity (CS) were analysed. Patients then randomly received timolol, dorzolamide or latanoprost treatment for 4 weeks. Patients then returned and all procedures were repeated and assessed. Arteriovenous passage times (AVPs), peripapillary arterial and venous diameters were assessed from SLO angiograms, using digital image processing. Calculated ocular perfusion pressure was determined for each treatment phase.. Intraocular pressure was significantly lowered by each drug compared to baseline (p < 0.0001). Arteriovenous passage times were significantly shortened after dorzolamide application compared to baseline (p = 0.009), whereas neither timolol nor latanoprost treatment resulted in significant AVP changes. Peripapillary arterial and venous diameters, systolic and diastolic blood pressure, heart rate and ocular perfusion pressures were not significantly altered during any treatment phase. Contrast sensitivity testing at 6 cycles/degree (c.p.d.) revealed a significant rise after dorzolamide compared to timolol (p = 0.007).. Our results suggest that dorzolamide treatment significantly shortened AVP times in newly diagnosed open-angle glaucoma patients, whereas timolol and latanoprost had no significant effect. Given that prolonged AVP times have been associated with disease progression in glaucoma; dorzolamide treatment may benefit optic nervehead preservation by increasing ocular perfusion.

Topics: Adrenergic beta-Antagonists; Arteries; Blood Pressure; Carbonic Anhydrase Inhibitors; Contrast Sensitivity; Cross-Over Studies; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Microscopy, Confocal; Middle Aged; Ophthalmoscopy; Prostaglandins F, Synthetic; Regional Blood Flow; Retinal Vessels; Sulfonamides; Thiophenes; Timolol; Veins

This was a 6-week, parallel, randomized, double-blind study comparing the efficacy and safety of the 0.5% timolol/2.0% MK-507 combination b.i.d. to the concomitant administration of 0.5% timolol b.i.d. and 2.0% MK-507 b.i.d. Patients with ocular hypertension or open-angle glaucoma from 21 to 85 years of age were enrolled in this study. Each of them should have intraocular pressure (IOP) of 20 mmHg or more in the study eye after they completed the wash-out period. The patients enrolled were randomly assigned to either combination (0.5% timolol/2.0% MK-507 b.i.d. and placebo b.i.d.) or concomitant (0.5% timolol b.i.d. and 2.0% MK-507 b.i.d.) treatment. During the study, no systemic or topical medication affecting IOP other than test drugs were allowed. A total of 20 randomized patients were included in the intention-to-treat population for analysis of data. The ten were assigned to the combination treatment and others were assigned to the concomitant treatment. There was no statistically significant difference between the two study treatments in terms of gender distribution, average age, and average IOP at the trough and the peak before starting the test medications. Mean reduction of the IOP from baseline to the final visit at the trough was 5.04 mmHg in the combination treatment and was 2.73 mmHg in the concomitant treatment. Mean reduction of the IOP at the peak was 2.19 mmHg in the combination treatment and was 2.53 mmHg in the concomitant treatment. There were no statistically significant differences in the above analyses between the two treatments. Safety evaluation was carried out, and number of adverse events in each treatment group did not differ substantially. Ocular signs and symptoms were evaluated in each visit, and all of the between-treatment values were not different significantly, either. Laboratory tests were performed, and showed no significant differences between pre- and post-treatment periods. None of these was found to be clinically serious, either. We concluded that the 0.5% timolol/2.0% MK-507 combination b.i.d. is equivalent in the efficacy of lowering IOP as well as safety compared to the concomitant administration of 0.5% timolol b.i.d. and 2.0% MK-507 b.i.d. in patients with ocular hypertension or open-angle glaucoma.

Topics: Adult; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Statistics, Nonparametric; Sulfonamides; Thiophenes; Timolol

A double-blind, randomised, controlled trial was carried out to evaluate the efficacy and safety of brimonidine, dorzolamide and latanoprost as an adjunctive therapy in patients with primary open angle glaucoma (POAG). A total of 200 males and 72 females with POAG uncontrolled with previous glaucoma therapy were randomly allocated to receive topical brimonidine 0.2% b.d. (n = 90), topical dorzolamide 2% b.d. (n=91) or topical latanoprost 0.005% o.d. (n = 91). One year post treatment, the mean percentage reduction in intraocular pressure (IOP) between the three groups was statistically significant (p < 0.0001). In an intergroup comparison of efficacy, there was a statistically significant difference between the brimonidine and dorzolamide groups (p = 0.018) and between the dorzolamide and latanoprost groups (p = 0.76) but the efficacy of brimonidine was not significantly higher than latanoprost in the brimonidine and latanoprost groups (p = 0.002). Patients experiencing mild to severe side-effects were statistically similar in the three groups. On an inter-drug comparison of side-effects, we found no statistically significant difference in the brimonidine and latanoprost groups (p = 0.25); and the brimonidine and dorzolamide groups (p = 0.067), while the number of side-effects with latanoprost was significantly higher in the dorzolamide and latanoprost groups (p<0.003). All three drugs caused a significant reduction in the mean IOP from pretreatment values. The brimonidine group had a higher number of patients experiencing severe side-effects necessitating alteration of therapy.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Chemotherapy, Adjuvant; Child; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Treatment Outcome

The European Glaucoma Prevention Study seeks to evaluate the efficacy of reducing intraocular pressure (IOP), with dorzolamide to prevent or delay patients affected by ocular hypertension from developing primary open-angle glaucoma.. Randomized, double-blinded, controlled clinical trial.. Patients (age > or =30 years) were enrolled from 18 European centers. The patients fulfilled a series of inclusion criteria including the measurements of IOP (22-29 mmHg), two normal and reliable visual fields (VFs) (on the basis of mean defect and corrected pattern standard deviation/corrected loss of variance of standard 30/II Humphrey or Octopus perimetry), and normal optic disc as determined by the Optic Disc Reading Center (vertical and horizontal cup-to-disc ratios; asymmetry between the two eyes < or =0.4).. Patients were randomized to the treatment with dorzolamide or a placebo.. End points are VF and/or optic disc changes. A VF change during the follow-up must be confirmed by two further positive tests. Optic disc change is defined by the agreement of two out of three independent observers evaluating optic disc stereo-slides.. One thousand seventy-seven subjects were randomized between January 1, 1997 and May 31, 1999. The mean age was 57.03 +/- 10.3 years; 54.41% were women and 99.9% were Caucasian. Mean IOP was 23.6 +/- 1.6 mmHg in both eyes. Mean visual acuity was 0.97 +/- 0.11 in both eyes; mean refraction was 0.23 +/- 1.76 diopters in the right eye and 0.18 +/- 1.79 diopters in the left eye. Previous use of medication for ocular hypertension was reported by 38.4% of the patients, systemic hypertension by 28.1%, cardiovascular diseases by 12.9%, and diabetes mellitus by 4.7%. The qualifying VFs were normal and reliable according to protocol criteria.. The mean IOP of the patients enrolled in the European Glaucoma Prevention Study is consistent with the estimated mean IOP (within the range of 22-29 mmHg) found in a large sample of the European population. The European Glaucoma Prevention Study should be able to better address the clinical question of whether pharmacological reduction of IOP (by means of dorzolamide) in ocular hypertension patients at moderate risk for developing primary open-angle glaucoma effectively lowers the incidence of primary open-angle glaucoma.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Double-Blind Method; Europe; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Research Design; Safety; Sulfonamides; Thiophenes; Visual Acuity; Visual Field Tests; Visual Fields

Topics: Antihypertensive Agents; Brimonidine Tartrate; Circadian Rhythm; Cross-Over Studies; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

To evaluate the ocular hypotensive effect of dorzolamide 2% in primary open-angle glaucoma (POAG) patients with intraocular pressure (IOP) of at least 22 mmHg despite ongoing twice daily treatment with brimonidine 0.2%.. Nineteen eyes of 19 patients with POAG and IOP >or= 22 mmHg, on twice daily brimonidine therapy, were included in the study. Intraocular pressure and adverse effects were recorded on days 2, 7, 14 and 30 after adding dorzolamide three times daily to the treatment.. Mean pretreatment IOP was 27.6 +/- 2.2 mmHg. This decreased to 24.2 +/- 2.2 mmHg after a mean duration of 23.8 +/- 12.1 days. After dorzolamide was added to the treatment, mean IOP was 20.8 +/- 2.3 mmHg on day 2, 19.3 +/- 2.2 mmHg on day 7, 18.0 +/- 2.5 mmHg on day 14 and 17.2 +/- 2.3 mmHg on day 30. The differences between pre- and post-treatment IOP values were statistically significant (p < 0.0001, anova test).. Dorzolamide administered three times daily has significant additive ocular hypotensive effect in POAG patients whose IOP is elevated despite ongoing treatment with brimonidine.

Topics: Adrenergic alpha-Agonists; Adult; Aged; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Drug Evaluation; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Middle Aged; Ophthalmic Solutions; Quinoxalines; Sulfonamides; Thiophenes

To compare the effects on intraocular pressure (IOP) of latanoprost 0.005% and the fixed combination of dorzolamide 2% and timolol 0.5%.. Overall, 226 patients whose IOP was insufficiently controlled by timolol alone were randomized to receive either latanoprost once daily or the fixed combination of dorzolamide plus timolol twice daily. Intraocular pressure was measured at 10:00 am and 5:00 pm at baseline and after 3 months of treatment.. Mean IOP was reduced from baseline in both groups (p < 0.001), with a mean +/- SEM reduction of - 4.3 +/- 0.3 mmHg (19%) for the latanoprost treatment group and - 4.0 +/- 0.3 mmHg (17%) for the dorzolamide plus timolol treatment group. The two therapies were similarly effective in lowering IOP levels (mean difference in reduction: - 0.4 +/- 0.4; 95% confidence interval: - 1.1, 0.4).. Monotherapy with latanoprost once daily was as effective in reducing mean IOP as the fixed combination of dorzolamide plus timolol twice daily in patients with IOP insufficiently controlled by timolol alone.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Treatment Outcome

The aim of this study was to investigate the haemodynamic effects of topical dorzolamide treatment in eyes with newly detected and previously untreated glaucoma.. Forty-seven patients with open angle glaucoma were consecutively randomized to dorzolamide versus placebo TID during a 6-week double-masked treatment trial. Ocular blood flow was investigated at baseline and on therapy using colour Doppler imaging of the retrobulbar vessels and scanning laser ophthalmoscope fluorescein angiograms of the retinal circulation.. None of the flow parameters, retrobulbar or retinal, changed significantly on therapy when the results were analysed with the Bonferroni method. Analysis with non-simultaneous tests also failed to reveal any significant changes either in retrobulbar flow velocities in the central retinal artery, ophthalmic artery or in the short posterior ciliary arteries, or in the retinal parameters (arm-retina time, arteriovenous passage time, mean dye velocity or macular capillary velocity), while capillary velocities at the optic disc decreased significantly in the dorzolamide group (P = 0.03). Intraocular pressure reduction was significantly more pronounced in the dorzolamide group (P = 0.002), with - 4.8 +/- 2.9 mmHg (P < 0.0001) versus -1.8 +/- 3.0 mmHg in the placebo group (P = 0.006).. The present study indicated no measurable vascular effects from topical dorzolamide treatment in previously untreated glaucoma eyes.

Topics: Administration, Topical; Aged; Aged, 80 and over; Blood Flow Velocity; Carbonic Anhydrase Inhibitors; Ciliary Arteries; Double-Blind Method; Eye; Female; Fluorescein Angiography; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Artery; Ophthalmic Solutions; Ophthalmoscopy; Retinal Artery; Sulfonamides; Thiophenes; Ultrasonography, Doppler, Color

Evaluate the safety and efficacy of dorzolamide versus acetazolamide when added to once daily 0.5% timolol maleate ophthalmic gel forming solution (timolol gel).. This was a randomized, double-masked, multicenter, active-controlled, parallel group study of 215 patients with open-angle glaucoma or ocular hypertension. Following a two-week treatment period with timolol gel, patients with IOP > or = 22 mm Hg and who tolerated one week of acetazolamide 250-mg q.i.d. either were randomized to acetazolamide or dorzolamide 2% three times daily for 12 weeks.. In 155 randomized patients (dorzolamide, N = 80, acetazolamide, N = 75), compared to the dorzolamide, acetazolamide had a statistically greater number of systemic adverse events (dorzolamide 50%, acetazolamide 75%, p = 0.001), adverse events associated with carbonic anhydrase inhibitor (CAI) therapy (dorzolamide 26%, acetazolamide 53%, p < 0.001) and discontinuations due to CAI adverse experiences (dorzolamide 8%, acetazolamide 24%, p = 0.007). Intent to treat analysis found that changes from baseline in IOP were similar at both troughs (dorzolamide 1.4 +/- 0.46 mm Hg, acetazolamide 0.8 +/- 0.47 mm Hg, p = 0.386). However, per-protocol analysis found statistically improved pressure control with acetazolamide (0.1 +/- 0.42 mm Hg) compared to dorzolamide (1.9 +/- 0.43 mm Hg) (p = 0.009).. This study found a greater incidence of systemic and CAI adverse experiences and discontinuations due to acetazolamide compared to dorzolamide.

Topics: Acetazolamide; Administration, Oral; Administration, Topical; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Sulfonamides; Thiophenes; Timolol

To compare the effect on intraocular pressure of latanoprost versus timolol plus dorzolamide in open-angle glaucoma.. Thirty-five patients with open-angle glaucoma were randomized, 18 to latanoprost once daily and 17 to timolol plus dorzolamide twice daily. Intraocular pressure and ocular side effects were recorded at baseline, and after 2 weeks and 3 months of treatment.. Latanoprost reduced the intraocular pressure 1.09 and 1.58 mm Hg more than timolol plus dorzolamide after 2 weeks and 3 months of treatment, respectively. These differences were statistically significant (p<0.05) at the end of the study. After 3 months of treatment, 32.3% of the eyes in the latanoprost group reduced the intraocular pressure in 30% or more with respect to baseline, while 15.6% of the eyes in the timolol plus dorzolamide group achieved this reduction.. Latanoprost administered once daily reduced the intraocular pressure at least as well as timolol plus dorzolamide twice daily in patients with open-angle glaucoma.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

It has been shown that oral carbonic anhydrase inhibitors improve visual function in glaucoma. Furthermore topical dorzolamide might improve ocular hemodynamics, as was demonstrated previously. This study was undertaken to evaluate whether topical dorzolamide affects visual function and ocular hemodynamics in glaucoma.. In a retrospective, open clinical trial, dorzolamide eye drops were administered to 28 patients with confirmed primary open angle glaucoma (POAG) in both eyes, 3 times daily for a mean follow up of 9 months. One eye was randomly chosen for evaluation. IOP, blood pressure, heart rate, pulsatile ocular blood flow (POBF) and Humphrey 30-2 visual fields were measured at baseline and after the start of the therapy. POBF was determined by pneumotonography. For statistical analysis the Wilcoxon-matched-paired test and the Bonferoni-Holm adjustment were used.. In dorzolamide-treated patients the IOP dropped from 18 mmHg to 15.5 mmHg after 9 months therapy (p < 0.01) and the visual field improved significantly by 18% (p < 0.05). A statistically significant change was found for POBF from 543 microliters/min to 675 microliters/min (p < 0.05).. The results showed the expected drop in intraocular pressure. Visual function and pulsatile ocular blood flow improved significantly which might be explained by an analogous, vasodilatory effect as was observed in orally applied carbonic anhydrase inhibitors.

Topics: Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Eye; Female; Follow-Up Studies; Glaucoma, Open-Angle; Hemodynamics; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Retrospective Studies; Sulfonamides; Thiophenes; Visual Fields

The aim was to compare topical brinzolamide 1% twice daily with dorzolamide 2% twice daily, each given with timolol 0.5% twice daily, for safety and effects on intraocular pressure in patients with primary open-angle glaucoma or ocular hypertension.. This double-blind, randomized, active controlled, parallel group study was conducted multinationally at 31 sites, in 241 patients as above, with assessments at baseline and monthly during 3 months of treatment. The primary end point was a diurnal reduction of trough/peak intraocular pressure from a timolol 0.5% twice daily baseline.. Both treatment regimens reduced intraocular pressure significantly at all time points (P <.001): brinzolamide plus timolol by -3.6 to -5.3 mm Hg (-14.2 to -21.9%), dorzolamide plus timolol by -3.6 mm Hg to -5.1 mm Hg (-14.1 to -21.2%). Clinically relevant intraocular pressure reductions (decreases 5 mm Hg or greater or absolute intraocular pressure values 21 mm Hg or less) were manifested by 50.0% to 89.3% of patients under brinzolamide plus timolol and by 43.9% to 85.4% under dorzolamide plus timolol. The treatments were equivalent in mean intraocular pressure-lowering. In general, both regimens were well tolerated. However, more patients (P =.001) experienced at least one adverse event with dorzolamide plus timolol (32.8%) as compared with brinzolamide plus timolol (14.7%); also, more patients (P =.001) experienced ocular discomfort (stinging and burning) after dorzolamide plus timolol (13.1%) than after brinzolamide plus timolol (1.7%).. In terms of intraocular pressure reduction, brinzolamide 1% twice daily was equivalent to dorzolamide 2% twice daily, each added to timolol 0.5% twice daily, but brinzolamide produced significantly less ocular burning and stinging.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Aged; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Safety; Sulfonamides; Thiazines; Thiophenes; Timolol; Treatment Outcome

To compare the intraocular pressure-lowering effect of latanoprost with that of dorzolamide when added to timolol.. This randomized, open-label study with two parallel groups was conducted in five centers in Greece. The study enrolled 148 patients with inadequately controlled open-angle or pseudoexfoliation glaucoma (intraocular pressure of at least 22 mm Hg) or ocular hypertension (intraocular pressure of at least 27 mm Hg) who were receiving monotherapy with a beta-blocker or dual therapy in which one of the agents was a beta-blocker. The patients were switched to timolol 0.5% twice daily for 2 to 4 weeks (run-in period) before the start of the study (baseline). At baseline, the patients were randomized to receive latanoprost 0.005% once daily or dorzolamide 2% twice daily as add-on therapy to timolol. The intraocular pressure was recorded at 9:30 AM, 12:30 PM, and 3:30 PM at baseline and at 3 months. Safety was followed throughout the study.. The diurnal intraocular pressure reduction was significant in both groups (P < 0.001). The mean intraocular pressure reduction from baseline was 32% for the latanoprost plus timolol group and 20% for the dorzolamide plus timolol group. The least square estimate of the mean diurnal intraocular pressure reduction after 3 months was -7.06 mm Hg in the latanoprost plus timolol group and -4.44 mm Hg in the dorzolamide plus timolol group (P < 0.001). Drugs administered in both treatment groups were well tolerated.. This study clearly showed that the additive diurnal intraocular pressure-lowering effect of latanoprost is superior to that of dorzolamide in patients treated with timolol.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Greece; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

Addition of dorzolamide to timolol in primary open-angle glaucoma shows augmented reduction of intraocular pressure. It is unknown as yet if addition of dorzolamide will alter hemodynamics.. Fifteen patients with primary open-angle glaucoma were placed on a medication-dependent 1-week to 4-week washout that included maintenance on timolol. After washout, baseline measurements were taken (timolol). They were studied after a month on timolol or dorzolamide-timolol (Cosopt; Merck, Inc, Whitehouse Station, New Jersey), with the second drug preceded by another month of timolol maintenance and second baseline measurements. At each visit, visual function, intraocular pressure, and ocular hemodynamics were monitored, including indocyanine green and fluorescein angiography and color Doppler imaging.. Cosopt significantly reduced intraocular pressure (14.7 to 13.4 mm Hg, P <.05) and increased arteriovenous passage time (superior temporal artery) of fluorescein dye (2.13 to 1.76 seconds, P =.01) but had no effect on visual function.. When compared with timolol in primary open-angle glaucoma, Cosopt augments ocular tension reduction and reduces the amount of time required for blood to pass through the superior retinal vasculature.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Blood Flow Velocity; Ciliary Arteries; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Eye; Fluorescein Angiography; Glaucoma, Open-Angle; Humans; Indocyanine Green; Intraocular Pressure; Laser-Doppler Flowmetry; Ophthalmic Artery; Ophthalmic Solutions; Ophthalmoscopy; Regional Blood Flow; Retinal Artery; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Ultrasonography; Visual Acuity

To investigate the clinical characteristics of docosanoid derivative, isopropyl unoprostone in the treatment of primary open angle glaucoma (POAG).. In 17 patients (22 eyes) with POAG we analysed prospectively the effect of Rescula upon intraocular pressure, aqueous flare, pupil size, ocular signs and symptoms. Patients were followed up every 2 weeks for at least 8 weeks with complete ocular examination. Concomitant topical therapeutics were used in the study: 0.5% Timolol--group I (16 eyes), and 0.5% Timolol + 2% Dorzolamide--group II (6 eyes).. Mean (+/- SD) pretreatment pressure was 24.7 +/- 4.3 mm Hg in group I and it was reduced by 3.7 mm Hg (13.5%) (p < 0.05) at the end of the follow up. In group I Rescula was very effective (delta T% > 25%) in 6/16 eyes (37.5%) and it was ineffective (delta T% < 10%) in the same number of eyes. In group II pretreatment pressure was 24.8 +/- 2.6 mm Hg and it was reduced by 2.6 mm Hg (10.6%) (p = 0.1). Rescula induced no elevation of the aqueous flare during the treatment. No effect on pupil size was observed, either. Eye stinging/conjunctival hyperaemia was noted in 2/17 patients and punctate epitheliopathy in 1 patient (5.9%) that caused discontinuation of drops.. Unoprostone produced significant additive effect to Timolol. Thus, it may be a valuable option for adjunctive therapy. However, interindividual differences need to be considered, as in some patients the response was insignificant.

Topics: Administration, Topical; Antihypertensive Agents; Dinoprost; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Timolol

To evaluate the relationship between the circadian blood pressure rhythm and the retrobulbar blood flow in glaucoma patients.. Cross-sectional study.. Circadian blood pressure measurements and color Doppler imaging (CDI) in the ophthalmic artery as well as the central retinal artery of one randomly selected eye were obtained in 193 primary open-angle glaucoma patients. CDI parameters were compared by means of analysis of covariance between patients with a nocturnal decrease in mean systemic blood pressure (MBP) below 20% of the average daytime MBP (over-dippers), patients with a decrease between 10% to 20% (dippers), and patients with a decrease of less than 10% (nondippers), using age, intraocular pressure (IOP), and MBP during color Doppler measurement as covariates.. An analysis of covariance disclosed, after correcting for age, IOP, and MBP during color Doppler imaging, a significantly lower EDV (P =.0096) and a significantly higher RI (P =.033) in the central artery of over-dipping glaucoma patients compared with nondippers or dippers. This effect seemed independent of the use of vasoactive drugs .. Glaucoma patients with a marked drop in nocturnal systemic blood pressure seem to have altered retrobulbar blood flow parameters, suggesting that an abnormal systemic blood pressure profile may be the manifestation of some kind of systemic vascular dysregulation relevant for the ocular circulation.

Topics: Adrenergic beta-Antagonists; Aged; Blood Flow Velocity; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Carbonic Anhydrase Inhibitors; Circadian Rhythm; Cross-Sectional Studies; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Laser-Doppler Flowmetry; Male; Middle Aged; Ophthalmic Artery; Retinal Artery; Sulfonamides; Thiophenes; Ultrasonography, Doppler, Color

The purpose of the study was to compare the effects on intraocular pressure (IOP) of adding dorzolamide to timolol or of switching from timolol to latanoprost monotherapy in glaucoma patients inadequately controlled on timolol.. The study was designed as a 3-month randomised, open-label, multicentre study comprising 183 patients with primary open-angle glaucoma, capsular glaucoma with IOP above 22 mmHg on treatment with one or two ocular hypotensive drugs, or ocular hypertension with IOP above 27 mmHg. After a 2- to 4-week run-in period on timolol, 0.5% twice daily, the patients were randomised to treatment with either latanoprost, 0. 005% once daily, or the combination of timolol, 0.5% twice daily, and dorzolamide, 2% twice daily. The mean diurnal IOP after 3 months of treatment was compared with baseline.. Switching from timolol to latanoprost reduced mean diurnal IOP by 4.5+/-0.2 mmHg (mean+/-SEM, ANCOVA; 20%), and adding dorzolamide to timolol reduced mean diurnal by 4.4+/-0.2 mmHg (mean+/-SEM, ANCOVA; 20%). No serious side effects were observed with either treatment.. Latanoprost monotherapy can be an alternative to combined treatment with two aqueous flow suppressors in patients whose IOP is insufficiently controlled by timolol alone.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Circadian Rhythm; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

A randomized, multicenter, double-masked, prospective, parallel study was designed to establish the intraocular pressure (IOP)-lowering efficacy, safety, and tolerability of brinzolamide 1.0% (Azopt) as a primary therapy compared with dorzolamide 2.0% (Trusopt) and placebo in patients diagnosed with open-angle glaucoma (with or without a pseudoexfoliative or a pigmentary dispersion component) or ocular hypertension. Brinzolamide 1.0%, dosed two times (b.i.d.) and three times (t.i.d.) a day, dorzolamide 2.0% (t.i.d.), and placebo (t.i.d) were administered to patients during a 3-month treatment period. Diurnally corrected IOP reduction from baseline, including peak and trough times, was the primary end point. Sample sizes were chosen to establish statistical equivalence between treatments. Mean IOP changes observed on treatment were as follows: -3.4 mm Hg (-13.2%) to -4.1 mm Hg (-16.7%) with brinzolamide 1.0% b.i.d.; -4.1 mm Hg (-16.6%) to -4.8 mm Hg (-19.1%) with brinzolamide 1% t.i.d.; and -4.3 mm Hg (-16.9%) to -4.9 mm Hg (-20.1%) with dorzolamide 2.0%. IOP reductions after administration of brinzolamide 1.0% b.i.d. and t.i.d. were equivalent to each other and also clinically and statistically equivalent to those with dorzolamide 2.0% t.i.d. The incidence of ocular discomfort (burning and stinging) upon instillation was significantly higher for dorzolamide (10.7%) than brinzolamide (b.i.d. or t.i.d., 3.0% each). The most frequent non-ocular event reported was taste perversion, which was less (3.7%) with brinzolamide 1.0% b.i.d., but brinzolamide t.i.d. was similar to dorzolamide t.i.d. (6.8% vs. 5.3%). Brinzolamide 1.0% b.i.d., brinzolamide 1.0% t.i.d., and dorzolamide 2.0% t.i.d. equaled each other in IOP-lowering efficacy, and brinzolamide was significantly more comfortable than dorzolamide upon instillation.

Topics: Adult; Aged; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Hypersensitivity; Female; Glaucoma, Open-Angle; Humans; Incidence; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Safety; Sulfonamides; Suspensions; Thiazines; Thiophenes; Treatment Outcome

Two independent, prospective, multicenter, double-masked, parallel group trials were conducted to compare the ocular comfort of brinzolamide 1.0% administered three times daily (t.i.d.) with t.i.d.-dosed dorzolamide 2.0% in patients with primary open-angle glaucoma or ocular hypertension. Patients were randomized to one of two treatment groups, receiving either brinzolamide 1.0% t.i.d. or dorzolamide 2.0% t.i.d. for 1 week. On the last day of dosing, patients received one drop of masked medication in both eyes, and ocular discomfort (burning or stinging) was evaluated by means of a 4-unit ocular discomfort scale. The incidence and extent of ocular discomfort across both treatment groups were analyzed. The results from both studies were confirmatory and demonstrated that the ocular discomfort score for brinzolamide 1.0% was 1.3 units lower than the score for dorzolamide 2.0%, which was both statistically significant and clinically relevant. In addition, a statistically significantly greater percentage of patients reported no ocular discomfort with brinzolamide 1.0% compared with dorzolamide. A greater percentage of patients receiving dorzolamide 2.0% also reported mild, moderate, severe, and very severe ocular discomfort compared with those treated with brinzolamide 1.0%. The most frequent ocular adverse event reported in the brinzolamide group was transient blurred vision, which ranged from 20% to 25%. Overall, adverse events associated with brinzolamide 1.0% and dorzolamide 2.0% were nonserious, were usually mild, and resolved without treatment. The findings of each study independently demonstrated that brinzolamide 1.0% was significantly more comfortable than dorzolamide 2.0% when instilled in the eye.

Topics: Adult; Carbonic Anhydrase Inhibitors; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Patient Satisfaction; Prospective Studies; Sulfonamides; Suspensions; Thiazines; Thiophenes; Treatment Outcome

To determine whether dosages of a selective beta-blocking agent (betaxolol) and a topical carbonic anhydrase inhibitor (dorzolamide), sufficient to significantly lower intraocular pressure (IOP), have similar or disparate impact on the retinal and retrobulbar circulation.. Counterbalanced crossover, with open-label use of medications.. Nine persons with normal-tension glaucoma (NTG).. After a 3-week drug washout, NTG patients were studied after 1 month of treatment with either dorzolamide or betaxolol, with determinations of IOP and retinal and retrobulbar hemodynamics.. At baseline and after treatment with each drug, retinal arteriovenous passage time was determined by scanning laser ophthalmoscopy after fluorescein dye injection, and flow velocities in the central retinal and ophthalmic arteries were measured with color Doppler ultrasonography imaging.. Betaxolol and dorzolamide each lowered IOP significantly, with these changes apparent and maximal after 2 weeks (each P < 0.05). In contrast, dorzolamide (but not betaxolol) accelerated arteriovenous passage of fluorescein dye in the inferior temporal quadrant of the retina (P < 0.05). Neither drug affected arteriovenous passage in the superotemporal retina or any aspect of central retinal or ophthalmic artery flow velocity after either 2 or 4 weeks.. Although both dorzolamide and betaxolol are effective ocular hypotensive agents and their topical instillation leaves retrobulbar hemodynamics unaltered, dorzolamide alone accelerates inferotemporal retinal dye transit.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Betaxolol; Blood Flow Velocity; Carbonic Anhydrase Inhibitors; Cross-Over Studies; Female; Fluorescein; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Artery; Ophthalmic Solutions; Retinal Artery; Sulfonamides; Thiophenes; Ultrasonography, Doppler, Color

To determine the efficacy and safety of adding dorzolamide 2% twice daily to timolol maleate solution 0.5% twice daily when treating exfoliation glaucoma or primary open-angle glaucoma.. This was a single-centre, crossover intra-individually controlled comparison. Sixty-two consecutive patients (31 with exfoliation glaucoma and 31 with primary open angle glaucoma) chronically treated with timolol maleate twice daily were included in this trial. Patients then had added dorzolamide 2% twice daily (08:00 and 20:00), instilled approximately 10 min after timolol maleate. Patients underwent diurnal intraocular pressure (IOP) testing (six measurements over 24 h), first on timolol maleate monotherapy and 2 months later following the addition of dorzolamide 2% as adjunctive therapy.. On timolol monotherapy patients with exfoliation glaucoma had a higher mean IOP at 02:00, 06:00, 10:00, 14:00 and 22:00 hour time points as well as a higher maximum, minimum and range of IOP throughout the day compared with the primary open-angle glaucoma group (p < 0.05). Following the addition of dorzolamide as adjunctive therapy to timolol maleate there was a significant reduction in IOP (p < 0.05) at all time points in both glaucomas, but mean IOP at 10:00, 14:00, 18:00 and 22:00 hour time points, as well as the peak and range of IOP, remained higher in the exfoliation glaucoma group. No serious adverse events were noted with dorzolamide. Bitter taste, the most common symptom, was noted in 30% of patients.. These data suggest that dorzolamide 2% used adjunctively with timolol maleate 0.5% solution is effective in reducing diurnal IOP in patients with primary open-angle and exfoliation glaucoma but does not alter the characteristics of higher IOP levels in the latter disease.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Circadian Rhythm; Cross-Over Studies; Drug Therapy, Combination; Exfoliation Syndrome; Female; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Prospective Studies; Sulfonamides; Thiophenes; Timolol

To study the additive effect of latanoprost 0.005% in patients who have uncontrolled intraocular pressure (IOP) using timolol 0.5% and dorzolamide 2%.. Fifty-two consecutive patients with open-angle glaucoma who were using timolol and dorzolamide and were considered to have IOP above their defined target pressure were included in this study. After a baseline diurnal tension curve (DTC) was performed, latanoprost once a day was added to the treatment, and a second DTC was performed 1 week later.. Five patients (9.6%) were discontinued from treatment because of side effects. The remaining 47 patients showed a significant IOP reduction of 3.1 mm Hg (16%) from a baseline of 19.3 mm Hg (mean IOP registered during DTC; P < or = 0.0001). Seventeen patients (36.3%) showed a mean IOP reduction greater than 20%.. Latanoprost had an additive effect when used as a third drug for patients on timolol and dorzolamide who were in need of further IOP reduction. These results suggest that latanoprost may be very effective in some patients with poorly controlled glaucoma on multiple therapy.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Circadian Rhythm; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

This study compared brimonidine with latanoprost as adjunctive therapy for the treatment of open-angle glaucoma and ocular hypertension.. Patients with open-angle glaucoma or ocular hypertension often require >1 medication to achieve control of intraocular pressure (IOP). Both brimonidine and latanoprost effectively lower IOP, but no previously reported clinical trials have directly compared these agents as adjunctive therapy.. This was a prospective, randomized, investigator-masked, multicenter, parallel-design clinical trial. Forty patients (69 study eyes) with uncontrolled IOP of < or =34 mm Hg while using a topical beta-blocker plus dorzolamide or pilocarpine were randomly assigned to receive either brimonidine 0.2% BID or latanoprost 0.005% QD over 6 months as adjunctive therapy. Tolerability was assessed by reports of adverse events, and efficacy was determined by reduction in IOP from baseline. Clinical success was defined as the achievement of a > or =15% reduction in IOP from baseline.. There were no significant between-group differences in any demographic variable. Most patients in each group were white, had open-angle glaucoma, and were being treated with a nonselective beta-blocker and dorzolamide. When brimonidine or latanoprost was used as an adjunctive agent with a beta-blocker and dorzolamide or pilocarpine, the rates of clinical success at month 1 were 85% (17/20 patients) with brimonidine versus 65% (13/20 patients) with latanoprost (P = 0.144). Overall mean IOP reduction at month 1 was 4.60+/-0.62 mm Hg (22.8%; P < 0.001) with brimonidine and 3.43+/-0.62 mm Hg (17.2%; P < 0.001) with latanoprost, with no significant differences between groups (P = 0.219). Among the patients with an inadequate IOP-lowering response (<15% reduction from baseline), the mean IOP reduction was 0.36+/-0.66 mm Hg with latanoprost (n = 7) and 0.50+/-2.18 mm Hg with brimonidine (n = 3). Brimonidine and latanoprost had comparable IOP-lowering efficacy in patients receiving concomitant pilocarpine therapy (mean change in IOP of -4.23 mm Hg vs -3.75 mm Hg, P = 0.173). In patients concurrently treated with dorzolamide, brimonidine produced a mean change in IOP of -5.29 mm Hg, compared with a mean change of -3.21 mm Hg in the latanoprost group (P = 0.159). Both brimonidine and latanoprost were well tolerated. Few adverse events leading to discontinuation were observed with either drug regimen (n = 2 with brimonidine; n = 0 with latanoprost).. Both brimonidine 0.2% BID and latanoprost 0.005% QD were well-tolerated and reduced IOP in most patients when used as third-line adjunctive therapy. However, clinical success was achieved by 17 of 20 patients (85%) who received brimonidine, compared with 13 of 20 patients (65%) who received latanoprost (P = 0.144). These results suggest that brimonidine 0.2% BID may be more reliable than latanoprost 0.005% QD as adjunctive therapy for glaucoma and ocular hypertension.

Topics: Aged; Antihypertensive Agents; Brimonidine Tartrate; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Miotics; Ocular Hypertension; Pilocarpine; Prospective Studies; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Treatment Outcome

To compare the effects on intraocular pressure (IOP) and side effects of monotherapy with either latanoprost or dorzolamide in patients with glaucoma or ocular hypertension.. 224 patients with open angle glaucoma or ocular hypertension were recruited to a 3 month open labelled study. Previous glaucoma medications were washed out and the patients were randomised to receive either latanoprost 0.005% once daily or dorzolamide 2% three times daily.. Of 224 patients 213 were included in the analysis of efficacy. After 3 months, latanoprost reduced mean baseline diurnal IOP from 27.2 (SD 3.0) mm Hg by 8.5 (3.3) mm Hg. The corresponding figures for dorzolamide were 27.2 (3.4) and 5.6 (2.6) mm Hg. The difference of 2.9 mm Hg (95% CI: 2.3-3.6) was highly significant (p<0.001, ANCOVA). Latanoprost reduced IOP at peak by 8.6 mm Hg (32%) compared with 6.2 mm Hg (23%) for dorzolamide, and the difference of 2.4 mm Hg was significant (p<0.001, ANCOVA). The corresponding figures at trough were 8.1 mm Hg (31%) for latanoprost and 4.7 mm Hg (17%) for dorzolamide, a significant difference of 3.4 mm Hg (p<0.001, ANCOVA). Both drugs were well tolerated systemically and locally.. Latanoprost was superior to dorzolamide in reducing the IOP, judged both from the effect on IOP at peak and trough and by the effect on diurnal IOP.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Antihypertensive Agents; Circadian Rhythm; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes

To assess the acute intraocular hypotensive efficacy of brimonidine tartrate 0.2% (a highly selective alpha2-adrenergic agonist) compared with dorzolamide 2% (a topical carbonic anhydrase inhibitor) as adjunct therapy to topical beta-blockers in patients with primary open-angle glaucoma.. A randomized cross-over masked study was performed. We enrolled one eye of each of 28 patients who were on different beta-blocker therapy. We measured the intraocular pressure (IOP) 2 h after the beta-blocker instillation; we then randomly administered one of the two drugs and we compiled an IOP diurnal curve. One month later we repeated the same procedures with the second drug. Unpaired Mann-Whitney U-test was used to compare decreases in IOP between the two drugs (P<0.05).. Both brimonidine 0.2% and dorzolamide 2% have good ocular hypotensive efficacy, significantly lowering IOP when compared to beta-blocker therapy alone, for the whole diurnal curve. Maximum mean percent IOP decrease from baseline was 22.0+/-15.7% (4.0+/-2.9 mmHg) for dorzolamide 2% 6 h after instillation and 35.5+/-16.4% (7.0+/-4.1 mmHg) for brimonidine 0.2% 8 h after administration of the drug. When we compared the two treatments, brimonidine 0.2% showed a higher hypotensive effect than 2% dorzolamide after 4 h (28.4+/-16.8% vs 17.6 +/-9.3%; P=0.04) and 8 h (35.5+/-16.4% vs 21.6 +/-10.8%; P=0.04).. This study indicates that 0.2% brimonidine acutely associated with beta-blockers is an interesting new combination treatment useful in the management of glaucoma.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Quinoxalines; Sulfonamides; Thiophenes; Tonometry, Ocular; Treatment Outcome

To evaluate the efficacy and safety of brimonidine compared with dorzolamide given three times daily as monotherapy in patients with primary open-angle glaucoma or ocular hypertension.. In a double-masked, multicenter, crossover comparison in 40 patients, qualified patients were washed out from their previous medication and randomized to dorzolamide 2% or brimonidine 0.2% for the first 6-week treatment period. Patients then were washed out for 2 weeks and started on the opposite medication for the second 6-week period.. Baseline intraocular pressure for all 40 subjects (76 eyes) was 24.1 +/- 2.0 mm Hg. This study found that the 8:00 AM trough intraocular pressure after 6 weeks of therapy for dorzolamide was 20. 7 +/- 3.1 mm Hg and for brimonidine 20.8 +/- 3.2 mm Hg (P =.99). The peak intraocular pressure (2 hours after dosing) for dorzolamide was 18.6 +/- 3.4 mm Hg and for brimonidine 17.8 +/- 2.7 mm Hg (P =.10 ). Dorzolamide caused more stinging upon instillation (P <.01) and brimonidine more itching (P =.01). No statistical differences existed between groups for systemic adverse events. Six patients, all on brimonidine, were discontinued from a treatment period early. Of these, two were discontinued for inadequate pressure control, two with dizziness and fatigue, one with ocular pain, and one for lifestyle reasons (P =.07).. This study found similar efficacy and safety between monotherapy treatment with dorzolamide or brimonidine when each was given three times daily to patients with ocular hypertension or primary open-angle glaucoma.

Topics: Adrenergic alpha-Agonists; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Cross-Over Studies; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Quinoxalines; Safety; Sulfonamides; Thiophenes; Treatment Outcome

To compare the around-the-clock intraocular pressure (IOP) reduction induced by timolol 0.5%, latanoprost 0.005%, and dorzolamide in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).. In this crossover trial, 20 patients with POAG (n = 10) or OHT (n = 10) were treated with timolol, latanoprost, and dorzolamide for 1 month. The treatment sequence was randomized. All patients underwent measurements for four 24-hour tonometric curves: at baseline and after each 1-month period of treatment. The patients were admitted to the hospital, and IOP was measured by two well-trained evaluators masked to treatment assignment. Measurements were taken at 3, 6, and 9 AM and noon and at 3, 6, and 9 PM and midnight by handheld electronic tonometer (TonoPen XL; Bio-Rad, Glendale, CA) with the patient supine and sitting, and a Goldmann applanation tonometer (Haag-Streit, Bern, Switzerland) with the patient sitting at the slit lamp. Systemic blood pressure was recorded at the same times. The between-group differences were tested for significance by means of parametric analysis of variance. The circadian IOP curve of a small group of untreated healthy young subjects was also recorded using the same procedures. To compare the circadian IOP rhythms in the POAG-OHT and control groups, the acrophases for each subject were calculated.. When Goldmann sitting values were considered, all the drugs significantly reduced IOP in comparison with baseline at all times, except for timolol at 3 AM. Latanoprost was more effective in lowering IOP than timolol at 3, 6, and 9 AM (P = 0.03), noon (P = 0.01), 9 PM, and midnight (P = 0.05) and was more effective than dorzolamide at 9 AM, noon (P = 0.03), and 3 and 6 PM (P = 0.04). Timolol was more effective than dorzolamide at 3 PM (P = 0.05), whereas dorzolamide performed better than timolol at midnight and 3 AM (P = 0.05). An ancillary finding of this study was that in the group of healthy subjects, the pattern of IOP curve was different that in patients with eye disease.. Latanoprost seemed to lead to a fairly uniform circadian reduction in IOP, whereas timolol seemed to be less effective during the nighttime hours. Dorzolamide was less effective than latanoprost but led to a significant reduction in nocturnal IOP. The reason for the difference in the pattern of the IOP curve of healthy subjects is currently unknown and deserves further investigation.

Topics: Aged; Antihypertensive Agents; Circadian Rhythm; Cross-Over Studies; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

Topics: Adrenergic beta-Antagonists; Aged; Carbonic Anhydrase Inhibitors; Drug Evaluation; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Therapeutic Equivalency; Thiophenes; Timolol

Topics: Administration, Topical; Adrenergic beta-Antagonists; Carbonic Anhydrase Inhibitors; Drug Evaluation; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Laser-Doppler Flowmetry; Ophthalmic Solutions; Retinal Vessels; Sulfonamides; Thiophenes; Timolol

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

Many patients with glaucoma or ocular hypertension initially receive beta-blocker monotherapy to control intraocular pressure (IOP), but some of these patients will require an additional IOP-lowering agent within 1 year. This active-controlled, double-masked, randomized, multicenter, 12-week study compared the effectiveness and tolerability of dorzolamide hydrochloride ophthalmic solution 2% TID with those of pilocarpine hydrochloride 2% QID as adjunctive therapy to timolol maleate ophthalmic gel-forming solution (TG) 0.5% QD as measured by changes in IOP and occurrence of adverse events. One hundred ninety-four patients with open-angle glaucoma or ocular hypertension participated in this study. Their mean age was approximately 63 years. Slightly more than one half were white, and approximately one third were black. After a 3-week run-in period during which all patients received TG 0.5% QD, patients with an IOP of > or = 22 mm Hg at the morning trough measurement were randomly assigned to receive additional double-masked therapy with either dorzolamide or pilocarpine. The primary outcome measure was the mean change in IOP at the morning trough measurement from baseline to week 12. The secondary outcome measure was the mean change in IOP at the morning peak measurement from baseline to week 12. There was no significant difference in IOP-lowering effect between the 2 drugs at either morning trough or morning peak. The mean change in IOP at morning trough was -3.17 mm Hg (-12%) in patients receiving dorzolamide; it was -3.45 mm Hg (-13%) in patients receiving pilocarpine. The mean change in IOP at morning peak was -2.25 mm Hg (-10%) for patients who received dorzolamide and -2.51 mm Hg (-11%) for those who received pilocarpine. In the pilocarpine group, 62 (63%) patients experienced > or =1 adverse event compared with 35 (36%) patients in the dorzolamide group (P < 0.001). Twenty-one (21%) patients in the pilocarpine group discontinued treatment because of an adverse event compared with 2 (2%) patients in the dorzolamide group (P < 0.001). These results demonstrate that dorzolamide and pilocarpine were equally effective as adjunctive therapy in lowering IOP but that dorzolamide was better tolerated.

Topics: Adjuvants, Pharmaceutic; Carbonic Anhydrase Inhibitors; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Ocular Hypertension; Parasympathomimetics; Patient Dropouts; Pilocarpine; Sulfonamides; Thiophenes; Time Factors; Timolol; Treatment Outcome

To compare the 2.0% dorzolamide/0.5% timolol fixed combination (COSOPT; Merck & Co., Whitehouse Station, NJ) to 0.5% timolol plus 2.0% pilocarpine given concomitantly, and to determine patient preference, tolerability, and impact on daily life in patients with elevated intraocular pressure (IOP).. Two multi-center, randomized, cross-over, observer masked studies were conducted, one in the United States (97 patients) and one in Europe (93 patients). The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference and perception of side effects and activity limitations resulting from study medications. Intraocular pressure was measured before and 2 hours after the morning dose of study medication (hour 0 and hour 2).. In both studies, among patients with a preference, the combination was preterred to timolol plus pilocarpine by a ratio of 4 to 1. The most commonly cited reason for this preference was side effects. Patients in both studies also reported that the combination interfered significantly less with daily life in terms of side effects and activity limitations. They also reported missing significantly fewer doses of study medication while taking the combination and being significantly more satisfied with it. The efficacy of these two treatments was not significantly different, based on IOP measurements at hour 0 and 2 hours after administration. Patients reported significantly more adverse events while receiving timolol plus pilocarpine in both studies, and in the U.S. study, significantly more patients discontinued therapy while receiving timolol plus pilocarpine than while receiving the combination.. Compared with timolol plus pilocarpine, patients preferred the combination of 2% dorzolamide/0.5% timolol, and reported less interference in daily activities, better tolerability, and better compliance with therapy.

Topics: Activities of Daily Living; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Miotics; Ocular Hypertension; Ophthalmic Solutions; Patient Satisfaction; Pilocarpine; Sulfonamides; Surveys and Questionnaires; Thiophenes; Timolol

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

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Safety; Sulfonamides; Thiophenes; Timolol

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

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Safety; Sulfonamides; Thiophenes; Timolol; Visual Acuity; Visual Fields

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

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Safety; Sulfonamides; Thiophenes; Timolol

Beyond intraocular pressure (IOP, German abbreviation: IOD) ocular perfusion is increasingly discussed in the pathogenesis of the glaucomas. The present study was designed to investigate for ocular pulse amplitude (OPA) in primary open angle glaucoma patients with elevated intraocular pressure (POAG, German abbreviation: POWG) following application of timolol, a beta-blocker and dorzolamide a topical carbonic anhydrase inhibitor.. OPA (Ocular Blood Flow System, OBF Labs U.K.) IOP, heart rate, systolic and diastolic brachial artery pressures were measured before and 4 weeks following application of timolol and additional 4 weeks following application of a timolol/dorzolamide combination in 14 POAG patients.. Following administration of timolol, IOP was highly significantly reduced in drug treated POAG eyes; this effect was additively enhanced by dorzolamide. Timolol did not affect OPA, whereas dorzolamide significantly increased OPA in drug treated POAG eyes. Systemic perfusion parameters were unchanged.. Timolol and dorzolamide drastically reduced IOP, in addition dorzolamide increased OPA in POAG, an ocular microcirculatory effect which may further help to improve prognosis of POAG.

Topics: Adrenergic beta-Antagonists; Aged; Blood Pressure; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Eye; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Pulsatile Flow; Sulfonamides; Thiophenes; Timolol

To analyze the hypotensive effect and ocular tolerance produced by the association of a topic carbonic anhidraze inhibitor (dorzolamide--Trusopt) and a prostaglandin derivative (latanoprost--Xalatan) in the treatment of the hypertensive glaucomas.. The study includes two steps: STEP I: A double-blind randomized prospective study which includes 32 eyes with primary open angle glaucoma, divided in two groups: group A, in which Trusopt is administrated for 7 days and then Xalatan is associated for another 7 days and group B, in which the order is reversed: for the first 7 days only Xalatan is administrated and then for another 7 days, Trusopt is associated in the treatment. The intraocular pressure and the secondary effects were assessed daily. STEP II: An open clinical trial that includes 47 eyes with different types of glaucomas in which the combination Trusopt + Xalatan was used for 90 days. The intraocular pressure and the secondary effects were assessed weekly.. In the first study (step I) the combination Trusopt + Xalatan induces an additive type of ocular hypotensive effect which is not depend by the order of the two drugs used in the beginning of the treatment (37.49% for group A and 39.16% for group B); In the clinical trial for medium term (step II), the combination Trusopt + Xalatan results in a decrease of IOP, which varies between 27.94% and 37.02% and was stable on the whole period of the study; We observed the following secondary effects: conjunctival hyperemia (6 cases), burning sensation (3 cases), foreign body sensation (1 case), itching (2 cases) and hazing (1 case).. The association Trusopt + Xalatan results in an additive ocular hypotensive effect which was stable on the whole period of the study (medium term); The ocular tolerance of this combination is good and was not followed by the interruption of the treatment.

Topics: Aged; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes

The study aimed to determine whether topical dorzolamide and systemic acetazolamide have an additive effect on intraocular pressure (IOP) and aqueous humor formation (AHF).. This was a prospective, open-label, two-protocol clinical study.. Sixteen patients with ocular hypertension or with primary open-angle glaucoma were studied.. Baseline AHF was measured by computerized fluorophotometry and IOP by pneumatonometry without antiglaucoma therapy. In the first protocol, dorzolamide was randomized to one eye (N = 10) and IOP and AHF measurements were repeated. One week later, having used dorzolamide in one eye three times daily, patients had measurements performed before and after the single administration of oral acetazolamide 250 mg. In the second protocol, having used acetazolamide 250 mg four times daily for 4 to 7 days (N = 6), patients had measurements performed before and after a single drop of dorzolamide was instilled randomly into one eye. The patient continued acetazolamide and unilateral dorzolamide for 4 to 7 more days and returned for IOP and AHF measurements.. Intraocular pressure and AHF were measured in treated and contralateral control eyes.. In the first protocol, IOP (mmHg +/- standard deviation) was significantly (P = 0.02) lower in the dorzolamide (16.3 +/- 2.6) than in the contralateral control (19.9 +/- 2.9) eyes. Aqueous humor formation (microliter/minute +/- standard deviation) also was lower (P = 0.02) in dorzolamide eyes (1.79 +/- 0.4 vs. 2.33 +/- 0.5). After oral acetazolamide 250 mg, IOP was unchanged in dorzolamide eyes (17.6 +/- 2.0 preacetazolamide vs. 17.9 +/- 2.0 postacetazolamide), whereas it was reduced (P = 0.003) in control eyes (20.5 +/- 2.2 preacetazolamide vs. 16.9 +/- 2.3 postacetazolamide). Aqueous humor formation was reduced in control eyes (2.31 +/- 0.8 preacetazolamide vs. 1.73 +/- 0.6 postacetazolamide; P = 0.005) but not in dorzolamide-treated eyes (1.56 +/- 0.45 preacetazolamide vs. 1.77 +/- 0.39 postacetazolamide). In the second protocol, acetazolamide 250 mg four times daily symmetrically reduced IOP and AHF in both eyes. After single-drop dorzolamide in one eye, IOP and AHF did not change significantly. After 4 to 7 days of acetazolamide and unilateral dorzolamide, IOP and AHF remained reduced to a similar level in dorzolamide and control eyes not receiving topical therapy.. Topical dorzolamide and oral acetazolamide, in the concentrations and doses used in this study, are not additive. Either drug alone results in maximum reduction in IOP and AHF. Concomitant glaucoma therapy of a topical and systemic carbonic anhydrase inhibitor is not warranted.

Topics: Acetazolamide; Administration, Oral; Administration, Topical; Adult; Aqueous Humor; Carbonic Anhydrase Inhibitors; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Fluorophotometry; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Tonometry, Ocular

A multicenter, 4-week, two-period crossover study, comparing 2% dorzolamide three times daily to 2% pilocarpine four times daily as adjunctive therapy to 0.5% timolol twice daily, was conducted on 81 patients with elevated intraocular pressure (IOP). The treatments were evaluated for patient preference, tolerability, impact on daily life, IOP control, and visual-field changes.. The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference, as well as the perception of side effects and activity limitations resulting from the study medications. IOP measurements and visual-field examinations were obtained at baseline and at the end of each crossover period.. Of the 77 patients who participated in both periods, 63 (82%) preferred dorzolamide. Patients who expressed a preference preferred dorzolamide over pilocarpine by a ratio of more than 10:1. Patients reported less interference with their daily life because of side effects and activity limitations while receiving dorzolamide than while receiving pilocarpine. Dorzolamide and pilocarpine were comparably effective in lowering IOP (16% to 17%). Also, significantly more patients reported adverse experiences and discontinued therapy as a result of adverse experiences while receiving pilocarpine than while receiving dorzolamide.. The results of this multicenter study support those of two previous single-center studies; these results show that dorzolamide was greatly preferred over pilocarpine and had better tolerability and less adverse impact on patients' daily lives than pilocarpine.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Chemotherapy, Adjuvant; Cross-Over Studies; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Miotics; Ocular Hypertension; Ophthalmic Solutions; Patient Satisfaction; Pilocarpine; Quality of Life; Sulfonamides; Thiophenes; Timolol; Visual Fields

To compare the long-term effects of dorzolamide hydrochloride (Trusopt, Merck and Co Inc, White-house Station, NJ), timolol maleate, and betaxolol hydrochloride on corneal endothelial cell density and corneal thickness.. This 1-year multicenter study was conducted in 298 patients with ocular hypertension or open-angle glaucoma who had a baseline central corneal endothelial cell density greater than 1500 cells/mm2 and central corneal thickness less than 0.68 mm in each eye. Patients were randomized to 0.5% betaxolol twice daily, 0.5% timolol twice daily, or 2.0% dorzolamide 3 times daily. Specular microscopy and ultrasonic pachymetry of the central cornea was performed at baseline and 6 and 12 months following institution of therapy. Endothelial cell densities were determined by a single masked observer.. The mean percent changes from baseline for both outcome measures were similar in all 3 treatment groups at both 6 and 12 months. After 1 year of treatment, the mean percent loss in endothelial cell density from baseline was 3.6%, 4.5%, and 4.2% for the dorzolamide, timolol, and betaxolol groups, respectively. The mean percent change from baseline for corneal thickness was 0.47%, -0.25%, and 0.39% for the dorzolamide, timolol, and betaxolol groups, respectively.. Dorzolamide is equivalent to timolol and betaxolol in terms of the change in central endothelial cell density and thickness after 1 year of therapy. All 3 treatments exhibit good long-term corneal tolerability in patients with normal corneas at baseline.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Betaxolol; Carbonic Anhydrase Inhibitors; Cell Count; Double-Blind Method; Endothelium, Corneal; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol

To determine the intraocular pressure-lowering efficacy and safety of brinzolamide 1.0%, compared with dorzolamide 2.0% and timolol 0.5%.. A multicenter, double-masked, prospective, parallel-group study was conducted to compare brinzolamide 1.0%, administered two and three times a day, dorzolamide 2.0% three times a day, and timolol 0.5% twice a day in 572 patients with primary open-angle glaucoma or ocular hypertension. The primary end point was diurnally corrected intraocular pressure reduction from baseline, evaluated at both peak and trough times during a 3-month period.. Mean intraocular pressure changes after twice daily (-3.8 to -5.7 mm Hg) and three times daily (-4.2 to -5.6 mm Hg) dosing with brinzolamide 1.0% were statistically equivalent (confidence limit < or = 1.5 mm Hg) to each other and also to dorzolamide 2.0% three times a day (-4.3 to -5.9 mm Hg). The range of intraocular pressure change with timolol 0.5% twice daily was -5.2 to -6.3 mm Hg. Clinically relevant intraocular pressure changes (reduction > or = 5 mm Hg or intraocular pressure < or = 21 mm Hg) were observed in up to 75.7% of patients taking brinzolamide twice daily and in up to 80.1% taking brinzolamide three times daily. Treatment with brinzolamide 1.0% was safe, comfortable, and well tolerated. The incidence of ocular discomfort (burning and stinging) on instillation of brinzolamide (twice daily, 1.8%; three times daily, 3.0%) was significantly less (P = .000) compared with treatment with dorzolamide (16.4%).. Brinzolamide 1.0% produced clinically relevant intraocular pressure reductions in substantial numbers of patients. Brinzolamide's effectiveness equaled that of dorzolamide 2.0% and it produced less ocular discomfort (burning and stinging) on instillation.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Aged; Carbonic Anhydrase Inhibitors; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Safety; Sulfonamides; Thiazines; Thiophenes; Timolol; Treatment Outcome

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

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Safety; Sulfonamides; Thiophenes; Timolol

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

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Safety; Sulfonamides; Thiophenes; Timolol

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

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Safety; Sulfonamides; Thiophenes; Timolol

To determine the additive effect on aqueous humor flow of short-term dorzolamide treatment in patients with glaucoma receiving long-term treatment with timolol.. Thirty-nine patients with glaucoma, 19 at Mayo Clinic, Rochester, Minn, and 20 at the University of Uppsala, Uppsala, Sweden, who had been receiving timolol treatment in both eyes for at least 1 year were studied. Aqueous flow was measured with fluorophotometry and intraocular pressure with tonometry. The effect of dorzolamide was compared with placebo when added to the long-term treatment regimen with timolol.. Dorzolamide reduced aqueous humor flow by 24% +/- 11% (mean +/- SD). The intraocular pressure as compared with placebo in the US cohort was reduced by 10% +/- 6% and in the Swedish cohort by 18% +/- 9%.. Dorzolamide, a carbonic anhydrase inhibitor, has additive effects as an ocular hypotensive agent with timolol, a beta-adrenergic antagonist, even though both drugs are suppressors of aqueous humor flow. Dorzolamide's effect on flow in these patients is the same as reported previously in normal subjects who are not taking a beta-adrenergic antagonist.

Topics: Adrenergic beta-Antagonists; Aged; Aqueous Humor; Carbonic Anhydrase Inhibitors; Cohort Studies; Drug Synergism; Female; Fluorophotometry; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

Economic evaluation of new treatments in the field of glaucoma represents a challenge. In the absence of a clear epidemiological link between intra-ocular pressure (IOP) and disease progression to blindness, the economic impact of treatments that lower IOP on long-term outcome cannot be estimated. As an alternative, effectiveness may be expressed as the ability to control IOP over time, making it possible to estimate the cost-effectiveness of therapies. The objective of this study was to investigate treatment strategies for patients newly diagnosed with primary open-angle glaucoma (POAG) or ocular hypertension (OH) in Germany and to estimate the impact of new topical therapies on the total cost of treatment.. We performed a retrospective analysis of 200 randomly selected patient charts in 50 ophthalmology practices. Demographics, diagnoses, IOP and detailed resource utilization over 2 years were collected. Resources were valued independently from the quantitative data collection, and a standard charge from the perspective of the third party payer, as well as a cost from the societal viewpoint, was determined for each item. A Markov model was created to calculate total treatment costs with the new therapy.. During the 2 years, 54% of patients had their therapy changed at least once. Mean total charge and cost per patient were DM 815 and DM 1274, respectively. Mean IOP at baseline was 31.2 mm at baseline and 18.8 mm after 2 years. IOP at baseline was positively correlated with costs, while IOP reduction after treatment initiation was negatively correlated with costs. Simulations of the effect of new topical therapies on treatment costs to third party payers and to society indicate that a potential reduction or delay of surgical interventions may partly offset the extra cost of the new drugs.. Observational data for glaucoma treatment indicate a high frequency of treatment changes that are associated with higher costs. New treatments that control IOP effectively over time may thus reduce the cost of patient management. Their cost-effectiveness for managing IOP will depend on both, their price and their effectiveness.

Topics: Adrenergic beta-Antagonists; Carbonic Anhydrase Inhibitors; Cost-Benefit Analysis; Drug Costs; Drug Therapy, Combination; Female; Germany; Glaucoma, Open-Angle; Humans; Insurance, Health, Reimbursement; Intraocular Pressure; Latanoprost; Male; Markov Chains; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Retrospective Studies; Sulfonamides; Thiophenes; Timolol

To evaluate the safety of open-label 2.0% dorzolamide as monotherapy and when used with timolol and/or pilocarpine for as long as 2 years.. The safety of dorzolamide was evaluated in patients with open-angle glaucoma or ocular hypertension over a 2-year period. The incidence of the most common drug-related adverse experiences in the first year was compared with that in the second year using McNemar's test. The ocular hypotensive effect of dorzolamide as monotherapy and with adjunctive therapy was assessed using percent change in intraocular pressure (IOP) from baseline.. Of the 304 patients enrolled, 164 (53.9%) continued to receive dorzolamide as monotherapy for 2 years and 140 (46.1%) required add-on therapy. Add-on therapy was initiated by month 6 in 112 of these 140 patients (80%). Of the 304 patients, 202 (66.4%) completed 2 years of therapy. Of the patients who received dorzolamide as monotherapy, drug-related adverse events occurred more frequently during the first year (29.7%) than the second year (13.8%), and the most common ocular drug-related adverse events included conjunctivitis, burning/stinging eye, follicular conjunctivitis, and eyelid edema. After 2 years of therapy, the mean percent decrease in peak IOP was 22.8% for patients receiving dorzolamide monotherapy and 31.2% to 36.0% for patients receiving add-on therapy.. Dorzolamide was generally well tolerated for up to 2 years as monotherapy and when used with timolol and/or pilocarpine. Drug-related adverse events were less frequent during the second year of monotherapy than during the first year. Most patients who required add-on therapy did so within the first 6 months of initiating dorzolamide therapy.

Topics: Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Pilocarpine; Safety; Sulfonamides; Thiophenes; Timolol

To compare the efficacy and tolerability of dorzolamide to acetazolamide.. Following a timolol and acetazolamide run-in, 105 patients with elevated intraocular pressure (IOP) were randomized to dorzolamide or acetazolamide, in addition to timolol, for 12 weeks.. More patients receiving acetazolamide discontinued due to clinical adverse experiences than patients receiving dorzolamide; 13 (25%) vs. 1 (2%); p<0.001. The prevalence of systemic adverse experiences for the dorzolamide group dropped by 50% by Week 12, but remained unchanged for the acetazolamide group, as compared to baseline; p<0.001. Ocular burning/stinging was more common in the dorzolamide group (21% vs. 0%; p<0.001). The mean trough IOP at Day 1 and Week 12 were 20.5 mmHg and 21.8 mmHg for the dorzolamide group, and 20.4 mmHg and 20.5 mmHg for the acetazolamide group. The mean peak IOP at Dayl and Week 12 were 18.9 mmHg and 20.0 mmHg for the dorzolamide group, and 18.7 mmHg and 18.6 mmHg for the acetazolamide group.. Mean IOP was slightly lower (by approximately 1 mmHg) with acetazolamide, while dorzolamide demonstrated much better tolerability.

Topics: Acetazolamide; Administration, Oral; Administration, Topical; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Chemotherapy, Adjuvant; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To compare the tolerability and efficacy of a fixed combination solution of dorzolamide/timolol (Cosopt), administered twice daily with the concomitant administration of its components, dorzolamide (Trusopt) twice daily and timolol (Timoptic) twice daily.. After a 2 week timolol run in, patients with open angle glaucoma or ocular hypertension were randomised (1:1) to receive treatment with either the dorzolamide/timolol combination solution twice daily (combination) or the dorzolamide solution twice daily plus timolol maleate solution twice daily (concomitant) for 3 months.. 299 patients were entered and 290 patients completed the study. Compared with the timolol baseline, additional IOP lowering of 16% was observed at trough (hour 0) and 22% at peak (hour 2) at month 3 in both the concomitant and combination groups. The IOP lowering effects of the two treatment groups were clinically and statistically equivalent as demonstrated by the extremely small point differences (concomitant--combination) observed in this study--0.01 mm Hg at trough and 0.08 mm Hg at peak. The safety variables of the concomitant and combination groups were very similar. Both combination and concomitant therapy were well tolerated and few patients discontinued due to adverse effects.. The dorzolamide/timolol combination solution administered twice daily is equivalent in efficacy and has a similar safety profile to the concomitant administration of the components administered twice daily.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

Ocular pulse amplitude (OPA) is reduced in normal tension primary open angle glaucoma (NTP) patients when compared with healthy age matched controls (CTL) while increased OPA appears to protect ocular hypertensive patients from visual field loss. If NTP is accompanied by vasospasm, as in roughly half of the primary open angle glaucoma (POAG) population (independent of intraocular pressure, IOP), calcium channel blockers increase OPA and thus stabilise visual fields in these patients. Current glaucoma drugs reduce IOP but do not activate (compromised) ocular perfusion.. The influence of dorzolamide, a topical carbonic anhydrase inhibitor in standard dosage (three times daily, one eye) on OPA, IOP, blood pressure, and heart rate was investigated in a randomised, prospective, masked clinical trial assessing the acute effects of dorzolamide v placebo before and 2 days after application in 33 cataract patients with (n = 14) and without (n = 19) high tension POAG (HTP) who provided informed consent.. Following application of dorzolamide (D) IOP (mm Hg, mean (SEM)) in HTPD (20.2 (0.5)/16.3 (0.5) and in CTLD (16.0 (0.5)/12.3 (0.5)) was highly significantly (p < 0.001) reduced and was significantly (p < 0.03) reduced in vehicle (V) treated eyes (HTPv: 20.3 (0.4)/19.0 (0.4)) and CTLv: 15.8 (0.4)/14.9 (0.3)) when compared with respective baseline measurements. OPA (mm Hg) in HTPD (2.1 (0.1)/2.5 (0.1)) and CTLD (2.2 (0.1)/2.6 (0.2)) eyes was significantly (p < 0.05) increased and unaffected in vehicle treated eyes when compared with respective baseline measurements. Systemic perfusion variables were also unchanged.. Dorzolamide increased OPA in HTP and CTL. Drugs stimulating OPA may improve prognosis of POAGs.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Carbonic Anhydrase Inhibitors; Cataract; Female; Glaucoma, Open-Angle; Heart Rate; Humans; Intraocular Pressure; Male; Middle Aged; Placebos; Prospective Studies; Pulsatile Flow; Sulfonamides; Thiophenes

The aim of this study is to evaluate the ocular hypotensive efficacy of a topical carbonic anhydrase inhibitor (dorzolamide) in primary open-angle glaucoma patients, administered alone or in association with beta-blockers or with beta-blockers and miotics, in a one-year follow-up.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Carbonic Anhydrase Inhibitors; Chronic Disease; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Miotics; Pilocarpine; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To evaluate the additive ocular hypotensive effect of latanoprost and dorzolamide in combination, on intraocular pressure reduction in patients with elevated intraocular pressure (IOP).. Thirty patients with ocular hypertension or early capsular or primary open-angle glaucoma and elevated IOP were randomly assigned to two parallel treatment groups. The treatment period was twenty days. Fifteen patients (Group 1) received latanoprost once daily during the first ten days and, in addition, dorzolamide three times daily during the second ten days. Fifteen patients (Group 2) received dorzolamide three times daily during the first ten days and, in addition latanoprost, once daily during the second ten days. IOP was measured and conjunctival hyperemia was evaluated.. In Group 1, the mean IOP on day 0 was 26.8 mm Hg; on day 10, 18.7 mm Hg; and on day 20, 15.9 mm Hg. In Group 2, the mean IOP on day 0 was 26.3 mm Hg; on day 10, 21.2 mm Hg; and on day 20, 16.1 mm Hg. Both groups had clinically significant IOP-lowering effect on day 10 as compared with baseline day (30.2% and 19.4% respectively) (p<0.01). When dorzolamide was added to latanoprost, the additional IOP reduction was 2.8 mm Hg (15%) (p<0.01) compared with 5.1 mm Hg (24.1%) (p<0.01) when latanoprost was added to dorzolamide. No local serious adverse reactions were observed. A mild but statistically significant increase in conjunctival hyperemia was seen in latanoprost applied patients.. The results showed that latanoprost and dorzolamide can be combined successfully to reduce IOP with their additive effects.

Topics: Adult; Carbonic Anhydrase Inhibitors; Cross-Over Studies; Drug Synergism; Drug Therapy, Combination; Exfoliation Syndrome; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Single-Blind Method; Sulfonamides; Thiophenes; Treatment Outcome

To determine the relationship between central corneal thickness (CCT) and applanation intraocular pressure (IOP) in normal, glaucomatous, and ocular hypertensive eyes.. One hundred nine subjects (184 eyes) were studied. Forty-eight patients (74 eyes) had glaucoma, 28 patients (51 eyes) had ocular hypertension, and 33 patients (59 eyes) were normal. Intraocular pressure as measured by applanation tonometry, refractive status, CCT, and axial length were measured for all subjects.. The CCT (mean +/- SD) of eyes with ocular hypertension was significantly greater (0.606 +/- 0.041 mm) than that of glaucomatous eyes (0.554 +/- 0.022 mm) (P < .001) or of normal controls (0.561 +/- 0.026 mm) (P < .001). There was no significant difference in CCT between normal and glaucomatous eyes (P = .40). The axial length (mean +/- SD) of eyes with ocular hypertension (23.54 +/- 1.34 mm) was not different compared with glaucomatous eyes (23.93 +/- 0.96 mm) (P = .13) or normal eyes (23.62 +/- 1.21 mm) (P = .83). There was no significant difference between the axial length for glaucomatous eyes compared with normal eyes (P = .18). Those eyes with glaucoma being treated with topical dorzolamide hydrochloride had a significantly increased CCT (0.560 +/- 0.025 mm) compared with those eyes with glaucoma not being treated with dorzolamide (0.551 +/- 0.20 mm) (P = .02).. The mean CCT is increased in eyes with ocular hypertension when compared with normal or glaucomatous eyes, which confirms the findings of other investigators. Increased CCT may give an artificially high IOP measurement by applanation tonometry. The CCT must be considered when developing a treatment approach for patients with ocular hypertension.

Topics: Aged; Carbonic Anhydrase Inhibitors; Cornea; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Tonometry, Ocular

Topics: Administration, Topical; Aged; Carbonic Anhydrase Inhibitors; Costs and Cost Analysis; Glaucoma, Open-Angle; Humans; Models, Economic; Muscarinic Agonists; Ophthalmic Solutions; Pilocarpine; Sulfonamides; Thiophenes

Topics: Acetazolamide; Administration, Oral; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Chronic Disease; Cross-Over Studies; Double-Blind Method; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Sulfonamides; Thiophenes; Treatment Outcome

To investigate the efficacy and dose-response relationship of three concentrations (0.2%, 0.7%, and 2.0%) of dorzolamide hydrochloride in lowering elevated intraocular pressure (IOP) in patients during a six-week period and to evaluate the efficacy of 0.7% and 2.0% dorzolamide administered for an additional year.. This prospective, double-masked, randomized, placebo-controlled, multinational study enrolled 333 adults with open-angle glaucoma or ocular hypertension. During the six-week dose-response phase, patients were randomized to thrice-daily dosing of four treatments: 0.2%, 0.7%, or 2.0% dorzolamide or placebo (vehicle of dorzolamide). During a one-year extension, patients received 0.7% or 2.0% dorzolamide, and, if needed, 0.5% timolol twice daily for elevated IOP.. In the dose-response phase, mean percent reduction of IOP (peak) was 16% to 18% for 2.0% and 0.7% dorzolamide and 4% to 7% for the placebo group, for a net reduction of IOP by dorzolamide of 11% to 14%. The 0.2% concentration of dorzolamide was not sufficiently active for further consideration. During the extension, dorzolamide maintained an adequate reduction of IOP in 55% (174 of 316) of patients. Throughout the study, the reduction in IOP was numerically greater for patients receiving 2.0% vs 0.7% dorzolamide. After 12 months of receiving dorzolamide, 20% to 28% of total carbonic anhydrase activity was observed.. Topical dorzolamide used three times daily in concentrations of 0.7% or 2.0% lowered IOP and was generally well tolerated as monotherapy or in combination with 0.5% timolol.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Sulfonamides; Thiophenes; Timolol

To assess the safety and intraocular pressure (IOP)-lowering activity of 2% dorzolamide (topical carbonic anhydrase inhibitor), compared to 0.5% timolol and 0.5% betaxolol eyedrops.. A parallel, masked, randomised one-year clinical trial was conducted in 16 patients with open-angle glaucoma or ocular hypertension, being a subset of a multicentre study which enrolled 523 subjects. Patients had IOP > 22 mmHg in one eye at baseline following washout of ocular hypotensive medications and were then randomised in a 3:1:1 ratio to receive 2% dorzolamide thrice daily, 0.5% timolol twice daily or 0.5% betaxolol twice daily respectively. IOP was measured at Hour 2 (morning peak), Hour 5 and Hour 8 (afternoon trough for dorzolamide) at baseline, Weeks 2 and 4 and Months 2, 3, 6, 9 and 12.. Topical dorzolamide 2% solution was well tolerated and safe. Mean IOP for dorzolamide at Hour 2 was 29.1 mmHg at baseline and 20.8 mmHg on treatment at one year, a 28.5% change. Mean IOP for dorzolamide at Hour 8 was 24.5 mmHg at baseline and 20.2 mmHg on treatment at one year, a 17.6% change. Comparable percent changes for timolol and betaxolol were 43.2/25.7 mmHg at Hour 2 and 21.9/13.5 mmHg at Hour 8 respectively.. Dozolamide 2% given thrice daily was well tolerated and safe, with a clinically significant effect on IOP comparable to betaxolol 0.5% twice daily, but not as great as timolol 0.5% twice daily.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Betaxolol; Carbonic Anhydrase Inhibitors; Double-Blind Method; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Multicenter Studies as Topic; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To report the results of two studies on the use of dorzolamide as adjunctive therapy to timolol in patients with elevated intraocular pressure (IOP). In the larger study, the additive effect of dorzolamide administered twice daily also was compared with 2% pilocarpine.. Both studies were parallel, randomized, double-masked, placebo-controlled comparisons. In the pilot study, 32 patients received 0.5% timolol twice daily plus either 2% dorzolamide twice daily or placebo twice daily for 8 days. In the Pilocarpine Comparison Study, 261 patients received 0.5% timolol twice daily plus 0.7% dorzolamide twice daily, 2% dorzolamide twice daily, 2% pilocarpine four times daily, or placebo (twice daily or 4 times daily) for 2 weeks. Patients then entered a 6-month extension period and received 0.5% timolol twice daily plus either 0.7% dorzolamide twice daily, 2% dorzolamide twice daily, or 2% pilocarpine four times daily.. In the pilot study, after 8 days, additional mean percent reductions in IOP for 2% dorzolamide and placebo were 17% and 3% at morning trough and 19% and 2% at peak, respectively. In the Pilocarpine Comparison Study, after 6 months, additional mean percent reductions in IOP (morning trough) were 9%, 13%, and 10% for 0.7% dorzolamide, 2% dorzolamide, and 2% pilocarpine, respectively. Patients receiving 2% pilocarpine had the highest rate of discontinuation due to a clinical adverse experience, and the use of dorzolamide was not associated with systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors.. Dorzolamide twice daily was effective and well tolerated by the patients in these studies as adjunctive therapy to timolol. The larger study demonstrated that both concentrations of dorzolamide produce similar IOP-lowering effects to 2% pilocarpine.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Chemotherapy, Adjuvant; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Muscarinic Agonists; Ocular Hypertension; Ophthalmic Solutions; Pilocarpine; Pilot Projects; Safety; Sulfonamides; Thiophenes; Timolol

To investigate the safety profile and efficacy of 2.0% dorzolamide hydrochloride, when administered three times daily for up to 1 year, compared with that of 0.5% timolol maleate and 0.5% betaxolol hydrochloride, each administered twice daily. In addition, the effect of adding dorzolamide to the regimen of patients with inadequate ocular hypotensive efficacy while they were receiving one of the two beta-adrenoceptor antagonists and the effect of adding timolol to the regimen of patients receiving dorzolamide were also evaluated.. A double-masked, randomized, parallel comparison.. Multinational study at 34 international sites.. Five hundred twenty-three patients with open-angle glaucoma or ocular hypertension, 17 to 85 years of age. Patients currently using ocular hypotensive medications were required to undergo a washout.. Two percent dorzolamide three times a day, 0.5% timolol (Timoptic, Merck, Whitehouse Station, NJ) twice daily, and 0.5% betaxolol solution (Betoptic, Alcon, Fort Worth, Tex) twice daily.. At 1 year, the mean percent reduction in intraocular pressure at peak of 2% dorzolamide, 0.5% timolol, and 0.5% betaxolol was approximately 23%, 25%, and 21%, respectively. At afternoon trough, the mean percent reduction in intraocular pressure was 17%, 20%, and 15% for dorzolamide, timolol, and betaxolol, respectively.. The ocular hypotensive efficacy of 2.0% dorzolamide, given three times a day, is comparable with that of 0.5% betaxolol, given twice daily, for up to 1 year. In addition, long-term use of dorzolamide was not associated with clinically meaningful electrolyte disturbances or systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Betaxolol; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol

In this study, we examined the relation between spontaneously reported adverse experiences and responses given on the comparison of ophthalmic medications for tolerability (COMTOL) checklist questionnaire which queries the frequency and bother of specific side-effects known to be associated with topical ophthalmic agents used to treat ocular hypertension or open-angle glaucoma, and the impact that the side-effects have on health-related quality of life. The study was a 4-week, randomized, open-label, two-period cross-over clinical trial comparing dorzolamide and pilocarpine in 92 patients who were also receiving timolol for the treatment of ocular hypertension or open-angle glaucoma. Patients completed the COMTOL questionnaire at baseline and at the end of each period and spontaneous reports of adverse experiences (AEs) were collected throughout the study by the investigator. Since there were only 3 spontaneously reported AEs related to drug treatment while patients received dorzolamide and since COMTOL scores indicated a low level of side-effects, the analyses were limited to pilocarpine treatment periods. We discovered that during the pilocarpine treatment periods, a large percentage (94%) of the 47 patients, who failed to spontaneously report any adverse experiences, indicated on the COMTOL that they had experienced side-effects. These discrepancies between the methods of spontaneous reports and a checklist questionnaire are similar to those previously reported in the literature for other drugs. Unlike previous literature, we went beyond identifying discrepancies with the two reporting methods and we looked for possible explanations for why the discrepancies existed. We discovered that patients who spontaneously reported AEs expressed more bother from these specific side-effects on the questionnaire than patients who did not spontaneously report AEs. As well, patients who spontaneously reported AEs and discontinued drug as a result of the AEs expressed on the COMTOL the greatest bother from side-effects. This trend of increasing negative impact (as patients reported AEs and discontinued) was also observed with COMTOL global question scores on the impact of side-effects on health-related quality of life, the impact of activity limitations on quality of life, satisfaction with medication and compliance with medication. Therefore, spontaneous reporting of side-effects appears to be detecting the most clinically meaningful side-effects.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Antihypertensive Agents; Cross-Over Studies; Female; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Surveys and Questionnaires; Thiophenes; Timolol

To investigate the activity and local and systemic safety of the topical carbonic anhydrase inhibitor, dorzolamide hydrochloride.. Four-week, double-masked, randomized, placebo-controlled, parallel, three-center study.. Referral centers.. Forty-eight patients with bilateral open angle glaucoma or ocular hypertension and intraocular pressure (IOP) greater than 22 mm Hg entered the study. Two of 28 patients receiving dorzolamide and two of 20 patients receiving placebo were withdrawn due to adverse experiences.. Dorzolamide (2%) or placebo to each eye three times daily for 4 weeks.. Diurnal IOP curves; ophthalmologic evaluations including corneal ultrasound pachymetry and endothelial cell count; and systemic evaluations including vital signs, blood chemistries, complete blood cell counts, urinalysis, electrocardiogram, and drug and carbonic anhydrase activity levels in red blood cells.. Mean IOP at morning trough (8 AM) decreased from 27.1 mm Hg at baseline to 23.5 mm Hg on day 29 with dorzolamide (-13.3%) compared with a decrease from 27.1 mm Hg to 26.4 mm Hg with placebo (-2.3%). Peak activity occurred 2 hours after administration, with IOP decreasing from 26.8 mm Hg at baseline to 21.8 mm Hg on day 29 with dorzolamide (-18.4%) vs 26.1 mm Hg to 25.5 (-2.4%) with placebo. Mean corneal thickness was slightly increased for the dorzolamide-treated group compared with the placebo-treated group (0.009 mm vs 0.001 mm, respectively, P < .05) and changes in endothelial cell counts were similar (-24 cells/mm2 vs -27 cells/mm2, respectively, P > .25). Mean carbonic anhydrase isoenzyme II activity in red blood cells decreased to 21% of baseline in dorzolamide-treated patients. There were no clinically significant differences in ocular or laboratory parameters between the dorzolamide and placebo groups.. Dorzolamide demonstrated significant IOP lowering activity over 4 weeks. It was well tolerated and there were no clinically significant changes in ocular or systemic safety parameters.

Topics: Administration, Topical; Adult; Aged; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Cell Count; Cornea; Double-Blind Method; Drug Tolerance; Endothelium, Corneal; Erythrocytes; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Safety; Sulfonamides; Thiophenes

The ocular hypotensive activities of the two potent topical carbonic anhydrase inhibitors sezolamide (previously known as MK-417) and dorzolamide (previously known as MK-507 and L-671,152) were compared formulated in Gelrite vehicle, a novel ophthalmic drug delivery system. This was a four-center, double-blind, randomized, placebo-controlled, parallel study in 73 patients with a diagnosis of bilateral primary open-angle glaucoma or ocular hypertension and a morning intraocular pressure (IOP) of greater than 23 mmHg in both eyes following washout of ocular hypotensive medications. Parallel 12-h modified diurnal curves were performed prestudy and on day 6, with a 4-h IOP curve on day 1. On day 6 the peak mean percentage decrease in IOP from baseline occurred 4 h after the dose of dorzolamide (22.1%) and 6 h after the dose of sezolamide (21.3%). There were no significant differences between 2% dorzolamide and 1.8% sezolamide at any time point, although the decrease in IOP for sezolamide tended to be slightly greater than that for dorzolamide. Duration of action of both compounds was, at most, slightly prolonged by the use of Gelrite vehicle when compared with former studies on sezolamide and dorzolamide.

Topics: Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Delivery Systems; Female; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Polysaccharides, Bacterial; Sulfonamides; Thiophenes

The multiple-dose, dose-response relationship and duration of action of the novel topical carbonic anhydrase inhibitor dorzolamide (previously known as MK-507) were investigated in a double-masked, randomized, placebo-controlled, parallel study in 73 patients with bilateral primary open angle glaucoma or ocular hypertension. Dorzolamide (0.7%, 1.4%, or 2%) or placebo was administered every 12 hours for 5 days and then every 8 hours for 7 days. Intraocular pressure was investigated with multiple 12-hour diurnal curves. All concentrations of dorzolamide demonstrated substantial lowering of intraocular pressure throughout the day when given twice daily (9% to 21%) or three times daily (14% to 24%). Although a dose-dependent response was observed immediately following the first dose, there were no significant differences between concentrations or dose response at either the twice or three times daily dosing regimen. Three times daily administration of 2% dorzolamide demonstrated a mean percent decrease in intraocular pressure of 18% to 22% throughout the day (mean decrease, 4.5 to 6.1 mm Hg). Dorzolamide appears to have substantial potential in the treatment of glaucoma and ocular hypertension.

Topics: Administration, Topical; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Placebos; Sulfonamides; Thiophenes

Topical carbonic anhydrase inhibitors MK-507 and sezolamide hydrochloride (previously known as MK-417) were compared in a double-masked, randomized, placebo-controlled study in 82 patients with bilateral primary open-angle glaucoma or ocular hypertension. MK-507 was given every 8 or 12 hours, sezolamide every 8 hours, or placebo every 8 or 12 hours for 4 days. Both drugs lowered intraocular pressure (IOP) substantially. MK-507 was somewhat more active than sezolamide, with a peak mean IOP reduction of 26.2% for MK-507 versus 22.5% for sezolamide, although the difference between the treatments was not statistically significant. These drugs may have potential in the treatment of glaucoma.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Sulfonamides; Thiophenes

Lowering intraocular pressure (IOP) is a mainstay of glaucoma therapy. It is, however, still an open question whether a comparable level of long-term IOP lowering achieved by different medications results in comparable protection for the retinal ganglion cells. The purpose of this study was to retrospectively analyze glaucoma damage progression in two cohorts of primary open-angle glaucoma patients with different and unchanged therapy over a period of 3 years, and the main objective of this study was to determine possible differences in terms of structural [retinal nerve fiber layer thickness (RNFL)] and functional [visual field (VF)] outcome.. The retrospective observational cohort analysis compared two differently treated groups of glaucoma patients with their original, at study entry, topical therapy unchanged over 3 years. The main endpoint was the time course of RNFL thickness and VF mean defect (MD).. Twenty-one eyes were included in each group. The first group (21 eyes) was on a fixed combination of timolol and dorzolamide twice a day and the second group on one drop of prostaglandin analog, either latanoprost alone (15 eyes) or travoprost alone (6 eyes), in an unchanged regimen over a period of 3 years. IOP in mmHg at baseline and at 36 months was 11.9 ± 2.4 and 13.0 ± 2.1 in the first, and 12.9 ± 3.0 and 14.1 ± 3.2 in the second group, respectively. RNFL thickness values in micrometers were at baseline and at 36 months 77.8 ± 12.3 and 76.6 ± 15.2 in the first, and 77.5 ± 15.2 and 72.8 ± 14.5 in the second group, respectively. VF MD in dB were 1.7 ± 2.5 and 1.2 ± 2.9 in the first, and 0.9 ± 2.3 and 0.7 ± 2.6 in the second group, respectively.. Both groups had comparable baseline, as well as mean overall IOP. However, the course of IOP levels over time was different in the two groups, showing earlier and more pronounced long-term drift in the prostaglandin analog-treated group. RNFL thickness was comparable at baseline, however, RNFL thinning over time was more pronounced in the prostaglandin analog-treated group. There were no statistical differences between the groups in terms of VF MD at baseline and over time.. Bei der Therapie von Glaukompatienten stellt sich immer noch die Frage, ob ein vergleichbares Niveau der langfristigen IOD-Senkung durch verschiedene Medikamente zu einem vergleichbaren Schutz der retinalen Ganglienzellen führt. Wir verglichen in dieser retrospektiven Analyse zwei Kohorten von Patienten mit primärem Offenwinkelglaukom mit unterschiedlicher und unveränderter medikamentösen Therapie über einen Zeitraum von drei Jahren. Bei vergleichbarem mittleren Gesamtdruck zeigte sich zwar kein signifikant unterschiedlicher Verlauf des Gesichtsfeldes, jedoch ein signifikant unterschiedlicher Verlauf der Retinalen Nervenfaserschichtdicke.

Topics: Administration, Topical; Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Retinal Ganglion Cells; Retrospective Studies; Timolol; Travoprost

Topics: Carbonic Anhydrase Inhibitors; Eye; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions

Topics: Carbonic Anhydrase Inhibitors; Eye; Glaucoma; Glaucoma, Open-Angle; Humans

A 62-year-old woman with mild myopia presented to her local optometrist for a routine examination and was found to have intraocular pressure (IOP) of 30 mm Hg in both eyes and cupped nerves. She had a family history of glaucoma in her father. She was started on latanoprost in both eyes and was referred for a glaucoma evaluation. On initial evaluation, her IOP was 25 mm Hg in the right eye and 26 mm Hg in the left eye. Central corneal thickness measured 592 µm in the right eye and 581 µm in the left eye. Her angles were open to gonioscopy without any peripheral anterior synechia. She had 1+ nuclear sclerosis with a corrected distance visual acuity (CDVA) of 20/25 in the right eye and 20/30- in the left eye and uncorrected near visual acuity of J1+ in each eye. Her nerves were 0.85 mm in the right eye and 0.75 mm in the left eye. Optical coherence tomography (OCT) showed retinal nerve fiber layer thinning and a dense superior arcuate scotoma into fixation in her right eye, and superior and inferior arcuate scotomas in her left eye (Figures 1 and 2JOURNAL/jcrs/04.03/02158034-202307000-00019/figure1/v/2023-06-26T195222Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202307000-00019/figure2/v/2023-06-26T195222Z/r/image-tiff, Supplemental Figures 1 and 2, available at http://links.lww.com/JRS/A882 and http://links.lww.com/JRS/A883). She was successively trialed on fixed combination brimonidine-timolol, dorzolamide, and netarsudil, in addition to her latanoprost, but her IOP remained in the mid- to upper 20s in both eyes. The addition of acetazolamide lowered the pressure to 19 mm Hg in both eyes, but she tolerated it poorly. Methazolamide was also attempted with similar side effects. We elected to perform left eye cataract surgery combined with 360-degree viscocanaloplasty and insertion of a Hydrus microstent (Alcon Laboratories, Inc.). Surgery was uncomplicated with IOP of 16 mm Hg on postoperative day 1 with no glaucoma medications. However, by postoperative week 3, IOP returned to 27 mm Hg, and despite restarting latanoprost-netarsudil and finishing her steroid taper, IOP remained at 27 mm Hg by postoperative week 6. Brimonidine-timolol was added back to her left eye regimen and at postoperative week 8, IOP had elevated to 45 mm Hg. Maximizing her therapy with the addition of topical dorzolamide and oral methazolamide brought her IOP back down to 30 mm Hg. At that point, the decision was made to proceed with trabeculectomy of the left eye. The trabeculectomy was un

Topics: Adolescent; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Latanoprost; Methazolamide; Middle Aged; Timolol; Treatment Outcome; United States

In this study, we aimed to assess the central corneal epithelial thickness (CET), central corneal stromal thickness (CST), and total central corneal thickness (CCT) thinning relationships with dry eye development monitoring and underestimated measurement of intraocular pressure (IOP) in primary open-angle glaucoma (POAG) patients treated with timolol, dorzolamide, and brimonidine.. This longitudinal cohort study included 106 patients with POAG. All patients underwent a detailed ophthalmic examination. In addition, CET, CST, and CCT were measured using anterior segment optical coherence tomography (AS-OCT). Subsequently, the cohort was divided into three groups based on the therapy administered. The Tomec group received monotherapy with benzalkonium chloride (BAK)-preserved timolol + dorzolamide fixed combination. The Alphagan group received monotherapy with purite-preserved brimonidine, and the Combigan group received monotherapy with BAK-preserved timolol + brimonidine fixed combination.. CET, CST, and CCT did not show a statistically significant decrease in the Alphagan group (p>0.05). However, the Tomec and Combigan groups showed significantly reduced measurements, except for stromal thickness (p<0.05). Finally, a significant positive correlation was found between changes in tear break-up time (TBUT) and CET during the follow-up period (r = 0.637, p = 0.001).. CET and CCT thinning were higher in the Tomec and Combigan groups than in the Alphagan group. Furthermore, although CCT reduction was significant in the Tomec and Combigan groups, its effect on IOP underestimation was approximately 1%. Furthermore, the positive correlation between CET and TBUT suggests that CET measurement with AS-OCT may also be useful in dry eye monitoring.

Topics: Brimonidine Tartrate; Brimonidine Tartrate, Timolol Maleate Drug Combination; Dry Eye Syndromes; Glaucoma; Glaucoma, Open-Angle; Humans; Longitudinal Studies; Photochemotherapy; Photosensitizing Agents; Timolol; Tomography, Optical Coherence

Impaired ocular blood flow is an important risk factor in the pathogenesis of open-angle glaucoma (OAG). Studies have reported that dorzolamide 2% may be effective in improving ocular blood flow (OBF) in OAG patients. The objective of this study was to determine the efficacy of dorzolamide 2% (DORZOX, Cipla Ltd.) in improving retrobulbar blood flow in an Indian setting.. The study was conducted as an interventional pilot project in 24 healthy subjects and 19 OAG patients. Baseline OBF measurements were done for all glaucoma patients with color Doppler imaging (CDI). Baseline ocular perfusion pressure (OPP) was calculated for all participants. Glaucoma patients were given dorzolamide 2% thrice daily for 12 weeks. The primary efficacy endpoints were mean changes in the CDI parameters of the retrobulbar vessels and OPP posttreatment. The secondary endpoint was mean change in the intraocular pressure (IOP) and adverse events, if any.. In comparison to healthy subjects, glaucoma patients displayed significantly reduced baseline OPP (P = 0.002). Treatment with dorzolamide 2% for 12 weeks led to a significant increase in OPP (P < 0.001) and a significant increase in end diastolic velocity (EDV) in all major ophthalmic arteries like ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary artery (SPCA) (P < 0.001, P = 0.04, and P = 0.0075, respectively). A significant reduction in the intraocular pressure (IOP; P = 0.007) was observed posttreatment, with no adverse events reported.. Dorzolamide 2% significantly improved parameters such as the EDV and OPP in major ophthalmic arteries. This pilot study shows promising results on using dorzolamide for treating Indian patients with OAG.

Topics: Carbonic Anhydrase Inhibitors; Glaucoma; Glaucoma, Open-Angle; Humans; Pilot Projects

In patients with normal-tension glaucoma (NTG), topical dorzolamide might enhance the vessel density (VD), topical carteolol decreased the VD in the inferior-temporal peripapillary retina, whereas topical brimonidine did not change the VD.. Topical antiglaucoma medications may improve ocular perfusion pressure or microcirculation in the optic nerve head. The study evaluated responses of retinal VD to topical carteolol, brimonidine, and dorzolamide in NTG using optical coherence tomography angiography.. This is a retrospective, nonrandomized, comparative study. The study included 131 individuals (77 men, 54 women) diagnosed with NTG, without systemic medication use, who visited the glaucoma clinic of Chang Gung Memorial Hospital, Taiwan, between January 2019 and May 2020. If both eyes were diagnosed with NTG, only the right eye was included. Of these, there were 80 carteolol-treated eyes, 27 brimonidine-treated eyes, and 24 dorzolamide-treated eyes. We studied the response of optical coherence tomography angiography parameters and retinal nerve fiber layer (RNFL) thickness to drugs, 6 months after treatment.. In dorzolamide-treated eyes, increases in the peripapillary superficial retinal VD, especially in the superior-nasal area, were significant; however, no RNFL thickness changes were observed. In contrast, the superficial retinal VD decreased at the inferior-temporal peripapillary area, and RNFL thickness decreased in the inferior-nasal peripapillary area of carteolol-treated eyes. Finally, in brimonidine-treated eyes, changes in either VD parameters or RNFL thickness were not significant.. Topical dorzolamide possibly enhanced the VD of the peripapillary retina in NTG eyes. On the contrary, topical carteolol possibly decreased VD in the inferior-temporal peripapillary retina. Finally, in cases treated with topical brimonidine, peripapillary microcirculation remained unchanged. The study shows preliminary results and future large-scale studies are needed to confirm findings.

Topics: Angiography; Brimonidine Tartrate; Carteolol; Female; Fluorescein Angiography; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Nerve Fibers; Retinal Ganglion Cells; Retinal Vessels; Retrospective Studies; Sulfonamides; Thiophenes; Tomography, Optical Coherence; Visual Fields

To report a case of reversible corneal endothelial abnormalities after treatment with netarsudil.. A 68-year-old woman presented with the complaint of blurred vision soon after starting treatment with the fixed-dose combination of netarsudil and latanoprost (FC-netarsudil-latanoprost). She had been receiving the fixed-dose combination of dorzolamide and timolol and latanoprost for primary open-angle glaucoma until her ophthalmologist switched latanoprost to FC-netarsudil-latanoprost 2 months before referral to our center.Best-corrected visual acuity was 20/20-1 in the right eye and 20/20-3 in the left eye. The slit-lamp biomicroscopic examination was remarkable for a guttata-like abnormality of the corneal endothelium of both eyes. The intraocular pressure was 10 mm Hg in both eyes. Specular microscopy revealed irregularly shaped corneal endothelial cells with indistinct borders between cells. FC-netarsudil-latanoprost was replaced with latanoprost in the left eye but continued in the right eye. Nine weeks later, best-corrected visual acuity remained 20/20-1 in the right eye but it improved to 20/20 in the left eye. Repeat specular microscopy was unchanged in the right eye and was normal in the left eye.. Topical therapy with netarsudil can result in guttata-like changes of the corneal endothelium and corneal endothelial cell abnormalities that can be detected with specular microscopy. These abnormalities seem to be transient and resolved upon the cessation of netarsudil. Ophthalmologists should consider the possibility of a corneal endothelial abnormality in patients treated with netarsudil who develop blurred vision.

Topics: Aged; Antihypertensive Agents; Benzoates; beta-Alanine; Corneal Diseases; Drug Therapy, Combination; Endothelium, Corneal; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Remission Induction; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Withholding Treatment

The case concerns an 81-year-old woman on treatment with a topical fixed combination of timolol and brimonidine who was diagnosed in the Emergency Department with acute anterior granulomatous hypertensive uveitis. The patient responded favourably to the withdrawal of the eye drops without showing any subsequent relapse.. Uveitis due to brimonidine is a rare adverse effect, but it must be known. Once the diagnosis is suspected, the effective treatment is the withdrawal of brimonidine, with or without the addition of topical corticosteroids to control inflammation depending on the severity of the condition. It is a process with an excellent prognosis.

Topics: Acute Disease; Adrenergic alpha-2 Receptor Agonists; Aged, 80 and over; Brimonidine Tartrate; Conjunctivitis, Allergic; Cyclopentolate; Drug Therapy, Combination; Epithelium, Corneal; Female; Glaucoma, Open-Angle; Granuloma; Humans; Latanoprost; Lubricant Eye Drops; Ocular Hypertension; Ophthalmic Solutions; Prednisolone; Sulfonamides; Thiophenes; Timolol; Uveitis, Anterior

To evaluate the efficacy and safety of bimatoprost plus timolol fixed combination (BTFC) in patients with primary open angle glaucoma (POAG) previously treated with dorzolamide plus timolol fixed combination (DTFC).. Retrospective, medical records review study. Medical records of patients with POAG previously treated with DTFC and then switched to BTFC for poor intraocular pressure (IOP) control or ocular discomfort were included in the analysis. One baseline IOP diurnal curve, and one diurnal curve under each treatment were required to be eligible for this study. The primary outcome was to compare the mean diurnal IOP between DTFC and BTFC. Secondary outcomes were to compare the IOP diurnal fluctuation, and the percentage of patients achieving a target IOP <14, <16, and <18 mmHg between the two treatments.. Medical records of 96 patients were analyzed (mean age 65.8 years ± 7.2, range 39-89 years). The mean diurnal IOP was 23.7 ± 3.8 mmHg at baseline, 16.9 ± 3.4 mmHg with DTFC and 15.1 ± 2.9 mmHg after therapy was switched to BTFC (p < 0.0001 each treatment vs baseline; p < 0.0001 DTFC vs BTFC). The proportion of patients achieving a mean diurnal IOP <18, <16, and <14 mmHg was 76%, 35.4%, and 12.5% with DTFC and 81.2%, 68.8%, and 37.5% with BTFC (p = 0.20, p < 0.01, and p < 0.0001 between the two treatments, respectively). IOP fluctuation did not differ significantly between the treatments.. BTFC can provide additional lowering in the mean diurnal IOP in patients previously treated with DTFC with no significant differences in the safety and tolerability profile.

Topics: Aged; Antihypertensive Agents; Bimatoprost; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ophthalmic Solutions; Retrospective Studies; Sulfonamides; Thiophenes; Time Factors; Timolol; Treatment Outcome

The aim of this study is to determine the most cost-effective strategy for the treatment of primary open-angle glaucoma (POAG) in Brazil, from the payer's perspective (Brazilian Public Health System) in the setting of the Glaucoma Referral Centers.. Study design was a cost-effectiveness analysis of different treatment strategies for POAG. We developed 3 Markov models (one for each glaucoma stage: early, moderate and advanced), using a hypothetical cohort of POAG patients, from the perspective of the Brazilian Public Health System (SUS) and a horizon of the average life expectancy of the Brazilian population. Different strategies were tested according to disease severity. For early glaucoma, we compared observation, laser and medications. For moderate glaucoma, medications, laser and surgery. For advanced glaucoma, medications and surgery. Main outcome measures were ICER (incremental cost-effectiveness ratio), medical direct costs and QALY (quality-adjusted life year).. In early glaucoma, both laser and medical treatment were cost-effective (ICERs of initial laser and initial medical treatment over observation only, were R$ 2,811.39/QALY and R$ 3,450.47/QALY). Compared to observation strategy, the two alternatives have provided significant gains in quality of life. In moderate glaucoma population, medical treatment presented the highest costs among treatment strategies. Both laser and surgery were highly cost-effective in this group. For advanced glaucoma, both tested strategies were cost-effective. Starting age had a great impact on results in all studied groups. Initiating glaucoma therapy using laser or surgery were more cost-effective, the younger the patient.. All tested treatment strategies for glaucoma provided real gains in quality of life and were cost-effective. However, according to the disease severity, not all strategies provided the same cost-effectiveness profile. Based on our findings, there should be a preferred strategy for each glaucoma stage, according to a cost-effectiveness ratio ranking.

Topics: Age Factors; Antihypertensive Agents; Brazil; Cost-Benefit Analysis; Glaucoma, Open-Angle; Health Care Costs; Humans; Lasers, Gas; Markov Chains; Prostaglandins; Quality of Life; Quality-Adjusted Life Years; Severity of Illness Index; Sulfonamides; Thiophenes; Timolol; Trabeculectomy; Watchful Waiting

Glaucoma patients frequently instill eye drops multiple times each day, which is a cause for reduced compliance. Additionally, eye drops suffer from other limitations including low bioavailability, which can lead to side effects. We propose to develop drug-eluting contact lenses for managing glaucoma with increased bioavailability and improved compliance. Contact lenses are developed for extended simultaneous release of timolol and dorzolamide, both of which are commonly prescribed hydrophilic drugs. The extended release is achieved by loading lenses with vitamin E barriers. In vitro release studies are performed with control and vitamin E loaded lenses for both drugs loaded separately and then together in the same lens. The safety and efficacy of combination therapy by contacts are demonstrated in a Beagle model of glaucoma. Simultaneous loading of timolol and dorzolamide increases the release duration of both drugs. Also vitamin E incorporation is highly effective in increasing the release durations of both drugs to about 2-days. The lenses loaded with both drugs exhibited superior IOP reduction compared to eye drops with about 6-fold lower drug loading. More importantly, combination therapy by continuous wear of vitamin E loaded contact for 2-days, followed by a new set of contacts for another two days, reduced IOP during the 4days of wear time and for another 8days after removal of the contacts. Vitamin E loading is very effective for providing combination therapy by contact lenses due to the increase in release durations of several drugs. The contact lens based therapy reduces IOP with lower drug dose compared to eye drops and may significantly improve the compliance as the effect of the therapy lasts significantly longer than the wear-duration.

Topics: Animals; Antihypertensive Agents; Biological Availability; Contact Lenses; Delayed-Action Preparations; Dogs; Drug Liberation; Drug Therapy, Combination; Glaucoma, Open-Angle; Heart Rate; Intraocular Pressure; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol; Vitamin E

To compare the ocular pulse amplitude (OPA) lowering effects of preservative-free tafluprost and dorzolamide-timolol fixed combination (DTFC) using dynamic contour tonometry.. In total, 66 eyes of 66 patients with normal tension glaucoma (NTG) (n = 34) or primary open angle glaucoma (POAG) (n = 32) were included. Patients were divided into two groups: the preservative-free tafluprost-treated group (n = 33) and the preservative-free DTFC-treated group (n = 33). Intraocular pressure (IOP) was measured using Goldmann applanation tonometry (GAT). OPA was measured using dynamic contour tonometry; corrected OPA (cOPA) was calculated at baseline and at 1 week and 1, 3, and 6 months after treatment.. After 6 months of treatment, tafluprost significantly reduced IOP (P < 0.001). The OPA lowering effects differed significantly between the two treatment groups (P = 0.003). The cOPA-lowering effect of tafluprost (1.09 mmHg) was significantly greater than that of DTFC (0.36 mmHg) after 6 months of treatment (P = 0.01).. Tafluprost and DTFC glaucoma treatments provided marked OPA and IOP lowering effects. Tafluprost had a greater effect than DTFC; thus, this drug is recommended for patients at risk of glaucoma progression, due to the high OPA caused by large fluctuations in IOP.

Topics: Drug Combinations; Eye; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Low Tension Glaucoma; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins F; Retrospective Studies; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

We report the case of an 83-year-old man who had had cataract surgery in both eyes and was being treated with timolol and dorzolamide in the right eye. Goldmann tonometry was 28 mm Hg in the right eye and 14 mm Hg in the left eye. Biomicroscopy of the right eye revealed pigment dispersion on the corneal endothelium, trabecular meshwork, and intraocular lens (IOL), as well as iris transillumination defects. After pupil dilation, a ciliary sulcus-implanted 1-piece IOL and a ruptured posterior capsule could be seen. Optical coherence tomography showed a diminished nerve fiber layer. Exchange for a 3-piece IOL was performed, but the intraocular pressure (IOP) remained high. For that reason, a trabeculectomy was performed. The final IOP was 12 mm Hg, and the visual fields were stable. This case highlights the importance of IOL choice for sulcus implantation.. No author has a financial or proprietary interest in any material or method mentioned.

Topics: Aged, 80 and over; Antihypertensive Agents; Ciliary Body; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Lens Implantation, Intraocular; Lenses, Intraocular; Male; Phacoemulsification; Prosthesis Design; Sulfonamides; Thiophenes; Timolol; Tomography, Optical Coherence; Tonometry, Ocular; Visual Acuity

We report a case of Urrets-Zavalia Syndrome after a glaucoma filtration device (g.f.d.) implantation. A 74-year-old woman with bilateral advanced glaucoma has been planned for surgery. The patient underwent to g.f.d. implantation in the right eye. On postoperative day 1, the patient had an edematous cornea with a dilated and non reactive pupil. In this article we describe the clinical history of this patient. To our knowledge, this is the first case of Urrets-Zavalia Syndrome after a g.f.d. implantation.

Topics: Acetazolamide; Aged; Brimonidine Tartrate; Cataract Extraction; Combined Modality Therapy; Drug Resistance; Drug Therapy, Combination; Female; Glaucoma Drainage Implants; Glaucoma, Open-Angle; Humans; Hypertension; Miotics; Mydriasis; Ocular Hypertension; Pilocarpine; Prostaglandins F; Quinoxalines; Sulfonamides; Syndrome; Thiophenes; Timolol

To determine the prevalence of signs and symptoms of ocular surface disease (OSD) in patients using topical intraocular pressure-lowering therapy.. In this cross-sectional study, 40 patients were consecutively recruited from the glaucoma clinic of a public hospital located in Rio de Janeiro, Brazil. Eligible patients were 18 years of age or older, with primary open-angle glaucoma or ocular hypertension and on the same topical ocular therapy for at least 6 months. The following data were considered: sex, age, medication history and number of years on topical intraocular pressure-lowering therapy. All patients underwent an evaluation of the ocular surface which included: an interview using the Ocular Surface Disease Index® (OSDI®) questionnaire, break-up time, biomicroscopy, fluorescein corneal staining and rose Bengal ocular surface staining.. The mean OSDI® score was 24.6 ± 20.7. Most patients (67.5%) had an abnormal score on the OSDI® questionnaire. In 25% of patients, the score was consistent with mild symptoms, 12.5% with moderate symptoms and 30% with severe symptoms. Blepharitis and punctate keratitis were diagnosed in 42.5% and 20% of patients respectively. Tear film instability was observed in 75% of patients and ocular surface staining with rose Bengal in 35%. A positive statistically significant correlation (r=0.4; p=0.01) was found between OSDI® scores and the duration of topical intraocular pressure-lowering therapy.. Patients with primary open-angle glaucoma or ocular hypertension on topical intraocular pressure-lowering therapy have high prevalence of OSD. Longer duration since diagnosis is significantly correlated with worsening of OSD symptoms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Blepharitis; Cornea; Cross-Sectional Studies; Female; Fluorescein; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Keratitis; Lacrimal Apparatus Diseases; Male; Microscopy, Acoustic; Middle Aged; Ocular Hypertension; Severity of Illness Index; Sulfonamides; Surveys and Questionnaires; Thiophenes; Timolol; Young Adult

To evaluate the long-term effects and costs of four treatment strategies for primary open-angle glaucoma compared to usual care.. Cost-effectiveness analyses with a lifelong horizon were made from a societal perspective. Data were generated with a patient-level model based on discrete event simulation. The model structure and parameter estimates were based on literature, particularly clinical studies on the natural course of glaucoma and the effect of treatment. We simulated heterogeneous cohorts of 3000 patients and explored the impact of uncertainty with sensitivity analyses.. The incremental cost-effectiveness ratio (ICER) of initial treatment with a prostaglandin analogue compared with a β-blocker was €12.931 per quality-adjusted life year (QALY) gained. A low initial target pressure (15 mmHg) resulted in 0.115 QALYs gained and €1550 saved compared to a gradual decrease from 21 to 15 mmHg upon progression. Visual field (VF) measurements every 6 rather than 12 months lead to health gains at increased costs (ICER €173,486 per QALY gained), whereas measurements every 24 months lead to health losses at reduced costs (ICER €21,516 per QALY lost). All treatment strategies were dominant over 'withholding treatment'.. From a cost-effectiveness point of view, it seems advantageous to aim for a low intraocular pressure in all glaucoma patients. The feasibility of this strategy should therefore be investigated. Additionally, the cost-effectiveness outcomes of initiating monotherapy with a prostaglandin analogue and reducing the frequency of VF testing may be acceptable.

Topics: Administration, Topical; Antihypertensive Agents; Brimonidine Tartrate; Cost-Benefit Analysis; Decision Support Techniques; Disease Progression; Drug Costs; Economics, Pharmaceutical; Follow-Up Studies; Glaucoma, Open-Angle; Health Care Costs; Humans; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Prostaglandins F, Synthetic; Quality-Adjusted Life Years; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To test the ability of dorzolamide hydrochloride and timolol maleate to display antioxidant effects.. Antioxidant activity was tested in whole trabecular meshwork (TM) tissue as collected from corneal donors' biopsy specimens, young (third passage) and old (10th passage) human TM cells, and acellular systems composed of pure DNA and subcellular fractions containing or devoid of mitochondria. Oxidative stress was induced by hydrogen peroxide. Monitored end points included DNA fragmentation as evaluated by the halo test, oxidative DNA damage in terms of 8-hydroxy-2'-deoxyguanosine, and mitochondrial function as evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide test.. The antioxidant effect of dorzolamide and timolol were observed on TM biopsy specimens and human TM cells exposed to hydrogen peroxide. As evaluated in cell subfractions, timolol displays antioxidant activity regardless of mitochondria presence. Conversely, the antioxidant activity of dorzolamide was maximized in the presence of mitochondria-containing subcellular fractions and in young human TM cells with functional mitochondria.. The antioxidant effect of timolol was direct. The antioxidant effect of dorzolamide involves mitochondria and is likely to be exerted mainly during the early glaucoma phases when the mitochondrial damage in the TM tissue still occurs at low levels. Clinical Relevance  Timolol has an antioxidant effect on the entire cell, whereas dorzolamide exerts protective activity toward oxidative stress only in the presence of intact mitochondria (ie, in endothelial cells that are younger when the cellular damage is still limited). The important role of mitochondrial damage in primary open- angle glaucoma is supported by the finding that mutant myocilin impairs mitochondrial functions in human TM meshwork cells.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antioxidants; Autoradiography; Cell Line; Chromatography, Thin Layer; Deoxyguanosine; DNA Fragmentation; Glaucoma, Open-Angle; Humans; Hydrogen Peroxide; Mitochondria; Oxidative Stress; Sulfonamides; Thiophenes; Timolol; Tissue Donors; Trabecular Meshwork

Argon Laser Trabeculoplasty (ALT) is a recognized method for reducing intraocular pressure (IOP) in patients with open angle glaucoma. The aim of this study was to compare the effects of primary medicament therapy and primary ALT on IOP regulation and stability of perimetry findings.. A total of 50 eyes of 35 patients were treated with primary ALT while 50 eyes of 36 patients were treated with primary medicament therapy with 0.5% timolol with 20, 0.005% latanoprost 18 and with 2% dorzolamid 12 eyes. IOP was controled at 3 months, and the visual field at 6 months during a 30-month follow-up period.. In the first 24 months of follow-up there was no statistically significant difference in percentage of eyes with successfully regulated IOP. At 27th and 30th month, in the group primarily treated with medicaments a statistically significant higher percentage of successfully regulated IOP was observed in 98%, and 96% of the eyes, respectively, while in the group primarily treated with ALT the decline in the percentage of successfully regulated IOP was observed in 78% and 76% of the eyes, (chi2-test, p = 0.002, p = 0.140). Both therapy groups showed stability of perimetry findings without statistically significant difference in the values of mean deviation (MD) index until the end of the monitoring period. The dynamics of change in MD index value showed a statistically significant greater decline in this parameter in subjects who had been primarily treated with medications during the last six months of follow-up, (two-factor analysis of variance with a repeated measurement, factor of time x type of therapy, p = 0.030).. Primary ALT equally successfully regulates IOP and restores stability of perimetry findings in patients with open angle glaucoma like the primary medicament therapy.

Topics: Aged; Antihypertensive Agents; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Laser Therapy; Lasers, Gas; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Trabeculectomy; Visual Field Tests

Purpose. To determine (1) the magnitude of retinal arteriolar vascular reactivity to normoxic hypercapnia in patients with untreated primary open-angle glaucoma (uPOAG) or progressive (p)POAG and in control subjects and (2) the effect of treatment with 2% dorzolamide on retinal vascular reactivity in uPOAG. Methods. The sample comprised 11 patients with uPOAG (after undergoing treatment, they became treated (t)POAG), 17 patients with pPOAG (i.e., manifesting optic disc hemorrhage), and 17 age-similar control subjects. The partial pressure of end-tidal CO(2) (PetCO(2)) was stabilized at 38 mm Hg at baseline. After baseline (10 minutes), normoxic hypercapnia was then induced (15 minutes) with an automated gas flow controller. Retinal arteriolar and optic nerve head (ONH) blood hemodynamics were assessed. The procedures were repeated after treatment with 2% dorzolamide for 2 weeks in tPOAG. Results. Baseline arteriolar hemodynamics were not different across the groups. In control subjects, diameter, velocity, and flow increased (P < 0.001) in response to normoxic hypercapnia. There was no change in all three hemodynamic parameters to normoxic hypercapnia in uPOAG, whereas only blood flow increased (P = 0.030) in pPOAG. Vascular reactivity was decreased in uPOAG and pPOAG patients compared with that in control subjects. After treatment with topical 2% dorzolamide for 2 weeks, the tPOAG group showed an increase in diameter, velocity, and flow (P

Topics: Administration, Topical; Aged; Arterioles; Blood Flow Velocity; Carbonic Anhydrase Inhibitors; Disease Progression; Glaucoma, Open-Angle; Humans; Hypercapnia; Intraocular Pressure; Laser-Doppler Flowmetry; Middle Aged; Optic Disk; Regional Blood Flow; Retinal Artery; Sulfonamides; Thiophenes

Topics: Antihypertensive Agents; Blood Flow Velocity; Disease Progression; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Optic Disk; Regional Blood Flow; Sulfonamides; Thiazines; Thiophenes; Timolol; Vision Disorders; Visual Fields

Novel bi-functional compounds with a nitric oxide (NO)-releasing moiety bound to a dorzolamide scaffold were investigated. Several compounds were synthesized and their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed different degrees of potency and selectivity to hCA II. A high resolution X-ray crystal structure for the CA II adduct with 8 confirmed the high affinity of this class of compounds for the enzyme. Compounds 4, 6, and 8 showed highly potent and efficacious NO-mediated properties as assessed by their vascular relaxant effect on methoxamine-precontracted rabbit aortic rings. Finally, compounds 4 and 6 exerted potent intraocular pressure (IOP) lowering effects in vivo in normotensive rabbits thereby anticipating their potential for the treatment of hypertensive glaucoma.

Topics: Animals; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Crystallography, X-Ray; Drug Discovery; Glaucoma, Open-Angle; Models, Molecular; Molecular Structure; Nitric Oxide; Rabbits; Structure-Activity Relationship; Sulfonamides; Thiophenes

To examine the response to intraocular pressure (IOP)-lowering medications as a function of glaucoma severity represented by visual field defects.. Post hoc analysis of a multicenter, double-masked, parallel study comparing the 24-h efficacy of the dorzolamide/timolol fixed combination (N = 117) versus timolol alone (N = 115) in patients with open-angle glaucoma or ocular hypertension. Visual field scoring was performed independently by three glaucoma specialists. Two scoring systems were used: the Advanced Glaucoma Intervention Study (AGIS) scoring system and a classical visual field scoring system. Patients were divided into three groups based on their visual field scores. The changes from baseline daytime and nighttime mean IOP, and 24-h IOP fluctuation after 8 weeks of treatment by baseline glaucoma severity, were compared across treatments using a simple linear regression analysis.. Most (approximately 73%) patients had no visual field damage at baseline. With either dorzolamide/timolol or timolol alone, there was no significant difference in IOP response from baseline over 24 h based on the level of visual field damage, as measured by either the AGIS or the classic visual field scoring systems. The Pearson's rho correlations between the baseline AGIS score and the change in daytime IOP, nighttime IOP, and 24-h IOP range were 0.0024 (P = 0.97), -0.086 (P = 0.21), and 0.076 (P = 0.26), respectively. Correlations by classic score were 0.024 (P = 0.72), -0.074 (P = 0.28), and 0.061 (P = 0.37), respectively.. This analysis showed no significant relation between the severity of baseline visual field defects and the ocular hypotensive efficacy of the dorzolamide/timolol fixed combination and timolol alone.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Double-Blind Method; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Linear Models; Male; Middle Aged; Ocular Hypertension; Randomized Controlled Trials as Topic; Severity of Illness Index; Sulfonamides; Thiophenes; Timolol; Visual Fields

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

Topics: Aged; Antihypertensive Agents; Choroid Diseases; Female; Fluorescein Angiography; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Sulfonamides; Thiophenes; Visual Acuity

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

Topics: Aged; Critical Care; Drug Therapy, Combination; Eye Diseases; Female; Glaucoma, Open-Angle; Humans; Metronidazole; Ophthalmic Solutions; Pheniramine; Prednisolone; Stevens-Johnson Syndrome; Sulfonamides; Thiophenes

Topics: Antihypertensive Agents; Cardiovascular Diseases; Diabetes Complications; Europe; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Prevalence; Risk Factors; Sulfonamides; Thiophenes; Treatment Outcome

There is evidence from theoretical models and animal studies that the biomechanical properties of the optic nerve head and the sclera play a role in the pathophysiology of glaucoma. There are, however, only a few data available that demonstrate such biomechanical alterations in vivo. In this study, the hypothesis was that patients with primary open-angle glaucoma (POAG) have an abnormal ocular structural stiffness based on measurements of intraocular pressure amplitude and ocular fundus pulsation amplitude (FPA).. Seventy patients with POAG and 70 healthy control subjects matched for age, sex, intraocular pressure and systemic blood pressure were included. The ocular PA and pulsatile ocular blood flow were assessed with pneumotonometry. The FPA was measured by using laser interferometry. Based on the Friedenwald equation, a coefficient of ocular rigidity (E1) was calculated relating PA to FPA.. There was no difference in systemic blood pressure, intraocular pressure, and ocular perfusion pressure (OPP) between the patients with glaucoma and the healthy control subjects. Both, FPA and PA were lower in the patients with glaucoma than in the control subjects. The calculated factor E1 was significantly higher in the patients with POAG (0.0454 +/- 0.0085 AU) than in the control subjects (0.0427 +/- 0.0058 AU, P = 0.03). Multiple regression analysis revealed that E1 was independent of age and sex, and correlated only slightly with OPP.. The present study indicates increased ocular rigidity in patients with POAG. This is compatible with a number of previous animal experiments and supports the concepts that the biomechanical properties of ocular tissues play a role in the diseases process.

Topics: Aged; Blood Pressure; Drug Therapy, Combination; Female; Fundus Oculi; Glaucoma, Open-Angle; Humans; Interferometry; Intraocular Pressure; Lasers; Latanoprost; Light; Male; Middle Aged; Prostaglandins F, Synthetic; Pulse; Reference Values; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

To investigate whether dorzolamide modifies peripapillary retinal haemodynamics in juvenile primary open-angle glaucoma (JPOAG) patients treated with timolol.. In 40 JPOAG subjects, before and after dorzolamide coadministration with timolol, the following examinations were achieved: intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), heart rate (HR), visual field and retinal flowmetry.. Adjunctive therapy with dorzolamide induced the following modifications: IOP reduction [1.75 mmHg, 95% confidence interval (CI) 1.23, 2.26; P < 0.05], OPP increase (5.09 mmHg, 95% CI 2.97, 7.20; P < 0.02) and retinal blood flow improvement (35.0 arbitrary units, 95% CI 12.20, 57.80; P < 0.03). BP, HR and visual field indices did not change.. Dorzolamide, in association or in fixed combination with timolol, significantly improves retinal blood flow in JPOAG patients.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Carbonic Anhydrase Inhibitors; Drug Interactions; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Regional Blood Flow; Sulfonamides; Thiophenes; Timolol

To report a case of pigmentary glaucoma treated with medical therapy, laser treatment, and trabeculotomy.. A 36-year-old man presented with the characteristic Krukenberg spindle on the corneal endothelial surface and heavily pigmented trabecular meshwork. He was diagnosed with pigmentary glaucoma and was initially placed on medical therapy which became less effective over time in controlling intraocular pressure (IOP). Ultrasound biomicroscopy revealing bilateral reverse pupillary block and laser iridotomy was performed in both eyes to eliminate irido-zonular contact causing pigment dispersion. However, argon laser trabeculoplasty (ALT) was subsequently performed in both eyes due to insufficient IOP control. The left eye responded well to ALT, and postoperative IOP has been 14-16 mmHg with medication. On the other hand, the right eye required selective laser trabeculoplasty for uncontrolled IOP after ALT. With little improvement in IOP control after laser treatment, the right eye eventually underwent trabeculotomy which resulted in long-term success in controlling IOP at about 16 mmHg and in preventing the progression of glaucomatous damage.. Improvement in IOP control with trabeculotomy was confirmed in a case of pigmentary glaucoma with heavily pigmented trabecular meshwork. Further studies are needed for evaluation of the management of pigmentary glaucoma.

Topics: Adrenergic alpha-Antagonists; Adult; Antihypertensive Agents; Argon; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iris; Laser Therapy; Male; Ophthalmic Solutions; Quinazolines; Sulfonamides; Thiophenes; Trabeculectomy; Treatment Outcome

Topics: Acute Disease; Antihypertensive Agents; Diclofenac; Drug Therapy, Combination; Female; Fluorescein Angiography; Glaucoma, Open-Angle; Humans; Middle Aged; Optic Disk; Optic Nerve Diseases; Retinal Detachment; Serum; Sulfonamides; Thiophenes; Timolol; Tomography, Optical Coherence; Vision Disorders; Visual Acuity

Hypotony with choroidal detachment is a rare complication of glaucoma medication. In this study, we report on a case which supports the hypothesis that has been proposed to explain this phenomenon.. This study was designed as an observational case report.. A woman with chronic glaucoma underwent trabeculectomy on both eyes. Low intraocular pressure (IOP) developed in 1 eye only, with no visual change for many years. After cataract surgery, the IOP increased, necessitating treatment with topical timolol 0.5% and dorzolamide 2%. She developed monocular hypotony and choroidal detachment 3 months later. This complication occurred in the eye that had previously had a low IOP and resolved completely when topical medication was stopped. The choroidal detachment recurred when rechallenged with the same medication.. Topical aqueous suppression therapy can result in hypotony and choroidal detachment in an eye in which relatively low IOP has been maintained for many years after glaucoma filtration surgery. The problem resolves on stopping the medication.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Cataract Extraction; Choroid Diseases; Chronic Disease; Drug Interactions; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Ocular Hypotension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Recurrence; Sulfonamides; Thiophenes; Timolol; Trabeculectomy

Topics: Antihypertensive Agents; Cardiovascular Diseases; Diuretics; Europe; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Optic Disk; Prevalence; Randomized Controlled Trials as Topic; Retinal Hemorrhage; Risk Factors; Sulfonamides; Thiophenes

To evaluate the changes in conjunctival impression cytology specimens from patients receiving various topical antiglaucoma medications.. Cross-sectional comparative study.. Impression cytology specimens were obtained from the eyes taking no topical medication (n = 20) and from the eyes taking various antiglaucoma medications (timolol n = 34; latanoprost n = 40; dorzolamide n = 32; timolol + latanoprost n = 30; timolol + dorzolamide n = 34). Specimens were graded on a scale of zero to three according to Nelson's method.. Cytology scores were significantly higher in the medication group than the control group. Mean cytology scores of the control, timolol, latanoprost, dorzolamide, timolol + latanoprost, and timolol + dorzolamide group were 0.20, 1.62, 2.00, 1.75, 2.13, and 2.44, respectively. Among the medication groups, cytology scores were significantly lower in the monotherapy group than the fixed-combination therapy group.. Various topical antiglaucoma medications induce a significant degree of squamous metaplasia. Conjunctival surface could be altered after the long-term use of antiglaucoma medication.

Topics: Administration, Topical; Antihypertensive Agents; Conjunctiva; Cross-Sectional Studies; Drug Therapy, Combination; Epithelium; Glaucoma, Open-Angle; Humans; Latanoprost; Metaplasia; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

Since its introduction in 1996, brimonidine tartrate 0.2% ophthalmic solution (Alphagan, Allergan) twice daily has become established as an effective intra ocular pressure-lowering treatment. While the efficacy of Alphagan cannot be questioned, we gained the clinical impression that the drug has an unacceptably high rate of allergy. Of greater concern, we suspected that patients suffering from local Alphagan allergy had a higher rate of allergy to subsequently used topical preparations. We analysed data from a large scale study of glaucoma patients to establish whether our suspicions were correct.. We have created a database of the entire glaucoma treatment histories for consecutive patients attending a single consultant's clinics (DMIM) at Glasgow Royal Infirmary between May 1999 and September 2001. All have undergone medical treatment for primary open angle glaucoma, ocular hypertension, or normal tension glaucoma. Patients with any other form of glaucoma, and patients in whom a full record of treatment was not available were excluded from the study.. Alphagan was discontinued due to allergy on 73 per 100,000 patient treatment days. This was a far higher frequency than for other preparations. In patients allergic to both Alphagan and another preparation (Timoptol, Trusopt and Xalatan), the mean interval between the first and second allergy was shorter when Alphagan allergy occurred first. This was statistically significant in Timoptol and Trusopt cross-reactivity.. Alphagan has high allergenicity, and may increase the likelihood of allergy to subsequently used preparations.

Topics: Adrenergic alpha-Agonists; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Cross Reactions; Drug Administration Schedule; Drug Hypersensitivity; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Longitudinal Studies; Male; Middle Aged; Ophthalmic Solutions; Quinoxalines; Retrospective Studies; Sulfonamides; Thiophenes; Timolol

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Conjunctival Diseases; Glaucoma, Open-Angle; Humans; Male; Quinoxalines; Sulfonamides; Thiophenes

Topics: Aged; Dermatitis, Allergic Contact; Diagnosis, Differential; Glaucoma, Open-Angle; Humans; Male; Ophthalmic Solutions; Patch Tests; Sulfonamides; Thiophenes

Topics: Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Europe; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Sulfonamides; Thiophenes

There is evidence that altered optic nerve head (ONH) blood flow may play a role in the development and progression of glaucoma. In the present study, the baseline characteristics were examined in a study population participating in a clinical trial in which the ocular hemodynamic effects of timolol and dorzolamide were compared.. One hundred forty patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) were included in this trial and their baseline parameters compared with those of a group of 102 age-matched control subjects. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the ONH. Pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. In addition, hemodynamic parameters and mean arterial pressure were calculated in both groups.. All ocular hemodynamic parameters were significantly lower in the POAG/OHT group compared with the healthy control group (P < 0.001 each). In addition, a significant positive correlation between laser Doppler flowmetry readings and mean arterial pressure was observed in patients with glaucoma but not in healthy control subjects. Likewise, the correlation coefficient between fundus pulsation amplitude and mean arterial pressure was higher in patients with glaucoma than in healthy control subjects.. The present study indicates reduced ONH and choroidal blood flow and an abnormal association between blood pressure and ocular perfusion in patients with primary open-angle glaucoma or ocular hypertension, independent of topical antiglaucoma medication. Hence, vascular dysregulation appears to be an early manifestation in glaucoma that is not caused by pharmacologic intervention.

Topics: Antihypertensive Agents; Blood Flow Velocity; Blood Pressure; Choroid; Clinical Trials as Topic; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Laser-Doppler Flowmetry; Male; Middle Aged; Ocular Hypertension; Optic Disk; Pulsatile Flow; Regional Blood Flow; Retrospective Studies; Sulfonamides; Thiophenes; Timolol; Visual Fields

Recent advances in pharmacotherapy that have improved the ability to effect sustained reductions in intraocular pressure may delay or obviate the need for surgery for open-angle glaucoma. This analysis explored this possibility by evaluating the frequency of surgeries for open-angle glaucoma in the US Medicare population before and after the 1996 introduction of latanoprost, a topical prostaglandin analogue with potent ocular antihypertensive efficacy and a better safety profile than older topical glaucoma medications.. Data from the Medicare 5% Standard Analytical File were used to develop national estimates of the frequency of glaucoma surgeries in the US yearly from 1994 through 1999.. While the number of US Medicare patients with a diagnosis of glaucoma remained constant from 1994 through 1999, the number of inpatient and outpatient glaucoma surgeries declined with a particularly sharp drop between 1996 and 1997. In 1999 relative to 1994, the number of annual glaucoma surgeries among unique patients with a diagnosis of glaucoma was reduced by 72% for inpatient procedures and 42% for outpatient procedures.. The number of glaucoma surgeries among US Medicare patients markedly decreased from 1994 to 1999, during which time the prevalence of glaucoma remained stable in this population. The decrease in surgeries coincided with the introduction of improved topical pharmacotherapies for the management of glaucoma. Although the ability to infer a causal relationship between introduction of new pharmacotherapy and the decrease in surgeries is limited, the consistency of these data with those of several other studies renders the findings compelling.

Topics: Administration, Topical; Antihypertensive Agents; Brimonidine Tartrate; Drug Therapy; Drug Utilization; Filtering Surgery; Glaucoma, Open-Angle; Humans; Inpatients; Latanoprost; Medicare; Ophthalmic Solutions; Outpatients; Prevalence; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; United States

Topics: Accelerated Idioventricular Rhythm; Antihypertensive Agents; Drug Combinations; Electrocardiography; Female; Glaucoma, Open-Angle; Humans; Middle Aged; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol

Choroidal detachment is a known complication of topical hypotensive agents when used to treat eyes sensitized by prior surgery. We document the abrupt development of an extensive choroidal detachment after initiation of dorzolamide therapy in a surgically untreated eye with primary open-angle glaucoma.. Observational case report.. A 76-year-old woman with primary open-angle glaucoma and no history of ocular surgery developed a choroidal detachment 12 hours after initiation of therapy with dorzolamide eye drops. Choroidal detachment was diagnosed clinically and confirmed by echography.. Withdrawal of the drug and initiation of corticosteroid drops resulted in prompt resolution of the choroidal detachment.. Choroidal detachment can occur in surgically untreated eyes after use of a topical carbonic anhydrase inhibitor.

Topics: Aged; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Choroid Diseases; Female; Glaucoma, Open-Angle; Humans; Sulfonamides; Thiophenes; Ultrasonography

The purpose of this study was to compare the efficacy of the fixed-combination solution of timolol 0.5%/dorzolamide 2% with the concomitant administration of its components, timolol 0.5% twice a day and dorzolamide 2% twice a day. Ninety-eight patients adequately controlled with a concomitant regimen of timolol and dorzolamide were switched to the fixed-combination regimen of the same components. Intraocular pressures at baseline and 4 weeks after the change in regimen were recorded. The mean baseline intraocular pressure (IOP) was 16.0 +/- 5.6 mmHg. Four weeks after the change in medication to the fixed-combination regimen, the mean IOP was 14.5 +/- 5.6 mmHg. The mean IOP change from baseline was -1.5 +/- 3.9 mmHg. The difference between the two treatment modalities was found to be statistically significant (p-value < 0.001). Eighty-one (83%) patients were considered successfully switched after 4 weeks of fixed-combination therapy, and seventeen eyes (17%) were deemed unsuccessful because a rise in IOP was detected. In conclusion, the fixed combination of timolol 0.5%/dorzolamide 2% twice a day provided equivalent or better intraocular pressure reduction in most patients who were successfully controlled on concomitant administration of its components, timolol and dorzolamide.

Topics: Adrenergic beta-Antagonists; Aged; Drug Combinations; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Retrospective Studies; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

The frequent systemic side effects associated with the use of systemic carbonic anhydrase inhibitors have adversely affected the compliance to treatment in glaucoma patients, obviating their long-term use. The introduction of the topical CAI dorzolamide has further reduced their use. However, the tolerability of dorzolamide in patients who have been intolerant to systemic CAIs has not been evaluated prospectively.. To study the tolerability and efficacy of dorzolamide (a topical CAI) in a selected group of glaucoma and ocular hypertensive patients who have been intolerant to systemic CAI.. A 3 month prospective study was conducted in 39 patients. Following recruitment, patients were evaluated on the day of switching from systemic CAI to dorzolamide and for five more visits. The SF-36 health assessment questionnaire was used to evaluate changes in well-being and quality of life, and the intraocular pressure was measured periodically.. Within 4 weeks of switching from systemic CAI to dorzolamide, the mean health assessment scores improved significantly in seven of the eight categories of the SF-36, and remained generally unchanged for the rest of the study. No significant differences were noted between the mean IOP on day 0 and the following measurements throughout the 84 days of dorzolamide therapy.. In glaucoma patients who were intolerant to systemic CAI, topical CAI dorzolamide offers a similar efficacy and better tolerability.

Topics: Aged; Carbonic Anhydrase Inhibitors; Female; Glaucoma; Glaucoma, Open-Angle; Health Status Indicators; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Quality of Life; Sulfonamides; Thiophenes

To evaluate the ocular factors contributing to keratoepitheliopathy in glaucoma patients treated with or without anti-glaucomatous eyedrops, and the influences of each anti-glaucomatous eyedrop to keratoepitheliopathy.. The presence and severity of keratoepitheliopathy was investigated in 193 eyes of 110 glaucoma patients. The ocular factors examined were the status of the lipid layer of the tear fluid as assessed by a specular reflection video-recording system, tear volume assessed by Schirmer's test, and tear film stability assessed by tear break-up time. The influences of combined anti-glaucomatous eyedrops and each anti-glaucomatous eyedrops to keratoepitheliopathy were investigated.. The overall occurrence of superficial punctate keratitis was 29.0%. Superficial punctate keratitis was more frequently observed in patients who used more than two anti-glaucomatous eyedrops (35.9%) than in those who used without (19.7%) and one (30.9%). Results of Schirmer's test and break-up time were worse in patients who used combined medication. The occurrence of superficial punctate keratitis in patients who used timolol (46.2%) was significantly more frequent than in those who used carteolol (4.2%). Severity of superficial punctate keratitis and break-up time in patients who used timolol were significantly worse than in those who used carteolol. There were no differences of keratoepitheliopathy and ocular factors between patients who used latanoprost and unoprostone.. The usage of multiple anti-glaucomatous eyedrops induces keratoepitheliopathy by reducing the tear volume and the tear film stability. Carteolol may be used more safely for corneal epithelium.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Carteolol; Dinoprost; Drug Therapy, Combination; Epithelium, Corneal; Female; Glaucoma, Open-Angle; Humans; Keratitis; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Prostaglandins F, Synthetic; Risk Factors; Sulfonamides; Tears; Thiophenes; Timolol

Topics: Adrenergic beta-Antagonists; Aged; Blood Flow Velocity; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Eye; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Pulsatile Flow; Sulfonamides; Thiophenes; Timolol

Examination of the influence of dorzolamide on the autoregulation of retinal vessel diameter in glaucoma patients.. Eleven patients with primary open angle glaucoma (age 60 +/- 11) without medication and four weeks after starting therapy with dorzolamid eye drops three times daily were examined in the study. Short-time rise of intraocular pressure (IOP) was obtained via suction-cup. Functional reaction of the diameter of a segment of a retinal artery and corresponding vein were assessed by retinal vessel analyzer.. Dorzolamid lowered the IOP from 23.3 +/- 1.3 to 17.6 +/- 2.2 mmHg (p = 0.004). Therapy did not influence the absolute diameter of retinal vessels regarding maximal dilatation caused by the pressure rising provocation. In eyes with treatment the diameter decreased faster to baseline values (arteries 100 sec, veins 220 sec) compared to those without treatment (arteries 350 sec, veins 480 sec).. Dorzolamid might possibly be able to accelerate autoregulation of retinal vessels in response to short term artificial IOP increase.

Topics: Adult; Aged; Antihypertensive Agents; Female; Fluorescein Angiography; Glaucoma, Open-Angle; Homeostasis; Humans; Intraocular Pressure; Male; Middle Aged; Retinal Vessels; Sulfonamides; Thiophenes; Vascular Resistance

The author investigated 23 patients with primary open angle glaucoma treated with pilocarpine, timolol, betoptic and latanoprost. Because of inadequate compensation of the basic disease dorsolamide was added and the patients were followed up for a 12-month period. All combinations decreased significantly the intraocular pressure during the long-term follow up. The greatest decrease was recorded after a combination of a prostaglandin analogue and dorsolamide.

Topics: Aged; Betaxolol; Carbonic Anhydrase Inhibitors; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Pilocarpine; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

Topics: Acute Disease; Aged; Angina Pectoris; Glaucoma, Open-Angle; Humans; Latanoprost; Male; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Sulfonamides; Thiophenes; Vasoconstrictor Agents

Topical carbonic anhydrase inhibitors have been used since 1995 for medical glaucoma therapy, when dorzolamide was approved. In 2000, a second carbonic anhydrase inhibitor, brinzolamide, has become available in most of Europe. Both substances exhibit a comparable intraocular pressure-lowering activity, however, the side-effects are somewhat different. In the five years since its introduction, dorzolamide has had a positive risk-benefit-profile. In combination with any other topical agent, carbonic anhydrase inhibitors have an additive effect on the reduction of the intraocular pressure. Animal studies suggest that dorzolamide may improve ocular blood flow independent of the intraocular pressure; however, the significance for human glaucoma remains to be established.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Animals; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Rabbits; Sulfonamides; Thiazines; Thiophenes; Time Factors; Timolol

The purpose of this study was to evaluate refractive and anterior chamber depth changes after short-term dorzolamide use in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study was prospective and non-comparative and included 34 patients. Baseline refraction and anterior chamber depth were compared to the refraction and anterior chamber depth 14 days after commencing dorzolamide to determine if refraction or anterior chamber depth had been affected. Before dorzolamide use, the mean refractive error was -0.88 +/- 3.53 D (+/-SD). The mean refractive error was -0.94 +/- 3.65 D (+/-SD) two hours post-dose after 14 days of dorzolamide use, which was not significantly different (P = 0.50). The mean pre-treatment anterior chamber depth was 3.088 +/- 0.385 mm (+/-SD), which did not differ significantly from the post-treatment anterior chamber depth mean of 3.092 +/- 0.389 mm (+/-SD) (P = 0.88). The results of the study show that refraction and anterior chamber depth are not significantly altered by short-term dorzolamide use in patients with POAG and OH with no history of previous dorzolamide use.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anterior Chamber; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Female; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Refractive Errors; Sulfonamides; Thiophenes

The purpose of this study was to evaluate the ocular hypotensive efficacy and safety of latanoprost 0.005% (Xalatan, Pharmacia & Upjohn), brimonidine (Alphagan, Allergan), and dorzolamide (Trusopt, Merck Inc.) when added to a beta-blocker in patients with ocular hypertension or primary open-angle glaucoma. This was a multicenter, retrospective analysis which included all reviewed patient records in which latanoprost, brimonidine or dorzolamide were added to a beta-blocker for at least three months. Patients who were treated for less than three months, who failed therapy due to ineffectiveness of the medicine or an adverse event also were included. The study included 141 patients. Latanoprost (n = 50) showed an intraocular pressure of 16.7 +/- 3.3 mm Hg (-6.3 +/- 4.1 mm Hg, P < 0.001), brimonidine (n = 24) 17.4 +/- 4.9 mm Hg (-4.2 +/- 4.5 mm Hg, P < 0.001), and dorzolamide (n = 67) 20.1 +/- 6.1 mm Hg (-3.1 +/- 5.1 mm Hg, P < 0.001) at three months. A significant difference was observed in the absolute level of intraocular pressure (P < 0.005) and the change from baseline between groups (P < 0.005) at three months. A significant difference was observed between groups in the success rate of therapy between latanoprost (70%), brimonidine (58%) and dorzolamide (40%) (P = 0.008). No significant differences were observed between groups for rate or type of adverse events leading to discontinued therapy. This study showed that latanoprost, when added to beta-blockers, compares favorably in ocular hypotensive efficacy and is similar in safety to brimonidine and dorzolamide.

Topics: Administration, Topical; Adrenergic alpha-Agonists; Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Quinoxalines; Retrospective Studies; Safety; Sulfonamides; Thiophenes; Tonometry, Ocular

To report a case of marginal keratitis resulting from topical dorzolamide hypersensitivity.. Case report.. A 68-year-old woman presented with bilateral marginal keratitis 2 weeks after commencing bilateral topical dorzolamide. One week after discontinuation of topical dorzolamide, the patient was asymptomatic with complete resolution of corneal infiltrates.. Topical dorzolamide may cause a hypersensitivity reaction in the form of marginal keratitis. Discontinuation of the offending medication should result in complete resolution.

Topics: Administration, Topical; Aged; Carbonic Anhydrase Inhibitors; Drug Hypersensitivity; Female; Glaucoma, Open-Angle; Humans; Keratitis; Ophthalmic Solutions; Sulfonamides; Thiophenes

The relation between Goldmann applanation tonometry and central corneal thickness (CCT) was investigated in several studies during the last thirty years. It was the aim of the present study to evaluate CCT in normals, patients with ocular hypertension, low-tension, and open-angle glaucomas.. CCT was measured in 135 normal eyes, 137 with ocular hypertension, 65 with low-tension, and 94 with primary and secondary open-angle glaucomas using the AL-11000-pachymeter (Tomey). The results were compared using the unpaired t-test.. CCT was significantly higher in the patients with ocular hypertension (586 +/- 43 microns) than in the normal group (566 +/- 37 microns, p < 0.0001), in low-tension glaucomas (555 +/- 46 microns, p < 0.0001), and in open-angle glaucomas (558 +/- 31 microns, p < 0.0001). The latter three groups did not differ significantly. There was no significant correlation between CCT and age, the actually measured IOP, the highest IOP in the patient's history, or the spherical equivalent.. Only patients with ocular hypertension showed a significant difference in CCT compared with normals. Pachymetry thus should be conducted in those patients to avoid overestimation of the IOP by applanation tonometry. In most of the patients with low-tension and open-angle glaucomas however, CCT regarded without other parameters (e.g. corneal or scleral rigidity) plays a minor role in detection of elevated IOP according to the results of this study.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Case-Control Studies; Cornea; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Reference Values; Sex Distribution; Sulfonamides; Thiophenes

Topics: Aged; Anorexia; Carbonic Anhydrase Inhibitors; Dementia; Depression; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ophthalmic Solutions; Sulfonamides; Thiophenes; Visual Acuity

We evaluated the accuracy and the reproducibility of central corneal thickness measurements using an ultrasound pachymeter, and its usefulness in clinical practice.. We calculated the intra-observer, inter-observer, and inter-session variability in control subjects (n = 38). We observed the diurnal variation (n = 8) and the role of surgery (n = 12) on central corneal thickness. We measured and compared central corneal thickness and intraocular pressure in 6 groups (control subjects n = 134, primary open-angle glaucoma n = 111, ocular hypertension n = 66, normal tension glaucoma n = 12, diabetes mellitus n = 62, corneal graft n = 27). We studied the influence of dorzolamide on central corneal thickness (n = 16).. The intra-observer variability was 9 +/- 4 microns, whereas the inter-observer and inter-session variabilities were 4 microns and 5% m respectively. The central corneal thickness in patients with ocular hypertension (587 +/- 41 microns) was significantly greater than control subjects (548 +/- 32 microns) and all the other groups (p < 0.001). No influence of dorzolamide was observed on central corneal thickness.. Central corneal thickness assessed with an ultrasound pachymeter may be a useful and accurate method in selected patients whose intraocular pressure measurement does not correlate with other clinical findings.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Antihypertensive Agents; Cornea; Corneal Transplantation; Diabetes Mellitus; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Observer Variation; Ocular Hypertension; Reproducibility of Results; Sulfonamides; Thiophenes; Ultrasonography

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Drug Therapy, Combination; Female; Glaucoma, Angle-Closure; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Levobunolol; Macula Lutea; Middle Aged; Ocular Hypotension; Ophthalmic Solutions; Prednisolone; Prodrugs; Pseudophakia; Recurrence; Retinal Diseases; Sulfonamides; Thiophenes; Ultrasonography

Dorzolamide (Trusopt) is the first topical carbonic anhydrase inhibitor (CAI) that is in clinical use in glaucoma therapy. It is known that CAI have a negative effect on corneal endothelial pumpfunction and therefore on the whole corneal physiology.. 20 patients with open angle glaucoma or ocular hypertension and an elevated intraocular pressure (IOP) over 21 mmHg and without prior oral CAI-treatment were included in this study. Trusopt was administered t.i.d. as monotherapy and b.i.d. in combination with other topical antiglaucoma drugs. Corneal ultrasound pachymetry, corneal endothelial cell count and aesthesiometry were performed prestudy and on days 1, 8, 15, 30, 60 and 90.. Mean corneal thickness was slightly increased on day one (statistically non-significant) and returned to baseline measurements at the following visits, no changes in endothelial cell count and corneal anesthesia were found. Topical dorzolamide is not associated with clinically meaningful changes of the cornea.

Topics: Administration, Topical; Aged; Carbonic Anhydrase Inhibitors; Cell Count; Chronic Disease; Cornea; Drug Therapy, Combination; Endothelium, Corneal; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ocular Hypertension; Ophthalmic Solutions; Pilocarpine; Sensation; Sulfonamides; Thiophenes; Timolol

Topics: Adrenergic alpha-Agonists; Antihypertensive Agents; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Clonidine; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Latanoprost; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Treatment Outcome

Dorzolamide is a powerful inhibitor of carbonic anhydrase (CA) II that penetrates the sclera and cornea to reach the ciliary process and lowers formation of HCO3 and aqueous humor. The usual dose applied to the eye in treatment of glaucoma is 1 drop (30 microL of 2% solution) every 8 hr to each eye, or a total daily dose of 4 mg. On this regime, the red cells accumulated drug over a period of 8 days, reaching a value of 20-25 microM, which corresponds to the concentration of CA II in human red cells. This drug concentration persisted throughout the 18 months of application. The plasma concentration was 0.034 microM, or 1/700 that of the red cells. This plasma concentration corresponds to that calculated from the dilution of administered drug into body water. The data are well fitted into the equilibrium expression for KI of dorzolamide against CA II at 37 degrees C, as 8 x 10(-9) M. The red cells also contain a small amount (5 microM) of the N-des-ethyl metabolite, probably reflecting its modest binding to CA I. In the initial 8-day drug period, virtually none appeared in the urine since CA II sites were being filled. At steady state, renal excretion was 1.3 mg/day and the renal clearance 90 ml/min. These excretion numbers include the small (20%) amount of the des-ethyl metabolite of dorzolamide. The relation of these data to lowering of intraocular pressure is clear. By the systemic route, an inhibitor such as acetazolamide is effective when free drug concentration in plasma is 2.5 microM. In the case of topical drugs, as shown here, the plasma concentration is some 100 x lower, but the concentration in ciliary process is 2-10 microM, comparable to that following systemic drugs (1). In conclusion, the concentration in plasma (reflecting free drug) of dorzolamide is about 1/200 of that needed for systemic effects as seen following acetazolamide or methazolamide. Thus, there is a clear pharmacological basis for the lack of any physiological effects of ocular dorzolamide, except on the eye itself.

Topics: Administration, Topical; Aged; Carbonic Anhydrase Inhibitors; Erythrocytes; Female; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Ocular Hypertension; Sulfonamides; Thiophenes

Seven patients with open angle glaucoma were treated using Dorsolamida twice daily together Betablocant treat. Five patients with secondary glaucoma were treated with Dorsolamida three time daily as well three patients with edematous postimplant keratopathy. Intraocular pressure decreased with an average of 3-4 mm Hg and at the patients with corneal edema that decreased.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Carbonic Anhydrase Inhibitors; Chronic Disease; Combined Modality Therapy; Corneal Edema; Drug Evaluation; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Sulfonamides; Thiophenes; Time Factors

Topics: Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Chemical Precipitation; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Sulfonamides; Thiophenes

Ocular perfusion is increasingly being discussed in the pathogenesis of glaucoma. The present study was designed to investigate ocular pulse amplitude (OPA) in primary open-angle glaucoma (POAG) patients with elevated intraocular pressure (HTG) and non-glaucomatous controls (CTL) following topical application of the carbonic anhydrase inhibitor dorzolamide.. OPA (Ocular Blood Flow System, OBF Labs UK) intraocular pressure (IOP), heart rate (HR), and systolic (BPsyst) and diastolic (BPdiast) bronchial artery pressures were measured before and 2 days after initiating treatment in 33 cataract patients with n = 14) and without (n = 19) POAG.. Following application of dorzolamide, IOP (mmHg) in drug-treated HTG and CTL eyes was highly significantly reduced (p < 0.001) and in vehicle-treated HTG and CTL eyes significantly reduced (p < 0.03) compared to respective baseline measurements. OPA (mmHg) in drug-treated HTG and CTL eyes was significantly increased (p < 0.05) and in vehicle-treated eyes in affected compared to respective baseline measurements. Systemic perfusion parameters were also unchanged.. Dorzolamide increased OPA in HTG and CTL eyes. An increase in OPA may improve the prognosis of HTG.

Topics: Adult; Aged; Blood Pressure; Carbonic Anhydrase Inhibitors; Eye; Female; Glaucoma, Open-Angle; Heart Rate; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Pulsatile Flow; Regional Blood Flow; Sulfonamides; Thiophenes

Topics: Carbonic Anhydrase Inhibitors; Cell Count; Cornea; Endothelium, Corneal; Glaucoma, Open-Angle; Humans; Image Processing, Computer-Assisted; Middle Aged; Ophthalmic Solutions; Sulfonamides; Thiophenes; Ultrasonography; Visual Acuity