dorzolamide and Ocular-Hypertension

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

Topics: Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Drug Combinations; Humans; Intraocular Pressure; Ocular Hypertension; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

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 efficacy and tolerability of the fixed combination of Latanoprost/Timolol versus Dorzolamide/Timolol in the treatment of patients with elevated intraocular pressure (IOP).. A comprehensive literature meta-analysis was performed according to the Cochrane Collaboration methodology to identify randomized clinical trials comparing latanoprost/timolol FC (FCLT) with dorzolamide/timolol (FCDT) in patients with elevated IOP. The efficacy estimates were measured by the weight mean difference (WMD) for the IOP reduction (IOPR) from baseline to end point, including the diurnal mean IOPR, 8 AM IOPR, 12 PM IOPR, and 4 PM IOPR. The tolerability estimates were measured by RR for adverse events. All outcomes were reported with a 95% confidence interval (CI). The data were synthesized by Stata 12.0 SE for Windows.. Eight studies involving 841 patients (841 eyes) were included in the meta-analysis. With a WMD of IOPR in the diurnal mean of 0.16 mmHg (95% CI, -0.31 to 0.63), the FCLT was as effective as FCDT in lowering IOP in patients with elevated IOP (P = 0.51). The WMDs of IOPR were 0.58 mmHg (95% CI: -0.002 to 1.17) at 8 AM, -0.07 mmHg (95% CI: -0.50 to 0.36) at 12 PM, and 0.41 mmHg (95% CI: -0.18 to 1.00) at 4 PM, and there were no significant difference between FCLT and FCDT. FCLT was associated with a significantly lower incidence of eye pain, bitter taste, and irritation/stinging than FCDT, with pooled RRs of 0.34 (95% CI: 0.14 to 0.82), 0.06 (95% CI:0.008 to 0.42), and 0.35 (95% CI: 0.14 to 0.85), respectively.. FCLT was associated with equivalent efficacy in IOP lowering comparing with FCDT. However, FCLT was better tolerated than FCDT.

Topics: Antihypertensive Agents; Drug Tolerance; Female; Humans; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Timolol

Dorzolamide and brinzolamide are topical carbonic anhydrase inhibitors (CAI) indicated for patients with glaucoma and ocular hypertension.. An evidence-based review of clinical trials of dorzolamide and brinzolamide was undertaken to determine an effect of these medications on visual function (primarily visual field) in open-angle glaucoma and ocular hypertension. Using the keywords 'dorzolamide' and 'brinzolamide', all articles describing trials of these medications reporting on visual acuity, contrast sensitivity and visual field from September 1966 to July 2009 were found in MEDLINE and EMBASE databases. No information from other sources was included in this review.. A relatively modest number of trials was identified, where impact of therapy on one or more of the visual function modes was reported. In the studies of less than 1 year duration (3 days to 1 year, 23 studies) in all but three studies treatment with topical CAIs did not influence visual function, in two studies with dorzolamide some improvement in the contrast sensitivity was observed and in one open-label retrospective no-control-group study with dorzolamide visual field indices improved significantly. A different picture was seen in long-term studies, which were designed and powered to detect changes in visual field. One large study (European Glaucoma Prevention Study) with dorzolamide versus placebo failed to detect significant protective effect of the drug on glaucoma occurrence in ocular hypertensives. Several interesting aspects of this study are discussed in detail. The other two long-term studies reported on the superiority of adding dorzolamide over timolol therapy alone, and the superiority of the combination of dorzolamide and timolol over brinzolamide and timolol in terms of improving ocular blood flow (retrobulbar Color Doppler Imaging--CDI parameters) as well as in terms of visual field preservation in glaucoma patients over 4 to 5 years.. For the first time one study could demonstrate that an improvement in ocular blood flow in the long run results in preservation of visual field in glaucoma patients. Dorzolamide, combined with the beta-blocker timolol, seems to be superior in this regard to brinzolamide plus timolol.

Topics: Administration, Topical; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Ocular Hypertension; Sulfonamides; Thiazines; Thiophenes; Visual Fields

The aim of this study was to evaluate the efficacy and tolerability of latanoprost, compared with the combination of dorzolamide and timolol, in the treatment of patients with elevated intraocular pressure (IOP).. Pertinent randomized, controlled trials were identified through systematic searches of the Cochrane Library, PubMed, EMBASE, Chinese Biomedicine Database, and internet searches of meeting abstracts and the manufacturers' databases. The main efficacy measures were the IOP reduction (IOPR), including diurnal mean IOPR, and 10:00 IOPR. The main tolerability measure was withdrawal due to adverse events and individual adverse events.. Fourteen (14) studies involving 2149 patients were included in the meta-analysis. Latanoprost was significantly more effective in lowering diurnal mean IOP than combined dorzolamide and timolol in patients with IOP insufficiently controlled by timolol alone, with a weighted mean difference (WMD) for the diurnal mean IOPR% of 3.12 (95% confidence interval, 0.47-5.78) at 3 months, and latanoprost was as effective as the combination of dorzolamide and timolol in patients without baseline timolol treatment. The combination of dorzolamide and timolol was associated with numerically greater reductions in 10:00 IOP, compared with latanoprost in patients with or without timolol treatment at baseline: only the result in patients with baseline timolol treatment at 1 month was statistically significant (WMD -4.14: range, -5.78 to -2.50). The combination of dorzolamide and timolol was less tolerated than latanoprost, with pooled relative risk for withdrawals due to adverse events being 0.34 (range, 0.13-0.84).. Latanoprost was associated with significantly greater efficacy in lowering diurnal mean IOP than combined dorzolamide and timolol in patients with IOP insufficiently controlled by timolol alone, and latanoprost was as effective as combined dorzolamide and timolol in patients without baseline timolol treatment. The combination of dorzolamide and timolol was less tolerated than latanoprost.

Topics: Antihypertensive Agents; Drug Combinations; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Timolol

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

Brimonidine and dorzolamide are intraocular pressure (IOP)-lowering medications most commonly used in second-line treatment of glaucoma and ocular hypertension.. An evidence-based review of comparative clinical trials of brimonidine and dorzolamide was undertaken to determine the relative efficacy and safety of these drugs in reducing IOP. Using the keywords 'brimonidine' and 'dorzolamide', all articles describing such trials from September 1966 to July 2007 were found in MEDLINE and EMBASE.. In all identified studies, brimonidine and dorzolamide were both found to provide significant IOP reduction from treated or untreated baseline levels. Results of eight trials reported to date indicate that brimonidine produced either a lower treated IOP or greater pressure reduction from baseline than dorzolamide at one or more measured timepoints, and provided comparable IOP lowering over all other measurements. Differences between the IOP reductions provided by brimonidine and dorzolamide were more pronounced when the medications were used adjunctively with other classes of drugs. Six other trials showed similar efficacy, and one additional monotherapy study showed lower IOP with dorzolamide treatment. Ocular burning was noted with dorzolamide more than any other adverse event with either drug. Trials ranged widely in duration of therapy and the time of day IOP measurements were taken, and many were too small for sufficient statistical power.. Brimonidine and dorzolamide are both efficacious and reasonably well tolerated. Possible overall distinctions in efficacy were obscured by differences in study designs and treatment regimens, but adjunctive therapy with brimonidine may reduce IOP as effectively or more effectively than adjunctive or fixed combination dorzolamide therapy. In certain patients with glaucoma and ocular hypertension brimonidine may be a better choice than dorzolamide for second-line treatment.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Clinical Trials as Topic; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Male; Ocular Hypertension; Quinoxalines; Sulfonamides; Thiophenes; Treatment Outcome

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 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

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

Dorzolamide (dorzolamide hydrochloride), the first topical carbonic anhydrase (CA) inhibitor to become available for clinical use, lowers intraocular pressure (IOP) by reducing aqueous humour formation. It is formulated as a 2% eyedrop for use in the management of glaucoma and ocular hypertension. When administered 3 times daily, dorzolamide is effective in lowering IOP in patients with open-angle glaucoma or ocular hypertension. Mean IOP was reduced by approximately 4 to 6 mm Hg at peak (2 hours postdose) and 3 to 4.5 mm Hg at trough (8 hours postdose) in clinical trails. A 1-year comparative study showed that the ocular hypotensive efficacy of dorzolamine 2% 3 times daily was similar to that of betaxolol 0.5% twice daily, but slightly inferior to that of timolol 0.5% twice daily. Dorzolamide has additive ocular hypotensive effects when used in conjunction with topical beta-adrenergic antagonists and was as effective as pilocarpine 2% 4 times daily as adjunctive therapy in patients receiving timolol. Dorzolamide does not appear to produce the acid-base or electrolyte disturbances and severe systemic adverse events associated with oral CA inhibitors, and unlike beta-adrenergic antagonists, it is not contraindicated in patients with asthma, reactive airways disease or heart disease. Furthermore, as CA inhibitors do not cause miosis, they may cause less interference with vision than pilocarpine or epinephrine (adrenaline). The most common adverse effects associated with dorzolamide are bitter taste and transient local burning or stinging. Conjunctivitis was the most common reason for discontinuation of dorzolamide in one large study. Thus, available data suggest that dorzolamide has potential as an alternative therapy option in patients with glaucoma or ocular hypertension who are intolerant of, or unable to receive, ophthalmic beta-adrenergic antagonists and as adjunctive therapy in patients already receiving these agents. Further efficacy and tolerability data are needed to determine the place of dorzolamide in therapy.

Topics: Absorption; Aging; Animals; Antihypertensive Agents; Aqueous Humor; Carbonic Anhydrase Inhibitors; Controlled Clinical Trials as Topic; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Quality of Life; Regional Blood Flow; Retina; Sulfonamides; Thiophenes; Tissue Distribution

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

Posterior capsular opacification is treated using neodymium-doped yttrium aluminium garnet laser capsulotomy that leads to increased intraocular pressure. Here, we compare the effects of dorzolamide hydrochloride + timolol maleate versus brimonidine on intraocular pressure. We also investigate their side effects after neodymium-doped yttrium aluminium garnet laser capsulotomy. In these patients, there are no prior studies comparing the results of these two drugs.. Ninety patients with posterior capsule opacification contributed to the study. They received yttrium aluminium garnet laser capsulotomy. After yttrium aluminium garnet laser capsulotomy, they were randomized into three groups. Group 1 received dorzolamide hydrochloride + timolol maleate; Group 2 took brimonidine; and Group 3, the control group, took no drug. Group 1 took dorzolamide hydrochloride + timolol maleate eye drops 1. Brimonidine had a similar side effect profile to the fix combination. Intraocular pressure on the first (. We suggest that brimonidine and a combination of dorzolamide + timolol are similarly effective at reducing eye pressure for routine cases. In cases where intraocular pressure attacks might be at higher risk, using the dorzolamide + timolol combination would be more appropriate.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Capsule Opacification; Glaucoma; Humans; Intraocular Pressure; Lasers, Solid-State; Neodymium; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol; Yttrium

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 with postsurgical 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.. A total of 37 patients (61 eyes) were analyzed. The mean age of the patients was 4.1 years (SD: 3.8). In total, 43 eyes were included in the efficacy analysis. A total of 33 eyes (76.7%; 95% confidence interval, 61.4-88.2) were considered responders: 19 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 central corneal thickness at the time of surgery and the age at the time of surgery. IOP reduction was 9.7 mm Hg (SD: 2.6) for latanoprost, 8.4 mm Hg (SD: 1.5) for the latanoprost/dorzolamide combination, and 9.3 mm Hg (SD: 2.5) for the dorzolamide monotherapy. None of the patients was withdrawn because of adverse events.. Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children after surgery. Nonresponders were mainly patients with early presentation of the disease.

Topics: Antihypertensive Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Glaucoma; Humans; Infant; Intraocular Pressure; Italy; Latanoprost; Male; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Tonometry, Ocular; Treatment Outcome

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

OBJECTIVE To assess the effects of topically applied 2% dorzolamide hydrochloride-0.5% timolol maleate ophthalmic solution (DHTM) on incidence and severity of postoperative ocular hypertension (POH; ie, intraocular pressure [IOP] > 25 mm Hg) in dogs undergoing cataract extraction by phacoemulsification. DESIGN Randomized, masked, controlled study. ANIMALS 103 dogs (180 eyes). PROCEDURES Pertinent history, signalment, and ophthalmic examination findings were recorded. Dogs received 1 drop of DHTM or sham treatment solution (sterile, buffered, isotonic eye drops) in both eyes 14 hours and 2 hours before anesthetic induction and at the time of corneal incision closure (ie, end of surgery); IOPs were assessed by rebound tonometry 2, 4, 6, and 8 hours after surgery and between 7:30 and 8:00 am on the following day. Dogs with IOPs of 26 to 45 mm Hg received 1 drop of 0.005% latanoprost solution topically; the surgeon's treatment of choice was used for dogs with IOPs > 45 mm Hg. Incidence of POH and postoperative IOPs were compared between treatment groups. RESULTS DHTM treatment resulted in significantly lower incidence of POH than did sham treatment at the level of the dog (18/53 [34%] vs 31/50 [62%]) and the eye (24/94 [26%] vs 42/86 [48%]). Mean IOP did not differ between groups at the time of POH detection. The DHTM-treated eyes that developed POH were significantly more likely to have a 1-hour follow-up IOP < 25 mm Hg after latanoprost administration than were sham-treated eyes (19/25 [76%] vs 18/35 [51%]; OR, 3.87). CONCLUSIONS AND CLINICAL RELEVANCE Multidose perioperative administration of DHTM in dogs undergoing phacoemulsification reduced the incidence of POH and improved responsiveness of POH to latanoprost treatment.

Topics: Animals; Antihypertensive Agents; Cataract Extraction; Dog Diseases; Dogs; Drug Combinations; Ocular Hypertension; Perioperative Care; Postoperative Complications; Sulfonamides; Thiophenes; Timolol

To compare the efficacy of fixed combinations of dorzolamide-timolol (FCDT) and brimonidine-timolol (FCBT) in patients with intraocular pressure (IOP) elevations after intravitreal triamcinolone acetonide (IVTA) injections.. This was a prospective, randomized, open-label study. Patients who received IVTA injections due to diffuse diabetic macular edema and who had an IOP of 24 mm Hg or higher after IVTA treatment were included. They were randomized to receive either FCBT or FCDT twice daily. Follow-up visits were scheduled on week 4 and 12 weeks after starting the study medication. At all follow-up visits, IOP was measured with Goldmann applanation tonometry. The primary outcome measure was mean IOP, the secondary outcome was reduction in mean IOP at 4 and 12 weeks compared with postinjection values.. Sixty patients were randomized in 1:1 ratio. The FCBT and FCDT groups were similar in terms of age, sex, and preinjection IOP (P>0.05 for all). Mean postinjection IOP was 31.95±7.39 and 29.83±5.17 mm Hg in FCBT and FCDT groups, respectively (P=0.239). After 4 weeks, mean IOP was 17.05±3.61 mm Hg in FCBT and 18.93±3.30 mm Hg in FCDT groups (P=0.063). After 12 weeks, mean IOP in the FCBT and FCDT study groups was 16.35±2.70 and 18.43±2.82 mm Hg, respectively (P=0.012). Both fixed combinations significantly reduced IOP in comparison with the postinjection values (P<0.05). Mean reduction in IOP after 4 weeks were 14.90±7.28 mm Hg in FCBT and 10.90±4.83 mm Hg in FCDT groups (P=0.024); after 12 weeks, these values were 15.60±7.77 and 11.40±5.89 mm Hg in FCBT and FCDT groups, respectively (P=0.035).. Both FCBT and FCDT are effective in controlling IOP elevations after IVTA injections. The results of this study suggest that FCBT is superior to FCDT in reducing IOP and provides better IOP control after IVTA injections.

Topics: Aged; Antihypertensive Agents; Brimonidine Tartrate; Diabetic Retinopathy; Drug Combinations; Female; Glucocorticoids; Humans; Intraocular Pressure; Intravitreal Injections; Macular Edema; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Triamcinolone Acetonide

To evaluate the effect of early aqueous suppressant treatment on Ahmed glaucoma valve (AGV) surgery outcomes.. Randomized clinical trial.. Ninety-four eyes of 94 patients with refractory glaucoma.. After AGV implantation, 47 cases (group 1) received topical timolol-dorzolamide fixed-combination drops twice daily when intraocular pressure (IOP) exceeded 10 mmHg, whereas 47 controls (group 2) received conventional stepwise treatment when IOP exceeded target pressure.. Main outcome measures included IOP and success rate (6 mmHg < IOP < 15 mmHg and IOP reduction of at least 30% from baseline). Other outcome measures included best-corrected visual acuity, complications, and hypertensive phase frequency.. Groups 1 and 2 were both followed up for a mean of 45±11.6 and 47.2±7.4 weeks, respectively (P = 0.74). Mixed model analysis revealed a significantly greater IOP reduction in group 1 at all intervals (P<0.001). At 1 year, the cases exhibited a significantly higher success rate (63.2% vs. 33.3%; P = 0.008) and reduced hypertensive phase frequency (23.4% vs. 66.0%; P<0.001).. Early aqueous suppressant treatment may improve AGV implantation outcomes in terms of IOP reduction, success rate, and hypertensive phase frequency.

Topics: Adult; Antihypertensive Agents; Aqueous Humor; Carbonic Anhydrase Inhibitors; Drug Combinations; Female; Glaucoma; Glaucoma Drainage Implants; Humans; Intraocular Pressure; Logistic Models; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Timolol; Visual Acuity

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 describe the study design and baseline factors of the Heidelberg Retina Tomograph ancillary study within the EGPS. Furthermore, to examine the relationship between HRT optic disc topographic measurements and baseline demographic and ocular factors.. Four hundred and eighty-nine ocular hypertensive participants were included. Each participant completed HRT imaging at least annually. The associations between HRT measurements and IOP, central corneal thickness (CCT), baseline photographic estimates of vertical CDR ratio (CDR), asymmetry between the two eyes in CDR ratio and baseline visual field indices were assessed using regression analysis.. Associations between HRT measurements and vertical CDR by photographs were found for almost all stereometric optic disc parameters in both univariate and multivariate analysis. The strongest association was found between vertical CDR measurements and disc, cup and rim area; cup and rim volume, CDR area, linear CDR, mean and maximum cup depth and cup shape measure (all p < 0.0001). In multivariate analysis, pattern standard deviation (PSD) and HRT disc area had significant associations with several HRT optic disc measurements. Furthermore, CCT was significantly associated with reference height and the glaucoma probability score (GPS, outside normal limits).. The EGPS is the first multicentre, placebo-controlled randomized clinical trial to use HRT for monitoring optic disc changes in participants with ocular hypertension. We found strong associations between stereophotographic vertical CDR estimates, HRT disc area, PSD and several HRT parameters. We found, furthermore, that the parameters reference height and GPS were significantly related to central corneal thickness.

Topics: Carbonic Anhydrase Inhibitors; Double-Blind Method; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmoscopy; Optic Disk; Optic Nerve Diseases; Research Design; Sulfonamides; Thiophenes; Tomography; Tonometry, Ocular; Visual Acuity; Visual Fields

To evaluate the interaction of intraocular pressure(IOP)–lowering medications with physiologic day and night changes in aqueous humor dynamics in participants with ocular hypertension.. Thirty participants were enrolled in thisdouble-masked, randomized, crossover study. Each participant underwent aqueous humor dynamics measurements at baseline and at 2 weeks of dosing in random order with latanoprost in the evening and placebo in the morning, timolol maleate twice daily, and dorzolamide hydrochloride twice daily. Measurements included central corneal thickness by ultrasound pachymetry, anterior chamber depth by A-scan, seated and habitual IOP by pneumatonometry, blood pressure by sphygmomanometry,episcleral venous pressure by venomanometry,and aqueous flow by fluorophotometry. Outflow facility was assessed by fluorophotometry and by tonography. Uveoscleral outflow was mathematically calculated using the Goldmann equation.. Latanoprost use significantly decreased IOP during the day and night. It increased daytime uveoscleral outflow by a mean (SD) of 0.90 (1.46) μL/min (P=.048), but a nighttime increase of 0.26 (1.10) μL/min (P=.47)did not reach statistical significance. Timolol use decreased IOP during the day by reducing aqueous flow by 25%. Dorzolamide use lowered IOP only at the noon measurement and reduced daytime aqueous flow by 16%. Neither dorzolamide nor timolol use added to the physiologic 47% reduction in nighttime aqueous flow.. The daytime IOP-lowering effects of latanoprost are mediated by an increase in uveoscleral outflow,and those of timolol and dorzolamide are mediated by aqueous flow suppression. Nighttime physiologic changes in uveoscleral outflow limit the nighttime pharmacodynamic efficacy of latanoprost. Aqueous flow suppression with timolol and dorzolamide was ineffective in obtaining IOP lowering at night.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Aqueous Humor; Blood Pressure; Carbonic Anhydrase Inhibitors; Circadian Rhythm; Cornea; Cross-Over Studies; Double-Blind Method; Female; Fluorophotometry; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F, Synthetic; Sphygmomanometers; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Ultrasonography

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

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

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 compare the efficacy and safety of latanoprost against a fixed combination of dorzolamide and timolol in eyes with elevated intraocular pressure (IOP) or glaucoma and anterior or intermediate uveitis.. Fifty-eight patients with anterior or intermediate uveitis and elevated IOP or glaucoma presented or followed up in the Ocular Inflammation and Immunology Service of General Hospital of Athens were randomly assigned to receive treatment either with latanoprost (30) or with dorzolamide/timolol (28). The main outcome measures were inflammatory relapses and IOP response to treatment.. Ten patients (34%) in the latanoprost group and sixteen patients (57%) in the dorzolamide/timolol group experienced relapses of anterior uveitis (p = 0.93). There was no statistical difference between the two groups in respect of inflammatory relapses (p = 0.21). Twenty-one patients were followed up before starting latanoprost. The number of recurrences of anterior uveitis per patient per year before treatment with latanoprost was 0.82 +/- 1.2. The rate of relapses per patient per year after starting latanoprost was 0.39 +/-0.7 for these patients (p = 0.038). After 1 year of treatment, intraocular pressure was dropped from 27.8 +/- 8.4 mmHg to 18.6 +/- 5.3 mmHg (p < 0.001) in the latanoprost group and from 28.2 +/-8.1 mmHg to 22.6 +/-10.1 mmHg (p < 0.001) in the dorzolamide/timolol group. Four patients during treatment with latanoprost and five patients during treatment with dorzolamide/timolol developed macular edema.. Latanoprost is safe and equally effective to a fixed combination of dorzolamide and timolol in the treatment of uveitic glaucoma.

Topics: Adult; Antihypertensive Agents; Drug Combinations; Female; Follow-Up Studies; Glaucoma; Gonioscopy; Humans; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Prostaglandins F, Synthetic; Recurrence; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Treatment Outcome; Uveitis, Anterior; Uveitis, Intermediate; Visual Acuity

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

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Drug Combinations; Female; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Osmolar Concentration; Quinoxalines; Sulfonamides; Thiophenes; Time Factors; Timolol

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 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 effects of dorzolamide-timolol combination and brimonidine on intraocular pressure (IOP) after phacoemulsification surgery.. This prospective, randomized study included 69 eyes of 43 patients undergoing phacoemulsification and foldable intraocular lens implantation. Twenty-one patients were women and 22 were men. The mean patient age was 69.7+/-12.4 years. Patients were randomly assigned to one of three treatment groups preoperatively. Group A (n=23) received one drop of dorzolamide-timolol fixed combination and group B (n=23) received one drop of brimonidine tartrate 0.2% immediately after surgery. In group C (n=23), patients received no treatment and served as a control group. IOP was measured by Goldmann applanation tonometry 6 hours and 24 hours after surgery.. Six hours after surgery, the mean IOP was significantly lower in group A (16.3+/-2.9 mm Hg) than in groups B (20.6+/-2.9 mm Hg) and C (24.6+/-5.4 mm Hg). However, 24 hours after surgery, the mean IOP was higher in group C (19.8+/-4.7 mm Hg) than in the other two groups (14.1+/-2.8 mm Hg in group A and 17.5+/-2.7 mm Hg in group B).. Prophylactic treatment with dorzolamide-timolol fixed combination was more effective than brimonidine in reducing IOP 6 hours and 24 hours after phacoemulsification surgery.

Topics: Aged; Antihypertensive Agents; Brimonidine Tartrate; Drug Combinations; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Intraocular Pressure; Lens Implantation, Intraocular; Male; Ocular Hypertension; Phacoemulsification; Postoperative Care; Postoperative Complications; Prospective Studies; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

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

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 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 measure central corneal thickness (CCT) within the participants of the European Glaucoma Prevention Study (EGPS). This study was designed to test if lowering intraocular pressure (IOP) by means of dorzolamide is able to prevent or delay conversion from ocular hypertension to glaucoma.. Randomized, double-masked, controlled, observational clinical trial.. Eight hundred fifty-four of 1077 ocular hypertensive participants within the EGPS were investigated. Four hundred twenty-nine patients were treated with dorzolamide and 425 patients received placebo.. Treatment with dorzolamide or placebo (the vehicle of dorzolamide) in 1 or both eyes.. Central corneal thickness as measured by ultrasound pachymetry (DGH-500 Pachette; DGH Technologies, Exton, PA). The CCT measurements were obtained in the morning before measuring IOP. Five measurements were taken from each eye of each patient within 5 minutes of application of anesthetic eye drops.. Mean CCT was 572.6+/-37.4 microm (range, 458.5-695.6 microm). The CCT was higher in younger patients, male patients, and diabetic patients. Mean CCTs for the 429 patients receiving dorzolamide were 574.2+/-38.48 microm (range, 458.5-695.6 microm) and 571.0+/-36.21 microm (469.7-690.1 microm) for the 425 patients receiving placebo (P = 0.205). Central corneal thickness did not correlate with refraction, baseline IOP, or systemic hypertension.. Central corneal thickness measurements within the EGPS were greater than those reported in other studies of normal eyes without ocular hypertension. Larger CCT measurements correlated with male gender, younger age, and diabetes.

Topics: Adult; Age Factors; Aged; Cornea; Diabetes Complications; Double-Blind Method; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Sex Factors; Sulfonamides; Thiophenes; Ultrasonography

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

To evaluate the efficacy of fixed combination brimonidine-timolol (FCBT) versus fixed combination dorzolamide-timolol (FCDT) given twice daily in patients with primary open angle glaucoma (POAG) or ocular hypertension (OH).. Prospective, multicentre, masked-observer, crossover comparison.. Sixteen patients with POAG and 14 with OH.. The participants of the study were washed out from their previous medication and randomized to fixed FCBT or FCDT for the first 4-week treatment period. Subjects then were washed for 4 weeks and started on the opposite medication for the second 4-week period. Intraocular pressure (IOP) was measured with a Goldmann applanation tonometer at 8:00 a.m., 12:00 noon and 4:00 p.m. at each baseline and at the end of each treatment period. Unsolicited ocular adverse events were also recorded.. Comparison of the IOP lowering effect of FCBT and FCDT.. The baseline mean diurnal IOP for all 30 subjects (30 eyes) was 22.9 +/- 1.6 mmHg. Both fixed combinations significantly reduced IOP compared with baseline (p < 0.00001). The mean diurnal IOP following 4 weeks of therapy was 15.0 +/- 2.1 mmHg for FCBT and 15.4 +/- 2.1 mmHg for FCDT (p = 0.510). The mean diurnal IOP reduction was 7.8 +/- 1.9 mmHg for FCBT and 7.4 +/- 1.8 mmHg for FCDT (p = 0.430). Overall, 14 subjects complained about ocular adverse events: two only for FCBT, seven only for FCDT and five for both drugs. Although there was no significant difference between the number of subjects that reported ocular adverse events with FCBT (n = 7) and FCDT (n = 12) (p = 0.359), FCDT caused more ocular stinging upon instillation (n = 9) than FCBT (n = 1) (p = 0.027).. This study suggests that FCBT and FCDT, each given twice daily, have similar efficacy in patients with POAG or OH.

Topics: Aged; Brimonidine Tartrate; Cross-Over Studies; Drug Therapy, Combination; Female; Humans; Instillation, Drug; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Quinoxalines; Sulfonamides; Thiophenes; Timolol

To assess the safety, in terms of the intraocular pressure (IOP), of cataract surgery with primary posterior continuous curvilinear capsulorhexis (PPCCC) and a postoperative dose of a fixed dorzolamide-timolol combination and evaluate the effect of intraocular lens (IOL) haptic angulation.. Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.. In this prospective randomized double-masked bilateral study, 88 eyes of 44 consecutive patients with age-related cataract were included in an intraindividual comparison study. All patients had standardized cataract surgery with PPCCC and IOL implantation in the capsular bag followed by a postoperative dose of a fixed dorzolamide-timolol combination. Patients were randomly assigned to receive an ACR6D SE IOL (Laboratoires Cornéal) in 1 eye and a Centerflex (C-flex) 570C IOL (Rayner Surgical GmbH) in the contralateral eye. The IOP was measured at baseline and postoperatively at 6 and 24 hours as well as 1 week.. Intraindividual comparison showed statistically significantly higher IOP measurements in the C-flex 570C nonangulated IOL group than in the ACR6D SE angulated IOL group at 24 hours (P = .003) and 1 week (P = .043). The highest IOP spikes (34 mm Hg) were at 6 hours in 2 eyes with a C-flex 570C IOL. The ACR6D SE group had statistically significant changes in IOP between preoperative and all postoperative time points. In the C-flex 570C group, the only statistically significant change in IOP was between preoperatively and 6 hours postoperatively.. Cataract surgery with PPCCC was safe in terms of the postoperative IOP course. Haptic angulation slightly decreased the overall IOP rise and the incidence of IOP rises above 30 mm Hg.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Capsulorhexis; Cataract; Combined Modality Therapy; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Intraocular Pressure; Lens Implantation, Intraocular; Lenses, Intraocular; Male; Middle Aged; Ocular Hypertension; Postoperative Complications; Prospective Studies; Prosthesis Design; Sulfonamides; Thiophenes; Timolol

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

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

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

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

In previous analyses of primary efficacy data from two randomized clinical trials, standard dosing regimens of the dorzolamide/timolol fixed combination (COSOPT) and latanoprost (XALATAN) were shown to have equivalent efficacy with regard to reduction in mean daytime diurnal intraocular pressure (IOP). We performed additional post hoc analyses of pooled data from these studies to compare further the efficacy of the two treatments. The studies used identical 3-month, parallel group, randomized, observer-masked and patient-masked, multicenter designs. Patients with a baseline IOP > or = 24 mm Hg were randomized to either the 2% dorzolamide/0.5% timolol combination eye drops twice daily (n = 273) or 0.005% latanoprost eye drops once daily (n = 271). The IOP measurements were made at 8 AM, 10 AM, 2 PM, and 4 PM at the baseline visit and then on each of the 3 monthly assessment days. The following measures were analyzed on a post hoc basis: 1) percentages of patients meeting target levels of IOP reduction; 2) mean IOP reduction in those patients with high IOP (> or =30 mmHg) at baseline; 3) mean IOP at each of the assessment time points during a day. A total of 259 patients in the dorzolamide/timolol group and 268 patients in the latanoprost group were included in the efficacy analysis. At 3 months, both treatments showed similar efficacy with regard to the percentages of patients who achieved target levels of IOP reduction (e.g., 40% IOP reduction in 15% of dorzolamide/timolol combination patients and 13% of latanoprost patients), mean IOP reduction in those patients with high IOP at baseline (dorzolamide/ timolol combination, 12.5 mmHg, latanoprost, 12.6 mmHg), and mean IOP at each time point during the day. By the measures used in this analysis, the dorzolamide/timolol combination and latanoprost were equally effective at lowering IOP in patients with ocular hypertension or glaucoma.

Topics: Double-Blind Method; Drug Combinations; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

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

Topics: Antihypertensive Agents; Child, Preschool; Double-Blind Method; Female; Glaucoma; Humans; Infant; Intraocular Pressure; Male; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Safety; Sulfonamides; Thiophenes; Timolol; 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

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 determine the effect on aqueous flow of topical dorzolamide 2%, topical timolol 0.5%, or oral acetazolamide 250 mg when used alone or when dorzolamide is combined with either timolol or acetazolamide.. In 30 patients with ocular hypertension, aqueous flow and intraocular pressure (IOP) were determined at baseline and on the following combinations of drugs in a crossover design: (1) vehicle alone, (2) dorzolamide alone, (3) acetazolamide alone, (4) timolol alone, (5) dorzolamide + acetazolamide, and (6) dorzolamide + timolol. Treated eyes were compared with control eyes and comparisons were made between treatments.. Compared with baseline, significant (P < 0.04) IOP reductions in the order of efficacy were: dorzolamide + timolol > dorzolamide + acetazolamide = acetazolamide = timolol > dorzolamide. Aqueous flow was reduced more by dorzolamide + timolol than by each drug alone (P < 0.04) and more by dorzolamide + acetazolamide than by dorzolamide alone (P < 0.04).. The combination of dorzolamide and timolol demonstrated significant aqueous flow additivity and had greater IOP efficacy than the combination of dorzolamide and acetazolamide.

Topics: Acetazolamide; Administration, Oral; Administration, Topical; Adult; Aged; Antihypertensive Agents; Aqueous Humor; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Fluorophotometry; Humans; Intraocular Pressure; Male; Manometry; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol

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

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

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 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

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

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 efficacy of dorzolamide compared to apraclonidine, in the prevention of the intra-ocular pressure (IOP) spike after Nd :YAG laser posterior capsulotomy. SITE: Department of Ophthalmology, State University of Campinas (UNICAMP) General Hospital, Campinas, São Paulo, Brazil.. In a double masked prospective clinical trial, 217 eyes from 217 patients were randomly assigned to receive either dorzolamide 2 h before and placebo 1 h before Nd : YAG laser capsulotomy or placebo 2 h before and apraclonidine 1 h before the procedure. Inclusion criteria were secondary cataracts with reduction in best corrected visual acuity (BCVA < 20/40), absence of manifest or suspected glaucoma and no known hypersensitivity to the study drugs. IOP was measured 2 h and 1 h before applying the laser, and 1 h, 2 h, 3 h and 7 days after.. There were no statistically significant differences between the two groups regarding the IOP 2 h and 1 h before the procedure, and 1 h, 2 h, 3 h and 7 days after the laser treatment (p values, respectively: 0.077, 0.21, 0.085, 0.36, and 0.60).. The results of this study suggest that dorzolamide is as safe and effective as apraclonidine in the prevention of the IOP elevation after Nd : YAG laser posterior capsulotomy. Synopsis. The efficacy of dorzolamide was compared to apraclonidine in the prevention of the intraocular pressure spike after Nd : YAG laser posterior capsulotomy in 217 patients and the results were similar with both drugs.

Topics: Adrenergic alpha-Agonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Clonidine; Double-Blind Method; Female; Humans; Intraocular Pressure; Laser Therapy; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Time Factors

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

The alpha-adrenergic agonist brimonidine and the carbonic anhydrase inhibitor dorzolamide have been studied both as monotherapy and in combination with beta-blockers in the treatment of glaucoma and ocular hypertension; however, a MEDLINE literature search failed to reveal any clinical studies directly comparing these 2 agents as adjunctive therapy.. The purpose of this study was to compare the intraocular pressure (IOP)-lowering efficacy of brimonidine and dorzolamide as adjunctive therapy to beta-blockers in adult patients with glaucoma or ocular hypertension.. In a prospective, investigator-masked, multicenter, parallel-design clinical trial, adult patients whose IOP was inadequately controlled with topical beta-blocker therapy were randomly assigned to receive brimonidine 0.2% twice daily or dorzolamide 2% 3 times daily as adjunctive therapy for 3 months. Efficacy was determined by the reduction in IOP from baseline. After 1 month of adjunctive treatment, patients who failed to meet a target 15% reduction in IOP at peak drug effect were crossed over to the other study medication.. A total of 106 patients were treated. Approximately 70% (74/106) of the patients were white, and 61.3% (65/106) had a diagnosis of open-angle glaucoma. Mean baseline IOP (ie, with beta-blocker monotherapy) was comparable between treatment groups (approximately 21 mm Hg). After 1 month of adjunctive treatment, the mean daily IOP reduction was significantly greater with brimonidine (4.40 mm Hg, 20.4%) than with dorzolamide (3.0 mm Hg, 14.4%, P = 0.033). At peak drug effect at month 1, the mean IOP reduction was significantly greater in the brimonidine group (5.95 mm Hg, 27.6%) than in the dorzolamide group (4.11 mm Hg, 19.7%; P = 0.007). Significantly more patients treated with brimonidine (44/51, 86.3%) than with dorzolamide (29/47, 61.7%) achieved the target 15% reduction in IOP at month 1 (P = 0.005). At month 3, the mean daily IOP reduction and the mean IOP reduction at peak drug effect were not significantly different in the 2 treatment groups. The mean daily IOP reduction was 4.98 mm Hg in the brimonidine group and 3.15 mm Hg in the dorzolamide group (P = 0.092). At peak drug effect, the mean IOP reduction was 6.39 mm Hg with brimonidine and 4.06 mm Hg with dorzolamide. The incidence of adverse events leading to discontinuation was 9.3% (5/54) in the brimonidine group (depression, 2; allergic conjunctivitis, 1; dry mouth and tearing, 1; dermatitis, 1) and 9.8% (5/51) in the dorzolamide group (ocular burning and stinging, 2; ocular itch, 1; gastrointestinal complaints, 1; lack of tolerance for beta-blocker, 1), with no significant difference between groups.. In this trial, brimonidine 0.2% twice daily produced greater mean decreases in IOP and was effective in more patients than dorzolamide 2% 3 times daily when used as adjunctive therapy to beta-blockers.

Topics: Adrenergic beta-Antagonists; Adult; Antihypertensive Agents; Brimonidine Tartrate; Cross-Over Studies; Down-Regulation; Female; Glaucoma; Humans; Immunologic Factors; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Quality of Life; Quinoxalines; Sulfonamides; Thiophenes

To compare the effect of a fixed dorzolamide-timolol combination with that of latanoprost on intraocular pressure (IOP) after small incision cataract surgery. Department of Ophthalmology, University of Vienna, Vienna, Austria. This prospective randomized study comprised 60 eyes of 30 patients scheduled for small incision cataract surgery in both eyes. The patients were randomly assigned to receive 1 drop of a fixed dorzolamide-timolol combination or latanoprost immediately after cataract surgery in the first eye. The second eye received the other antiglaucomatous agent. Cataract surgery was performed under sodium hyaluronate 1% with a temporal 3.5 mm sutureless posterior limbal incision, phacoemulsification, and implantation of a foldable intraocular lens. The IOP was measured preoperatively as well as 6 and 20 to 24 hours and 1 week postoperatively. Six hours after surgery, the mean IOP decreased by -0.8 mm Hg +/- 3.2 (SD) (P =.184) in the dorzolamide-timolol group and increased by 3.6 mm Hg +/- 3.5 (P <.001) in the latanoprost group. Twenty to 24 hours after surgery, the mean IOP decreased by -2.8 +/- 2.4 mm Hg (P <.001) in the dorzolamide-timolol group and increased by 0.6 +/- 3.5 mm Hg (P =.353) in the latanoprost group. The differences between groups were significant at 6 hours (P <.001) and 20 to 24 hours (P <.001). The fixed dorzolamide-timolol combination was more effective than latanoprost in reducing IOP after small incision cataract surgery. Only the fixed dorzolamide-timolol combination prevented a postoperative IOP increase and occasional IOP spikes of 30 mm Hg or higher.

Topics: Antihypertensive Agents; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Intraocular Pressure; Latanoprost; Lens Implantation, Intraocular; Male; Middle Aged; Minimally Invasive Surgical Procedures; Ocular Hypertension; Ophthalmic Solutions; Phacoemulsification; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

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 study the effect of timolol maleate, dorzolamide, or a combination of both in post photorefractive keratectomy (PRK) eyes with an elevated intraocular pressure (IOP) after topical steroid administration.. Refractive Surgery Outpatient Department, 1st Department of Ophthalmology, Semmelweis University, Budapest, Hungary.. Forty-five patients with elevated IOP were randomly enrolled in 3 groups: Group 1 received timolol maleate 0.5% twice a day; Group 2 received timolol maleate 0.5% twice a day and dorzolamide 2% 3 times a day; and Group 3 received only topical dorzolamide 2% 3 times a day. Intraocular pressure was measured 3 days and 1, 3, and 6 weeks after the antiglaucoma medication was started.. The mean preoperative IOP was 15.25 mm Hg +/- 1.28 (SD). Following administration of topical fluorometholone, the IOP increased a mean of 27.39 +/- 2.88 mm Hg. Six weeks after the antiglaucoma therapy was started, the mean IOP reduction was 6.6 mm Hg in Group 1, 8.86 mm Hg in Group 2, and 4.64 mm Hg in Group 3.. A combination therapy of timolol 0.5% and dorzolamide 2% was most effective in treating secondary IOP elevation after PRK. Dorzolamide alone did not adequately control secondary post-PRK IOP elevation.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Adult; Anti-Inflammatory Agents; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Female; Fluorometholone; Glucocorticoids; Humans; Intraocular Pressure; Lasers, Excimer; Male; Ocular Hypertension; Ophthalmic Solutions; Photorefractive Keratectomy; Prospective Studies; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

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

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

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 investigate whether dorzolamide alters corneal hydration control in patients with glaucoma or ocular hypertension.. Pachymetry, tonometry, and endothelial cell density were measured by a masked observer in 19 subjects with bilateral glaucoma or ocular hypertension. They were treated with 2% dorzolamide in one eye, and with saline in the other, before wearing contact lenses under patched eyes. Corneal thickness, measured each 30 minutes up to 4.5 hours after contact lens removal, enabled estimation of percentage recovery per hour and time for 95% of corneal thickness recovery for both eyes. Seven patients repeated this test after 1 year of dorzolamide use, and their results were compared with those of the preceding year.. After induction of hypoxic corneal edema, there was no significant difference between paired corneas in swelling levels (60.0+/-11.8 and 59.8+/-12.9 microm) (P = .94), time to 95% recovery (440.6+/-255.8 and 445.4+/-186.7 minutes) (P = .93), and percentage recovery per hour (38.1%+/-10.9% and 36.1%+/-9.6%) (P = .40). Subjects followed up after 1 year of dorzolamide use did not differ significantly in values of endothelial cell density, percentage recovery per hour, or time to 95% recovery from those obtained a year before. One subject developed persistent corneal edema after his stress test in the eye treated with dorzolamide.. There is no significant difference in the recovery from induced corneal edema after either a short-term or 1-year use of dorzolamide in patients with glaucoma or ocular hypertension with a normal corneal endothelium. One patient had persistent corneal edema after the stress test was performed on the dorzolamide-treated eye.

Topics: Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Cell Count; Contact Lenses; Cornea; Corneal Edema; Double-Blind Method; Endothelium, Corneal; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Sulfonamides; Thiophenes; Tonometry, Ocular

To determine whether topical aqueous suppressant therapy applied after pars plana vitrectomy with gas tamponade prevents postoperative intraocular pressure (IOP) elevation.. Prospective, nonrandomized comparative study.. Forty-one patients who met inclusion criteria and underwent pars plana vitrectomy with gas tamponade (SF6 18%-20% or C3F8 12%-16%) over a 1-year period.. Treatment eyes received topical aqueous suppressants at the end of surgery.. Postoperative IOP at 4 to 6 hours, 1 day, and 1 week.. Twenty-one control and 20 treatment eyes met the inclusion criteria. The IOP (in mmHg) measured at 4 to 6 hours (23.05 [control, 14.73 [treatment]) and 1 day (23.24 [control], 17.28 [treatment]) postoperatively showed a statistically significant difference between the groups (P = 0.0038) at 4 to 6 hours and a trend toward significance (P = 0.057) at 1 day. Eleven control and three treatment eyes had an IOP spike above 25 mmHg at 4 to 6 hours or 1 day postoperatively (P = 0.02), and six control eyes and one treatment eye had postoperative IOP greater than 30 mmHg. A pressure rise greater than 40 mmHg was seen in two control eyes and no treatment eyes.. Use of topical aqueous suppressants after pars plana vitrectomy with long-acting gas tamponade is effective in preventing significant postoperative IOP elevation in most cases.

Topics: Administration, Topical; Antihypertensive Agents; Aqueous Humor; Brimonidine Tartrate; Clonidine; Fluorocarbons; Humans; Intraocular Pressure; Ocular Hypertension; Prospective Studies; Quinoxalines; Sulfonamides; Sulfur Hexafluoride; Thiophenes; Timolol; Vitrectomy

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 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

To formulate aqueous eye drops containing methazolamide 1% in cyclodextrin solution and to evaluate their effect on intraocular pressure (IOP) in a double-blind randomized trial in humans. Methazolamide, a carbonic anhydrase inhibitor (CAI), has been used in oral doses in the treatment of glaucoma but hitherto has not been successfully formulated in eye drops. In this study the effects of methazolamide are compared with those of dorzolamide (Trusopt).. Methazolamide 1% was formulated in a 2-hydroxypropyl-beta-cyclodextrin with hydroxypropyl methylcellulose in aqueous solution. Eight persons with ocular hypertension were treated with the methazolamide-cyclodextrin eye drops and eight persons with dorzolamide (Trusopt), both groups at dosages of three times a day for 1 week. IOP was measured before treatment was begun and on days 1, 3, and 8 at 9 AM (peak) and 3 PM (trough).. After 1 week of treatment, the peak IOP in the methazolamide group had decreased from 24.4 +/- 2.1 mm Hg (mean +/- SD) to 21.0 +/- 2.0 mm Hg, which is a 14% pressure decrease (P: = 0.006). In the dorzolamide group, the peak IOP decreased from 23.3 +/- 2.1 mm Hg to 17.2 +/- 3.1 mm Hg, which is a 26% pressure decrease (P: < 0.001). On average, the IOP declined 3.4 +/- 1.8 mm Hg after methazolamide administration and 6.1 +/- 3.6 mm Hg after dorzolamide.. Through cyclodextrin complexation, it is possible to produce topically active methazolamide eye drops that lower IOP. This is the first double-blind clinical trial that demonstrates the efficacy of the classic CAIs in eye drop formulation.

Topics: Carbonic Anhydrase Inhibitors; Cyclodextrins; Double-Blind Method; Female; Humans; Intraocular Pressure; Male; Methazolamide; Ocular Hypertension; Ophthalmic Solutions; Pharmaceutical Vehicles; Sulfonamides; Thiophenes

To compare the effectiveness of 2% dorzolamide and 0.5% apraclonidine on intraocular pressure (IOP) following phacoemulsification cataract surgery.. This prospective, randomised study comprised 54 eyes of 27 consecutive patients with age-related cataract scheduled for cataract surgery in both eyes. In each patient the eye with the higher degree of cataract was randomly assigned to receive one drop of either dorzolamide or apraclonidine immediately after surgery. The fellow eye was operated on later and received the other treatment. Cataract surgery was performed with a superior 6.0 mm sutureless frown incision, phacoemulsification and implantation of a three-piece PMMA intraocular lens. The IOP was measured pre-operatively as well as 6 h and 20-24 h and 1 week post-operatively.. The mean pre-operative IOP was not significantly different between the groups (dorzolamide group, 14.9 +/- 2.3 mmHg; apraclonidine group, 14.6 +/- 2.5 mmHg; p = 0.450). At 6 h post-operatively, the mean IOP was significantly lower in the dorzolamide than in the apraclonidine group (15.6 +/- 3.9 mmHg vs 18.0 +/- 4.0 mmHg; p < 0.001). An IOP increase of more than 5 mmHg at 6 h post-operatively occurred in 3 (12%) eyes in the dorzolamide group and in 9 (36%) eyes in the apraclonidine group (p = 0.034). At 20-24 h post-operatively and at 1 week post-operatively no difference was found between the groups.. 2% Dorzolamide is more effective than 0.5% apraclonidine in preventing the early post-operative IOP increase following phacoemulsification cataract surgery.

Topics: Adrenergic alpha-Agonists; Aged; Aged, 80 and over; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Clonidine; Female; Humans; Male; Middle Aged; Ocular Hypertension; Phacoemulsification; Prospective Studies; Sulfonamides; Thiophenes

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: 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

To evaluate the efficacy of 2% dorzolamide hydrochloride opthalmic solution in preventing spikes in intraocular pressure (IOP) after anterior segment laser surgery.. This 24-hour, placebo-controlled, randomized, double-masked, multicenter evaluation was conducted to determine the efficacy of dorzolamide hydrochloride 2% in controlling IOP after neodimium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy, argon laser trabeculoplasty, or laser iridotomy. The 122 patients enrolled were assigned in randomized fashion to receive dorzolamide or placebo 1 hour before and immediately after the procedure; IOP was measured 1, 2, 3, 4, and 24 hours after the procedure.. Of 61 patients receiving dorzolamide, only one (1.7%) had a spike in IOP of 10 mmHg or more, compared with 9 (14.8%) of the 61 patients receiving placebo. Mean IOP among patients receiving dorzolamide was significantly reduced both from baseline and compared with that among patients receiving placebo from 1 to 4 hours after administration. Only 5 (8%) of the 61 patients receiving dorzolamide experienced at least one adverse event, compared with 15 (25%) of the 61 patients receiving placebo.. Dorzolamide was effective in preventing spikes in IOP after anterior segment laser surgery. Dorzolamide was generally well tolerated after short-term use.

Topics: Anterior Eye Segment; Carbonic Anhydrase Inhibitors; Double-Blind Method; Humans; Intraocular Pressure; Laser Therapy; Ocular Hypertension; Ophthalmic Solutions; Postoperative Complications; Sulfonamides; Thiophenes

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

To evaluate the effect of dorzolamide 2% and latanoprost 0.005% on intraocular pressure (IOP) after small incision cataract surgery.. Department of Ophthalmology, University of Vienna, Vienna, Austria.. This prospective study comprised 102 eyes of 102 consecutive patients scheduled for small incision cataract surgery. The patients were assigned preoperatively to 1 of 3 groups of 34 each: dorzolamide, latanoprost, and control (no treatment). One drop of the assigned medication was instilled immediately after surgery. Intraocular pressure was measured preoperatively and 6 and 20 to 24 hours postoperatively.. Six hours after surgery, the mean increase in IOP was 1.9 mm Hg +/- 3.9 (SD) in the dorzolamide group (P = .004 versus control), 2.2 +/- 3.0 mm Hg in the latanoprost group (P = .005 versus control), and 4.8 +/- 5.2 mm Hg in the control group. Twenty to 24 hours postoperatively, IOP decreased a mean of -0.9 +/- 3.5 mm Hg in the dorzolamide group (P = .012 versus control) and increased a mean of 0.3 +/- 3.6 mm Hg in the latanoprost group (P = 0.24 versus control) and 1.3 +/- 4.2 mm Hg in the control group. One eye in the dorzolamide group, 1 eye in the latanoprost group, and 4 eyes in the control group had an IOP of 30 mm Hg or higher 6 hours postoperatively.. Six hours postoperatively, dorzolamide and latanoprost were effective in reducing the IOP increase after small incision cataract surgery; however, at 20 to 24 hours, only dorzolamide was effective. Neither drug prevented IOP spikes of 30 mm Hg or higher.

Topics: Aged; Carbonic Anhydrase Inhibitors; Cataract Extraction; Drug Therapy, Combination; Female; Humans; Intraocular Pressure; Latanoprost; Lens Implantation, Intraocular; Male; Minimally Invasive Surgical Procedures; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Treatment Outcome

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

Two parallel, randomized, double-masked, placebo-controlled studies were conducted to assess the efficacy and safety of 2% dorzolamide hydrochloride as adjunctive therapy to 0.5% timolol maleate ophthalmic gellan (gel-forming) solution in patients with elevated intraocular pressure (IOP) that was inadequately controlled with 0.5% timolol maleate gellan solution alone.. Both studies began with an open-label 2-week run-in period on 0.5% timolol maleate gellan solution once a day. The only variation in method between the two studies was the dosage of 2% dorzolamide. In one study, 202 patients received 0.5% timolol maleate gellan solution once daily plus either 2% dorzolamide or placebo three times daily. In the other study, 181 patients received 0.5% timolol maleate gellan solution once daily plus either 2% dorzolamide or placebo twice daily.. After 85 days, additional mean percent reductions in IOP from baseline at morning trough for the groups receiving 2% dorzolamide three times daily and placebo three times daily were 12.5% and 8.4%, respectively. Mean percent reductions for the groups receiving 2% dorzolamide twice daily and placebo twice daily were 13.1% and 6.5%, respectively. Burning and/or stinging on instillation were the only adverse experiences that affected significantly more of the patients receiving 2% dorzolamide twice or three times daily than those receiving placebo.. When administered concomitantly with 0.5% timolol maleate gellan solution, 2% dorzolamide three times daily or twice daily produced a statistically significant reduction in IOP at morning trough and peak and was generally 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; Gels; Humans; Male; Middle Aged; Ocular Hypertension; Solutions; Sulfonamides; Thiophenes; Timolol

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

Topics: Carbonic Anhydrase Inhibitors; Cornea; Glaucoma; Humans; Ocular Hypertension; Sulfonamides; Thiophenes

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

The aim of this study was to evaluate the effectiveness of topical dorzolamide versus systemic acetazolamide in preventing the intraocular pressure (IOP) spike, following routine phacoemulsification surgery. In this prospective study, 59 eyes (59 patients), undergoing routine phacoemulsification surgery with posterior intraocular implant, were divided into three groups. Group 1 received acetazolamide 250 mg SR orally, immediately post-operatively. Group 2 received one drop of dorzolamide immediately after surgery. Group 3 or control, received neither. The IOP, was checked 4 h, 24 h and 2 weeks post-operatively. When compared with mean baseline pre-operative IOP, the 4 h mean post-operative IOP was slightly higher in the dorzolamide group by a mean of +2.49 mmHg (P = 0.2502). It was significantly higher in the acetazolamide group by a mean of +6.13 mmHg (P = 0.0034) and in the control group by a mean of +11.81 mmHg (P = 0.000). At 24 h the mean IOP in the control group remained significantly elevated by a mean of +5.87 mmHg (P = 0.003). Topical dorzolamide is effective in reducing the early IOP rise during the first 24 h following routine uncomplicated phacoemulsification surgery.

Topics: Acetazolamide; Administration, Oral; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Female; Humans; Intraocular Pressure; Lens Implantation, Intraocular; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Phacoemulsification; Postoperative Care; Prospective Studies; Sulfonamides; Thiophenes

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

The aim of the present study was to examine the influence of the topical carbonic anhydrase-II-inhibitor dorzolamide hydrochloride (Trusopt) in regarding to behaviour of intraocular eyepressure after Nd:YAG-laser-capsulotomy.. The study was carried out as a double-blind-test. In a period of nine months, 120 patients underwent Nd:YAG-laser-capsulotomy. One group was given dorzolamide hydrochloride (Trusopt), the other group (placebo) remained without medication. The intraocular pressure was measured before capsulotomy and four hours post-op. For statistical evaluation the t-test of not-associated spot-checks was performed.. The prophylactic use of the topical carbonic anhydrase-II-inhibitor dorzolamide hydrochloride (Trusopt) after nd:YAG-laser-capsulotomy shows a highly significant lowering of intraocular pressure, i.e. 1.09 mm Hg in the average.. It was demonstrated that a single dose of dorzolamide hydrochloride (Trusopt) after Nd:YAG-laser-capsulotomy could lower intraocular pressure significantly. Prophylactical usage of dorzolamide hydrochloride (Trusopt) is a useful method to prevent the increase of intraocular pressure and thus to protect the eye against hazardous damage.

Topics: Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Cataract Extraction; Double-Blind Method; Female; Humans; Intraocular Pressure; Laser Therapy; Male; Ocular Hypertension; Ophthalmic Solutions; Postoperative Complications; Premedication; Sulfonamides; Thiophenes; 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

The purpose of the study is to compare the efficacy and safety profile of 2.0% dorzolamide (three times daily) and 0.5% timolol (twice daily) for up to 6 months in patients with glaucoma or ocular hypertension associated with pseudoexfoliation. The additive effects of dorzolamide and timolol in patients requiring add-on therapy also was evaluated.. This was a double-masked, randomized, parallel comparison study at 15 Scandinavian sites. One hundred eighty-four patients with pseudoexfoliation and either glaucoma or ocular hypertension who were 21 to 85 years of age were studied. The treatment groups were 2.0% dorzolamide three times daily and 0.5% timolol maleate twice daily.. At 6 months, the mean percent reduction in intraocular pressure of 2% dorzolamide and 0.5% timolol was 24% and 29%, respectively, at morning peak and 21% and 23%, respectively, at afternoon trough. The additional intraocular pressure-lowering effect of adding 2.0% dorzolamide twice daily to patients receiving timolol was 14% and 15%, at peak and trough, respectively. There were no differences between treatment groups in the incidence of clinical adverse experiences, and dorzolamide was not associated with the systemic adverse effects typically ascribed to the use of oral carbonic anhydrase inhibitors.. Two percent dorzolamide (three times daily) was effective and well tolerated in patients with glaucoma or ocular hypertension associated with pseudoexfoliation over the course of 6 months; 0.5% timolol (twice daily) had a greater level of intraocular pressure-lowering activity than did dorzolamide, although the difference between the two treatments became less pronounced during the study period. Finally, 2.0% dorzolamide (twice daily) produced additional lowering of intraocular pressure when given with 0.5% timolol (twice daily).

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

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

To compare the efficacy and safety of topical 2.0% dorzolamide hydrochloride with oral acetazolamide in preventing intraocular pressure (IOP) rise following neodymium:YAG (Nd:YAG) laser posterior capsulotomy.. A prospective, randomized, double-masked, placebo-controlled study.. Two hundred ten patients undergoing Nd:YAG laser posterior capsulotomy.. Pretreatment with dorzolamide, acetazolamide, or placebo. Dorzolamide administration as a single drop (1 drop approximately 20 microL) 1 hour before capsulotomy. Acetazolamide administration as a single dose of 125 mg orally 1 hour before capsulotomy.. At first and third hour postoperatively, IOPs and IOP changes from baseline were significantly (P<.001) higher in the placebo group than in the dorzolamide or acetazolamide group. At the same time, IOPs and IOP changes from baseline were similar (P>.50) in the dorzolamide and acetazolamide groups. No patient treated with dorzolamide or acetazolamide experienced an IOP higher than 30 mm Hg after capsulotomy, but 15.7% of patients receiving placebo had an IOP above this level (P<.001). Of patients receiving placebo, 5.7% experienced IOP higher than 35 mm Hg. No serious side effects were recorded in any of the studied patients.. Topical 2.0% dorzolamide and oral acetazolamide, given prophylactically as a single administration 1 hour before Nd:YAG laser posterior capsulotomy, have comparable high efficacy and safety in preventing IOP elevation following this procedure.

Topics: Acetazolamide; Administration, Oral; Administration, Topical; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Cataract Extraction; Double-Blind Method; Female; Follow-Up Studies; Humans; Intraocular Pressure; Laser Therapy; Lens Capsule, Crystalline; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Postoperative Complications; Prospective Studies; Safety; 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

Since the introduction of carbonic anhydrase inhibitors, a topical preparation has been sought to avoid the complications of systemic medication while retaining the effect of lowering intraocular pressure. Recently, a topical carbonic anhydrase inhibitor, MK-507, has been found superior to others and introduced for multicentre clinical trial.. As part of an international multicentre trial, we compared MK-507 with beta blockers for one year in 20 patients with raised intraocular pressure, both as monotherapy and in combination.. Twelve patients with a mean peak pressure of 31.9 +/- 6.8 mmHg (range, 22 to 49 mmHg) off all medication received MK-507. After two weeks, mean peak pressure was 24.7 +/- 6.1 mmHg (range, 14 to 41 mmHg)--a 22.6% fall in pressure. Six of these patients had a mean peak pressure of 27.8 +/- 6.4 mmHg (range, 21 to 41 mmHg), a fall of 19.2% from day one and were given timolol as add-on therapy. This resulted in a fall to 19.1 +/- 2.8 (range, 15 to 24 mmHg) at year one, a fall of 31.3% after add-on. Four patients on timolol and four on betaxolol gave similar falls in pressure with an additional fall when MK-507 was used as add-on therapy.. MK-507 demonstrated its effectiveness as an ocular hypotensive agent in this trial of patients with an unusually high rise in pressure. It showed a hypotensive effect roughly equivalent to beta blockers. It is likely that either a topical carbonic anhydrase inhibitor or a cardioselective beta blocker will be the medication of first choice in newly diagnosed glaucoma.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Australia; Betaxolol; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

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

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

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Dermatitis, Allergic Contact; Eyelids; Facial Dermatoses; Female; Humans; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes

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

Two lead 1,3-oxazole-based carbonic anhydrase inhibitors (CAIs) earlier identified as selective, picomolar inhibitors of hCA II (a cytosolic target for treatment of glaucoma) have been investigated further. Firstly, they were found to be conveniently synthesized on multigram scale, which enables further development. These compounds were found to be comparable in efficacy to dorzolamide eye drops when applied in the eye drop form as well. Finally, the reasons for unusually high potency of these compounds became understood from their high-resolution X-ray crystallography structures. These data significantly expand our understanding of heterocycle-based primary sulfonamides, many of which have recently emerged from our labs - particularly, from the corneal permeability standpoint.

Topics: Animals; Binding Sites; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Crystallography, X-Ray; Humans; Intraocular Pressure; Male; Molecular Conformation; Molecular Dynamics Simulation; Ocular Hypertension; Oxazoles; Protein Structure, Tertiary; Rabbits

To determine whether topical hypotensive medications prevent postoperative ocular hypertension (POH) after phacoemulsification.. 52 client-owned dogs (88 eyes).. Diabetic and nondiabetic dogs having undergone phacoemulsification were included in this retrospective study. The control group received no ocular hypotensive medications. The treatment groups received latanoprost, dorzolamide, or dorzolamide/timolol, beginning immediately after surgery, for 2-week duration. IOPs were obtained at initial examination followed by 4 h, 24 h, 7 days, and 14 days postoperatively. POH was defined as an IOP above 20 mmHg (POH20) or 25 mmHg (POH25).. POH20 occurred in 33 of 87 eyes (37.93%), including 11 of 21 eyes (52.38%) in the control group, three of 23 eyes (13.04%) in the latanoprost group, eight of 15 eyes (53.33%) in the dorzolamide group, and 11 of 28 eyes (39.29%) in the dorzolamide/timolol group. Active treatment groups were compared to the control group, and the overall group effect was not significant (P = 0.11). POH25 occurred in 22 of 86 eyes (25.58%), including seven of 21 eyes (33.33%) in the control group, two of 23 eyes (8.70%) in the latanoprost group, five of 15 eyes (33.33%) in the dorzolamide group, and eight of 27 eyes (29.63%) in the dorzolamide/timolol group. Active treatment groups were compared to the control group, and the overall group effect was not significant (P = 0.31). Intraoperative use of intracameral tissue plasminogen activator significantly decreased the chances of POH25 (P = 0.0063).. The latanoprost group had a substantially lower percentage of POH 20 and POH25 compared to the control and other active treatment groups, although statistical significance was not achieved. Intraoperative intracameral tissue plasminogen activator decreased the incidence of POH25.

Topics: Administration, Topical; Animals; Dog Diseases; Dogs; Female; Incidence; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Ophthalmic Solutions; Phacoemulsification; Postoperative Complications; Pre-Exposure Prophylaxis; Prostaglandins F, Synthetic; Retrospective Studies; Sulfonamides; Thiophenes; Timolol

Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.

Topics: Animals; Antihypertensive Agents; Brimonidine Tartrate; Catalase; Dexamethasone; Disease Models, Animal; Female; Glutathione; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Oxidative Stress; Pilocarpine; Prostaglandins F, Synthetic; Quinoxalines; Rats, Sprague-Dawley; Retina; Sulfonamides; Superoxide Dismutase; Thiophenes; Timolol

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

Socially anxious cannabis users are influenced by cannabis expectancies and normative perceptions. The present study examines the influence of psychosocial factors on cannabis use vulnerability factors as the result of interactions between norms perceptions, social anxiety, and expectancies.. Participants were 149 (36.2% female) current cannabis users aged 18-36 (. Among cannabis users with perceptions of greater injunctive norms, social anxiety was associated with greater cannabis craving when tension reduction expectancies were greater. However, social anxiety was unrelated to cannabis craving when expectances were low. This suggests that cannabis craving among socially anxious adults was greatest when cannabis use was viewed as acceptable and expected to reduce tension, and highlights the importance of considering norms, expectancies, and social anxiety in understanding cannabis-related behaviors.. The A876P-substitution bridges in vitro and in vivo studies using J6/JFH1-based recombinants. We provide the first in vivo evidence that HVR1 protects cross-genotype conserved HCV neutralisation epitopes, which advocates the possibility of using HVR1-deleted viruses as vaccine antigens to boost broadly reactive protective nAb responses.. We conclude that the photo-processing of eVSGs leads to the production of PAHs with attached aliphatic sidegroups that are revealed by the 3.4. De 4,331 publicaciones encontradas, 16 estudios cumplieron con los criterios de inclusión. El 50 % (8/16) de los estudios revisados fueron realizados en países de Sur América, Centro América y del Caribe. El diseño de casos y controles fue el más frecuente. El anterior sistema de clasificación de casos (OMS-1997) fue utilizado en todos los estudios incluidos en esta revisión.. El estrés oxidativo-nitrosativo se encuentra presente en el curso de la infección por virus dengue, demostrado por los cambios en las concentraciones plasmáticas de óxido nítrico, antioxidantes y marcadores de lipoperoxidación y de oxidación de proteínas. Por último, parece existir una asociación entre la elevación de los niveles plasmáticos de los carbonilos proteicos y malondialdehído con la severidad del dengue.

Topics: Acid-Base Imbalance; Acidosis, Renal Tubular; Aged; Air Pollution, Indoor; Amino Acid Substitution; Animals; Animals, Newborn; Anti-Bacterial Agents; Antibodies, Neutralizing; Apoptosis; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Bone Marrow Transplantation; Carbonic Anhydrase Inhibitors; Castleman Disease; Cat Diseases; Cats; Cell Proliferation; Cell- and Tissue-Based Therapy; Chemical and Drug Induced Liver Injury; Chemotaxis, Leukocyte; Clinical Trials as Topic; Coated Materials, Biocompatible; Diagnosis, Differential; Disease Models, Animal; Environmental Monitoring; Female; Gas Chromatography-Mass Spectrometry; Genotype; Granuloma, Foreign-Body; Heart Failure; Hepacivirus; Hepatitis C; Horse Diseases; Horses; Housing; Humans; Hypercalcemia; Hypokalemia; Immunophenotyping; In Vitro Techniques; Liver; Liver Function Tests; Lymphocytes; Macrophages; Male; Medicine, Chinese Traditional; Metabolomics; Mice; Mice, Inbred C57BL; Middle Aged; Models, Animal; Mutation; Myocardial Ischemia; Neovascularization, Physiologic; Neutrophil Infiltration; Ocular Hypertension; Ophthalmic Solutions; Parathyroid Hormone; Particulate Matter; Polyethylene Terephthalates; Prednisolone; Prospective Studies; Prosthesis Design; Prosthesis-Related Infections; Rats; Rats, Wistar; Reactive Oxygen Species; Rifampin; Saponins; Sepsis; Skin; Stem Cells; Stroke Volume; Sulfonamides; Texas; Thiophenes; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left; Viral Hepatitis Vaccines; Viral Nonstructural Proteins; Viral Proteins; Vitamin D; Wound Healing

A wild young adult western screech owl (Megascops kennicottii) of unknown sex was presented for evaluation of an abnormal left eye (OS). Ophthalmic examination OS revealed raised intraocular pressure (37 mm Hg; reference interval 7-16 mm Hg), mydriasis, conjunctival and episcleral hyperemia, shallow anterior chamber due to anterior displacement of the lens and iris, rubeosis iridis, and engorgement of the pecten. The intraocular pressure in the right eye (OD) was 11 mm Hg. Multifocal pale, variably translucent, curvilinear to vermiform opacities were observed in the medial and ventral peripheral regions of the retina OD, consistent with focal retinitis. Mannitol (0.46 g/kg IV) was administered over 10 minutes. Forty minutes later, the intraocular pressure was 27 mm Hg OS and 13 mm Hg OD. Dorzolamide (one drop OS q12h), diclofenac (one drop OU q8-12h), and meloxicam (0.5 mg/kg PO q24h) were administered for 3 days. The intraocular pressure OS was within normal limits 1 day (11 mm Hg), 7 days (13 mm Hg), and 4 weeks (14 mm Hg) after this treatment. Complications arising during hospitalization and rehabilitation included superficial corneal ulceration of both eyes presumed secondary to trauma on being caught and superficial damage to a talon. The owl was released after a period of rehabilitation. Characteristic presenting signs as well as response to therapy suggest aqueous misdirection was the cause of ocular hypertension in this owl. To our knowledge, this is the first report of suspected aqueous misdirection and its medical management in a raptor.

Topics: Acute Disease; Animals; Bird Diseases; Carbonic Anhydrase Inhibitors; Diclofenac; Mannitol; Meloxicam; Ocular Hypertension; Strigiformes; Sulfonamides; Thiazines; Thiazoles; Thiophenes

Poor drug penetration and rapid clearance after topical instillation of a drug formulation into the eyes are the major causes for the lower ocular bioavailability from conventional eye drops. Along with this, poor encapsulation efficiency of hydrophilic drug in polymeric nanoparticles remains a major formulation challenge. Taking this perspective into consideration, dorzolamide (DZ)-loaded PLGA nanoparticles were developed employing two different emulsifiers (PVA and vitamin E TPGS) and the effects of various formulation and process variables on particle size and encapsulation efficiency were assessed. Nanoparticles emulsified with vitamin E TPGS (DZ-T-NPs) were found to possess enhanced drug encapsulation (59.8±6.1%) as compared to those developed with PVA as emulsifier (DZ-P-NPs). Transcorneal permeation study revealed a significant enhancement in permeation (1.8-2.5 fold) as compared to solution. In addition, ex vivo biodistribution study showed a higher concentration of drug in the aqueous humour (1.5-2.3 fold). Histological and IR-camera studies proved the non-irritant potential of the formulations. Pharmacoscintigraphic studies revealed the reduced corneal clearance, as well as naso-lachrymal drainage in comparison to drug solution. Furthermore, efficacy study revealed that DZ-P-NPs and DZ-T-NPs significantly reduced the intraocular pressure by 22.81% and 29.12%, respectively, after a single topical instillation into the eye.

Topics: Animals; Carbonic Anhydrase Inhibitors; Glaucoma; Intraocular Pressure; Lactic Acid; Microscopy, Electron, Scanning; Nanoparticles; Ocular Hypertension; Polyethylene Glycols; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rabbits; Radionuclide Imaging; Sulfonamides; Thiophenes; Vitamin A; Vitamin E

To evaluate prospectively whether anti-glaucomatic drugs administered prior to intravitreal anti-vascular endothelial growth factor (VEGF) injection bevacizumab (Avastin,® Roche) or ranibizumab (Lucentis,® Novartis) prevents intraocular hypertension after the injection.. In total, 166 patients (175 eyes) scheduled for intravitreal anti-VEGF injection treatment were prophylactically treated 1 hour before the procedure with Dorzolamide/Timolol (Cosopt,® MSD) (Group 1, 53 eyes) or Brinzolamide/Timolol (Elazop,® Alcon) (Group 2, 84 eyes) or left untreated (Group 3, 29 eyes). Intraocular pressure was analyzed 5 minutes prior to the injection, every 5 minutes for 30 minutes after the procedure, and 1 hour, 1 day, 7 days, and 1 month after the procedure.. The intraocular pressures 5 minutes before the procedure (baseline) for Groups 1, 2, and 3 were 12.06 ± 1.85, 13.98 ± 2.68, and 13.81 ± 2.24 mmHg, respectively. Five and 30 minutes after the procedure, the intraocular pressures of the three groups were 14.12 ± 4.18, 14.87 ± 3.35, and 28.21 ± 3.16 mmHg, respectively, and 10.87 ± 1.58, 14.25 ± 2.43, and 17.48 ± 2.34 mmHg, respectively. For all three groups, the changes relative to baseline 5 and 30 minutes after injection were significant. When the three groups were divided according to whether they received bevacizumab or ranibizumab and the changes in intraocular pressure relative to baseline were analyzed, all six subgroups exhibited significant changes in intraocular pressure 5 and 30 minutes after the procedure.. The prophylactic administration of anti-glaucomatic drugs prior to intravitreal anti-VEGF injection effectively reduced the early intraocular pressure elevation. This approach was also safe and could be performed accurately.

Topics: Administration, Topical; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antihypertensive Agents; Bevacizumab; Drug Therapy, Combination; Female; Humans; Intraocular Pressure; Intravitreal Injections; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Ranibizumab; Retinal Diseases; Sulfonamides; Thiazines; Thiophenes; Timolol; Tonometry, Ocular; Vascular Endothelial Growth Factor A

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

Several aromatic/heterocyclic sulfonamide scaffolds have been used to synthesize compounds incorporating NO-donating moieties of the nitrate ester type, which have been investigated for the inhibition of five physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms: hCA I (offtarget), II, IV and XII (antiglaucoma targets) and IX (antitumor target). Some of the new compounds showed effective in vitro inhibition of the target isoforms involved in glaucoma, and the X-ray crystal structure of one of them revealed factors associated with the marked inhibitory activity. In an animal model of ocular hypertension, one of the new compounds was twice more effective than dorzolamide in reducing elevated intraocular pressure characteristic of this disease, anticipating their potential for the treatment of glaucoma.

Topics: Animals; Carbonic Anhydrase Inhibitors; Crystallography, X-Ray; Disease Models, Animal; Glaucoma; Humans; Models, Molecular; Molecular Structure; Nitric Oxide; Ocular Hypertension; Protein Isoforms; Rabbits; Sulfonamides; Thiophenes

To assess the impact of 2 strategies for initiating therapy in ocular hypertension (OH) on drug use, intraocular pressure (IOP), and blindness caused by glaucoma.. Using a simulation model, initiating therapy with timolol (strategy 1) and with latanoprost (strategy 2) was simulated for a hypothetic cohort of ocular hypertension patients with an initial IOP distribution (data of 1000 patients). Adjustment of therapy within 15 months and a subsequent lifelong follow-up, with an IOP dependent conversion to glaucoma, were modeled. The IOP lowering effect of medication (based on a meta-analysis) was applied by Monte Carlo simulation. Therapy could be maintained or changed, depending on the achieved IOP and side effects. Four drugs (latanoprost, timolol, brimonidine, dorzolamide) were used as monotherapy or in combination. Glaucoma conversion rate was based on literature.. Treatment goal was achieved in both strategies in 90% by monotherapy. This was 60% for patients with initial IOP's of 30 mm Hg. The originally prescribed medication was maintained in 66% (1) and in 77% (2). IOP decreased with approximately 34%, from 25.4 mm Hg (mean) to 16.7 mm Hg (1) and to 16.5 mm Hg (2) Blindness per person within 18.7 years of life expectancy was 0.0923 years (1) and 0.0870 years (2), which corresponds to approximately 1 month. The difference between strategies was 2 days spent in blindness per patient.. The difference in clinical effects of the strategies is small. This is largely owing to the key concept of a target pressure, which underlies both strategies.

Topics: Adult; Antihypertensive Agents; Blindness; Brimonidine Tartrate; Decision Trees; Disease Progression; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Markov Chains; Middle Aged; Models, Biological; Monte Carlo Method; Ocular Hypertension; Prostaglandins F, Synthetic; Quinoxalines; Risk Assessment; Sulfonamides; Thiophenes; Timolol

A rapid, sensitive and selective method for the simultaneous quantification of carteolol and dorzolamide in rabbit aqueous humor (AH) and ciliary body (CB) has been developed and validated using reversed phase-high performance liquid chromatography (RP-HPLC) with isocratic elution coupled with atmospheric pressure chemical ionization mass spectrometry/mass spectrometry (APCI-MS/MS). The analytes and nadolol (used as internal standard, IS) were purified from AH by protein precipitation. The sample preparation from CB was based on a two steps extraction procedure at different pH, utilizing a liquid-liquid extraction with a mixture of ethyl acetate, toluene and isopropanol 50:40:10 (v/v) at pH 8, followed by a second extraction with ethyl acetate at pH 11. The combined organic extracts were then back extracted into 0.1% aqueous trifluoroacetic acid (TFA). The accuracy and precision values, calculated from three different sets of quality control samples analyzed in sestuplicate on three different days, were within the generally accepted criteria for analytical methods (<15%). The assay proved to be accurate and precise when applied to the in vivo study of carteolol and dorzolamide in rabbit AH and CB after single administration of an eye drops containing both drugs.

Topics: Animals; Antihypertensive Agents; Aqueous Humor; Carteolol; Chromatography, High Pressure Liquid; Ciliary Body; Disease Models, Animal; Humans; Male; Ocular Hypertension; Rabbits; Spectrometry, Mass, Electrospray Ionization; 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

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

The aim of this study was to examine intraocular pressure lowering, change of antiapoptotic molecules expression, and neuroretinal changes by a commercially available dorzolamide 2%/timolol 0.5% combination in a chronic ocular hypertension rat model. Chronic ocular hypertension was induced by three episcleral vein cauterizations. The expression of antiapoptotic molecules and the effect of dorzolamide 2%/timolol 0.5% combination in chronic ocular hypertensive retina were evaluated. Retinal ganglion cell (RGC) retrograde labeling and quantification with 4-di-10-ASP (DiA) and expression of glial fibrillary acidic protein (GFAP) were detected before and after the administration of dorzolamide 2%/timolol 0.5%. Treatment of ocular hypertensive eyes with dorzolamide 2%/timolol 0.5% significantly reduced, intraocular pressure when compared to the control eyes. Labeling of RGCs with DiA showed a significant decrease in RGC loss after the administration of dorzolamide 2%/timolol 0.5%. GFAP expression revealed a significant decrease in retinal damage after dorzolamide 2%/timolol 0.5% administration. However, dorzolamide 2%/timolol 0.5% did not affect Bcl-2 and Bcl-xL mRNA expression. In conclusion, dorzolamide 2%/timolol 0.5% may have neuroprotective potential in the animal model, which is not mediated by Bcl-2 or Bcl-xL. The mechanism of neuroprotection by dorzolamide 2%/timolol 0.5% in chronic glaucoma models requires further investigation.

Topics: Animals; bcl-X Protein; Cell Survival; Disease Models, Animal; Drug Combinations; Glial Fibrillary Acidic Protein; Intraocular Pressure; Male; Ocular Hypertension; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Retinal Ganglion Cells; RNA, Messenger; Sulfonamides; Thiophenes; Timolol

Topics: Antihypertensive Agents; Brimonidine Tartrate; Drug Therapy, Combination; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Quinoxalines; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

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

To analyse a response to the therapy switch from the concomitant application of beta-blocker and topical carbonic anhydrase inhibitor to the fixed combination of timolol and dorzolamide (Cosopt) in glaucoma/ocular hypertensive patients under everyday, office-practice conditions.. The data source was a survey among practising ophthalmologists in Switzerland assessing their experience with glaucoma patients/ocular hypertensives put for the first time on the fixed combination of timolol and dorzolamide. A total of 98 patients underwent the therapy switch in at least one eye. The intraocular pressure (IOP) change between the baseline visit before switch to the timolol-dorzolamide fixed combination occurred, and the first follow-up control after the switch, served as an indicator of compliance.. The IOP decreased on average from 19.43 +/- 5.64 mmHg to 17.97 +/- 3.58 mmHg (p < 0.01). The time to the follow-up visit ranged from 4 to 354 days, and the magnitude of IOP change demonstrated a significant dependence on the time to the follow-up visit, also when corrected for baseline IOP level. A total of 87 (85.3%) continued on the timolol-dorzolamide fixed combination therapy after the first control visit. In 68 of these 98 patients the contralateral eyes underwent the same therapy switch, and their IOP followed an identical pattern of behaviour.. The average IOP decrease of 1.5 mmHg upon therapy switch to the timolol-dorzolamide fixed combination suggests a better efficacy due to improved compliance. Short-term compliance benefit seems to be more pronounced. The high timolol-dorzolamide fixed combination therapy continuation rate reflects an improvement in compliance and subjectively-perceived convenience.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Cluster Analysis; Drug Combinations; Female; Humans; Intraocular Pressure; Male; Ocular Hypertension; Ophthalmic Solutions; Ophthalmology; Sulfonamides; Switzerland; Thiophenes; Timolol

To evaluate persistency with monotherapy in the treatment of glaucoma in patients new to pharmacological management.. This population-based, retrospective cohort study, using managed care administrative claims data, included patients who were 20 years of age and older and who initiated monotherapy with betaxolol, brimonidine, dorzolamide, latanoprost, or timolol between May 1999 and January 2001. Follow-up continued through January 31, 2001, and prescription refill records for all ocular hypotensive medications were extracted for the full 21-month study period. The primary outcome measures were discontinuation and change (switching/adding on) of the index ocular hypotensive medication. Rates of discontinuation and discontinuation/change were compared using Cox regression methods; survival curves were generated.. In all, 14,539 patients were prescribed any ocular hypotensive drug during the study period, and 2850 patients met all inclusion criteria. Patients treated with betaxolol, brimonidine, dorzolamide, or timolol were significantly (p < 0.05) more likely to discontinue and to discontinue/change the index therapy than were those treated with latanoprost. Results were confirmed in analyses adjusted for age and sex.. Patients initially treated with latanoprost monotherapy are more persistent than those who begin treatment with beta-blockers, brimonidine, or the carbonic anhydrase inhibitor dorzolamide. Greater persistency with an initial ocular hypotensive therapy may improve health outcomes and reduce long-term costs to patients and health plans by limiting the increased resource use associated with discontinuations or changes in therapy.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Antihypertensive Agents; Brimonidine Tartrate; Cohort Studies; Drug Utilization; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Ocular Hypertension; Patient Compliance; Prostaglandins F, Synthetic; Quinoxalines; Retrospective Studies; Sulfonamides; Thiophenes

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

Topics: Aged; Antihypertensive Agents; Cataract Extraction; Choroid Diseases; Drug Therapy, Combination; Female; Humans; Ocular Hypertension; Sulfonamides; Thiophenes; 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

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

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: Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Conjunctiva; Conjunctivitis; Female; Glaucoma, Angle-Closure; Humans; Male; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes

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

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

L-671,152 is a water-soluble, carbonic anhydrase inhibitor structurally similar to MK-927, a carbonic anhydrase inhibitor that, on topical administration, lowers the intraocular pressure (IOP) of experimental animals and humans. L-671,152 was more potent than MK-927 at inhibiting purified, human erythrocyte carbonic anhydrase II in vitro, as reflected in their respective IC50 values of 0.16 nM and 1.19 nM. Both compounds were compared for topical, ocular hypotensive activity in pigmented rabbits and cynomolgus monkeys. Ocular hypertension was induced in the latter by argon laser photocoagulation of the trabecular meshwork. A 2% solution of L-671,152 was more potent than 2% MK-927 in lowering the IOP of ocular hypertensive monkeys, the maximum reductions being 13.8 mm Hg (37%) and 9.6 mm Hg (27%) at 5 hr and 4 hr, respectively. Moreover, the duration of action of L-671,152 was superior to that of MK-927. The ocular hypotensive effect of L-671,152 was greater than that of MK-927 over a range of concentrations (0.5%-2%) in pigmented rabbits whose IOP was inherently elevated. The peak declines in the IOP of these rabbits after the instillation of 2% solutions of L-671,152 and MK-927 were 6.1 mm Hg and 4.8 mm Hg, respectively. L-671,152 was very effective in lowering the elevated IOP of alpha-chymotrypsinized rabbits and the unilateral instillation of 0.5% L-671,152 into the contralateral eye failed to decrease the elevated IOP of the alpha-chymotrypsinized eye. This finding indicates that the site of action of topically applied L-671,152 is local. The enhancement in the potency of L-671,152 over MK-927 is attributed to a greater inhibition of carbonic anhydrase activity.

Topics: Administration, Topical; Animals; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Chymotrypsin; Ciliary Body; Erythrocytes; Female; In Vitro Techniques; Iris; Light Coagulation; Macaca fascicularis; Male; Ocular Hypertension; Ocular Hypotension; Rabbits; Sulfonamides; Thiophenes; Trabeculectomy