Adjunctive therapy with brinzolamide 1% ophthalmic suspension (Azopt) in patients with open-angle glaucoma or ocular hypertension maintained on timolol therapy

This prospective, multicenter, double-masked, placebo-controlled study evaluated the safety and efficacy of brinzolamide 1% ophthalmic suspension (Azopt) when used adjunctively with open-label timolol maleate 0.5% (Timoptic). One-hundred-thirty-two patients requiring an adjunctive therapy to timolol 0.5% for the treatment of open-angle glaucoma or ocular hypertension were randomized to receive brinzolamide or placebo three times daily (t.i.d.) in addition to timolol 0.5% twice daily (b.i.d.) for 3 months. Qualifying intraocular pressure (IOP) on timolol 0.5% b.i.d. was 24-36 mm Hg in at least one eye at 8:00 A.M. and 21-36 mm Hg at 10:00 A.M., with no greater than a 5-mm Hg difference between eyes, during two eligibility visits separated by at least 7 days. Treatments were compared using a repeated-measures analysis of variance. Adjunctive therapy with brinzolamide resulted in clinically and statistically significant reductions in IOP from the timolol baseline at all visits. IOP changes from a diurnal baseline ranged from -3.3 mm Hg to -4.1 mm Hg for brinzolamide (N = 53) compared with -0.9 mm Hg to -2.5 mm Hg for placebo (N = 55). Abnormal taste (7.7%) and transient blurred vision (6.2%) were the most frequently reported adverse events. No clinically significant differences in the incidence or severity of ocular signs, visual acuity, cup/disk ratio, or parameters studied on dilated fundus examination were observed between treatment groups. Brinzolamide 1% t.i.d., used adjunctively with timolol 0.5% b.i.d., is safe and well tolerated, and produces clinically and statistically significant additional IOP reductions.     

Effect of brinzolamide and dorzolamide on aqueous humor flow in human eyes.

PURPOSE: To measure the relative efficacy of brinzolamide hydrochloride 1% ophthalmic suspension, a new carbonic anhydrase inhibitor, compared with the currently used dorzolamide hydrochloride 2% ophthalmic solution as suppressors of aqueous humor flow in human eyes, and to study the difference of effect during the day and at night. METHODS: A randomized, double-masked, placebo-controlled study of 25 normal human subjects was carried out at Mayo Clinic. The daytime rate of aqueous humor flow was measured every 2 hours from 8 AM to 4 PM by means of fluorophotometry. Likewise, the night-time rate of aqueous humor flow was measured every 2 hours from 12 AM to 6 AM. Intraocular pressure was measured at 4 PM and 6 AM. RESULTS: Brinzolamide reduced aqueous flow by 0.47+/-0.20 microl per min (mean+/-SD) during the day, whereas dorzolamide reduced flow by 0.34+/-0.20 microl per min. Brinzolamide reduced aqueous flow by 0.16+/-0.12 microl per min during the night, whereas dorzolamide reduced flow by 0.10+/-0.13 microl per min. Brinzolamide reduced afternoon intraocular pressure by 1.5+/-1.1 mm Hg, and dorzolamide reduced afternoon intraocular pressure by 1.1+/-1.0 mm Hg. Brinzolamide reduced the morning awakening intraocular pressure by 0.3+/-1.6 mm Hg, and dorzolamide reduced it by 0.8+/-1.0 mm Hg. CONCLUSIONS: Our data support the idea that brinzolamide is at least as efficacious as dorzolamide as a suppressor of aqueous humor flow in normal human eyes and that there is probably not a clinically significant difference between the two drugs in this efficacy. Clinicians who prescribe brinzolamide should expect similar ocular hypotensive responses from brinzolamide and dorzolamide.     

Ocular comfort of brinzolamide 1.0% ophthalmic suspension compared with dorzolamide 2.0% ophthalmic solution: results from two multicenter comfort studies. Brinzolamide Comfort Study Group

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.     

Dose-response evaluation of the ocular hypotensive effect of brinzolamide ophthalmic suspension (Azopt). Brinzolamide Dose-Response Study Group

Brinzolamide is a novel carbonic anhydrase inhibitor that elicits an ocular hypotensive effect when instilled topically. A multicenter, double-masked, placebo-controlled, parallel trial was conducted to evaluate the optimal intraocular pressure (IOP)-lowering concentration and ocular tolerability of topically administered brinzolamide (0.3%, 1%, 2%, and 3%) in patients with primary, open-angle glaucoma or ocular hypertension. After a washout phase, patients were administered brinzolamide or placebo twice daily for 2 weeks. The IOP was measured on days 8 and 15 at 8:00 A.M., and then 2, 4, 8, and 12 hours after dosing, and these measurements were compared with IOP values obtained at the corresponding times during an off-therapy diurnal baseline. All concentrations of brinzolamide produced significantly greater (P<0.005) mean percent IOP reductions and mean IOP reductions compared with placebo. Mean percent IOP changes (mean IOP changes) from baseline for brinzolamide 0.3%, 1%, 2%, and 3% were -11.3% (-3.0 mm Hg), -16.1% (-4.3 mm Hg), -16.1% (-4.4 mm Hg), and -15.4% (-4.2 mm Hg), respectively, when pooled over visit and visit time. Comparisons between concentrations demonstrated that the mean percent IOP reduction for brinzolamide 1.0% was significantly greater than that for the 0.3% concentration (P<0.03), with no difference in efficacy between the 1%, 2%, and 3% concentrations. The incidence of adverse events was dose-dependent, and those related to therapy were usually mild and resolved without treatment. Blurred vision, ocular discomfort, and abnormal taste were the most frequently reported adverse events. Based on these findings, the optimal IOP-lowering concentration of brinzolamide was 1%. When administered twice daily, brinzolamide 1% was well tolerated by patients with primary open-angle glaucoma or ocular hypertension.     

The efficacy and safety of topical brinzolamide and dorzolamide when added to the combination therapy of latanoprost and a beta-blocker in patients with glaucoma.

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

Blurred vision after instillation of topical carbonic anhydrase inhibitor

PURPOSE: The aim of this study was to compare brinzolamide with dorzolamide in regard to blurred vision after instillation. We also compared saline with two topical carbonic anhydrase inhibitor drugs. SUBJECTS AND METHODS: The study population comprised 21 healthy volunteers whose best corrected visual acuity was 1.0 or better. Brinzolamide 1% or dorzolamide 1% was applied to one eye the contralateral eye was exposed to the other drug. At 30 sec after instillation, visual acuity was measured every 30 sec until best visual acuity was recovered. Because visual acuity can fluctuate widely with blinking, subjects blinked for 5 sec before visual acuity measurement. As control, we applied saline alone to both eyes of 14 subjects and measured the change in visual acuity in the same way. Subjective sensations in each eye were recorded after measurement. RESULTS: Average visual acuity every 30 sec for 5 min was 0.41, 0.56, 0.68, 0.86, 0.87, 0.96, 1.04, 1.08, 1.11, and 1.12 after dorzolamide instillation, and 0.28, 0.42, 0.60, 0.69, 0.81, 0.91, 0.93, 0.99, 1.06, and 1.10 after brinzolamide instillation. In contrast, the average visual acuity after saline instillation for 2 min was 1.09, 1.13, 1.16 and 1.16. Of the 21 subjects, 15 (71.4%) felt moderate or severe irritation when dorzolamide was instilled; 2 (9.5%) felt moderate or severe irritation when brinzolamide was instilled. CONCLUSIONS: Both brinzolamide and dorzolamide caused significantly prolonged blurring of vision, from 30 sec to 2 or 3 min after instillation, as compared with saline only. The average visual acuity after brinzolamide instillation was lower than after dorzolamide for 5 min after instillation, although there was no significant difference. Judging from the subjects' sensations, it is suggested that with dorzolamide the prolonged blurred vision was due to reflex tearing from irritation, as explained above, whereas with brinzolamide it was due to opaque tears on the ocular surface.     

Comparison of ocular hypotensive effect and safety of brinzolamide and timolol added to latanoprost

PURPOSE: To compare the ocular hypotensive effect and safety of brinzolamide and timolol added to latanoprost monotherapy. METHODS: In prospective randomized fashion, we evaluated the ocular hypotensive effect and safety of brinzolamide or timolol in 1 eye of 32 patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had been treated with latanoprost for more than 1 month. Intraocular pressure (IOP), blood pressure, and pulse were measured before and at 4, 8, and 12 weeks. Corneal endothelial cell density was measured at baseline and at 12 weeks. RESULTS: The IOP was 17.8+/-1.7 mm Hg (mean+/-SD) before the addition of brinzolamide (n=15) and 15.7+/-2.1 mm Hg at 12 weeks (P<0.01). In comparison, the IOP was 18.5+/-3.7 mm Hg before the addition of timolol (n=15) and 15.8+/-3.2 mm Hg at 12 weeks (P<0.01). Both brinzolamide and timolol significantly decreased IOP at 12 weeks, by a mean of 2.0 mm Hg and mean 2.7 mm Hg, respectively, and were more effective than latanoprost alone (P<0.01), but there were no significant differences between the drugs and no significant differences in corneal endothelial cell density and blood pressure before and after addition of either drug. At 12 weeks, pulse was decreased in patients receiving timolol (P<0.01). As systemic adverse events, there was one instance of malar flushing after brinzolamide addition and episodes of chest discomfort after timolol addition in 1 patient. Ocular adverse events were slight. CONCLUSIONS: Brinzolamide and timolol added to latanoprost have similar ocular hypotensive effects and safety in primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension.     

Comparison of topical brinzolamide 1% and dorzolamide 2% eye drops given twice daily in addition to timolol 0.5% in patients with primary open-angle glaucoma or ocular hypertension

PURPOSE: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.     

Therapy of normal tension glaucoma: effect of brinzolamide on ocular haemodynamics

BACKGROUND: Altered ocular perfusion plays a role in the pathophysiology of normal tension glaucoma. Dorzolamide, a locally applied inhibitor of carbonic anhydrase, is thought to increase ocular blood flow. Less data are available regarding the influence exercised on ocular perfusion by brinzolamide, another and different, locally administered, inhibitor of carbonic anhydrase. PATIENTS AND METHODS: n = 15 eyes of 8 normal tension glaucoma patients were subjected to colour Doppler imaging and Langham-OBF (LOBF) before and during a therapy for 3 - 5 weeks with brinzolamide. RESULTS: Brinzolamide reduces intraocular pressure from 15.8 +/- 0.9 to 12.6 +/- 0.9 mm Hg (n = 15; P < 0.05). Systolic as well as diastolic blood flow velocities, resistive (RI) and pulsatility index (PI), measured by CDI, remained unchanged in the presence of brinzolamide. LOBF values are also not influenced by brinzolamide (1014 + 115 before vs. 1113 +/- 178 microl under therapy; n = 15; n. s.). DISCUSSION: Brinzolamide does not exercise any impact on ocular haemodynamics. This is different from the properties of dorzolamide that had been reported previously.     

The long-term safety and efficacy of brinzolamide 1.0% (azopt) in patients with primary open-angle glaucoma or ocular hypertension. The Brinzolamide Long-Term Therapy Study Group

PURPOSE: Oral carbonic anhydrase inhibitors used to treat glaucoma have significant systemic side effects. Brinzolamide 1.0%, a new topical ocular carbonic anhydrase inhibitor, is effective apparently without significant systemic side effects. This study was performed to establish the long-term safety and efficacy of brinzolamide 1.0% two and three times daily for primary open-angle glaucoma and ocular hypertension. METHODS: An 18-month, multicenter, double-masked, parallel, controlled study was conducted. Patients were randomized to brinzolamide two or three times daily or timolol 0.5% twice daily in a 2:2:1 ratio (n = 150, 153, and 75, respectively). Intraocular pressure was measured at 8:00 AM at eligibility and months 1, 3, 6, 9, 12, 15, and 18. Efficacy was based on intraocular pressure reduction from baseline. Safety was also evaluated. RESULTS: All regimens produced clinically relevant and statistically significant (P<.05) intraocular pressure reductions from baseline. Mean changes in intraocular pressure trough measurements ranged from -2.7 to -3.9 mm Hg with brinzolamide twice-daily dosing and -2.8 to -3.8 mm Hg three times daily dosing compared with -4.7 to -5.6 mm Hg with timolol. The intraocular pressure reductions with brinzolamide two and three times daily were clinically and statistically equivalent. One hundred forty-four patients were discontinued from the study after randomization with the most common reasons being the occurrence of an adverse event (46), inadequate intraocular pressure control (23), patient decision unrelated to study medication (11), lost to follow-up (16), and noncompliance (9). Adverse events were nonserious and resolved without sequelae. There were no clinically relevant changes in safety parameters. Brinzolamide produced less ocular discomfort (burning/stinging) than timolol, and total carbonic anhydrase inhibition levels remained below that known to cause systemic side effects. CONCLUSION: Brinzolamide produced significant and equivalent reductions in intraocular pressure when dosed two and three times daily for 18 months. Brinzolamide was safe and well tolerated by patients, with minimal ocular discomfort.     

Additive effect of dorzolamide or carteolol to latanoprost in primary open-angle glaucoma: a prospective randomized crossover trial

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

Preclinical overview of brinzolamide

The development of topically active carbonic anhydrase inhibitors (CAIs) is a significant recent achievement in glaucoma medical treatment. Brinzolamide, the newest topical CAI, exhibits selectivity, high affinity, and potent inhibitory activity for the carbonic anhydrase type II isozyme (CA-II), which is involved in aqueous humor secretion. These characteristics, along with good ocular bioavailability, make brinzolamide maximally effective in lowering intraocular pressure (IOP) by locally inhibiting CA-II in the ciliary processes and suppressing aqueous humor secretion. Notable among its attributes as a safe and efficacious glaucoma drug is brinzolamide's superior ocular comfort profile because of its optimized suspension formulation at physiologic pH. The degree of tolerability in the eye is considered an important determinant of a patient's willingness to comply with the dosing regimen for a long-term glaucoma medication. Results from the preclinical pharmacologic evaluation of brinzolamide indicated that it acts specifically to inhibit CA without significant other pharmacologic actions that could introduce undesired side effects. Moreover, the typical side effects associated with systemically administered CAIs are expected to occur at a lower incidence or not occur at all with brinzolamide, as its therapeutic dose and low systemic absorption do not produce a problematic level of systemic CA inhibition. Brinzolamide's long tissue half-life in the eye, particularly in the iris-ciliary body, favors a prolonged duration of IOP lowering. This was substantiated in clinical trials, which showed that twice-daily brinzolamide provides as significant an IOP reduction as three-times-daily brinzolamide or dorzolamide in a relatively high percentage of patients. Brinzolamide has been shown by the laser Doppler flowmetry technique to improve blood flow to the optic nerve head in pigmented rabbits after topical administration, without producing an increase of blood pCO2, indicating a potential for a local vasodilatory effect involving the optic nerve head circulation. The mean concentration of brinzolamide found in the retina of pigmented rabbits (0.338 microg equivalents/g) after a single dose of 14C-brinzolamide is sufficient to inhibit CA-II. These data suggest that topical brinzolamide could improve the blood flow in the optic nerve head in humans should it inhibit carbonic anhydrase in that vascular bed. Brinzolamide is a new topically active CAI that is safe and efficacious for reducing intraocular pressure. It offers the convenience of topical dose administration and greater freedom from side effects related to the inhibition of CA seen with the systemic administration of CAIs. Its formulation has been optimized to provide greater comfort upon instillation, and this can result in a higher compliance rate by the patient. Results of studies in animals show that brinzolamide has promise for increasing blood flow to the optic nerve head; however, this requires further assessment in the clinic. Brinzolamide represents a significant technical achievement and an important addition to the medical treatment of glaucoma as both a primary and an adjunctive drug.     

The efficacy and ocular discomfort of substituting brinzolamide for dorzolamide in combination therapy with latanoprost, timolol, and dorzolamide.

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

Comparison of the ocular hypotensive effect of brimonidine, dorzolamide, latanoprost, or artificial tears added to timolol in glaucomatous monkey eyes

PURPOSE: To investigate the additive ocular hypotensive effect of brimonidine, dorzolamide, latanoprost, or artificial tears to timolol in monkey eyes with laser-induced unilateral glaucoma. METHODS: Eight monkeys were used and each animal received all four combinations of drugs in a randomized fashion during the study. The washout period between each combination was at least 2 weeks. Intraocular pressure (IOP) was measured at 8:30 AM, 11:00 AM, 1:00 PM, and 3:30 PM on day 1 (untreated baseline), day 2 (timolol treatment alone), and days 3 through 5 (combination therapy with two drugs). One drop of 0.5% timolol was topically applied at 3:45 PM on day 1 and at 8:45 AM and 3:45 PM on days 2 through 5. One drop of 0.2% brimonidine or 2% dorzolamide or artificial tears was added on day 2 at 4:00 PM and at 9:00 AM and 4:00 PM on days 3 through 5, or latanoprost was added at 9:00 AM on days 3 through 5. RESULTS: Compared with timolol alone, the maximal additive reduction in IOP which occurred on day 5 was 4.8 +/- 0.8 mm Hg (mean +/- standard error of the mean) with timolol plus brimonidine, 5.6 +/- 1.0 mm Hg with timolol plus dorzolamide, 4.3 +/- 1.0 mm Hg with timolol plus latanoprost, and 2.0 +/- 0.5 mm Hg with timolol plus artificial tears (P < 0.01). At all measurements, timolol plus brimonidine, timolol plus dorzolamide, and timolol plus latanoprost caused greater (P < 0.05) IOP reductions than did timolol plus artificial tears. The additive IOP-lowering effect was similar (P > 0.60) when comparing timolol plus brimonidine and timolol plus dorzolamide, timolol plus brimonidine and timolol plus latanoprost, timolol plus dorzolamide and timolol plus latanoprost at all measurements, but timolol plus dorzolamide caused a greater (P < 0.05) reduction of IOP than did timolol plus latanoprost at 0 hours on day 5. CONCLUSIONS: The addition of brimonidine, dorzolamide, or latanoprost to timolol caused similar additional reductions of IOP in glaucomatous monkey eyes.     

Brinzolamide 1% versus apraclonidine 0.5% to prevent intraocular pressure elevation after neodymium:YAG laser posterior capsulotomy

PURPOSE: To compare the efficacy of brinzolamide 1% with that of apraclonidine 0.5% in preventing intraocular pressure (IOP) rise after neodymium:YAG (Nd:YAG) laser posterior capsulotomy. SETTING: Department of Ophthalmology, Akdeniz University, Antalya, Turkey. METHODS: One hundred fifteen patients who had Nd:YAG laser posterior capsulotomy for posterior capsule opacification were prospectively randomized to receive brinzolamide 1% (57 patients) or apraclonidine 0.5% (58 patients) approximately 1 hour before laser surgery. A masked observer measured IOP by Goldmann applanation tonometry before treatment and after treatment at 1, 2, and 3 hours and 7 days. RESULTS: The mean IOP changes from baseline were not statistically different between the study groups at 1, 2, and 3 hours and 7 days (P =.109, P = .764, P =.275, and P =.879, respectively). The incidence of IOP elevation of 5 mm Hg or higher was 12.2% (7 of 57 eyes) in the brinzolamide group and 10.3% (6 of 58 eyes) in the apraclonidine group (P = .743); IOP elevations of 10 mm Hg and greater occurred in 3.5% (2 of 57 eyes) and 1.7% (1 of 58 eyes) (P = .618), respectively. There were no IOP elevations greater than 20 mm Hg in either group. CONCLUSION: Brinzolamide 1% and apraclonidine 0.5% given prophylactically before Nd:YAG laser capsulotomy were effective in preventing IOP spikes after treatment.     

Medical control of intraocular pressure after phacoemulsification

PURPOSE: To compare the effectiveness of oral acetazolamide, topical brinzolamide 1%, and no ocular hypotensive medication after phacoemulsification. SETTING: Adnan Menderes University Department of Ophthalmology, Aydin, Turkey. METHODS: This prospective randomized double-blind study comprised 60 eyes of 52 patients having phacoemulsification under topical anesthesia. There were no intraoperative complications. Eyes were randomized to receive oral acetazolamide 500 mg 1 hour preoperatively followed by 250 mg acetazolamide every 6 hours, 1 drop of brinzolamide 1% every 12 hours starting immediately after speculum removal, or no ocular hypotensive medication. Intraocular pressure (IOP) was measured using a Perkins tonometer preoperatively and 4 to 6 hours and 18 to 24 hours postoperatively. RESULTS: The preoperative IOP was not significantly different between the 3 groups. Four to 6 hours postoperatively, the acetazolamide group (P=.002) and brinzolamide group (P=.001) had significantly lower IOP than the control group. The same trend was observed at 18 to 24 hours in the brinzolamide group (P=.001) but not the acetazolamide group (P=.018). The IOP levels were not significantly different between the acetazolamide group and brinzolamide group at any postoperative time point. No eye receiving medication and 2 eyes (10%) in the control group had an IOP of 30 mm Hg or higher 4 to 6 hours postoperatively. Compared with preoperatively, an IOP increase of more than 5 mm Hg was seen at 4 to 6 hours in 3 eyes (15%), 2 eyes (10%), and 14 eyes (70%) in the acetazolamide, brinzolamide, and control group, respectively. CONCLUSION: Brinzolamide was as effective as acetazolamide in preventing IOP elevation 4 to 6 hours after phacoemulsification and more effective than acetazolamide at 18 to 24 hours.     

Tolerability and efficacy of dorzolamide versus acetazolamide added to timolol.

PURPOSE: Evaluate the safety and efficacy of dorzolamide versus acetazolamide when added to once daily 0.5% timolol maleate ophthalmic gel forming solution (timolol gel). METHODS: 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. RESULTS: 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). CONCLUSIONS: This study found a greater incidence of systemic and CAI adverse experiences and discontinuations due to acetazolamide compared to dorzolamide.     

1%派立明滴眼液联合0.25%贝特舒混悬液的临床降眼压疗效及安全性观察

目的:观察派立明滴眼液联合贝特舒混悬液对中国人青光眼患者的降眼压疗效及安全性方法:选取原发性开角型青光眼、高眼压症、术后残余青光眼患者共26例44只眼,给予派立明滴眼液及贝特舒混悬液早晚各2次点眼,共观察2个月,分别于用药后2周、4周、6周、8周复查,观察用药前后的眼压及不良反应。结果:派立明联合应用贝特舒每日2次点眼,降眼压效果显著且稳定,眼压平均降低5.03～6.65mmHg(1mmHg=0.133kPa),平均降幅为20.55%～37.30%且不良反应少。结论:派立明滴眼液联合贝特舒混悬液对中国人具有良好的降眼压效果,毒副作用少,可作为临床上青光眼药物治疗的主要用药。     

Comparison of the safety and efficacy of dorzolamide 2% and brimonidine 0.2% in patients with glaucoma or ocular hypertension

PURPOSE: To compare the intraocular pressure (IOP) reduction between dorzolamide 2% and brimonidine 0.2% in primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Methazolamide 1% in cyclodextrin solution lowers IOP in human ocular hypertension

PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.