Effects of 0.005% latanoprost on optic nerve head and peripapillary retinal blood flow

Fifty-two eyes of 26 healthy volunteers were recruited for evaluating the effects of 0.005% latanoprost on optic nerve head (ONH) and peripapillary retinal blood flow. In a randomized double-blind design, one eye received one drop of 0.005% latanoprost and its fellow eye received one drop of a placebo eyedrop. Intraocular pressure (IOP), ONH and peripapillary retinal blood flow were measured with Heidelberg retinal flowmetry (HRF) before, 2 and 24 h after administration of eyedrops. IOP was decreased significantly in latanoprost-treated eyes at 2 and 24 h after administration (p < 0.05). In the volume, flow or velocity of ONH and peripapillary retina, there were no significant changes from the baseline values at 2 and 24 h after latanoprost administration in either latanoprost-treated eyes or their fellow eyes (p > 0.05). No significant differences were found in the measured quantities between latanoprost-treated eyes and their fellow eyes at each time point (p > 0.05). This result may suggest that 0.005% latanoprost in healthy subjects does not have any adverse effect on ONH and peripapillary retinal blood flow. Copyright Copyright 1999 S.Karger AG, Basel     

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.     

Effect of topical brinzolamide 1% and brimonidine 0.2% on intraocular pressure after phacoemulsification

PURPOSE: To compare the effectiveness of brinzolamide 1% (Azopt) and brimonidine 0.2% (Alphagan) with a placebo in preventing an early increase in intraocular pressure (IOP) after phacoemulsification. SETTING: Department of Ophthalmology, Baskent University, School of Medicine, Ankara, Turkey. METHODS: In this prospective double-masked study, 90 eyes of 90 patients having clear corneal phacoemulsification were randomly divided into 3 groups of 30 eyes each. One hour before surgery, 1 group received 1 drop of brinzolamide 1%, another received 1 drop of brimonidine 0.2%, and the third received 1 drop of a balanced saline solution (placebo). The IOP was measured preoperatively and 3 and 16 to 20 hours postoperatively. RESULTS: Three hours postoperatively, the mean IOP increased by 4.2 mm Hg +/- 7.0 (SD), 3.2 +/- 6.4 mm Hg, and 5.3 +/- 4.2 mm Hg in the brinzolamide, brimonidine, and placebo groups, respectively. The IOP increase from baseline was significant in all 3 groups (all P<.01), with no difference between the groups (P>.05). The change in IOP at 16 to 20 hours was 0.2 +/- 2.8 mm Hg, 0.2 +/- 2.4 mm Hg, and -0.8 +/- 2.4 mm Hg, respectively. The changes were not significant compared to baseline (all P>.05). Six eyes (20%) in the brinzolamide group, 5 eyes (16.7%) in the brimonidine group, and 7 eyes (23.3%) in the placebo group had an IOP higher than 25 mm Hg 3 hours postoperatively; the difference between groups was not significant (P =.8). CONCLUSION: Prophylactic use of 1 drop of brinzolamide or brimonidine was not more effective than a placebo in controlling early postoperative IOP elevations after clear corneal phacoemulsification.     

Assessment of retinal hemodynamics with the Canon laser blood flowmeter after a single dose of 2% dorzolamide hydrochloride eyedrops

BACKGROUND: Dorzolamide hydrochloride is a carbonic anhydrase inhibitor that reduces intraocular pressure (IOP) by decreasing the production of aqueous humour in the ciliary body. Theoretically, topical use of this agent has the potential to directly affect retinal vasculature through local induced acidosis. We performed a study to determine whether there are changes in retinal arteriole hemodynamics, as assessed with the Canon laser blood flowmeter, in healthy subjects following topical administration of dorzolamide. METHODS: We recruited 17 healthy volunteers, nine men and eight women aged 25 to 55 years (mean 31.4 [standard deviation (SD) 9.88] years). The inclusion criteria were Snellen visual acuity of 20/30 or better, normal anterior eye examination, IOP of 21 mm Hg or less, and a normal fundus appearance. One eye of each subject was randomly assigned to receive a drop of 2% dorzolamide. The contralateral eye of 10 of the subjects received a placebo drop (artificial tears). Before and 1 hour after drop administration, we obtained blood flow measurements from an inferotemporal arteriole approximately 1 disc diameter from the optic nerve head rim using the Canon laser blood flowmeter, model 100. The IOP was measured by means of Goldmann applanation tonometry before and 1 hour after drop administration. RESULTS: The mean IOP was significantly reduced in the dorzolamide-treated eyes, from 14.4 mm Hg (SD 2.94 mm Hg) to 11.7 mm Hg (SD 2.50 mm Hg) (p < 0.001). The IOP was also reduced in the placebo group (15.6 mm Hg [SD 3.41 mm Hg] vs. 14.6 mm Hg [SD 3.28 mm Hg]), but the difference was not significant. There was no significant difference in mean arteriole diameter, mean blood velocity or mean blood flow after drug administration in the dorzolamide-treated eyes. INTERPRETATION: Our results indicate that a single topical application of dorzolamide in healthy subjects has no effect on retinal arteriole diameter, blood velocity or blood flow, as measured with the Canon laser blood flowmeter. Longer-term studies of retinal hemodynamics in patients with glaucoma are warranted as evolving treatments aim to improve ocular blood flow as well as reduce IOP.     

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.     

The efficacy and safety of brinzolamide 1% ophthalmic suspension (Azopt) as a primary therapy in patients with open-angle glaucoma or ocular hypertension. Brinzolamide Primary Therapy Study Group

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.     

Medical control of intraocular pressure with brinzolamide 1% after phacoemulsification

Background: To compare the effectiveness of only 1 drop of topical brinzolamide 1% with dosing every 12 hours and with no ocular hypotensive medication following clear corneal phacoemulsification surgery.Methods: This prospective, randomized, double-blind study was composed of 60 eyes of 60 patients who underwent uneventful clear corneal phacoemulsification surgery under topical anesthesia. There were no intraoperative complications. Eyes were randomized to receive only 1 drop of topical brinzolamide 1% immediately after surgery, 1 drop of brinzolamide 1% every 12 (q12h) hours starting immediately after speculum removal, or no ocular hypotensive medication (control group). Intraocular pressure (IOP) was measured preoperatively and at 4 to 6 hours and 18 to 24 hours postoperatively by a Perkins tonometer.Results: Preoperative IOP was not significantly different among the 3 groups. IOPs of both the brinzolamide 1 drop group (p = 0.000) and the brinzolamide q12h group (p = 0.001) were significantly lower than those of the control group at 4 to 6 hours postoperatively. The same result was observed at 18 to 24 hours postoperatively in the brinzolamide q12h group (p = 0.001) but not the brinzolamide 1 drop group (p = 0.489). The brinzolamide q12h group had significantly lower IOP compared with the brinzolamide 1 drop group (p = 0.000) at 18 to 24 hours postoperatively. None of the eyes in the medication groups, but 1 eye (5%) in the control group, had postoperative IOP elevation ≥30 mm Hg at 4 to 6 hours; such an elevation was not encountered at postoperative 18 to 24 hours. Preoperative to postoperative IOP increase of >5 mm Hg at 4 to 6 hours postoperatively was seen in 4 (20%), 4 (20%), and 14 (70%) eyes in the brinzolamide 1 drop group, the brinzolamide q12h group, and the control group, respectively.Interpretation: The current study reveals that 1 drop of brinzolamide 1% is sufficient to control IOP within the first 4 to 6 hours following uneventful phacoemulsification, whereas 12-hour dosing is necessary for prolonged control of IOP.     

最新型局部碳酸酐酶抑制剂派立明的临床前及临床研究

派立明是一种最新型的局部碳酸酐酶抑制剂。此药可选择性、高亲和力及明显地抑制碳酸酐酶同功酶Ⅱ的活性,有效地降低眼压。本品滴眼后可快速进入眼组织,在虹膜、睫状体、脉络膜、视网膜、晶状体和血液中有较长的半衰期(数天)。虽然用派立明滴眼后,可在全血中测出药物浓度,提示陔药可全身吸收,但主药和其代谢产物的血浆浓度非常低,在稳定状态下药物与红细胞内碳酸酐酶的结合达不到完全饱和。因此,不会出现全身酸中毒或其他与口服碳酸酐酶抑制剂有关的副作用。对兔眼滴用派立明还町增加视乳头血流量,而对全身酸碱平衡的影响极小。如这一作用在人眼被证实,将对有视神经病变的青光眼患者十分有益。1％派立明每日滴眼2次的降眼压效果最好,且患者的耐受性较多佐胺好,这可提高患者长期用药的依从性。滴眼后最常见的剐作用是视物模糊(6％)及口苦、口酸等味觉异常(6％),总之,派立明的降眼压作用强,副作用小,滴眼舒适,患者耐受性好,是一种非常有价值的抗青光眼新药。     

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.     

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.     

Effect of concomitant use of latanoprost and brinzolamide on 24-hour variation of IOP in normal-tension glaucoma

PURPOSE: To study the effect of the concomitant use of latanoprost and brinzolamide on the 24-hour variation in the intraocular pressure (IOP) in patients with normal-tension glaucoma (NTG). METHODS: We studied a total of 44 eyes from 22 NTG patients. Mean 24-hour IOP variation was determined after a washout period of > or =4 weeks. Latanoprost monotherapy was continued in both eyes for 8 weeks. Thereafter, patients were randomized to continue latanoprost monotherapy in 1 eye whereas brinzolamide was added as an adjunct to latanoprost therapy in the other eye. Eight weeks after the initiation of brinzolamide treatment, the 24-hour IOP variation was remeasured. IOP was measured in the sitting position 8 times daily using a Goldmann applanation tonometer before and after treatment. RESULTS: The eyes treated with latanoprost monotherapy and those treated with latanoprost and brinzolamide showed a significant decrease in IOP at all time points. Percent reductions in the diurnal mean IOP (mean IOP at 10 AM, 1 PM, and 4 PM) and in nocturnal mean IOP (mean IOP at 10 PM, 1 AM, and 3 AM) were significantly greater in the eyes treated with the combination of latanoprost and brinzolamide than those with latanoprost alone (diurnal mean IOP: latanoprost and brinzolamide=19.8%, latanoprost=14.1%, P<0.001; nocturnal mean IOP: latanoprost and brinzolamide=13.4%, latanoprost=10.0%, P<0.05). CONCLUSIONS: For the treatment of NTG, the combination of latanoprost and brinzolamide demonstrated additive effects in lowering IOP, not only during the day, but also at night.     

Pharmacological and ocular hypotensive properties of topical carbonic anhydrase inhibitors

There was a time gap of over 40 years between the demonstrated oral effectiveness of acetazolamide in lowering the intraocular pressure (IOP) of glaucoma patients and the introduction of a topical carbonic anhydrase (CA) inhibitor. This is due to the fact that CA-II, the isoenzyme which most likely plays an important role in the production of aqueous humor in humans, must be essentially inhibited by 100% to elicit a pharmacological response. The lack of success with earlier attempts to obtain a topical agent stems from an inability to attain and maintain a sufficiently high intraocular concentration of drug to achieve the required inhibition of CA. Dorzolamide and brinzolamide are two topical CA inhibitors which are currently available to treat ocular hypertension and/or glaucoma. Dorzolamide is a very potent inhibitor of CA-II and its site of action is local within the eye. Like oral CA inhibitors, topically applied dorzolamide lowers IOP by decreasing the production of aqueous humor. The drug is used in monotherapy as a 2% solution administered three times daily. Its ocular hypotensive effect is comparable to that of timolol at peak but is somewhat less at trough. The IOP lowering effect of timolol is enhanced by the twice daily administration of 2% dorzolamide either concomitantly or in combination. Topically applied dorzolamide is generally well tolerated and had a low drop-out rate in clinical studies. The most frequent ocular adverse experience is burning and/or stinging. Corneal and lenticular problems have generally not been encountered with long-term therapy with dorzolamide. Topically applied dorzolamide penetrates directly to the posterior segment of the eye and its presence is consistent with the initial report that dorzolamide increases retinal blood flow velocity in patients with normal tension glaucoma. The most frequent systemic adverse experience is a transient bitter taste. Biochemical changes indicative of the systemic inhibition of CA have not been observed in monotherapy studies lasting up to 2 years. This is in harmony with the inability of dorzolamide at steady-state to saturate CA in the red blood cell and the failure to detect its presence in plasma. A 1% suspension of brinzolamide is comparable to 2% dorzolamide in lowering IOP, both drugs being administered three times daily. Although brinzolamide has a lower incidence of burning/ stinging, it elicits more blurred vision.     

Comparative study of the pressure lowering efficacy and variations in the ocular pulse amplitude between fixed combinations of dorzolamide/timolol and brinzolamide/timolol

ObjectiveTo determine possible differences in the intraocular pressure (IOP) and ocular pulse amplitude (OPA) lowering capacity of the fixed drug combinations dorzolamide/timolol and brinzolamide/timolol.MethodsIn this cross-sectional study, one of the eyes of 25 healthy subjects was randomly assigned to treatment with dorzolamide/timolol and the other eye with brinzolamide/timolol. After instilling the drops, possible adverse effects (e.g., blurred vision, itching) were assessed in each eye. This assessment was repeated 30 minutes later. IOP and OPA were determined In each eye by dynamic contour tonometry at baseline and two hours following treatment.ResultsBoth fixed drug combinations significantly reduced IOP and OPA with no differences detected between treatment groups. Among the adverse effects recorded, itching was significantly greater in the first assessment in the eyes treated with dorzolamide/timolol (P = .011). This difference was no longer apparent in the second assessment.ConclusionsBoth fixed combinations were similarly effective in reducing intraocular pressure and ocular pulse amplitude. Adverse effects related to both treatments were mild and well-tolerated, though itching occurred most frequently in the eyes treated with dorzolamide/timolol.     

Comparing the effects of travoprost and brinzolamide on intraocular pressure after phacoemulsification

PURPOSE: To evaluate the intraocular pressure (IOP) lowering effect of travoprost and brinzolamide within the first 24 h after phacoemulsification cataract surgery. METHODS: This prospective, randomized, double-masked, controlled study comprised 90 eyes of 90 consecutive patients with senile cataract who had uneventful phacoemulsification surgery. Eyes in the first group received travoprost 0.0015%, second group received brinzolamide 1%. Eyes in the third group received balanced salt solution and were used as control. One drop was instilled immediately after surgery. IOP was measured 24 h preoperatively, 6 and 24 h postoperatively. Analysis of variance, Student's-t and chi2-tests were used for statistical analyses. RESULTS: Preoperatively IOP was not significantly different among the three groups (P = 0.653). At 6 and 24 h postoperatively IOP was lower in both travoprost and brinzolamide group when compared to control group (P = 0.018 and 0.015 at 6 h, P = 0.010 and 0.007 at 24 h between travoprost and brinzolamide group was not significant (P = 0.744 at 6 h and P = 0.672 at 24 h). CONCLUSION: Both travoprost and brinzolamide significantly lowered IOP after small incision phacoemulsification cataract surgery within the first 24 h without any side effect.     

Dorzolamide and timolol saves retinal ganglion cells in glaucomatous adult rats.

PURPOSE: This study was designed to evaluate the effects of a dorzolamide-timolol combination or dorzolamide on retinal ganglion cell (RGC) density and intraocular pressure (IOP) in glaucomatous eyes of adult rats. METHODS: Glaucoma was induced in the right eye of adult Wistar rats by episcleral venous occlusion. One experimental group was administered dorzolamide 2%-timolol 0.5% combination eye drops, while the other experimental group was administered dorzolamide 2% eye drops. Control groups had surgery without drug administration. Drug application was initiated either 2 weeks before surgery (Group A), from the day of surgery (Group B), 2 weeks after surgery (Group C), or 4 weeks after surgery (Group D). RGCs were labeled by intratectal Fluorogold injections and counted from flat-mount preparations, and IOP was measured using Tonopen. RESULTS: Both dorzolamide-timolol combination and dorzolamide, when applied topically, significantly reduced IOP and improved RGC densities in experimental eyes when compared to control eyes. Earlier initiation, as well as longer duration of drug application, resulted in higher RGC densities. CONCLUSIONS: Topical application of a dorzolamide-timolol combination or dorzolamide saved RGCs to a significant extent and reduced IOP in glaucomatous rat eyes.     

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.     

A comparison of dorzolamide-timolol combination versus the concomitant drugs

PURPOSE: To compare the intraocular pressure (IOP) lowering effect of fixed combination dorzolamide 2% and timolol 0.5% therapy to that of concomitant administration of a topical beta-blocker and dorzolamide. METHODS: Seventy-four consecutive glaucoma patients were changed from a regimen including a topical beta-blocker and dorzolamide to the fixed combination dorzolamide-timolol in 1 eye, with the other eye used as the control. The average IOP readings before and 1 month after the change were compared. RESULTS: The mean baseline IOP in the entire study population was 19.4 +/- 4.2 mm Hg in the study eyes and 16.9 +/- 4.2 mm Hg in the control eyes. Four weeks after the medication change, the mean IOP was 17.3 +/- 3.9 mm Hg in the study eyes (P <.001) and 16.1 +/- 4.1 mm Hg in the control eyes (P =.02). The difference between the mean IOP change of 2.1 mm Hg in the study eyes and 0.8 mm Hg in the control eyes was found to be statistically significant (P =.01). CONCLUSION: These findings suggest that the fixed combination dorzolamide-timolol therapy achieves additional lowering of the intraocular pressure compared with the concomitant administration of a beta-blocker and dorzolamide.     

Effects of brinzolamide on aqueous humor dynamics in monkeys and rabbits.

This study examines the mechanisms by which brinzolamide reduces intraocular pressure (IOP) in healthy rabbits and in monkeys with unilateral ocular hypertension. Intraocular pressures were measured by pneumatonometry and aqueous flow was determined by fluorophotometry before and after three twice-daily drops of 1% brinzolamide to both eyes per monkey and after similar treatment to one eye per rabbit. In monkeys, outflow facility was determined by fluorophotometry and uveoscleral outflow was calculated. In rabbits, outflow facility was determined by two-level constant pressure infusion and uveoscleral outflow was measured by an intracameral tracer technique. Compared with contralateral vehicle-treated rabbit eyes, IOP was reduced in brinzolamide-treated eyes by 2.5 +/- 1.9 mmHg (mean +/- standard deviation; p =.006) at four hours after the second dose. Aqueous flow was reduced by 0.50 +/- 0.65 microl/min (p =.02). This effect was found in rabbits previously treated with brinzolamide but not in naive rabbits. Treated hypertensive eyes of monkeys had a reduction in IOP of 7.3 +/- 8.8 mmHg (p = 0.01) and aqueous flow of 0.69 +/- 1.10 microL/min (p = 0.05) when compared with baseline. Brinzolamide did not affect outflow facility or uveoscleral outflow in either rabbits or monkeys. It is concluded that, in normotensive eyes of rabbits and hypertensive eyes of monkeys, brinzolamide reduces IOP by reducing aqueous flow and not by affecting aqueous humor drainage.     

Comparative acute effects of brimonidine 0.2% versus dorzolamide 2% combined with beta-blockers in glaucoma

Purpose: To assess the acute intraocular hypotensive efficacy of brimonidine tartrate 0.2% (a highly selective α₂-adrenergic agonist) compared with dorzolamide 2% (a topical carbonic anhydrase inhibitor) as adjunct therapy to topical β-blockers in patients with primary open-angle glaucoma. Methods: A randomized cross-over masked study was performed. We enrolled one eye of each of 28 patients who were on different β-blocker therapy. We measured the intraocular pressure (IOP) 2 h after the β-blocker instillation; we then randomly administered one of the two drugs and we compiled an IOP diurnal curve. One month later we repeated the same procedures with the second drug. Unpaired Mann-Whitney U-test was used to compare decreases in IOP between the two drugs (P<0.05). Results: Both brimonidine 0.2% and dorzolamide 2% have good ocular hypotensive efficacy, significantly lowering IOP when compared to β-blocker therapy alone, for the whole diurnal curve. Maximum mean percent IOP decrease from baseline was 22.0±15.7% (4.0± 2.9 mmHg) for dorzolamide 2% 6 h after instillation and 35.5±16.4% (7.0±4.1 mmHg) for brimonidine 0.2% 8 h after administration of the drug. When we compared the two treatments, brimonidine 0.2% showed a higher hypotensive effect than 2% dorzolamide after 4 h (28.4±16.8% vs 17.6 ±9.3%; P=0.04) and 8 h (35.5±16.4% vs 21.6 ±10.8%; P=0.04). Conclusion: This study indicates that 0.2% brimonidine acutely associated with β-blockers is an interesting new combination treatment useful in the management of glaucoma. Received: 29 July 1999 Revised: 14 September 1999 Accepted: 29 September 1999     

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.