The effects of dorzolamide 2% and dorzolamide/timolol fixed combination on retinal and optic nerve head blood flow in primary open-angle glaucoma patients

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

Efficacy and safety of Indomethacin 0.1% versus Flurbiprofen 0.03% eyedrops in inflammation after argon laser trabeculoplasty

After Argon Laser Trabeculoplasty (ALT), non steroidal anti-inflammatory drugs (Indomethacin 1% suspension and Flurbiprofen 0.03% solution) were shown to be efficient in the management of post laser inflammation. To evaluate the efficacy and safety of Indomethacin 0.1% solution versus Flurbiprofen 0.03% eyedrops in that purpose, 64 patients suffering from glaucoma were recruited in a multicenter randomized double masked study. The results demonstrate that Indomethacin 0.1% eyedrops is as efficient as Flurbiprofen 0.03% in terms of control of post ALT inflammation, with a good tolerance.     

Scanning laser Doppler flowmeter study of retinal blood flow in macular area of healthy volunteers

AIM: To compare the interocular and intraocular differences of capillary perfusion, and the intraocular regional differences of retinal blood flow in the macular area of healthy volunteers. METHODS: Tissue blood flow in the macula was examined in both eyes of 20 healthy volunteers with the Heidelberg retinal flowmeter. Blood flow measurements were made in a 10 degrees x 2.5 degrees area superior and inferior to the macula. The mean blood flow (MBF) was calculated by an automatic full field perfusion image analyser program. The MBF in the right and left eyes and in the superior and inferior macular areas of the same eye were compared. RESULTS: The ratios of the MBF in the right eye to the left eye in the macular areas were 1.00, and 1.03, respectively. The ratio of the MBF in the superior macular area to the inferior area was 1.01 for the right eyes and 1.04 for the left eyes. CONCLUSIONS: Because no significant differences were found in the MBF between the two eyes and between the superior and inferior macular areas in the same eye, interocular (for example, affected eye versus fellow eye) and intraocular (superior versus inferior macular areas) comparisons of MBF can be made to determine if changes in retinal perfusion have occurred.     

Tear concentrations of azithromycin following topical administration of a single dose of azithromycin 0.5%, 1.0%, and 1.5% eyedrops (T1225) in healthy volunteers

PURPOSE: To evaluate azithromycin tear concentrations after one drop of T1225 0.5%, 1.0%, and 1.5% eyedrops. METHODS: In this randomized, double-masked study, 91 healthy volunteers received one drop into each eye of T1225 0.5% (n=23), T1225 1.0% (n=38), or T1225 1.5% (n=38). Azithromycin tear concentrations were measured by HPLC-MS at seven time points for 24 hours. Tolerability was evaluated. RESULTS: T1225 1.0% and 1.5% had similar pharmacokinetic profiles. After a post-instillation peak (167 to 178 mg/L after 10 minutes), mean concentrations remained above 7 mg/L for 24 hours (except for T1225 1% at H24). A delayed increase of the azithromycin mean tear concentration might be explained by the known late azithromycin release from tissues after storage in cells. Areas under inhibitory curve (AUICs) of T1225 1.0% and 1.5% were higher than AUICs of T1225 0.5% and ranged between 47 and 90. The three T1225 concentrations were safe for the ocular surface. CONCLUSIONS: Once daily instillation of T1225 1.0% and 1.5% was shown to reach an AUIC markedly above the required threshold for an antibacterial activity against Gram-positive bacteria (25-35). These results suggest that a BID instillation is more likely to ensure antimicrobial activity against Gram-negative bacteria (threshold >100).     

1% carteolol hydrochloride eyedrops: long-term experience in the treatment of chronic open-angle glaucoma

The response by 14 patients with open-angle glaucoma to treatment with carteolol 1% eye drops was investigated during a study lasting up to 15 months. Statistical analysis of the data revealed that carteolol had a highly significant IOP-lowering effect in all the patients studied. The mean decrease in IOP was as much as 41% of the initial value after the first day of treatment and after one week of treatment all the IOP values were close to 16-17 mm Hg. No long-term drift was noticed during the period of the study; no patient experienced any adverse reactions which could be related to the treatment with carteolol. This study therefore confirms the results of former investigations into the IOP-lowering effect of carteolol performed on Japanese subjects and classifies carteolol as a safe antiglaucoma agent which is also effective in Caucasian patients.     

Acute and chronic ocular symptoms of dorzolamide 2% compared with placebo

PURPOSE: To characterize and compare the ocular comfort and symptoms of dorzolamide and tear-replacement drops (placebo) in healthy volunteers. PATIENTS AND METHODS: Subjects were randomized in a double-masked fashion to receive each medicine for 6 days twice daily. Patients used a visual analog scale to assess the quality and intensity of pain temporally after initial (acute) dosing and after 6 days of chronic dosing. The visual analog scale, an objective measure of pain, allows a subject to grade their perceived intensity of pain on a line between 0 and 100 mm. RESULTS: Of 28 subjects enrolled in the study, 27 completed the protocol (1 subject was lost to follow-up). Dorzolamide demonstrated statistically greater peak ocular pain (21.4 +/- 22.3 mm) compared with placebo (1.9 +/- 4.4 mm) (P<0.0001) after chronic dosing. Time of mean peak pain for dorzolamide products was 15 seconds after dosing. The pain was statistically greater with dorzolamide compared with placebo for 50 seconds after dosing. On average the discomfort associated with dorzolamide lasted 38.9 +/- 17.9 seconds after dosing. The average pain per second for the first minute was 7.1 +/- 10.1 mm for dorzolamide. No differences in pain intensity were observed after acute and chronic dosing. The discomfort with dorzolamide was characterized after chronic dosing as "burning" (14.8 +/- 25.0 mm) and was associated with tearing (1.9 +/- 5.2 mm). CONCLUSION: Dorzolamide caused more ocular pain after instillation than placebo. However, the pain was characterized as mild and quickly resolved.     

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     

双氯芬酸钠滴眼剂在视网膜脱离手术前后的应用

在视网膜脱离术前、术后应用国内研制０１％双氯芬酸钠滴眼剂（３５例），同时用生理盐水设置对照组（３１例）。结果表明此药可以有效地防止术中瞳孔缩小及减轻术后炎症反应。     

Anti-inflammatory efficacy of a single posterior subtenon injection of triamcinolone acetonide versus prednisolone acetate 1% eyedrops after pars plana vitrectomy

PURPOSE: To compare the safety and anti-inflammatory efficacy of a single posterior subtenon injection of triamcinolone acetonide (TA) with prednisolone acetate 1% eyedrops after pars plana vitrectomy (PPV). METHODS: The study included 40 consecutive phakic eyes of 40 patients undergoing PPV for non-clearing vitreous haemorrhage with attached retina (verified by echography), epiretinal membrane or macular hole. At the end of the surgical procedure, eyes were randomized to receive either a single posterior subtenon injection of TA (40 mg in 1 ml) plus sham eyedrops (prednisolone acetate 1% vehicle) postoperatively (group TA), or a posterior subtenon sham injection (1 ml balanced salt solution) plus prednisolone acetate 1% eyedrops postoperatively (group ED). RESULTS: There was no difference in the severity of anterior chamber cell and flare between the two groups at any time-point during the study period (p > 0.05). Separate within-group analysis revealed a significant decrease in anterior chamber cell and flare from postoperative day 1 to postoperative days 7, 14 and 28 in both groups (p < 0.05). There was no difference in pain, photophobia, conjunctival erythema, ciliary flush or chemosis scores between the two groups at any time-point during the study period (p > 0.05). Steroid-induced intraocular hypertension was not observed in either group. CONCLUSIONS: A single posterior subtenon injection of TA can be as effective and safe as a 4-week regimen of prednisolone acetate 1% eyedrops in controlling intraocular inflammation after PPV.     

激光治疗对糖尿病视网膜病变患者视网膜血流动力学的影响

目的以彩色多普勒成像(colorDopplerimaging,CDI)技术探讨激光治疗对糖尿病视网膜病变(diabeticretinopathy,DR)患者视网膜血流动力学的影响。方法用CDI技术检测激光治疗前后DR患者视网膜中央动脉的收缩期峰值流速、舒张末期血流速度与阻力指数,以及激光治疗前后视力的改变,并作对照比较。结果激光治疗后DR患者视网膜中央动脉的收缩期峰值流速、舒张末期血流速度均有所增加,阻力指数稍下降,视力不同程度提高或保持不变。结论激光治疗能改善DR患者视网膜的血流灌注,对视力提高及保持原有视力有很好的临床价值。     

Changes in retinal blood flow after application of topical dipivefrine 0.1 %

Hintergrund: Viele der antiglaukomat?sen Medikamente beeinflussen den okul?ren Blutflu?. Die Blutflu?ver?nderungen in der vorderen Uvea sind in der Literatur beschrieben. über den Effekt von Antiglaukomatosa auf den Blutflu? des hinteren Augenpols wird in neuerer Zeit vermehrt berichtet. Wir pr?sentieren eine Placebo-kontrollierte Studie mit Blick auf den kurz- und mittelfristigen Einflu? von topisch appliziertem Dipivefrin 0,1 % auf den retinalen und papill?ren Blutflu?.     

Changes in retinal blood flow after application of topical dipivefrine 0.1 %

PURPOSE: Most of the antiglaucomatous drugs affect ocular blood flow. Blood flow of the anterior uvea under the effect of glaucoma medication has been described in the literature, but measurement of microcirculation at the posterior pole correlated to glaucoma medication is rarely found. We present a placebo-controlled study in which we focused on the short and long-term effects of topical dipivefrine 0.1% on the microcirculation of the retina and optic nerve head. PATIENTS AND METHODS: In a randomized, placebo-controlled double-masked study we examined 40 healthy persons (21 male and 19 female) with a mean age of 35 +/- 4.6 years. Two groups of volunteers (n = 20) were treated either with placebo or dipivefrine 0.1% for 5 days twice a day. Measurement of microcirculation was done at baseline, 30 min after the first application and on days 3 and 5. Microcirculation was evaluated by scanning-laser Doppler flowmetry (SLDF, Heidelberg Engineering; Heidelberg, Germany) [retinal and optic nerve head capillary blood flow (ONH)]. Systemic parameters were checked at all times of blood flow measurement (blood pressure, pulse); intraocular pressure (IOP) was also measured at baseline, 30 min after and on days 3 and 5. RESULTS: Systemic parameters: None of serum medications affected blood pressure or pulse. Dipivefrine 0.1% lowered the IOP significantly (P = 0.01). Microcirculation: dipivefrine 0.1% leads to a significant reduction of retinal capillary blood flow (P = 0.01). ONH blood flow was not significantly affected by dipivefrine 0.1%. CONCLUSION: Retinal capillary perfusion is affected by dipivefrine 0.1% medication. In neuroprotection, it is of interest that glaucoma medication did not alter the microcirculation in a way that leads to an increase of hypoxemia. Therefore, we consider dipivefrine 0.1% not to be useful for long-term glaucoma treatment.     

0．2％阿法根滴眼液对视网膜血流影响的研究

目的 研究0．2％阿法根（Brimonidine）滴眼液对视网膜血流的影响。方法 选取开角型青光眼或高眼压症患者15例,采用自身对照方法,于0．2％阿法根滴眼液治疗前和治疗后2h分别行海德堡视网膜血流计（HRF）检查,观察视网膜中央动脉颞上、颞下、鼻上、鼻下4条分支血管血容量、血流及血流速度的变化。结果 0．2％阿法根滴眼液治疗前后视网膜中央动脉颞止、颞下、鼻上、鼻下4条分支血管的血容量、血流及血流速度无明显改变。结论 0．2％阿法根滴眼液局部使用对视网膜血流无影响。     

Management of severe allergic conjunctivitis with topical cyclosporin a 0.05% eyedrops

PURPOSE: To evaluate the efficacy of topical cyclosporin A 0.05% in the management of severe allergic conjunctivitis. METHODS: Seven patients with severe allergic conjunctivitis who were not responding to topical steroids, antihistamines, and mast cell stabilizers were given topical cyclosporin A 0.05%. All patients had an active disease when they were included in the study. Signs and symptoms were recorded before and after treatment. RESULTS: Seven patients, 6 boys and 1 girl, 6-14 years old, 6 with vernal keratoconjunctivitis and 1 with atopic keratoconjunctivitis, were enrolled in the study. Treatment with topical cyclosporin A 0.05% decreased the severity of symptoms and clinical signs significantly after 6 months (P < 0.05, Wilcoxon signed rank test). In addition, the need for steroids was reduced or even stopped. The patients experienced no side effects during the follow-up periods (mean, 14.0 +/- 2.1 months; range, 8-18 months). CONCLUSIONS: Topical cyclosporin A is an effective treatment in the management of severe allergic conjunctivitis with a benefit as a steroid-sparing agent.     

Assessment of ocular hemodynamics after laser in situ keratomileusis using color Doppler imaging

To investigate ocular blood flow changes in healthy myopic patients following laser in situ keratomileusis (LASIK) using color Doppler imaging. Sixteen eyes of 16 myopic patients were studied. LASIK was performed and intraocular pressure was raised to levels ≥65 mmHg. Color Doppler images were obtained to study the ophthalmic and central retinal arteries preoperatively and postoperatively at 1 day, 1 week, and 1 month. There was no significant correlation between patient age and preoperative ocular blood flow parameters. A significant positive correlation between the degree of myopia and the peak systolic volume of the ophthalmic artery (r = 0.6, P = 0.01) was found. A highly significant decrease in the peak systolic volume and end-diastolic volume with an increase in the resistive index of both arteries (P < 0.005) was seen at 1 day and 1 week postoperatively. There was no significant difference between the preoperative and postoperative data 1 month after the procedure. The findings of this study show temporary alterations in ocular blood flow parameters after LASIK. LASIK is an increasingly common lifestyle procedure and further studies on larger groups are still recommended.     

Ocular comfort of combination glaucoma therapies: brimonidine 0.2%/timolol 0.5% compared with dorzolamide 2%/timolol 0.5%.

PURPOSE: Successful management of glaucoma and ocular hypertension requires patient compliance with the therapeutic regimen. Because ocular discomfort affects compliance, we compared the comfort of brimonidine 0.2%/timolol 0.5% and dorzolamide 2%/timolol 0.5%. METHODS: In this single-centre, randomized, double-masked, internally controlled/paired-eye study, 30 subjects without a significant ocular surface disease received brimonidine 0.2%/timolol 0.5% in 1 eye and dorzolamide 2%/timolol 0.5% in the fellow eye. They evaluated discomfort at 30-40 s and 5 min postinstillation. RESULTS: At 30-40 s, brimonidine 0.2%/timolol 0.5% provided significantly lower mean ocular discomfort scores than dorzolamide 2%/timolol 0.5% (P < 0.0001). This pattern persisted at 5 min but was not statistically significant. Significant differences were seen in the subjects' determination of the more comfortable treatment (P < 0.0001): brimonidine 0.2%/timolol 0.5% was rated as more comfortable than dorzolamide 2%/timolol 0.5% by 80% of subjects at 30-40 s and by 27% at 5 min. Only 10% of subjects at each time point rated dorzolamide 2%/timolol 0.5% as more comfortable. The remaining subjects reported no preference at either time point. No adverse events were reported. CONCLUSIONS: Brimonidine 0.2%/timolol 0.5% was significantly more comfortable than dorzolamide 2%/timolol 0.5% upon instillation. Patients with ocular hypertension or glaucoma may be more compliant with brimonidine 0.2%/timolol 0.5% treatment.     

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.     

Population pharmacokinetics of 2% topical dorzolamide in the aqueous humor of humans.

PURPOSE: To evaluate the concentration and kinetics of dorzolamide in the aqueous humor after its topical application. METHODS: Samples of aqueous humor were collected at the beginning of routine cataract surgery at defined intervals after topical application of a 2% solution of dorzolamide. After deep-frozen storage of the samples, drug extraction was achieved with a mixture of solvents. Quantification was carried out by high-performance liquid chromatography on a reversed-phase column. RESULTS: Peak concentrations of dorzolamide in aqueous humor were reached approximately 2 hours after application with 1000 ng/ml. Average values were approximately 1000 to 700 ng/ml after 4 to 6 hours and approximately 200 ng/ml after 12 hours. Mean half-life of absorption was 1.2 hours and for elimination 3.0 hours. CONCLUSIONS: Pharmacokinetics of dorzolamide in the aqueous humor of humans are in comparable dimensions as previously reported in experimental trials in pigmented rabbits. There is a clear linear absorption and elimination kinetic, which is demonstrated using the Bateman function. A better knowledge of the distribution and kinetics of dorzolamide will help to explain its reported effects on intraocular hemodynamics, distinct from its intraocular pressure lowering effect.     

Intraocular pressure and ocular hemodynamics in patients with primary open‐angle glaucoma treated with the combination of morning dosing of bimatoprost and dorzolamide hydrochloride

Acta Ophthalmol. 2011: 89: e57–e63

Abstract.

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