Long-term use of corticosteroid eye drops delays the spontaneous remission of pulmonary sarcoidosis

Topical corticosteroid eye drops are commonly used for ocular sarcoidosis. That systemic absorption of corticosteroids by eye drops may influence the clinical course of sarcoidosis may be speculated because it has been reported that the serum concentration of corticosteroids after drop administration was dose-related. To evaluate the effects of corticosteroid eye drops on the clinical course of patients with stage I pulmonary sarcoidosis, we compared the serum levels of angiotensin converting enzyme (ACE) and bilateral hilar lymphadenopathy (BHL) on chest radiographs of group CS, which is consisted of patients who received topical therapy of betamethasone in the form of eye drops for anterior uveitis, and group CN, which is consisted of patients who did not receive any medications throughout the entire course of the disease. Although the serum ACE level was not significantly different between groups CS and CN at the time of the diagnosis of pulmonary sarcoidosis, the level of serum ACE in group CS was significantly higher than that in group CN 20 months after the topical corticosteroid treatment (24 IU/ml and 16 IU/ml, respectively). Further, the size of BHL on chest radiography in group CS was significantly larger than that in group CN 20 months after the topical treatment (82% and 37% of before control, respectively). These findings suggest the possibility that the topical corticosteroid therapy influenced the clinical course of pulmonary sarcoidosis, inducing some delay in the spontaneous remission in the longterm course.     

Efficacy Assessment of Celecoxib Oil Drops Versus Arachidonic Acid Stimulated Ophthalmic Inflammation in Rabbits

The most comfortable approach to deliver an active pharmaceutical ingredient to the eye has been via topical instillation of aqueous drops. However, the aqueous drops suffer a major setback due to the rapid drainage leading to loss of drug. The aim of the present work was to formulate oil preparations of celecoxib in different oils. Partition behavior, trans-corneal permeation, viscosity, in vivo anti-inflammatory study and gamma scintigraphy of the preparations were investigated. Incorporation of benzyl alcohol resulted in a significant increase in drug permeation across the cornea (p < 0.05). The in vivo efficacy of optimized castor oil formulation was found to be better than control as well as CXB-aqueous suspensions in arachidonic acid triggered eye swelling model in rabbits. Further, results of gamma scintigraphy also indicated prolonged retention. Therefore, the oil eye drops may be a promising alternative, to aqueous eye drops circumventing poor retention in management of ocular ailments.     

Voriconazole concentration in human aqueous humor and plasma during topical or combined topical and systemic administration for fungal keratitis

Voriconazole (VRC) is an antifungal drug that effectively treats keratitis caused by yeasts and molds when administered orally. We retrospectively evaluated clinical outcomes and plasma and aqueous humor drug concentrations in five patients with fungal keratitis and one patient with posttraumatic endophthalmitis who were treated with VRC. VRC was administered either topically (1% eye drops every hour) or orally (400 mg twice a day). Plasma and aqueous humor samples from affected eyes were taken 12 h after oral administration or 1 h after eye drop application. The drug concentration was measured by liquid chromatography with UV or mass spectrometric detection. All six patients responded well to VRC treatment. The VRC concentration ranged from 2.93 to 3.40 mg/liter in the aqueous humor and from 3.20 to 4.20 mg/liter in the plasma after combined oral and topical treatment. Topical administration alone resulted in highly variable trough VRC concentrations of 0.61 to 3.30 mg/liter in the aqueous humor. VRC concentrations were above the MIC for Candida albicans Aspergillus fumigatus and clinical improvement was seen in all four patients with C. albicans and A. fumigatus keratitis. Combined orally and topically administered VRC resulted in aqueous humor drug concentrations of > or =2.93 mg/liter, which is above the VRC MIC for most fungi. Topical VRC treatment resulted in an aqueous humor drug concentration >0.61 mg/liter, which is above the MIC for most Candida species. The results from this small series of patients suggest that both topical and combined systemic and topical VRC therapy can be effective in treating fungal keratitis. Furthermore, the data provide preliminary support for initiation of VRC treatment with a combined topical and systemic administration until the causative fungus and its MIC are identified.     

Stability of cefazolin sodium eye drops

Objective: Assessing the stability of cefazolin sodium in preservative-free and preservative-containing eye drops. Method: Extemporaneous formulations of eye drops were prepared from a commercially-available parenteral product of cefazolin sodium: eye drops ‘A’ contained 50 mg/ml of cefazolin sodium in 0·45% w/v sodium chloride solution, and eye drops ‘B’ contained 50 mg/ml, 0·005% w/v thiomersal and 1% w/v glycerol in water-for-injection. Cefazolin sodium concentrations in these eye drops were monitored by a stability-indicating HPLC assay method. Measurements of pH and osmolality, as well as tests for microbial contamination, were conducted. Results: The eye drops stored at 4 °C were stable for 42 days with minimal changes in pH and osmol- ality, but eye drops stored at room temperature were only stable for a few days with greater incre- ments in pH and osmolality. None of the samples cultured had bacterial or fungal growth after 7 days of incubation. Conclusion: Extemporaneously prepared formula- tions of cefazolin are unstable at room temperature and should be stored in a refrigerator.     

Tetrahydrozoline (Visine®) concentrations in serum and urine during therapeutic ocular dosing: A necessary first step in determining an overdose

Introduction. No information exists on therapeutic or toxic concentrations of tetrahydrozoline, which has been reported to be used in drug facilitated sexual assaults. The primary aim of this investigation was to establish baseline therapeutic serum and urine concentrations in a sample of healthy volunteers. Methods. Ten healthy volunteers consented to have two drops of Original Visine® eye drops (0.05% tetrahydrozoline solution) placed directly into the conjunctival sac of each eye, 30 s apart, at times 0, 4, 8, and 12 h. Blood and urine samples were then collected at 2, 5, 9, 13, and 24 h post-application and analyzed for concentrations. Tetrahydrozoline concentrations are described using measures of central tendency and dispersion at each time point, with predictions of serum and urine concentrations over time calculated using a linear mixed effects regression model. Results. Tetrahydrazoline concentrations were detectable in both serum and urine after therapeutic ocular administration. The mean serum half-life of tetrahydrozoline was approximately 6 h. Systemic absorption varied among subjects, with the maximum serum concentrations ranging from 0.068 to 0.380 ng/ml. At 24 h, all patients had detectable urine concentrations of tetrahydrozoline (range = 13–210 ng/ml). Conclusion. When used as directed by the manufacturer for therapeutic ocular administration, tetrahydrozoline concentrations were detectable in both serum and urine up to 12 h after the last administered dose. A concentration greatly exceeding the 95% confidence interval of drug present during therapeutic ocular use may be suggestive of illegal adulterant use or accidental or suicidal overdose.     

Tear concentrations of levofloxacin following topical administration of a single dose of 0.5% levofloxacin ophthalmic solution in healthy volunteers

BACKGROUND: Several fluorinated carboxyquinolones are used to treat ocular infectious disease. Levofloxacin, in particular, has demonstrated activity against both gram-negative and gram-positive bacteria. OBJECTIVES: An open-label study was undertaken to assess the pharmacokinetics and ocular bioavailability of levofloxacin in human tears, and to determine the tear concentration of levofloxacin in healthy volunteers, following topical administration of a single-dose of 0.5% levofloxacin ophthalmic solution. METHODS: Volunteers received 1 drop of 0.5% levofloxacin in each eye and were assigned sequentially to 1 of 5 groups for tear sampling. Tear samples were collected on Schirmer test strips at 9 predetermined time points ranging from 5 minutes to 24 hours after administration. Six tear samples were collected at each time point (1 eye each from 6 volunteers), except the 24-hour time point, at which 12 samples were collected (both eyes of 6 volunteers). No eye had > 1 tear sample taken during the study. Levofloxacin concentrations were measured using reverse-phase high-performance liquid chromatography. RESULTS: Thirty volunteers were enrolled, with 6 assigned to each of the 5 sampling groups. At 5 minutes after administration of a single topical dose of levofloxacin, the mean tear concentration was 49.19 +/- 26.73 microg/mL. The mean peak concentration of levofloxacin in the tear film, 221.06 +/- 256.68 microg/mL, was reached at 15 minutes after administration. At 4 hours after administration, the mean tear concentration of levofloxacin was 17.04 +/- 15.13 microg/mL. At 6 hours after administration, the mean concentration of levofloxacin was 6.57 +/- 5.26 microg/mL. At 24 hours after administration, levofloxacin concentrations > 2 microg/mL were measured in 2 of 6 (33%) subjects. CONCLUSIONS: Levofloxacin concentrations in the tear fluid after a single topical dose (1 drop) reached high levels quickly and remained above the minimum inhibitory concentration for most suspected ophthalmic pathogens (< or = 2 microg/mL) for at least 6 hours in most healthy volunteers, and for up to 24 hours in some volunteers.     

左氧氟沙星滴眼液治疗细菌性角膜炎的临床研究

目的比较0.3%盐酸左氧氟沙星滴眼液和0.3%氧氟沙星滴眼液治疗细菌性角膜炎的疗效和安全性。方法共纳入观察患者30例,试验组15例应用左氧氟沙星滴眼液,对照组15例应用氧氟沙星滴眼液,观察疗效和不良反应,疗程3～14d,主要疗效参数为治疗第7、14d的临床疗效。结果用药7d试验组有效率为80.0%;对照组有效率为60.0%;试验组和对照组经检验有显著性差异（P〈0.05）。用药14d试验组有效率为93.33%;对照组有效率为73.33%,两组间有效率有显著性差异（P〈0.05）。治疗前试验组和对照组细菌培养阳性率均为100%。治疗后试验组细菌转阴率为86.67%;对照组细菌转阴率为60.0%。两组间细菌阴转率比较有显著性差异（P〈0.05）。试验组与对照组均有良好的耐受性,无明显不良反应发生。结论0.3%盐酸左氧氟沙星滴眼液具有疗效好、起效快、使用安全等特点,是治疗细菌性角膜炎的良好药物。     

Efficacy of topical anesthetics to reduce pain in premature infants during eye examinations for retinopathy of prematurity

BACKGROUND: Eye examinations for retinopathy of prematurity (ROP) are stressful and probably painful, but many ophthalmologists do not apply topical anesthetics because their efficacy in reducing pain has not been established. OBJECTIVE: To evaluate the potential benefits of topical anesthetic eye drops in reducing pain during neonatal eye examination for ROP. METHODS: Neonates born at < or =30 weeks' gestation and expected to have at least 2 examinations for ROP were included. Patients were randomly assigned to receive either proparacaine HCl ophthalmic solution 0.5% or NaCl 0.9% (saline) eye drops prior to an eye examination. In a subsequent examination, each patient received the alternate treatment. Eye drops were prepared in the pharmacy in identical tuberculin syringes, and physicians, nurses, and pharmacists were blinded to the treatment given. Pain was measured using a scoring system with both physical and physiologic measures of pain (Premature Infant Pain Profile [PIPP], possible range 1-21), which has been validated in preterm infants. PIPP scoring was performed simultaneously by 2 nurses: 1 and 5 minutes before and after the eye examination and during initial placement of the eye speculum. The same ophthalmologist performed all examinations. RESULTS: Twenty-two patients were studied, with 11 infants receiving proparacaine and 11 receiving saline as the first treatment. Crossover was performed with a median of 17.5 days between treatments. Patients experienced significantly less pain at speculum insertion with proparacaine than with saline (paired difference -2.5 +/- 3.4; p = 0.001). CONCLUSIONS: Topical anesthetic pretreatment reduces the pain response to eye examination for ROP and should become routine practice. Because this is not effective in all infants, additional measures to reduce pain should be taken.     

Comparing the fixed combination dorzolamide-timolol (Cosopt) to concomitant administration of 2% dorzolamide (Trusopt) and 0.5% timolol -- a randomized controlled trial and a replacement study

PURPOSE: To compare the intraocular pressure (IOP) lowering effect of concomitant administration of 0.5% timolol and 2% dorzolamide and a fixed combination dorzolamide-timolol (Cosopt) To critically evaluate discrepancies between phase 3 clinical trials and prior replacement studies. DESIGN: A prospective, randomized, controlled clinical trial and a prospective, non-randomized comparative replacement trial. PARTICIPANTS/INTERVENTIONS: In a national multicentre trial, 131 patients were randomized to dorzolamide-timolol or a topical carbonic anhydrase inhibitor (CAI) and non-selective beta-blocker following a 1-month run-in using the separate components. Peak (maximal drug effect) and trough (minimal drug effect) IOPs were measured at baseline and 1 month after treatment. The replacement therapy study enrolled 404 consecutive glaucoma patients using a non-selective beta-blocker and dorzolamide and changed treatment to the fixed combination. Mean IOPs at the same time of day were compared before and 1 month after changeover. MAIN OUTCOME MEASURE: The main outcome measure was IOP, comparing baseline and on-therapy measurements at study conclusion between the two arms of the randomized trial and before and after switching therapy in the replacement trial. RESULTS: In the randomized trial, the mean baseline peak and trough IOPs were 18.4 and 21.0 mmHg in the group randomized to combination therapy and 17.6 and 19.8 mmHg in the dual drug group. After randomization and treatment for four weeks, the peak and trough IOPs were 17.6 and 19.5 mmHg in the combination group and 17.3 and 19.0 mmHg in the concomitant group. The percentage change in IOP was -3.2% at peak and -6.5% at trough for the combination and -0.3 and -3.2% for the concomitant group. These differences did not show statistical significance. In the replacement study, mean baseline IOP was 19.4 mmHg. Four weeks after initiation of treatment on the fixed combination, a significant additional IOP reduction of 1.7 mmHg (-8.8%) was observed (P < 0.0001). Overall, 81% of eyes exhibited equal or lower IOP on the fixed combination compared with concomitant therapy. CONCLUSION: The results of the randomized trial indicate that the fixed combination dorzolamide-timolol (Cosopt) was as effective as its components in controlling IOP, confirming results seen in phase 3 clinical trials. However, in the replacement study, utilization of the combination drug offered a statistically significant additional IOP reduction (P < 0.0001), which duplicates results from previous replacement studies.     

碱性成纤维细胞生长因子促进芥子气致角膜损伤的修复

目的观察碱性成纤维细胞生长因子(basic fibroblast growth factor, bFGF)对芥子气角膜损伤修复的促进作用.方法新西兰白兔 8只,用浓度为 200 mL/L的液态芥子气致伤双眼角膜 5 min,一眼为治疗组,用 bFGF稀释液滴眼, 6次 /d,另一眼为对照组,用 2.5 g/L氯霉素眼液滴眼, 6次 /d,分别于染毒后 2,8,16,24,36,48和 72 h对角膜荧光素着色区拍照,计算其上皮愈合速率和上皮破损率.结果治疗组和对照组的角膜上皮愈合速率分别为 1.276 mm2/h和 1.094 mm2/h,两者差异显著 (t=14.94, P< 0.01);角膜上皮破损率分别为 51.8%和 68.0%,两者差异显著 (χ 2=11.81,P< 0.01).结论碱性成纤维细胞生长因子能促进芥子气染毒引起的兔眼角膜损伤的上皮愈合.     

Sustained in vivo release from imprinted therapeutic contact lenses

In this paper, we demonstrate the successful in vivo extended release of a small molecular weight therapeutic, ketotifen fumarate (MW=425), from molecularly imprinted, therapeutic contact lenses. This is the first time that a steady, effective concentration of drug is maintained in the tear film from a contact lens for an extended period of time for the entire duration of lens wear. Poly(HEMA-co-AA-co-AM-co-NVP-co-PEG200DMA) soft contact lenses were prepared (100±5 μm thickness, diameter 11.8 mm, power zero), and a constant tear film concentration of 170±30 μg/mL was measured for up to 26 hrs in a New Zealand white rabbit model. The results showed a dramatic increase in ketotifen mean residence time (MRT) and bioavailability compared to topical drop therapy and drug soaked lenses. The MRT for imprinted lenses was 12.47±3.99 hrs, ~4 and 50 fold greater than non-imprinted lenses and 0.035% eye drops (Zaditor?), respectively. Furthermore, AUC(0-26 hrs) was 9 and 94 fold greater for imprinted lenses than non-imprinted lenses and eye drops, respectively. The results indicate that molecular imprinting provides an exciting rational engineering strategy for sustained release. It is clear that imprinted lenses are very promising combination devices and are much more effective and efficient delivery devices than eye drops.     

抗生素滴眼液在白内障术前应用疗效分析

目的探讨两种不同的抗菌素滴眼液在白内障术前应用的临床效果。方法选取收治的126例(178眼)行白内障摘除手术患者的临床资料,A组(左氧氟沙星滴眼液治疗)66例,B组(妥布霉素滴眼液治疗)60例,比较两组患者术后细菌培养阳性率。结果给药前,A组细菌培养阳性率52.22%,给药后,其阳性率28.89%,给药前后阳性率的差异具有明显统计学意义(P<0.05),B组给药前细菌培养阳性率51.14%,给药后,其阳性率28.41%,给药前后阳性率的差异具有明显统计学意义(P<0.05)。结论左氧氟沙星和妥布霉素滴眼液均具有较佳的清除细菌作用,可以有效预防白内障术后感染,值得临床广泛推广和应用。     

Stability of extemporaneously prepared 0.5-percent caspofungin eye drops: a potential cost-savings exercise

While the successful use of topical caspofungin for patients has been reported, topical caspofungin is not commercially available and its stability is unknown, limiting its usefulness in treating fungal keratitis. Caspofungin (0.5%) eye drops were aseptically prepared, and the concentrations were measured using a validated high-performance liquid chromatography (HPLC) analysis. The preparations remained stable for 28 days under refrigerated condition but not at 25.0 °C. Our study supports the cost-saving use of caspofungin eye drops in the clinical setting.     

Efficacy and safety of brimonidine, dorzolamide and latanoprost as adjunctive therapy in primary open angle glaucoma

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

Adoption of new antiglaucoma drugs in Finland: impact of changes in copayment

BACKGROUND: Copayments are common measures intended to control drug expenditures and promote rational prescribing. In Finland, new antiglaucoma drugs start with a high copayment, but once sufficient clinical experience is available, they are reevaluated and can receive a lower copayment status. OBJECTIVE: This study assessed the effect of changes in copayment level on the adoption of 2 antiglaucoma drugs. METHODS: A retrospective analysis was performed from 1997 to 2001 using the Finnish national register of reimbursed drug purchases, which covers approximately 98% of all antiglaucoma drug purchases in the country. There were 172,293 purchases of dorzolamide (plain or combined with timolol) and 281,377 purchases of latanoprost. An interrupted time-series design from approximately 30 months before and 20 months after the change in copayment was used in the analysis. The main outcome measures were the numbers of defined daily doses (DDDs) purchased and the monthly numbers of patients who purchased the study drugs for the first time before and after the change in copayment. RESULTS: A substantial increase in consumption of both dorzolamide and latanoprost was seen immediately after the introduction of the lower copayment. The monthly consumption of dorzolamide was 60,713 DDDs higher and the monthly consumption of latanoprost was 49,330 DDDs higher than expected according to the utilization trend during the higher copayment period. Twelve months later, the observed consumption of dorzolamide was 109% higher and that of latanoprost was 21% higher than if the copayment had remained the same. The number of new patients using the study drugs peaked within 2 months of the lower copayment, but the amount consumed per patient per day remained quite stable. CONCLUSIONS: Decreasing the copayment of a new antiglaucoma drug to the same level as the copayments of alternative drugs accelerated the adoption of these new products in Finland.     

Thermosetting gels with modulated gelation temperature for ophthalmic use: the rheological and gamma scintigraphic studies.

For ophthalmic drug delivery, Pluronic F127 solutions have a phase transition temperature too low for them to be instilled into the eye at room temperature. Refrigerator storage is usually required to make administration easier, whereas the potential irritation of cold to the sensitive ocular tissues may result in poor topical bioavailability. The purpose of this study is to develop a thermosetting gel with a suitable phase transition temperature by combining Pluronic analogs and to examine the influence of incorporating mucoadhesive polysaccharide, sodium hyaluronate (HA-Na), on the ocular retention of the gel. Dynamic rheological method and single photon emission computing tomography (SPECT) technique were used to ex/in vivo evaluate the thermosetting gels, respectively. An optimized formulation containing 21% F127 and 10% F68 increased the phase transition temperature by 9 degrees C as evaluated by elasticity modulus compared to that of individual 21% F127 solution. Rheological behaviors of the Pluronic solutions showed that the combined Pluronic formulation was free flowing liquid below 25 degrees C and converted to a firm gel under the physiological condition. Furthermore, this formulation possessed the highest viscosity both before and after tear dilution at 35 degrees C. Gamma scintigraphic data demonstrated that the clearance of the thermosetting gel labeled with 99mTc-DTPA was significantly delayed with respect to the phosphate buffered solution, and at least a threefold increase of the corneal residence time was achieved. However, no further improvement in the ocular retention was observed when adding HA-Na into the thermosetting gel due to the substantially decreased gel strength.     

金栀清目方联合玻璃酸钠滴眼液治疗睑板腺功能障碍性干眼症

目的:探讨金栀清目方联合玻璃酸钠滴眼液治疗睑板腺功能障碍性干眼症的临床疗效。方法:本次研究纳入湖南中医药大学第一附属医院眼科2017年12月1日—2018年12月1日门诊患者102例,随机分为对照组与实验组,对照组(51例)予以单纯玻璃酸钠滴眼液滴眼,实验组(51例)予以玻璃酸钠滴眼液联合金栀清目方滴眼。治疗前后分别予以对比结膜充血程度、泪膜破裂时间、泪液分泌试验、角膜荧光素钠染色以及观察其用药后不良反应。结果:实验组患者疗效有效率为(98.04),高于对照组(88.23),P<0.05;治疗前后两组患者泪膜破裂时间、泪液分泌试验、角膜荧光素钠染色均改善,实验组明显优于对照组,P<0.05;两组用药不良反应发生率比较差异无统计学意义(P>0.05)。结论金栀清目方联合玻璃酸钠滴眼液治疗睑板腺功能障碍性干眼症临床效果显著,患者症状较前明显改善,不良反应率发生较低,值得广泛应用于临床。     

Efficacy of brimonidine 0.2% and dorzolamide 2% as adjunctive therapy to beta-blockers in adult patients with glaucoma or ocular hypertension

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