Efficacy and safety of latanoprost/timolol fixed combination dosed twice daily compared to once daily in patients with primary open angle glaucoma

AIM:To evaluate whether latanoprost/timolol fixed combination(LTFC)dosed twice daily may provide further intraocular pressure(IOP)reduction and evaluate the safety profile at this dose.METHODS:This is an open-labeled,randomized,prospective crossover study on fourty primary open angle glaucoma patients.Two weeks of washout period were followed by randomization to either once daily(OD,group A)or twice daily dosing(BD,group B)of LTFC for 4wk.After another 2-week washout period,the patients’treatment dose was crossed-over for another 4wk.IOP reduction alongside ocular and systemic side effects were evaluated.RESULTS:Mean baseline IOP was 18.57±2.93 and 17.8±3.01 mm Hg before OD and BD dose respectively,(P=0.27).Mean IOP after BD dose was statistically lower(12.49±1.59 mm Hg)compared to OD(13.48±1.81 mm Hg,P=0.017).Although IOP reduction after BD dose was more(5.32±3.24 mm Hg,29.89%)than after OD dosing(5.04 mm Hg,27.14%),it did not reach statistical significance(P=0.68).Patients switched from OD to BD(group A)showed mean IOP reduction by 0.69 mm Hg[95%confidence interval(CI):-0.09 to 1.48 mm Hg,P=0.078];but patients switched from BD to OD(group B)had significantly higher mean IOP by 1.25 mm Hg(95%CI:-2.04 to-0.46 mm Hg,P=0.006).BD dose had more ocular side effects albeit mild.CONCLUSION:Mean IOP after LTFC dosed twice daily is statistically lower,with additional mild side effects.

Intraocular pressure-lowering effects of commonly used fixed combination drugs with timolol in the management of primary open angle glaucoma

AIM:To evaluate intraocular pressure(IOP)-lowering effect and ocular tolerability of brimonidine/timolol,dorzolamide/timolol and latanoprost/timolol fixed combination therapies in the management of primary open angle glaucoma.· METHODS:Each drug was administered for two months, after which a circadian tonometric curve was recorded using a Goldmann applanation tonometer.Ocular discomfort(conjunctival hyperemia, burning or stinging, foreign body sensation, itching, ocular pain) of each eye was assessed by the subject on a standardized ocular discomfort scale.RESULTS:Among the three study groups, there were no significant differences in the mean baseline IOP measurements, mean 2ndmo IOP measurements, and mean(%) change of IOPs from baseline. Among the three study groups, there were no significant differences in the mean IOP measurements obtained at circadian tonometric curves at baseline and at two months controls. In sum brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar effects on IOP levels.· CONCLUSION:Brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar lowering efficaties on IOP levels whereas there was no any difference between each other.

D-Timolol和L-Timolol对大鼠脉络膜新生血管及内皮细胞的作用(英文)

目的:老年黄斑变性患者存在脉络膜血流灌注障碍。据此,我们推测血管活性药物,由于能减小脉络膜血流的阻力,可能会防止脉络膜新生血管的发展。D-Timolol和L-timolol是应用于心血管和青光眼治疗的降血压药物。本文旨在评价二者对激光诱发的大鼠脉络膜新生血管模型和人脐静脉内皮细胞(HUVEC)的作用。方法:雄性BrownNorway大鼠,麻醉下行Nd:YAG激光击穿Bruch膜。激光后,予D-Timolol和L-Tim-olol每日一次腹腔注射4wk。2wk末及4wk末时行荧光造影检查。观察不同浓度D-Timolol和L-Timolol对体外培养的HUVEC细胞增殖和黏附的影响。结果:在激光诱发的大鼠脉络膜新生血管模型中,予D-Timolol腹腔注射15mg/(Kg·d),可减少荧光渗漏的位点,至对照组的83%。而L-Timolol对脉络膜新生血管的形成没有影响,即使注射更高的治疗剂量20mg/(kg·d)。D-Timolol300mg/L可抑制内皮细胞的生长。L-Timolol在1000mg/L可以显著抑制细胞的增殖,但在相对低的浓度300mg/L,则没有发现明显的抑制作用。在HUVEC细胞黏附的观察中,两者均未有显著的影响。结论:D-Timolol可减少激光诱发的脉络膜新生血管的形成,也能抑制血管内皮细胞的增殖。而L-Tim-olol在同样的浓度不影响内皮细胞的增殖,也不能影响大鼠脉络膜新生血管的形成。这两种同分异构体对动物模型和培养细胞的不同作用,可能对探索脉络膜新生血管的治疗有新的意义。

Effect of latanoprost/timolol and dorzolamide/tiomolol on intraocular pressure after phacoemulsification surgery

·AIM:To evalaute the effect of fixed-combination latanoprost 0.005%/timolol maleate 0.5% and dorzolamide hydrochloride 2%/timolol maleate 0.5% on postoperative intraocular pressure after phacoemulsification cataract surgery.·METHODS:This study is a prospective,randomized,double-masked and placebo-controlled.The study included 90 eyes of 90 patients which were scheduled to have phacoemulsification surgery.Patients were randomly assigned preoperatively to 1 of 3 groups (30 eyes of 30 patients).Two hour before surgery,the patients received one drop latanoprost/timolol (group 1),dorzolamide/timolol (group 2) and placebo (group 3,control group).The IOPs were measured at preoperative and postoperative 4,8,and 24 hours.·RESULTS:The preoperative mean intraocular pressure was not statistically significant between both drug groups and control group.In group 1 and 2,the postoperative mean IOP [group1:(14.03?à3.15)mmHg and group 2:(14.16?à4.43)mmHg] at 24 hours were significantly lower than the control group [(16.93?à3.70)mmHg,(P <0.05)].In addition,the postoperative mean IOP of group 1 [(14.90±3.69)mmHg] at 8 hours was significantly lower than the control group [(17.70?à3.89)mmHg,(P <0.05)],but there was no significant difference between group 2 [(16.16?à5.23)mmHg] and control group at 8 hours (P >0.05).·CONCLUSION:When compared with placebo,the use of preoperative fixed combination of latanoprost/timolol and dorzolamide/timolol is an effective method for preventing intraocular pressure elevation in 24 hours after phacoemulsification surgery,but did not completely prevent IOP spikes.·

A novel fixed-combination timolol-netarsudillatanoprost ophthalmic solution for the treatment of glaucoma and ocular hypertension

Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration,poor efficacy and side effects.Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution(FC-TNL)has the ability to treat glaucoma by lowering the intraocular pressure(IOP)with great efficacy and improving patient compliance.However,the commercialized netarsudil dimesylate precipitated when the p H of the solution was above 5.4,or when maleic acid,the salt of commercial timolol maleate,was mixed with netarsudil dimesylate.Consequently,the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in p H 4.8–5.2 solution by synthesizing timolol mesylate.Next,the morphology of timolol mesylate was observed by scanning electron microscopy,differential scanning calorimetry,thermogravimetric analysis,and powder X-ray diffraction.The prepared FC-TNL showed good stability during refrigeration storage.Additionally,FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study.Importantly,oncedaily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells.The FC-TNL was stable,safe and effective,being a promising glaucoma therapeutic.

Long-term assessment of prostaglandin analogs and timolol fixed combinations vs prostaglandin analogs monotherapy

AIM： To draw a Meta-analysis over the comparison of the intraocular pressure （lOP）-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs （PGAs） monotherapy. METHODS： After searching the published reports from MEDLINE, EMBASE, the Cochrane Library, all randomized controlled clinical trials （RCTs） comparing the fixed combination of PGAs/timolol therapy （FCs） and PGAs monotherapy with treatment duration at least 6mo were included. The efficacy outcomes were mean diurnal lOP, percentage of participants whose lOP were lower than 18 mm Hg, incidence of visual field change, while the safety outcomes included corneal side effects, hyperemia and eye irritation. The analysis was carried out in RevMan version 5.3 software. RESULTS： After six-month medical intervention, the mean diurnal lOP of FCs was lower than PGAs （MD -1.14, 95% CI -1.82 to -0.46, P=0.001）; the percentage of target lOP achieving between FCs and PGAs showed no significant difference （RR 1.18, 95% Cl 0.97 to 1.43, P=0.10）. No statistically significant differences of the incidence of hyperemia （RR 0.67, 95% CI 0.45 to 1.01, p=0.06） and eye irritation （RR 1.20, 95% CI 0.95 to 1.51, P=0.12） between the FCs and PGAs monotherapy were detected. Only one research involved in corneal events, result of this trial revealed no difference between two intervention groups regarding corneal effects （central endothelial cell density, MD -0.20, 95% CI -0.72 to 0.32, P=0.45; central corneal thickness, MD -0.01, 95% Cl -0.02 to 0.00, P=0.23）. The evaluation of visual field change was not performed due to the limited duration of the trials included in this Meta-analysis. CONCLUSION： The long-term efficacy of the FCs overweighed the PGAs monotherapy in lowering lOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant. More RCTs with detailed and authentic data over the assessments of visual functions and morphology of optic nerve heads are hoped to be conducted.

Switching Study of Tafluprost/Timolol Fixed-Combination Ophthalmic Solution, Following Unfixed Combination of Tafluprost Ophthalmic Solution 0.0015% and Timolol Ophthalmic Gel-Forming Solution 0.5%

Purpose: Fixed-combination medication to treat glaucoma can reduce intraocular pressure (IOP) without negative effects of concomitant medication. Tafluprost/timolol fixed-combination ophthalmic solution (TTFC) has been reported to show similar effectiveness in lowering IOP, compared with concomitant use of its component drugs, tafluprost and timolol. However, the difference in IOP-lowering effects between TTFC and concomitant use of tafluprost and gel-forming timolol is unknown. Hence, we conducted this switching study from tafluprost and gel-forming timolol to TTFC in glaucoma patients undergoing multi-drug therapy. Design: Multi-center, open-label, interventional clinical study. Methods: Twenty-eight patients (28 eyes;safety analysis set) with primary open-angle glaucoma and ocular hypertension, who had completed the 4-week-concomitant phase of tafluprost and gel-forming timolol, were treated for 8 weeks with TTFC. IOP, adherence, ocular surface safety, and the usability of ophthalmic solution were compared before and after switching. This study was approved by the ethics committees of Kitasato University Hospital and all other study sites. All patients provided written informed consent to participate. Results: IOP at 8 weeks after switching was significantly lower than before switching (P = 0.0001) in the efficacy analysis set (n = 24). The self-reported adherence rate remained high after switching;moreover, there was no meaningful change in ocular surface safety. Patient questionnaires regarding usability of medication revealed that 85.7% of patients preferred their instillation prescription after switching, including TTFC. Among the safety analysis set (n = 28), no adverse events were reported in relation to the study drug. Conclusion: TTFC showed greater IOP reduction than concomitant therapy. Thus, TTFC may be a better option in glaucoma patients than concomitant therapy.

Fixed combination of latanoprost and timolol vs the individual components for primary open angle glaucoma and ocular hypertension:a systematic review and meta-analysis

AIM:To assess the effects of the fixed combination of0.005% latanoprost and 0.5% timolol(FCLT) vs their individual components for primary open angle glaucoma(POAG) and ocular hypertension(OHT).· METHODS:After searched PubMed, EMBASE, the Cochrane Library and SCI, all randomized controlled clinical trials(RCTs) and cross-over studies were included. The control groups were the monotherapy or the concomitant therapy of latanoprost and timolol. The outcomes were visual field defect, optic atrophy, mean intraocular pressure(IOP) and IOP fluctuation. The analysis was carried out in RevMan version 5.1 software.RESULTS:Thepost-interventionmeanIOPofFCLTwas significantly lower compared to timolol [mean difference(MD)-2.92, 95%CI-3.28 to-2.55, P 【0.00001] and latanoprost(MD-1.11, 95%CI-1.51 to-0.72, P 【0.00001). The postintervention IOP fluctuation was also significantly lower compared to timolol(MD-0.88, 95%CI-1.23 to-0.53, P 【0. 00001) and latanoprost( MD- 0. 63, 95 % CI- 1. 04to-0.22, P =0.002). The mean IOP was higher in FCLT morning dose group than the one in unfixed combination of 0.005% latanoprost and 0.5% timolol(UFCLT)(MD1.10, 95% CI 0.81 to 1.39, P 【0.00001). Otherwise, there was no difference between FCLT evening dose group and UFCLT(MD 0.34, 95% CI-0.01 to 0.69, P =0.06).There was no statistical difference for the incidence ofvisual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.visual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.

Effect of 1%brinzolamide and 0.5%timolol fixed combination on intraocular pressure after cataract surgery with phacoemulsification

AIM:To evaluate the effect of brinzolamide-timolol fixed combination on intraocular pressure(IOP)after cataract surgery.METHODS:The study included 92 eyes of 87 patients who underwent cataract surgery and intraocular lens implantation.Patients scheduled for phacoemulsification were assigned to 1 of 2 groups.The treatment group received 1 drop of brinzolamide-timolol fixed combination immediately after surgery,and the control group received no treatment.The IOP was measured preoperatively and at 2h and 24h postoperatively.RESULTS:The mean IOP change was lower in the treatment group than in the control group at 2h postoperatively.The difference between the mean IOP values of the two groups at 2h postoperatively was found to be statistically significant.Twenty-four hours after the surgery,the mean IOP change was still higher in the control group when compared to the treatment group.CONCLUSION:The fixed combination brinzolamidetimolol can effectively reduce IOP after cataract surgery.

Bimatoprost/timolol fixed combination(BTFC) in patients with primary open angle glaucoma or ocular hypertension in Greece

AIM：To evaluate the efficacy and tolerability of the fixed combination of bimatoprost 0.03%and timolol 0.5%（BTFC）in patients in Greece with primary open angle glaucoma（POAG）or ocular hypertension（OHT）whose previous therapy provided insufficient lowering of intraocular pressure（IOP）.·METHODS：A multicenter,prospective,open-label,non-interventional,observational study of the use of BTFC in clinical practice was conducted at 41 sites in Greece.The primary endpoint was the reduction in IOP from baseline at study end,approximately 12wk after initiation of BTFC therapy.·RESULTS：A total of 785 eligible patients were enrolled in the study and 97.6%completed the study.The mean±SD IOP reduction from baseline at 12wk after initiation of BTFC was 6.3±2.8 mm Hg（=764;〈0.001）.In patients（=680）who replaced their previous IOP-lowering monotherapy（a single drug,or a fixed combination of 2drugs in a single ophthalmic drop）with once-daily BTFC,the mean±SD IOP reduction from baseline at 12wk was 6.2±2.8 mm Hg（〈0.001）.IOP was reduced from baseline in 99.2%of patients,and 58.0%of patients reached or exceeded their target IOP.Substantial mean IOP reductions were observed regardless of the previous therapy.BTFC was well tolerated,with 96.0%of patients who completed the study rating the tolerability of BTFC as＂good＂or＂very good.＂Adverse events were reported in 8.3%of patients;only 0.6%of patients discontinued the study due to adverse events.·C ONCLUSION：In clinical practice in Greece,BTFC is well tolerated and effectively lower the IOP in patients with POAG or OHT who requires additional IOP lowering on their previous therapy.

Effect of dorzolamide-timolol fixed combination prophylaxis on intraocular pressure spikes after intravitreal bevacizumab injection

AIM: To evaluate the effect of topical dorzolamide-timolol fixed combination prophylaxis on short term intraocular pressure(IOP) changes in patients who had intravitreal bevacizumab injection.METHODS: One hundred and fifty one eyes of 151 patients which were followed up in retina clinic in Ulucanlar Eye Training and Research Hospital were evaluated in this study. Patients were divided into two groups. Group 1 consists of 75 patients who had topical dorzolamid-timolol medication two hours before injection;while Group 2 consists of 76 patients without prophylaxis. Demographic data, IOP measurements prior to the injection and one, thirty and sixty minutes and twenty-four hours after the injection were recorded. The data were analyzed using SPSS software version 15.0(SPSS Inc., Chicago, IL, USA).RESULTS: There were no significant difference between two groups in age, gender distrubition and indications for injections. The mean IOPs in Groups 1 and 2 prior to the injection(T0) were 17.84±0.43 and 18.15±0.43 mm Hg,one minute after the injection(T1) were 29.75 ±1.6 and34.44 ±1.59 mm Hg, 30 minutes after the injection(T30)were 20.06 ±0.6 and 21.71 ±0.59 mm Hg respectively. The mean IOPs were 18.26 ±0.56 mm Hg in Group 1 and19.78 ±0.56 mm Hg in Group 2 sixty minutes after the injection(T60). All IOP values after the injection were compared between two groups, there was a significant difference between two groups only on T1; one minute after the injection(P =0.04). There were a statisciallysignificant difference between the baseline values and other recorded values; except on T60, in Groups 1 and 2(P 【0.05).CONCLUSION: After intravitreal bevacizumab injection;we observe a transient IOP elevation which normalizes about one hour after intravitreal injection. In patients who had topical dorzolamid-timolol combination prophylaxis before injections, a significant decrease is seen in IOP spikes due to this injection. The appropiate approach will monitor IOP after intravitreal injection and evaluate the using prophylactic antiglaucomatous drugs before the injection in patients with ganglion nerve cell damage.

Long-term cost and efficacy analysis of latanoprost versus timolol in glaucoma patients in Germany

AIM: To evaluate 5-year effectiveness and cos between latanoprost or timolol monotherapy in a pilot trial.METHODS: A retrospective, multi-center trial performed at 6 sites in Germany of patients who had a diagnosis of primary open-angle or pigmentary glaucoma, in at least one eye, initiated on monotherapy with latanoprost or timolol maleate. Qualified consecutive charts were reviewed in which 5-year efficacy, safety and cost data was abstracted.RESULTS: Seventy-seven latanoprost and 49 timolo patients were included, at the final visit no difference existed between the two groups in disc parameters including: rim area, rim area/disc area ratio, cup volume or vertical cup/disc ratio (P 】0.05). There was no difference in intraocular pressure (IOP) between the initial latanoprost (17.4 ±2.6) and timolol (16.3 ±2.8mmHg) groups. There was less change in medicines over the follow-up period (0.1 vs 0.8) and fewer medications at the final visit (1.2 vs 1.8) with latanoprost compared to timolol. No patient treated with latanoprost discontinued therapy during follow-up, while 12% discontinued timolol mostly due to inadequate IOP control. Cost/year was less with initial timolol ($458±236) as compared to latanoprost ($552±202). CONCLUSION: Patients begun on latanoprost o timolol and followed over 5 years may have similar clinical outcomes. However, timolol patients may require more medicines and medicine changes to control IOP for long-term, but at a lower cost.

Comparison of brimonidine-timolol and dorzolamidetimolol in the management of intraocular pressure increase after phacoemulsification

AIM: To compare the effectiveness of brimonidine/timolol fixed combination(BTFC) and dorzolamide/timolol fixed combination(DTFC) in the management of short-term intraocular pressure(IOP) increase after phacoemulsification surgery.·METHODS: Eighty eyes of 80 patients undergoing phacoemulsification and intraocular lens(IOL)implantation were randomly assigned into three groups.Group 1 consisted of 28 eyes and represented the control group. Group 2 consisted of 25 eyes undergoing phacoemulsification surgery and BTFC was instilled at the end of surgery. Group 3 consisted of 27 eyes undergoing phacoemulsification surgery and DTFC was instilled at the end of surgery. IOP was measured preoperatively and 6, 24 h and 1wk postoperatively.·RESULTS: There was no statistically significant difference in preoperative baseline IOP among the three groups(P =0.84). However, IOP was significantly lower in groups 2 and 3 compared to the control group(P <0.05 for all comparisons) at all postoperative visits. There was no significant difference between groups 2 and 3 at any visit. Eight eyes(28.6%) in the control group, two(8%) in Group 2 and one(3.7%) in Group 3 had IOP >25 mm Hg at 6h after surgery(P =0.008). However, IOP decreased and was >25 mm Hg in only one eye in each group at24 h after surgery.·CONCLUSION: BTFC and DTFC have similar effects in reducing increases in IOP after phacoemulsificationsurgery and can both be recommended for preventing IOP spikes after such surgery.

Stripping Voltammetric Determination of Timolol Drug in Pharmaceuticals and Biological Fluids

A sensitive and reliable stripping voltammetric method was developed to determine timolol drug. This method is based on the adsorptive accumulation of the drug at a hanging mercury drop electrode (HMDE) and then a negative sweep was initiated, which yield a well defined cathodic peak at –850 mV versus (Ag/AgCl) silver reference electrode. To achieve high sensitivity, various experimental and instrumental variables were investigated such as supporting electrolyte, pH, accumulation time and potential, scan rate, frequency, pulse amplitude, convection rate and working electrode area. The monitored adsorptive current was directly proportional to the concentration of timolol and it shows a linear response in the range from 1 × 10–7 to 1.5 × 10–6 mol●l–1 of this drug (correlation coefficient = 0.998) and the detection limit (S/N = 3) is 1.26 × 10–9 mol●l–1 at an accumulation time of 30 sec. The developed adsorptive stripping voltammetry (AdSV) procedure shows a good reproducibility, the relative standard deviation RSD% (n = 8) at a concentration level of 1 × 10–6 mol●l–1 of timolol was 0.13%, whereas the method accuracy was indicated via the mean recovery of 110% ± 1.414%. Possible interferences by several substances usually present in the pharmaceutical formulations have been also evaluated. The applicability of this approach was illustrated by the determination of the drug in pharmaceutical preparation and biological fluids such as serum and urine.

A 4-year retrospective study of add-on therapy to the fixed combination of dorzolamide/timolol for the treatment of POAG

AIM:To evaluate the long-term response to the fixed combination of dorzolamide/timolol in patients with primary open angle glaucoma(POAG)and the addition of other intraocular pressure(IOP)lowering medications such as prostaglandin analogs and brimonidine.METHODS:A retrospective,non-randomized,and descriptive clinical study was performed with 182 eyes diagnosed with POAG.Patients were divided into three groups:a group with fixed combination of dorzolamide/timolol only,a second group with prostaglandin analogs plus fixed combination of dorzolamide/timolol,and a third group with the addition of brimonidine to the same fixed combination.IOP data were gathered retrospectively and the differences between groups were calculated.RESULTS:IOP was reduced satisfactorily in all three groups;however,a progressive IOP reduction was noted in the group with the fixed combination plus prostaglandin analogs.In this group,a progressive,significant and more homogeneous response of the reduction was noted in comparison with the other groups.CONCLUSION:IOP reduction was efficacious in all three groups.The addition of prostaglandin analogs showed progressive IOP reduction,progressive responseand absence of long-term drift.Brimonidine did not show a significant additive effect.

Comparative Evaluation of the Efficacy of the Bimatoprost 0.03%, Brimonidine 0.2%, Brinzolamide 1%, Dorzolamide 2%, and Travoprost 0.004%/Timolol 0.5%-Fixed Combinations in Patients Affected by Open-Angle Glaucoma

Purpose: This is a retrospective, comparative, head-to-head, not commissioned study about the efficacy of bimato-prost 0.03%, brimonidine 0.2%, brinzolamide 1%, dorzolamide 2%, and travoprost 0.004%/timolol 0.5%-fixed combinations in patients affected by na?ve open-angle glaucoma and IOP > 25 mmHg. Patients and Methods: Files from 70 patients (35 M, 35 F, mean age 69.52 y, S.D. 11.56, range: 37-87y) in our Glaucoma Service were retrospectively analyzed as long as 12 months. Every subgroup, including 14 age- and sex-matched patients, was allocated to 1 of the 5 groups of the fixed combinations monotherapy. Data recorded after 3 months follow-up were statistically analyzed by descriptive and ANOVA statistics as percentage of IOP reduction from baseline. Results: All the fixed combinations were effective in lowering IOP. The mean percentage reduction was: brimonidine/timolol 43.57%, dorzolamide/timolol 37.67%, bimatoprost/timolol 35.60%, travoprost/timolol 33.25% and brinzolamide/timolol 23.0%. The brimonidine/timolol fixed combination showed to be statistically significant more effective only than brinzolamide/timolol fixed combination (p = 0.001). Setting the α error to 5%, the power of the study is 26%, phi: 0.842. Discussion: In all this cohort of patients the target IOP was successfully achieved. All the fixed combinations used in this study had a very good profile of efficacy. Brimonidine, dorzolamide, bimatoprost and travoprost/timolol fixed combinations statistically significantly reduced the percentage of IOP from baseline (p = 0.001) more than brinzolamide/timolol fixed combination.

A Stability Indicating Reverse Phase-HPLC Method Development and Validation for the Estimation of Bimatoprost 0.3% &Timolol 0.5% Pharmaceutical Ophthalmic Dosage Form

The research was carried out to establish a new reverse phase-HPLC stability indicating method for quantifying Bimatoprost & Timolol in ophthalmic solution. The experiment of Bimatoprost & Timolol in ophthalmic solution method development was determined on Waters HPLC instrument using a UV Detector. The separation was done by using L11, Zorbex SB phenyl (4.6 mm × 250 mm internal diameter) 5 μm analytical column, containing mobile phase of Phosphate buffer (0.02 M), methanol, and acetonitrile [50:30:20 % v/v]. The method was run at 1 ml·min-1 at 210 nm for Bimatoprost and 295 nm for Timolol for detection. The drug was eluted at 10.81 min for Bimatoprost and 3.77 min for Timolol. After developing the method, it was assured for the intended use by validation, which was done according to ICH Q2B guidelines. The analytical parameters checked were Specificity/Selectivity, linearity, Range, accuracy, ruggedness, and robustness. It was observed that the response of the detector was linear in the range of 6 - 18 μg/ml with a correlation coefficient of 0.999. The results of all the parameters were found to be within the acceptance criteria. The stability-indicating assay method was established by using the samples generated by the forced degradation process. The forced degradation was carried out by subjecting the drug to acid, alkali, thermal, oxidative, and photolytic degradation, and the results showed that the degradation products were successfully separated from the drug. Hence, this can be applied perfectly later for the quantitative analysis of Bimatoprost 0.3% + Timolol 0.5% Ophthalmic Solution drugs for pharmaceutical use. Currently, there is no official method for Bimatoprost & Timolol combination products in USP or BP. Available research work related to single Bimatoprost or Timolol products was not suitable for testing Bimatoprost and Timolol combination drugs. Additionally, there is no stability-indicating method to test Bimatoprost & Timolol combination products which insist us to do research and develop a new reverse phase-HPLC indicating method which will be faster and more accurate.

Efficacy and Safety of Travoprost and Timolol Fixed Combination Compared to Travoprost in Patients with Primary Open Angle Glaucoma and Ocular Hypertension

Purpose: To compare intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004% and travoprost 0.004% and beta-blocker 0.5% fixed combination ophthalmic solution in patients with open-angle glaucoma and ocular hypertension. Methods: In this prospective, multicentre clinical trial, 62 patients received travoprost 0.004% (n = 31) or travoprost 0.004% and beta-blocker 0.5% fixed combination (n = 31). Efficacy and safety were compared across treatment groups over 2 years. IOP reduction and adverse events were examined at 3, 6, 12 and 24 months for each group. Results: Mean IOP at the first visit in the travoprost 0.004% group was 26.4 (SD ± 2.1), and travoprost 0.004%/timolol 0.5% group was 26.3 (SD ± 2.1). Mean IOP after 24 months in the travoprost 0.004% group was 20.5 (SD ± 1.5) and travoprost 0.004%/timolol 0.5% group was 18.5 (SD ± 1.5). There were statistically significant differences in IOP in both eyes after third visit (after 1 year) and fourth visit (after 2 years). Conclusion: After 2 year of treatment, travoprost 0.004%/timolol 0.5% produced clinically relevant IOP reductions in patients with open-angle glaucoma or ocular hypertension that were greater than those produced by travoprost 0.004% alone.

A BLIND RANDOMIZED CROSS -OVER TRIAL COMPARING BETAXOLOL WITH TIMOLOL IN OPEN-ANGLE GLAUCOMA AND OCULAR HYPERTENSION

Purpose: To compare the short-term efficacy and side effects of betaxolol and timoloi in treatment of primary open angle glaucoma or ocular hypertension. Methods: Fourteen patients with newly diagnosed early primary open angle glaucoma or ocular hypertension were included.Each patient received 0.5% timoloi and 0.5% betaxolol twice daily for four weeks in two phases. Between two courses of treatment there was four weeks wash out period. At the end of study the effect of these two drugs on intraocular pressure, mean arterial blood pressure,pulse rate,basic tear secretion and ocular symptoms were evaluated and statistically analyzed,using wilcoxon and chi-squar test.RESULTS:The study was performed on fourteen patients with baseline IOP of 26.7 ±1.5 mmHg.After four weeks treatmem,timoiol and betax-olol reduced IOP by 7.8±1.2mmHg or 29% and 6.1±1.3mmHg or 23%, respectively (P<0.001). The difference between two groups was significant(P<0.001). Mean arterial blood pressure was reduced with betaxolol and

噻吗洛尔滴眼液在急性房角关闭危象序贯治疗中的疗效

目的观察噻吗洛尔滴眼液在急性房角关闭危象序贯治疗中的疗效。方法前瞻性随机双盲病例对照研究。连续纳入2021年4月至2023年10月河北大学附属医院诊断为急性房角关闭危象(acute angle-closure crisis,AACC)的患者,收集其病例资料并以随机数字表法分为应用噻吗洛尔组(A组)与安慰剂组(B组)。所有患者序贯应用药物治疗、前房穿刺、激光周边虹膜成形术,以治疗后2 h、4 h、6 h为治疗节点,记录并统计在各个节点2组患者的眼压下降值、AACC得到控制的眼数及所需时间。结果在序贯治疗后2 h、4 h、6 h的3个节点,A组的眼压下降值分别为(13.87±13.85)mmHg(1 mmHg=0.133 kPa)、(28.42±12.87)mmHg、(35.69±8.51)mmHg,AACC得到控制的眼数分别为23眼(29.87%)、51眼(66.23%)、71眼(92.20%);B组的眼压下降值分别为(15.88±14.95)mmHg、(28.17±13.63)mmHg、(33.90±13.59)mmHg,AACC得到控制的眼数分别为30眼(36.59%)、58眼(70.73%)、75眼(91.46%);治疗有效的患者中,AACC控制的时间A组为(3.29±1.31)h,B组为(3.38±1.34)h。2组患者在序贯治疗各个节点的眼压下降值、AACC缓解的眼数及病情缓解所需时间差异均无统计学意义(P>0.05)。结论在AACC的序贯治疗过程中,噻吗洛尔滴眼液对于提高治疗成功率无明显帮助。