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Aims: This prospective drug trial was done to compare latanoprost versus combination therapy of latanoprost and timolol maleate. Methods and Materials: Patient were screened for primary open angle glaucoma and grouped as per pharmacological drugs used and measured IOP baseline before initiation of study. Group I consisting all patients with latanoprost monotherapy and Group II consisting of patients already using either latanoprost or timolol. Further A,B & C was assigned as per IOP baseline. Results: In group I (Monotherapy), 28 patients were completed the follow up. The mean baseline IOP was 27.4 millimeter of Hg with standard deviation of 2.59. After 12 weeks of study, mean IOP was 19.66 millimeter of Hg with SD of 2.76. Mean IOP difference from baseline was 7.4 millimeter of Hg. So fall of 27.3% in IOP from pre-treatment level. In group II (Combination therapy), 19 patients were completed the follow up. The mean baseline IOP was 27.35 millimeter of Hg with standard deviation of 2.6. After 12 weeks of study mean IOP difference from baseline was 8.1 millimeter of Hg with SD of 2.0 millimeter of Hg i.e. a fall of 29.63% in IOP from pre-treatment level. Conclusions: Combination therapy fared slightly better that Latanoprost alone in overall pressure reduction. Keywords: Prostaglandins, Glaucoma, Timolol, Beta adrenergic, Dual therapy

Purpose To investigate the short-term intraocular pressure-lowering efficacy and safety of switching from a fixed combination of latanoprost/timolol to a fixed combination of latanoprost/carteolol. Patients and Methods The subjects were 30 eyes of 30 adult patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who were using a latanoprost-/timolol-fixed combination with insufficient intraocular pressure-lowering efficacy or adverse reactions. The subjects were switched from once-daily latanoprost/timolol to once-daily latanoprost/carteolol with no washout interval. Intraocular pressure, tear film break-up time, corneal epithelial defects, conjunctival hyperemia, blood pressure, and pulse rate were measured and compared before and 1 and 3 months after switching. Patients were monitored for adverse reactions at each visit, and dropouts were recorded. Results The mean intraocular pressure at 1 month (15.9±3.1 mmHg) and 3 months (16.3±3.8 mmHg) was not significantly different from that at baseline (16.1±3.1 mmHg). The tear film break-up time and corneal epithelial defects were significantly improved after switching (p

Background: To evaluate the effect of an "escalation" of topical glaucoma therapy by switching form prostaglandin monotherapy to two different prostaglandin-timolol fixed combinations.Methods: 30 patients (60 eyes) with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) were initially treated with the prostaglandin analog latanoprost in a preservative-free formulation. 15 patients each were for 6 months - because of IOP levels considered still too high - treated with preservative-free tafluprost/timolol fixed-dose combination or preservative-free latanoprost/timolol fixed-dose combination therapy. Results: Six months after switching from latanopost monotherapy to preservative-free prostaglandin-timolol combinations, patients being treated with the latanoprost-timolol fixed combination had a mean IOP reduction by 4.16 mm Hg and those treated with the tafluprost-timolol fixed combination a mean IOP reduction by 5.38 mm Hg. Regarding safety and tolerability, there were no issues in the tafluprost-timolol group.Conclusions: Switching from prostaglandin monotherapy to a prostaglandin-timolol fixed combination led to a sufficient IOP lowering in our group of patients. Tolerability of, and satisfaction with, the fixed combination therapies was high.

Introduction: Glaucoma is a leading cause of blindness and represents a significant global health and economic concern. Prostaglandin analogs such as latanoprost – which act to reduce intraocular pressure by enhancing uveoscleral flow and slow the development and progression of glaucoma – are recommended as a first-line monotherapy.Areas covered: We review recent efficacy and safety data for latanoprost, both alone and in combination therapy, and vs. other prostaglandin analogs, focusing on the tolerability and adherence to the drug and the subsequent impact on patient-perceived quality of life. Relevant studies were identified by an electronic literature search using MEDLINE PubMed, and current global glaucoma guidelines were reviewed.Expert commentary: Prostaglandin analogs represent the cornerstone in glaucoma therapy. Individual studies demonstrate differences in efficacy between prostaglandin analogs, but within-class differences are generally small – and, on balance, latanoprost presents a g...

Background: This study aimed to evaluate the non-inferiority and safety of a newly developed preservative-free (PF) multi-dose latanoprost/timolol ophthalmic solution, compared with the benzalkonium chloride (BAK)-preserved fixed combination, in patients with open-angle glaucoma and ocular hypertension.Methods: A Phase III randomized multi-center observer-blind parallel-group clinical trial was conducted. A total of 210 adult patients (aged over 18 years) were randomly treated with the PF- or the BAK-preserved latanoprost/timolol solution once daily in the affected eye(s) for 12 weeks. Follow-up visits were scheduled at weeks 2, 6, and 12; intraocular pressure (IOP) was recorded at 8:00 AM, 12:00 PM, and 4:00 PM. The primary efficacy endpoint to prove non-inferiority was the IOP change at 8:00 AM (± 1 hour) from the baseline to the end of treatment (week 12) in the studied eye. Safety parameters were also assessed.Results: In total, 196 patients completed the study. The pressure-lowering effect of the PF eye drops was comparable to that of the preserved formulation at all time points. Latanoprost/timolol PF formulation was non-inferior to the BAK-preserved solution as shown by the change in IOP from day 0 to week 12. The point estimate of the inter-treatment difference was 0.624 mmHg (95% CI: -0.094, 1.341). Both treatments were well-tolerated during the study, and they had similar adverse event profiles.Conclusions: PF-latanoprost/timolol combination was found to be non-inferior to the BAK-preserved formulation based on the efficacy at all times, with similar local tolerance.

In the original publication, the range to derive the P values is incorrectly represented in Table 2 and Table 3. The corrected tables are provided below.

To evaluate the effect of bimatoprost/timolol maleate fixed combination (BTFC), latanoprost/timolol maleate fixed combination (LTFC), and travoprost/timolol maleate fixed combination (TTFC) on 24-h intraocular pressure (IOP) in patients with open-angle glaucoma. This prospective, observer-masked, randomized study included 50 patients with primary open-angle glaucoma. All patients were using hypotensive lipids and timolol maleate fixed combination treatment for ≥4 weeks and had an IOP ≤ 21 mmHg. Group 1 (n = 18) received BTFC, group 2 (n = 14) received LTFC, and group 3 (n = 18) received TTFC. All patients were hospitalized, and IOP was monitored for 24-h (10:00, 14:00, 18:00, 22:00, 02:00, and 06:00). Mean diurnal IOP variation measurements were taken between 06:00 and 18:00, and mean nocturnal IOP variation measurements were taken between 22:00 and 02:00. Mean IOP and IOP variation in the three groups were compared. Mean 24-h IOP did not differ significantly between the three groups (group 1: 14.6 ± 2.9 mmHg; group 2: 14.1 ± 3.7 mmHg and group 3: 15.8 ± 2.0 mmHg; P > 0.05). Mean diurnal IOP variation was 4.6 ± 2.3 mmHg in group 1, 5.8 ± 2.4 mmHg in group 2, and 4.3 ± 1.7 mmHg in group 3, and mean nocturnal IOP variation was 3.2 ± 2.8 mmHg in group 1, 2.9 ± 1.9 mmHg in group 2, and 3.0 ± 1.6 mmHg group 3. There were not any significant differences in diurnal or nocturnal IOP variation between the three groups (P

UNLABELLED: PRéCIS:: Noninferiority of efficacy was demonstrated for a preservative-free latanoprost-timolol fixed combination compared with a BAK-containing formulation at 84 days after treatment in patients with open-angle glaucoma or ocular hypertension. PURPOSE: The purpose of this study was to compare the effect on intraocular pressure and safety of preservative-free latanoprost-timolol fixed combination (T2347) to benzalkonium chloride-preserved latanoprost-timolol fixed combination in patients with open-angle glaucoma or ocular hypertension. METHODS: Phase III, randomized, parallel-group, investigator-masked study in 10 countries. A total of 242 patients aged 18 years or older with open-angle glaucoma or ocular hypertension in both eyes controlled with a preserved latanoprost-timolol fixed combination (15.7±2.4 mm Hg overall before inclusion) were randomized at day 0 with no washout period to receive the preservative-free alternative T2347 (N=127) or remain on the preserved comparator (N=115) for 84 days. Intraocular pressure changes from day 0 were measured at 9:00 am (±1 hour) on day 42 and day 84, and noninferiority of T2347 to the preserved comparator was analyzed statistically at day 84. Safety parameters were also reported. RESULTS: The mean change in intraocular pressure from baseline to day 84 was -0.49±1.80 mm Hg for preservative-free T2347 and -0.49±2.25 mm Hg for the preserved comparator. These results met the noninferiority limits. Similar results were observed at day 42. There was no difference between groups in the incidence of adverse events or ocular signs. The total ocular symptoms score was better for T2347 than BPLT upon instillation at day 84 (45.9%/44.3%/9.8% of patients with improvement/no change/worsening vs. 33.6%/47.3%/19.1%; P=0.021), reflecting improvements in individual symptoms such as irritation/burning/stinging (P

Studies comparing the effect of fixed and unfixed combination of latanoprost and timolol are limited globally and nearly absent among the Nigerian population. This study therefore compares the effect of fixed and unfixed combination of latanoprost and timolol on intraocular hypertension among Nigerian population. The study was a randomized control trial consisting of 102 patients with ocular hypertension who received latanoprost/timolol fixed combination (n=48) and latanoprost/timolol unfixed combination (n=54) for medical reasons. Follow-up visits over 30 weeks was scheduled for 2 weeks from entry date and thereafter every 4 weeks for the remaining 28 weeks making a total of 9 clinic visitations. During the period of the study, the ophthalmologists followed usual care routines and intraocular pressures were recorded while also observing adverse events and evaluating efficacy, safety, tolerability and compliance. Overall, there was 47.73% reduction of intraocular pressure with fixed combination of latanoprost/timolol as against 43.26% reduction with unfixed combination. The greatest reduction impacts were observed two weeks after commencing treatment (-8.27mmHg and -5.74mmHg for fixed and unfixed combinations respectively) and then efficacy reduces progressively for both drugs. This study showed that latanoprost and timolol combinations are effective for intraocular hypertension. However, fixed combination was observed to be more effective compared to unfixed combination at least among Nigerian population.

To evaluate the effect of a latanoprost/timolol fixed combination (LTFC) versus a latanoprost and timolol gel-forming solution unfixed combination (LTuFC) on daytime intraocular pressure (IOP) levels and fluctuations.This was an 8-week, randomized, parallel-group study. Ninety eyes of 90 patients diagnosed with primary open-angle glaucoma or ocular hypertension that were insufficiently controlled with latanoprost monotherapy were enrolled. Randomized patients received either a single evening dose of LTFC or unfixed combination of latanoprost administered once daily in the evening and timolol gel-forming solution administered once daily in the morning without a washout period. IOP measurements were taken at 8 AM, 11 AM, 2 PM, and 5 PM. The mean IOP, daytime IOP measurements, and fluctuation in IOP were assessed at weeks 4 and 8.The mean IOP reduction from baseline to each visit was significant in both groups (P0.01). There was a significant difference in the mean IOP between groups at week 4 (P=0.0021). At week 8, the mean IOP reduction was 3.2 ± 2.1 and 5.7 ± 3.2 mm Hg in LTFC and LTuFC groups, respectively, and the difference was significant (P=0.001). A decrease in the daytime IOP fluctuation was observed in both groups over time, but the decrease in each group was not significant. At week 8, the mean IOP measurements at 8 AM, 11 AM, 2 PM, and 5 PM in LTuFC group were significantly lower than in the LTFC group (P=0.024, 0.0001, 0.0008, and 0.0011, respectively).The concomitant use of latanoprost and timolol gel-forming solution leads to a larger additional IOP reduction and lower daytime IOP levels as compared with the fixed combination.

Purpose: To compare latanoprost/timolol (LT) versus travoprost/timolol (TT) fixed combinations for ocular hypertension (OHT) associated with uveitis.Methods: Thirty-six patients (55 eyes) who were treated with LT (28 eyes) or TT (27 eyes) for OHT associated with uveitis were reviewed retrospectively. Intraocular pressure (IOP) and inflammation scores at the initiation of treatment and at the last visit during therapy were analyzed.Results: Although IOP was reduced significantly in both LT and TT groups, the reduction rate was significantly greater with TT group than with LT. The differences in the reduction of IOP between the groups remained significant when the cases were classified into inflammation-induced OHT and steroid-induced OHT. Inflammation score was not exacerbated by LT or TT treatment.Conclusions: Both LT and TT are safe and effective for the treatment of OHT associated with uveitis and greater IOP reduction may be achieved by TT than by LT treatment.

The combination of timolol and latanoprost, which are ocular hypotensive agents, has a greater ocular hypotensive effect than each as monotherapy. However, the protective effect of the combination is not well understood. In the present study, we investigated whether latanoprost/timolol in combination has an additive or synergistic cytoprotective effect on neuro retinal cells (RGC-5). To investigate the protective effects of timolol/latanoprost in combination, cultured RGC-5 were treated with various concentrations of these two agents, singly or together, after which the cells were exposed to oxidative stress, serum deprivation, or endoplasmic reticulum (ER) stress in vitro. Cells were also treated with an Akt inhibitor, LY294002, to examine the mechanism of the protective effect. Latanoprost, timolol, and the two in combination reduced cell death induced by oxidative stress, serum deprivation, or ER stress. The latanoprost/timolol combination reduced cell death to a greater extent than monotherapy with latanoprost or timolol on serum deprivation only, and LY294002 inhibited the protective effect of their combination. These findings suggest that timolol/latanoprost in combination have a protective effect against serum deprivation only by activation of Akt signaling. Furthermore, this combination has not only an ocular hypotensive effect but also a neuroprotective effect.

Yuko Maruyama,1,2 Yoko Ikeda,1,3 Kazuhiko Mori,1 Morio Ueno,1 Haruna Yoshikawa,1 Shigeru Kinoshita41Department of Ophthalmology, Kyoto Prefectural University of Medicine, 2Fukuchiyama City Hospital, 3Oike-Ganka Ikeda Clinic, 4Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, JapanBackground: The purpose of this study was to prospectively evaluate and compare intraocular pressure (IOP) reduction efficacy and safety between bimatoprost and latanoprost-timolol fixed combination (LTFC) in Japanese patients with open-angle glaucoma.Methods: In this prospective, randomized, non-masked study, after enrolling 70 eyes of 70 Japanese open-angle glaucoma patients who had used latanoprost monotherapy for more than 4 weeks, the subjects were randomly divided into a bimatoprost group or an LTFC group. Both groups were switched from latanoprost to bimatoprost or LTFC for 12 weeks. IOP, conjunctival injection score, corneal epitheliopathy score (area density classification; AD score), tear film break-up time, heart rate, and blood pressure were evaluated at 0, 4, and 12 weeks after switching. The paired t-test and Mann–Whitney U-test were used for the statistical analysis.Results: After 13 of the 70 patients dropped out, 57 were analyzed for IOP reduction and safety. There was a significant decrease in mean IOP at 4 weeks compared with week 0 in both groups (both P

Ocular blood flow dysregulation has been implicated in the pathogenesis of glaucoma. Whereas the effect of single antiglaucoma substances on ocular blood flow has been addressed in various experiments, evidence for fixed combinations is sparse. In the present study, we set out to compare the effects of latanoprost 0.005%/timolol 0.5% (LT) fixed combination and brimonidine 0.2%/timolol 0.5% (BT) fixed combination on intraocular pressure (IOP) and ocular blood flow.In the present study, which followed a randomized, double-masked 2-way crossover design, 16 patients with primary open-angle glaucoma and 2 patients with ocular hypertension were included. The patients underwent a 6-week treatment with LT and a 6-week treatment with BT after a washout for previous antiglaucoma medication. Optic nerve head blood flow (ONHBF) was measured using laser Doppler flowmetry; retrobulbar flow velocities were measured using color Doppler imaging in the ophthalmic artery, the central retinal artery, and the posterior ciliary arteries. IOP was measured at 8 AM, 12 PM, and 4 PM.The mean baseline IOP was 25.3±2.8 mmHg. Both drugs were equally effective in reducing IOP (LT: -35.0%±10.0%; BT: -33.6%±8.8%, P=0.463 between groups). In addition, no difference in ocular perfusion pressure was observed between the 2 treatment groups (P=0.1, between groups). Neither LT nor BT altered ONHBF (P=0.4, baseline vs. treatment) and no effect on flow velocities in the retrobulbar vessels was seen with either of the 2 treatments.In the present study, a 6-week treatment with LT or BT was equally effective in reducing IOP. In addition, none of the administered drugs induced a significant effect on ocular blood flow parameters.

Purpose To compare the safety and efficacy of fixed-dose tafluprost/timolol combination (Taf/T-FDC) with those of fixed-dose latanoprost/timolol combination (Lat/T-FDC) by measuring the intraocular pressure (IOP)-lowering effect, ocular pharmacokinetics, and ocular surface toxicity. Methods The IOP-lowering effect of Taf/T-FDC and Lat/T-FDC in ocular normotensive monkeys was evaluated at 4 and 8 h after instillation in study A, at 12, 14, 16, and 18 h after instillation in study B, and at 24, 26, 28, and 30 h after instillation in study C. Drug penetration into the eye was evaluated by measuring the concentrations of timolol, tafluprost acid (active metabolic form of tafluprost), and latanoprost acid (active metabolic form of latanoprost) using liquid chromatography coupled with tandem mass spectrometry after single instillation of Taf/T-FDC or Lat/T-FDC to Sprague Dawley rats. Cytotoxicity following 1–30 min exposure of SV40-transformed human corneal epithelial cells to Taf/T-FDC or Lat/T-FDC was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays. Undiluted and 10-fold diluted solutions of each FDC were evaluated. Results The IOP-lowering effect of Taf/T-FDC was almost equivalent to that of Lat/T-FDC at 4–8 h after instillation. The peak IOP reduction of Taf/T-FDC and Lat/T-FDC was observed at 8 h after instillation, and there is no difference between the two. The difference between them was observed at 24–30 h after instillation, and Taf/T-FDC demonstrated a significantly greater IOP-lowering effect than Lat/T-FDC at 24–30 h after instillation. The IOP-lowering effect of Taf/T-FDC was sustained up to 30 h after instillation, while that of Lat/T-FDC had almost disappeared at 28 h after instillation. Timolol concentrations in aqueous humor after Taf/T-FDC instillation were higher than those after Lat/T-FDC instillation (Cmax, 3870 ng/mL vs 1330 ng/mL; AUCinf, 3970 ng·h/mL vs 1250 ng·h/mL). The concentrations of tafluprost acid and latanoprost acid in aqueous humor after instillation of Taf/T-FDC and Lat/T-FDC, respectively, were similar to those after instillation of mono-preparations of tafluprost and latanoprost, respectively. The cytotoxic effect of Taf/T-FDC to the human corneal epithelial cells was significantly lower than that of Lat/T-FDC at all evaluated time points in both undiluted and 10-fold diluted FDCs. Conclusion Taf/T-FDC provides increased IOP-lowering effect duration and lower potential ocular surface toxicity than Lat/T-FDC.

To compare the efficacy and safety of dorzolamide hydrochloride 2%/timolol maleate 0.5% fixed combination (DTFC) with latanoprost 0.005%/timolol maleate 0.5% fixed combination (LTFC) on diurnal intraocular pressure (IOP) in patients with primary open-angle glaucoma.Thirty-three primary open-angle glaucoma patients with IOP of 22-32 mmHg measured at any time were included. Patients were randomized to either DTFC twice daily or latanoprost 0.005%/timolol maleate 0.5% fixed combination (LTFC) once a day in the evening. After a 6-week treatment period with each combination, IOP were measured every 4 h during 24 h (first diurnal curve) and after 6 weeks of washout period, the patients were switched to the other treatment for 6 weeks of the second diurnal curve.The mean baseline IOP was 25.09±2.8 mmHg. After the treatment period, mean diurnal IOP was statistically lower with LTFC (16.3 mmHg) than with DTFC (17.3 mmHg), and the peak IOP value was 18.5 mmHg with LTFC and 19.9±2.6 mmHg with DTFC (P0.05). No significant side effects were reported except stinging and bitter taste with the DTFC group.Mean diurnal IOP and peak IOP were lower with LTFC than with DTFC in patients with primary open-angle glaucoma.

Objectives: We aimed to compare the effects of fixed combinations of dorzolamide/timolol maleate (DTFC) and la-tanoprost/timolol maleate (LTFC) at primary open angle glaucoma patients and assess the patient compliance to treatment. Materials and Methods: Forty-four eyes of 24 patients taking LTFC, 35 eyes of 24 patients taking DTFC and totally 79 eyes of 48 patients were included in this study. Patients were followed for 6 months. At 3rd month, diurnal in-traocular pressure (IOP) fluctuations were assessed. Perimetry and retinal nerve fiber layer (RNFL) analyze were repeated at 6th month. Results: Both medicines had efficiently controlled the IOP and diurnal fluctuations and statistically no significant dif-ference was observed (p>0.05). Perimetric and RNFL measurements were not different in both groups(p>0.05).When we have compared the results of baseline and 6th months, MD and sLV values decreased, RNFL in some cases in-creased on the other hand we have also observed a decrease in some cases(p0.05). Most of the patients did not forget to take their medicines (DTSK %54.2 and LTSK %66.7) and in following visits, compliance and adherence were improved in both groups. It is detected that duration of medi-cine use may affect the compliance (p=0.007). Conclusion: It is observed that two medicines controlled the IOP and diurnal fluctuations clinically efficient and effec-tively, had reasonable side effects and had high patient compliance to treatment., Amaç: Primer açık açılı glokomu olan hastalarda, dorzolamid-timolol maleat (DTSK) ve latanoprost-timolol maleat (LTSK) sabit kombinasyonlarının etkilerini karşılaştırmayı ve tedaviye hasta uyumunu değerlendirmeyi amaçladık. Gereç ve yöntem: LTSK kullanan 24 hastanın 44 gözü, DTSK kullanan 24 hastanın 35 gözü olmak üzere toplam 48 hastanın 79 gözü çalışma kapsamına alındı. Hastalar 6 ay takip edildi. Üçüncü ayda gün içi göz içi basıncı (GİB) dal-galanmalarına bakıldı. Görme alanı ve retina sinir lifi tabakası (RSLT) analizi 6.ayda tekrarlandı. Bulgular: Her iki ilacın da GİB\'nı ve gün içi dalgalanmalarını etkin bir şekilde kontrol ettiği ve aralarında istatistiksel olarak anlamlı bir fark bulunmadığı gözlendi(p>0.05). Görme alanı ve RSLT ölçümlerinde iki grup arasında istatistik-sel olarak anlamlı bir fark yoktu(p>0.05). Başlangıç ve altıncı ay karşılaştırıldığında, MD ve sLV değerlerinde azalma, RSLT ölçümlerinde ise azalma ve artma yönünde değişiklikler istatistiksel olarak anlamlı bulundu(p0.05). Her iki grupta da başlangıçta hastaların çoğu ilaç alımını unutmadı(DTSK %54.2 ve LTSK %66.7). Ta-kip eden kontrollerde, iki grupta da kompliyans ve adherens arttı. İlaç kullanım süresinin kompliyansı etkileyebildiği bulundu (p=0.007). Sonuç: Her iki ilacın da, GİB\'nı ve gün içi dalgalanmalarını etkin ve klinik olarak yeterli bir şekilde kontrol edebildiği, tolere edilebilir yan etkilere sahip oldukları ve hastaların tedavi uyumlarının yüksek olduğu görüldü.

Shunsuke Nakakura1, Hitoshi Tabuchi1, Yukio Baba2, Futoshi Maruiwa2, Nobuko Ando2, Takashi Kanamoto3, Yoshiaki Kiuchi31Department of Ophthalmology, Saneikai Tsukazaki Hospital, Himeji, Hyogo Prefecture, Japan; 2Department of Ophthalmology, Baba Eye Clinic, Hiroshima, Japan, 3Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima City, JapanObjective: To compare the safety and effectiveness of fixed-combination regimes (latanoprost–timolol and brinzolamide 1% compared to dorzolamide 1%/timolol and latanoprost) in open-angle glaucoma patients after switching from a combination of three topical antiglaucoma eye drops.Methods: We conducted an open, randomized 12-week multicenter prospective study. We randomly allocated 39 patients who had been treated with three antiglaucoma eye drops (prostaglandin F2α analogues plus beta-blockers and carbonic anhydrase inhibitors) into two groups. Group A (n = 20) were treated with latanoprost–timolol and brinzolamide 1% therapy and Group B (n = 16) were treated with dorzolamide 1%/timolol and latanoprost. Thirty-six patients completed all 12 weeks of this study. The major clinical parameters measured were intraocular pressure (IOP), conjunctive hyperemia, superficial punctate keratopathy and hyperpigmentation of eyelid at baseline, 4, and 12 weeks. Additionally noted were adverse events and patient preferences, measured using a questionnaire at study initiation and at 12 weeks.Results: At baseline, IOPs were (Group A: 14.1 ± 2.9 mmHg, B: 14.5 ± 2.9 mmHg; P = 0.658), (Group A: 13.8 ± 2.6 mmHg, B: 14.3 ± 2.8 mmHg; P = 0.715) at 4 weeks, and (Group A: 14.1 ± 2.7 mmHg, B: 14.2 ± 2.7 mmHg; P = 0.538) at 12 weeks. Among the groups, there was no significant difference at any time point after baseline (P = 0.923, 0.951, respectively). All adverse events were not remarkably different after therapy. In regards to patient preference before and after switching therapy, 10 patients (50%) in Group A and 10 patients (63%) in Group B preferred using fixed-combination eye drop therapy.Conclusions: Effectiveness and safety were maintained in both groups after switching therapy. Overall, patients generally preferred using a fixed-combination therapy.Keywords: glaucoma, latanoprost–timolol, dorzolamide–timolol, brinzolamide, fixed combination, intraocular pressure

Background Glaucoma is a leading cause of irreversible blindness. The fundamental problem in medical management of glaucoma is of patient compliance. An ideal drug or a drug combination is needed to slow the progression of this majorly symptomless disease. Aim To compare the efficacy and tolerability of the fixed combination latanoprost and timolol instilled once daily in the evening vs fixed combination of dorzolamide and timolol instilled twice daily in primary open angle glaucoma or ocular hypertension. Materials and methods A 12-week, randomized, open, parallel group study including 50 patients with primary open angle glaucoma or ocular hypertension was conducted at a tertiary care hospital. Patients were randomized to group 1, (fixed combination (FC) latanoprost and timolol eye drops, once daily in evening) and group 2, (FC dorzolamide and timolol eye drops, twice daily). At baseline, 2, 4 and 12 weeks, IOP was recorded at 9 AM and 12 noon. The difference in IOP reduction in two treatment groups from baseline to 12 weeks was the main outcome measure. Results Mean diurnal IOP was similar at baseline for both groups. Mean reduction in IOP from baseline to 12 weeks was 9.92 mm Hg (p = 0.001) in group 1 and 9.22 (p = 0.001) in group 2. The reduction in IOP in both groups 1 and 2 was statistically significant at all time intervals. There was a statistically significant advantage for group 1 at 12 weeks for both time readings (p = 0.013 and 0.002 respectively) as compared to group 2. Conclusion The fixed combination of latanoprost and timolol was more effective than that of dorzolamide and timolol in reducing mean diurnal IOP and both treatments were well tolerated. To confirm further such studies are required. How to cite this article Ratol S, Walia R, Chaudhry M. A Comparative Analysis of the Efficacy and Safety of fixed Combinations of Latanoprost/Timolol vs Dorzolamide/Timolol in Primary Open Angle Glaucoma or Ocular Hypertension. J Postgrad Med Edu Res 2012;46(4):172-176.

Purpose: To evaluate the safety of fixed-combination latanoprost/timolol (Xalacom) in patients requiring additional intraocular pressure (IOP) reduction over 5 years. Methods: This phase 3b, open-label, multicenter study included prostaglandin-naive participants with open-angle glaucoma or ocular hypertension insufficiently responsive to beta-blockers and requiring additional IOP reduction. Participants were evaluated at eleven 6-month visits. A masked assessor evaluated iris/eyelash changes at baseline and 12, 36, and 60 months. Increased iris pigmentation incidence was compared with a historic control from a similarly designed study evaluating latanoprost. Ocular and systemic adverse events were recorded. Results: Among 828/974 treated participants with assessable iris photographs, 233 (28.1%) developed increased iris pigmentation versus 127/380 (33.4%) in the historic controls. Participants with mixed eye colors exhibited greater susceptibility to overall increased iris pigmentation (85.8% in both studies). In this study, most participants (80.3%) with increased iris pigmentation developed only a weak increase. Eyelash changes were seen in 58.1% of participants and darkening of the eyelids in 5-6%; 14.1% experienced a serious adverse event. Adverse events resulted in treatment withdrawal in 133 (13.7%) participants. Most were nonserious ocular adverse events, about half of them ocular irritation. Only 3 of 13 serious systemic adverse events were considered to be drug related by the investigator. Mean IOP reductions were stable over 5 years. Conclusions: After 5 years, more than 70% of participants treated with fixed-combination latanoprost/timolol had no increased iris pigmentation. The fixed combination is safe and well tolerated for long-term treatment in patients with open-angle glaucoma or ocular hypertension.

To report the long-term effect of the dorzolamide/timolol (DTFC) and latanoprost/timolol (LTFC) fixed combinations on intraocular pressure (IOP) and visual field defects over time in naïve primary open-angle glaucoma (POAG) patients.Prospective, 4-year, open-label, interventional study.high-volume outpatient clinic.178 patients were assigned to receive medical treatment with either DTFC or LTFC.over 4 years, tri-monthly IOP and yearly visual field assessment (Octopus 101, Program G2). outcomes: effect of treatment on IOP, visual field indices mean defect (MD), and visual field indices variance loss (VL) over time.DTFC and LTFC significantly (por = 0.001) reduced mean IOP over time (from 22.6 +/- 3.0 to 13.8 +/- 1.9 mmHg and from 22.3 +/- 4.0 to 14.7 +/- 1.9 mmHg, respectively). In all, 56 patients (70.9%) and 14 (17.9%) showed a significant MD improvement in the DTFC- and LTFC-treated groups, respectively, p = 0.0001. DTFC progressively and significantly decreased mean VL (from 30.21 +/- 23.88 to 8.11 +/- 8.50 dB). Mean sensitivity slopes during follow-up were 1.14 dB/year and -0.34 dB/year for DTFC and LTFC treatment groups, respectively; p = 0.028.Both treatments significantly reduced IOP as compared with baseline. Additionally, treatment with dorzolamide/timolol fixed combination seem to be effective in preventing glaucomatous visual field progression. This study has some limitations that should be noted, among them its open-label design.

To evaluate 24-h efficacy of travoprost/timolol fixed combination (TTFC) vslatanoprost/timolol fixed combination (LTFC) in exfoliative glaucoma (XFG). A prospective, single-masked, crossover, active-controlled, randomized 24-h comparison. After up to a 6-week medicine-free period, XFG patients were randomized to either TTFC or LTFC for 3 months, dosed each evening, and then changed to the opposite treatment for another 3 months. At the end of the washout, and both treatment periods, a 24-h intraocular pressure (IOP) curve was measured. In total, 40 patients completed the study. The TTFC group showed a lower mean absolute 24-h IOP (18.7±2.6 vs19.6±2.6 mm Hg, P

Purpose. To evaluate the efficacy and safety of fixed combination latanoprost/timolol versus latanoprost or timolol monotherapy. Methods. This 12-week, randomized, double-masked study was designed to overcome potential shortcomings of previous trials. We enrolled 788 subjects with open-angle glaucoma or ocular hypertension treated with a beta-blocker for ≥4 weeks before screening. After washout, 500 subjects with a baseline mean intraocular pressure (IOP) ≥26 and Results. The statistical superiority of the fixed combination was demonstrated at 7/9 time points versus latanoprost and 9/9 time points versus timolol. Mean diurnal IOP levels were similar at baseline but significantly lower with the fixed combination than with either monotherapy at weeks 6 and 12 (each pConclusions. Fixed combination latanoprost/timolol safely reduces IOP levels in patients with glaucoma or ocular hypertension, though only slightly more than does latanoprost monotherapy.

Aims To compare intraocular pressure (IOP) reductions with fixed-combination (FC) latanoprost/timolol once daily in the evening vsFC dorzolamide/timolol twice daily. Methods This evaluator-masked, multicentre, controlled clinical trial randomized subjects with primary open-angle glaucoma or ocular hypertension with IOP insufficiently responsive to Β-blocker therapy (screening IOP>21 and

To evaluate 24-hr intraocular pressure (IOP) and blood pressure (BP) with timolol or latanoprost/timolol fixed combination (LTFC).Patients with primary open-angle glaucoma or ocular hypertension with normal blood pressure were randomized to LTFC, dosed each evening, or timolol dosed twice daily in a cross-over design for 8 weeks and the opposite medicine for 8 weeks. IOP was measured at 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours in the sitting position with Goldmann applanation tonometry and BP monitoring every 30 min while awake and every hour while asleep at the end of each 8-week treatment period.Twenty-nine patients had a 24-hr baseline IOP of 26.3 +/- 2.5 mmHg, systolic BP (SBP) of 121.4 +/- 12.4 mmHg, diastolic BP (DBP) 72.9 +/- 7.1 mmHg, and ocular perfusion pressure (OPP) of 33.9 +/- 5.7 mmHg. No statistical differences were found between untreated and treated 24-hr SBP, DBP, mean BP (MBP), heart rate, or nocturnal BP dipping status with either medication. LTFC lowered IOP more at each timepoint compared to timolol (difference between treatments 2.7 mmHg, p = 0.0002).Neither timolol or evening-dosed LTFC reduced SBP, DBP, MBP, OPP, or increased nocturnal dipping. LTFC was more effective than timolol in decreasing IOP.

Purpose: The efficacy of dorzolamide/timolol fixed combination (DTFC) versus latanoprost/timolol fixed combination (LTFC) in open-angle glaucoma or ocular hypertensive patients. Methods: Patients were randomized to DTFC or LTFC for 6 weeks and switched to opposite treatment for Period 2. Results: Thirty-two completed patients had a mean diurnal IOP of 19.5 ± 3.2 mmHg for DTFC and 18.9 ± 3.4 mmHg for LTFC (p = 0.12), with no significant difference found between DTFC and LTFC at any timepoint following a Bonferroni correction (p ≥ 0.01). Conclusions: Patients treated with DTFC and LTFC have a statistically similar ocular hypotensive effect.

Purpose To compare intraocular pressure (IOP) reduction profiles of latanoprost-timolol maleate fixed combination (LTFC) administered in the morning or evening in primary open angle glaucoma (POAG). Methods A prospective, randomized study including 60 eyes of 30 patients with POAG was carried out. Patients were randomized to treatment with LTFC at 8 PM (Group 1) or at 8 AM (Group 2). After therapy of 4 weeks, IOP was measured at 2 AM, 6 AM, 10 AM, 2 PM, 6 PM, and 10 PM and compared with baseline values and latanoprost therapy alone. Results Mean diurnal baseline IOPs and IOPs after treatment with latanoprost and LTFC were 23.6±2.6, 16.7±2.3, and 15.5±2.2 mmHg in Group 1 and 23.1±2.6, 16.9±2.4, and 15.7±2.4 mmHg in Group 2. LTFC lowered IOP more than latanoprost at all time points in both groups (p0.05). According to IOP reduction from baseline, there was a statistically significant difference between groups in favor of Group 1 at 6 AM, 10 AM, and mean diurnal measurement (pConclusions Both morning and evening dosing of LTFC were effective in lowering diurnal IOP in patients with POAG. However, evening dosing of LTFC seemed to be more effective in controlling IOP especially in the morning and avoiding the fluctuations with lower range of IOP

The aim of this study was to confirm randomized clinical trial results showing that a fixed timolol/travoprost combination (TT; DuoTrav) controls intraocular pressure (IOP) better than a fixed timolol/latanoprost combination (TL; Xalacom) in everyday ophthalmic practice, when measured in the morning and24 hours after instillation.Patients with ocular hypertension or primary open angle glaucoma stabilized on TT or TL were included in this retrospective cross-sectional study. Data on demographics, medical history and previous treatments were extracted from the patients' medical records. Last treatment instillation times and IOP values were recorded at clinic visits. Treatments were compared by analyses of variance, logistic regressions and propensity scores adjusted for confounding factors.Out of 316 patients included, 124 instilled TT, 192 instilled TL and 266 (84.2%) overall had instilled their eye drops within 24 hours. The patients' mean age was 64.5 years and 51.6% were female. Treatment groups were comparable except for longer disease and treatment durations in TL recipients. Worse eye mean IOPs were 25.8 mmHg at diagnosis and 21.9 mmHg on starting their designated fixed combination treatment. The best IOP control was provided by TT instillations (mean IOP 17.1 and 19.0 mmHg in the TT and TL groups, respectively; p0.001). This difference was reinforced by results in the subgroup of patients who instilled treatment24 hours prior to IOP measurement (mean IOP 17.0 and 20.3 mmHg in the TT and TL groups, respectively; p0.004). Also, 82.6% of TT patients satisfied their ophthalmologists' IOP targets versus 51.1% of TL patients (p0.001). All significant differences persisted after adjustment for confounding factors.This study, conducted in routine ophthalmic practice, confirmed published clinical trial results showing that TT provides better IOP control than TL when measured in the morning, and that travoprost has longer-lasting residual effects than latanoprost when IOP is measured24 hours after instillation. However, readers should interpret these findings in the context of a cross-sectional observational study conducted in a naturalistic setting.

Purpose: Mast cells participate in ocular allergic inflammation by releasing biologically active mediators. Leukotrienes are released from activated mast cells via an IgE-dependent mechanism, and play a crucial role in ocular allergic inflammation. In this study, the effect of three topical antiglaucoma drugs, that is, latanoprost, timolol and GLC756, a novel dopamine D2 agonist and D1 antagonist, on leukotriene C4 (LTC4) release after rat mast cell activation was examined. Methods: A rat basophilic leukaemia RBL-2H3 mast cell line was activated via IgE/anti-IgE. Rat mast cells were incubated with latanoprost, timolol, or GLC756 at concentrations of 0.1, 1, 10 and 30 μM. LTC4 concentration in supernatant was assessed 5 h post activation by EIA. Results: Compared with controls, timolol showed no relevant effect on LTC4 release, 5 h after mast cell activation. Latanoprost and GLC756, in contrast, revealed an inhibitory effect on LTC4 release, which was dose-related and statistically significant at the concentrations of 10 and 30 μM. Conclusion: The results of this study suggest that timolol has no significant influence on LTC4 release from activated mast cells. By contrast, latanoprost and GLC756 inhibited LTC4 release, suggesting a possible anti-inflammatory effect on ocular allergic inflammatory processes in topical glaucoma medication.

Latanoprost is one of the greatest success stories of medical treatment of glaucoma. Latanoprost was developed in the early 1990s and quickly became the best selling eye drop for glaucoma treatment replacing timolol as the drug of choice in the USA within 3 years. Its use led to a sharp decline in surgical treatment for glaucoma in the developed world. Timolol had been introduced with similar success in the 1970s, replacing pilocarpine, a drug that needed more frequent instillation and caused significant topical side effects including pain and blurred vision. Fixed-combination therapy with latanoprost and timolol was introduced in Europe several years ago with the hope that convenience and better compliance would improve clinical outcomes. However, the results of this therapy have been disappointing with less intraocular pressure lowering than might be expected from the two most effective eye drops for the treatment of glaucoma.

To compare the efficacy and tolerability of a once daily evening dose of the latanoprost/timolol fixed combination (LTFC) with that of a once-daily evening dose of the bimatoprost/timolol fixed combination (BTFC) in patients with open-angle glaucoma with elevated intraocular pressure (IOP) insufficiently responsive to monotherapy with prostaglandin analogues/prostamides.Prospective, randomized, evaluator masked, single-center study.36 patients with a diagnosis of open-angle glaucoma, with or without pseudoexfoliation, and inadequate control of IOP, insufficiently responsive to monotherapy with prostaglandin analogues/prostamides.The primary end-points were the change in IOP at 9:00 am from baseline to week 4, and the difference between treatment groups in the mean diurnal IOP reduction from baseline to week 4.BTFC provided significantly greater mean diurnal IOP reduction [mean (standard deviation)] 2.8 (0.9) mmHg, compared with LTFC 2.1 (0.6) mmHg, p = 0.0214. Both treatments significantly reduced the IOP from baseline at each IOP time-point measured, p0.0001, and for the mean diurnal IOP; p = 0.0049 for the LTFC, and p0.0001 for the BTFC. There were no significant differences in average hyperemia scores among groups, 1.25 (0.5) vs. 1.62 (0.69), p = 0.3835, for the LTFC and the BTFC, respectively.The results of this study showed a significantly higher IOP-lowering effect of a once-daily evening dose of the BTFC compared to that of a once-daily evening administration of the LTFC.

Summary The objective of this study was to compare the effect of the latanoprost/timolol fixed combination (LTFC) and the dorzolamide/timolol fixed combination (DTFC) on the retrobulbar haemodynamic and intraocular pressure (IOP) in patents with open-angle glaucoma (OAG). This was a prospective, examiner masked, randomised and crossover study. Participants were 32 consecutive subjects, who met the inclusion/exclusion criteria, with newly diagnosed OAG. Patients were randomised to either LTFC or DTFC for the first 1-month treatment phase after a 1-month washout period, without medical treatment, patients began with the opposite treatment for the second 1-month treatment period. Colour Doppler parameters in ophthalmic artery (OA) and posterior ciliary arteries (PCA), ocular perfusion pressure, IOP and systemic haemodynamics were assessed at each baseline and at the end of each treatment period. The main outcomes include peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) in OA and PCA. DTFC significantly increased EDV in OA from 7.55 (1.16) to 9.32 (1.22), p

Purpose To compare the efficacy and tolerability of fixed-combination latanoprost and timolol applied in the evening with the concomitant use of the individual components. Design Twelve-week, randomized, double-masked, multicenter study. Participants Five hundred seventeen randomized patients with ocular hypertension; open-angle, pigmentary, or exfoliation glaucoma; and baseline (after washout) intraocular pressure (IOP) levels between 23 and 33 mmHg. Methods Patients received either the fixed combination of latanoprost and timolol once daily in the evening and a placebo in the morning and evening or the unfixed combination of latanoprost once daily in the evening and timolol in the morning and evening. Study visits were at weeks 2, 6, and 12. Main Outcome Measures The primary efficacy end point was mean change from baseline to week 12 in diurnal IOP (mean IOPs of 8 am, 12 pm, and 4 pm). The fixed combination was considered noninferior to the unfixed combination if the upper limit of the 95% confidence interval (CI) of the difference was Results In all, 502 patients were included in intent-to-treat analyses (fixed combination, n=255; unfixed combination, n=247). For the fixed- and unfixed-combination groups, mean baseline diurnal IOP levels were 25.4 mmHg and 25.2 mmHg, respectively, and mean diurnal IOP reductions were 8.7 mmHg and 9.0 mmHg (between-treatment difference, 0.3 mmHg; 95% CI, −0.1 to 0.7 mmHg; P = 0.15). Both treatments were well tolerated. Conclusions The fixed combination of latanoprost and timolol administered once daily in the evening is not inferior to the unfixed combination of latanoprost once daily in the evening and timolol twice daily. The fixed combination provides an effective and well-tolerated alternative to multiple instillations.

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.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.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.Substituting brinzolamide for dorzolamide maintained stable IOP with improvement in ocular comfort in patients with glaucoma.

To evaluate efficacy and safety in patients with ocular hypertension or open angle glaucoma changed to latanoprost/timolol fixed combination (LTFC).A prospective, multicentre, historical control in which qualified patients had their previous therapy substituted by LTFC and were followed for at least 2 months.In 1676 patients LTFC was continued in 93% throughout the observation period. In all patients LTFC reduced the intraocular pressure (IOP) from 20.6 (SD 3.8) to 17.7 (3.0) mm Hg (p0.001) compared to previous monotherapies including latanoprost, timolol, alpha agonists or carbonic anhydrase inhibitors (CAI). LTFC provided more efficacy after changing from adjunctive therapies including: a beta blocker added to either CAI, alpha agonist, or pilocarpine, or CAI added to an alpha agonist, or latanoprost added to either CAI, alpha agonist, or beta blocker (unfixed combination), and travoprost added to timolol (p0.007). LTFC was as effective as latanoprost used with dorzolamide/timolol fixed combination (-0.9 mm Hg, p = 0.1792). The most common reason to discontinue therapy was lack of efficacy (n = 70, 4%) and adverse event (n = 17, 1%).In a clinical setting, patients who have their monotherapy or adjunctive therapy substituted with LTFC may experience reduced IOP, good tolerability, and continuation of therapy for the first 2-3 months of treatment.

Background Approximately 40% of patients with glaucoma are concomitantly prescribed ⩾2 differentintraocular pressure (IOP)-lowering medications. An effective and well-tolerated fixed combination of agents requiring once-daily instillation may improve patient compliance. Objective The purpose of this study was to compare the efficacy and safety profile of the fixed combination latanoprost 0.005% + timolol maleate 0.5% QD with those of latanoprost 0.005% monotherapy QD in patients whose elevated IOP (⩾21 mm Hg) was inadequately controlled by latanoprost. Methods This 21-day, randomized, double-masked, active-control study was conducted at 49 study sites in Argentina, Brazil, Colombia, Mexico, Peru, the United States, and Venezuela. Adults with glaucoma or ocular hypertension who had failed to reach an IOP of Results A total of 350 patients were enrolled. In all, 348 patients were included in the ITT and tolerability analyses (fixed combination, n = 175; latanoprost, n = 173; mean [SD] age, 64.4 [13.2] and 63.2 [14.0] years, respectively; 103 women in each group). Baseline demographic and clinical characteristics were similar between groups. A higher percentage of patients receiving the fixed combination had IOP decreases of ⩾2 mm Hg on day 21 relative to baseline compared with latanoprost-treated patients (79.4% vs 51.4%, respectively; P Conclusion In this selected population of patientswith an inadequate initial IOP response to latanoprost, switching to fixed-combination latanoprosttimolol resulted in a greater decrease in IOP and similar tolerability compared with continuing latanoprost therapy.

To compare the efficacy and safety of the concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily with those of a fixed combination of latanoprost 0.005%/timolol 0.5% once daily.Forty-four patients with primary open-angle glaucoma or ocular hypertension with elevated IOP insufficiently responsive to monotherapy were randomly assigned to one of the two treatment groups: concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily (TB group: 22 patients) or latanoprost 0.005% plus timolol 0.5% once daily (LT group: 22 patients). Visits were undertaken at screening (current ocular hypotensive therapy was discontinued), baseline (randomization), and after 2 weeks, 1 month, 2 months and 3 months of therapy.IOP was determined at 9 a.m., 12 p.m. and 4 p.m. at each study visit, and diurnal IOP was calculated as the mean of these recordings. Adverse events were recorded at each visit.IOP at the baseline visit was similar in both groups. Overall mean IOP was significantly lower in the TB as compared to the LT group after 1 month, 2 month and 3 month follow-up; only 9 a.m. measurements were significantly different, reaching a maximum difference (16.9 +/- 0.9 mmHg vs 18.4 +/- 1.8 mmHg, p0.001) at the 3 month check. The percentage of responders (IOP decreaseor = 30%) was higher in the TB group. Both treatments were well tolerated and there were no cases of withdrawal from treatment.Travoprost 0.004% and brinzolamide 0.1% concomitant therapy showed a greater efficacy than the fixed latanoprost 0.005%/timolol 0.5% combination in terms of absolute IOP decreases. Travoprost/brinzolamide therapy also offered the advantages of a greater percentage of responders.

Purpose: To evaluate the efficacy and safety of the timolol maleate/latanoprost fixed combination (TLFC) given once each evening versus brimonidine and timolol solution given twice daily as concomitant therapy in primary open-angle glaucoma or ocular hypertension patients. Methods: Qualified subjects were begun on timolol alone twice daily for 1 month and then randomized to either TLFC or brimonidine and timolol concomitant therapy for 6 weeks. Patients were then switched to the other treatment regimen. Intraocular pressures (IOPs) were measured every 2 hours between 08 : 00 and 20 : 00 hours at baseline and at the end of periods 1 and 2. Results: This study found that in 32 subjects the IOP diurnal curve on timolol alone (20.9 ± 2.8 mmHg) decreased to 17.9 ± 3.2 mmHg when patients were treated with TLFC and to 19.0 ± 2.4 mmHg when patients were treated with brimonidine and timolol (p = 0.02). Intraocular pressures at individual time-points were statistically similar between the groups at the 08 : 00 trough and 2 and 4 hours after dosing. However, beyond 4 hours after dosing, TLFC-treated subjects demonstrated a trend towards lower IOPs at each 2-hour time-point that was not statistically significant after a Bonferroni correction (p ≤ 0.05). The incidence of both solicited and unsolicited side-effects was similar between groups. Conclusion: This study suggests that TLFC given in the evening reduces the mean daytime diurnal IOP more than brimonidine and timolol given concomitantly twice daily.

We present a case of bilateral diffuse serous detachment associated with latanoprost/timolol fixed combination treatment which was recovered after changing treatment.

To evaluate morning vs evening once daily concomitant latanoprost 0.005%/timolol maleate 0.5% therapy in ocular hypertensive or primary open-angle glaucoma patients.Prospective single-center double-masked crossover comparison.Patients who responded to timolol maleate 0.5% given twice daily were randomized to either evening or morning dosing of concomitant latanoprost 0.005% and timolol maleate 0.5% therapy for 7 weeks. Twenty-four hour diurnal curve intraocular pressure (IOP) testing was performed following each period.Thirty-six patients completed this study. There was a significant reduction at each time point in the 24-hour diurnal curve of both evening (17.1 +/- 2.7 mm Hg) and morning (17.3 +/- 3.1 mm Hg) dosed latanoprost/timolol maleate compared with timolol maleate given twice daily (21.1 +/- 3.3 mm Hg) (P.0001). When the morning and evening dosing groups were compared directly, the 06:00 time point was statistically lower with evening dosing (16.4 +/- 2.3 mm Hg) vs morning dosing (17.9 +/- 2.8 mm Hg) (P =.01). Overall, a trend existed for greater daytime reduction with night-time dosing of the concomitant therapy, whereas morning dosing tended to give lower night-time pressures. There was a significantly lower mean range of diurnal pressure with evening (3.6 mm Hg) vs morning (4.3 mm Hg) dosing (P =.02). No differences in adverse events existed between the treated arms.This study suggests that latanoprost and timolol maleate, both given once daily in the morning or evening, effectively reduce the IOP for the 24-hour diurnal curve when compared with timolol maleate twice daily.

To compare the 24-h intraocular pressure (IOP) control and tolerability of travoprost/timolol benzalkonium chloride (BAK)-free (TTFC) vs. latanoprost/timolol fixed combination preserved with BAK (LTFC) in open-angle glaucoma patients insufficiently controlled with latanoprost 0.005% monotherapy given once in the evening. The authors have conducted a prospective, observer-masked, active-controlled, cross-over, comparison study. Qualified open-angle glaucoma patients who demonstrated a latanoprost-treated morning IOP (10:00 ± 1 h) greater than 20 mmHg on two separate visits were randomized for 3 months to receive either TTFC or LTFC. Patients were then crossed over to the opposite treatment for another 3 months. At the end of the latanoprost run-in and after each 3-month therapy period patients underwent 24-h IOP monitoring in the habitual position using Goldmann applanation tonometry in the sitting position during the day (10:00, 14:00, 18:00 and 22:00) and Perkins tonometry in the supine position at night (02:00 and 06:00). Selected ocular surface parameters were evaluated after each therapy period. Forty-two open-angle glaucoma patients completed the study. The mean 24-h baseline IOP on latanoprost was 21.5 ± 1.6 mmHg. Both fixed combinations significantly reduced the IOP at each time point, for the mean, peak and fluctuation of 24-h IOP compared with latanoprost monotherapy (P

Purpose.We retrospectively reviewed medical records of glaucoma patients to investigate how switching medications may affect intraocular pressure (IOP) management. Three concomitant medications were changed to two medications: one combination drop and one single-action drop. Associated adverse effects were also examined.Subjects and Methods.A total of 112 patients with primary open-angle glaucoma or ocular hypertension were examined. All patients were concomitantly using a prostaglandin (PG) analog, aβ-blocker, and a carbonic anhydrate inhibitor (CAI). Fifty-five patients began using latanoprost (PG analog)/timolol (β-blocker) fixed-combination (LTFC) drops and a CAI (group 1), and 57 patients began using dorzolamide (CAI)/timolol fixed-combination (DTFC) drops and a PG analog (group 2). The IOP was measured every 6 months for 2 years following medication changes. Changes in visual field mean deviation (MD) and medication discontinuations were also examined.Results.There were no significant differences in IOP or MD values before and after medication changes in either group. The proportion of medication discontinuations, uncontrolled IOP, and adverse reactions was similar in both groups.Conclusion.Switching patients from multiple single-action medications to combination medications was not associated with changes in IOP, visual field testing results, or adverse event frequency.

To measure the effect on intraocular pressure (IOP) for 24 hours after repeated administration of the fixed combination of latanoprost 0.005% and timolol 0.5%.A randomized, double-masked placebo-controlled crossover study including 20 patients with ocular hypertension was carried out. Patients were randomized to treatment with the fixed combination of latanoprost and timolol or with placebo. The eyedrop was taken at 8 AM. After 2 weeks of treatment, the patients were hospitalized, and the IOP was measured at 8 AM, and thereafter every other hour until midnight, and also at 3 AM, 6 AM, and 8 A.M. After a washout period of 4 weeks, they switched to the other eyedrop, and after 2 weeks of treatment were hospitalized and the IOP measurements were repeated at the same intervals.The mean 24-hour IOP was 14.7 +/- 0.3 mm Hg (mean +/- standard error of the mean) for latanoprost and timolol and 19.4 +/- 0.3 mm Hg for placebo. This corresponds to a significant IOP difference of 4.7 +/- 0.4 mm Hg (95% confidence interval 3.8-5.8; P0.001) between the two treatments in favor of the combination. At all measured time points, except at 3 AM, the mean IOP was lower with latanoprost and timolol than with placebo. During daytime measurements the mean IOP was 13.9 +/- 0.7 mm Hg for the fixed combination and 19.5 +/- 0.7 mm Hg for the placebo. Corresponding figures at nighttime were 16.1 +/- 0.7 mm Hg and 19.2 +/- 0.7 mmHg, respectively.The fixed combination of latanoprost and timolol significantly reduced IOP after administration once daily for 2 weeks in patients with ocular hypertension. A reduction of IOP during a 24-hour period was seen, with a greater IOP reduction during daytime compared with nighttime. The fixed combination applied once daily could be a convenient alternative to concomitant therapy with its individual components.

Objective To evaluate the efficacy and tolerability of the fixed combination of Latanoprost/Timolol versus Dorzolamide/Timolol in the treatment of patients with elevated intraocular pressure (IOP). Methods A comprehensive literature meta-analysis was performed according to the Cochrane Collaboration methodology to identify randomized clinical trials comparing latanoprost/timolol FC (FCLT) with dorzolamide/timolol (FCDT) in patients with elevated IOP. The efficacy estimates were measured by the weight mean difference (WMD) for the IOP reduction (IOPR) from baseline to end point, including the diurnal mean IOPR, 8 AM IOPR, 12 PM IOPR, and 4 PM IOPR. The tolerability estimates were measured by RR for adverse events. All outcomes were reported with a 95% confidence interval (CI). The data were synthesized by Stata 12.0 SE for Windows. Results Eight studies involving 841 patients (841 eyes) were included in the meta-analysis. With a WMD of IOPR in the diurnal mean of 0.16 mmHg (95% CI, -0.31 to 0.63), the FCLT was as effective as FCDT in lowering IOP in patients with elevated IOP (P = 0.51). The WMDs of IOPR were 0.58 mmHg (95% CI: -0.002 to 1.17) at 8 AM, -0.07 mmHg (95% CI: -0.50 to 0.36) at 12 PM, and 0.41 mmHg (95% CI: -0.18 to 1.00) at 4 PM, and there were no significant difference between FCLT and FCDT. FCLT was associated with a significantly lower incidence of eye pain, bitter taste, and irritation/stinging than FCDT, with pooled RRs of 0.34 (95% CI: 0.14 to 0.82), 0.06 (95% CI:0.008 to 0.42), and 0.35 (95% CI: 0.14 to 0.85), respectively. Conclusion FCLT was associated with equivalent efficacy in IOP lowering comparing with FCDT. However, FCLT was better tolerated than FCDT.

Purpose: To evaluate the effects of topical latanoprost and timolol in combined therapy on retinal blood flow and tissue circulation in the optic nerve head (ONH) of the cynomolgus monkey. Methods: Latanoprost (30 μL, 0.005%) was instilled once daily and timolol (30 μL, 0.5%) twice daily for 6 days into 1 eye, and physiological saline into the other eye to serve as control. Blood velocity through retinal veins was determined using Kowa Laser Speckle Blood Flow Meter. The ONH tissue blood velocity (NBONH) was determined using the Laser Speckle Tissue Circulation Analyzer. Retinal blood flow and NBONH determinations were carried out before the first instillation and 4 hours after the first instillation on the 2nd experimental day, and the last instillation at the same sites at the same time of day. The intraocular pressure (IOP) was also measured periodically. Results: After the first instillation, on the 2nd experimental day, the retinal blood flow decreased compared with the baseline, but 6-day instillation caused no significant change from the baseline. Six-day instillation increased the NBONH in the treated eyes by 10% from the baseline and by 7% from that in the fellow control eye. After 6-day instillation, the IOP was lowered by 7.8±2.7 mm Hg and 3.6±4.3 mm Hg in the treated and control eyes, respectively. Conclusions: Combined 6-day instillation of latanoprost once daily and timolol twice daily has no significant effect on the retinal blood flow, but significantly increases the ONH tissue blood velocity in monkey eyes. Jpn J Opthalmol 2000;44:227–234

PURPOSE: To compare the 24-hour diurnal ocular hypotensive efficacy of two dosing regimens of latanoprost, once daily (8 am or 10 pm), vs timolol maleate, twice daily. METHODS: We measured six diurnal intraocular pressure curves (6 am, 10 am, 2 pm, 6 pm, 10 pm, and 2 am) in one randomly selected eye of 34 Greek patients newly diagnosed with primary open-angle glaucoma. The first diurnal curve was an untreated baseline. Patients began taking timolol 0.5%, twice daily, for 2 months. Patients were randomly assigned to latanoprost 0.005% given at 8 am or 10 pm for 1 month and then changed to the other dosing regimen for 1 month. A diurnal curve was performed after each dosing period. RESULTS: The baseline diurnal pressure for all 34 subjects was 23.1 ± 3.7 mm Hg. The average intraocular pressures at 6 am for patients who were given latanoprost in the evening (17.9 ± 2.9 mm Hg) was statistically lower than that in patients given timolol solution (20.1 ± 2.5 mm Hg, P = .003); however, patients who were given timolol demonstrated a similar diurnal intraocular pressure (19.1 ± 2.8 mm Hg) to both morning (18.8 ± 3.7 mm Hg) and evening doses (18.8 ± 3.6 mm Hg) of latanoprost ( P =.329). When the two latanoprost dosages were compared directly, evening administration provided a statistically lower intraocular pressure at 10 am ( P = .0001) and morning administration at 10 pm ( P = .0001). This study had an 80% power to exclude a 1.2–mm Hg difference between groups. CONCLUSIONS: This study indicates that in a small population, both latanoprost and timolol are effective in lowering intraocular pressure throughout a 24-hour period; however, latanoprost is most effective in the 12-hour to 24-hour period after administration.

· Objective: To compare the intraocular pressure (IOP)-reducing effect of the fixed combinations of timolol 0.5% and latanoprost 0.001% or 0.005% after 4 weeks’ treatment. · Design: Following a 1-week run-in period on timolol 0.5% once daily, 139 patiens were randomized to once-daily treatment with a fixed combination of timolol 0.5% and latanoprost 0.001% (comb. 10) or latanoprost 0.005% (comp. 50) or to the individual monotherapies. The IOP was measured at inclusion and at 8 a.m., noon and 4 p.m. on days 1, 7 and 28. · Results: Comb. 10, comb. 50, latanoprost and timolol reduced IOP by 3.7, 6.1, 4.9 and 2.1 mmHg, respectively, from a baseline mean diurnal IOP (±SEM) of 24.8±0.5, 24.1±0.4, 25.2±1.2 and 24.8±0.9 mmHg, respectively. The difference in IOP reduction was significant between comb. 50 and comb. 10 (P