A Double-Masked Randomized Crossover Study Comparing the Effect of Latanoprost/Timolol and Brimonidine/Timolol Fixed Combination on Intraocular Pressure and Ocular Blood Flow in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension

Hommer, Anton; Sperl, Philipp; Resch, Hemma; Popa-Cherecheanu, Alina; Qiao, Chunyan; Schmetterer, Leopold; Garhöfer, Gerhard

doi:10.1089/jop.2011.0165

Cited by 19 publications

(14 citation statements)

References 51 publications

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“…Other fixed combinations produced and commercialized by Allergan are 0.2% brimonidine-0.5% timolol (BRIMOTFC, Combigan ® ) and 0.03% bimatoprost-0.5% timolol (BIMATOFC, Ganfort ® ). Different studies stress the efficacy and safety of BRIMOTFC versus the unfixed components or another fixed combination [2][3][4][5][6][7][8][9]. Other papers underline the efficacy and safety of DTFC, even three times a day [10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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

Giuffrè¹

2012

OJOph

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Purpose: This is a retrospective, comparative, head-to-head, not commissioned study about the efficacy of bimatoprost 0.03%, brimonidine 0.2%, brinzolamide 1%, dorzolamide 2%, and travoprost 0.004%/timolol 0.5%-fixed combinations in patients affected by naΐve 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: 37-87 y) 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.

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Section: Introductionmentioning

confidence: 99%

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

Giuffrè¹

2012

OJOph

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“…Monotherapy with timolol decreases aqueous humor production to reduce IOP, and protects retinal ganglion cells in a rat glaucoma model. 11,12) Latanoprost and timolol in a fixed combination greatly reduced IOP in patients with primary open angle glaucoma in a double masked, randomized clinical trial.12) The latanoprost/timolol combination provides a greater ocular hypotensive effect than monotherapy with latanoprost or timolol.13) Although the greater ocular hypotensive effect of combination is well-understood, it is not known if the combination has a greater neuroprotective effect than either drug alone.In the present study, we have investigated the neuroprotective effects of a latanoprost/timolol combination on retinal damage and the mechanism of the protective effect of this combination of drugs in vitro. …”

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confidence: 99%

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confidence: 99%

Neuroprotective Effect of Ocular Hypotensive Drugs: Latanoprost/Timolol in Combination Are More Effective than Each as Monotherapy in RGC-5

Fuma

Shimazawa

Imamura

et al. 2016

Biological & Pharmaceutical Bulletin

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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.Key words glaucoma; latanoprost; neuroprotective effect; phosphatidyl inositol 3-kinase (PI3K); Akt; timolol Glaucoma is a progressive neurodegenerative disease affecting over 60 million people worldwide and predicted to affect more than 80 million people by 2020. 1) Glaucoma is also the second most common cause of irreversible blindness. An increase in intraocular pressure (IOP) contributes to the pathogenesis of glaucoma.2) Treatment of glaucoma is focused on decreasing IOP, because IOP is one of the most important risk factors for disease progression.3) Glaucoma drugs that reduce IOP include beta blockers, carbonic anhydrase inhibitors, prostaglandin analogs, sympathomimetics, and miotics. Retinal ganglion cells are highly sensitive to increased IOP, and retinal ganglion cell damage is caused by several types of cell stress. 4,5) For example, retinal ganglion cell death in glaucoma is not only related to oxidative stress, but also to endoplasmic reticulum (ER) stress and ischemic stress. 6,7) Moreover, a previous report suggested that this retinal ganglion cell death is mediated by phosphatidyl inositol 3-kinase (PI3K)/Akt pathway, and the inhibition of PI3K/Akt pathway promoted retinal ganglion cell survival in rat optic nerve injury model. 8) Many patients with glaucoma have normal IOP. Therefore, it is important to not only decrease IOP, but also to protect retinal cells during glaucoma therapy.Prostaglandin analogs, such as latanoprost, are the major therapy that reduces IOP by stimulating drainage of the aqueous humor. Latanoprost is a prostaglandin F2α analog and is effective at reducing IOP when used alone. 9) Additionally, latanoprost p...

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“…Only one study comparing LTFC to 0.2% Brimonidine/0.5% timolol (BTFC) met the criteria, so we included that study in the system review but did not conduct a meta-analysis. This is a moderate study involving 18 patients [28]. The results showed that there was no significant difference in reductions in the mean diurnal IOP as of 1.5 months of treatment (MD = 0.50 mmHg; P = 0.57).…”

Section: Effects Of Interventionsmentioning

confidence: 86%

The efficacy of the fixed combination of latanoprost and timolol versus other fixed combinations for primary open-angle glaucoma and ocular hypertension: A systematic review and meta-analysis

et al. 2020

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Background Fixed-combination (FC) therapy is used in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients who require more than one medication to reach their target intraocular pressure (IOP). Currently, there are several FC therapies available for the treatment of glaucoma. The FC of latanoprost/timolol (LTFC) is a commonly used FC. Here, we conducted systematic review to compare the IOP-lowering effects of LTFC with other FCs for patients with POAG and OHT. Materials and methods We searched PubMed, EMBASE, the Cochrane Library, and Web of Science for randomized-controlled clinical trials and cross-over studies. The outcomes were mean IOP and IOP fluctuation after one month of treatment. Meta-analysis was carried out using RevMan (version 5.1) software. After conducting meta-analyses, we rated the quality of each meta-analysis as high, moderate, low, or very low using the "GRADE" system. Results We included 16 trials in this meta-analysis. Moderate-quality meta-analysis showed that LTFC had a comparable mean IOP to that of a fixed combination of travoprost and timolol (TTFC) [mean difference (MD): 0.07 mmHg] and a fixed combination of dorzolamide and timolol (DTFC) [MD: −0.31 mmHg], and it also had a comparable IOP-fluctuation effect compared to that of TTFC [MD: 0.13 mm Hg] and DTFC [MD: 0.25 mmHg]. Compared to the fixed combination of bimatoprost and timolol (BiTFC), moderate-quality evidence showed a higher mean IOP in the LTFC group [MD 0.76 mmHg], whereas low-quality meta-analysis showed higher IOP fluctuation [MD 1.09 mmHg] in the LTFC group.

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A Double-Masked Randomized Crossover Study Comparing the Effect of Latanoprost/Timolol and Brimonidine/Timolol Fixed Combination on Intraocular Pressure and Ocular Blood Flow in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension

Abstract: 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.

Cited by 19 publications

References 51 publications

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

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

Neuroprotective Effect of Ocular Hypotensive Drugs: Latanoprost/Timolol in Combination Are More Effective than Each as Monotherapy in RGC-5

The efficacy of the fixed combination of latanoprost and timolol versus other fixed combinations for primary open-angle glaucoma and ocular hypertension: A systematic review and meta-analysis

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