A Randomized Trial of Brimonidine Versus Timolol in Preserving Visual Function: Results From the Low-pressure Glaucoma Treatment Study

Krupin, Theodore; Liebmann, Jeffrey M.; Greenfield, David S.; Ritch, Robert; Gardiner, Stuart K.

doi:10.1016/j.ajo.2010.09.026

Cited by 330 publications

(232 citation statements)

References 51 publications

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“…Other than the IOP-lowering effect, this drug has been touted as having a potential in neuroprotection (Krupin, 2011). This first prospective clinical trial demonstrated that normotensional glaucoma patients showed a slower progression rate when treated with brimonidine when compared with their beta-blocker-treated, IOP-adjusted counterparts.…”

Section: Wwwintechopencommentioning

confidence: 95%

A Vascular Approach to Glaucoma

Pinto¹,

Stalmans²

2011

Glaucoma - Basic and Clinical Concepts

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Section: Wwwintechopencommentioning

confidence: 95%

A Vascular Approach to Glaucoma

Pinto¹,

Stalmans²

2011

Glaucoma - Basic and Clinical Concepts

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“…Previous studies have shown that alpha-2-adrenergic receptor subtype A could mediate signals to regulate Müller cell functions through activation of mitogen-activated protein kinase (MAPK) pathway by extracellular signal-activated kinase (ERK) phosphorylation, triggering to cytoplasmic signals transduction into transcriptional activation in the nucleus (36) . The MAPK pathway is known to trigger the appropriate responses to chemical and physical stresses, and play a key role in cell survival and adaptation (37) . Thus, the modulation of MAPK activation could play a possible role on interrupting pathways that stimulate apoptosis, thereby shifting the balance in retinal cells toward survival.…”

Section: Discussionmentioning

confidence: 99%

Brimonidine tartrate effect on retinal spreading depression depends on Müller cells

Oliveira¹,

Rodrigues²,

Alencar³

et al. 2014

Revista Brasileira De Oftalmologia

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Objective: Demonstrate the Brimonidine effect over Retinal Spreading Depression (SD). Brimonidine is an alpha-2-adrenergic receptor agonist, used in the management of glaucoma. Alpha2-agonists have been shown to be neuroprotective in various experimental models, however the molecular and cellular targets leading to these actions are still poorly defined. The SD of neuronal electric activity is a wave of cellular massive sustained depolarization that damages the nervous tissue. Local trauma, pressure, ischemic injuries and other chemical agents as high extracellular potassium concentration or glutamate, can trigger SD, leading to exaggerated focal electrical followed by an electrical silence. Methods: Using chicken retina as model, we performed alpha2-receptor detection by Western Blotting and Immunohistochemistry. After that we obtained electrical signals of SD by microelectrodes on retina in the absence or presence of Brimonidine. For in vivo visualization we observed retina with optical coherence tomography on normal state, with SD passing, and with SD + Brimonidine. Results: Our data demonstrated that: (1) alpha2-adrenergic receptors are present in Müller cells, (2) the treatment with Brimonidine decreases the SD's velocity as well as the voltage of SD waves and (3) OCT revealed that SD creates a hyper reflectance at inner plexiform layer, but on retinal treatment with brimonidine, SD was not visualized. Conclusion: Our study about brimonidine possible pathways of neuroprotection we observed it reduces SD (a neuronal damage wave), identified a new cellular target -the Müller cells, as well as, firstly demonstrated SD on OCT, showing that the inner plexiform layer is the main optically affected layer on SD.Keywords: Retina/drug effects; Adrenergic alpha-2 receptor agonists/therapeutic use; Glaucoma RESUMOObjetivo: Demonstrar o efeito do Tartarato de Brimonidina, um alfa2-agonista usado no manejo do glaucoma, sobre a depressão alastrante (DA) retiniana. Esses agonistas têm demonstrado ser neuroprotetores em vários modelos experimentais, contudo seus alvos celulares e moleculares continuam indefinidos. A DA da atividade elétrica neuronal é uma onda de despolarização celular massiva e sustentada que leva ao dano no tecido nervoso. Trauma local, pressão, isquemia e outros agentes químicos como o aumento do potássio extracelular e o glutamato podem disparar a DA, levando a uma atividade elétrica exagerada seguida de silêncio elétrico. Métodos: Usando a retina de pinto como modelo, realizamos a detecção do alfa2-receptor por Western Blotting e ensaio Imunohistoquímico. Após isso, obtivemos os sinais elétricos da DA através de microeletrodos inseridos na retina durante sua passagem na presença ou ausência de Brimonidina. Para visualização do tecido utilizamos o tomógrafo de coerência optica (OCT), analisando como é a retina no seu estado de repouso, durante a passagem da DA, e a DA + brimonidina. Resultados: Nossos dados demonstraram que: (1) os receptores alfa adrenérgicos presentes na retina são do subtipo-...

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“…The Low-pressure Glaucoma Treatment Study compared the effects of brimonidine and timolol in monotherapy for NTG. Brimonidine-treated patients were less likely to have VF progression despite known comparable IOP decreases (95) . Although these results should be interpreted carefully because of the high rates of discontinuation in the brimonidine group, the results suggested that brimonidine was relatively protective, possibly due to IOP-independent pathways.…”

Section: Treatmentmentioning

confidence: 99%

Normal-tension glaucoma: an update

Esporcatte¹,

Tavares²

2016

Arquivos Brasileiros De Oftalmologia

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However, several structural and functional differences support the fact that different mechanisms may have a stronger role in the pathogenesis of NTG versus high-pressure POAG. Also, a recent study reported genetic variants associated with different tendencies towards POAG with lower or higher IOP (6) . Furthermore, clinical impression and anecdotal evidence suggest that NTG with mean IOP in the high teens (>15 mmHg), in which circadian fluctuation and CCT could lead to a possible misdiagnosis of an IOP ≤21 mmHg, would differ from NTG with mean IOP in the low teens (≤15 mmHg), with different ABSTRACT Descritores: Glaucoma de ângulo aberto; Pressão in traocular; Doenças do nervo óptico; Anti-hipertensivos/uso terapêuticopathogenesis and progression patterns, harder to achieve target IOP, and higher incidence of disc hemorrhages. Nonetheless, a recent report does not support this assumption and underscores low-teens NTG as an important entity (7) . The proportion of NTG varies depending on different population studies. In Asian epidemiological protocols, NTG constituted the majority of open-angle glaucomas (52%-92%), depending on the country and study methodology (8) . Normal IOP was measured in 57.1% cases of POAG in a South African study (9) . In white populations, the proportion of NTG was lower than that observed in Asian and African populations. In studies conducted in the United States, Netherlands, and Italy, NTG presented proportions of 31. 7%, 38.9%, and 30%, respectively (10-12) . The etiology of NTG is most likely multifactorial and still not well defined. Moreover, several alternative treatments based on this different pathogenesis have been discussed. The objective of this study was to review the mechanisms involved in the onset and progression of NTG and the efficacy of established and alternative therapies for NTG treatment. PathogenesisThe pathogenesis of NTG is unclear, and perhaps the development of the disease is a consequence of a complex interaction of several systemic and ocular factors. Different studies have shown that the cardiovascular system and intracranial pressure may be involved in the main pathways of optic nerve damage. Nevertheless, the complex relationship between these mechanisms and glaucoma pro gression continues to be debated.

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A Randomized Trial of Brimonidine Versus Timolol in Preserving Visual Function: Results From the Low-pressure Glaucoma Treatment Study

Cited by 330 publications

References 51 publications

A Vascular Approach to Glaucoma

A Vascular Approach to Glaucoma

Brimonidine tartrate effect on retinal spreading depression depends on Müller cells

Normal-tension glaucoma: an update

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