To compare the alpha2-adrenergic agonist brimonidine tartrate 0.2% to the beta-adrenergic antagonist timolol maleate 0.5% in preserving visual function in low-pressure glaucoma.
Randomized, double-masked, multicenter clinical trial.
Exclusion criteria included untreated intraocular pressure (IOP) >21 mm Hg, visual field mean deviation worse than -16 decibels, or contraindications to study medications. Both eyes received twice-daily monotherapy randomized in blocks of 7 (4 brimonidine to 3 timolol). Standard automated perimetry and tonometry were performed at 4-month intervals. Main outcome measure was field progression in either eye, defined as the same 3 or more points with a negative slope ≥-1 dB/year at P<5%, on 3 consecutive tests, assessed by pointwise linear regression. Secondary outcome measures were progression based on glaucoma change probability maps (GCPM) of pattern deviation and the 3-omitting method for pointwise linear regression.
Ninety-nine patients were randomized to brimonidine and 79 to timolol. Mean (± SE) months of follow-up for all patients was 30.0 ± 2. Statistically fewer brimonidine-treated patients (9, 9.1%) had visual field progression by pointwise linear regression than timolol-treated patients (31, 39.2%, log-rank 12.4, P=.001). Mean treated IOP was similar for brimonidine- and timolol-treated patients at all time points. More brimonidine-treated (28, 28.3%) than timolol-treated (9, 11.4%) patients discontinued study participation because of drug-related adverse events (P=.008). Similar differences in progression were observed when analyzed by GCPM and the 3-omitting method.
Low-pressure glaucoma patients treated with brimonidine 0.2% who do not develop ocular allergy are less likely to have field progression than patients treated with timolol 0.5%.
"y approved by the United States Food and Drug Administration for use in human patients with glaucoma ( Lee and McCluskey 2008 ) . A recent clinical trial of low - pressure human glaucoma patients demonstrated that brimonidine 0 . 2% prevented visual field loss in comparison to timolol 0 . 5% despite both agents decreasing IOP to a similar extent ( Krupin et al . 2011 ) . These results suggest that brimonidine 0 . 2% may have a neuroprotective effect in glaucoma in addition to decreasing IOP ( Pfeiffer et al . 2013 ) . While brimonidine ' s safety profile is excellent in rabbits , primates and man ( Arthur and Cantor 2011 ) , it significantly reduced heart rate and pupil size in Beagles with primary "
"Patients were randomly assigned to receive monotherapy with either topical brimonidine tartrate (0.2%) or timolol maleate (0.5%), and the visual field progression was studied. Visual field loss was preserved in patients treated with brimonidine despite similar IOP-lowering effect by the two drugs . These results are consistent with brimonidine's known neuroprotective properties of enhancing RGC survival and blocking axonal degeneration  . "
[Show abstract][Hide abstract] ABSTRACT: Glaucoma is a group of heterogeneous disorders involving progressive optic neuropathy that can culminate into visual impairment and irreversible blindness. Effective therapeutic interventions must address underlying vulnerability of retinal ganglion cells (RGCs) to degeneration in conjunction with correcting other associated risk factors (such as elevated intraocular pressure). However, realization of therapeutic outcomes is heavily dependent on suitable delivery system that can overcome myriads of anatomical and physiological barriers to intraocular drug delivery. Development of clinically viable sustained release systems in glaucoma is a widely recognized unmet need. In this regard, implantable delivery systems may relieve the burden of chronic drug administration while potentially ensuring high intraocular drug bioavailability. Presently there are no FDA-approved implantable drug delivery devices for glaucoma even though there are several ongoing clinical studies. The paper critically assessed the prospects of polymeric implantable delivery systems in glaucoma while identifying factors that can dictate (a) patient tolerability and acceptance, (b) drug stability and drug release profiles, (c) therapeutic efficacy, and (d) toxicity and biocompatibility. The information gathered could be useful in future research and development efforts on implantable delivery systems in glaucoma.
"Furthermore, we have recently demonstrated that the application of melatoninergic compounds reduces the IOP of rabbits with ocular hypertension induced by the Trendelenburg position (Martinez-Aguila et al., 2013). The neuroprotective action of brimonidine has been confirmed in experimental models of glaucoma and even in patients with low pressure glaucoma (Wheeler et al., 2003; Krupin et al., 2011; Pinar-Sueiro et al., 2011), and our results with a 2 -adrenergic receptor upregulation mediated mainly by 5-MCA-NAT seem to suggest a possible additional beneficial effect of this melatoninergic treatment. However, confirmation of 5-MCA- NAT neuroprotection and of its ocular hypotensive potentiating effect in glaucomatous animal models is necessary to increase confidence in the use of 5-MCA-NAT as a viable therapy for glaucoma. "
[Show abstract][Hide abstract] ABSTRACT: Melatonin is currently considered as a promising drug for glaucoma treatment due to its ocular hypotensive and neuroprotective effects. We have investigated the effect of melatonin and its analogue 5-methoxycarbonylamino-N-acetyltryptamine, 5-MCA-NAT, on β2/α2A-adrenergic receptor mRNA as well as protein expression in cultured rabbit non-pigmented ciliary epithelial cells. Quantitative PCR and immunocytochemical assays revealed a significant β2-adrenergic receptor down-regulation as well as α2A-adrenergic receptor up-regulation of treated cells (p<0.001, maximal significant effect). In addition, we have studied the effect of these drugs upon the ocular hypotensive action of a non-selective β-adrenergic receptor (timolol) and a selective α2-adrenergic receptor agonist (brimonidine) in normotensive rabbits. IOP experiments showed that the administration of timolol in rabbits pre-treated with melatonin or 5-MCA-NAT evoked an additional IOP reduction of 14.02 ± 5.8 % or 16.75 ± 5.48 % (p<0.01) in comparison with rabbits treated with timolol alone for 24 hours. Concerning brimonidine hypotensive action, an additional IOP reduction of 29.26 ± 5.21 % or 39.07 ± 5.81 % (p<0.001) was observed in rabbits pretreated with melatonin or 5-MCA-NAT when compared with animals treated with brimonidine alone for 24 hours. Additionally, a sustained potentiating effect of a single dose of 5-MCA-NAT was seen in rabbits treated with brimonidine once daily for up four days (extra IOP decrease of 15.57 ± 5.15%, p<0.05, compared to brimonidine alone). These data confirm the indirect action of melatoninergic compounds on adrenergic receptors and their remarkable effect upon the ocular hypotensive action mainly of α2-adrenergic receptor agonists but also of β-adrenergic antagonists.
Journal of Pharmacology and Experimental Therapeutics 04/2013; 346(1). DOI:10.1124/jpet.112.202036 · 3.97 Impact Factor
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