Brimonidine for Autoregulation in Normal-Tension Glaucoma
Whether NTG is entirely different from primary open-angle glaucoma (POAG), or whether it is simply on a continuum of the same disease process, is under debate.
NTG is distinct from POAG in that intraocular pressure (IOP) in NTG is within normal limits or even on the lower end of the scale, even though elevated IOP is considered a prevalent risk factor for glaucomatous optic nerve damage. The visual field damage is frequently different in POAG, which is associated with paracentral visual field defects. Even the optic nerve suggests that NTG may be a unique entity, because optic disc hemorrhages are more common than in POAG. This certainly seems to support the theories and previous data suggesting that retinal vasculature dysregulation and instability are a factor in the pathophysiology of NTG.
What is not debated by glaucoma specialists is that treating NTG poses an exceptional challenge, because optic neuropathy commonly progresses even with excellent IOP control. Therefore, medications that alter not only IOP but also the underlying pathology may be better suited to the management of this subset of patients with glaucoma.
Correction of retinal blood flow instability may be the key to slowing progression of visual field defects, as demonstrated in the Low-Pressure Glaucoma Treatment Study. In that study, brimonidine was found to be superior to timolol in preserving visual fields after 3 years of treatment, but the mechanism was only hypothesized.
Feke and colleagues prospectively evaluated the effect of brimonidine 0.15% on retinal hemodynamics, as well as the short-term effects of the drug on visual function, to seek support for this hypothesis. In their nonrandomized trial, only patients with a maximum untreated IOP of less than 22 mm Hg were included, to keep the focus on NTG. Of note, only 50% of the recruited patients exhibited vascular dysregulation and continued in the study. Therefore, not all patients with NTG have hemodynamic instability; therefore, this cannot be the sole cause of optic neuropathy in the setting of a normal IOP. Other mechanisms leading to progressive visual field loss in this disease still need to be investigated.
The results of this study are promising in that most patients (14/17) demonstrated a return to normal blood flow dynamics with an 8-week course of brimonidine. The hope was that this would normalize ocular perfusion pressure, posing less chance of ganglion cell death from ischemic damage. Unfortunately, this study did not find that a reversal of vascular dysregulation translates to short-term improvement in visual function. Although this may be disappointing, long-term studies to assess the effect on visual fields need to be performed. There may be no reversal of visual field defects and damage, but even a halting of progression would be a boon for many patients.
Brimonidine may be superior to other IOP-lowering medications because it can not only lower the pressure but also provide an additional benefit to the subset of patients with vascular dysregulation. In a population whose visual fields are progressing despite low IOP, brimonidine may be an option for primary or adjuvant therapy.
Abstract
Viewpoint
Whether NTG is entirely different from primary open-angle glaucoma (POAG), or whether it is simply on a continuum of the same disease process, is under debate.
NTG is distinct from POAG in that intraocular pressure (IOP) in NTG is within normal limits or even on the lower end of the scale, even though elevated IOP is considered a prevalent risk factor for glaucomatous optic nerve damage. The visual field damage is frequently different in POAG, which is associated with paracentral visual field defects. Even the optic nerve suggests that NTG may be a unique entity, because optic disc hemorrhages are more common than in POAG. This certainly seems to support the theories and previous data suggesting that retinal vasculature dysregulation and instability are a factor in the pathophysiology of NTG.
What is not debated by glaucoma specialists is that treating NTG poses an exceptional challenge, because optic neuropathy commonly progresses even with excellent IOP control. Therefore, medications that alter not only IOP but also the underlying pathology may be better suited to the management of this subset of patients with glaucoma.
Correction of retinal blood flow instability may be the key to slowing progression of visual field defects, as demonstrated in the Low-Pressure Glaucoma Treatment Study. In that study, brimonidine was found to be superior to timolol in preserving visual fields after 3 years of treatment, but the mechanism was only hypothesized.
Feke and colleagues prospectively evaluated the effect of brimonidine 0.15% on retinal hemodynamics, as well as the short-term effects of the drug on visual function, to seek support for this hypothesis. In their nonrandomized trial, only patients with a maximum untreated IOP of less than 22 mm Hg were included, to keep the focus on NTG. Of note, only 50% of the recruited patients exhibited vascular dysregulation and continued in the study. Therefore, not all patients with NTG have hemodynamic instability; therefore, this cannot be the sole cause of optic neuropathy in the setting of a normal IOP. Other mechanisms leading to progressive visual field loss in this disease still need to be investigated.
The results of this study are promising in that most patients (14/17) demonstrated a return to normal blood flow dynamics with an 8-week course of brimonidine. The hope was that this would normalize ocular perfusion pressure, posing less chance of ganglion cell death from ischemic damage. Unfortunately, this study did not find that a reversal of vascular dysregulation translates to short-term improvement in visual function. Although this may be disappointing, long-term studies to assess the effect on visual fields need to be performed. There may be no reversal of visual field defects and damage, but even a halting of progression would be a boon for many patients.
Brimonidine may be superior to other IOP-lowering medications because it can not only lower the pressure but also provide an additional benefit to the subset of patients with vascular dysregulation. In a population whose visual fields are progressing despite low IOP, brimonidine may be an option for primary or adjuvant therapy.
Abstract
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