Abstract:ABSTRACT.Purpose: To investigate whether the amount of intraocular pressure (IOP) reduction with topical medications is associated with the progression of normal-tension glaucoma (NTG) and to identify risk factors for NTG progression. Methods: The medical records of 121 eyes of 121 NTG patients, who were treated with topical medications for more than 7 years, were reviewed. NTG progression was defined by either structural (optic disc or retinal nerve fibre layer) or functional (visual field) deterioration. Pat… Show more
“…The hallmark feature of glaucoma is damage and loss of retinal ganglion cells (RGCs), the neurons that connect the eyes to the brain (Quigley, 1999;Weinreb and Khaw, 2004;Casson et al, 2012). Glaucoma is often associated with elevated intraocular pressure (IOP;Sommer, 1989;Peters et al, 2014) and pressure-lowering agents can be effective in slowing RGC loss (Morrison et al, 1998;Heijl et al, 2002;Kass et al, 2002;Lichter, 2002;Kim et al, 2013). Even with pressurelowering drugs, however, RGCs eventually die.…”
Retinal ganglion cell (RGC) loss is a hallmark of glaucoma and the second leading cause of blindness worldwide. The type and timing of cellular changes leading to RGC loss in glaucoma remain incompletely understood, including whether specific RGC subtypes are preferentially impacted at early stages of this disease. Here we applied the microbead occlusion model of glaucoma to different transgenic mouse lines, each expressing green fluorescent protein in 1-2 specific RGC subtypes. Targeted filling, reconstruction, and subsequent comparison of the genetically identified RGCs in control and bead-injected eyes revealed that some subtypes undergo significant dendritic rearrangements as early as 7 d following induction of elevated intraocular pressure (IOP). By comparing specific On-type, On-Offtype and Off-type RGCs, we found that RGCs that target the majority of their dendritic arbors to the scleral half or "Off" sublamina of the inner plexiform layer (IPL) undergo the greatest changes, whereas RGCs with the majority of their dendrites in the On sublamina did not alter their structure at this time point. Moreover, M1 intrinsically photosensitive RGCs, which functionally are On RGCs but structurally stratify their dendrites in the Off sublamina of the IPL, also underwent significant changes in dendritic structure 1 week after elevated IOP. Thus, our findings reveal that certain RGC subtypes manifest significant changes in dendritic structure after very brief exposure to elevated IOP. The observation that RGCs stratifying most of their dendrites in the Off sublamina are first to alter their structure may inform the development of new strategies to detect, monitor, and treat glaucoma in humans.
“…The hallmark feature of glaucoma is damage and loss of retinal ganglion cells (RGCs), the neurons that connect the eyes to the brain (Quigley, 1999;Weinreb and Khaw, 2004;Casson et al, 2012). Glaucoma is often associated with elevated intraocular pressure (IOP;Sommer, 1989;Peters et al, 2014) and pressure-lowering agents can be effective in slowing RGC loss (Morrison et al, 1998;Heijl et al, 2002;Kass et al, 2002;Lichter, 2002;Kim et al, 2013). Even with pressurelowering drugs, however, RGCs eventually die.…”
Retinal ganglion cell (RGC) loss is a hallmark of glaucoma and the second leading cause of blindness worldwide. The type and timing of cellular changes leading to RGC loss in glaucoma remain incompletely understood, including whether specific RGC subtypes are preferentially impacted at early stages of this disease. Here we applied the microbead occlusion model of glaucoma to different transgenic mouse lines, each expressing green fluorescent protein in 1-2 specific RGC subtypes. Targeted filling, reconstruction, and subsequent comparison of the genetically identified RGCs in control and bead-injected eyes revealed that some subtypes undergo significant dendritic rearrangements as early as 7 d following induction of elevated intraocular pressure (IOP). By comparing specific On-type, On-Offtype and Off-type RGCs, we found that RGCs that target the majority of their dendritic arbors to the scleral half or "Off" sublamina of the inner plexiform layer (IPL) undergo the greatest changes, whereas RGCs with the majority of their dendrites in the On sublamina did not alter their structure at this time point. Moreover, M1 intrinsically photosensitive RGCs, which functionally are On RGCs but structurally stratify their dendrites in the Off sublamina of the IPL, also underwent significant changes in dendritic structure 1 week after elevated IOP. Thus, our findings reveal that certain RGC subtypes manifest significant changes in dendritic structure after very brief exposure to elevated IOP. The observation that RGCs stratifying most of their dendrites in the Off sublamina are first to alter their structure may inform the development of new strategies to detect, monitor, and treat glaucoma in humans.
“…With regard to IOP-related parameters in NTG patients, insufficient IOP reduction 36,38,113 and large IOP fluctuation 39 were found to be significant risk factors for progression. Therefore, major therapeutic goals for NTG patients include achievement of a large extent of IOP reduction and maintenance of low and stable IOP.…”
Section: Monitoring Of Structural and Functional Progressionmentioning
confidence: 99%
“…33 Such findings were also seen in NTG patients similar to POAG patients, indicating that hyperbaric damage also plays a role even in eyes within the IOP reference range. 34 Based on the multitude of epidemiologic studies (conducted in populations with large NTG proportions) reporting high IOP as a common risk factor 15,16,22,35 and longitudinal studies reporting clinical treatment outcomes in NTG patients, [36][37][38][39] it can be concluded that there is a protective effect of IOP-lowering treatment for NTG patients. Moreover, despite NTG patients having IOP within the reference range, epidemiological data have confirmed significantly higher IOPs than those of control subjects.…”
Section: Iop-dependent Mechanismsmentioning
confidence: 99%
“…[37][38][39][120][121][122] Despite lingering questions on whether disc hemorrhage is an indicator of progression or a risk factor for progression, there is no doubt that it has a significant impact on glaucoma progression.…”
Section: Monitoring Of Structural and Functional Progressionmentioning
Glaucoma is a leading cause of blindness worldwide. Normal-tension glaucoma (NTG) is a type of open-angle glaucoma with intraocular pressure measurements always 21 mm Hg or less. A controversy surrounding NTG is the question of whether it should be regarded as a disease within the spectrum of primary open-angle glaucoma or as a distinctive disease entity. Nonetheless, NTG does have distinctive features compared with primary open-angle glaucoma: intraocular pressure-independent risk factors for development of NTG, characteristic patterns of structural and functional damage, and a unique disease course. This review provides an overview and update on the current issues surrounding the prevalence, etiology, diagnosis, and monitoring of NTG.
“…Despite the low IOP after treatment, approximately 50% of patients with NTG had VF damage progression as detected by perimetry (120,121) . It is possible that patients with this condition have a lower threshold for IOP mechanical injury than those with other glaucoma phenotypes and that more substantial IOP reduction is often necessary compared with the one achieved with topical medications or trabeculoplasty.…”
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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