Bilateral normal tension glaucoma: Can this be nutritional?
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ABSTRACT:
SUBMITTER: Senthil S
PROVIDER: S-EPMC5549421 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:Normal-tension glaucoma (NTG) is a multifactorial optic neuropathy which, similar to open-angle glaucomas, is characterized by progressive retinal ganglion cell death and glaucomatous visual field loss. The major distinction of NTG from open-angle glaucomas is that the intraocular pressure (IOP) does not exceed the normal range. Missing the major risk factor and target of therapy, the elevated IOP, NTG poses a clinical challenge. Several insightful reviews have been published on the pathophysiology of NTG describing the possible underlying mechanisms. The current literature available also suggests that a significant percentage of patients with NTG (as high as 21%) have a family history of glaucoma, indicating a genetic predisposition to the disease. These facts strengthen the indication that NTG remains an enigmatic process. The aim of this review was to summarize the vascular, mechanical and genetic components considered to be responsible for NTG development and to discuss the mechanisms through which they are involved in the pathogenesis of NTG.
| S-EPMC6307418 | biostudies-literature
Project description:Normal-tension glaucoma (NTG) is a common cause of vision loss.To investigate the role of TANK binding kinase 1 (TBK1) gene duplications in NTG to gain insights into the causes of glaucoma that occurs at low intraocular pressure (IOP).In this multicenter case-control study, we investigated patients who met the criteria for NTG, including glaucomatous optic neuropathy, visual field defects, and maximum recorded untreated IOP of 21 mm Hg or less, and matched controls. Participants (N?=?755) were recruited from Southampton, United Kingdom (180 patients and 178 controls), Rochester, Minnesota (65 patients and 12 controls), New York, New York (96 patients and 16 controls), and Iowa City, Iowa (208 controls).Detection of TBK1 gene duplications and comparison of the extent of the identified DNA that is duplicated with prior TBK1 copy number variations associated with NTG.A TBK1 gene duplication was detected in 1 of 96 patients (1.0%) from New York and none of the controls. Analysis of duplication borders with comparative genome hybridization demonstrated that this patient has a novel duplication that has not been previously reported. No gene duplications were detected in any of the other cohorts of patients or controls.Duplication of the TBK1 gene is a rare cause of NTG. The identification of another case of NTG attributed to TBK1 gene duplication strengthens the case that this mutation causes glaucoma.
| S-EPMC4372533 | biostudies-literature
Project description:Importance:Mutations in the myocilin (MYOC) gene are the most common molecularly defined cause of primary open-angle glaucoma that typically occurs in patients with high intraocular pressures (IOP). One MYOC mutation, p.Gln368Ter, has been associated with as many as 1.6% of primary open-angle glaucoma cases that had a mean maximum recorded IOP of 30 mm Hg. However, to our knowledge, the role of the p.Gln368Ter mutation in patients with normal-tension glaucoma (NTG) with an IOP of 21 mm Hg or lower has not been investigated. Objective:To evaluate the role of the p.Gln368Ter MYOC mutation in patients with NTG. Design, Setting, and Participants:In this case-control study of the prevalence of the p.Gln368Ter mutation in patients with NTG, cohort 1 was composed of 772 patients with NTG and 2152 controls from the United States (Iowa, Minnesota, and New York) and England and cohort 2 was composed of 561 patients with NTG and 2606 controls from the Massachusetts Eye and Ear Infirmary and the NEIGHBORHOOD consortium. Genotyping was conducted using real-time polymerase chain reaction that was confirmed with Sanger sequencing, the imputation of genome-wide association study data, or an analysis of whole-exome sequence data. Data analysis occurred between April 2007 and April 2018. Main Outcomes and Measures:Comparison of the frequency of the p.Gln368Ter MYOC mutation between NTG cases and controls with the Fisher exact test. Results:Of 6091 total participants, 3346 (54.9%) were women and 5799 (95.2%) were white. We detected the p.Gln368Ter mutation in 7 of 772 patients with NTG (0.91%) and 7 of 2152 controls (0.33%) in cohort 1 (P = .03). In cohort 2, we detected the p.Gln368Ter mutation in 4 of 561 patients with NTG (0.71%) and 10 of 2606 controls (0.38%; P = .15). When the cohorts were analyzed as a group, the p.Gln368Ter mutation was associated with NTG (odds ratio, 2.3; 95% CI, 0.98-5.3; P = .04). Conclusions and Relevance:In cohorts 1 and 2, the p.Gln368Ter mutation in MYOC was found in patients with IOPs that were 21 mm Hg or lower (NTG), although at a frequency that is lower than previously detected in patients with higher IOP. These data suggest that the p.Gln368Ter mutation may be associated with glaucoma in patients with normal IOPs as well as in patients with IOPs that are greater than 21 mm Hg.
| S-EPMC6512256 | biostudies-literature
Project description:Although primary open-angle glaucoma (OAG) generally occurs in older individuals and manifests in eyes with elevated intraocular pressure (IOP), it may also occur in young patients or in eyes with an IOP that always measures within the statistically normal range. Recent advances in optical coherence tomography angiography have enabled noninvasive visualization of the vasculature around the optic disc. In this study, we investigated the clinical features of young Korean patients with OAG and compared the peripapillary vessel density of patients with normal-tension glaucoma (NTG) to those with high-tension glaucoma (HTG). The peripapillary vessel density was reduced in eyes with HTG compared with that in normal subjects (HTG: 23.18?±?2.06% vs. normal subjects: 24.74?±?1.88%, P value?=?0.013). In contrast, the peripapillary vessel density of eyes with NTG was comparable with that of normal eyes (NTG: 23.98?±?2.30% vs. normal subjects: 24.74?±?1.88%, P value?=?0.505). These findings suggest that young patients with HTG show greater peripapillary microvascular attenuation than healthy subjects or young patients with NTG, indicating that different levels of the initial untreated IOP may have different effects on the peripapillary vessel density in young patients with OAG.
| S-EPMC6914787 | biostudies-literature
Project description:Duplication of the TBK1 gene is associated with 1-2% of normal tension glaucoma, a common cause of vision loss and blindness that occurs without grossly abnormal intraocular pressure. We generated a transgenic mouse that has one copy of the human TBK1 gene (native promoter and gene structure) incorporated into the mouse genome (Tg-TBK1). Expression of the TBK1 transgene in the retinae of these mice was demonstrated by real-time PCR. Using immunohistochemistry TBK1 protein was predominantly localized to the ganglion cell layer of the retina, the cell type most affected by glaucoma. More intense TBK1 labelling was detected in the retinal ganglion cells (RGCs) of Tg-TBK1 mice than in wild-type littermates. Tg-TBK1 mice exhibit the cardinal sign of glaucoma, a progressive loss of RGCs. Hemizygous Tg-TBK1 mice (with one TBK1 transgene per genome) had a 13% loss of RGCs by 18 months of age (P?=?1.5 × 10-8). Homozygous Tg-TBK1 mice had 7.6% fewer RGCs than hemizygous Tg-TBK1 mice and 20% fewer RGCs than wild-type mice (P?=?1.9 × 10-5) at 6 months of age. No difference in intraocular pressures was detected between Tg-TBK1 mice and wild-type littermates as they aged (P?>?0.05). Tg-TBK1 mice with extra doses of the TBK1 gene recapitulate the phenotype of normal tension glaucoma in human patients with a TBK1 gene duplication. Together, these studies confirm the pathogenicity of the TBK1 gene duplication in human glaucoma and suggest that excess production of TBK1 kinase may have a role in the pathology of glaucoma.
| S-EPMC6075615 | biostudies-literature
Project description:ObjectivesTo evaluate the association between serum retinol concentration and normal-tension glaucoma (NTG).MethodsA total of 345 study subjects were recruited in a prospective cross-sectional study: 101 patients with NTG, 106 patients with high-pressure primary open-angle glaucoma (POAG) and 138 healthy control subjects. Serum retinol concentration in fasting blood samples was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). All study subjects were given complete ophthalmic examinations and diagnosed by two glaucoma sub-specialists.ResultsSerum retinol concentrations in NTG, POAG, and controls were 338.90 ± 103.23 ng/mL, 405.22 ± 114.12 ng/mL, and 408.84 ± 122.36 ng/mL respectively. NTG patients had lower serum retinol concentrations than POAG (p < 0.001) or healthy controls (p < 0.001). There was no statistical difference between the POAG and healthy controls (p = 0.780). Higher proportion of NTG patients (37.6%) than POAG (17.9%) or controls (21.7%) had serum retinol concentrations lower than 300 ng/mL. Serum retinol was positively correlated with optic nerve sheath diameter (ONSD) (r = 0.349, p = 0.001) in glaucoma patients and not associated with any other demographic features or ophthalmic biometric parameters in the NTG patients. Multivariate logistic regression showed that serum retinol (OR = 0.898, 95CI%: 0.851-0.947) was associated with incident NTG.ConclusionsNTG patients had lower serum retinol concentrations. Serum retinol uniquely associated with NTG makes it a new potential option for the diagnosis and treatment of the disease.
| S-EPMC9391421 | biostudies-literature
Project description:Besides intraocular pressure, vascular factors play a role in the pathogenesis of glaucomatous optic neuropathy. One of these potential vascular factors is Flammer syndrome. The purpose of the present study was to determine in a Korean population whether signs and symptoms of Flammer syndrome occur more often in normal tension glaucoma patients than in control subjects.Two hundred forty-six normal tension glaucoma patients and 1116 control subjects responded to a multiple-choice questionnaire asking about 15 signs and symptoms of Flammer syndrome.Seven of the 15 signs and symptoms of Flammer syndrome (increased drug sensitivity, good smell perception, reversible skin blotches, tinnitus, long sleep onset time, tendency to perfectionism, and cold hands/feet) were significantly more often positive in normal tension glaucoma patients than in controls. Six additional signs and symptoms (migraines, low blood pressure, headaches, dizziness, increased pain sensation, and feeling cold) also occurred more often, but did not reach statistical significance. Only two items (low body weight and reduced feeling of thirst) were more frequently (not significant) positive in the controls.There is an association between normal tension glaucoma and Flammer syndrome. If future studies confirm this relationship, treatment of Flammer syndrome may help to prevent normal tension glaucoma or to slow down its progression.
| S-EPMC5486531 | biostudies-other
Project description:PurposeTo investigate whether the position of the central retinal vascular trunk (CRVT), as a surrogate of lamina cribrosa (LC) offset, was associated with the presence of glaucoma in normal-tension glaucoma (NTG) patients.MethodsThe position of the CRVT was measured as the deviation from the center of the Bruch's membrane opening (BMO), as delineated by spectral-domain optical coherence tomography imaging. The offset index was calculated as the distance of the CRVT from the BMO center relative to that of the BMO margin. The angular deviation of CRVT was measured with the horizontal nasal midline as 0° and the superior location as a positive value. The offset index and angular deviation were compared between glaucoma and fellow control eyes within individuals.ResultsNTG eyes had higher baseline intraocular pressure (P = 0.001), a larger β-zone parapapillary atrophy area (P = 0.013), and a larger offset index (P<0.001). In a generalized linear mixed-effects model, larger offset index was the only risk factor of NTG diagnosis (OR = 31.625, P<0.001). A generalized estimating equation regression model revealed that the offset index was larger in the NTG eyes than in the control eyes for all ranges of axial length, while it was the smallest for the axial length of 23.4 mm (all P<0.001).ConclusionsThe offset index was larger in the unilateral NTG eyes, which fact is suggestive of the potential role of LC/BMO offset as a loco-regional susceptibility factor.
| S-EPMC8291707 | biostudies-literature
Project description:Normal-tension glaucoma (NTG) is a heterogeneous disease characterized by retinal ganglion cell (RGC) death leading to cupping of the optic nerve head and visual field loss at normal intraocular pressure (IOP). The pathogenesis of NTG remains unclear. Here, we describe a single nucleotide mutation in exon 2 of the methyltransferase-like 23 (METTL23) gene identified in 3 generations of a Japanese family with NTG. This mutation caused METTL23 mRNA aberrant splicing, which abolished normal protein production and altered subcellular localization. Mettl23-knock-in (Mettl23+/G and Mettl23G/G) and -knockout (Mettl23+/- and Mettl23-/-) mice developed a glaucoma phenotype without elevated IOP. METTL23 is a histone arginine methyltransferase expressed in murine and macaque RGCs. However, the novel mutation reduced METTL23 expression in RGCs of Mettl23G/G mice, which recapitulated both clinical and biological phenotypes. Moreover, our findings demonstrated that METTL23 catalyzed the dimethylation of H3R17 in the retina and was required for the transcription of pS2, an estrogen receptor α target gene that was critical for RGC homeostasis through the negative regulation of NF-κB-mediated TNF-α and IL-1β feedback. These findings suggest an etiologic role of METTL23 in NTG with tissue-specific pathology.
| S-EPMC9621137 | biostudies-literature
Project description: Not available
| S-EPMC9829667 | biostudies-literature