Dysfunction of axonal transport in normal-tension glaucoma: a biomarker of disease progression and a potential therapeutic target.
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ABSTRACT:
SUBMITTER: Hirooka K
PROVIDER: S-EPMC7996034 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
Dysfunction of axonal transport in normal-tension glaucoma: a biomarker of disease progression and a potential therapeutic target.
Hirooka Kazuyuki K Yamamoto Tohru T Kiuchi Yoshiaki Y
Neural regeneration research 20210301 3
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Project description:PurposeIdentify risk factors of progression in treated normal-tension glaucoma (NTG) in highly myopic and non-highly myopic eyes.MethodsThis retrospective, observational case series study included 42 highly myopic glaucoma (HMG, <-6D) eyes and 39 non-highly myopic glaucoma (NHG,≧-6D) eyes. Glaucoma progression was determined by serial visual field data. Univariate and multivariate logistic regression method were used to detect associations between potential risk factors and glaucoma progression.ResultsAmong 81 eyes from 81 normal-tension glaucoma patients (mean follow-up, 3.10 years), 20 of 42 eye (45.24%) in the HMG and 14 of 39 eyes (35.90%) in the NHG showed progression. The HMG group had larger optic disc tilt ratio (p = 0.007) and thinner inferior macular thickness (P = 0.03) than the NHG group. Changes in the linear regression values for MD for each group were as follows: -0.652 dB/year for the HMG and -0.717 dB/year for the NHG (P = 0.298). Basal pattern standard deviation (PSD) (OR: 1.55, p = 0.016) and post treatment IOP (OR = 1.54, p = 0.043) were risk factors for visual field progression in normal tension glaucoma patients. In subgroup analysis of HMG patients, PSD (OR: 2.77, p = 0.017) was a risk factor for visual field progression.ConclusionReduction IOP was postulated to be contributing in the prevention of visual field progression, especially in highly myopic NTG patients with large basal pattern standard deviation.
| S-EPMC10289344 | biostudies-literature
Project description:PurposeTo characterize the natural history of normal-tension glaucoma (NTG) in Chinese patients.MethodsThe prospective observational cohort study included patients with untreated NTG with a minimum follow-up of 2 years. Functional progression was defined by visual field (VF) deterioration, while structural progression was characterized by thinning of the retinal nerve fiber layer (RNFL) or ganglion cell inner plexiform layer (GCIPL).ResultsAmong 84 participants (mean age, 60.5 years; mean deviation, -5.01 decibels [dB]) with newly diagnosed NTG followed for an average of 69.7 months, 63.1% progressed during the observation period. Specifically, 29.8% progressed by VF, and 48.8% progressed by either RNFL or GCIPL. In Cox proportional hazards analysis, disc hemorrhage (hazard ratio [HR], 2.82; 95% confidence interval [CI], 1.48-5.35), female gender (HR, 1.98; 95% CI, 1.08-3.62), and mean IOP during the follow-up period (HR, 1.14 per mm Hg; 95% CI, 1.00-1.31) were significant predictors of glaucomatous progression. Additionally, longer axial length (AL; HR, 0.57 per millimeter; 95% CI, 0.35-0.94) was protective against VF progression faster than -0.50 dB/y, and higher minimum diastolic blood pressure (DBP; HR, 0.96 per mm Hg; 95% CI, 0.92-1.00) was protective against structural progression.ConclusionsNearly two-thirds of untreated Chinese patients with NTG progressed over an average follow-up of 70 months by VF, RNFL, or GCIPL. Disc hemorrhage, female gender, higher mean IOP, shorter AL, and lower minimum DBP were significant predictors for disease progression.
| S-EPMC10959195 | biostudies-literature
Project description:ObjectivesTo investigate differences in progression patterns of normal-tension glaucoma (NTG) patients in three clusters classified by hierarchical cluster analysis (HCA).Materials and methodsIn a retrospective study, 200 eyes of NTG patients classified by HCA in 2015 who were followed up to the current date were evaluated. Peripapillary retinal nerve fibre layer (RNFL) thicknesses were measured by Cirrus HD-OCT and progression rate was calculated by trend analysis (Guided Progression Analysis [GPA]). VF progression rate was evaluated by linear regression analysis of mean deviation (MD). Progression patterns of three clusters were compared by histograms.ResultsIn total, 153 eyes of 153 patients were followed up. Mean observation period was 5 years. RNFL reduction rate was -0.83 μm/year in cluster 1, which showed early glaucomatous damage in previous reports; -0.45 μm/year in cluster 2, which showed moderate glaucomatous damage; and -0.36 μm/year in cluster 3, which showed young and myopic glaucomatous damage. The progression pattern of cluster 3 showed a double-peak distribution; RNFL reduction rate was 0.11 μm/year in the non-progressive group and -1.07 μm/year in the progressive group.ConclusionThe progression patterns were different among three NTG groups that were divided by HCA. In particular, the group of young and myopic eyes showed a mixture of two different patterns.
| S-EPMC8027441 | biostudies-literature
Project description:Glaucoma is a neurodegenerative disease of the eye, which involves degeneration of retinal ganglion cells (RGCs): the output neurons of the retina to the brain, which with their axons comprise the optic nerve. Recent studies have shown the possible involvement of oxidative stress in the pathogenesis of glaucoma, especially in the subtype of normal tension glaucoma. Basic experiments utilizing rodent and primate models of glaucoma revealed that antioxidants protect RGCs under various pathological conditions including glutamate neurotoxicity and optic nerve injury. These results suggested that existing drugs and food factors may be useful for prevention and hence therapy of glaucoma. In this review, we highlight some therapeutic candidates, particularly those with antioxidant properties, and discuss the therapeutic potential of RGC protection by modulating gene expressions that prevent and ameliorate glaucoma.
| S-EPMC7554707 | biostudies-literature
Project description:PurposeTo identify sectors of the optical coherence tomography (OCT) macular map that could be used to effectively assess structural progression in patients with normal-tension glaucoma (NTG).MethodsThis study examined 117 eyes of 117 NTG patients to establish axonal tract-dependent macular sectors, and also examined a separate group of 122 eyes of 81 NTG patients to evaluate the ability of these sectors to reveal glaucoma progression. Longitudinal data, including macular maps from at least 5 OCT examinations performed over at least 2 years, was available for all patients in this group. Circumpapillary retinal nerve fiber layer thickness (cpRNFLT), temporal clockwise sector scans (from 7 to 11 o'clock), macular retinal nerve fiber layer thickness (mRNFLT), and macular ganglion cell layer plus inner plexiform layer thickness (mGCIPLT) were measured with spectral-domain OCT (3D OCT-2000, TOPCON). The axonal tract-dependent macular sectors were identified by calculating Spearman's rank correlation coefficient for each point on a grid overlaid on the macular map and cpRNFLT in each clockwise scan sector. Trend and event analyses for the slope of progression in each sector and macular map were performed. Visual field progression in the macula was defined by the presence of more than 2 progressive test points in the 16 central test points of the Humphrey field analyzer SITA standard 24-2 program, evaluated with Progressor software.ResultsThe slope of progression in the entire macular area was -0.22 ± 0.58 μm/year for mRNFLT and -0.35 ± 0.52 μm/year for mGCIPLT. The fastest-progressing mRNFLT sector (-1.00 ± 0.84 μm/year, p < 0.001) and mGCIPLT sector (-1.16 ± 0.63 μm/year, p < 0.001) progressed significantly faster than the overall macula. Classifying patients according to visual field progression showed that baseline mRNFLT in the inferior hemifield, 7 and 8 o'clock sectors, as well as baseline mGCIPLT in the overall macular map, inferior hemifield, and 8 o'clock sector, were significantly lower in progressors (22 eyes) than non-progressors (100 eyes). There were significant differences in mRNFLT slope in 8 o'clock sector and in the fastest progressing sector in progressors and non-progressors, but mGCIPLT did not differ, even in the fastest-progressing sector. Event analysis showed that progression occurred most frequently in inferior mRNFLT and superior mGCIPLT in this study.ConclusionAxonal tract-dependent OCT macular sectors could effectively reveal structural change in patients with NTG. Furthermore, mRNFLT slope was consistent with visual field progression. This method promises to open new avenues for the OCT-based evaluation of glaucoma progression.
| S-EPMC5626427 | biostudies-literature
Project description:PurposeTo compare forecasted changes in mean deviation (MD) for patients with normal-tension glaucoma (NTG) and high-tension open-angle glaucoma (HTG) at different target intraocular pressures (IOPs) using Kalman filtering, a machine learning technique.DesignRetrospective cohort study.ParticipantsFrom the Collaborative Initial Glaucoma Treatment Study or Advanced Glaucoma Intervention Study, 496 patients with HTG; from Japan, 262 patients with NTG.MethodsUsing the first 5 sets of tonometry and perimetry measurements, each patient was classified as a fast progressor, slow progressor, or nonprogressor. Using Kalman filtering, personalized forecasts of MD changes over 2.5 years' follow-up were generated for fast and slow progressors with HTG and NTG with IOPs maintained at hypothetical IOP targets of 9 to 21 mmHg. Future MD loss with different percentage IOP reductions from baseline (0%-50%) were also assessed for the groups.Main outcome measuresMean forecasted MD change at different target IOPs.ResultsThe mean (± standard deviation) patient age was 63.5 ± 10.5 years for NTG and 66.5 ± 10.9 years for HTG. Over the 2.5-year follow-up, at target IOPs of 9, 15, and 21 mmHg, respectively, the mean forecasted MD losses for fast progressors with NTG were 2.3 ± 0.2, 4.0 ± 0.2, and 5.7 ± 0.2 dB; for slow progressors with NTG, losses were 0.63 ± 0.02, 1.02 ± 0.03, and 1.49 ± 0.07 dB; for fast progressors with HTG, losses were 1.8 ± 0.1, 3.4 ± 0.1, and 5.1 ± 0.1 dB; and for slow progressors with HTG, losses were 0.55 ± 0.06, 1.04 ± 0.08, and 1.59 ± 0.10 dB. Fast progressors with NTG had greater MD decline than fast progressors with HTG at each target IOP (P ≤ 0.007 for all). The MD decline for slow progressors with HTG and NTG were similar (P ≥ 0.24 for all target IOPs). Fast progressors with HTG had greater MD loss than those with NTG with 0%-10% IOP reduction since baseline (P ≤ 0.01 for all), but not 25% (P = 0.07) or 50% (P = 0.76) reduction since baseline.ConclusionsMachine learning algorithms using Kalman filtering techniques demonstrate promise at forecasting future MD values at different target IOPs for patients with NTG and HTG.
| S-EPMC7965784 | biostudies-literature
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:A single-center prospective cohort study was conducted to investigate whether intraocular pressure (IOP)-related 24-h contact lens sensor (CLS) profile parameters can help predict glaucoma progression in patients with normal-tension glaucoma (NTG). CLS measurements (Triggerfish; SENSIMED, Etagnières, Switzerland) at baseline without medication were performed for 24 h in one eye, following diurnal IOP measurements using Goldmann applanation tonometry at 3-h intervals. Glaucoma progression during the follow-up period of ≥ 2 years was determined based on the Guided Progression Analysis of Humphrey visual fields and/or structural progression using fundus photographs. Among 79 patients (mean values: follow-up periods, 48.1 months; age, 51.5 years; baseline IOP, 14.0 mmHg; mean deviation, - 6.04 dB), 23 showed glaucoma progression. A smaller standard deviation of nocturnal ocular pulse amplitude in the CLS profile, a larger range of diurnal IOP at baseline, and the presence of optic disc hemorrhage (DH) during the study period were significant risk factors for glaucoma progression in the multivariate Cox proportional hazards model (hazard ratio, 0.30/mVeq, 1.23/mmHg, and 4.37/presence of DH; P = 0.016, 0.017, and 0.001, respectively). CLS measurements may be useful for assessing the risk of future glaucoma progression in patients with NTG, providing supplementary information to routine IOP measurements.
| S-EPMC11405842 | biostudies-literature
Project description:An objective method to predict individual visual field progression will contribute to realise personalised medication. The purpose of this study was to establish a predictive formula for glaucomatous visual field progression in patients with Primary open-angle glaucoma, mainly including normal tension glaucoma. This study was a large-scale, longitudinal and retrospective study including 498 eyes of 312 patients visiting from June 2009 to May 2015. In this analysis, 191 eyes of 191 patients meeting all eligible criteria were used. A predictive formula to calculate the rate of glaucomatous visual field progression (mean deviation slope) was obtained through multivariate linear regression analysis by adopting "Angle of Retinal Nerve Fibre Layer Defect" at the baseline, "Vertical Cup-Disc ratio" at the baseline, "Presence or absence of Disc Haemorrhage" during the follow-up period, and "Mean IOP change (%)" during the follow-up period as predictors. Coefficient of determination of the formula was 0.20. The discriminative ability of the formula was evaluated as moderate performance using receiver operating characteristic analysis, and the area under the curve was approximately 0.75 at all cut-off values. Internal validity was confirmed by bootstrapping. The predictive formula established by this type of approach might be useful for personalised medication.
| S-EPMC5678075 | biostudies-literature
Project description:ImportanceNormal-tension glaucoma (NTG) is a common cause of vision loss.ObjectiveTo 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).Design, setting, and participantsIn 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).Main outcomes and measuresDetection 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.ResultsA 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.Conclusions and relevanceDuplication 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