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AimsTo compare the baseline clinical characteristics and patterns of visual field defects between high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) in the Laser in Glaucoma and Ocular Hypertension (LiGHT) China subjects.MethodsAll patients (n=622) were recruited at Zhongshan Ophthalmic Center from 2015 to 2019. 1105 open-angle glaucoma eyes of 622 patients were classified as NTG (n=559) and HTG eyes (n=546) according to the baseline intraocular pressure (IOP) of 21 mm Hg. The mean deviation (MD), regional MD of the Glaucoma Hemifield Test regions and regional difference values were calculated. Daytime phasing IOP was recorded at 8:00, 10:00, 11:30, 14:30 and 17:00 hour. Multiple regression analyses were conducted for each regional difference.ResultsPatients with NTG were older, more likely to be female, hypertensive and suffer ischaemic heart disease than patients with HTG (p<0.05 for all comparisons). HTG showed higher mean daytime phasing IOP and higher daytime fluctuations than NTG (p<0.001 for all comparisons). HTG and NTG showed similar MD overall (p=0.665). NTG showed significantly greater hemifield asymmetry than HTG. The two arcuate regional differences in NTG were significantly associated with daytime IOP fluctuations (p<0.01 in both regions).ConclusionsIn the LiGHT China trial, NTG and HTG showed similar visual field defects severity at enrolment. However, NTG showed more severe hemifield asymmetry compared with HTG, and higher short-time IOP fluctuations might exacerbate this asymmetry in NTG.

To investigate optic disc perfusion differences in normal, primary open-angle glaucoma (POAG), and normal tension glaucoma (NTG) eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique. Cross-sectional, observational study. Twenty-eight normal, 30 POAG, and 31 NTG subjects. One eye from each subject was scanned with a 68 kHz Cirrus HD-OCT 5,000-based OMAG prototype system centered at the optic nerve head (ONH) (Carl Zeiss Meditec Inc, Dublin, CA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program. Optic disc perfusion, quantified as flux, vessel area density, and normalized flux (flux normalized by the vessel area) within the ONH. Glaucomatous eyes had significantly lower optic disc perfusion in preLC in all three perfusion metrics (p<0.0001) compared to normal eyes. The visual field (VF) mean deviation (MD) and pattern standard deviation (PSD) were similar between the POAG and NTG groups, and no differences in optic disc perfusion were observed between POAG and NTG. Univariate analysis revealed significant correlation between optic disc perfusion and VF MD, VF PSD, and rim area in both POAG and NTG groups (p≤0.0288). However, normalized optic disc perfusion was correlated with some structural measures (retinal nerve fiber layer thickness and ONH cup/disc ratio) only in POAG eyes. Optic disc perfusion detected with OMAG was significantly reduced in POAG and NTG groups compared to normal controls, but no difference was seen between POAG and NTG groups with similar levels of VF damage. Disc perfusion was significantly correlated with VF MD, VF PSD, and rim area in glaucomatous eyes. Vascular changes at the optic disc as measured using OMAG may provide useful information for diagnosis and monitoring of glaucoma.

Normal tension glaucoma (NTG) is an exception in the “glaucoma family” where the major risk factor, increased intraocular pressure, is missing. If not increased intraocular pressure, then what other causes can then lead to glaucomatous optic disc change and visual field loss in NTG? Several possibilities will be discussed. Among them a higher sensitivity to normal pressure, vascular dysregulation, an abnormally high translaminar pressure gradient and a neurodegenerative process due to impaired cerebrospinal fluid dynamics in the optic nerve sheath compartment. There are many excellent review papers published on normal tension glaucoma (NTG). The aim of this paper is therefore not to add another extensive review on NTG but rather to focus on and to discuss some possible mechanisms that are thought to be involved in the pathophysiology of NTG and to discuss the stronger and weaker aspects of each concept. The fact that several concepts exist suggests that NTG is still not very well understood and that no single mechanism on its own might adequately explain NTG.

Background/AimsTo compare intraocular pressure (IOP) measurements using a prototype smartphone tonometer with other tonometers used in clinical practice.MethodsPatients from an academic glaucoma practice were recruited. The smartphone tonometer uses fixed force applanation and in conjunction with a machine-learning computer algorithm is able to calculate the IOP. IOP was also measured using Goldmann applanation tonometry (GAT) in all subjects. A subset of patients were also measured using ICare, pneumotonometry (upright and supine positions) and Tono-Pen (upright and supine positions) and the results were compared.Results92 eyes of 81 subjects were successfully measured. The mean difference (in mm Hg) for IOP measurements of the smartphone tonometer versus other devices was +0.24 mm Hg for GAT, −1.39 mm Hg for ICare, −3.71 mm Hg for pneumotonometry and −1.30 mm Hg for Tono-Pen. The 95% limits of agreement for the smartphone tonometer versus other devices was −4.35 to 4.83 mm Hg for GAT, −6.48 to 3.70 mm Hg for ICare, −7.66 to −0.15 mm Hg for pneumotonometry and −5.72 to 3.12 mm Hg for Tono-Pen. Overall, the smartphone tonometer results correlated best with GAT (R2=0.67, p<0.001). Of the 92 videos, 90 (97.8%) were within ±5 mm Hg of GAT and 58 (63.0%) were within ±2 mm Hg of GAT.ConclusionsPreliminary IOP measurements using a prototype smartphone-based tonometer was grossly equivalent to the reference standard.

Primary open-angle glaucoma typically presents as two subtypes. This study aimed to elucidate the shared and distinct genetic architectures of normal-tension (NTG) and high-tension glaucoma (HTG), motivated by the need to develop intraocular pressure (IOP)-independent drug targets for the disease. We conducted a comprehensive multi-ethnic meta-analysis, prioritized variants based on functional annotation, and explored drug-gene interactions. We further assessed the genetic overlap between NTG and HTG using pairwise GWAS analysis. We identified 22 risk loci associated with NTG, 17 of which have not previously been reported for NTG. Two loci, BMP4 and TBKBP1 , have not previously been associated with glaucoma at the genome-wide significance level. Our results indicate that while there is a significant overlap in risk loci between tension subtypes, the magnitude of the effect tends to be lower in NTG compared to HTG, particularly for IOP-related loci. Additionally, we identified a potential role for biologic immunomodulatory treatments as neuroprotective agents. This study investigates the genetic similarities and differences between two subtypes of glaucoma (normal tension and high tension). Multi-ethnic meta-analysis reveals overlapping risk loci, with a lower effect magnitude in normal tension glaucoma. The authors also use their gene discovery approach to highlight possible neuro-protective drug targets for glaucoma.

This study investigated the relationship between thin central corneal thickness (CCT) and lamina cribrosa (LC) morphology in patients with normal-tension glaucoma. Thin CCT was defined as a corneal thickness of less than 500 μm in both eyes, and all included patients had a corrected intraocular pressure of less than 20 mmHg. To investigate the LC-morphological characteristics observed in the Thin-CCT group (N = 60) , the Normal-CCT group (N = 36) was set as the control. A subgroup analysis was performed on Progressors and Non-progressors using the visual field’s progression rate to identify progression-related risk factors. The LC posterior displacement index was higher in the Thin-CCT group and the temporal anterior laminar insertion depth (ALID) was deeper in Progressors . In multivariate analyses, the risk of glaucoma progression increased with older age, thinner CCT, worse visual filed, deeper temporal ALID, and deeper mean LC depth. Notably, ALID showed a significant correlation with CCT. These findings suggest that in patients with normal-tension glaucoma, thinner CCT is associated with a more pronounced posterior displacement and deeper insertion of the LC, even under similar intraocular pressure conditions. The altered LC morphology observed in thin CCT may help explain the higher rate of glaucoma progression in this patient population.

Corneal hysteresis (CH) is associated with glaucomatous structural changes. We retrospectively investigated the association between CH and the regional circumpapillary retinal nerve fibre layer thickness (cpRNFLT) in 419 eyes of 419 patients with normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG). CH was used as the explanatory variable, and cpRNFLT (total and quadrant) was used as the dependent variable. Standardized β coefficients were compared both overall and between the NTG and POAG groups. Multiple regression analysis with CH as the explanatory variable and cpRNFLT parameters as the dependent variables suggested that even after adjusting for age, sex, intraocular pressure (IOP), axial length, and central corneal thickness, all areas of the cpRNFLT were significantly associated with CH, except for the nasal quadrant. In the stratified analysis by glaucoma type, a positive relationship between CH and regional cpRNFLT tended to be maintained in the NTG group but not in the POAG group ( P  = 0.060 for interaction). Additionally, in the NTG group, the CH-inferior cpRNFLT relationship was particularly strong in the less-IOP fluctuation group. These results suggest that CH may be a potential predictor of anatomical vulnerability around the optic nerve, particularly enhancing the inferior regions of NTG.

To investigate the relationship between nocturnal blood pressure (BP) dip and parapapillary choroidal vessel density (pCVD) in patients with normal-tension glaucoma (NTG). This study analyzed 267 eyes of 267 untreated NTG patients who underwent 24-hour (h) intraocular pressure (IOP) and ambulatory BP monitoring in the habitual position. Patients were classified into 3 groups [non-dippers (nocturnal BP dip < 10%), dippers (nocturnal BP dip between 10% and 20%, and over-dippers (nocturnal BP dip > 20%)], and pCVDs were measured by using optical coherence tomography angiography (OCTA) images. Logistic regression analyses were performed to identify clinical factors associated with \"over-dipper\" cases. Linear regression analyses were conducted to determine the correlation between various clinical variables and pCVD. In clinical characteristics, over-dippers exhibited lower pCVD values compared to non-dippers or dippers (P = 0.004). High diurnal intraocular pressure (IOP) fluctuation (P = 0.031), high diurnal mean arterial pressure (MAP) fluctuation (P = 0.001), and low pCVD (P = 0.002) were identified as predictors of being \"over-dipper\" in multivariable logistic regression analyses. Moreover, peripapillary retinal vessel density (P = 0.040), presence of choroidal microvasculature dropout (P = 0.039), and nocturnal MAP dip % (P = 0.002) showed significant correlations with pCVD according to multivariable linear regression analyses. Over-dippers presented with lower pCVD than non-dippers or dippers as measured by OCTA choroidal images. Low pCVD was a predictor of \"over-dipper\" cases and associated with a greater percentage of nocturnal MAP dip in NTG patients. 24-h ambulatory BP monitoring may provide further information for detecting low pCVD in NTG patients with nocturnal BP dip.

Background/aimsTo assess the performance of deep-learning (DL) models for prediction of conversion to normal-tension glaucoma (NTG) in normotensive glaucoma suspect (GS) patients.MethodsDatasets of 12 458 GS eyes were reviewed. Two hundred and ten eyes (105 eyes showing NTG conversion and 105 without conversion), followed up for a minimum of 7 years during which intraocular pressure (IOP) was lower than 21 mm Hg, were included. The features of two fundus images (optic disc photography and red-free retinal nerve fibre layer (RNFL) photography) were extracted by convolutional auto encoder. The extracted features as well as 15 clinical features including age, sex, IOP, spherical equivalent, central corneal thickness, axial length, average circumpapillary RNFL thickness, systolic/diastolic blood pressure and body mass index were used to predict NTG conversion. Prediction was performed using three machine-learning classifiers (ie, XGBoost, Random Forest, Gradient Boosting) with different feature combinations.ResultsAll three algorithms achieved high diagnostic accuracy for NTG conversion prediction. The AUCs ranged from 0.987 (95% CI 0.978 to 1.000; Random Forest trained with both fundus images and clinical features) and 0.994 (95% CI 0.984 to 1.000; XGBoost trained with both fundus images and clinical features). XGBoost showed the best prediction performance for time to NTG conversion (mean squared error, 2.24). The top three important clinical features for time-to-conversion prediction were baseline IOP, diastolic blood pressure and average circumpapillary RNFL thickness.ConclusionDL models, trained with both fundus images and clinical data, showed the potential to predict whether and when normotensive GS patients will show conversion to NTG.

Background/objectivesTo investigate the correlation between obstructive sleep apnea (OSA) severity and the structural and functional progression in patients with glaucoma.Subjects/methodsThis retrospective comparative cohort study included subjects from the polysomnography database in Chang Gung Memorial Hospital between June 1, 2009, and June 1, 2017, by identifying patients who had received diagnoses of primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), or glaucoma suspect. Patients with follow-up time of <3 years and/or <3 consecutive reliable optical coherence tomography (OCT) or visual field (VF) tests were excluded. Progression of overall peripapillary retinal nerve fiber layer (RNFL) thickness on OCT scans and VF mean deviation (MD) or VF index (VFI) were determined through linear regression trend analysis.ResultsThirty-two patients were included. There was a trend to higher percentage of progression on RNFL thickness and VF in higher OSAS severity. After stratifying patients to no OSA/mild OSA (group 1) and moderate/severe OSA (group 2), group 2 exhibited a significantly higher percentage of RNFL thickness progression than did group 1 (64.7% vs 26.7%, P = 0.042). Multivariate Cox regression analysis showed that severe OSA had an 8.448-fold higher risk of RNFL thickness progression after age, sex, diabetes mellitus, hypertension, hyperlipidemia, and body mass index adjustment (95% confidence interval, 1.464–48.752, P = 0.017).ConclusionsSevere OSA is significantly correlated with a higher risk of structural deterioration in patients with glaucoma.