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BackgroundTo report on the optic nerve sheath diameter (ONSD) in patients with normal-tension glaucoma (NTG) compared with controls without known optic nerve (ON) or intracranial disease.MethodsIn 18 patients with NTG (mean age 64.9±8.9 years; 7 women and 11 men), CT of the orbit was performed. 17 age- and gender-matched patients without ON or intracranial disease, who underwent CT of the orbits for non-ophthalmological reasons, served as controls. The widest intraorbital ONSD in axial sections was measured using a standardised technique. Study design: unmasked. Statistical analysis was performed using an independent two-tailed t Test and the non-parametric Spearman correlation test.ResultsONSD was significantly (p<0.001) increased in NTG patients (right side: mean 7.9±0.9 mm SD; left: 8.0±1.1 mm) compared with controls (right: 6.3±0.5 mm; left: 6.1±0.6 mm). Neither the NTG nor the control group had a significant difference in ONSD between males and females or between right and left sides.ConclusionsAn increased ONSD is generally associated with increased intracranial pressure; however, ONSDs in a group of NTG patients also were significantly increased compared with controls. ON sheath compartmentation and thinning of the ON sheath are two possible explanations for an increase in the ONSD in patients with NTG.

To compare parapapillary choroidal microvascular (PPCMv) densities between myopic eyes with and without glaucoma. In this retrospective study, OCTA images (4.5 × 4.5 mm) were obtained using a commercial spectral-domain OCTA system. PPCMv density was calculated in inner and outer annuli using customized software. Marginal model of generalized estimating equations was established to adjust for confounding factors and intraclass correlations. This study included 35 myopic eyes with glaucoma (MG), 96 non-myopic eyes with glaucoma (NMG) matched for visual field mean deviation, 37 myopic eyes without glaucoma (MNG), and 73 control eyes from three tertiary centers. The participant ages were (mean [standard deviation, SD]) 57.43 [11.49], 60.40 [10.07], 52.84 [9.35], and 54.74 [12.07] years. Inner and outer annular PPCMv densities (mean [SD]) decreased in the following order: control (0.15 [0.04] and 0.12 [0.04]), MNG (0.14 [0.08] and 0.12 [0.08]), NMG (0.09 [0.05] and 0.07 [0.04]), and MG (0.09 [0.04] and 0.07 [0.03]). The mean differences in PPCMv density between glaucoma groups (NMG and MG) and the control group (mean difference [95% confidence interval]) were -0.06 (-0.08 to -0.04, P < 0.001 for inner whole annular PPCMv density in NMG vs control) and -0.07 (-0.10 to -0.04, P < 0.001 for inner whole annular PPCMv density in MG vs control), consistent across all regions of interest (ROIs). No significant interaction was observed between glaucoma and myopia after adjustment for potential confounders (P > 0.112). Parapapillary choroidal microvascular density attenuation tends to be greater in eyes with glaucoma than in eyes with myopia.

To evaluate optic nerve vascular density using swept source optical coherence tomography angiography (OCTA) in patients with early primary open angle glaucoma (POAG), pre-perimetric glaucoma and normal eyes. This is a prospective, observational study including 56 eyes in total and divided into 3 groups; 20 eyes with mild POAG, 20 pre-perimetric glaucoma eyes, and 16 age-matched normal eyes as controls. The optic disc region was imaged by a 1050-nm-wavelength swept-source OCT system (DRI OCT Triton, TOPCON). Vessel density was assessed as the ratio of the area occupied by the vessels in 3 distinct regions: 1) within the optic nerve head; 2) in the 3 mm papillary region around the optic disc; and 3) in the peripapillary region, defined as a 700-μm-wide elliptical annulus around the disc. The potential associations between vessel density and structural, functional measures were analyzed. There was a statistically significant difference for the peripapillary vessel density, optic nerve head vessel density, and papillary vessel density among all the groups (p<0.001). Control eyes showed a significant difference for all measured vessel densities compared to glaucomatous eyes (p values from 0.001 to 0.024). There was a statistically significant difference between control and pre-perimetric glaucoma eyes for peripapillary, optic nerve head and papillary vessel density values (p values from 0.001 to 0.007). The optic nerve head vessel density, superior and inferior papillary area vessel density (Pearson r = 0.512, 0.436, 0.523 respectively) were highly correlated with mean overall, superior and inferior RNFL thickness in POAG eyes (p = 0.04, p = 0.02 and p = 0.04 respectively). Multiple linear regression analysis of POAG group showed that optic nerve head vessel density in POAG group was more strongly linked to RNFL thickness than to any other variables. Eyes with mild POAG could be differentiated from pre-perimetric glaucoma eyes, which also could be differentiated from normal eyes using OCTA-derived retinal vessel density measurements.

AimsTo evaluate the diagnostic ability of peripapillary vessel density measurements on optical coherence tomography angiography (OCTA) in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and to compare these with peripapillary retinal nerve fibre layer (RNFL) thickness measurements.MethodsIn a cross-sectional study, 48 eyes of 33 healthy control subjects, 63 eyes of 39 patients with POAG and 49 eyes of 32 patients with PACG underwent OCTA (RTVue-XR, Optovue, Fremont, California, USA) and RNFL imaging with spectral domain OCT. Diagnostic abilities of vessel density and RNFL parameters were evaluated using area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities.ResultsAUCs of peripapillary vessel density ranged between 0.48 for the temporal sector and 0.88 for the inferotemporal sector in POAG. The same in PACG ranged between 0.57 and 0.86. Sensitivities at 95% specificity ranged from 13% to 70% in POAG, and from 10% to 67% in PACG. AUCs of peripapillary RNFL thickness ranged between 0.51 for the temporal sector and 0.91 for the inferonasal sector in POAG. The same in PACG ranged between 0.61 and 0.87. Sensitivities at 95% specificity ranged from 8% to 68% in POAG, and from 2% to 67% in PACG. AUCs of all peripapillary vessel density measurements were comparable (p>0.05) to the corresponding RNFL thickness measurements in both POAG and PACG.ConclusionsDiagnostic ability of peripapillary vessel density parameters of OCTA, especially the inferotemporal sector measurement, was good in POAG and PACG. Diagnostic abilities of vessel density measurements were comparable to RNFL measurements in both POAG and PACG.

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.

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide. Although deep learning methods have been proposed to diagnose POAG, it remains challenging to develop a robust and explainable algorithm to automatically facilitate the downstream diagnostic tasks. In this study, we present an automated classification algorithm, GlaucomaNet, to identify POAG using variable fundus photographs from different populations and settings. GlaucomaNet consists of two convolutional neural networks to simulate the human grading process: learning the discriminative features and fusing the features for grading. We evaluated GlaucomaNet on two datasets: Ocular Hypertension Treatment Study (OHTS) participants and the Large-scale Attention-based Glaucoma (LAG) dataset. GlaucomaNet achieved the highest AUC of 0.904 and 0.997 for POAG diagnosis on OHTS and LAG datasets. An ensemble of network architectures further improved diagnostic accuracy. By simulating the human grading process, GlaucomaNet demonstrated high accuracy with increased transparency in POAG diagnosis (comprehensiveness scores of 97% and 36%). These methods also address two well-known challenges in the field: the need for increased image data diversity and relying heavily on perimetry for POAG diagnosis. These results highlight the potential of deep learning to assist and enhance clinical POAG diagnosis. GlaucomaNet is publicly available on https://github.com/bionlplab/GlaucomaNet .

A wave of less invasive surgical options that target or bypass the conventional aqueous outflow system has been incorporated into routine clinical practice to mitigate surgical risks associated with traditional glaucoma drainage surgery. A blanket surgical approach for open-angle glaucoma is unlikely to achieve the desired IOP reduction in an efficient or economical way. Developing a precise approach to selecting the most appropriate surgical tool for each patient is dependent upon understanding the complexities of the aqueous outflow system and how devices influence aqueous drainage. However, homoeostatic control of aqueous outflow in health and glaucoma remains poorly understood. Emerging imaging techniques have provided an opportunity to study aqueous outflow responses non-invasively in clinic settings. Haemoglobin Video Imaging (HVI) studies have demonstrated different patterns of aqueous outflow within the episcleral venous system in normal and glaucomatous eyes, as well as perioperatively after trabecular bypass surgery. Explanations for aqueous outflow patterns remain speculative until direct correlation with findings from Schlemm’s canal and the trabecular meshwork are possible. The redirection of aqueous via targeted stent placement may only be justifiable once the role of the aqueous outflow system in IOP homoeostasis has been defined.

Purpose: To map the 3-dimensional (3D) strain of the optic nerve head (ONH) in vivo after intraocular pressure (IOP) lowering by trabeculectomy (TE) and to establish associations between ONH strain and retinal sensitivity.Design: Observational case series.Participants: Nine patients with primary open-angle glaucoma (POAG) and 3 normal controls.Methods: The ONHs of 9 subjects with POAG (pre-TE IOP: 25.3 +/- 13.9 mmHg; post-TE IOP: 11.8 +/- 8.6 mmHg) were imaged (1 eye per subject) using optical coherence tomography (OCT) (Heidelberg Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany) before (< 21 days) and after (< 50 days) TE. The imaging protocol was repeated for 3 controls in whom IOP was not altered. In each post-TE OCT volume, 4 tissues were manually segmented (prelamina, choroid, sclera, and lamina cribrosa [LC]). For each ONH, a 3D tracking algorithm was applied to both post-and pre-TE OCT volumes to extract IOP-induced 3D displacements at segmented nodes. Displacements were filtered, smoothed, and processed to extract 3D strain relief (the amount of tissue deformation relieved after TE). Strain relief was compared with measures of retinal sensitivity from visual field testing.Main Outcome Measures: Three-dimensional ONH displacements and strain relief.Results: On average, strain relief (averaged or effective component) in the glaucoma ONHs (8.6%) due to TE was higher than that measured in the normal controls (1.07%). We found no associations between the magnitude of IOP decrease and the LC strain relief (P > 0.05), suggesting biomechanical variability across subjects. The LC displaced posteriorly, anteriorly, or not at all. Furthermore, we found linear associations between retinal sensitivity and LC effective strain relief (P < 0.001; high strain relief associated with low retinal sensitivity).Conclusions: We demonstrate that ONH displacements and strains can be measured in vivo and that TE can relieve ONH strains. Our data suggest a wide variability in ONH biomechanics in the subjects examined in this study. We further demonstrate associations between LC effective strain relief and retinal sensitivity.

Background/aimsOptical coherence tomography angiography (OCT-A) images are subject to variability, but the extent to which learning impacts OCT-A measurements is unknown. We determined whether there is a learning effect in glaucoma patients and healthy controls imaged with OCT-A.MethodsNinety-one open-angle glaucoma patients and 54 healthy controls were imaged every 4 months over a period of approximately 1 year in this longitudinal cohort study. We analysed 15°×15° scans, centred on the fovea, in one eye of each participant. Two-dimensional projection images for the superficial, intermediate and deep vascular plexuses were exported and binarised after which perfusion density was calculated. Linear mixed-effects models were used to investigate the association between perfusion density and follow-up time.ResultsThe mean (SD) age of glaucoma patients and healthy controls was 67.3 (8.1) years and 62.1 (9.0) years, respectively. There was a significant correlation between perfusion density and scan quality in both glaucoma patients (r=0.50 (95% CI 0.42 to 0.58); p<0.05) and healthy controls (r=0.41 (95% CI 0.29 to 0.52); p<0.05). An increase in perfusion density occurred over time and persisted, even after adjustment for scan quality (1.75% per year (95% CI 1.14 to 2.37), p<0.01).ConclusionsPerfusion density measurements are subject to increasing experience of either the operator or participant, or a combination of both. These findings have implications for the interpretation of longitudinal measurements with OCT-A.

To develop a self-supervised learning (SSL) model that classifies optic disc phenotypes in primary open angle glaucoma (POAG) and explores novel phenotypic patterns with optic disc photographs (ODPs). We collected 850 ODPs from patients with POAG and applied data augmentation to address class imbalances, yielding 10,493 images. Using the DINO Vision Transformer as the backbone model, we trained an SSL model to extract 2048-dimensional latent features. These features were used for both supervised classification of six known phenotypes and unsupervised clustering. Classification performance was evaluated with Random Forest and XGBoost models. UMAP (Uniform Manifold Approximation and Projection) was used for dimensionality reduction and feature visualization, and attention maps were generated for model interpretability. The DINO-EYE model features enabled phenotype classification with 91% accuracy with Random Forest and 92.1% after merging clinically similar phenotypes. Unsupervised clustering revealed coherent groupings, particularly for concentric thinning and extensive Peripapillary Atrophy (PPA), though no new phenotypes were unanimously confirmed by clinicians. The proposed model outperformed the RETFound SSL model in phenotype classification and demonstrated interpretable attention regions consistent with expert criteria. Our DINO-EYE effectively extracts clinically meaningful features from fundus images and enables accurate classification of optic disc phenotypes in POAG. It surpasses existing SSL models in performance and interpretability, offering promise for real-world glaucoma decision support and individualized care planning.