Glaucoma Diagnostic Performance of Retinal Blood Flow Measurement With Doppler Optical Coherence Tomography.

Purpose: The purpose of this study was to evaluate the diagnostic performance of retinal blood flow (RBF) measured with the Doppler optical coherence tomography (OCT) segmental scanning method to distinguish between healthy and glaucoma eyes. Methods: Fifty-eight patients with normal tension glaucoma (NTG) who had a single-hemifield visual field defect and 44 age-matched healthy subjects were enrolled. Retinal nerve fiber layer thickness (RNFLT) was measured with swept-source OCT. Superior and inferior temporal arteries (TAs) and temporal veins (TVs) RBF were measured with Doppler OCT. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to compare the diagnostic performances in the damaged and normal hemispheres. Results: Multivariate regression analysis showed TA RBF and TV RBF were significantly reduced in the damaged and normal hemispheres. The ROC analysis showed that the AUC for quadrant RNFLT, TA RBF, and TV RBF were 0.973, 0.909, and 0.872 in the damaged hemisphere, respectively. The AUC values in the normal hemisphere were 0.783, 0.744, and 0.697, respectively. The combination of quadrant RNFLT and TA/TV RBF had a greater AUC than quadrant RNFLT alone in both damaged (AUC = 0.987) and normal (AUC = 0.825) hemispheres. Conclusions: In NTG eyes with single-hemifield damage, the RBF was found to be significantly reduced in the damaged and normal hemispheres independent from structural changes. The combination of RNFLT and RBF could improve diagnostic performances for glaucoma. Translational Relevance: Combining morphological and blood flow measurements with Doppler OCT may be useful in glaucoma diagnosis.

Difference in topographic morphology of optic nerve head and neuroretinal rim between normal tension glaucoma and central retinal artery occlusion.

Although central retinal artery occlusion (CRAO) has its own defining pathomechanism and clinical characteristics, morphologic feature of the optic nerve head (ONH) during its later stage is not diagnostic, which makes it difficult to differentiate CRAO from other optic neuropathies. This cross-sectional study was performed to investigate the differences in the topographic morphology of the ONH in eyes with normal-tension glaucoma (NTG) and CRAO. Thirty-one eyes with NTG; 31 eyes with CRAO; and 31 healthy fellow eyes of the subjects with CRAO were included. ONH morphology was evaluated by measuring horizontal rim width (HRW), minimal rim width in the selected horizontal image (MRW), and lamina cribrosa curvature index (LCCI) in horizontal B-scan images obtained using enhanced depth-imaging optical coherence tomography. HRW was smaller and LCCI was larger in NTG eyes than in both CRAO and healthy fellow eyes (both P < 0.001), while both were comparable between CRAO and healthy fellow eyes. MRW differed significantly among the three groups, being smallest in NTG eyes followed by CRAO and healthy fellow eyes (P < 0.001). NTG and CRAO eyes with a similar degree of RNFL loss differed in ONH morphology, indicating that mechanisms of ONH damage differ between these two conditions.

Prospective Pilot Clinical Study of Noninvasive Cerebrovascular Autoregulation Monitoring in Open-Angle Glaucoma Patients and Healthy Subjects.

PURPOSE: To analyze the cerebrovascular autoregulation (CA) dynamics in patients with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) as well as healthy subjects using noninvasive ultrasound technologies for the first time. METHODS: The CA status of 10 patients with NTG, 8 patients with HTG, and 10 healthy subjects was assessed, using an innovative noninvasive ultrasonic technique, based on intracranial blood volume slow-wave measurements. Identified in each participant were intraocular pressure, ocular perfusion pressure, and CA-related parameter volumetric reactivity index (VRx), as well as the duration and doses of the longest cerebral autoregulation impairment (LCAI). In addition, we calculated the associations of these parameters with patients' diagnoses. RESULTS: The VRx value, the LCAI dose, and duration in healthy subjects were significantly lower than in patients with NTG (P < 0.05). However, no significant differences were noted in these parameters between healthy subjects and HTG and between NTG and HTG groups. CONCLUSIONS: NTG is associated with the disturbed cerebral blood flow and could be diagnosed by performing noninvasive CA assessments. TRANSLATIONAL RELEVANCE: The VRx monitoring method can be applied to a wider range of patient groups, especially patients with normal-tension glaucoma.

Proteome alterations in the aqueous humor reflect structural and functional phenotypes in patients with advanced normal-tension glaucoma.

Previous reports have shown possible association between altered protein levels in aqueous humor (AH) and normal-tension glaucoma (NTG), but the underlying pathogenetic mechanism as well as specific molecular biomarkers for NTG remains still elusive. Here, we aimed to identify novel biomarkers for advanced NTG by analyzing the proteome of patient-derived AH and their correlation with various functional and structural parameters from the visual field test (VF), optical coherence tomography (OCT), and OCT angiography (OCTA). We determined differentially expressed proteins (DEPs) of the AH of patients with advanced NTG (n = 20) using label-free quantitative (LFQ) proteomics with pooled samples and data-independent acquisition (DIA) analysis with individual samples, and the roles of AH DEPs in biological pathways were evaluated using bioinformatics. We identified 603 proteins in the AH of patients with advanced NTG, and 61 of them were selected as DEPs via global proteome LFQ profiling. Individual DIA analyses identified a total of 12 DEPs as biomarker candidates, seven of which were upregulated, and five were downregulated. Gene ontology enrichment analysis revealed that those DEPs were mainly involved in the immune response. Moreover, IGFBP2, ENO1, C7, B2M, AMBP, DSP, and DCD showed a significant correlation with the mean deviation of VF and with peripapillary and macular parameters from OCT and OCTA. The present study provides possible molecular biomarkers for the diagnosis of advanced NTG.

Comparison of optical coherence tomography angiography metrics in primary angle-closure glaucoma and normal-tension glaucoma.

To investigate the peripapillary vascular metrics in early normal tension glaucoma (NTG) and early primary angle closure glaucoma (PACG) eyes using optical coherence tomography angiography (OCT-A). One or both eyes of each subject were imaged for a 3 × 3 mm peripapillary region by swept-source OCT-A (DRI-OCT Triton, Topcon, Japan) and assessed by an automated MATLAB program. OCT-A metrics including circumpapillary vessel density (cpVD) and fractal dimension (cpFD) were compared. Their association with visual field (VF) parameters and retinal nerve fiber layer (RNFL) thickness were determined. Sixty-eight eyes of 51 PACG, 68 eyes of 48 NTG, and 68 eyes of 49 control subjects were cross-sectionally analyzed. NTG eyes had significantly lower global cpVD (52.369 ± 0.781%) compared with PACG eyes (55.389 ± 0.721%, P = 0.004) that had comparable disease severity and average RNFL thickness. Multivariable analysis revealed that, for PACG and NTG eyes, decreased cpVD ([PACG] ß = -4.242; CI: -8.120, -0.363 vs [NTG] ß = -5.531; CI: -9.472, -1.590) and cpFD ([PACG] ß = -8.894;CI: -11.925, -5.864 vs [NTG] ß = -12.064; CI: -17.095, -6.932) were associated with decreased RNFL thickness (all P ≤ 0.032); with a stronger association between decrease cpFD and decreased RNFL thickness in NTG eyes (P = 0.028). Decreased cpVD was associated with decrease mean deviation (MD) in NTG eyes (ß = -0.707; CI: -1.090, -0.324; P ≤ 0.001) and not associated with the visual field parameters in PACG eyes. Early NTG had lower global cpVD compared with early PACG, despite similar disease severity and average RNFL thickness.

WDR36-Associated Neurodegeneration: A Case Report Highlights Possible Mechanisms of Normal Tension Glaucoma.

WDR36 is one of a number of genes implicated in the pathogenesis of adult-onset primary open angle glaucoma (POAG). Here we describe in detail the phenotype of a patient with pathogenic variation in WDR36 who presented with a protracted history of central vision loss. On exam visual acuities were at 20/100 level, had a tritan color defect and showed central arcuate visual field defects on visual field testing. Enlarged cup-to-disk ratios with normal intraocular pressures were associated with severe thinning of the ganglion cell layer (GCL) and retinal nerve fiber layer consistent with a clinical diagnosis of normal tension glaucoma. Full-field electroretinograms revealed a severe inner retinal dysfunction with reduced amplitudes and remarkably delayed timings of the b-wave, but preserved photoreceptor (a-wave) function. The pattern described herein recapitulates some of the findings of an animal model of WDR36-associated POAG and suggests a mechanism of disease that involves a retina-wide inner retinal dysfunction and neurodegeneration beyond the GCL. Further detailed structural and functional characterizations of patients with a pathogenic variant in the WDR36 gene are required to confirm these findings.

Association between Topographic Features of the Retinal Nerve Fiber Bundle and Good Visual Acuity in Patients with Glaucoma.

Purpose: Maintaining visual acuity in glaucoma patients is an important part of preventing the deterioration of quality of vision. We identified specific areas of the papillomacular bundle (PMB) that were strongly associated with visual acuity, based on en-face images derived from optical coherence topography (OCT) wide scans.Methods: The study recruited 23 eyes of 21 glaucoma patients (age: 61.3 ± 13.0 years, M: F = 9:12, Humphrey field analyzer-measured mean deviation: -19.9 ± 6.5 dB) with good best-corrected visual acuity (20/20 or more) and a remaining PMB with a maximum width no more than half that of the vertical disc diameter. En-face images were derived from 12 × 9 mm wide-scan images made with DRI-OCT (Triton, Topcon). Averaged en-face images were created by identifying the disc center and fovea line (DFL) and aligning it between images. We then measured the frequency of remaining PMB at 10 µm intervals along a vertical line intersecting the DFL at its midpoint. Finally, we used a logistic analysis in a much larger group of patients to identify cases of glaucoma with low BCVA (<20/20).Results: In the averaged en-face image, the residual PMB area appeared as a high-intensity region above the DFL. Analysis showed that residual PMB was most common in an area 830-870 µm above the DFL. The correlation coefficient of residual PMB in this area to BCVA was -0.57 (p < .01), and among OCT parameters in this residual PMB area, the AUC to identify decreased BCVA was highest for ganglion cell complex thickness (0.85, p < .01), with a cutoff of 87.5 µm.Conclusions: This study identified specific areas of the PMB that were associated with BCVA in wide-scan, en-face OCT images from glaucoma patients. This suggests that it may be possible to identify visual impairment during glaucoma treatment by measuring this area.

Investigation of the Peripapillary Choriocapillaris in Normal Tension Glaucoma, Primary Open-angle Glaucoma, and Control Eyes.

PRECIS: The peripapillary choriocapillaris (CC) was observed to be significantly impaired in normal tension glaucoma (NTG) subjects compared with normal controls using optical coherence tomography angiography (OCTA). PURPOSE: The aim was to quantitatively evaluate the peripapillary CC in NTG, primary open-angle glaucoma (POAG), and control eyes using OCTA. MATERIALS AND METHODS: Ninety eyes (30 controls, 30 NTG, and 30 POAG) from 73 patients were imaged using the Zeiss Plex Elite 9000. Five repeat 3×3 mm OCTA scans were acquired both nasally and temporally to the optic disc and subsequently averaged. Four CC flow deficit (FD) measures were calculated using the fuzzy C-means approach: FD density (FDD), mean FD size (MFDS), FD number (FDN), and FD area (FDA). RESULTS: Temporal NTG CC parameters were associated with visual field index and mean deviation (P<0.05). The control group showed a significantly lower nasal FDD (nasal: 3.79±1.26%, temporal: 4.48±1.73%, P=0.03), FDN (nasal: 156.43±38.44, temporal: 178.40±45.68, P=0.02), and FDA (nasal: 0.22±0.08, temporal: 0.26±0.10, P=0.03) when compared with temporal optic disc. The NTG group showed a significantly higher FDD (NTG: 5.04±2.38%, control: 3.79±1.26%, P=0.03), FDN (NTG: 185.90±56.66, control: 156.43±38.44, P=0.04), and FDA (NTG: 0.30±0.14 mm2, control: 0.22±0.08 mm2, P=0.03) nasal to the optic disc compared with controls. CONCLUSIONS: Association between CC parameters and glaucoma severity in NTG, but not POAG subjects, suggests vascular abnormalities may be a potential factor in the multifactorial process of glaucoma damage in NTG patients.

Macular vessel density, branching complexity and foveal avascular zone size in normal tension glaucoma.

The aim of this study was to investigate the relationship between glaucoma severity and perifoveal vessel density (pfVD), branching complexity, and foveal avascular zone (FAZ) size in normal tension glaucoma (NTG). 31 patients with NTG washed out of glaucoma medications were subjected to tests including; intraocular pressure measurement; standard automated perimetry; optical coherence tomography (OCT) measurement of macular ganglion cell complex (mGCC), inner macular thickness (IMT) and circumpapillary retinal nerve fibre layer (cpRNFL); and OCT angiography measurement of pfVD, FAZ perimeter and multispectral fractal dimensions (MSFD). Eyes with more severe glaucoma had significantly thinner mGCC and cpRNFL and lower pfVD. MD decreased by 0.4 dB (95% CI 0.1 to 0.6 dB, P = 0.007) for every 1% decrease in pfVD. Lower MSFD was observed in eyes with lower pfVD and in patients with systemic hypertension. Multivariable analysis, accounting for age and OCTA quality, found lower pfVD remained significantly associated with thinner IMT, thinner mGCC and worse MD but not with MSFD. pfVD was reduced in NTG and was diminished in eyes with worse MD. Macular vessel branching complexity was not related to severity of visual field loss but was lower in patients with systemic hypertension.

Nocturnal blood pressure dip and parapapillary choroidal microvasculature dropout in normal-tension glaucoma.

Choroidal microvasculature dropout (CMvD) implies compromised optic nerve head perfusion in glaucoma patients. However, there are conflicting findings whether office-hour systemic blood pressure (BP) is related to the presence of CMvD. The present study investigated which systemic BP parameters, derived from 24-h ambulatory BP monitoring (ABPM), are associated with CMvD as assessed by optical coherence tomography angiography (OCT-A) in normal-tension glaucoma (NTG). This study included 88 eyes of 88 NTG patients who underwent 24-h ABPM and OCT-A imaging. Various systemic BP parameters associated with the presence of CMvD were evaluated using logistic regression analyses. CMvD was detected in 38 NTG eyes (43.2%). NTG eyes with CMvD had nighttime diastolic BP (DBP) dip of greater magnitude and longer duration than eyes without CMvD. In multivariate logistic regression, worse VF mean deviation (MD) (odds ratio [OR] 0.786; P = 0.001), greater nighttime DBP dip "%" (OR 1.051; P = 0.034), and higher daytime peak IOP (OR 1.459; P = 0.013) were significantly associated with the presence of CMvD. Based on our findings that the eyes with CMvD are closely associated with having nighttime DBP dip, NTG patients with CMvD should be recommended to undergo 24-h ABPM.

Use of rsfMRI-fALFF for the detection of changes in brain activity in patients with normal-tension glaucoma.

BACKGROUND: We know little about the changes of brain activity in patients with normal-tension glaucoma (NTG). PURPOSE: To investigate the altered spontaneous brain activity in patients with NTG through the resting state functional magnetic resonance imaging-fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF) technique, and to explore the relationship with optical coherence tomography (OCT) and field of vision. MATERIAL AND METHODS: Twenty patients with NTG and 20 healthy controls (HCs) (matched for sex, age, and level of education) were enrolled. Spontaneous cerebral activity variations were investigated using the rsfMRI-fALFF technique in all individuals. The average fALFF values of patients with NTG and HCs were compared. RESULTS: Compared with HCs, patients with NTG had significantly lower fALFF values in the right angular gyrus and precuneus; however, higher fALFF values in the brain regions were not observed. The values showed statistically significant negative correlation with those of the retinal nerve fiber layer (right angular gyrus: r = -0.607, P = 0.010; right precuneus: r = -0.504, P = 0.020). There was no significant correlation between the fALFF value and cup-disc ratio (right angular gyrus: r = 0.158, P = 0.494; right precuneus: r = -0.087, P = 0.706), mean deviation (right angular gyrus: r = 0.096, P = 0.468; right precuneus: r = 0.026, P = 0.845), and pattern SD value (right angular gyrus: r = 0.064, P = 0.626; right precuneus: r = -0.145, P = 0.268). CONCLUSION: Abnormal spontaneous activities were detected in numerous brain regions of patients with NTG, which may provide useful information for understanding the dysfunction in NTG. These activity changes in brain regions may be used as effective clinical indicators for NTG.

Global assessment of arteriolar, venular and capillary changes in normal tension glaucoma.

Microcirculatory insufficiency has been hypothesized in glaucoma pathogenesis. There is a scarcity of data to comprehensively examine the changes in retinal microvasculature and its role in normal tension glaucoma (NTG). We conducted a cross-sectional case-control study and included 168 eyes from 100 NTG patients and 68 healthy subjects. Quantitative retinal arteriolar and venular metrics were measured from retinal photographs using a computer-assisted program. Radial peripapillary capillary network was imaged with OCT-A and quantitative capillary metrics (circumpapillary vessel density (cpVD) and circumpapillary fractal dimension (cpFD)) were measured with a customized MATLAB program. We found that NTG was associated with decreased arteriolar and venular tortuosity, arteriolar branching angle, cpVD and cpFD. Decreased venular caliber, arteriolar and venular branching angles, cpVD and cpFD were associated with thinner average RNFL thickness. Decreased arteriolar and venular branching angles, cpVD and cpFD were also associated with worse standard automated perimetry measurements (mean deviation and visual field index). Compared with retinal arteriolar and venular metrics, regression models based on OCT-A capillary metrics consistently showed stronger associations with NTG and structural and functional measurements in NTG. We concluded that NTG eyes showed generalized microvascular attenuations, in which OCT-A capillary metrics attenuations were more prominent and strongly associated with NTG.

Comparison of lamina cribrosa properties and the peripapillary vessel density between branch retinal vein occlusion and normal-tension glaucoma.

PURPOSE: To compare the properties of the lamina cribrosa (LC) and the peripapillary vessel density between branch retinal vein occlusion (BRVO) and normal-tension glaucoma (NTG), using swept-source optical coherence tomography and optical coherence tomography angiography. METHODS: This retrospective study included 21 eyes of 21 patients with BRVO and 43 eyes of 43 patients with NTG who were treated from June 2016 to September 2017. The anterior LC depth (ALCD) and LC thickness (LCT) at the mid-superior, central, and mid-inferior levels; the mean difference in ALCD; and the peripapillary vessel density in the superficial and deep capillary plexuses and the choriocapillaris were compared between groups. RESULTS: ALCD at the mid-superior, central, and mid-inferior levels was significantly greater in the NTG group (P < 0.05), while LCT was comparable between the groups. The mean difference in ALCD was significantly greater in the BRVO group (P = 0.03). The peripapillary vessel density in the superotemporal segment of the superficial capillary plexus was significantly lower in the BRVO group, while the density in all segments of the choriocapillaris was significantly lower in the NTG group (P < 0.05 for all). CONCLUSIONS: Our findings demonstrate that BRVO and NTG have different LC structures and peripapillary vessel densities.

OCT ANGIOGRAPHY AND DOPPLER SONOGRAPHY IN NORMAL-TENSION GLAUCOMA.

AIMS: To investigate the dependence of blood vessel density and velocity in ophthalmic artery and arteria centralis retinae of the same eye in patients with normotensive glaucoma. METHODS: The sample consisted of 20 patients with normotensive glaucoma (NTG). There were 17 women (mean age 56.1) and 3 men (mean age 60 years). Inclusion criteria for study: visual acuity 1.0 with correction up to ±3 dioptres, approximately equal changes in the visual field, whereby it was incipient NTG and diagnosis was confirmed by electrophysiological examination, without further ocular or neurological disease. Parameters of vessel density (VD) were evaluated by Avanti RTVue XR (Optovue). Perfusion parameters such as peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI) were evaluated for ophthalmic artery (AO) and arteria centralis retinae (ACR) using Doppler sonography (Affinity 70G Philips, probe 5-12 MHz). Visual field (VF) was evaluated by automated perimeter (Medmont M700) using fast threshold glaucoma strategy test. The sum of sensitivity levels in apostilb (asb) were evaluated in range 0-22 degrees of visual field. Resulting values of VF were compared with VD and perfusion parameters in AO and ACR at the same eye. RESULTS: Pearsons correlation coefficient was used to evaluate the dependence. Data shows, that changes in visual fields are mainly caused by peripapillary VD of small and all vessels, and vessels throughout measured image area also. Correlation of small vessels throughout measured image area was weak (r = 0.23). Moderate negative correlation was found for PSV in AO and peripapillary small VD (r = -0.46), all peripapillary VD (r = -0.49), VD in whole area (r = -0.45), then between EDV in AO and VD in whole area (r = -0.42). Other correlations between VD and perfusion parameter were insignificant. CONCLUSIONS: Study confirms, that changes of visual field in NTG patients are mainly caused by VD rather than perfusion parameters, especially in AO. Perfusion parameters in ACR are not significantly correlated with changes of VF in NTG patients.

Results of Neuroimaging in Patients with Atypical Normal-Tension Glaucoma.

AIM: The aim of the study was to determine the frequency of pathologies which can mimic normal-tension glaucoma (NTG), observed in neuroimaging of NTG patients, and to evaluate the frequency of pathologies in determined additional indications for neuroimaging. Material and Methods. The studied group consisted of 126 NTG patients who met at least one of the following criteria: unilateral NTG, damage in the visual field (VF) inconsistent with optic disc appearance, fast VF progression, worsening of visual acuity, predominant optic disc pallor rather than optic disc excavation, diagnosis under the age of 50, and scotoma in VF restricted by a vertical line. The patients included in the research underwent MRI scans of the brain and both orbits. RESULTS: After neuroimaging, the results of 29 (23%) patients were qualified as positive; 18 (14.2%) of the identified pathologies were found to clinically affect the visual pathway. The most frequent brain pathology was intracranial meningiomas, observed in 4 patients (3.1%), followed by optic nerve sheath meningiomas diagnosed in 3 cases (2.4%), and brain glioma in 1 patient (0.8%). Pituitary gland adenomas were described in 6 patients (4.5%); 3 of the tumours were in contact with the optic chiasm. 53 (40%) patients had minimal ischemic changes in different regions of the brain. In the case of worsening BCVA or fast VF progression, the frequency of positive results was the highest (50% and 40%), whereas in the case of diagnosis at a young age and unilateral involvement, neuropathology was the rarest (0% and 6.9%). CONCLUSIONS: In the case of NTG, the decision to perform neuroimaging should be made after a detailed assessment of clinical status, rather in the event of finding the signs of possible compressive optic neuropathy than as an obligatory procedure for every patient.

Comparison of Lamina Cribrosa Morphology in Normal Tension Glaucoma and Autosomal-Dominant Optic Atrophy.

Purpose: To compare lamina cribrosa (LC) morphology in patients with normal tension glaucoma (NTG) and autosomal-dominant optic atrophy (ADOA). Methods: This cross-sectional study matched 24 patients diagnosed with ADOA (24 eyes) by age and retinal nerve fiber layer thickness with 48 patients diagnosed with NTG (48 eyes) by age with 48 healthy controls (48 eyes). Optic nerve heads were scanned by enhanced-depth imaging (EDI) optical coherence tomography (OCT). The LC curvature index (LCCI) and LC depth (LCD) on B-scan images obtained using EDI-OCT were measured at seven locations spaced equidistantly across the vertical optic disc diameter and compared among the NTG, ADOA, and control groups. Results: Mean LCCI and LCD were significantly greater in NTG than in ADOA and healthy eyes (P < 0.001 each) but did not differ significantly in ADOA and healthy eyes. Conclusions: NTG eyes have a more posteriorly curved and deeper LC than ADOA and healthy eyes. This finding provides insight into the role of LC morphology in NTG and provides a clinical clue to distinguish between NTG and ADOA.

Altered information flow and microstructure abnormalities of visual cortex in normal-tension glaucoma: Evidence from resting-state fMRI and DKI.

Normal tension glaucoma (NTG) is a neurodegenerative disease involves multiple brain areas, but the mechanism remains unclear. The aim of this study is to investigate the correlation between structural injury and functional reorganization in the brain of NTG, using resting-state functional MRI and diffusion kurtosis imaging (DKI) data acquired for 26 NTG patients and 24 control subjects. Granger causality analysis (GCA) was used to calculate the effective connectivity (EC) between visual cortices and the whole brain to reflect the information flow. The fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) derived from DKI of visual cortices were extracted to evaluate structural injury. Microstructural abnormalities were detected in bilateral BA17, BA18, and BA19. NTG patients showed significantly decreased EC from BA17 to higher visual cortices and increase EC from higher visual cortices to BA17. The EC from BA17 to posterior cingulate cortex (PCC) and from PCC to BA17 both significantly increased, while the EC from right BA18 and BA19 to PCC significantly decreased. Decreased EC between somatosensory cortex and BA17, as well as the decreased ECs between supramarginal gyrus (SMA) and BA17/BA19 were detected. Several abnormal ECs were significantly correlated with microstructural injuries of BA17 and BA18. In conclusion, NTG causes reorganization of information flows among visual cortices and other brain areas, which is consistent with brain microstructural injury.

Characteristics of Normal-tension Glaucoma Patients with Temporal Retinal Nerve Fibre Defects.

Glaucomatous visual field (VF) damage usually involves in the Bjerrum area, which refers to outside the central 10° region. However, some reports suggest that structural damage to the macula occurs even in the early stages of glaucoma. We investigated the characteristics of normal tension glaucoma (NTG) patients with temporal retinal nerve fibre layer (RNFL) defects. Ninety eyes from 90 subjects including 30 normal eyes, 30 eyes of 30 patients with normal-tension glaucoma with temporal RNFL defects, and 30 eyes of 30 patients with normal-tension glaucoma with inferotemporal or superotemporal RNFL defects were enrolled. The best-corrected visual acuity (BCVA) decreased significantly in glaucomatous eyes with temporal RNFL defects as compared with in controls and glaucomatous eyes with inferotemporal or superotemporal RNFL defects. VF tests showed more frequent central or cecocentral VF defects involving the central 10° region in glaucomatous eyes with temporal RNFL defects. VF defects were more frequently detected on short-wavelength automated perimetry (SWAP). Eyes with temporal RNFL defects had generally reduced ganglion cell-inner plexiform layer (GCIPL) thickness. In addition, the BCVA, GCIPL thicknesses, and SWAP findings were significantly different in glaucoma patients with temporal RNFL defects according to their colour vision deficiency, not RNFL thickness or standard automated perimetry (SAP) results.

Evaluation of Papillomacular Nerve Fiber Bundle Thickness in Glaucoma Patients with Visual Acuity Disturbance.

PURPOSE: Assessing the papillomacular nerve fiber bundle (PMB) can identify glaucoma patients with decreased visual acuity. In this study, we explore efficient methods for evaluating PMB thickness in glaucoma patients, based on swept source-optical coherence tomography (SS-OCT). METHODS: This study included 347 eyes of 205 open-angle glaucoma (OAG) patients. Patients were excluded if they had best-corrected decimal visual acuity < 0.3, axial length >28 mm, non-glaucoma ocular disease, or systemic disease affecting the visual field. We obtained vertical 12.0 × 9.0 mm 3D volume scans covering both the macular and optic disc regions with SS-OCT (DRI OCT Triton, Topcon), and measured the thickness of the PMB, as well as average macular retinal nerve fiber layer thickness (mRNFLT) and macular ganglion cell complex thickness (mGCCT) in the macular map and temporal-quadrant circumpapillary RNFL thickness (tcpRNFLT). We also measured central-strip RNFLT (csRNFLT) and GCC (csGCCT) in a 1.5 × 6.6 mm area of the scan centered between the fovea and optic nerve head. CsRNFLT and csGCCT were divided lengthwise into three 1.5 × 2.2 mm sections. We then calculated Spearman's rank correlation coefficient between these OCT measurements and visual acuity. Logistic regression analysis was used to find the cutoff value for the OCT measurements to predict logMAR < 0. RESULTS: The correlation coefficients with logMAR were 0.38 for mRNFLT, 0.44 for mGCCT, 0.37 for middle csRNFLT, 0.50 for middle csGCCT, and 0.33 for tcpRNFLT (all P < .0001). For middle csGCCT, the area under the curve indicating decreased visual acuity was 0.80, with a cutoff value of 88.6 µm (P < .001). CONCLUSIONS: We found strong associations between OCT parameters in the PMB, especially middle csGCCT, and visual acuity in patients with OAG. The thickness of the PMB may therefore be valuable information for glaucoma care and may help prevent visual acuity disturbance.

Thinning rates of retinal nerve layer and ganglion cell-inner plexiform layer in various stages of normal tension glaucoma.

AIMS: To compare the changes in the macular retinal nerve fibre layer (mRNFL), macular ganglion cell layer and inner plexiform layer (mGCIPL), and circumpapillary retinal nerve fibre layer (cpRNFL) in various stages of normal tension glaucoma (NTG) using spectral domain optical coherence tomography. METHODS: Eyes with NTG (n=218) were assigned into three groups based on initial mean deviation (MD) as follows: mild (MD>-6 dB), moderate (-6 dB≥MD≥-12 dB) and severe (-12 dB>MD>-20 dB). Annual rates of change in mRNFL, mGCIPL and cpRNFL thickness were calculated by linear regression analysis. RESULTS: Age, gender, spherical equivalent, and average intraocular pressure during follow-up were not significantly different among the three groups. There were significant differences in the mRNFL, mGCIPL and cpRNFL among the three groups at baseline (p<0.0001 in all sectors except for the mRNFL in the superonasal sector). The average thinning rates of the mRNFL, mGCIPL and cpRNFL were -0.38±0.32 µm/year, -0.62±0.46 µm/year and -0.86±0.83 µm/year, respectively. No significant difference in the rates of change in the mRNFL and mGCIPL were found among the groups in any sector. However, there was a significant difference in the rate of change in the cpRNFL among the groups (in all sectors: p<0.0001). CONCLUSIONS: Changes in the mRNFL and mGCIPL can reflect the progression of NTG even in its advanced stage. However, careful interpretation of changes in the cpRNFL in the advanced stage of glaucoma is warranted due to a potential floor effect.