Relationship between corneal hysteresis and the site of damage to peripapillary retinal nerve fibre layer thickness in open-angle glaucoma.

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 ß 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.

Differentiating Branch Retinal Artery Occlusion From Normal Tension Glaucoma With Optical Coherence Tomography Angiography.

BACKGROUND: To describe a patient with branch retinal artery occlusion that was misdiagnosed as normal tension glaucoma (NTG). CASE PRESENTATION: A female 76-year-old patient presenting inferior nasal visual field scotoma, neuroretinal thinning in the optic disk of the right eye with corresponding atrophy of superior retinal nerve fiber layer in optical coherence tomography (OCT). She was treated with latanoprost eye drops for NTG. However macular OCT angiography showed a localized thinning of the inner retina following the superior temporal branch retinal artery path, along with a superficial and medium capillary plexus reduction and superior macular ganglion cell layer atrophy. Further investigation with carotid arteries angio-tomography revealed an atheromatous lesion in the right and left carotid bulb with stenosis of 50-60%, in addition to aneurysms of the cavernous, pituitary and communicating segments of the left and right internal carotid artery, reinforcing the diagnosis of superior temporal branch retinal artery ischemic. CONCLUSION: This case highlights the importance of establishing differential diagnosis in cases of presumed NTG and reinforces the use of the OCT angiography in clinical practice.

Profiles of microRNA in aqueous humor of normal tension glaucoma patients using RNA sequencing.

We aimed to identify and compare microRNAs (miRNAs) from individual aqueous humor samples between normal-tension glaucoma (NTG) patients and normal controls. Aqueous humor (80 to 120 µl) was collected before cataract surgery. Six stable NTG patients and seven age-matched controls were included in the final analysis. RNA sequencing was conducted for RNA samples extracted from the 13 aqueous humor samples, and bioinformatics analysis was employed for the miRNA targets and related pathways. Two hundred and twenty-eight discrete miRNAs were detected in the aqueous humor and consistently expressed in all samples. Eight significantly upregulated miRNAs were found in the NTG patients compared to the controls (fold-change > 2, p < 0.05). They were hsa-let-7a-5p, hsa-let-7c-5p, hsa-let-7f-5p, hsa-miR-192-5p, hsa-miR-10a-5p, hsa-miR-10b-5p, hsa-miR-375, and hsa-miR-143-3p. These miRNAs were predicted to be associated with the biological processes of apoptosis, autophagy, neurogenesis, and aging in the gene ontology categories. The related Kyoto encyclopedia of genes and genomes pathways were extracellular matrix-receptor interaction, mucin-type O-glycan biosynthesis, biotin metabolism, and signaling pathways regulating the pluripotency of stem cells. The differentially expressed miRNA in the NTG samples compared to the controls suggest the possible roles of miRNA in the pathogenesis of NTG. The underlying miRNA-associated pathways further imply novel targets for the pathogenesis of NTG.

Neuroprotective effects of bone marrow Sca-1+ cells against age-related retinal degeneration in OPTN E50K mice.

Glaucoma is characterized by retinal ganglion cell (RGC) death, the underlying mechanisms of which are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal-tension glaucoma (NTG), which directly affects RGCs in the absence of high intraocular pressure and causes severe glaucomatous symptoms in patients. Bone marrow (BM) stem cells have been demonstrated to play a key role in regenerating damaged tissue during ageing and disease through their trophic effects and homing capability. Here, we separated BM stem cells into Sca-1+ and Sca-1- cells and transplanted them into lethally irradiated aged OPTN E50K mice to generate Sca-1+ and Sca-1- chimaeras, respectively. After 3 months of BM repopulation, we investigated whether Sca-1+ cells maximized the regenerative effects in the retinas of NTG model mice with the OPTN E50K mutation. We found that the OPTN E50K mutation aggravated age-related deficiency of neurotrophic factors in both retinas and BM during NTG development, leading to retinal degeneration and BM dysfunction. Sca-1+ cells from young healthy mice had greater paracrine trophic effects than Sca-1- cells and Sca-1+ cells from young OPTN E50K mice. In addition, Sca-1+ chimaeras demonstrated better visual functions than Sca-1- chimaeras and untreated OPTN E50K mice. More Sca-1+ cells than Sca-1- cells were recruited to repair damaged retinas and reverse visual impairment in NTG resulting from high expression levels of neurotrophic factors. These findings indicated that the Sca-1+ cells from young, healthy mice may have exhibited an enhanced ability to repair retinal degeneration in NTG because of their excellent neurotrophic capability.

Plasma GDF-15 concentration is not elevated in open-angle glaucoma.

AIM: Recently, the level of growth differentiation factor 15 (GDF-15) in blood, was proposed as biomarker to detect mitochondrial dysfunction. In the current study, we evaluate this biomarker in open-angle glaucoma (OAG), as there is increasing evidence that mitochondrial dysfunction plays a role in the pathophysiology of this disease. METHODS: Plasma GDF-15 concentrations were measured with ELISA in 200 OAG patients and 61 age-matched controls (cataract without glaucoma). The OAG patient group consisted of high tension glaucoma (HTG; n = 162) and normal tension glaucoma (NTG; n = 38). Groups were compared using the Kruskal-Wallis nonparametric test with Dunn's multiple comparison post-hoc correction. GDF-15 concentration was corrected for confounders identified with forward linear regression models. RESULTS: Before correcting for confounders, median plasma GDF-15 levels was significantly lower in the combined OAG group (p = 0.04), but not when analysing HTG and NTG patients separately. Forward linear regression analysis showed that age, gender, smoking and systemic hypertension were significant confounders affecting GDF-15 levels. After correction for these confounders, GDF-15 levels in OAG patients were no longer significantly different from controls. Subgroup analysis of the glaucoma patients did not show a correlation between disease severity and plasma GDF-15, but did reveal that for NTG patients, intake of dietary supplements, which potentially improve mitochondrial function, correlated with lower plasma GDF-15. CONCLUSION: The present study suggests that plasma GDF-15 is not suited as biomarker of mitochondrial dysfunction in OAG patients.

Proteomic analysis of aged and OPTN E50K retina in the development of normal tension glaucoma.

Progressive degeneration of retinal ganglion cells (RGCs) is a major characteristic of glaucoma, whose underlying mechanisms are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal tension glaucoma (NTG), directly affecting RGCs without high intraocular pressure and causing severe glaucomatous symptoms in clinical settings. A systematic analysis of the NTG mouse model is crucial for better understanding of the underlying pathological mechanisms for glaucoma. To elucidate proteomic and biochemical pathway alterations during NTG development, we established an OPTN E50K mutant mouse model through CRISPR/Cas9. Retinal proteins from resulting mice exhibiting glaucomatous phenotypes were subject to tandem mass tag-labeled quantitative proteomics and then analyzed through bioinformatics methods to characterize the molecular and functional signatures of NTG. We identified 6364 quantitative proteins in our proteomic analysis. Bioinformatics analysis revealed that OPTN E50K mice experienced protein synthesis dysregulation, age-dependent energy defects and autophagy-lysosome pathway dysfunction. Certain biological features, including amyloid deposition, RNA splicing, microglia activation and reduction of crystallin production, were similar to Alzheimer's disease. Our study is the first to describe proteomic and biochemical pathway alterations in NTG pathogenesis during disease advancement. Several proteomic signatures overlapped with retinal changes found in the ad mice model, suggesting the presence of common mechanisms between age-related degenerative disorders, as well as prospective new targets for diagnostic and therapeutic strategies.

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.

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.

EAAT1 variants associated with glaucoma.

Glaucoma is one of the leading causes of blindness characterized by progressive loss of retinal ganglion cells (RGCs) and their axons. We reported that glutamate/aspartate transporter (GLAST) knockout mice showed progressive RGC loss and optic nerve degeneration that are similar to glaucoma. To explore the possibility that rare variants in the EAAT1 gene (the human homolog of GLAST) cause susceptibility to glaucoma, we performed targeted sequencing of EAAT1 in 440 patients with glaucoma and 450 control subjects. We identified 8 rare variants in 20 out of 440 patients, including 4 synonymous and 4 missense variants located at protein coding regions. One of these rare variants (rs117295512) showed significant association with the risk of glaucoma (OR = 10.44, P = 0.005). Furthermore, the allele frequency for loss-of-function EAAT1 variants, pAla169Gly and pAla329Thr, was 5.5 folds higher in the glaucoma (1.1%) compared with the control cohort (0.2%). These findings suggest that these rare variants may contribute to the pathogenesis of glaucoma and that loss-of-function variants in EAAT1 are present in a small number of patients with glaucoma.

No association between POU4F1, POU4F2, ISL1 polymorphisms and normal-tension glaucoma.

BACKGROUND: Normal-tension glaucoma (NTG) that occurs despite normal intraocular pressure has genetic predisposition. Since retinal ganglion cells (RGCs) are a key node in pathogenesis of glaucoma, neurodegeneration of RGCs is thought to be the main cause increasing the risk of NTG development. Here, we aimed to investigate the association of polymorphisms in RGC development genes with NTG development. MATERIALS AND METHODS: We performed a case-control association study of 435 patients with NTG and 419 normal controls. We genotyped four single nucleotide polymorphisms (SNPs) in genes responsible for RGC development, namely POU4F2 (rs13152799 and rs1504360), POU4F1 (rs9601092), and ISL1 (rs2288468), by either real-time PCR or PCR-RFLP, and evaluated its association with the risk of NTG development. RESULTS: No significant association was observed between the candidate SNPs and NTG development. CONCLUSIONS: To the best of our knowledge, this is the first report exploring the association between genes regulating RGC development and NTG susceptibility. Our data could provide a reference for further researches that focus on finding additional potential SNPs of POU4F2, POU4F1, ISL1 or other RGC development genes for NTG.

Comparison of Lamina Cribrosa Morphology in Eyes with Ocular Hypertension and Normal-Tension Glaucoma.

Purpose: To characterize differences in the lamina cribrosa (LC) morphology between healthy, ocular hypertension (OHT), and naive normal-tension glaucoma (NTG) eyes. Methods: Each group consisted of 80 eyes of 80 participants who were matched for age, sex, and axial length. The participants underwent enhanced-depth-imaging volume scanning of the optic nerve head using spectral-domain optical coherence tomography. The lamina cribrosa curvature index (LCCI) and lamina cribrosa thickness (LCT) were measured in horizontal B-scan images spaced equidistantly across the vertical diameter of the optic disc. Results: The LCCIs in all seven planes were smaller in both OHT and healthy eyes than in NTG eyes (all P < 0.001), and did not differ significantly between the OHT and healthy eyes. The LCTs in all three planes were greatest in OHT eyes followed by healthy and then NTG eyes (all P < 0.001). Overall, the larger LCCI was associated with smaller LCT (P < 0.001). Conclusions: The LC was thin and steeply curved in NTG eyes than in healthy and OHT eyes. In OHT eyes, the LC was thick, and its curvature was comparable to healthy eyes. Longitudinal studies are required to examine whether the straight and thickened LCs in OHT eyes precede the onset of OHT or are a protective response to elevated intraocular pressure.

Topographic correlation between macular superficial microvessel density and ganglion cell-inner plexiform layer thickness in glaucoma-suspect and early normal-tension glaucoma.

BACKGROUND/AIMS: To investigate the topographic relationship between macular superficial microvessel density (SMD) and macular ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with glaucoma-suspect (GS) and early normal-tension glaucoma (NTG). METHODS: A total of 86 eyes of 86 patients with early NTG (standard automated perimetry mean deviation >-5.5 decibels) and a total of 25 eyes of 25 patients with GS were retrospectively reviewed. All of the subjects underwent optical coherence tomography (OCT) and OCT angiography (OCTA) scan. On the OCTA scan images, macular SMD was analysed by customised software. RESULTS: In GS and patients with early NTG, macular GCIPL thickness showed significant correlations with macular SMD in the superotemporal (ST), inferotemporal (IT) and inferoinferior (II) sectors (r=0.191, 0.373 and 0.346 for ST, IT and II sector, respectively). Additionally, circumpapillary retinal nerve fibre layer (RNFL) thickness and macular SMD showed significant correlations between the ST sector of the macula and the 1, 9 clock-hour peripapillary regions and between the IT and II sectors of the macula and the 6, 7, 8 clock-hour peripapillary regions. The IT sector macular SMD showed fair diagnostic power (area under the receiver operating characteristic curve [AUROC] = 0.758) and showed high diagnostic power when combined with IT sector macular GCIPL thickness (AUROC=0.954). CONCLUSIONS: Sectoral macular SMD showed topographic correlations with macular GCIPL thickness and circumpapillary RNFL thickness in patients with GS and early-stage NTG. Macular SMD analysis is potentially useful in the clinical evaluation of early glaucoma.

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.

Age dependence of plasma endothelin levels in glaucoma patients.

The aim of the study was to investigate the endothelin-1 (ET-1) plasma level and its age dependence in patients with normal tension glaucoma (NTG), high tension glaucoma (HTG), and healthy controls. In blood samples from 35 NTG patients, 34 HTG patients, and 36 controls, ET-1 plasma levels were determined by enzyme-linked immunosorbent assay (ELISA). After adjustment for age and gender, the mean ET-1 levels were found to be similar in all three study groups. The age dependency however was highest in NTGs and significantly different from that of the controls. For the HTGs, this dependence was weaker and not significantly different from that of the controls. Our findings suggest that age had a significantly greater influence on ET plasma level in the NTG patients than in the HTG patients and controls. This supports previous reports indicating that ET plays a role in the pathogenesis of glaucoma, and in particular normal NTG.

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.

Peripapillary Vessel Density in Young Patients with Open-Angle Glaucoma: Comparison between High-Tension and Normal-Tension Glaucoma.

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.

Survival of Alpha and Intrinsically Photosensitive Retinal Ganglion Cells in NMDA-Induced Neurotoxicity and a Mouse Model of Normal Tension Glaucoma.

Purpose: We assess if α retinal ganglion cells (αRGCs) and intrinsically photosensitive retinal ganglion cells (ipRGCs) survive in mouse models of glaucoma. Methods: Two microliters of N-methyl-D-aspartate (NMDA; 1 mM) or PBS were injected intraocularly 7 days before sacrifice. Immunohistochemical analyses of the retina were performed using antibodies against RNA-binding protein with multiple splicing (RBPMS), osteopontin, and melanopsin. Immunohistochemical analyses also were performed in adult mice with glutamate/aspartate transporter (GLAST) deletion (GLAST knockout [KO] mice), a mouse model of normal tension glaucoma. Results: NMDA-induced loss of RBPMS-positive total RGCs was 58.4% ± 0.4% compared to PBS-treated controls, whereas the loss of osteopontin-positive αRGCs was 5.0% ± 0.6% and that of melanopsin-positive ipRGCs was 7.6% ± 1.6%. In GLAST KO mice, the loss of total RGCs was 48.4% ± 0.9% compared to wild-type mice, whereas the loss of αRGCs and ipRGCs was 3.9% ± 0.4% and 9.3% ± 0.5%, respectively. The distribution of survived total RGCs, αRGCs, and ipRGCs was similar regardless of the location of the retina. Conclusions: These results suggest that αRGC and ipRGC are highly tolerant to NMDA-induced neurotoxicity and NTG-like neurodegeneration in GLAST KO mice.

Impact of Posterior Sclera on Glaucoma Progression in Treated Myopic Normal-Tension Glaucoma Using Reconstructed Optical Coherence Tomographic Images.

Purpose: To investigate factors associated with visual field (VF) progression in treated myopic normal-tension glaucoma (NTG) using a novel posterior sclera reconstruction method involving swept-source optical coherence tomography (OCT). Methods: Fifty-six myopic patients on ocular hypotensive therapy with the diagnose NTG had five or more VF tests during a period of 72.63 ± 20.46 months in clinical follow-up. Glaucomatous VF progression was decided by the standards of Early Manifest Glaucoma Trial criteria. Coronally reconstructed OCT images were used to obtain the position of the deepest point of the eye (DPE), and parameterized the distance (Disc-DPE distance), depth (Disc-DPE depth) and angle (Disc-DPE angle) of the posterior sclera. The Cox proportional hazards model and Kaplan-Meier curves were used to determine the risk factors for VF progression. Results: Among 56 eyes, 28 showed VF progression. Eyes with progression had significantly different distance, depth, and angle of the DPE position (P = 0.049, P = 0.032, and P = 0.006, respectively). A multivariate Cox proportional hazard model revealed that the vertical tilt angle (hazard ratio [HR] 0.835, P = 0.026) and the DPE positioned temporal to fovea (HR 4.314, P = 0.001) were associated with VF progression. Among eyes with DPE positioned temporal to fovea, in addition to percentage reduction in IOP from baseline (HR 0.915, P = 0.012), shorter axial length (HR 0.542, P = 0.044) was found to be associated with VF progression. Conclusions: Eyes with a particular posterior sclera structure are at increased risk for glaucoma progression in treated myopic NTG patients. This finding highlights the significance of investigating posterior sclera structure and its relevance to initiate or augment treatment for myopic glaucoma patients.

Optic disc cupping characteristics of normal pressure hydrocephalus patients with normal-tension glaucoma.

We examined the potential association of idiopathic normal pressure hydrocephalus (iNPH) with the generation of normal-tension glaucoma (NTG), to explore possible relationships between intracranial pressure (ICP) and the presence of glaucoma, and to compare disc morphology of NTG patients with or without iNPH. We investigated 20 iNPH patients, examined the prevalence of glaucoma, and compared the optic discs of NTG patients with iNPH (n = 11) and age-matched NTG patients without iNPH (n = 16). All data were collected prior to the treatment of iNPH, to eliminate the possibility that the treatment may have contributed to the progression of NTG. The diagnoses of NTG were made using visual field data, intraocular pressure measurements, fundoscopy, and optical coherence tomography (OCT). Using OCT, the optic nerve disc depth was also measured. The ICP was higher in the iNPH with NTG compared to iNPH without NTG (p = 0.0425), and the cupping depths of the discs of NTG patients with iNPH were significantly shallower compared with those of NTG patients without iNPH (p = 0.0097). Based on the difference in cupping depth, NTG patients with iNPH may have a different morphology from typical glaucoma patients, which could in turn reflect a different pathogenesis compared to NTG patients without iNPH.