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Primary open-angle glaucoma (POAG) is subdivided depending on eye pressure. Patients with normal-tension glaucoma (NTG) have never had high intraocular pressure (IOP) measured while patients with ocular hypertension (OHT) have high eye pressure but no signs of glaucoma. Although IOP is considered to be a risk factor for all glaucoma patients, it is reasonable to assume that other risk factors such as inflammation play a role. We aimed to characterize the proteome and cytokine profile during hypoxia in plasma from patients with NTG (n = 10), OHT (n = 10), and controls (n = 10). Participants were exposed to hypoxia for two hours, followed by 30 min of normoxia. Samples were taken before ("baseline"), during ("hypoxia"), and after hypoxia ("recovery"). Proteomics based on liquid chromatography coupled with mass spectrometry (LC–MS) was performed. Cytokines were measured by Luminex assays. Bioinformatic analyses indicated the involvement of complement and coagulation cascades in NTG and OHT. Regulation of high-density lipoprotein 3 (HDL3) apolipoproteins suggested that changes in cholesterol metabolism are related to OHT. Hypoxia decreased the level of tumor necrosis factor-α (TNF-α) in OHT patients compared to controls. Circulating levels of interleukin-1β (IL-1β) and C-reactive protein (CRP) were decreased in NTG patients compared to controls during hypoxia. After recovery, plasma interleukin-6 (IL-6) was upregulated in patients with NTG and OHT. Current results indicate an enhanced systemic immune response in patients with NTG and OHT, which correlates with pathogenic events in glaucoma. Apolipoproteins may have anti-inflammatory effects, enabling OHT patients to withstand inflammation and development of glaucoma despite high IOP. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the structural, microvascular, and functional progression of normal tension glaucoma (NTG) with or without high myopia by examining longitudinal changes in optical coherence tomography angiography (OCTA) and visual field (VF) parameters. Methods: We evaluated 61 NTG eyes and classified 25 of the eyes with axial lengths (ALs) of ≥26 mm as highly myopic. We assessed the rate of change in OCTA parameters, namely radial peripapillary capillary (RPC) vessel density (VD), parafovea VD, deep parafovea VD, retinal nerve fibre layer (RNFL) thickness, and ganglion cell complex thickness. We evaluated the correlation of the rate of change in OCTA parameters with VF loss and AL. Results: Among the 61 NTG eyes, rates of loss of RPC VD, parafovea VD, deep parafovea VD, and RNFL thickness were significantly different from zero despite the nonsignificant rate of change in VF mean deviation (MD). Changes in these OCTA parameters did not differ significantly in highly myopic NTG eyes. The rate of change in VF MD was significantly correlated with the rate of change in parafovea VD in highly myopic and non‐highly myopic NTG eyes. In highly myopic NTG eyes, AL was negatively correlated with the rates of loss of RNFL thickness, VF MD, and VF PSD. Conclusion: NTG eyes with a relatively stable VF exhibited loss of VD and RNFL thickness. VF progression in NTG was correlated with decreasing parafovea VD, indicating a structure–function correlation. Greater AL may indicate faster VF loss and RNFL thinning in highly myopic NTG eyes. [ABSTRACT FROM AUTHOR]

In this study, intraocular pressure (IOP) was measured in sitting, supine, prone, and standing (ST) positions and again five minutes after standing (ST-5) utilizing a Tono-Pen AVIA in 124 eyes of 62 healthy subjects with ages ranging from 21 to 59 years (mean 30 ± 10 years). In each subject, the average IOP of both eyes was used for the statistical evaluation. The mean IOP difference between the ST and sitting positions was −0.13 ± 1.63 mmHg (p = 0.548); between ST-5 and sitting, it was 0.53 ± 1.24 mmHg (p = 0.001); between supine and sitting, it was 1.30 ± 1.48 mmHg (p < 0.001); between ST and supine, it was −1.43 ± 1.74 mmHg (p < 0.001); between ST-5 and supine, it was −0.77 ± 1.59 mmHg (p < 0.001); between prone and supine, it was 2.24 ± 1.92 mmHg (p < 0.001); between ST and ST-5, it was −0.67 ± 1.84 mmHg (range: −7.5 to 5 mmHg) (p = 0.007); between prone and ST, it was 3.46 ± 2.01 mmHg (p < 0.001); between ST-5 and prone, it was −2.46 ± 1.67 mmHg (p < 0.001); and between sitting and prone, it was −3.22 ± 1.56 mmHg (p < 0.001). The results show a significant IOP increase in the ST-5 position, suggesting that such measurements need to be performed in an attempt to explain the progression of glaucoma in apparently normal-tension patients. [ABSTRACT FROM AUTHOR]

Abstract Background Minimally invasive bleb surgery using the XEN-45 gel stent has not been established for the treatment of normal-tension glaucoma (NTG). The main objective of this study was to evaluate the long-term treatment efficacy and safety of XEN-45 in eyes with uncontrolled NTG. Methods A retrospective analysis of patients with NTG who underwent XEN-45 gel stent implantation at university hospital Tuebingen between 2016 and 2021. The primary outcome measure was surgical success after three years defined as lowering of intraocular pressure (IOP) of ≥ 20%, with target IOP between 6 and 15 mmHg. Success was complete without and qualified irrespective of topical antiglaucoma medication use. The need for further glaucoma surgery, except for needling, was regarded as a failure. The secondary outcome measures included changes in mean IOP, number of antiglaucoma medications, and needling and complication rates. Results Twenty-eight eyes from 23 patients were included in the final analysis. Complete and qualified success rates were 56.5% and 75% after three years, respectively. Mean postoperative IOP ± standard deviation decreased significantly after three years from 19.3 ± 2.0 mmHg at baseline to 13.7 ± 4.2 mmHg (n = 22; p

Abstract Backgroud The aim of this study was to investigate the associations between fluctuation in blood pressure (BP), ocular perfusion pressure (OPP) and visual field (VF) progression in normal-tension glaucoma (NTG). Methods This prospective, longitudinal study included 44 patients with NTG. Only newly diagnosed NTG patients who had not been treated with a glaucoma medication were included. Patients were examined every year for 7 years. Intraocular pressure (IOP), heart rate (HR), systolic BP (SBP), diastolic BP (DBP), ocular perfusion pressure (OPP), and diastolic ocular perfusion pressure (DOPP) were measured at the same time. Ophthalmic examinations, including perimetry, were performed also. Initial VF were compared with follow-up data after 7 years. Results After 7 years of follow-up, 9 of the 44 patients showed VF progression. The standard deviation (SD) of SBP and OPP were significantly associated with VF progression (P = 0.007,

Background: Minimally invasive bleb surgery using the XEN-45 gel stent has not been established for the treatment of normal-tension glaucoma (NTG). The main objective of this study was to evaluate the long-term treatment efficacy and safety of XEN-45 in eyes with uncontrolled NTG. Methods: A retrospective analysis of patients with NTG who underwent XEN-45 gel stent implantation at university hospital Tuebingen between 2016 and 2021. The primary outcome measure was surgical success after three years defined as lowering of intraocular pressure (IOP) of ≥ 20%, with target IOP between 6 and 15 mmHg. Success was complete without and qualified irrespective of topical antiglaucoma medication use. The need for further glaucoma surgery, except for needling, was regarded as a failure. The secondary outcome measures included changes in mean IOP, number of antiglaucoma medications, and needling and complication rates. Results: Twenty-eight eyes from 23 patients were included in the final analysis. Complete and qualified success rates were 56.5% and 75% after three years, respectively. Mean postoperative IOP ± standard deviation decreased significantly after three years from 19.3 ± 2.0 mmHg at baseline to 13.7 ± 4.2 mmHg (n = 22; p < 0.0001). The median number of antiglaucoma medications decreased from 2 (range 0–4) to 0 after three years (range 0–3; p < 0.0001). Sixteen eyes (57%) required a median of 1 (range 1–3) needling procedures. One eye required further glaucoma surgery. No sight-threatening complications were observed. Conclusion: The XEN-45 stent is effective and safe for the long-term treatment of NTG. However, needling was frequently required to improve outcomes. [ABSTRACT FROM AUTHOR]

Backgroud: The aim of this study was to investigate the associations between fluctuation in blood pressure (BP), ocular perfusion pressure (OPP) and visual field (VF) progression in normal-tension glaucoma (NTG). Methods: This prospective, longitudinal study included 44 patients with NTG. Only newly diagnosed NTG patients who had not been treated with a glaucoma medication were included. Patients were examined every year for 7 years. Intraocular pressure (IOP), heart rate (HR), systolic BP (SBP), diastolic BP (DBP), ocular perfusion pressure (OPP), and diastolic ocular perfusion pressure (DOPP) were measured at the same time. Ophthalmic examinations, including perimetry, were performed also. Initial VF were compared with follow-up data after 7 years. Results: After 7 years of follow-up, 9 of the 44 patients showed VF progression. The standard deviation (SD) of SBP and OPP were significantly associated with VF progression (P = 0.007, < 0.001, respectively). Multiple regression analysis showed that VF progression was significantly associated with SD of OPP (odds ratio, OR = 2.012, 95% CI = 1.016–3.985; P = 0.045). Conclusions: Fluctuation in OPP was associated with VF progression in patients with NTG. [ABSTRACT FROM AUTHOR]

Abstract Background Many individuals suffer from normal tension glaucoma (NTG) in China. This study utilized Markov models to evaluate the cost-utility of applying many medications and surgery for mild-stage NTG when disease progression occurred at a mild stage. Methods A 10-year decision-analytic Markov model was developed for the cost-utility analysis of treating mild-stage NTG with surgery and increased application of medication. We hypothesized that all 100,000 samples with a mean age of 64 were in mild stages of NTG. Transitional probabilities from the mild to moderate to severe stages and the basic parameters acquired from the CNTGS were calculated. Incremental cost-utility ratios (ICUR) were calculated for treating all patients with NTG by probabilistic sensitivity analysis (PSA) and Monte Carlo simulation. One-way sensitivity analysis were conducted by adjusting the progression rate, cost of medications or trabeculectomy, cost of follow-up, and surgical acceptance rate. Results The ICUR of treating mild stage NTG with medication over 10 years was $12743.93 per quality-adjusted life years (QALYs). The ICUR for treating mild stage NTG patients with a 25% and 50% surgery rate with medication were $8798.93 and $4851.93 per QALYs, respectively. In this model, the cost-utility of treating NTG was sensitive to disease progression rate, surgical treatment rate, and medication costs. Conclusions According to the results of the cost-utility analysis, it was a reasonable and advantageous strategy to administer a lot of medication and surgery for NTG in the mild stages of the disease. In the model, the greater the probability of patients undergoing surgery, the strategy becomes more valuable.

This article is an English translation of the 4th Finnish Current Care Guideline for diagnostics, treatment and follow‐up of primary open‐angle glaucoma, normal‐tension glaucoma and pseudoexfoliative glaucoma. This guideline is based on systematic literature reviews and expert opinions with Finland's geographical and operational healthcare environment in mind. [ABSTRACT FROM AUTHOR]

Background: Impaired cerebrospinal fluid (CSF) dynamics is involved in the pathophysiology of neurodegenerative diseases of the central nervous system and the optic nerve (ON), including Alzheimer's and Parkinson's disease, as well as frontotemporal dementia. The smallness and intricate architecture of the optic nerve subarachnoid space (ONSAS) hamper accurate measurements of CSF dynamics in this space, and effects of geometrical changes due to pathophysiological processes remain unclear. The aim of this study is to investigate CSF dynamics and its response to structural alterations of the ONSAS, from first principles, with supercomputers. Methods: Large-scale in-silico investigations were performed by means of computational fluid dynamics (CFD) analysis. High-order direct numerical simulations (DNS) have been carried out on ONSAS geometry at a resolution of 1.625 μm/pixel. Morphological changes on the ONSAS microstructure have been examined in relation to CSF pressure gradient (CSFPG) and wall strain rate, a quantitative proxy for mass transfer of solutes. Results: A physiological flow speed of 0.5 mm/s is achieved by imposing a hydrostatic pressure gradient of 0.37–0.67 Pa/mm across the ONSAS structure. At constant volumetric rate, the relationship between pressure gradient and CSF-accessible volume is well captured by an exponential curve. The ONSAS microstructure exhibits superior mass transfer compared to other geometrical shapes considered. An ONSAS featuring no microstructure displays a threefold smaller surface area, and a 17-fold decrease in mass transfer rate. Moreover, ONSAS trabeculae seem key players in mass transfer. Conclusions: The present analysis suggests that a pressure drop of 0.1–0.2 mmHg over 4 cm is sufficient to steadily drive CSF through the entire subarachnoid space. Despite low hydraulic resistance, great heterogeneity in flow speeds puts certain areas of the ONSAS at risk of stagnation. Alterations of the ONSAS architecture aimed at mimicking pathological conditions highlight direct relationships between CSF volume and drainage capability. Compared to the morphological manipulations considered herein, the original ONSAS architecture seems optimized towards providing maximum mass transfer across a wide range of pressure gradients and volumetric rates, with emphasis on trabecular structures. This might shed light on pathophysiological processes leading to damage associated with insufficient CSF flow in patients with optic nerve compartment syndrome. [ABSTRACT FROM AUTHOR]

Background: Many individuals suffer from normal tension glaucoma (NTG) in China. This study utilized Markov models to evaluate the cost-utility of applying many medications and surgery for mild-stage NTG when disease progression occurred at a mild stage. Methods: A 10-year decision-analytic Markov model was developed for the cost-utility analysis of treating mild-stage NTG with surgery and increased application of medication. We hypothesized that all 100,000 samples with a mean age of 64 were in mild stages of NTG. Transitional probabilities from the mild to moderate to severe stages and the basic parameters acquired from the CNTGS were calculated. Incremental cost-utility ratios (ICUR) were calculated for treating all patients with NTG by probabilistic sensitivity analysis (PSA) and Monte Carlo simulation. One-way sensitivity analysis were conducted by adjusting the progression rate, cost of medications or trabeculectomy, cost of follow-up, and surgical acceptance rate. Results: The ICUR of treating mild stage NTG with medication over 10 years was $12743.93 per quality-adjusted life years (QALYs). The ICUR for treating mild stage NTG patients with a 25% and 50% surgery rate with medication were $8798.93 and $4851.93 per QALYs, respectively. In this model, the cost-utility of treating NTG was sensitive to disease progression rate, surgical treatment rate, and medication costs. Conclusions: According to the results of the cost-utility analysis, it was a reasonable and advantageous strategy to administer a lot of medication and surgery for NTG in the mild stages of the disease. In the model, the greater the probability of patients undergoing surgery, the strategy becomes more valuable. [ABSTRACT FROM AUTHOR]

Insufficient blood supply, vascular dysregulation, perfusion pressure and endothelial dysfunction may account for the pathogenic mechanism. OCT angiography (OCTA) measurements have been reported to be useful for glaucoma diagnostics. OCTA microvasculature could serve as a potential biomarker for glaucoma diagnosis. One of the important criteria for the treatment of NTG is the reduction of IOP, which is achieved by both conservative methods of treatment and laser and surgical interventions. With timely diagnosis, control of IOP and monitoring of morphofunctional changes in the eyes with NTG, it becomes possible to suspend the development of glaucoma optic neuropathy and preserve the patient’s vision for a long time.

Glaucoma is a complex and multifactorial disease defined as the loss of retinal ganglion cells (RGCs) and their axons. Besides an elevated intraocular pressure (IOP), other mechanisms play a pivotal role in glaucoma onset and progression. For example, it is known that excitotoxicity, immunological alterations, ischemia, and oxidative stress contribute to the neurodegeneration in glaucoma disease. To study these effects and to discover novel therapeutic approaches, appropriate animal models are needed. In this review, we focus on various glaucoma animal models beyond an elevated IOP. We introduce genetically modified mice, e.g., the optineurin E50K knock-in or the glutamate aspartate transporter (GLAST)-deficient mouse. Excitotoxicity can be mimicked by injecting the glutamate analogue N-methyl-D-aspartate intravitreally, which leads to rapid RGC degeneration. To explore the contribution of the immune system, the experimental autoimmune glaucoma model can serve as a useful tool. Here, immunization with antigens led to glaucoma-like damage. The ischemic mechanism can be mimicked by inducing a high IOP for a certain amount of time in rodents, followed by reperfusion. Thereby, damage to the retina and the optic nerve occurs rapidly after ischemia/reperfusion. Lastly, we discuss the importance of optic nerve crush models as model systems for normal-tension glaucoma. In summary, various glaucoma models beyond IOP increase can be utilized. [ABSTRACT FROM AUTHOR]

Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs). The main risk factor is elevated intraocular pressure (IOP), but the actual cause of the disease remains unknown. Emerging evidence indicates that metabolic dysfunction plays a central role. The aim of the current study was to determine and compare the effect of universal hypoxia on the metabolomic signature in plasma samples from healthy controls (n = 10), patients with normal-tension glaucoma (NTG, n = 10), and ocular hypertension (OHT, n = 10). By subjecting humans to universal hypoxia, we aim to mimic a state in which the mitochondria in the body are universally stressed. Participants were exposed to normobaric hypoxia for two hours, followed by a 30 min recovery period in normobaric normoxia. Blood samples were collected at baseline, during hypoxia, and in recovery. Plasma samples were analyzed using a non-targeted metabolomics approach based on liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Multivariate analyses were conducted using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and univariate analysis using the Wilcoxon signed-rank test and false discovery rate (FDR) correction. Unique metabolites involved in fatty acid biosynthesis and ketone body metabolism were upregulated, while metabolites of the kynurenine pathway were downregulated in OHT patients exposed to universal hypoxia. Differential affection of metabolic pathways may explain why patients with OHT initially do not suffer or are more resilient from optic nerve degeneration. The metabolomes of NTG and OHT patients are regulated differently from control subjects and show dysregulation of metabolites important for energy production. These dysregulated processes may potentially contribute to the elevation of IOP and, ultimately, cell death of the RGCs. [ABSTRACT FROM AUTHOR]

Glaucoma is one of the main causes of irreversible blindness in the world. The most common form, primary open-angle glaucoma, is an optic neuropathy that is characterized by a progressive loss of retinal ganglion cells and their axons, leading to structural changes in the optic nerve head and associated visual field defects. Elevated intraocular pressure remains the most important modifiable risk factor for primary open-angle glaucoma. However, a significant proportion of patients develop glaucomatous damage in the absence of increased intraocular pressure, a condition known as normal-tension glaucoma (NTG). The pathophysiology underlying NTG remains unclear. Several studies have revealed that vascular and cerebrospinal fluid (CSF) factors may play significant roles in the development of NTG. Vascular failure caused by functional or structural abnormalities, and compartmentation of the optic nerve subarachnoid space with disturbed CSF dynamics have been shown to be associated with NTG. In the present article, based on the concept of the glymphatic system and observations in patients with NTG, we hypothesize that failure of fluid transport via the glymphatic pathway in the optic nerve may be involved in the pathogenesis of some if not many cases of NTG. According to this hypothesis, vascular and CSF factors may share reduced glymphatic transport and perivascular waste clearance in the optic nerve as a final common pathway leading to the development of NTG. In addition, we speculate that some cases of NTG may reflect glymphatic dysfunction in natural brain aging and central nervous system diseases, such as Alzheimer's disease. Clearly, further studies are needed to gain additional insight into the relative contribution of these factors and conditions to reduced glymphatic transport in the optic nerve. [ABSTRACT FROM AUTHOR]

In the modern world, glaucoma is one of the main causes of irreversible vision loss. Normal tension glaucoma (NTG) constitutes the major proportion of POAG, which is common in Asian populations. NTG is a disease resulted from the interaction of multiple genetic risk factors. But other factors are also important, such as thinning of the scleral lamina cribrosa and a lesion of the transmembrane pressure gradient. Central visual field defects and disc hemorrhage are characteristics finding that is highly associated with the progression of NTG.

Purpose: To study predictors of open‐angle glaucoma (OAG) in newly diagnosed patients detected in clinical practice in a defined population and to estimate the frequency of normal‐tension glaucoma (NTG). Methods: Predictors of OAG were analysed in a case–control study, nested in a cohort of 481 people, 55–84 years of age, in two rural districts in Sweden, examined at the Eye Department in Tierp from 1988 to 2003. To make the sample complete, 63 residents first examined at the Uppsala University Hospital (UUH), 60 of whom were identified with the help of registers, were invited to attend the study. In this way, the cohort included 544 individuals. Automated perimetry was used to find cases of OAG. Results: In people first examined in Tierp, incident OAG was found in 99 subjects. Of these cases, six were diagnosed with NTG. Increased intraocular pressure (IOP), higher age, male sex, a positive family history, pseudoexfoliation (PEX), and haemorrhages of the optic disc were associated with OAG. In a logistic regression model including PEX, every increase in IOP by 5 mmHg increased the risk for OAG four‐fold (odds ratio 4.04; 95% confidence interval 2.91–5.62). The effect of PEX was essentially mediated by increased pressure. The inclusion of the 63 subjects first examined at the UUH had no impact on the results. Conclusion: In this study on patients aged 55–84‐years old in clinical practice in Sweden, increased IOP was strongly associated with incident OAG, while NTG was a rare finding. [ABSTRACT FROM AUTHOR]

Purpose. The aim of this study was to compare the results of optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT) examinations in patients with normal-tension glaucoma (NTG) in comparison to high-tension pseudoexfoliative glaucoma (HTG) patients at the early stage of glaucoma. Material and methods. The studied groups consisted of patients in the early stage of NTG (70 eyes) and the early stage of HTG (71 eyes). In NTG and HTG groups, a detailed ophthalmic examination was performed. Optic disc OCT with peripapillary RNFL measurements and OCTA examination with the evaluation of the macula and optic disc were performed for all participants using Zeiss Cirrus 5000. Results. NTG and HTG groups were statistically similar as far as the MD was concerned, and both groups had early glaucoma. When evaluating the RNFL thickness, the only statistical difference between early NTG and HTG was observed in the thicknesses in the temporal sector of peripapillary RNFL, with thinner values in the NTG group (53.94 vs. 59.94, p = 0.0071). When the OCTA results of the macula and optic disc were evaluated, there were no statistical differences between early NTG and HTG. Conclusions. The vascular density and flow parameters assessed in OCTA were equal between early NTG and HTG, and therefore the involvement of vascular factors in NTG pathogenesis could not be confirmed. Our results confirm the preponderance of more frequent temporal RNFL involvement in early NTG. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether there are quantifiable structural or functional differences that can distinguish between high‐tension glaucoma (HTG; intraocular pressure [IOP] > 21 mm Hg) and low‐tension glaucoma (LTG; IOP ≤ 21 mm Hg) at diagnosis. Method: This was a retrospective, cross‐sectional study. Clinical results of one eye from 90 newly diagnosed HTG and 319 newly diagnosed LTG patients (117 with very‐low‐tension glaucoma [vLTG; ≤15 mm Hg] and 202 with middling LTG [mLTG; >15 mm Hg, ≤21 mm Hg]) were extracted, which included relevant demographic covariates of glaucoma, quantitative optical coherence tomography (including the optic nerve head, retinal nerve fibre layer and ganglion cell‐inner plexiform layer) measurements and standard automated perimetry global metrics. We used binary logistic regression analysis to identify statistically significant clinical parameters distinguishing between phenotypic groups for inclusion in principal component (PC) (factor) analysis (PCA). The separability between each centroid for each cohort was calculated using the Euclidean distance (d(x,y)). Results: The binary logistic regression comparing HTG and all LTG identified eight statistically significant clinical parameters. Subsequent PCA results included three PCs with an eigenvalue >1. PCs 1 and 2 accounted for 21.2% and 20.2% of the model, respectively, with a d(x,y) = 0.468, indicating low separability between HTG and LTG. The analysis comparing vLTG, mLTG and HTG identified 15 significant clinical parameters, which were subsequently grouped into five PCs. PCs 1 and 2 accounted for 24.1% and 17.8%, respectively. The largest separation was observed between vLTG and HTG (d(x,y) = 0.581), followed by vLTG and mLTG (d(x,y) = 0.435) and lastly mLTG and HTG (d(x,y) = 0.210). Conclusion: Conventional quantitative structural or functional parameters could not distinguish between pressure‐defined glaucoma phenotypes at the point of diagnosis and are therefore not contributory to separating cohorts. The overlap in findings highlights the heterogeneity of the primary open‐angle glaucoma clinical presentations among pressure‐defined groups at the cohort level. [ABSTRACT FROM AUTHOR]

Aim The aim of this study is to clinically investigate the challenges and pitfalls of normaltension glaucoma (NTG) diagnostic methods by ophthalmic clinical and investigative examinations. Setting This study was conducted at Al-Agouza Police Authority Hospital and Badr University Hospital. Methods A cross-sectional comparative study between the diagnosis of normal nonglaucoma patients and NTG. It included 40 normal nonglaucoma patients' eyes as controls and 40 NTG patients' eyes who met inclusion criteria. They were assessed by a complete ophthalmic exam., visual field (VF), and optical coherence tomography (OCT) variables between January 2022 and September 2022. Results The median age of the control group was 38 years old, while that of glaucomatous patients was 41 years old. The mean intraocular pressure (IOP) for the normal group was 15.53 mmHg (±1.935), while that for the glaucomatous group was 16.85 mmHg (±1.703). The intraocular pressure was considerably higher in the NTG group compared with the control (P=0.0017). The mean deviation (MD) in dB of VF loss was considerably higher in the NTG group compared with the control (P=0.0001). Also, the mean standard deviation (MSD) was considerably varied between the two groups (P < 0.0001). The average Retinal Nerve Fiber Layer (RNFL) in the NTG group, with a mean of 72.3Õ½m(±10.239) was significantly lower than in the control group with a mean of 102.025 Õ½m (±7.454), P=0.0001. Optic Disc Parameters: The Cup Area (mm2) was significantly wider in the NTG group with a mean of 1.62 (±0.476) than in the control with a mean of 1.297 (±0.44), P=0.0024. Also, the Rim Area was significantly smaller in the NTG group with a mean of 0.614 (±0.342) than in the control with a mean of 1.135 (±0.319), P=0.0024. The Cup/disc ratio was significantly larger in the NTG group than in the control group (P < 0.0001). The average Ganglion cell complex (GCC) was considerably thinner in the NTG patients in comparison to the controls (P=0.0001). Conclusion The effects of NTG on VF and optic nerve seems to be more intensive. More focal notches and disc hemorrhage were noted in NTG. In the NTG group, the Cup Area was potentially wider, the rim area was significantly thinner, and the Cup/disc ratio was significantly larger. [ABSTRACT FROM AUTHOR]

Disc hemorrhage (DH) is often associated with glaucoma progression. A vertically asymmetrical pattern is typical of glaucoma progression, but it remains unclear whether the association between DH and glaucoma progression differs between the superior and inferior hemiretinas. We compared the thickness changes of the macular ganglion cell complex (GCC) in the hemiretinas of normal-tension glaucoma patients with or without DH, as well as between hemiretinas positive and negative for DH, during five years. Both the superior and inferior hemiretinas in the DH-positive group had a more negative GCC thickness slope in association with more DH counts compared to those in the DH-negative group. Conversely, only the inferior hemiretina exhibited a significant relationship between GCC thickness slope and DH counts when hemiretinas positive and negative for DH in the DH-positive group were compared. In the superior hemifield, the slope of the total deviation changes in the DH-positive hemifield of the DH-positive group was more negative compared to that of the DH-negative group. The association between DH and glaucoma progression in the macular GCC may be stronger in the inferior hemiretina, suggesting that more attention should be paid to DH in the inferior disc area as a sign of glaucoma progression. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate myopic shift after the administration of omidenepag isopropyl (OMDI) in patients with normal-tension glaucoma (NTG). Methods: In this retrospective observational study, we enrolled 105 patients (105 eyes) with NTG who had received initial doses of OMDI between December 2018 and October 2022. We recorded the data on subjective refraction (diopters, D) at baseline and at the first visit after administration. We investigated and followed-up patients with myopic shift ?0.75?D from the baseline value. The main outcome measures were refractive changes from baseline to the first visit after administration. Results: This study included 105 patients (52 men and 53 women). The mean refractions at baseline and at the first visit after administration were ?3.87 ? 3.77 and ?3.99 ? 3.79?D, respectively (p < 0.01). Three patients (2.9%) developed myopia ??0.75?D. Among these three patients, OMDI administration was continued in two, and their refraction value returned to 0.75?D of the baseline value; the medication of the other patient was changed because of blurred vision, and the refraction returned to

Aim The aim of this study is to clinically investigate the challenges and pitfalls of normal-tension glaucoma (NTG) diagnostic methods by ophthalmic clinical and investigative examinations. Setting This study was conducted at Al-Agouza Police Authority Hospital and Badr University Hospital. Methods A cross-sectional comparative study between the diagnosis of normal nonglaucoma patients and NTG. It included 40 normal nonglaucoma patients’ eyes as controls and 40 NTG patients’ eyes who met inclusion criteria. They were assessed by a complete ophthalmic exam., visual field (VF), and optical coherence tomography (OCT) variables between January 2022 and September 2022. Results The median age of the control group was 38 years old, while that of glaucomatous patients was 41 years old. The mean intraocular pressure (IOP) for the normal group was 15.53 mmHg (±1.935), while that for the glaucomatous group was 16.85 mmHg (±1.703). The intraocular pressure was considerably higher in the NTG group compared with the control (P = 0.0017). The mean deviation (MD) in dB of VF loss was considerably higher in the NTG group compared with the control (P = 0.0001). Also, the mean standard deviation (MSD) was considerably varied between the two groups (P < 0.0001). The average Retinal Nerve Fiber Layer (RNFL) in the NTG group, with a mean of 72.3 սm (±10.239) was significantly lower than in the control group with a mean of 102.025 սm (±7.454), P = 0.0001. Optic Disc Parameters: The Cup Area (mm2) was significantly wider in the NTG group with a mean of 1.62 (±0.476) than in the control with a mean of 1.297 (±0.44), P = 0.0024. Also, the Rim Area was significantly smaller in the NTG group with a mean of 0.614 (±0.342) than in the control with a mean of 1.135 (±0.319), P = 0.0024. The Cup/disc ratio was significantly larger in the NTG group than in the control group (P < 0.0001). The average Ganglion cell complex (GCC) was considerably thinner in the NTG patients in comparison to the controls (P = 0.0001). Conclusion The effects of NTG on VF and optic nerve seems to be more intensive. More focal notches and disc hemorrhage were noted in NTG. In the NTG group, the Cup Area was potentially wider, the rim area was significantly thinner, and the Cup/disc ratio was significantly larger.

Purpose: The purpose of this study is to measure the quality of life (QoL) in patients with glaucoma using the Glaucoma QoL-15 (GQL-15) questionnaire. Methods: A cross-sectional study with a prospective enrollment of glaucoma patients was conducted. A total of 308 patients were participated in the study. Informed consent was obtained before the administration of the GQL-15 questionnaire. The QoL was assessed using an orally administered GQL-15 questionnaire. Patients' QoL was assessed based on their age, gender, visual field (VF) defect, severity of glaucoma, laterality of disease, history of previous glaucoma surgery, and the number of antiglaucoma medications (AGMs) they were taking. Participants were divided into mild, moderate, and severe glaucoma depending on the severity of VF defects using the Hodapp–Anderson–Parrish grading system. Results: A total of 308 glaucoma patients were interviewed. The mean age of participants was 57.7 ± 12.9 years; 173 (56.1%) of them were female. The average mean deviation (MD) of the patients was 7.8 ± 4.8 dB. There were 135 (43.8%) patients with mild, 122 (39.6%) with moderate, and 51 (16.6%) with severe glaucoma. In total, 114 (37%) patients had unilateral glaucoma, whereas 138 (44.4%) patients had previous glaucoma surgery. Sixty-two (22.1%) patients did not take any AGM. The correlation coefficient between VF MD and QoL was 0.7, which was significant at 0.01 level (two-tailed). Conclusion: The findings of this study demonstrated that the severity of VF defects has a negative impact on patient's QoL.

Introduction: The aim of this study was to compare the patterns of visual field (VF) defects in primary angle-closure glaucoma (PACG) to control groups of eyes with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Methods: Forty-eight eyes with PACG were enrolled, and control eyes with HTG and NTG matched for age, sex, and mean deviation of VF defect were selected. VF tests were performed using the 24-2 program of the Humphrey field analyzer. VF defects were classified into six patterns with the Ocular Hypertension Treatment Study classification system and were categorized into three stages (early, moderate, and advanced). Each hemifield was divided into five regions according to the Glaucoma Hemifield Test (GHT). The mean total deviation (TD) of each GHT region was calculated. Results: Compared with HTG and NTG groups, the partial arcuate VF defects were more common in the PACG group. In the PACG group, the nasal GHT region in the inferior hemifield had the worst mean TD (−8.48 ± 8.62 dB), followed by the arcuate 1 (−7.81 ± 7.91 dB), arcuate 2 (−7.46 ± 7.43 dB), paracentral (−7.19 ± 7.98 dB), and central (−5.14 ± 6.24 dB) regions; the mean TD of the central region was significantly better than those for all other regions (all p < 0.05). A similar trend was observed in the superior hemifield in the PACG group but not the VF hemifields of the HTG and NTG groups. Conclusion: Patterns of VF defect in PACG patients differ from those with HTG and NTG. This discrepancy might be due to the differences in the pathogenic mechanisms of glaucomatous optic neuropathy. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether the values of vessel density (VD) and perfusion parameters in the ophthalmic artery (OA) and central retinal artery (CRA) of the same eye differ in patients with hypertensive glaucoma (HTG) from patients with normotensive glaucoma (NTG). The first group consisted of 20 HTG patients (40 eyes). Patients with HTG were verified to have primary open-angle glaucoma (POAG). The second group consisted of 20 HTG patients (40 eyes). VD was used to determine the Avanti RTVue XR from Optovue (USA). Peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) were measured in both the central retinal artery (CRA) and ophthalmic artery (OA) using Doppler sonography on the Affinity 70G from Philips (USA). The visual field (VF) was examined by a fast threshold glaucoma program using a Medmont M700 (Australia). We showed no differences in VF, VD, PSV-OA and EDV-CRA between the two groups. Statistically significant differences between the two groups were observed in PSV in CRA (p = 0.04), EDV in OA (p = 0.009) and in RI in both CRA and OA. Other values were without significant differences in both groups. In both HTG and NTG, we observed in PSV-CRA, EDV-OA, RI-CRA and RI-OA. [ABSTRACT FROM AUTHOR]

Glaucoma is a complex and multifactorial disease defined as the loss of retinal ganglion cells (RGCs) and their axons. Besides an elevated intraocular pressure (IOP), other mechanisms play a pivotal role in glaucoma onset and progression. For example, it is known that excitotoxicity, immunological alterations, ischemia, and oxidative stress contribute to the neurodegeneration in glaucoma disease. To study these effects and to discover novel therapeutic approaches, appropriate animal models are needed. In this review, we focus on various glaucoma animal models beyond an elevated IOP. We introduce genetically modified mice, e.g., the optineurin E50K knock-in or the glutamate aspartate transporter (GLAST)-deficient mouse. Excitotoxicity can be mimicked by injecting the glutamate analogue N-methyl-D-aspartate intravitreally, which leads to rapid RGC degeneration. To explore the contribution of the immune system, the experimental autoimmune glaucoma model can serve as a useful tool. Here, immunization with antigens led to glaucoma-like damage. The ischemic mechanism can be mimicked by inducing a high IOP for a certain amount of time in rodents, followed by reperfusion. Thereby, damage to the retina and the optic nerve occurs rapidly after ischemia/reperfusion. Lastly, we discuss the importance of optic nerve crush models as model systems for normal-tension glaucoma. In summary, various glaucoma models beyond IOP increase can be utilized.

Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs). The main risk factor is elevated intraocular pressure (IOP), but the actual cause of the disease remains unknown. Emerging evidence indicates that metabolic dysfunction plays a central role. The aim of the current study was to determine and compare the effect of universal hypoxia on the metabolomic signature in plasma samples from healthy controls (n = 10), patients with normal-tension glaucoma (NTG, n = 10), and ocular hypertension (OHT, n = 10). By subjecting humans to universal hypoxia, we aim to mimic a state in which the mitochondria in the body are universally stressed. Participants were exposed to normobaric hypoxia for two hours, followed by a 30 min recovery period in normobaric normoxia. Blood samples were collected at baseline, during hypoxia, and in recovery. Plasma samples were analyzed using a non-targeted metabolomics approach based on liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Multivariate analyses were conducted using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and univariate analysis using the Wilcoxon signed-rank test and false discovery rate (FDR) correction. Unique metabolites involved in fatty acid biosynthesis and ketone body metabolism were upregulated, while metabolites of the kynurenine pathway were downregulated in OHT patients exposed to universal hypoxia. Differential affection of metabolic pathways may explain why patients with OHT initially do not suffer or are more resilient from optic nerve degeneration. The metabolomes of NTG and OHT patients are regulated differently from control subjects and show dysregulation of metabolites important for energy production. These dysregulated processes may potentially contribute to the elevation of IOP and, ultimately, cell death of the RGCs.

Introduction: Although acupuncture and moxibustion are complementary or alternative therapies for glaucoma, studies on their effectiveness reported in the Cochrane Database of Systematic Reviews are inconclusive. Stress-free (SF) therapy is a type of moxibustion therapy that targets acupuncture points and increases blood flow in the ocular fundus. This study aimed at evaluating the clinical efficacy of SF therapy in treating normal-tension glaucoma. Methods: In addition to visual field test (mean deviation [MD]) and visual acuity measurement, blood tests were performed to measure the following in a man aged 63 years and a woman aged 69 years with glaucoma without ophthalmic intervention and with mild cataract: triglycerides (TG), arteriosclerosis index (AI) determined as the low-density lipoprotein/high-density lipoprotein ratio, total lipids (TL), and estrogen (estradiol-2 [E-2]). SF therapy was performed by the patients themselves for 45?min daily for 4 weeks at a total of four points: Zusanli Point (ST36), Point F (the intersection between the 1st or 2nd toe line of the left sole and the medial/lateral malleolus line), Point N (the intersection between the vertical line of the right pupil and the middle line of the nasolabial fold), and Point P (the center of the closed left eyelid). Results and Discussion: In both patients after SF therapy, TG, AI, and TL levels were reduced, while E-2 levels were elevated. These changes may improve lipid metabolism and decrease vascular resistance, affecting ciliary-regulated circulation of the visual field. Elevated estrogen has a protective effect on the retinal ganglion cells and improves blood flow. Estrogen therapy after menopause is associated with a reduced incidence of glaucoma. Thus, in our patients, estrogen (E-2) levels elevating from 15.5?pg/mL at baseline to 22.5?pg/mL after SF therapy may have contributed to the improved visual function. Conclusion: SF therapy improved the visual acuity and visual field (MD score) in two patients with normal-tension glaucoma.

Purpose. To compare the thickness of the prelaminar layer of nerve fibers and the depth of the lamina cribrosa in patients with diverse forms of open-angle glaucoma, measured by optical coherence tomography (OCT).Material and methods. 130 patients aged 71.4 ± 9.7 with stage II (advanced) glaucoma were divided into three groups depending on the form of glaucoma: group 1 of 39 patients with primary openangle glaucoma (POAG); group 2 of 26 patients with normal-tension glaucoma (NTG); group 3 of 22 patients with pseudoexfoliative glaucoma (PEG). The control group consisted of 43 patients without ophthalmic pathology. All patients were scanned for the optic disc and the macular areas in the OCT Disk + Macula 3D regimen and in the Disk Raster regimen (Optopol Revo 60 OCT device (Optopol Technology, Poland). The depth of the lamina cribrosa (LC) and the thickness of the prelaminar layer of nerve fibers (tPLNF) were calculated.Results. No significant differences were found between the LC depth in patients with different forms of glaucoma compared with the control group. LC depth averaged 426.9 ± 98.7 μm (p < 0.164) in patients with POAG, 416.9 ± 161.0 μm (p < 0.818) with NTG and 425.5 ± 88.04 μm, (p < 0.18) with PEG. The thinnest layer of prelaminar nerve fibers was found in patients with NTG (134,0 ± 91.4 μM), where the value was half as much as the control (p < 0.001). There were no differences in the tPNFL parameter in POAG (193.2 ± 114.6 μm) and PEG (190.7 ± 115.3 μm) but both were significantly lower as compared to the control group (p < 0.001, p < 0.002) respectively.Conclusion. The study of LC parameters contributes to a better understanding of the pathogenesis of optic neuropathy in diverse forms of glaucoma. It opens up new opportunities in the differential diagnosis and prediction of the glaucoma course.

Growing evidence suggests that intracranial pressure (ICP) plays an important role in the pathophysiology of glaucoma, especially in normal-tension glaucoma (NTG) patients. Controversial results exist about ICP's relationship to visual field (VF) changes. With the aim to assess the relationship between ICP and VF zones in NTG patients, 80 NTG patients (age 59.5 (11.6) years) with early-stage glaucoma were included in this prospective study. Intraocular pressure (IOP) (Goldmann), visual perimetry (Humphrey) and non-invasive ICP (via a two-depth Transcranial Doppler, Vittamed UAB, Lithuania) were evaluated. Translaminar pressure difference (TPD) was calculated according to the formula TPD = IOP − ICP. The VFs of each patient were divided into five zones: nasal, temporal, peripheral, central, and paracentral. The average pattern deviation (PD) scores were calculated in each zone. The level of significance p < 0.05 was considered significant. NTG patients had a mean ICP of 8.5 (2.4) mmHg. Higher TPD was related with lower mean deviation (MD) (p = 0.01) and higher pattern standard deviation (PSD) (p = 0.01). ICP was significantly associated with the lowest averaged PD scores in the nasal VF zone (p < 0.001). There were no significant correlations between ICP and other VF zones with the most negative mean PD value. (p > 0.05). Further studies are needed to analyze the involvement of ICP in NTG management. [ABSTRACT FROM AUTHOR]

(1) Background: To compare optic nerve sheath diameter (ONSD) in normal-tension glaucoma (NTG) and healthy eyes and to investigate the association between ONSD and lamina cribrosa (LC) morphology. (2) Methods: This cross-sectional study included 69 NTG eyes and 69 healthy eyes matched for age, axial length, and intraocular pressure. The LC curvature index (LCCI) was measured from horizontal Cirrus HD-OCT B-scan images from five uniformly divided positions vertically of the optic nerve. The average LCCI was defined as the mean of the measurements at these five locations. ONSD was measured as the width of the optic nerve sheath at the site perpendicular 3 mm behind the posterior globe. LCCI and ONSD were compared in eyes with NTG and healthy eyes. The clinical factors that could affect LCCI were analyzed. (3) Results: NTG eyes had significantly smaller mean ONSD (4.55 ± 0.69 mm vs. 4.97 ± 0.58 mm, p < 0.001) and larger average LCCI (11.61 ± 1.43 vs. 7.58 ± 0.90, p < 0.001) than matched healthy control eyes. LCCI was significantly correlated with smaller ONSD, higher intraocular pressure, thinner global retinal nerve fiber thickness, and worse visual field loss in all subjects (all Ps ≤ 0.022). (4) Conclusions: NTG eyes had smaller ONSD and greater LCCI than healthy control eyes. In addition, a negative correlation was observed between ONSD and LCCI. These findings suggest that cerebrospinal fluid pressure, which ONSD indirectly predicts, may affect LC configuration. Changes in the retrolaminar compartment may play a role in glaucoma pathogenesis. [ABSTRACT FROM AUTHOR]

To study the associations between optic nerve head (ONH) strains under intraocular pressure (IOP) elevation with retinal sensitivity in patients with glaucoma. Clinic-based cross-sectional study. Two hundred twenty-nine patients with primary open-angle glaucoma (subdivided into 115 patients with high-tension glaucoma [HTG] and 114 patients with normal-tension glaucoma [NTG]). For 1 eye of each patient, we imaged the ONH using spectral-domain OCT under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 35 mmHg) achieved through ophthalmodynamometry. A 3-dimensional strain-mapping algorithm was applied to quantify IOP-induced ONH tissue strain (i.e., deformation) in each ONH. Strains in the prelaminar tissue (PLT), the retina, the choroid, the sclera, and the lamina cribrosa (LC) were associated (using linear regression) with measures of retinal sensitivity from the 24-2 Humphrey visual field test (Carl Zeiss Meditec). This was performed globally, then locally according to a previously published regionalization scheme. Associations between ONH strains and values of retinal sensitivity from visual field testing. For patients with HTG, we found (1) significant negative linear associations between ONH strains and retinal sensitivity (P < 0.001; on average, a 1% increase in ONH strains corresponded to a decrease in retinal sensitivity of 1.1 decibels [dB]), (2) that high-strain regions colocalized with anatomically mapped regions of high visual field loss, and (3) that the strongest negative associations were observed in the superior region and in the PLT. In contrast, for patients with NTG, no significant associations between strains and retinal sensitivity were observed except in the superotemporal region of the LC. We found significant negative associations between IOP-induced ONH strains and retinal sensitivity in a relatively large glaucoma cohort. Specifically, patients with HTG who experienced higher ONH strains were more likely to exhibit lower retinal sensitivities. Interestingly, this trend in general was less pronounced in patients with NTG, which could suggest a distinct pathophysiologic relationship between the two glaucoma subtypes. [ABSTRACT FROM AUTHOR]

Due to the reactive medical approach applied to disease management, stroke has reached an epidemic scale worldwide. In 2019, the global stroke prevalence was 101.5 million people, wherefrom 77.2 million (about 76%) suffered from ischemic stroke; 20.7 and 8.4 million suffered from intracerebral and subarachnoid haemorrhage, respectively. Globally in the year 2019 — 3.3, 2.9 and 0.4 million individuals died of ischemic stroke, intracerebral and subarachnoid haemorrhage, respectively. During the last three decades, the absolute number of cases increased substantially. The current prevalence of stroke is 110 million patients worldwide with more than 60% below the age of 70 years. Prognoses by the World Stroke Organisation are pessimistic: globally, it is predicted that 1 in 4 adults over the age of 25 will suffer stroke in their lifetime. Although age is the best known contributing factor, over 16% of all strokes occur in teenagers and young adults aged 15–49 years and the incidence trend in this population is increasing. The corresponding socio-economic burden of stroke, which is the leading cause of disability, is enormous. Global costs of stroke are estimated at 721 billion US dollars, which is 0.66% of the global GDP. Clinically manifested strokes are only the "tip of the iceberg": it is estimated that the total number of stroke patients is about 14 times greater than the currently applied reactive medical approach is capable to identify and manage. Specifically, lacunar stroke (LS), which is characteristic for silent brain infarction, represents up to 30% of all ischemic strokes. Silent LS, which is diagnosed mainly by routine health check-up and autopsy in individuals without stroke history, has a reported prevalence of silent brain infarction up to 55% in the investigated populations. To this end, silent brain infarction is an independent predictor of ischemic stroke. Further, small vessel disease and silent lacunar brain infarction are considered strong contributors to cognitive impairments, dementia, depression and suicide, amongst others in the general population. In sub-populations such as diabetes mellitus type 2, proliferative diabetic retinopathy is an independent predictor of ischemic stroke. According to various statistical sources, cryptogenic strokes account for 15 to 40% of the entire stroke incidence. The question to consider here is, whether a cryptogenic stroke is fully referable to unidentifiable aetiology or rather to underestimated risks. Considering the latter, translational research might be of great clinical utility to realise innovative predictive and preventive approaches, potentially benefiting high risk individuals and society at large. In this position paper, the consortium has combined multi-professional expertise to provide clear statements towards the paradigm change from reactive to predictive, preventive and personalised medicine in stroke management, the crucial elements of which are: Consolidation of multi-disciplinary expertise including family medicine, predictive and in-depth diagnostics followed by the targeted primary and secondary (e.g. treated cancer) prevention of silent brain infarction Application of the health risk assessment focused on sub-optimal health conditions to effectively prevent health-to-disease transition Application of AI in medicine, machine learning and treatment algorithms tailored to robust biomarker patterns Application of innovative screening programmes which adequately consider the needs of young populations Stroke is a severe brain disease which has reached an epidemic scale worldwide: in 2019, the global stroke prevalence was 101.5 million people. The World Stroke Organisation predicted that globally, 1 in 4 adults over the age of 25 will get a stroke in their lifetime. Not only old people but also teenagers and young adults are affected. Current global costs of stroke are estimated at 721 billion US dollars. Due to undiagnosed so-called "silent" brain infarction, the number of affected individuals is about 14 times greater in the population than clinically recorded. If it remains untreated, silent brain infarction may cause many severe and fatal disorders such as dementia, depression and even suicide. In this position paper, the consortium describes how the rudimental approach to treating severely diseased people could be replaced by an innovative predictive and preventive one to protect people against the health-to-disease transition. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate and correlate corneal endothelium parameters with the severity of primary glaucoma. Methods: This prospective case-control study was conducted on 150 eyes of 80 newly diagnosed primary open-angle glaucoma (POAG), chronic primary angle-closure glaucoma (cPACG), and normal-tension glaucoma (NTG) patients in a tertiary care center. Endothelial parameters including endothelial cell count (ECC), percentage of hexagonal cells, and coefficient of variation of cell size were analyzed. Glaucoma cases were further sub-grouped into early, moderate, and severe glaucoma and compared for endothelial parameters. Chi-square, Fischer's exact test, independent sample t-test, and analysis of variance were performed using IBM® SPSS® Statistics version 28. Results: The ECC was markedly reduced in cases (2281 cells/mm2) versus controls (2611 cells/mm2) (P < 0.001). The POAG (2251 cells/mm2) and cPACG (2287 cells/mm2) eyes had significantly a lower ECC compared to healthy controls (P < 0.001), whereas NTG eyes had a lower mean ECC (2538 cells/mm2), but it was not statistically significant (P > 0.05) when compared with controls. The ECC decreased with an increase in severity as patients with early glaucoma had an ECC of 2284 cells/mm2, moderate 2261 cells/mm2, and severe 2086 cells/mm2, and the difference was statistically significant. Conclusion: A significant decrease in corneal ECC was observed in POAG and cPACG patients when compared with healthy controls of the same age group. Mechanical damage following an elevated intra-ocular pressure for a longer duration may be attributed to morphological and consequent functional damage to endothelial cells.

Purpose: To evaluate and correlate corneal endothelium parameters with the severity of primary glaucoma.Methods: This prospective case-control study was conducted on 150 eyes of 80 newly diagnosed primary open-angle glaucoma (POAG), chronic primary angle-closure glaucoma (cPACG), and normal-tension glaucoma (NTG) patients in a tertiary care center. Endothelial parameters including endothelial cell count (ECC), percentage of hexagonal cells, and coefficient of variation of cell size were analyzed. Glaucoma cases were further sub-grouped into early, moderate, and severe glaucoma and compared for endothelial parameters. Chi-square, Fischer's exact test, independent sample t-test, and analysis of variance were performed using IBM® SPSS® Statistics version 28.Results: The ECC was markedly reduced in cases (2281 cells/mm2) versus controls (2611 cells/mm2) (P < 0.001). The POAG (2251 cells/mm2) and cPACG (2287 cells/mm2) eyes had significantly a lower ECC compared to healthy controls (P < 0.001), whereas NTG eyes had a lower mean ECC (2538 cells/mm2), but it was not statistically significant (P > 0.05) when compared with controls. The ECC decreased with an increase in severity as patients with early glaucoma had an ECC of 2284 cells/mm2, moderate 2261 cells/mm2, and severe 2086 cells/mm2, and the difference was statistically significant.Conclusion: A significant decrease in corneal ECC was observed in POAG and cPACG patients when compared with healthy controls of the same age group. Mechanical damage following an elevated intra-ocular pressure for a longer duration may be attributed to morphological and consequent functional damage to endothelial cells. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively evaluate the 1-year efficacy and safety of single-agent of omidenepag isopropyl in patients with normal-tension glaucoma (NTG). Methods: One hundred patients (100 eyes) newly administered omidenepag isopropyl were enrolled. Intraocular pressure (IOP) was compared at baseline and 3, 6, 9, and 12 months after administration. The mean deviation values at baseline and 12 months measured using the Humphrey visual field test (30-2 Swedish Interactive Threshold Algorithm standard) were compared. Adverse reactions and dropouts were observed. Results: IOP significantly decreased from 15.5 ± 2.7 mmHg at baseline to 13.3 ± 2.5 mmHg after 3 months, 13.7 ± 2.3 mmHg after 6 months, 13.9 ± 2.4 mmHg after 9 months, and 13.7 ± 2.3 mmHg after 12 months (P < 0.0001). There was no significant difference in the mean deviation values at baseline (-3.66 ± 3.49 dB) and after 12 months (-3.41 ± 3.80 dB). Adverse reactions occurred in 9 patients (9.0%): conjunctival hyperemia (n = 6), eye pain (n = 1), iritis (n = 1), and blepharitis (n = 1). Twenty-one patients (21.0%) discontinued administration because of changes in medication (n = 7), interruption of visits (n = 5), adverse reactions (n = 4), and others. Conclusions: After administering omidenepag isopropyl, the IOP in patients with NTG decreased within 1 year, visual fields were maintained, and safety was satisfactory. Omidenepag isopropyl can be used as the first-line medication for patients with NTG. [ABSTRACT FROM AUTHOR]

Purpose: Vasospasm represents an early event in systemic sclerosis (SSc). Ocular vasospasm may induce optic nerve head (ONH) damage and has been involved in the pathogenesis of glaucoma, especially normal-tension glaucoma (NTG). We aimed to investigate the presence of structural abnormalities associated with NTG using swept-source optical coherence tomography (SS-OCT) and to correlate the OCT parameters with clinical, capillaroscopy and digital blood flow measures in patients with SSc. Methods: In this cross-sectional study, 40 patients with SSc and 23 age-matched controls were included. The following parameters were measured using SS-OCT: mean and sectoral retinal nerve fibre layer (RNFL) thickness, macular ganglion cell layer complex (GCC) thickness and ONH morphology. Nailfold capillaroscopy (NFC) and digital blood flow measurements using laser Doppler imaging (LDI) were performed in all subjects. Results: Patients with SSc showed a thinner temporal RNFL than the controls (69.23 ± 11.74 versus 83.35 ± 20.19 µm, p = 0.001). The other parameters were similar between the two groups. In SSc patients, there was an inverse correlation between the disease duration and the average, superior and inferior RNFL thickness and the GCC thickness and between Raynaud's phenomenon duration and the average RNFL and GCC thickness (p < 0.05). NFC and LDI measurements did not show correlations with OCT parameters. Conclusion: A thinner temporal RNFL and the correlation between Raynaud's phenomenon and disease duration and structural abnormalities on OCT suggest the presence of early ganglion cell damage in patients with SSc. Although mild, these findings indicate the need to monitor ocular abnormalities in SSc. [ABSTRACT FROM AUTHOR]

Background: Normal-Tension_Glaucoma (NTG) is an eye disease and characterize with low intraocular pressure (IOP) levels. In population-based settings, the diagnose of glaucoma is based on the IOP levels of 21 mmHg, and its usually delayed. A recent study HbA1c levels could lead to IOP changes. Obstructive Sleep Apnea (OSA) result oxidative stress that results an altered function of neutrophil in patients with NTG. Objective: To_evaluate the association of HbA1c, Netrophil-to-Lymphocyte Ratio_(NLR) toward NTG as its novel early detection. Methods: This study divided into two groups consisted of Metabolic Syndrome ( MS) + OSA without eye disorder as control (15 subjects) and MS + OSA + NTG patients (14 subjects). IDF criteria was used to established MS, and risk of OSA determined by STOP-BANG Questionnaire. The diagnosis of NTG was confirmed by normal IOP measured by Tonopen. Mean Defect (MD) of visual field evaluated by Automated Humphrey Perimetry, Retinal Nerve Fiber Layer (RNFL) established by OCT. HbA1c measured by ELISA and NLR by flowcytometry. Statistical analysis consisted of comparison and correlation test Results: The ratio of CD was significantly higher in NTG patients (0.54 ± 0.13) compared to control (0.26 ± 0.07; p

Background: Open-angle glaucoma (OAG) and Alzheimer’s disease (AD) are two age-related neurodegenerative diseases of significant public health importance. Epidemiological studies have indicated that there might be an association between the disorders. Methods: Predictors of AD, including mixed and unspecified dementia, were analysed in a cohort of 712 residents aged 65–74 years, examined in a population survey in the rural district of Tierp, Sweden, from 1984 to 1986. To expand the sample size, 821 people were recruited by means of glaucoma case records established at the Eye Department in Tierp from 1978 to 2007. In this way, the cohort comprised 1,533 people, representing more than 21,000 person-years at risk. Medical records were reviewed to identify subjects diagnosed with dementia. Those with a follow-up duration shorter than 2 years were excluded. Results: By the conclusion of the study, in August 2020, 307 subjects had received a diagnosis of AD, including mixed and unspecified dementia. Of these cases, 55 were affected with definite OAG at baseline. Higher age and ischemic heart disease were the only predictors of AD identified. In multivariate analysis, adjusting for age, participation in the population survey and competing events, no association was found between OAG and AD (hazard ratio 1.08; 95% confidence interval: 0.80–1.47). Conclusion: In this long-term follow-up study of subjects aged 65–74 years old in Sweden, OAG was not associated with AD.

Abstract Background The prevalence of open-angle glaucoma (OAG) varies from 0.5% to 7.0% among populations of diverse ancestry, suggesting the existence of genetic differences. The purposes of this study were to provide insights into genetic causes of OAG, which can result in prevalence and phenotype differences among populations of diverse ancestry for OAG, and to compare allele frequencies of intraocular pressure (IOP) elevation-related SNPs in OAG among Koreans and other ethnic groups. Methods We collected the data on a total of 135 OAG-associated single nucleotide polymorphisms (SNPs) from a genome-wide association studies (GWAS) catalog. The population-level allele frequencies of these SNPs were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher's exact test to assess whether the effect allele at a given SNP was significantly enriched or depleted. Results European, American, and South Asian populations showed similar heatmap patterns, while African, East Asian, and Korean populations had distinct patterns. Korean population presented different profiles compared to other groups; rs1579050 (FMNL2 gene), rs2024211 (CAV2;CAV1), and rs8141433 (GNB1L;TXNRD2 gene), which are known to be associated with IOP variation, were enriched in Americans, Europeans, and Africans, and depleted in Koreans. These can be the candidates for the causative genes of differences in the prevalence of IOP variation in OAG according to ethnic groups. Conclusions Differences in allele frequencies associated with IOP related SNPs between Koreans and other ethnicities were observed, which may explain the high prevalence of OAG with normal IOP predominantly in Koreans and East Asians.

The aim of this study was to determine whether the values of vessel density (VD) and perfusion parameters in the ophthalmic artery (OA) and central retinal artery (CRA) of the same eye differ in patients with hypertensive glaucoma (HTG) from patients with normotensive glaucoma (NTG). The first group consisted of 20 HTG patients (40 eyes). Patients with HTG were verified to have primary open-angle glaucoma (POAG). The second group consisted of 20 HTG patients (40 eyes). VD was used to determine the Avanti RTVue XR from Optovue (USA). Peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) were measured in both the central retinal artery (CRA) and ophthalmic artery (OA) using Doppler sonography on the Affinity 70G from Philips (USA). The visual field (VF) was examined by a fast threshold glaucoma program using a Medmont M700 (Australia). We showed no differences in VF, VD, PSV-OA and EDV-CRA between the two groups. Statistically significant differences between the two groups were observed in PSV in CRA (p = 0.04), EDV in OA (p = 0.009) and in RI in both CRA and OA. Other values were without significant differences in both groups. In both HTG and NTG, we observed in PSV-CRA, EDV-OA, RI-CRA and RI-OA.

Purpose: To evaluate ocular hypotensive efficacy and the safety of sovesudil (formally known as PHP‐201), a novel Rho‐associated protein kinase (ROCK) inhibitor, in patients with normal‐tension glaucoma (NTG). Design: Multicentre, prospective, double‐masked, randomized, placebo‐controlled, parallel clinical study. Methods: Patients with NTG (unmedicated baseline IOP ≤ 21 mmHg) were randomized in 3 groups and treated with sovesudil in concentrations of 0.25% and 0.5%, or with a placebo three times daily (TID) for 4 weeks. The primary end‐point was the mean diurnal IOP change from the baseline at week 4. Safety was recorded over a 4‐week treatment period and the following 2‐week observation period. Results: A total of 119 patients were included in the primary efficacy analysis. The mean diurnal IOP change from the baseline at week 4 was −1.56 mmHg for the high‐dose group, −1.10 mmHg for the low‐dose group and −0.65 mmHg for the placebo group. The difference between the high‐dose and the placebo groups was −0.91 mmHg (95% confidence intervals: −1.73, −0.09). 0.5% sovesudil TID met the criteria for superiority to the placebo. The most frequent ocular adverse event among sovesudil‐treated patients was conjunctival hyperaemia (24.4% for the high‐dose and 17.5% for the low‐dose group) and predominately classified as mild. Conclusions: Sovesudil 0.25% and 0.5% TID showed statistically significant IOP‐lowering effects and 0.5% concentration's IOP‐lowering effects met the superiority criteria in comparison with the placebo at week 4. Sovesudil was well tolerated with mild adverse events including relatively low incidence of conjunctival hyperaemia in patients with NTG. [ABSTRACT FROM AUTHOR]

Purpose: To study the relationship between intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) in patients with POAG and NTG. The secondary objective was to identify other contributory ischemic factors.Methods: This was an observational cross-sectional study from a tertiary eye hospital in patients who underwent full-day diurnal variation of tension (DVT). Blood pressure (BP) and IOP measurements were done every 3 h over 24 h. Mean arterial pressure (MAP) and MOPP were calculated. The nocturnal dip in BP was assessed; patients were classified as non-dippers, dippers, and over-dippers. The circadian MOPP fluctuation (CMF) was calculated using the Kruskal-Wallis test, and its relationship with type and severity of visual field was assessed.Results: In total, 149 patients were evaluated; 109 were classified as NTG, and 40 were classified as POAG. A nocturnal dip in BP was noted in 20% of NTG and 17.5% of POAG. The MAP was found to be lower in patients with NTG than POAG. In the NTG subgroup, we found that 20% of patients were over-dippers, 32% were dippers, and 48% were non-dippers. The CMF showed a greater fluctuation for over-dippers (P = 0.004 for the RE and 0.003 for the LE) than dippers and non-dippers. A weak positive correlation of CMF with the severity of fields was found.Conclusion: A 24-h monitoring of IOP, BP, MOPP, and assessment of systemic risk factors for primary glaucoma acts as an invaluable tool for the comprehensive management of NTG despite the limitations posed by DVT and BP recording. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the effect of applying negative pressure (vacuum) to the periocular space on intraocular pressure (IOP) and retrobulbar pressure (RBP) by use of the Multi-Pressure Dial (MPD) system (Equinox Ophthalmic, Inc.). Methods: Two eyes of two full body cadavers were studied. In each subject, the retrobulbar space, posterior segment and intra-goggle space were cannulated to provide direct IOP, RBP and intra-goggle pressure measurements via a pressure transducer data acquisition system. The goggles of the MPD system were placed over the eyes of each subject, and multiple test runs were performed, with negative pressure settings programmed to 5, 10 and 20 mmHg. IOP and RBP measurements were continuously obtained during each run and plotted against time for analysis. Results: For both subjects, the mean reduction (± standard deviation) in IOP was 1.6 ± 0.9 (10%), 3.5 ± 1.8 (23%) and 5.6 ± 2.0 (37%) mmHg at programmed negative pressure levels of − 5, − 10 and − 20 mmHg, respectively. The overall mean change in RBP (mmHg) during negative pressure application was 0.02 ± 0.14 at − 5 mmHg, 0.03 ± 0.19 at − 10 mmHg and − 0.01 ± 0.18 at − 20 mmHg. In both subjects, the magnitude of RBP change during application of negative pressure fell below the uncertainty of the measurement system. Conclusions: The application of negative pressure to the periocular space with the MPD decreases IOP but does not affect RBP. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of nimodipine on peripapillary and macular capillary vessel density (VD) in patients with normal-tension glaucoma (NTG) using optical coherence tomography angiography (OCTA). Sixty mg nimodipine was administered to 20 enrolled NTG patients for 3 months. Patients were treated with glaucoma medication simultaneously. The macular and peripapillary VD were measured automatically by OCTA at baseline, 1.5 h after administering nimodipine, and after 3 months of administering the drug. The retinal nerve fibre layer (RNFL), ganglion cell complex thickness, visual field (VF) testing, intraocular pressure (IOP), blood pressure and pulse rate in each subject were assessed during each follow-up. Compared with the baseline, the parafovea VD was higher (50.89 ± 4.26 versus 46.80 ± 5.40, P =.044) 1.5 h after administration of nimodipine. After administration of nimodipine for 3 months, the parafovea VD was obviously increased (51.14 ± 5.68 versus 46.80 ± 5.40, P =.039), while IOP, systolic blood pressure, mean arterial pressure and mean ocular perfusion pressure were decreased compared to baseline (all P <.05). No significant differences were found between the radial peripapillary capillary and disc VD. The parafovea VD was positively correlated with the administration of nimodipine (β = 0.39, P =.004), RNFL thickness (β = 0.49, P =.022), and VF mean deviation (β = 0.4, P =.040) in the multivariate analysis. Nimodipine effectively increased superficial macular capillary VD, but did not affect peripapillary capillary VD in patients with NTG. This finding indicates that patients with NTG may benefit from the administration of nimodipine. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the features of the small‐to‐medium (choriocapillaris and Sattler's layer) and large (Haller's layer) sized vessel layers of the macular choroid in normal‐tension glaucoma (NTG) patients using swept‐source optical coherence tomography (SS‐OCT). Methods: We conducted an observational cross‐sectional study in 234 NTG eyes from 134 patients, and 203 normal eyes from 109 non‐glaucomatous control subjects. We used Image J to segment the choroidal layer and then a Python script to measure the average macular choroidal thickness (MCT) and choroidal vascular index (CVI) of two vessel layers at five different locations. Quantitative optical coherence tomography angiography (OCTA) metrics for the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at macular region were also measured by a customized MATLAB program. Generalized estimating equations (GEE) models were performed to determine ocular and demographic factors associated with the choroidal metrics, adjusting for inter‐eye correlation. Results: Significant average MCT thinning was found in NTG eyes at all five locations of the two layers, in comparison with controls (all p ≤ 0.05). In addition, compared with control eyes, significant decrease in CVI was found in NTG eyes at all five sections of the large sized vessel layer: 500 µm nasal and temporal to macula (p = 0.002), 1500 µm nasal (p < 0.001), 2500 µm nasal (p = 0.001), 1500 µm temporal (p < 0.001) and 2500 µm temporal (p = 0.004). In contrast, no significant CVI difference was detected in the small‐to‐medium sized vessel layer. In the comparison of OCTA metrics of SCP and DCP at macular region between NTG and normal eyes, there were no significant difference of parafoveal vessel density (VD), foveal avascular zone (FAZ) area, FAZ circularity and fractal dimension (FD) in both layers. Conclusion: We found significant alterations in macular choroidal vascularity (reduced CVI and thinner layer) in NTG patients. Such alterations are more pronounced in the Haller's layer, rather than the choriocapillaris & Sattler's layer, in NTG. Choroidal layer may be more related to vasculature changes at macular region in NTG. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to compare the levels of brain-derived neurotrophic factor (BDNF) in the serum and aqueous humor (AH) of patients with primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). Methods: This prospective, observational study consists of 30 patients with POAG, 30 patients with NTG, and 30 healthy controls. The serum and AH BDNF levels were assessed using an enzyme-linked immunosorbent assay. Results: BDNF levels in serum and AH were markedly lower in the glaucoma groups (POAG and NTG) than in the control group (p < 0.05). When comparing the NTG and POAG groups, the average serum BDNF level was significantly lower in the NTG group than in the POAG group (p < 0.05). The difference in the mean BDNF levels in AH between the POAG and NTG groups was not statistically significant. (p = 0.538). Conclusion: We confirmed that serum BDNF levels were lower in patients with NTG than in those with POAG. BDNF could be a causative systemic biomarker in NTG. [ABSTRACT FROM AUTHOR]

Koji Nitta,1 Yutaro Yamada,1 Satomi Morokado,1 Kazuhisa Sugiyama2 1Department of Ophthalmology, Fukui-Ken Saiseikai Hospital, Fukui, Fukui Prefecture, Japan; 2Department of Ophthalmology, Kanazawa University, Kanazawa, Ishikawa Prefecture, JapanCorrespondence: Koji NittaFukui-Ken Saiseikai Hospital, Funabashi 7-1, Wadanaka-Cho, Fukui City, Fukui 918-8503, JapanTel +81 776 23 1111Email nitta.koji7001@fukui.saiseikai.or.jpIntroduction: This study assesses two-year efficacy and safety following implantation of a single trabecular micro-bypass stent (iStent®) with concomitant phacoemulsification cataract surgery in Japanese patients with open-angle glaucoma (OAG).Materials and Methods: This retrospective, consecutive case series included eyes that underwent iStent implantation with phacoemulsification and were followed for 24 months postoperative. Efficacy and safety measures included intraocular pressure (IOP), number of glaucoma medications, adverse events, secondary surgeries, visual fields, and endothelial cell counts.Results: Of 73 operated eyes, 53 eyes had 24 months of follow-up and are analyzed. Diagnoses included primary open-angle glaucoma (POAG, n=25), normal-tension glaucoma (NTG, n=16), and pseudoexfoliative glaucoma (PXG, n=12). At 24 months, mean IOP reduced by 18% to 13.6± 3.0 mmHg versus 16.5± 3.4 mmHg preoperatively (p< 0.0001), and mean medication number reduced by 81% to 0.37± 0.74 versus 1.96± 0.98 preoperatively (p< 0.0001). The percentage of medication-free eyes was 77% versus 0% preoperatively, and 81% of eyes had IOP ≤ 15 mmHg versus 42% preoperatively. Results were similarly favorable across glaucoma subtypes (POAG, NTG, PXG). Notably, mean IOP in NTG eyes decreased to 12.8± 1.4 mmHg from 14.4± 3.0 mmHg preoperatively (p=0.03), and medications decreased by 87% to 0.31± 0.70 versus 2.38± 0.72 preoperatively (p< 0.0001). At 24 months, 81% of NTG eyes were medication-free (versus 0% preoperatively); 2 NTG eyes (13%) were on ≥ 2 medications (versus 100% preoperatively). Throughout the follow-up, visual fields and endothelial cell counts remained stable; 1 eye (1.9%) underwent filtration surgery.Discussion: Favorable safety and significant IOP and mediation reductions were achieved through two years following iStent implantation with phacoemulsification in a Japanese population. These gains were achieved across all glaucoma subtypes (including POAG, NTG, PXG).Conclusion: This real-world study supports the viability of iStent implantation to treat Japanese patients with glaucoma and shows that the benefits extend to those with NTG or PXG in addition to POAG.Keywords: microinvasive glaucoma surgery, MIGS, iStent, trabecular micro-bypass, Japanese, normal-tension glaucoma