Manometric Intraocular Pressure Reduction with Negative Pressure Using Ocular Pressure Adjusting Pump Goggles.

OBJECTIVE: The Ocular Pressure Adjusting Pump is a novel, non-invasive and non-pharmacological intraocular pressure (IOP)-lowering device consisting of goggles attached to a negative pressure (NP) pump. This study aimed to determine the effect of negative pressure in Ocular Pressure Adjusting Pump goggles on IOP using continuous direct manometry. DESIGN: Prospective, single-arm, single center, basic physiological research trial. SUBJECTS: Adult patients undergoing cataract surgery. METHODS: Direct manometry was performed via an anterior chamber cannula attached to an IOP sensor. This was placed just prior to each subject's previously scheduled cataract surgery. IOP was continuously monitored every 0.5 seconds through the following sequence of 30 seconds each: baseline IOP measurement, NP -10 mmHg, NP off, NP -20 mmHg, and NP off. MAIN OUTCOME MEASURES: IOP response to application of negative pressure. RESULTS: All seventeen subjects had a dose-dependent reduction in IOP, with a mean IOP decrease from 16.9 to 11.3 (33%) with -10 mmHg of NP and from 15.7 to 7.7 (51%) mmHg with -20 mmHg of NP. IOP returned to baseline for each cycle when NP was discontinued. There were no patients with increased IOP. CONCLUSIONS: Negative pressure with the Ocular Pressure Adjusting Pump results in a consistent dose-dependent reduction in IOP, with return to baseline IOP when NP is discontinued.

Diagnostic dilemma: Leber's hereditary optic neuropathy in a 70-year-Old woman.

Purpose: Reports of atypical cases have increased awareness that Leber's hereditary optic neuropathy (LHON) is not solely a disease of young men. Here, we present a case of a 70-year-old woman who presented with bilateral sequential loss of vision, and, after several diagnostic dilemmas, was ultimately found to have LHON. Observations: Our patient presented with a one-month history of progressive central vision loss in the right eye. Her visual acuities were 20/200-1 and 20/25-2. She had no afferent pupillary defect and intraocular pressures were normal. Fundus examination revealed cup-to-disc ratios of 0.9 and 0.7 with an inferior notch on the right. Visual fields showed superior arcuate and cecocentral depressions on the right and an inferior nasal step on the left. Ocular coherence tomography showed bilateral, superior and inferior retinal nerve fiber layer thinning. She was diagnosed with normal-tension glaucoma. Laboratory studies and neuroimaging were unremarkable. One month later, she presented with new central vision loss in the left eye. Ocular coherence tomography revealed new, mild optic nerve swelling in the left eye. Due to concern for an acute-on-chronic process, she was hospitalized and treated with intravenous steroids and later plasmapheresis with modest improvement. An extensive laboratory evaluation, lumbar puncture, temporal artery biopsy, and PET CT were normal. Mitochondrial genetic testing was ordered. After a six-week delay, the results revealed a pathogenic variant at mitochondrial position 11778, consistent with a diagnosis of LHON. She began treatment with idebenone. At the most recent visit, her vision had improved to 20/40 and 20/30. Conclusions and importance: LHON is typically not part of the initial differential diagnosis of an optic neuropathy in patients outside the typical demographic. As genetic testing has become more widely available, clinicians should consider including LHON in their differential diagnosis of any optic neuropathy, especially if other, more common causes have been ruled out.

Genetic association of lipid traits and lipid-related drug targets with normal tension glaucoma: a Mendelian randomization study for predictive preventive and personalized medicine.

Background: Glaucoma is the leading cause of irreversible blindness worldwide. Normal tension glaucoma (NTG) is a distinct subtype characterized by intraocular pressures (IOP) within the normal range (< 21 mm Hg). Due to its insidious onset and optic nerve damage, patients often present with advanced conditions upon diagnosis. NTG poses an additional challenge as it is difficult to identify with normal IOP, complicating its prediction, prevention, and treatment. Observational studies suggest a potential association between NTG and abnormal lipid metabolism, yet conclusive evidence establishing a direct causal relationship is lacking. This study aims to explore the causal link between serum lipids and NTG, while identifying lipid-related therapeutic targets. From the perspective of predictive, preventive, and personalized medicine (PPPM), clarifying the role of dyslipidemia in the development of NTG could provide a new strategy for primary prediction, targeted prevention, and personalized treatment of the disease. Working hypothesis and methods: In our study, we hypothesized that individuals with dyslipidemia may be more susceptible to NTG due to a dysregulation of microvasculature in optic nerve head. To verify the working hypothesis, univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were utilized to estimate the causal effects of lipid traits on NTG. Drug target MR was used to explore possible target genes for NTG treatment. Genetic variants associated with lipid traits and variants of genes encoding seven lipid-related drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). GWAS data for NTG, primary open angle glaucoma (POAG), and suspected glaucoma (GLAUSUSP) were obtained from FinnGen Consortium. For apolipoproteins, we used summary statistics from a GWAS study by Kettunen et al. in 2016. For metabolic syndrome, summary statistics were extracted from UK Biobank participants. In the end, these findings could help identify individuals at risk of NTG by screening for lipid dyslipidemia, potentially leading to new targeted prevention and personalized treatment approaches. Results: Genetically assessed high-density cholesterol (HDL) was negatively associated with NTG risk (inverse-variance weighted [IVW] model: OR per SD change of HDL level = 0.64; 95% CI, 0.49-0.85; P = 1.84 × 10-3), and the causal effect was independent of apolipoproteins and metabolic syndrome (IVW model: OR = 0.29; 95% CI, 0.14-0.60; P = 0.001 adjusted by ApoB and ApoA1; OR = 0.70; 95% CI, 0.52-0.95; P = 0.023 adjusted by BMI, HTN, and T2DM). Triglyceride (TG) was positively associated with NTG risk (IVW model: OR = 1.62; 95% CI, 1.15-2.29; P = 6.31 × 10-3), and the causal effect was independent of metabolic syndrome (IVW model: OR = 1.66; 95% CI, 1.18-2.34; P = 0.003 adjusted by BMI, HTN, and T2DM), but not apolipoproteins (IVW model: OR = 1.71; 95% CI, 0.99-2.95; P = 0.050 adjusted by ApoB and ApoA1). Genetic mimicry of apolipoprotein B (APOB) enhancement was associated with lower NTG risks (IVW model: OR = 0.09; 95% CI, 0.03-0.26; P = 9.32 × 10-6). Conclusions: Our findings supported dyslipidemia as a predictive causal factor for NTG, independent of other factors such as metabolic comorbidities. Among seven lipid-related drug targets, APOB is a potential candidate drug target for preventing NTG. Personalized health profiles can be developed by integrating lipid metabolism with life styles, visual quality of life such as reading, driving, and walking. This comprehensive approach will aid in shifting from reactive medical services to PPPM in the management of NTG. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00373-5.

Intraocular Pressure Measurements in Standing, Sitting, Prone, and Supine Positions.

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.

Proteomic and Cytokine Profiling in Plasma from Patients with Normal-Tension Glaucoma and Ocular Hypertension.

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-1ß (IL-1ß) 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.

Age-related effects of optineurin deficiency in the mouse eye.

Optineurin (OPTN) is a gene associated with familial normal tension glaucoma (NTG). While NTG involves intraocular pressure (IOP)-independent neurodegeneration of the visual pathway that progresses with age, how OPTN dysfunction leads to NTG remains unclear. Here, we generated an OPTN knockout mouse (Optn-/-) model to test the hypothesis that a loss-of-function mechanism induces structural and functional eye deterioration with aging. Eye anatomy, visual function, IOP, retinal histology, and retinal ganglion cell survival were compared to littermate wild-type (WT) control mice. Consistent with OPTN's role in NTG, loss of OPTN did not increase IOP or alter gross eye anatomy in young (2-3 months) or aged (12 months) mice. When retinal layers were quantitated, young Optn-/- mice had thinner retina in the peripheral regions than young WT mice, primarily due to thinner ganglion cell-inner plexiform layers. Despite this, visual function in Optn-/- mice was not severely impaired, even with aging. We also assessed relative abundance of retinal cell subtypes, including amacrine cells, bipolar cells, cone photoreceptors, microglia, and astrocytes. While many of these cellular subtypes were unaffected by Optn deletion, more dopaminergic amacrine cells were observed in aged Optn-/- mice. Taken together, our findings showed that complete loss of Optn resulted in mild retinal changes and less visual function impairment, supporting the possibility that OPTN-associated glaucoma does not result from a loss-of-function disease mechanism. Further research using these Optn mice will elucidate detailed molecular pathways involved in NTG and identify clinical or environmental risk factors that can be targeted for glaucoma treatment.

Comparison of 1-year effectiveness between phaco-microhook ab-interno trabeculotomy and phaco-iStent trabecular micro-bypass stent in primary open-angle glaucoma with low-teen intraocular pressure.

PURPOSE: To investigate the surgical effectiveness of combined cataract surgery with microhook ab-interno trabeculotomy (phaco-µLOT) or iStent trabecular micro-bypass stent (phaco-iStent) in eyes with primary open-angle glaucoma (POAG) and preoperative intraocular pressure (IOP) controlled below 15 mmHg (low-teen IOP). METHODS: This retrospective cohort study included consecutive patients with POAG and low-teen IOP who underwent phaco-µLOT or phaco-iStent as their initial glaucoma surgery and were followed up for 1 year postoperatively. Surgical failure was defined as the inability to achieve the following criteria twice in a row: (A) IOP of 6-15 mmHg with over 20% IOP reduction; (B) IOP of 6-12 mmHg with over 20% IOP reduction. RESULTS: A total of 75 eyes from 75 subjects were included, with 48 in the phaco-µLOT group and 27 in the phaco-iStent group. The mean preoperative IOP and number of antiglaucoma medications were 13.1 ± 2.1 mmHg and 3.4 ± 0.9 in the phaco-µLOT group, and 12.6 ± 2.0 mmHg and 2.5 ± 1.2 in the phaco-iStent group, respectively. The number of antiglaucoma medications was significantly reduced to 2.5 ± 0.9 (phaco-µLOT) and 2.0 ± 1.1 (phaco-iStent) at 1-year postoperatively (all p < 0.05). For criteria A and B, the survival rates were significantly higher in the phaco-µLOT group than in the phaco-iStent group (all p < 0.01). CONCLUSION: Both phaco-µLOT and phaco-iStent hold promise in reducing the need for antiglaucoma medications in POAG eyes with low-teen IOP. Phaco-µLOT may be more effective than phaco-iStent in controlling IOP. KEY MESSAGES: What is known Minimally invasive glaucoma surgeries (MIGS) procedures target the pressure gradient pathways in patients with higher preoperative intraocular pressure (IOP) levels, however, evidence on their effectiveness in normotensive glaucoma patients remains limited. What is new Combined cataract surgery with microhook ab-interno trabeculotomy (phaco-µLOT) or iStent trabecular micro-bypass stent (phaco-iStent) significantly reduced the number of antiglaucoma medications in primary open-angle glaucoma (POAG) eyes with preoperative IOP controlled below 15 mmHg (low-teen IOP). Phaco-µLOT may be more effective than phaco-iStent in controlling IOP. These procedures should be limited to reducing the number of antiglaucoma medications used, as they did not significantly reduce the postoperative IOP in POAG eyes with low-teen IOP.

OCT Angiography of the Retina and the Choroid in the Macula in Patients with Normal Tension Glaucoma and Primary Open Angle Glaucoma.

The aim of this study was to compare vessel density (VD) in the retina and choroid in eyes with primary open angle glaucoma (POAG), normal tension glaucoma (NTG) and controls. Patients with POAG, NTG and controls underwent OCT scanning of the macula and the disc followed by 6 × 6 mm macula OCT angiography (OCTA) imaging. Global and hemifield VD were recorded for the superficial (SVP) and deep (DVP) vascular plexus and the choriocapillaris (CC). The OCT thickness of the nerve fiber layer (NFL) and ganglion cell layer (GCC) was also measured. Data from 65 POAG, 33 NTG and 40 control eyes matched for age were analyzed. Mean SVP VD was lower in NTG and POAG eyes compared to controls (38.8 ± 5.3, 40.7 ± 6.8 and 48.5 ± 4.0%, p < 0.001). Mean DVP VD was lower in NTG and POAG eyes compared to controls (43.1 ± 6.1, 44.5 ± 7.6 and 48.6 ± 5.8%, p = 0.002). There was no difference in SVP VD or DVP VD between the glaucoma groups (p > 0.050). No difference was noted in CC VD between the groups (68.3 ± 2.3, 67.6 ± 3.7 and 68.5 ± 2.6%, p = 0.287). Lower SVP and DVP VD was seen in eyes with glaucoma compared to normal eyes. NTG and POAG eyes had similar VD loss. Eyes with glaucoma manifested similar CC VD compared to controls.

Angle-based minimally invasive glaucoma surgery in normal tension glaucoma: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis quantitatively examines the efficacy of angle-based minimally invasive glaucoma surgery (MIGS) in normal tension glaucoma (NTG). METHODS: A literature search was performed on Medline, Embase, PubMed, CINAHL and Cochrane Library from inception until 20 December 2022. Pilot, cohort, observational studies and randomised controlled trials including at least 5 subjects undergoing angle-based MIGS (trabecular-bypass devices, excisional trabeculotomy, goniotomy and ab-interno canaloplasty) for NTG, with or without cataract surgery, were included. Meta-analysis of continuous outcome using the meta routine in R version 2022.12.0+353 was performed to determine mean intraocular pressure (IOP) and anti-glaucoma medication (AGM) reduction post-operatively. RESULTS: Of the 846 studies initially identified, 15 studies with a pooled total of 367 eyes which underwent combined phacoemulsification and angle-based MIGS were included for final meta-analysis. Outcomes of the iStent were reported in 5 studies, iStent inject in 7 studies, Hydrus Microstent in 1 study, Kahook Dual Blade in 3 studies, and Trabectome in 2 studies. There was significant reduction in both IOP and AGM post-operatively at 6 months (2.44 mmHg, 95%CI: 1.83-3.06; 1.21 AGM, 95%CI: 0.99-1.44), 12 months (2.28 mmHg, 95%CI: 1.71-2.84; 1.18 AGM, 95%CI: 0.90-1.47), 24 months (2.10 mmHg, 95%CI: 1.51-2.68; 1.26 AGM, 95%CI: 0.85-1.68) and 36 months (2.43 mmHg, 95%CI: 1.71-3.15, 0.87 AGM, 95%CI: 0.21-1.53) (all p < 0.05). Subgroup analysis on combined phacoemulsification-iStent inject surgery demonstrated a reduction in both IOP (2.31 mmHg, 95%CI: 1.07-3.56, p < 0.001) and AGM (1.07 AGM, 95%CI: 0.86-1.29, p < 0.001) at 12 months post-operatively. CONCLUSIONS: Angle-based MIGS combined with phacoemulsification effectively reduces IOP and AGM in NTG eyes for up to 36 months after surgery.

Evaluation of lamina cribrosa curvature index in different types of glaucoma.

OBJECTIVE: The aim of this study was to evaluate the lamina cribrosa curvature index in different types of glaucoma in comparison with clinical findings and conventional measurement methods. MATERIAL AND METHOD: Patients older than 18 years who were followed up in Glaucoma Unit of Department of Ophthalmology at Firat University Faculty of Medicine, whose disease had been under control at least for 1 year, who had at least three reliable visual fields, whose refractive error was between - 6 and + 5 diopter and who did not have any disease other than glaucoma that would affect the visual field, were included in the study. Clinical and demographic characteristics, visual field, optical coherence tomography and lamina cribrosa curvature index (LCCI) results were evaluated. The study patients were divided into six groups: early-stage primary open-angle glaucoma (POAG) as group 1 and intermediate-advanced stage POAG as group 2, pseudo-exfoliation glaucoma (PEXG) as group 3, normal tension glaucoma (NTG) as group 4, ocular hypertension patients whom subsequently developed POAG as group 5 and healthy control as group 6. RESULTS: A total of 189 eyes of 101 patients were included in our study. Forty-seven patients were male (46.5%) and 54 were female (53.5%). The mean age was 62.43 ± 1.49 years. LCCI, mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD) and retinal nerve fiber layer thickness (RNFL) values were analyzed in all groups and Pearson correlation analysis showed statistically significant correlation between PSD and RNFL measurements with LCCI values in all groups. MD value was correlated with LCCI in groups 2, 3 and 4, while VFI value was correlated with LCCI in all groups except group 5. When the groups were compared with each other according to the Post-Hoc Tamhane test, LCCI measurement showed statistically significant results in accordance with MD, VFI, PSD and RNFL values. CONCLUSION: The LCCI assessment is mostly consistent with conventional tests. In this study, in which different types of glaucoma and healthy subjects were examined simultaneously, LCCI shows promise as a detailed and reliable assessment method.

Long-term efficacy and safety of XEN-45 gel stent implantation in patients with normal-tension glaucoma.

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.

Absence of causative genetic association between Helicobacter pylori infection and glaucoma: a bidirectional two-sample mendelian randomization study.

Background: While clinical research has indicated a potential link between Helicobacter pylori infection and the onset of glaucoma, the causality of this association remains uncertain due to the susceptibility of observational studies to confounding factors and reverse causation. Methods: A comprehensive two-sample bidirectional Mendelian randomization (MR) analysis was conducted to assess the causal connection between H. pylori infection and glaucoma. Glaucoma was categorized into primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and pseudo-exfoliation glaucoma (PEG). Various methods, including inverse variance weighted, MR-Egger regression, weighted median, and mode-based estimator, were employed for effect estimation and pleiotropy testing. To enhance result robustness, a sensitivity analysis was performed by excluding proxy single nucleotide polymorphisms. Results: Genetic predisposition for H. pylori infection has no causal effect on glaucoma: (OR 1.00; 95% CI 0.95-1.06, p = 0.980), (OR 0.97; 95% CI 0.86-1.09, p = 0.550), and (OR 0.99; 95% CI 0.90-1.08, p = 0.766) with POAG, NTG, and PEG, respectively. An inverse MR showed no causal effect of POAG, NTG, and PEG on H. pylori infection (OR 1.01; 95% CI 0.97-1.05, p = 0.693), (OR 1.00; 95% CI 0.98-1.03, p = 0.804), and (OR 0.99; 95% CI 0.96-1.01, p = 0.363), respectively. Heterogeneity (p > 0.05) and pleiotropy (p > 0.05) analysis confirmed the robustness of MR results. Conclusion: These results indicated that there was no genetic evidence for a causal link between H. pylori and glaucoma, suggesting that the eradication or prevention of H. pylori infection might not benefit glaucoma and vice versa.

Associations of long-term fluctuation in blood pressure and ocular perfusion pressure with visual field progression in normal-tension glaucoma.

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.

Neuroimaging in atypical normal tension glaucoma: debating routine implementation in the absence of classic neurological findings.

AIM: To assess the necessity of neuroimaging in patients with neurological or atypical findings of normal tension glaucoma (NTG) who do not exhibit typical glaucoma manifestations. METHODS: A retrospective analysis was conducted on 90 atypical NTG patients who underwent cranial magnetic resonance imaging (MRI) due to atypical symptoms. The demographic characteristics, clinical parameters, and radiological findings were recorded. RESULTS: Among the patients, 66.7% had abnormal radiology results, with the most common findings being gliosis (34.4%), sequelae of cerebrovascular events and vascular malformations (14.4%), and benign intracranial mass lesions (11%). Non-glaucomatous visual field defects were more frequently observed in patients with abnormal neuroimaging results. However, there were no significant differences in intraocular pressure, optic disc parameters, retinal nerve fiber layer thickness, and visual field indices between patients with normal and abnormal radiological results. The mean age of the patients was 58.74y. Interestingly, there was a significant age difference, with the abnormal radiology group having a higher median age (P=0.021). CONCLUSION: The study highlights the importance of cranial imaging in older NTG patients to detect underlying pathologies and prevent misdiagnosis. It suggests that neuroimaging may be warranted in NTG patients with atypical visual field defects incompatible with glaucoma. However, routine neuroimaging in all NTG patients without classic neurological signs may not be necessary.

Drug Treatment Attenuates Retinal Ganglion Cell Death by Inhibiting Collapsin Response Mediator Protein 2 Phosphorylation in Mouse Models of Normal Tension Glaucoma.

Normal tension glaucoma (NTG) is a progressive neurodegenerative disease in glaucoma families. Typical glaucoma develops because of increased intraocular pressure (IOP), whereas NTG develops despite normal IOP. As a subtype of open-angle glaucoma, NTG is characterized by retinal ganglion cell (RGC) degeneration, gradual loss of axons, and injury to the optic nerve. The relationship between glutamate excitotoxicity and oxidative stress has elicited great interest in NTG studies. We recently reported that suppressing collapsin response mediator protein 2 (CRMP2) phosphorylation in S522A CRMP2 mutant (CRMP2 KIKI) mice inhibited RGC death in NTG mouse models. This study evaluated the impact of the natural compounds huperzine A (HupA) and naringenin (NAR), which have therapeutic effects against glutamate excitotoxicity and oxidative stress, on inhibiting CMRP2 phosphorylation in mice intravitreally injected with N-methyl-D-aspartate (NMDA) and GLAST mutant mice. Results of the study demonstrated that HupA and NAR significantly reduced RGC degeneration and thinning of the inner retinal layer, and inhibited the elevated CRMP2 phosphorylation. These treatments protected against glutamate excitotoxicity and suppressed oxidative stress, which could provide insight into developing new effective therapeutic strategies for NTG.

Normal-Tension Glaucoma and Potential Clinical Links to Alzheimer's Disease.

Glaucoma is a group of optic neuropathies and the world's leading cause of irreversible blindness. Normal-tension glaucoma (NTG) is a subtype of glaucoma that is characterized by a typical pattern of peripheral retinal loss, in which the patient's intraocular pressure (IOP) is considered within the normal range (<21 mmHg). Currently, the only targetable risk factor for glaucoma is lowering IOP, and patients with NTG continue to experience visual field loss after IOP-lowering treatments. This demonstrates the need for a better understanding of the pathogenesis of NTG and underlying mechanisms leading to neurodegeneration. Recent studies have found significant connections between NTG and cerebral manifestations, suggesting NTG as a neurodegenerative disease beyond the eye. Gaining a better understanding of NTG can potentially provide new Alzheimer's Disease diagnostics capabilities. This review identifies the epidemiology, current biomarkers, altered fluid dynamics, and cerebral and ocular manifestations to examine connections and discrepancies between the mechanisms of NTG and Alzheimer's Disease.

Three-year efficacy and safety of omidenepag isopropyl in patients with normal tension glaucoma.

PURPOSE: To retrospectively evaluate the 3-year efficacy and safety of single-agent omidenepag isopropyl in patients with normal tension glaucoma (NTG). STUDY DESIGN: Retrospective. METHODS: One hundred patients (100 eyes) who had newly been administered omidenepag isopropyl were enrolled in this study. Intraocular pressure (IOP) was compared at baseline and 6, 9, 12, 18, 24, 30, and 36 months after administration. The mean deviation values at baseline and 12, 24, and 36 months measured using the Humphrey visual field test (30-2 Swedish Interactive Threshold Algorithm standard) were compared. Adverse reactions and dropouts were assessed. RESULTS: IOP significantly decreased from 15.5±2.7 mmHg at baseline to 13.8 ±2.3 mmHg after 6 months, 13.9± 2.3 mmHg after 12 months, 13.9±2.3 mmHg after 18 months, 13.8±2.1 mmHg after 24 months, 13.9±2.0 mmHg after 30 months, and 13.6±1.7 mmHg after 36 months (P < 0.0001). There was no significant difference in the mean deviation values at baseline (-3.66±3.49 dB), 12 months (-3.41±3.80 dB), 24 months (-3.13±3.81 dB), and 36 months (-3.06±3.30 dB). Adverse reactions occurred in 11 patients (11.0%), including conjunctival hyperemia in 6 patients. Fifty-two patients (52.0%) were excluded from the analysis because they discontinued treatment either due to IOP measurement by NCT or the use of additional drugs. CONCLUSION: After the administration of omidenepag isopropyl, IOP in patients with NTG decreased within 3 years, visual fields were maintained, and safety was satisfactory. Thus, omidenepag isopropyl can be used as the first-line treatment for patients with NTG.

Prevalence and Characteristics of Glaucoma Among Patients Presenting to Ophthalmology Clinics in a Tertiary Hospital in the Kingdom of Bahrain.

Introduction The aim of this study was to determine the prevalence and characteristics of glaucoma in patients presenting to the ophthalmology department in a tertiary hospital in Bahrain for the first time. Methods A retrospective study was conducted at the Salmaniya Medical Complex, Manama, Bahrain. The medical records of all patients who presented for the first time to an eye clinic between January and December 2019 were reviewed. Patients who were diagnosed with glaucoma were included in this study. Data regarding age, sex, ethnicity, type of glaucoma, previous treatment, best corrected visual acuity, cup-to-disc ratio, intraocular pressure, central corneal thickness, optical coherence tomography (OCT) retinal nerve fiber layer (RNFL), and visual field findings were collected. Results Of a total of 18,238 new patients in 2019, 173 patients (0.97%) had glaucoma. The mean age of patients with glaucoma was 59.6 ± 11.3 years and approximately 60% of them were males (n=103, 59.5%). In 93% of the cases, glaucoma involved both eyes (n=161). Primary open-angle glaucoma (n=97, 56.1%), normal tension glaucoma (n=28, 16.2%), and chronic angle closure glaucoma (n=15, 8.7%) were the most frequently encountered types of glaucoma. Approximately 16.76% (n=29) of the patients were blind in one or two eyes at the time of presentation. Conclusion There seems to be a low prevalence of glaucoma among the encountered cases on the first visit to ophthalmology clinics in Bahrain, with primary open-angle glaucoma being the most common type.

Cost-utility analysis of treating mild stage normal tension glaucoma by surgery in China: a decision-analytic Markov model.

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.

Unveiling the silent link: Normal-tension glaucoma's enigmatic bond with cardiac blood flow.

This comprehensive review embarks on a captivating journey into the complex relationship between cardiology and normal-tension glaucoma (NTG), a condition that continues to baffle clinicians and researchers alike. NTG, characterized by optic nerve damage and visual field loss despite normal intraocular pressure, has long puzzled clinicians. One emerging perspective suggests that alterations in ocular blood flow, particularly within the optic nerve head, may play a pivotal role in its pathogenesis. While NTG shares commonalities with its high-tension counterpart, its unique pathogenesis and potential ties to cardiovascular health make it a fascinating subject of exploration. It navigates through the complex web of vascular dysregulation, blood pressure and perfusion pressure, neurovascular coupling, and oxidative stress, seeking to uncover the hidden threads that tie the heart and eyes together in NTG. This review explores into the intricate mechanisms connecting cardiovascular factors to NTG, shedding light on how cardiac dynamics can influence ocular health, particularly in cases where intraocular pressure remains within the normal range. NTG's enigmatic nature, often characterized by seemingly contradictory risk factors and clinical profiles, underscores the need for a holistic approach to patient care. Drawing parallels to cardiac health, we examine into the shared vascular terrain connecting the heart and the eyes. Cardiovascular factors, including systemic blood flow, endothelial dysfunction, and microcirculatory anomalies, may exert a profound influence on ocular perfusion, impacting the delicate balance within the optic nerve head. By elucidating the subtle clues and potential associations between cardiology and NTG, this review invites clinicians to consider a broader perspective in their evaluation and management of this elusive condition. As the understanding of these connections evolves, so too may the prospects for early diagnosis and tailored interventions, ultimately enhancing the quality of life for those living with NTG.