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.

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.
METHODS: Patients older than 18 years who were followed up in Glaucoma Unit of Department of Ophthalmology at Fırat 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.
CONCLUSIONS: 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.

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.

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.

OBJECTIVE: 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).
CONCLUSIONS: 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.

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.

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.

OBJECTIVE: To retrospectively evaluate the 3-year efficacy and safety of single-agent omidenepag isopropyl in patients with normal tension glaucoma (NTG).
METHODS: 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.
CONCLUSIONS: 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.

OBJECTIVE: To investigate differences in peripapillary choroidal thickness (PPCT) between primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and healthy eyes, additionally comparing differences between POAG and NTG eyes.
CONCLUSIONS: Peripapillary choroidal thickness is a well-established OCT parameter in eyes with glaucoma and other ocular pathologies. The relationship between PPCT and glaucoma, if better understood, may facilitate the development of PPCT as a potential diagnostic and monitoring metric for glaucoma. In particular, there has yet to be a synthesis that directly compares PPCT between POAG eyes and NTG eyes.
METHODS: A comprehensive literature search was performed on PubMed, EMBASE, and Cochrane Library, identifying studies from inception to December 2022. We included studies that measured PPCT using OCT in POAG, NTG, and healthy eyes. Mean difference (MD) among groups was calculated. Statistical analysis was performed using R version 4.2.0. Risk of bias of included studies was assessed using the Newcastle Ottawa Scale (NOS).
RESULTS: Eighteen studies were included in this meta-analysis, with a pooled total of 935 healthy control eyes, 446 NTG eyes, and 934 POAG eyes. There was a significant reduction of PPCT in POAG eyes compared with healthy eyes [MD = -16.32; 95% confidence interval (CI) (-27.55 to -5.09)]. Reduction in PPCT was also significant in NTG eyes compared with healthy eyes [MD = -34.96; 95% CI (-49.97 to -19.95)]. NTG eyes had significantly reduced PPCT compared with POAG eyes [MD = -26.64; 95% CI (-49.00 to -4.28)].
CONCLUSIONS: Glaucomatous eyes appear to have significantly reduced PPCT compared with normal healthy eyes. In addition, PPCT in NTG eyes appear significantly thinner compared with that in POAG eyes.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.