Normal Tension Glaucoma Research Articles

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.

Peripapillary Versus Macular Thinning to Detect Progression According to Initial Visual Field Loss Location in Normal-Tension Glaucoma

PurposeTo investigate the predictive capabilities of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thinning to detect visual field (VF) progression in normal-tension glaucoma patients with an initial parafoveal scotoma (IPFS) or nasal step (INS). DesignRetrospective cohort study. Methods185 early-stage glaucoma eyes, followed for 10 years, were retrospectively stratified into IPFS and INS groups. Progressive pRNFL and mGCIPL thinning were assessed using spectral-domain optical coherence tomography and VF progression using both event- or trend-based analysis. Kaplan-Meier survival analysis compared VF survival in each VF phenotype with or without progressive pRNFL and mGCIPL thinning. Cox proportional regression analysis identified VF progression factors. ResultsVF progression was detected in 42 IPFS (n=86) and 47 INS (n=99) eyes. Among VF progressors, pRNFL thinning was significantly faster in INS group compared to IPFS group (P < 0.01), while mGCIPL thinning was similar (P = 0.16). At five years, eyes with progressive mGCIPL thinning showed significantly lower VF survival in both VF phenotypes (all P < 0.05). Progressive pRNFL thinning showed significantly lower VF survival only in INS eyes (P = 0.015). Cox multivariate regression revealed that mGCIPL thinning predicted subsequent VF progression in IPFS eyes, while mGCIPL and pRNFL thinning had significant associations with VF progression in INS eyes. ConclusionsmGCIPL outperforms pRNFL at early follow-up in detecting VF progression in IPFS eyes but not INS eyes. Appropriate selection of structural parameters (mGCIPL vs pRNFL) maximizes early VF progression detection according to initial VF defect location.

High-intensity interval training in patients with glaucoma (HIT-GLAUCOMA): protocol for a multicenter randomized controlled exercise trial.

Glaucoma stands as a prominent global cause of irreversible blindness and the primary treatment approach involves reducing intraocular pressure (IOP). However, around one-third of patients exhibit disease progression despite effective IOP reduction. Microvascular endothelial function, chronic inflammation, and oxidative stress are known to affect retinal neuronal networks and have been associated with disease severity and progression. Exercise training has the potential to counteract these mechanisms as add-on treatment to usual care. The HIT-GLAUCOMA study will investigate the effects of a 6-month high-intensity interval training (HIIT) on intermediate endpoints such as local retinal microvascular and systemic large artery function, inflammation, and oxidative stress as well as clinical endpoints such as visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology. The study is a multi-center randomized controlled clinical trial in patients with both normal tension and high-tension primary open angle glaucoma. Across two study centers, 128 patients will be enrolled and randomized on a 1:1 basis into an exercise intervention group and a usual care control group. The primary microvascular endpoints are retinal arteriolar and venular flicker light-induced dilation at 6months. The primary endpoint in the systemic circulation is brachial artery flow-mediated dilation at 6months. We hypothesize that exercise therapy will improve retinal microvascular function and thus ocular blood flow in patients with glaucoma. As clinical outcomes, we will investigate the effect of exercise on visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology. HIT-GLAUCOMA is a blueprint trial design to study the effect of exercise training on neurodegenerative and cardiovascular diseases. Importantly, patients are also expected to benefit from improvements in general health and cardiovascular co-morbidities. If proven effective, exercise may offer a new add-on treatment strategy to slow glaucoma progression. The trial is registered at Clinicaltrials.gov under the identifier NCT06058598 and is currently in the recruitment stage.

A meta-analysis of the association between high-sensitivity c-reactive protein level and glaucoma.

Glaucoma is the second-leading cause of blindness in the US for people over the age of 40; the most common form is primary open-angle glaucoma (POAG). It has been suggested that inflammatory markers have a role in the development and the progression of glaucoma (GL). High-sensitivity C reactive protein (HsCRP) is an inflammatory marker that has been linked to cardiovascular disease and a possible link to GL. Although a number of studies have found a link between CRP and GL; POAG, normal tension glaucoma (NTG), exfoliation glaucoma (XFG), Exfoliation syndrome (XFS), other research has shown the opposite. This systematic review is to determine the association between HsCRP and GL. A literature search was conducted using the MEDLINE database. We identified thirty-six peer-reviewed studies. Five retrospective studies were included and summed up to 164305 study participants, 161759 POAG patients, and 2546 controls. The pooled result of all studies revealed that HsCRP (SMD: 0.44 mg/dl; [95% confidence interval -0.10 to 0.99]; P = 0.11, I2 89%) concentration was not significantly higher in POAG patients compared to the healthy controls. The SMD for NTG, XFG and XFS; 0.64 mg/dl; 0.03 mg/dl, 0.03 mg/dl respectively. The pooled result revealed that HsCRP concentration was not significantly higher in POAG, NTG, XFG, and XFS. No publication bias was found using the funnel plot. The meta-analysis concluded that there is no correlation between the elevated plasma levels of HsCRP and GL. Future studies should be conducted.

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

BackgroudThe 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).MethodsThis 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.ResultsAfter 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).ConclusionsFluctuation in OPP was associated with VF progression in patients with NTG.

Increased late-onset glaucoma risk following vitrectomy for macular pucker or hole.

The long-term risk of developing glaucoma after vitrectomy remains uncertain. This retrospective population-based cohort study aimed to explore this risk following vitrectomy for macular pucker or hole. Utilizing Taiwan's National Health Insurance Research Database (NHIRD), we included patients who were older than 18 years and had undergone vitrectomy surgery between 2011 and 2019. Exclusions were made for patients with prior diagnoses of glaucoma, congenital or secondary glaucoma, as well as those who had received previous vitreoretinal treatments or had undergone multiple vitrectomies. After an average follow-up period of 51 and 53 months respectively for the vitrectomized and non-vitrectomized group, our results showed a relative risk of 1.71 for glaucoma development in the vitrectomized group. Higher adjusted hazard ratios were also observed for open-angle glaucoma and normal tension glaucoma. Increased risks were associated with male sex, obstructive sleep apnoea, and migraine. In the subgroup analysis, phakic eyes at baseline and those who had undergone cataract surgery post-vitrectomy were associated with a lower risk of glaucoma development during follow-up. Among all glaucoma events, pseudophakic status at baseline had the shortest interval to glaucoma development following vitrectomy. These findings underscore the potential relationship between vitrectomy and glaucoma onset, emphasizing the need for vigilant monitoring and early detection of glaucoma in post-vitrectomy patients.

Rapid Retinal Nerve Fiber Layer Thinning in the Unaffected Contralateral Eyes of Patients with Unilateral Normal-Tension Glaucoma: A Retrospective Observational Study

PurposeTo observe the rate of progressive retinal nerve fiber layer (RNFL) thinning in the unaffected eyes of patients with unilateral normal-tension glaucoma (NTG), in comparison with that of healthy subjects, and to identify the factors associated with progressive RNFL thinning. DesignRetrospective, longitudinal, observational study. ParticipantsNinety-five patients with unilateral NTG and 61 healthy controls MethodsThis study included unilateral NTG and healthy control subjects who were followed up for longer than 4 years and in whom at least 5 reliable RNFL thickness (RNFLT) measurements were performed using optical coherence tomography. Factors associated with the rate of thinning of the unaffected eyes of unilateral NTG patients were identified using regression analysis. Main Outcome MeasuresThe rate of progressive RNFL thinning and the associated factors. ResultsRNFLT decreased significantly in both the unaffected eyes of unilateral NTG patients and the healthy eyes (both P<0.001). The RNFL thinning was significantly faster in the unaffected eyes of unilateral NTG patients than in the healthy eyes (P<0.001), specifically in the temporal-inferior sector (P=0.003). Factors associated with faster RNFL thinning in the unaffected eyes of unilateral NTG patients were thicker baseline RNFL of the unaffected eyes (P=0.002) and a worse visual field (VF) mean deviation (MD) in the NTG eyes (P=0.040). In the healthy controls, the rate of RNFL thinning in the contralateral eyes was the only factor associated with faster thinning (P=0.007). ConclusionsThe unaffected eyes of unilateral NTG patients showed faster RNFL thinning than healthy control eyes, more obviously in the temporal-inferior sector, and were likely to progress faster when they had a thicker baseline RNFL, and when the NTG eyes had a worse VF MD. In unilateral NTG patients, initiation of prophylactic treatment could be considered for the unaffected eyes when they are accompanied by a risk of developing glaucoma.

Age related cerebrospinal fluid flow dynamics in the subarachnoid space of the optic nerve in patients with normal tension glaucoma, measured by diffusion weighted MRI

Background/objectivesWe aimed to measure cerebrospinal fluid (CSF) flow rates in the subarachnoid space (SAS) of the optic nerve (ON) by applying non-invasive diffusion-weighted MRI in patients with normal tension glaucoma (NTG) compared to age-matched controls.Subjects/methodsIn this prospective study, an analysis of diffusion-weighted images of 26 patients with NTG (49ONs) and age-matched volunteers (52ONs) was conducted. Subjects were classified into 4 groups: group I (50–59 y., n = 12 eyes), group II (60–69 y., n = 16 eyes), group III (70–79 y., n = 18 eyes) and group IV ( > 80 y., n = 6 eyes) for NTGs and healthy volunteers, respectively. The flow-range ratio (FRR) between the frontal lobe SAS and the SAS of the ON was calculated for each age category group and then compared between age-categories as well as between NTGs and controls.ResultsThe mean FRR for age groups were (I) 0.54 ± 0.06 and 0.62 ± 0.03 (p < 0.05), (II) 0.56 ± 0.08 and 0.63 ± 0.03 (p < 0.05), (III) 0.54 ± 0.06 and 0.62 ± 0.02 (p < 0.001) as well as (IV) 0.61 ± 0.03 and 0.61 ± 0.04, for NTGs and controls, respectively. Using pooled data, the difference between the FRR in NTGs and controls was statistically significant (p < 0.0001). There were no statistically significant differences within the age categories of the control group. When comparing the FRR of NTGs by age categories, no statistically significant difference was found between the subgroups.ConclusionsFRR was significantly reduced in NTGs compared to age-matched controls without any significant differences within the age groups themselves. Given the physiological importance of CSF for the integrity of neurons, axons and glial cells, reduced CSF flow dynamics might be part of the underlying neurodegenerative process of NTG.

Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma

Glaucoma is characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, and its risk increases with aging. Yet comprehensive insights into the complex mechanisms are largely unknown. Here, we found that anti-aging molecule Sirt6 was highly expressed in RGCs. Deleting Sirt6 globally or specifically in RGCs led to progressive RGC loss and optic nerve degeneration during aging, despite normal intraocular pressure (IOP), resembling a phenotype of normal tension glaucoma. These detrimental effects were potentially mediated by accelerated RGC senescence through Caveolin-1 upregulation and by the induction of mitochondrial dysfunction. In mouse models of high tension glaucoma, Sirt6 level was decreased after IOP elevation. Genetic overexpression of Sirt6 globally or specifically in RGCs significantly attenuated high tension-induced degeneration of RGCs and their axons, whereas partial or RGC-specific Sirt6 deletion accelerated RGC loss. Importantly, therapeutically targeting Sirt6 with pharmacological activator or AAV2-mediated gene delivery ameliorated high IOP-induced RGC degeneration. Together, our studies reveal a critical role of Sirt6 in preventing RGC and optic nerve degeneration during aging and glaucoma, setting the stage for further exploration of Sirt6 activation as a potential therapy for glaucoma.

Exploring the role of apolipoprotein E gene promoter polymorphisms in susceptibility to normal-tension glaucoma in a Korean population

Glaucoma, particularly primary open-angle glaucoma (POAG), poses a significant global health concern. Distinguished by intraocular pressure (IOP), POAG encompasses high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Apolipoprotein E (APOE) is a multifaceted protein with roles in lipid metabolism, neurobiology, and neurodegenerative diseases. However, controversies persist regarding the impact of APOE single-nucleotide polymorphisms (SNPs) on open-angle glaucoma and NTG. This study aimed to identify APOE-specific SNPs influencing NTG risk. A cohort of 178 patients with NTG recruited from Uijeongbu St. Mary’s Hospital and 32,858 individuals from the Korean Genome and Epidemiology Study (KoGES) cohort were included in the analysis. Genotype and haplotype analyses were performed on three promoter SNPs (rs449647, rs769446, and rs405509) and two exonic SNPs (rs429358 and rs7412) located on chromosome 19. Among the five SNPs, rs769446 genotypes exhibited significant differences between cases and controls. The minor allele C of rs769446 emerged as a protective factor against NTG. Furthermore, haplotype analysis of the five SNPs revealed that the A-T-G-T-T haplotype was a statistically significant risk factor for NTG. This study indicated an association between APOE promoter SNPs and NTG in the Korean population. Further studies are required to understand how APOE promoter SNPs contribute to NTG pathogenesis.

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 subtypeof open-angle glaucoma, NTG is characterized by retinal ganglion cell (RGC) degeneration, gradualloss of axons, andinjury 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.

Association of Gene Polymorphisms with Normal Tension Glaucoma: A Systematic Review and Meta-Analysis.

Normal tension glaucoma (NTG) is becoming a more and more serious problem, especially in Asia. But the pathological mechanisms are still not illustrated clearly. We carried out this research to uncover the gene polymorphisms with NTG. We searched in Web of Science, Embase, Pubmed and Cochrane databases for qualified case-control studies investigating the association between single nucleotide polymorphisms (SNPs) and NTG risk. Odds ratios (ORs) and 95% confidence intervals (CIs) for each SNP were estimated by fixed- or random-effect models. Sensitivity analysis was also performed to strengthen the reliability of the results. Fifty-six studies involving 33 candidate SNPs in 14 genetic loci were verified to be eligible for our meta-analysis. Significant associations were found between 16 SNPs (rs166850 of OPA1; rs10451941 of OPA1; rs735860 of ELOVL5; rs678350 of HK2; c.603T>A/Met98Lys of OPTN; c.412G>A/Thr34Thr of OPTN; rs10759930 of TLR4; rs1927914 of TLR4; rs1927911 of TLR4; c.*70C>G of EDNRA; rs1042522/-Arg72Pro of P53; rs10483727 of SIX1-SIX6; rs33912345 of SIX1-SIX6; rs2033008 of NCK2; rs3213787 of SRBD1 and c.231G>A of EDNRA) with increased or decreased risk of NTG. In this study, we confirmed 16 genetic polymorphisms in 10 genes (OPA1, ELOVL5, HK2, OPTN, TLR4, EDNRA, P53, NCK2, SRBD1 and SIX1-SIX6) were associated with NTG.

The need for more pragmatic trials in glaucoma research.

There have been a number of clinical trials in glaucoma research published in the past two decades. Most of these trials were designed to evaluate very specific issues in selected populations placing them in the explanatory end of the pragmatic-explanatory continuum. The purpose of this study was to assess the level of pragmatism of published randomized controlled trials in glaucoma. A PubMed search using 'glaucoma' from 1995 to 2022 and randomized controlled trial (RCT) article type was done. Each study was assessed by three independent examiners using the Pragmatic-Explanatory Continuum Indicator Summary version 2 (PRECIS-2) toolkit. Scores were calculated for each study to determine the level of pragmatism. A summed score ≥36 was indicative of a very pragmatic study. Thirty-two different articles were included in the analysis. These papers represented 13 different landmark trials. The median PRECIS-2 score was 32 (range, 25 for the Early Manifest Glaucoma Trial (EMGT) to 34 to the Collaborative Normal Tension Glaucoma Study (CNTGS) and the Ocular Hypertension Treatment Study). The Treatment of Advanced Glaucoma Study (TAGS), was considered very pragmatic and scored 33 points. Despite the number of RCTs in glaucoma, there is still a need for more pragmatic studies.

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

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

The Effect of Phacoemulsification on the Intraocular Pressure of Patients With Open Angle Glaucoma: A Systematic Review and Meta-Analysis.

There is evidence that cataract surgery can reduce intraocular pressure in patients with primary open angle, normal tension, or exfoliative glaucoma. The complete effect of phacoemulsification is masked by topical intraocular pressure-lowering medications. To assess the impact of phacoemulsification and intraocular lens implantation on intraocular pressure (IOP) level in individuals with primary open angle glaucoma (POAG), exfoliative glaucoma (XFG), exfoliation syndrome (XFS), normal tension glaucoma (NTG), ocular hypertension (OH), or healthy controls 12 months after the surgery. In July 2023, a comprehensive literature review was conducted across six databases. The analysis focused on the phacoemulsification arms of randomized controlled trials (RCTs). The primary outcome of interest was the mean IOP change observed 12 months after phacoemulsification. This meta-analysis included 9 arms from 9 RCTs, comprising a total of 502 participants. Overall, the average IOP was reduced by 3.77mm Hg (95% CI: -5.55 to -1.99, I2 =67.9%) 12 months after surgery. The subgroup analysis, focused on whether a washout period was used before measuring IOP, revealed that studies with a washout period exhibited a more pronounced IOP reduction of 5.25mm Hg (95% CI: -7.35 to -3.15, I2 =0%), while studies without a washout period exhibited a reduction of 3.13mm Hg (95% CI: -5.46 to -0.81, I2 =75.8%). The sensitivity analysis for the latter group, excluding an outlier study, showed a reduction of 1.81mm Hg (95% CI: -2.95 to -0.67, I2 =0%). The findings of this systematic review and meta-analysis indicate that cataract surgery meaningfully lowers IOP in POAG, XFG/XFS, or OH 12 months after surgery. However, the use of topical medications masks the precise impact of phacoemulsification upon postoperative IOP. Further research using appropriate washout periods is warranted.

Efficacy and safety of first-line or second-line selective laser trabeculoplasty for normal-tension glaucoma: a multicentre cohort study

Background/aimsThis study aimed to investigate and compare the efficacy and safety of first-line and second-line selective laser trabeculoplasty (SLT) in Japanese patients with normal-tension glaucoma (NTG).Methods100 patients with NTG were...

Is Glaucoma a Two-Pressure-Related Optic Neuropathy? A Systematic Review and Meta-Analysis.

To review the current literature related to the correlation between translaminar pressure difference (TLPD) and glaucoma. In this article, we conducted a literature review using MEDLINE via PubMed, Cochrane Eyes and Vision, and Google Scholar from 01/01/2010 to 31/12/2022. Search terms included "glaucoma", "intraocular pressure", "translaminar cribrosa pressure gradient/difference", "intracranial pressure", and "cerebrospinal fluid pressure". Of 471 results, 8 articles were selected for the meta-analysis. Our meta-analysis demonstrated significantly higher intraocular pressure, lower cerebrospinal fluid pressure (CSFp), and greater TLPD in high-tension and normal-tension glaucoma groups compared to healthy groups. The differences in CSFp and TLPD between glaucoma and healthy people detected in current studies suggests a potential relationship between TLPD and glaucoma.

Effect of Dorzolamide-Timolol fixed dose combination on central Corneal Thickness in patients of Primary Open Angle Glaucoma Versus Normal Tension Glaucoma

PURPOSE: To evaluate the effect of dorzolamide/timolol fixed dose combination on central corneal thickness in primary open-angle and normal tension glaucoma. METHOD: This retrospective cohort study was approved by the Ethical Review Board of College of Ophthalmology and Allied vision Sciences (1469/23) and was conducted at Diagnostic clinic Mayo Hospital, Lahore from March, 2023 to September, 2023. Sample size was calculated by a formula whose level of significance (????) was 5%, standard deviation (????) 30.9 and test values of population mean (µ̥) was 540. Using non-probability convenient sampling method total sample size was 80 patients of age group 30 to 60 which divided into normal tension and primary open angle glaucoma of 40 each. Patients with corneal edema, diabetes, and allergic to dorzolamide-timolol fixed dose combination were excluded. Data was analyzed using SPSS version 25.00. Wilcoxon signed ranks test and chi-square test were used for the significance of the study. Data p-value &lt;0.005 considered significant. All the tests were performed after patient’s informed consent. Intraocular pressure (IOP) and central corneal thickness (CCT) were measured by Goldmann applanation tonometer and ultrasound Pachymeter respectively. RESULTS: IOP and CCT in right eye 16.17± 7.05 (p=0.000) and 545.50± 22.2 (p=0.098) respectively and of left eye 16.56± 7.00 (p=0.003) and 549.16± 20.0 (p=0.133) respectively. This illustrates significant difference in intraocular pressure after treatment in both eyes but insignificance difference in central corneal thickness. CONCLUSION: Dorzolamide-Timolol combination successfully reduces IOP as intended and leads to no statistically significant change in central corneal thickness.

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.

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

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. 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. 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). 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.