Normal Tension Glaucoma Patients Research Articles

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.

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.

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.

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.

Molecular genetics of inherited normal tension glaucoma.

Normal tension glaucoma (NTG) is a complex optic neuropathy characterized by progressive retinal ganglion cell death and glaucomatous visual field loss, despite normal intraocular pressure (IOP). This condition poses a unique clinical challenge due to the absence of elevated IOP, a major risk factor in typical glaucoma. Recent research indicates that up to 21% of NTG patients have a family history of glaucoma, suggesting a genetic predisposition. In this comprehensive review using PubMed studies from January 1990 to December 2023, our focus delves into the genetic basis of autosomal dominant NTG, the only known form of inheritance for glaucoma. Specifically exploring optineurin ( OPTN ), TANK binding kinase 1 ( TBK1 ), methyltransferase-like 23 ( METTL23 ), and myocilin ( MYOC ) mutations, we summarize their clinical manifestations, mutant protein behaviors, relevant animal models, and potential therapeutic pathways. This exploration aims to illuminate the intricate pathogenesis of NTG, unraveling the contribution of these genetic components to its complex development.

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

BackgroundMany 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.MethodsA 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.ResultsThe 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.ConclusionsAccording 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.

Mitochondrial DNA D-loop variants correlate with a primary open-angle glaucoma subgroup

IntroductionPrimary open-angle glaucoma (POAG) is a characteristic optic neuropathy, caused by degeneration of the optic nerve-forming neurons, the retinal ganglion cells (RGCs). High intraocular pressure (IOP) and aging have been identified as major risk factors; yet the POAG pathophysiology is not fully understood. Since RGCs have high energy requirements, mitochondrial dysfunction may put the survivability of RGCs at risk. We explored in buffy coat DNA whether mtDNA variants and their distribution throughout the mtDNA could be risk factors for POAG.MethodsThe mtDNA was sequenced from age- and sex-matched study groups, being high tension glaucoma (HTG, n=71), normal tension glaucoma patients (NTG, n=33), ocular hypertensive subjects (OH, n=7), and cataract controls (without glaucoma; n=30), all without remarkable comorbidities.ResultsNo association was found between the number of mtDNA variants in genes encoding proteins, tRNAs, rRNAs, and in non-coding regions in the different study groups. Next, variants that controls shared with the other groups were discarded. A significantly higher number of exclusive variants was observed in the D-loop region for the HTG group (~1.23 variants/subject), in contrast to controls (~0.35 variants/subject). In the D-loop, specifically in the 7S DNA sub-region within the Hypervariable region 1 (HV1), we found that 42% of the HTG and 27% of the NTG subjects presented variants, while this was only 14% for the controls and OH subjects. As we have previously reported a reduction in mtDNA copy number in HTG, we analysed if specific D-loop variants could explain this. While the majority of glaucoma patients with the exclusive D-loop variants m.72T&amp;gt;C, m.16163 A&amp;gt;G, m.16186C&amp;gt;T, m.16298T&amp;gt;C, and m.16390G&amp;gt;A presented a mtDNA copy number below controls median, no significant association between these variants and low copy number was found and their possible negative role in mtDNA replication remains uncertain. Approximately 38% of the HTG patients with reduced copy number did not carry any exclusive D-loop or other mtDNA variants, which indicates that variants in nuclear-encoded mitochondrial genes, environmental factors, or aging might be involved in those cases.ConclusionIn conclusion, we found that variants in the D-loop region may be a risk factor in a subgroup of POAG, possibly by affecting mtDNA replication.

The impact of intraocular pressure on optical coherence tomography angiography: A review of current evidence

Abstract A scoping review of 45 peer-reviewed manuscripts involving intraocular pressure (IOP) change and concurrent optical coherence tomography angiography (OCTA) assessments was performed to aggregate knowledge, summarize major findings, and identify gaps in literature and methodology relating to the effect of IOP change on OCTA. Articles were identified through PubMed/Medline, Google Scholar, Cochrane, Web of Science, and article reference lists. A total of 838 results were identified, and 45 articles met the inclusion and exclusion criteria for detailed analysis. OCTA metrics including vessel density (VD), perfusion density, and flow density of the superficial capillary plexus and the radial peripapillary capillaries were analyzed in relation to relative temporal IOP changes. Overall, IOP changes were found to affect superficial vascular plexus (VD) measurements on OCTA, especially when IOP elevated above the physiologic normal range (10-21 mmHg). No significant association was found between diurnal IOP variation and OCTA metrics. Cataract surgery improved the whole-image signal strength and VD regardless of changes in IOP. Beta-blockers were associated with paradoxically reduced vessel density in normal tension glaucoma patients in two studies. Although glaucoma surgical intervention studies were inconsistent and limited by scan quality and low sample sizes, patients requiring glaucoma surgery exhibited attenuated postoperative superficial VD recovery despite significant IOP reductions with surgical intervention. In addition to ensuring near-perfect signal strength with minimal media opacities and controlling for high myopia, central corneal thickness, and the presence of retinopathy, clinicians should consider the statistically significant impact of IOP on OCTA metrics when interpreting results.

Distinct metabolic profiles in ocular hypertensive individuals responding

Aims/Purpose: To determine the effect of hypoxia on the plasma metabolic signature of patients with normal‐tension glaucoma (NTG) and ocular hypertension (OHT), compared to healthy controls.Methods: Metabolomic profiles of plasma from patients with NTG (n = 10) and OHT (n = 10) were compared to age‐matched controls (n = 10) to investigate the signature of hypoxia. Participants underwent two hours of exposure to normobaric hypoxia, followed by a 30‐min recovery period in normobaric normoxia. Blood samples were collected at baseline, during hypoxia, and recovery. Plasma samples were analysed 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), as well as univariate analysis with Wilcoxon signed‐rank test and false discovery rate (FDR) correction.Results: Overall, controls, OHT, and NTG patients had similar regulatory patterns. Only few metabolites involved in fatty acid biosynthesis, ketone body metabolism and kynurenine pathway were affected in OHT patients exposed to hypoxia, whereas metabolites related to energy production were not modified in NTG and OHT patients. No differences were found when comparing them pairwise at baseline, or during hypoxia and recovery.Conclusions: OHT patients have altered regulation of ketogenesis and kynurenine pathway, that may explain why they do not suffer from degeneration of the optic nerve. The metabolomes of NTG and OHT patients are regulated differently from controls, and omit to regulate metabolites that are important for energy production. This can potentially contribute to neurodegeneration and ultimately cell death in retinal ganglion cells.

New methods for detection of early loss of rapid flicker, spatial vision, and chromatic sensitivity in glaucoma

Purpose: To examine whether ocular hypertension and early glaucoma cause measurable changes in spatial vision, rapid flicker sensitivity and red/green and yellow/blue colour vision.Methods: We examined subjects aged 40 to 78 years with ocular hypertension (OHT), primary open angle glaucoma (POAG), normal tension glaucoma (NTG), and age matched controls. Monocular best corrected visual acuity (BCVA) was tested using EDTRS charts.VA and Functional Contrast Sensitivity (FCS) with Landolt ring stimuli of both positive and negative contrast were also measured monocularly with the Acuity‐Plus test. Red/green (RG) and yellow/blue (YB) colour thresholds were measured with the Colour Assessment and Diagnostics (CAD) test. Photopic (cone‐enhanced) and mesopic (rod‐enhanced) rapid flicker thresholds were measured at the fovea (0°) and at an eccentricity of 5° in each of the four quadrants using the Flicker‐Plus test. All subjects had their visual fields measured using the Humphrey visual field analyser (24–2 SITA standard protocol). Peripapillary retinal nerve fibre layer thickness (pRNFLT) and macular retinal layer thicknesses were measured using the Heidelberg Spectralis OCT.Results: The mean, logMAR BCVA for OHT patients was 0.00 and for POAG and NTG patients was −0.10 and 0.10, respectively. For control participants, mean logMAR BCVA was 0.00. Mean pRNFL thickness was significantly reduced for glaucoma patients (59.5 ± 7.7 μm) as compared to control subjects (94.6 ± 5.13 μm) and OHT patients (115.5 ± 3.5 μm). POAG and NTG patients showed significantly higher colour thresholds (mean red/green threshold 4.97, blue/yellow 5.28 CAD units) compared to control subjects (mean red/green threshold 2.07, blue/yellow 1.62 CAD units). One OHT patient showed acquired loss of blue/yellow colour vision (3.23 CAD units), with normal VA. The Acuity‐Plus test which employs briefly presented stimuli, also revealed significant loss of VA (3.78 and 3.64 min of arc) and FCS (141.32% and 100%) in an NTG patient, with results outside normal limits for both positive and negative contrast, respectively. Central FCS was higher and outside the normal age limits for POAG patients (73.41% and 89.27%) as compared to age matched controls (61.27% and 33.63%). OHT patients, on the other hand, produced FCS thresholds within normal limits. Flicker modulation thresholds were higher for both rod and cone enhanced stimulus conditions in glaucoma and OHT patients, when compared to control subjects.Conclusion: The results reveal non‐uniform, losses that can affect selectively each of the visual attributes examined in this study. These preliminary findings suggest that in addition to VA and FCS tests, colour vision and rapid flicker sensitivity should also be examined in patients with optic nerve pathologies like glaucoma.

Incidence Rates and Risk Ratios of Normal Tension Glaucoma in Patients with Chronic Rhinosinusitis: A Population-Based Longitudinal Follow-Up Study.

Several studies have investigated the association between chronic rhinosinusitis (CRS) and ophthalmological complications. However, it remains uncertain whether CRS is independently associated with the development of normal tension glaucoma (NTG). Therefore, this retrospective cohort study aimed to investigate the prospective association between CRS and the increased incidence and risk of NTG using a representative population-based dataset. The selection of both the CRS and comparison groups was meticulously conducted through the propensity scoring method. The incidence and risk ratios of NTG were measured using person-years at risk and a weighted Cox proportional hazards model. We enrolled 30,284 individuals without CRS (comparison group) and 15,142 individuals with CRS. The NTG incidence rates were 1.19 and 0.81 in the CRS and comparison groups, respectively. The CRS group showed a significantly increased risk of subsequent development for NTG (adjusted hazard ratio = 1.41, 95% confidence interval = 1.16-1.72), regardless of the CRS subtype. Additionally, the risk of developing NTG was relatively higher in the first 2 years after CRS diagnosis. Moreover, a subgroup analysis revealed a higher risk of NTG in elderly female individuals with CRS. The present findings underscore the importance of monitoring and managing NTG risk in individuals with CRS, especially in elderly female patients.

Abnormal Topological Organization of White Matter Structural Networks in Normal Tension Glaucoma Revealed via Diffusion Tensor Tractography.

Normal tension glaucoma (NTG) is considered a neurodegenerative disease with glaucomatous damage extending to diffuse brain areas. Therefore, this study aims to explore the abnormalities in the NTG structural network to help in the early diagnosis and course evaluation of NTG. The structural networks of 46 NTG patients and 19 age- and sex-matched healthy controls were constructed using diffusion tensor imaging, followed by graph theory analysis and correlation analysis of small-world properties with glaucoma clinical indicators. In addition, the network-based statistical analysis (NBS) method was used to compare structural network connectivity differences between NTG patients and healthy controls. Structural brain networks in both NTG and NC groups exhibited small-world properties. However, the small-world index in the severe NTG group was reduced and correlated with a mean deviation of the visual field (MDVF) and retinal nerve fiber layer (RNFL) thickness. When compared to healthy controls, degree centrality and nodal efficiency in visual brain areas were significantly decreased, and betweenness centrality and nodal local efficiency in both visual and nonvisual brain areas were also significantly altered in NTG patients (all p < 0.05, FDR corrected). Furthermore, NTG patients exhibited increased structural connectivity in the occipitotemporal area, with the left fusiform gyrus (FFG.L) as the hub (p < 0.05). NTG exhibited altered global properties and local properties of visual and cognitive-emotional brain areas, with enhanced structural connections within the occipitotemporal area. Moreover, the disrupted small-world properties of white matter might be imaging biomarkers for assessing NTG progression.

Determination of the Trans-Lamina Cribrosa Pressure Difference in a Community-Based Population and its Association with Open-Angle Glaucoma

To determine the trans-lamina cribrosa pressure difference (TLCPD) in a cohort of normal community-based patients and the relationship to primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). Retrospective cohort study of the Mayo Clinic Study of Aging. The Mayo Clinic Study of Aging is a prospective study evaluating the normal aging population. Mayo Clinic Study of Aging patients who underwent routine lumbar puncture (LP) studies with eye examinations were reviewed. The trans-lamina cribrosa pressure difference was calculated in 2 contexts of intraocular pressure (IOP): (1) maximum IOP at eye visit closest in time to the LP (closest-in-time TLCPD); and (2) IOP before IOP-lowering treatment (pretreatment IOP and pretreatment TLCPD) in POAG and NTG patients. Glaucoma patients without POAG or NTG were excluded. Regression analyses were performed to determine the relationship with glaucoma. IOP, intracranial pressure, TLCPD, POAG, normal-tension glaucoma (NTG) diagnosis, glaucoma parameters. Five hundred forty-eight patients were analyzed. Of these, there were 38 treated glaucoma patients (14 POAG and 24 NTG) and 510 nonglaucomatous patients. Cerebral spinal fluid (CSF) opening pressure was 155.0 ± 42.2 mmH2O in nonglaucomatous patients, 144.0 ± 34.0 mmH2O in POAG (P= 0.15 vs. nonglaucomatous patients), and 136.6 ± 29.3 mmH2O in NTG (P= 0.017 vs. nonglaucomatous patients). Intraocular pressure was 15.47 ± 2.9 mmHg in nonglaucomatous patients, 26.6 ± 3.7 mmHg in POAG, and 17.4 ± 3.4 mmHg in NTG. The closest-in-time TLCPD in the nonglaucomatous cohort was 4.07 ± 4.22 mmHg, which was lower than both the POAG cohort (7.19 ± 3.6 mmHg) and the NTG cohort (5.79 ± 4.5 mmHg, P= 0.04). Pretreatment TLCPD for the overall glaucoma cohort was 10.57 ± 6.1 mmHg. The POAG cohort had a higher pretreatment TLCPD (16.05 ± 5.2 mmHg) than the NTG cohort (7.37 ± 4.1 mmHg; P < 0.0001). Closest-in-time TLCPD for the nonglaucoma cohort (4.07± 4.2 mmHg) was significantly lower than pretreatment TLCPDs for both POAG (16.05 ± 5.2 mmHg; P < 0.0001) and NTG (7.37 ± 4.1 mmHg; P < 0.0001) cohorts. This study establishes the baseline TLCPD in a large cohort of normal, community-based patients. The differences in regression analysis between TLCPD and IOP suggests NTG pathophysiology is partially driven by TLCPD, but is also likely multifactorial. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Implications of Central Corneal Thickness-corrected Intraocular Pressure in Normal-tension Glaucoma with Reduced Central Corneal Thickness

Purpose: Reduced central corneal thickness (CCT) is a risk factor for glaucoma progression and can impact intraocular pressure (IOP) measurement. Therefore, we investigated the glaucoma progression pattern and associated risk factors among individuals with normal-tension glaucoma (NTG) and reduced CCT.Methods: This retrospective study enrolled 187 eyes of 187 NTG patients with an open angle and a baseline IOP &lt; 20 mmHg, adjusted for CCT. Reduced CCT was defined as &lt; 500 µm thickness in both eyes. Patients with a history of corneal disease or surgery affecting CCT were excluded. We used Goldmann tonometry to measure baseline and CCT-corrected IOP (ccIOP; [IOP - [CCT - 545]/50 × 2.5]). The participants were divided into progressing and stable subgroups.Results: The mean CCT was 481.2 ± 17.5 µm and the mean follow-up period was 6.3 ± 2.5 years. The baseline IOP and ccIOP were 13.7 ± 2.4 and 16.6 ± 2.5 mmHg, respectively. The average visual field progression rate was -0.79 ± 1.26 dB/yr. Of the participants, 47 (26.6%) and 140 (73.4%) were in the progressing and stable group, respectively. Participants in the progressing group were older, had a higher baseline ccIOP, and had a higher proportion of pseudophakia than those in the stable group. Multivariate analysis showed that baseline ccIOP was a significant risk factor.Conclusions: Individuals presenting with NTG and reduced CCT had a relatively stable glaucoma progression rate. However, glaucoma progression was associated with old age, pseudophakia, and high baseline IOP in individuals with reduced CCT. In particular, the only significant factor associated with glaucoma progression was ccIOP. Therefore, ccIOP is a clinically significant factor in individuals with NTG and reduced CCT.

Vasoreactivity of the optic nerve head, nailfold, and facial skin in response to cold provocation in normal-tension glaucoma patients

BackgroundThe dysfunction of optic nerve head (ONH) hemodynamics has been suggested to be involved in the pathogenesis of normal-tension glaucoma (NTG). The aim of this study was to compare vasoreactivity in the ONH, nailfold, and facial skin in response to cold-water provocation in NTG patients and healthy controls.MethodsWe performed cold-water provocation in 14 eyes of 14 NTG patients and 15 eyes of 15 age-matched control subjects. Laser speckle flowgraphy-derived tissue-area mean blur rate (MT), skin blood flowmetry-derived pulse wave amplitude (PA), nailfold capillaroscopy-derived nailfold capillary diameter, and other clinical parameters were recorded at baseline and 4 and 6 min after the cold stimulus. We compared changes (as percentages) in these variables in the NTG and control subjects with a linear mixed-effects model and evaluated correlations between these changes with Spearman’s rank correlation coefficient.ResultsThe interaction term between the NTG group (reference, control group) and the 4-min protocol step (reference, baseline) significantly affected the changes in MT, nailfold capillary diameter and PA (β = -9.51%, P = 0.017, β = -20.32%, P = 0.002; β = + 18.06%, P = 0.017, respectively). The change in MT was positively correlated with the change in nailfold capillary diameter, and negatively correlated with the change in PA (r = 0.39, P = 0.036; r = -0.40, P = 0.031, respectively).ConclusionNTG patients showed abnormal vasoconstriction in the ONH and nailfold and vasodilation in the facial skin in response to cold-water provocation.

Diurnal change of retinal vessel density related to hemodynamic variation in treatment-naïve low-teens normal-tension glaucoma

This study undertook to investigate the diurnal variation of optical coherence tomography angiography (OCTA) -derived retinal vessel density (RVD) in glaucoma patients with low baseline intraocular pressure (IOP). A prospective evaluation was performed on low-teens normal-tension glaucoma (low-teens NTG) patients with pre-treatment IOP < 15 mmHg and 32 healthy subjects. Superficial peripapillary and macular RVD by OCTA, IOP, and systemic blood pressure (BP) were all measured four times per day (from 9:00 a.m. to 6:00 p.m.). In the low-teens NTG group, the magnitude of diurnal changes in peripapillary RVD and macular RVD were greater than those in the healthy group. Diurnal variations of diastolic BP (DBP) and mean ocular perfusion pressure (MOPP) also were greater in the low-teens NTG group. As for the patterns of diurnal RVD change, the inferior and temporal sections of macular RVD showed significant differences between the two groups. Diurnal changes of RVD and MOPP and were greater than those in healthy eyes. The macular RVD and MOPP showed different diurnal patterns between the two groups. From these findings, OCTA-derived RVD variation could be related to hemodynamic variability in low-teens NTG.

Factors Associated with Vascular Changes at the Level of Retinal Ganglion Cell Axon versus Soma/Dendrite in Glaucoma Patients.

Superficial and deep macular vessel density (VD) is decreased in eyes with glaucoma. Superficial VD comprises both the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GC/IPL), and various terms have been used previously to describe the layers of macular VD. In our study, we readjusted the macular segmentation. We obtained RNFL and GC/IPL VDs separately to evaluate VD changes of axon versus soma/dendrite of the retinal ganglion cells (RGCs) in detail. We included 66 eyes of normal tension glaucoma patients with inferior localized RNFL defects solely impacting the inferior hemiretina. Macular VD was measured as RNFL VD and GC/IPL VD. VD ratio was calculated by dividing the VD from the affected hemiretina by the VD from the unaffected hemiretina. RNFL VD ratio was related to RNFL and GC/IPL thicknesses (p = 0.005, p = 0.001), whereas GC/IPL VD ratio was not (p = 0.596, p = 0.783). A lower GC/IPL VD ratio was associated with lower RNFL VD (p = 0.017) and systemic hypertension (p = 0.03) in multivariate analysis. Patients with a reduced GC/IPL VD ratio were more prone to poor visual field defects (p = 0.022) and paracentral scotoma (p = 0.046) and more likely to be on treatment for systemic hypertension (p = 0.024). Therefore, glaucoma patients on systemic hypertension treatment and reduced GC/IPL VD require cautious management.

Morning Blood Pressure Surge and Glaucomatous Visual Field Progression in Normal-Tension Glaucoma Patients With Systemic Hypertension

To investigate the impact of a morning blood pressure surge (MBPS) at baseline on subsequent visual field (VF) progression in hypertensive, normal-tension glaucoma (NTG) patients receiving oral anti-hypertensive treatment. Retrospective cohort study. A total of 127 eyes from 127 newly diagnosed NTG patients treated for systemic hypertension and followed up for at least 2 years were analyzed. All patients underwent baseline 24-hour ambulatory blood pressure monitoring (ABPM) and at least 5 serial VF examinations during the follow-up period. VF progression was defined according to the Early Manifest Glaucoma Trial criteria. The associations of VF progression with 24-hour ABPM-based blood pressure (BP) parameters (including MBPS) and other clinical variables were analyzed using Cox regression analyses. Kaplan-Meier survival analysis was used to compare VF survival estimates in patients with and without MBPS. VF progression was detected in 38 eyes (29.9%) over a 5.2-year mean follow-up. In the multivariate Cox regression model, a greater MBPS (hazard ratio [HR]=1.033; P=.024) and lower nighttime mean arterial pressure (MAP) trough (HR=0.965; P=.031) at baseline were significant independent predictors of subsequent VF progression. The likelihood of VF progression was significantly greater in patients with higher MBPS (P=.021) at baseline according to Kaplan-Meier survival analysis. An increased MBPS at baseline is a significant independent predictor of subsequent VF progression in NTG patients with systemic hypertension. This may be another relevant BP parameter associated with VF progression in hypertensive NTG patients receiving oral anti-hypertensive treatment.

Reduced Plasma BDNF Levels in Normal Tension Glaucoma Compared to Open Angle Glaucoma.

The study suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner. To evaluate differences in systemic brain-derived neurotrophic factor (BDNF) levels between primary open angle glaucoma (POAG) patients and normal tension glaucoma (NTG) patients. This study collected blood samples from 260 NTG patients, 220 age-matched POAG patients, and 120 age-matched cataract patients (as controls). BDNF levels were measured with an antibody-conjugated bead assay system (Luminex). We found that plasma BDNF levels in the NTG group were significantly lower than in the POAG and cataract control groups. There was no significant difference between the POAG and cataract groups. This result suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner.

Association between Glaucoma Progression in Macular Ganglion Cell Complex and Disc Hemorrhage: Differences between Superior and Inferior Hemiretinas.

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.