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.

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.

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.

The relationship between equol production status and normal tension glaucoma.

PURPOSE: Equol is metabolized by intestinal bacteria from soy isoflavones and is chemically similar to estrogen. Dietary habits, such as consumption of soy products, influence equol production. A relationship between glaucoma and estrogen has been identified; here, we investigated the relationship between equol production status and glaucoma in Japan. METHODS: We recruited 68 normal-tension glaucoma (NTG) patients (male to female ratio 26:42, average age 63.0 ± 7.6 years) and 31 controls (male to female ratio 13:18, average age 66.0 ± 6.3 years) from our hospital. All women included were postmenopausal. Urinary equol concentration was quantified with the ELISA method. MD was calculated based on the Humphrey visual field. The association between MD and equol was analyzed with Spearman's rank correlation coefficient. The Mann-Whitney U test was used to compare the equol-producing (> 1 µM) and non-producing (< 1 µM) subjects. We also investigated the association between equol and glaucoma with a logistic regression analysis. RESULTS: There was a significant association between equol and MD (r = 0.36, P < 0.01) in the NTG patients. Glaucoma, represented by MD, was significantly milder in the equol-producing subjects than the non-equol producing subjects (P = 0.03). A multivariate analysis revealed the independent contributions of equol, cpRNFLT, and IOP to MD (P = 0.03, P = 0.04, and P < 0.01, respectively). CONCLUSION: Our results suggest that equol, acting through estrogen receptor-mediated neuroprotective effects, might be involved in suppressing the progression of NTG. This result also adds to evidence that glaucoma may be influenced by lifestyle.

Use of rsfMRI-fALFF for the detection of changes in brain activity in patients with normal-tension glaucoma.

BACKGROUND: We know little about the changes of brain activity in patients with normal-tension glaucoma (NTG). PURPOSE: To investigate the altered spontaneous brain activity in patients with NTG through the resting state functional magnetic resonance imaging-fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF) technique, and to explore the relationship with optical coherence tomography (OCT) and field of vision. MATERIAL AND METHODS: Twenty patients with NTG and 20 healthy controls (HCs) (matched for sex, age, and level of education) were enrolled. Spontaneous cerebral activity variations were investigated using the rsfMRI-fALFF technique in all individuals. The average fALFF values of patients with NTG and HCs were compared. RESULTS: Compared with HCs, patients with NTG had significantly lower fALFF values in the right angular gyrus and precuneus; however, higher fALFF values in the brain regions were not observed. The values showed statistically significant negative correlation with those of the retinal nerve fiber layer (right angular gyrus: r = -0.607, P = 0.010; right precuneus: r = -0.504, P = 0.020). There was no significant correlation between the fALFF value and cup-disc ratio (right angular gyrus: r = 0.158, P = 0.494; right precuneus: r = -0.087, P = 0.706), mean deviation (right angular gyrus: r = 0.096, P = 0.468; right precuneus: r = 0.026, P = 0.845), and pattern SD value (right angular gyrus: r = 0.064, P = 0.626; right precuneus: r = -0.145, P = 0.268). CONCLUSION: Abnormal spontaneous activities were detected in numerous brain regions of patients with NTG, which may provide useful information for understanding the dysfunction in NTG. These activity changes in brain regions may be used as effective clinical indicators for NTG.

Twenty-four-Hour Intraocular Pressure-Related Patterns from Contact Lens Sensors in Normal-Tension Glaucoma and Healthy Eyes: The Exploring Nyctohemeral Intraocular pressure related pattern for Glaucoma Management (ENIGMA) Study.

PURPOSE: To investigate 24-hour nyctohemeral intraocular pressure (IOP)-related patterns with contact lens sensors (CLSs) in eyes with primary open-angle glaucoma (POAG) with normal baseline IOP (i.e., normal-tension glaucoma [NTG]) and healthy controls. DESIGN: Prospective, case-control study. PARTICIPANTS: Thirty eyes of 30 patients with NTG, who had had a wash-out period for their IOP-lowering treatment, and 20 eyes of 20 healthy volunteer subjects. METHODS: Patients and subjects were hospitalized for the purposes of 24-hour CLS (SENSIMED Triggerfish; Sensimed AG, Lausanne, Switzerland) measurement. The IOP-related patterns during wake and sleep times over the course of the 24 hours were compared between the 2 groups. The 24-hour ambulatory blood pressure and posture were monitored simultaneously. A generalized linear model was used to find the factors associated with NTG. MAIN OUTCOME MEASURES: The IOP-related patterns, including mean and standard deviation (SD) of measurements, amplitude of cosine-fit curve, acrophase (signal peak), and bathyphase (signal trough) values (millivolt equivalents [mVEq]). RESULTS: The SDs of the 24-hour CLS measurements were significantly greater in NTG eyes than in healthy controls (112.51±26.90 vs. 85.18±29.61 mVEq, P = 0.002). The amplitudes of cosine-fit curve (141.88±39.96 vs. 106.08±41.49 mVEq, P = 0.004) and acrophase values (277.74±129.80 vs. 190.58±127.88 mVEq, P = 0.024), mostly measured during nocturnal period, were significantly greater in NTG eyes than in healthy controls. The NTG subjects slept longer in the lateral decubitus posture than the healthy controls (199.1±137.8 vs. 113.2±86.2 minutes, P = 0.009). In the multivariable generalized linear model, the greater amplitude of cosine-fit curve (ß = 0.218, P = 0.012) and greater time of decubitus posture during sleep (ß = 0.180, P = 0.004) were found to be significantly associated with NTG. CONCLUSIONS: Continuous monitoring of 24-hour IOP-related values with CLS can be useful for assessment of glaucoma risk, especially for patients with NTG whose IOP appears to be in the normal range. Fluctuation of 24-hour IOP-related values and posture during sleep time might be associated with NTG.

Real-World Outcomes of Selective Laser Trabeculoplasty in the United Kingdom.

PURPOSE: Selective laser trabeculoplasty (SLT) is a common treatment option for managing glaucoma and ocular hypertension. We assessed the real-world effectiveness of SLT and baseline factors associated with treatment success in the United Kingdom. DESIGN: Retrospective observational study of de-identified electronic medical records (Medisoft Glaucoma module [Medisoft Ltd, Leeds, UK]) from 5 UK ophthalmology teaching centers. PARTICIPANTS: Adult patients undergoing their first recorded SLT. For bilateral SLT (same day), analyses included 1 randomly selected eye. METHODS: Patient demographics, procedure details, and clinical outcomes data were extracted. Factors associated with treatment success were assessed using multivariable Cox regression. MAIN OUTCOME MEASURES: Change from baseline in intraocular pressure (IOP) and glaucoma medication use at 12 to 18 and 24 to 36 months post-SLT. A Kaplan-Meier survival analysis was also conducted. Failure of SLT was defined as any further glaucoma procedure post-SLT or any of the following at 2 consecutive visits: IOP >21 mmHg, IOP reduction <20% from baseline, or increase in glaucoma medications from baseline. RESULTS: A total of 831 SLT-treated eyes (mean baseline IOP 22.0 mmHg) of 831 patients were analyzed. At 12 to 18 and 24 to 36 months post-SLT, respectively, significant reductions in IOP (-4.2 [95% confidence interval {CI}, -4.7 to -3.7] and -3.4 [95% CI, -4.1 to -2.7] mmHg; both P < 0.0001) and significant increases in the number of glaucoma medications (0.13 [95% CI, 0.04-0.23], P = 0.007, and 0.20 [95% CI, 0.06-0.33], P = 0.005) were observed. Survival analysis demonstrated treatment success in 70%, 45%, and 27% of eyes at 6, 12, and 24 months post-SLT, respectively. Higher baseline IOP was strongly associated with treatment success (hazard ratio [HR], 0.67 for baseline IOP >21 mmHg vs. ≤21 mmHg, 95% CI, 0.57-0.80; P < 0.001). Selective laser trabeculoplasty success was not significantly associated with age (P = 0.78), baseline visual field mean deviation (P = 1.00), or concurrent use of IOP-lowering medication (P = 0.52). CONCLUSIONS: Most patients initially responded to SLT, but the majority failed within 1 year. Efficacy of SLT was better in patients with higher baseline IOP but did not differ by glaucoma severity or concurrent use of IOP-lowering medication. These findings may help inform which patients are suitable for SLT therapy.

Baseline Systolic versus Diastolic Blood Pressure Dip and Subsequent Visual Field Progression in Normal-Tension Glaucoma.

PURPOSE: To investigate the impact of systolic and diastolic blood pressure (DBP) dip at baseline on subsequent visual field (VF) progression in eyes with normal-tension glaucoma (NTG). DESIGN: Prospective cohort study. PARTICIPANTS: This study included 119 eyes of 119 newly diagnosed NTG patients followed up for at least 2 years (average, 40.4±16.9 months). METHODS: All participants underwent baseline 24-hour ambulatory blood pressure (BP) monitoring and measurements of intraocular pressure (IOP) and at least 5 serial VF examinations. Participants were followed up as outpatients at 4- to 6-month intervals. Visual field progression was defined according to Early Manifest Glaucoma Trial criteria. The associations of VF progression with systolic BP (SBP) and DBP measured during the day and at night and other clinical variables were analyzed. MAIN OUTCOME MEASURES: Factors associated with VF progression over time. RESULTS: During follow-up, 41 eyes (34%) showed VF progression. In the multivariate Cox regression model, lower nighttime trough DBP (hazard ratio, 0.953; P = 0.023) and greater nighttime DBP dip area (time multiplied by nighttime DBP > 10 mmHg less than mean daytime DBP; hazard ratio, 1.017; P = 0.003) at baseline were significant predictors of subsequent VF progression. None of the SBP parameters was associated with VF progression. Nocturnal DBP dip showed a greater association with VF progression than SBP dip. CONCLUSIONS: Nocturnal trough DBP and DBP dip area at baseline are significant predictors of subsequent VF progression in NTG. Nocturnal DBP dip may be more relevant to future VF progression than SBP dip in NTG eyes.

Factors Associated with Progression of Japanese Open-Angle Glaucoma with Lower Normal Intraocular Pressure.

PURPOSE: To characterize the natural history and define the risk factors associated with the progression of normal-tension glaucoma (NTG) in Japanese patients who were followed up closely without treatment. DESIGN: Prospective 5-year study. PARTICIPANTS: Patients with NTG with intraocular pressure (IOP) consistently ≤15 mmHg without treatment at baseline. METHODS: Visual field (VF) examinations were performed every 3 months, and disc/peripapillary retina photographs were taken every 6 months. Patients were followed up without treatment. MAIN OUTCOME MEASURES: Deterioration in VF was defined by reference to Guided Progression Analysis Software of the Humphrey VF Swedish Interactive Thresholding Algorithm 24-2 (Carl Zeiss Meditec, Jena, Germany) and disc/peripapillary retina deterioration as adjudged by 3 independent observers. Life table analysis was used for evaluating the time to disease progression, as defined by VF or deterioration of the optic nerve head structure. The Cox proportional hazards model was used to identify risk factors for glaucoma progression. RESULTS: We enrolled 90 patients (mean age, 53.9 years; baseline IOP, 12.3 mmHg; mean deviation [MD], -2.8 decibels [dB]). The MD slope averaged -0.33 dB/year (median, -0.23; 95% confidence interval [CI], -0.44 to -0.22). Glaucoma progression probability at 5 years was 66% (95% CI, 55-78), as defined by VF deterioration or disc/peripapillary retina deterioration (criterion 1): 52% (95% CI, 37-60), as defined by VF deterioration (criterion 2), and 50% (95% CI, 38-71), as defined by disc/peripapillary retina deterioration (criterion 3). Presence or history of disc hemorrhage (DH) (P < 0.001), long-term IOP fluctuation (P = 0.020), and a greater vertical cup-to-disc ratio (v-C/D) (P = 0.018) were significant predictors for progression defined by criterion 1. Long-term IOP fluctuation (P = 0.011) and a greater v-C/D (P = 0.036) were significant predictors for progression by criterion 2. Presence or history of DH (P = 0.0018) and long-term IOP fluctuation (P = 0.022) were significant predictors for progression by criterion 3. CONCLUSIONS: In Japanese patients with NTG with mean baseline IOP of 12.3 mmHg without treatment, estimated mean MD slope for 5 years was -0.33 dB/year; probability of glaucoma progression based on VF or disc/peripapillary end points at 5 years was 66%. Presence or history of DH, long-term IOP fluctuation, and greater v-C/D significantly contributed to progression.

Intraocular pressure change during laparoscopic sacral colpopexy in patients with normal tension glaucoma.

INTRODUCTION AND HYPOTHESIS: The steep Trendelenburg position, high pneumoperitoneum pressure, and longer surgical time may lead to significantly increased intraocular pressure (IOP), which could result in unexpected eye disease complications, including perioperative visual loss (POVL). We monitored IOP to induce early laparoscopic sacral colpopexy (LSC) safely. METHODS: This prospective study enrolled 39 patients with pelvic organ prolapse (POP), including 10 with eye diseases (6 with normal tension glaucoma and 4 with a narrow anterior chamber and normal range IOP). Enrolled patients underwent LSC under the same surgical settings involving a pneumoperitoneum of 10 mmHg and a Trendelenburg position of 15°. We measured IOP at seven time points during surgery and estimated IOP changes with time in patients with or without eye diseases. RESULTS: All patients, with or without eye diseases, experienced significantly elevated IOP during LSC. There were no significant differences between these groups. The average maximal IOP reached 20 mmHg at the end of surgery, and recovered to baseline values with the patient in the supine position at the end of anesthesia. No patient had an IOP of >40 mmHg as a critical threshold during surgery, and no substantial clinical eye symptoms were seen after LSC. CONCLUSIONS: Laparoscopic sacral colpopexy using an pneumoperitoneum of 10 mmHg and a Trendelenburg position of 15° during a 3-h surgical period could be performed within a safe range of IOP.

Associations between changes in radial peripapillary capillaries and occurrence of disc hemorrhage in normal-tension glaucoma.

PURPOSE: In order to clarify the association between peripapillary vascular changes and disc hemorrhage (DH) occurrences over time, we analyzed the density of radial peripapillary capillary (RPC) and clinical parameters during follow-up periods in patients with normal-tension glaucoma (NTG). METHODS: Seventy-seven eyes of 77 NTG patients were subjected to analysis. We selected patients who had an initial optical coherence tomography angiography (OCTA) scan in 2015 and who had another OCTA scan in 2018 with both OCTA scans showing good-quality images. We investigated the relationships between DH occurrence and each of the following parameters: RPC density, circumpapillary retinal nerve fiber layer (cpRNFL) thickness slope and total deviation (TD) slope. RESULTS: In the period between the initial and final OCTA, we categorized the patients into 53 sides with DH (DH group) and 101 sides without DH (non-DH group). The ΔRPC density of sides with DH was significantly greater than that of sides without DH (DH, - 4.42 ± 6.43%; without DH, - 2.48 ± 5.29%; p = 0.0469). The cpRNFL thickness slope of sides with DH was significantly faster than that of sides without DH (DH, - 2.85 ± 3.17; without DH, - 0.74 ± 2.46 µm/y; p < 0.0001). The TD slope of sides with DH was significantly faster than that of sides without DH (DH, - 0.50 ± 0.77; without DH, - 0.22 ± 0.53 dB/y; p = 0.0163). As DH occurrence increased, the RPC density significantly decreased (r = -0.255, p = 0.0014). Stepwise multiple regression analysis to identify factors influencing RPC changes showed that frequency of DH (ß = - 0.224, p = 0.008) and central corneal thickness (ß = - 0.220, p = 0.009) were significantly associated with RPC changes. CONCLUSIONS: DH occurrence may prompt the structural and vascular deterioration of NTG.

Correlation between Basal Macular Circulation and Following Glaucomatous Damage in Progressed High-Tension and Normal-Tension Glaucoma.

OBJECTIVES: Evaluate the correlation between basal macular circulation and late structural damage in progressed high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) via optical coherence tomography angiography (OCTA). METHODS: Patients who received an OCTA examination were divided into progressed HTG, progressed NTG, and well-controlled HTG (control) groups. Superficial macular vessel density (SmVD), deep macular vessel density (DmVD), foveal avascular zone (FAZ), and flow area of the outer retina and choriocapillaris were obtained by one OCTA device. Associations between macular angiography and glaucoma parameters, including the visual field, retinal nerve fiber layer, and ganglion cell complex, were analyzed. RESULTS: A total of 60 eyes from 60 patients were enrolled. The progressed HTG and NTG groups had lower SmVD than the control group, while the progressed NTG group had lower DmVD and a larger FAZ than the control group. The flow area of the outer retina in the progressed HTG group was lower than that of the control. A significant correlation between SmVD and glaucoma parameters was found in the progressed HTG group, while a similar correlation between SmVD and DmVD to glaucoma parameters was observed in the progressed NTG group. CONCLUSION: The progressed HTG and NTG patients showed an impaired vascular intake before significant disease development compared to well-controlled cases.

Choroidal hypoperfusion: an indicator of low tension neovascular glaucoma.

PURPOSE: To report a case of low tension neovascular glaucoma in ocular ischemic syndrome. METHODS: An elderly man presenting with vision loss after an episode of hemiparesis was investigated to look for the cause of vision loss and treated. RESULTS: Fluorescein angiography demonstrated poor uveal perfusion and treatment with panretinal photocoagulation led to rapid closure of the angle. CONCLUSION: This case highlights the typical ophthalmic features of ocular ischemic syndrome and emphasizes the necessity of patient education and prognostication.

Diffuse brain damage in normal tension glaucoma.

Brain changes within and beyond the visual system have been demonstrated in primary open angle glaucoma (POAG), the most common type of glaucoma. These changes have been often interpreted as a neurodegenerative process due, at least partially, to the raised intraocular pressure (IOP). In this context, normal tension glaucoma (NTG), a form of POAG with IOP <21 mm Hg despite the typical glaucomatous findings, represents the most suitable model of glaucoma to test the validity of this hypothesis. We acquired multimodal brain MRI in NTG patients (n = 17) and compared them with demographically matched groups of POAG patients with raised IOP (n = 17) and normal controls (NC, n = 29). Voxelwise statistics was performed with nonparametric permutation testing. Both NTG and POAG patients showed, compared to NC, significantly more gray matter atrophy in both the visual system and in nonvisual brain regions and altered diffusion tensor imaging-derived anatomical connectivity (AC; lower fractional anisotropy and/or higher diffusivities). Compared with NTG, POAG had both more atrophic visual cortex and higher axial diffusivity in nonvisual regions. Functional connectivity (FC) with respect to NC was altered in NTG at short-range level [visual network (VN), ventral attention network] and in POAG at long-range level (between secondary VN and limbic network). FC of POAG was higher than NTG in both VN and executive network. This study provides further evidence that diffuse structural and functional abnormalities across glaucoma brain may be, at least partially, independent of raised IOP and the consequent retinal degeneration. This further defines glaucoma as a condition with neurodegeneration spreading. Hum Brain Mapp 39:532-541, 2018. © 2017 Wiley Periodicals, Inc.

Normal-Tension Glaucoma Has Normal Intracranial Pressure: A Prospective Study of Intracranial Pressure and Intraocular Pressure in Different Body Positions.

PURPOSE: To test the hypothesis that normal-tension glaucoma (NTG) is caused by an increased pressure difference across the lamina cribrosa (LC) related to a low intracranial pressure (ICP). DESIGN: Prospective case-control study. PARTICIPANTS: Thirteen NTG patients (9 women; median 71 [range: 56-83] years) were recruited for investigation with the same protocol as 11 healthy volunteers (8 women; 47 [30-59] years). A larger control group (n = 51; 30 women; 68 [30-81] years) was used only for ICP comparison in supine position. METHODS: ICP and intraocular pressure (IOP) were simultaneously measured in supine, sitting, and 9° head-down tilt (HDT) positions. Trans-lamina cribrosa pressure difference (TLCPD) was calculated using ICP and IOP together with geometric distances estimated from magnetic resonance imaging to adjust for hydrostatic effects. MAIN OUTCOME MEASURES: ICP, IOP, and TLCPD in different body positions. RESULTS: Between NTG patients and healthy volunteers, there were no differences in ICP, IOP, or TLCPD in supine, sitting, or HDT (P ≥ 0.11), except for IOP in HDT (P = 0.04). There was no correlation between visual field defect and TLCPD, IOP, or ICP and in any body position (P ≥ 0.39). Mean ICP in supine was 10.3 mmHg (SD = 2.7) in the NTG group (n = 13) and 11.3 (2.2) mmHg in the larger control group (n = 51) (P = 0.24). CONCLUSIONS: There was no evidence of reduced ICP in NTG patients as compared with healthy controls, either in supine or in upright position. Consequently, the hypothesis that NTG is caused by an elevated TLCPD from low ICP was not supported.

Comparison of retinal microvascular changes in eyes with high-tension glaucoma or normal-tension glaucoma: a quantitative optic coherence tomography angiographic study.

PURPOSE: The aim of this study is to determine and compare the changes in the retinal vasculature in eyes with high-tension glaucoma (HTG) or normal-tension glaucoma (NTG). METHODS: The right eyes of 43 HTG subjects, 33 NTG subjects, and 51 age- and sex-matched normal subjects were included in this cross-sectional study. Signals were projected from the internal limiting membrane to retinal pigment epithelium. The retinal perfused vessel densities in the peripapillary and parafoveal regions were measured automatically with optic coherence tomography angiography and the split-spectrum amplitude-decorrelation angiography algorithm. RESULTS: Compared with normal eyes, glaucomatous eyes had a smaller retinal nerve fibre layer (RNFL) thickness, smaller full parafoveal retinal thickness, and lower retinal perfused vessel density (PVD) in the peripapillary and parafoveal regions (all P < 0.01). The visual field, RNFL and retinal thicknesses, and PVD in the parafoveal region in the HTG eyes were similar to those in the NTG eyes. However, the NTG eyes had a significantly lower mean PVD than the HTG eyes in the peripapillary region. When the different sectors of the peripapillary region were studied, the difference was still significant in most sectors (all P < 0.05), except the inferotemporal sector (P = 0.676). CONCLUSIONS: The retinal perfused vessel density is significantly reduced in HTG and NTG eyes, and more prominently in the peripapillary region in NTG eyes.

Relationship between corneal biomechanical properties and structural biomarkers in patients with normal-tension glaucoma: a retrospective study.

BACKGROUND: We evaluated the relationships between corneal biomechanical properties and structural parameters in patients with newly diagnosed, untreated normal-tension glaucoma (NTG). METHODS: All subjects were evaluated using an Ocular Response Analyzer (ORA) measuring corneal hysteresis (CH) and the corneal resistance factor (CRF). Central corneal thickness (CCT), Goldmann applanation tonometric (GAT) data, axial length, and the spherical equivalent (SE), were also measured. Confocal scanning laser ophthalmoscopy was performed with the aid of a Heidelberg retina tomograph (HRT III). We sought correlations between HRT parameters and different variables including CCT, CH, and the CRF. Multiple linear regression analysis was performed to identify significant associations between corneal biomechanical properties and optic nerve head parameters. RESULTS: We enrolled 95 eyes of 95 NTG patients and 93 eyes of 93 normal subjects. CH and the CRF were significantly lower in more advanced glaucomatous eyes (P = 0.001, P = 0.008, respectively). The rim area, rim volume, linear cup-to-disc ratio (LCDR), and mean retinal nerve fiber layer (RNFL) thickness were significantly worse in more advanced glaucomatous eyes (P < 0.001, P < 0.001, P < 0.001, and P = 0.001). CH was directly associated with rim area, rim volume, and mean RNFL thickness (P = 0.012, P = 0.028, and P = 0.043) and inversely associated with LCDR (P = 0.015), after adjusting for age, axial length, CCT, disc area, GAT data, and SE. However, in normal subjects, there were no significant associations between corneal biomechanical properties and HRT parameters. CONCLUSIONS: A lower CH is significantly associated with a smaller rim area and volume, a thinner RNFL, and a larger LCDR, independent of disc size, corneal thickness, intraocular pressure, and age.

Association between the Frequency of Optic Disk Hemorrhage and Progression of NTG Related with the Initial Location of RNFL Defect.

PURPOSE: This study aimed to investigate the association of the frequency of optic disk hemorrhage (DH) and progression of normal tension glaucoma (NTG) between each group based on the location of the initial retinal nerve fiber layer (RNFL) defect. METHODS: In this retrospective, observational cohort study, 142 NTG patients who underwent more than 5 reliable visual field tests with initial superior hemifield (group 2, n = 51), inferior hemifield (group 1, n = 44), or both hemifield (group 3, n = 47) defects were included. The number of DHs was inspected in serial optic disk photographs by 2 different ophthalmologists. Progression rates, which are the slope of mean thresholds from the 52 points, were calculated using a linear mixed effect model. RESULTS: The mean follow-up period was 8.19 ± 3.30 years. DHs related with the initial RNFL defect occurred significantly more frequently in group 2 (35 in inferior hemifield) than in group 1 (6 in superior hemifield) (p = 0.009) or group 3 (6 in inferior hemifield) (p = 0.006). The progression rate in group 2 was significantly faster than in group 1 (p = 0.019) or the superior hemifield of group 3 (p = 0.001). The progression rate of subjects showing recurrent DH was significantly faster than those showing single DH from all groups (-0.5460 vs. -0.2867 dB/year, p = 0.0053). CONCLUSIONS: More careful examination and caution are required when NTG patients show recurrent DH in the inferior hemifield related to the initial RNFL defect.

Flow dynamics of cerebrospinal fluid between the intracranial cavity and the subarachnoid space of the optic nerve measured with a diffusion magnetic resonance imaging sequence in patients with normal tension glaucoma.

IMPORTANCE: This study offers a new approach for the quantification of CSF dynamics. BACKGROUND: Non-invasive method to quantify the CSF dynamics in the subarachnoid space of the optic nerve is highly desirable. The aim of the study was to measure slow-flow CSF velocities in healthy controls and normal tension glaucoma patients between the intracranial cavity and the subarachnoid space of the optic nerve. DESIGN: Prospective observational study. PARTICIPANTS: Eleven age-matched healthy volunteers and 15 normal tension glaucoma patients. METHODS: Using phase contrast images, the phase shift in MRI diffusion images can be used to determine the flow velocity. Flow-range ratio between the intracranial cavity and the subarachnoid space of the optic nerve was calculated. MAIN OUTCOME MEASURE: Flow-range ratio between the intracranial cavity and the subarachnoid space of the optic nerve was calculated. RESULTS: First, phantom measurements were provided to validate the slow-flow velocity calculations. Second, flow-range ratio was validated for the healthy controls (0.63 ± 0.05), with the range being similar for the right and left optic nerve (P = 0.1). Statistically significant results were obtained (P < 0.05) when comparing the flow-range ratio in the optic nerve of healthy controls (n = 22 eyes, 0.63 ± 0.05) with the flow-range ratio in pathological optic nerves (n = 23, 0.55 ± 0.08) of normal tension glaucoma patients. MANOVA revealed no dependency between flow-range ratio and patient dependent variables. CONCLUSION AND RELEVANCE: Diffusion-weighted imaging provides a method to evaluate CSF flow within the subarachnoid space of the optic nerve in a non-invasive manner. Compared to healthy controls, patients with normal tension glaucoma measure a significantly lower flow-range ratio. This finding suggests a possible role of impaired CSF dynamics in the pathophysiology in normal tension glaucoma.

Impact of laser pulse duration on the reduction of intraocular pressure during selective laser trabeculoplasty.

PURPOSE: To evaluate the efficacy of selective laser trabeculoplasty (SLT) to lower intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) or ocular hypertension (OHT), when performed with laser pulse duration of 1 ns compared with standard 3-5 ns. METHODS: Bilateral SLT with a 532 nm Q-switched neodymium-doped yttrium aluminium garnet laser was conducted in 30 patients (60 eyes) with POAG (n = 5), NTG (n = 2) or OHT (n = 23). Pulse duration was 1 ns in the right eye (30 eyes; cases) and 3-5 ns in all left eyes (controls). Main outcome measures were IOP at 1 h, 1 day, 8 weeks and 6 months, and the rate of adverse ocular tissue reactions in all eyes. RESULTS: Mean 1 ns and 3-5 ns SLT IOPs were 24.1 and 24.3 mmHg, respectively, at baseline. No statistically significant difference in mean 1 ns and 3-5 ns SLT IOP was observed at 1 h (P = 0.761), 1 day (P = 0.758), 8 weeks (P = 0.352) and 6 months postoperatively (P = 0.879). No significant difference in postoperative anterior chamber inflammation was observed between the eyes (P = 0.529). Treatment with both laser pulse durations resulted in minor ultrastructural changes in the drainage angle. CONCLUSIONS: SLT performed with a 1 ns laser pulse duration does not appear to be inferior to SLT performed with the standard 3-5 ns duration at lowering IOP in treatment-naïve patients with POAG, NTG or OHT.