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

Objectives: To review the current literature related to the correlation between translaminar pressure difference (TLPD) and glaucoma. Materials and Methods: 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. Results: 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. Conclusion: The differences in CSFp and TLPD between glaucoma and healthy people detected in current studies suggests a potential relationship between TLPD and glaucoma.

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

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

Natural History and Risk Factors for Glaucoma Progression in Chinese Patients With Normal-Tension Glaucoma.

Purpose: To characterize the natural history of normal-tension glaucoma (NTG) in Chinese patients. Methods: The prospective observational cohort study included patients with untreated NTG with a minimum follow-up of 2 years. Functional progression was defined by visual field (VF) deterioration, while structural progression was characterized by thinning of the retinal nerve fiber layer (RNFL) or ganglion cell inner plexiform layer (GCIPL). Results: Among 84 participants (mean age, 60.5 years; mean deviation, -5.01 decibels [dB]) with newly diagnosed NTG followed for an average of 69.7 months, 63.1% progressed during the observation period. Specifically, 29.8% progressed by VF, and 48.8% progressed by either RNFL or GCIPL. In Cox proportional hazards analysis, disc hemorrhage (hazard ratio [HR], 2.82; 95% confidence interval [CI], 1.48-5.35), female gender (HR, 1.98; 95% CI, 1.08-3.62), and mean IOP during the follow-up period (HR, 1.14 per mm Hg; 95% CI, 1.00-1.31) were significant predictors of glaucomatous progression. Additionally, longer axial length (AL; HR, 0.57 per millimeter; 95% CI, 0.35-0.94) was protective against VF progression faster than -0.50 dB/y, and higher minimum diastolic blood pressure (DBP; HR, 0.96 per mm Hg; 95% CI, 0.92-1.00) was protective against structural progression. Conclusions: Nearly two-thirds of untreated Chinese patients with NTG progressed over an average follow-up of 70 months by VF, RNFL, or GCIPL. Disc hemorrhage, female gender, higher mean IOP, shorter AL, and lower minimum DBP were significant predictors for disease progression.

Adduction induces large optic nerve head deformations in subjects with normal-tension glaucoma.

PURPOSE: To assess intraocular pressure (IOP)-induced and gaze-induced optic nerve head (ONH) strains in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). DESIGN: Clinic-based cross-sectional study. METHODS: The ONH from one eye of 228 subjects (114 subjects with HTG (pre-treatment IOP≥21 mm Hg) and 114 with NTG (pre-treatment IOP<21 mm Hg)) was imaged with optical coherence tomography (OCT) under the following conditions: (1) OCT primary gaze, (2) 20° adduction from OCT primary gaze, (3) 20° abduction from OCT primary gaze and (4) OCT primary gaze with acute IOP elevation (to approximately 33 mm Hg). We then performed digital volume correlation analysis to quantify IOP-induced and gaze-induced ONH tissue deformations and strains. RESULTS: Across all subjects, adduction generated high effective strain (4.4%±2.3%) in the LC tissue with no significant difference (p>0.05) with those induced by IOP elevation (4.5%±2.4%); while abduction generated significantly lower (p=0.01) effective strain (3.1%±1.9%). The lamina cribrosa (LC) of HTG subjects exhibited significantly higher effective strain than those of NTG subjects under IOP elevation (HTG: 4.6%±1.7% vs NTG: 4.1%±1.5%, p<0.05). Conversely, the LC of NTG subjects exhibited significantly higher effective strain than those of HTG subjects under adduction (NTG: 4.9%±1.9% vs HTG: 4.0%±1.4%, p<0.05). CONCLUSION: We found that NTG subjects experienced higher strains due to adduction than HTG subjects, while HTG subjects experienced higher strain due to IOP elevation than NTG subjects-and that these differences were most pronounced in the LC tissue.

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

PURPOSE: 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). DESIGN: Retrospective cohort study of the Mayo Clinic Study of Aging. PARTICIPANTS: The Mayo Clinic Study of Aging is a prospective study evaluating the normal aging population. METHODS: 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. MAIN OUTCOME MEASURES: IOP, intracranial pressure, TLCPD, POAG, normal-tension glaucoma (NTG) diagnosis, glaucoma parameters. RESULTS: 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. CONCLUSIONS: 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. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Contributing factors for intraocular pressure control in patients with mostly normal-tension glaucoma after initial Ex-PRESS drainage device implantation.

PURPOSE: To investigate the postoperative intraocular pressure (IOP) control and identify the factors associated with failure of initial Ex-PRESS surgery in patients with open-angle glaucoma for 3 years. METHODS: A total of 79 patients with medically uncontrolled open-angle glaucoma (55 normal-tension glaucoma and 24 primary open-angle glaucoma) were enrolled. All patients underwent Ex-PRESS implantation (including combined cataract surgery). The outcome measure was the survival rate using life table analysis, the failure was defined as IOP of > 18 mmHg (criterion A), > 15 mmHg (criterion B) or > 12 mmHg (criterion C) and/or IOP reduction of < 20% from baseline (each criterion) without any glaucoma medications. The Cox proportional hazards model was used to identify risk factors for IOP management defined as the above criterion.  RESULTS: The mean preoperative IOP was 19.3 ± 5.8 mmHg. At 36 months, the mean IOP was 11.8 ± 3.6 mmHg with a mean IOP change of 7.5 mmHg (reduction rate 39.0%). The cumulative probability of success was 58% (95%CI: 42-64%) (criterion A), 48% (95%CI: 37-59%) (criterion B) and 30% (95%CI: 20-40%) (criterion C). In multivariate analyses, factors that predicted poor IOP control included the intervention of bleb needling after 6 months after the surgery (HR: 2.43; 95%CI: 1.35-4.37; P = 0.032). Transient hypotony was observed in 4 patients. CONCLUSION: The implementation of bleb needling after Ex-PRESS surgery in the late postoperative period was suggested to be the main risk factor for achieving lower IOP.

Peripapillary vessel density in healthy people, primary open-angle glaucoma, and normal-tension glaucoma.

OBJECTIVE: To compare peripapillary vessel density using optical coherence tomography angiography (OCT-A) in eyes of healthy people, primary open-angle glaucoma (POAG), and normal-tension glaucoma (NTG). METHODS: Thirty patients with POAG, 27 patients with NTG, and 29 healthy individuals in the control group were assessed. Capillary vessels in peripapillary retinal nerve fiber layer (RNFL) represented by whole image RPC (radial peripapillary capillary) density in an AngioDisc scan 4.5 × 4.5 mm centered on the optic disc, and ONH morphological variables (disc area, rim area, cup to disc area ratio (CDR)), and average peripapillary RNFL thickness were measured. RESULTS: Differences in mean RPC, RNFL, disc area, rim area, and CDR between the groups were statistically significant (P < 0.05). The difference in RNFL thickness and rim area was not significant between NTG and healthy groups, while RPC and CDR showed a statistically significant difference between all pairs. The vessel density in the POAG group was 8.25% and 11.7% lower compared to the NTG and healthy groups, respectively; while the mean difference was less (2.97%) for the NTG and healthy group. In the POAG group, 67.2% of the variation in RPC can be explained by a model containing CDR and RNFL thickness, and in normal eyes 38.8% of the changes using a model containing RNFL. CONCLUSION: The peripapillary vessel density is reduced in both types of glaucoma. The vessel density in NTG was significantly lower than in the healthy eyes, despite the lack of significant difference in RNFL thickness and neuroretinal rim area between them.

Peripapillary Perfusion Analysis Using Optical Coherence Tomography Angiography in Patients with Normal Tension Glaucoma.

PURPOSE: This study aimed to assess the difference in the vascular parameters of perfusion in the optic nerve head in normal tension glaucoma (NTG) across disease stages using optical coherence tomography angiography and its correlation with peripapillary retinal nerve fiber layer (RNFL) thickness. METHODS: In this retrospective study, 83 eyes with varying stages of NTG (25 mild, 31 moderate, and 27 severe) and 90 healthy eyes were enrolled. The perfusion density (PD) and flux index (FI) of the optic nerve head divided into four sectors were determined. We compared the vascular, structural, and functional parameters between normal and glaucomatous eyes and performed a subgroup analysis among the NTG stages. Pearson correlation coefficient was used to assess the topographic correlation between vascular parameters and RNFL thickness. RESULTS: PD and FI were significantly decreased in the NTG group. Subgroup analysis revealed a significant decrease in vascular parameters in most regions in the NTG group, except for the nasal PD and temporal FI. Post hoc analysis showed a significant decrease in PD in the inferior region across all severity levels (mild vs. moderate, p = 0.012; moderate vs. severe, p = 0.012; mild vs. severe, p < 0.001). PD and FI were strongly correlated with RNFL thickness in all quadrants (all p < 0.001), with the strongest correlation observed in the inferior region. CONCLUSIONS: Vascular parameters were significantly decreased in glaucomatous eyes, and the degree of decrease in vascular parameters was proportional to glaucoma severity. Peripapillary perfusion analysis using optical coherence tomography angiography may complement other measurements used for glaucoma diagnosis.

Optic Nerve Subarachnoid Space Posture Dependency - An MRI Study in Subjects With Normal Tension Glaucoma and Healthy Controls.

Purpose: The purpose of this study was to examine the differences of optic nerve subarachnoid space (ONSAS) volume in patients with normal tension glaucoma (NTG) and healthy controls in different body positions. Methods: Eight patients with NTG and seven healthy controls underwent magnetic resonance imaging (MRI) examinations in head up tilt (HUT) +11 degrees and head down tilt (HDT) -5 degrees positions according to a randomized protocol determining the starting position. The ONSAS volume in both body positions was measured and compared between the two groups. The results were analyzed using a generalized linear model. Results: Between HDT and HUT, the postural ONSAS volume change was dependent on starting position (P < 0.001) and group (P = 0.003, NTG versus healthy). A subgroup analysis of those that were randomized to HUT examination first, coming directly from an upright position, showed that the patients with NTG had significantly larger positional ONSAS volume changes compared to the healthy controls; 121 ± 22 µL vs. 65 ± 37 µL (P = 0.049). Analysis of the ONSAS volume distribution showed different profiles for patients with NTG and healthy controls. Conclusions: There was a significant difference in ONSAS volume change between patients with NTG and healthy subjects when subjected to posture changes, specifically when going from upright to head-down posture. This indicates that patients with NTG had been exposed to a lower ONSAS pressure when they came from the upright posture, which suggests an increased translaminar pressure difference in upright position. This may support the theory that NTG has a dysfunction in an occlusion mechanism of the optic nerve sheath that could cause abnormally negative ONSAS pressures in upright posture.

Diagnostic value of three-dimensional neuroretinal rim thickness for differentiation of superior segmental optic nerve hypoplasia.

Little is known about the diagnostic utility of three-dimensional neuroretinal rim thickness (3D-NRRT) for differentiating patients with superior segmental optic nerve hypoplasia (SSOH) from normal-tension glaucoma (NTG). Since SSOH is defined by characteristic optic nerve head features, investigation of diagnostic usefulness of 3D-NRRT is necessary. In this cross-sectional study, 49 SSOH eyes, 52 NTG eyes, and 41 normal eyes were enrolled. Retinal nerve fiber layer thickness (RNFLT) and 3D-NRRT values, as obtained in the right-eye orientation by optical coherence tomography (OCT), were recorded. On RNFLT clock-hour comparison, the 11-3 clock-hour sectors were significantly thinner for SSOH than for NTG (all P < 0.01). As for 3D-NRRT, whereas the 1 and 2 sectors were significantly thinner for SSOH (P < 0.001, P = 0.004), the 6-11 sectors were significantly thinner for NTG (all P < 0.01). The area under receiver operating characteristic (AUROC) curves of the superior and nasal quadrants of RNFLT (0.838, 0.729) were significantly greater than those of 3D-NRRT (0.518, 0.588; P < 0.001, P = 0.043). However, the AUROCs of the inferior and temporal quadrants were significantly greater for 3D-NRRT (0.728, 0.760) than for RNFLT (0.527, 0.550; P = 0.008, P = 0.019). The appropriate use of 3D-NRRT can be useful in differentiating SSOH from NTG.

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

BACKGROUND: The 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. METHODS: We 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. RESULTS: The 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 (ß = -9.51%, P = 0.017, ß = -20.32%, P = 0.002; ß = + 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). CONCLUSION: NTG patients showed abnormal vasoconstriction in the ONH and nailfold and vasodilation in the facial skin in response to cold-water provocation.

Familial normal tension glaucoma genetics.

Glaucoma is defined by characteristic optic nerve damage and corresponding visual field defects and is the leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) is a strong risk factor for developing glaucoma. However, glaucoma can occur at any IOP. Normal tension glaucoma (NTG) arises with IOPs that are within what has been defined as a normal range, i.e., 21 mm Hg or less, which may present challenges in its diagnosis and management. Identifying inheritance patterns and genetic mutations in families with NTG has helped elucidate mechanisms of NTG, however the pathophysiology is complex and not fully understood. Approximately 2% of NTG cases are caused primarily by mutations in single genes, optineurin (OPTN), TANK binding kinase 1 (TKB1), or myocilin (MYOC). Herein, we review pedigree studies of NTG and autosomal dominant NTG caused by OPTN, TBK1, and MYOC mutations. We review identified mutations and resulting clinical features of OPTN-associated and TBK1-associated NTG, including long-term follow up of these patients with NTG. In addition, we report a new four-generation pedigree of NTG caused by a Glu50Lys OPTN mutation, including six family members with a mean follow up of 17 years. Common features of OPTN -associated NTG due to Glu50Lys mutation included early onset of disease with an IOP <21 mm Hg, marked optic disc cupping, and progressive visual field loss which appeared to stabilize once an IOP of less than 10 mm Hg was achieved. Lastly, we review risk factor genes which have been identified to contribute to the complex inheritance of NTG.

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

PRCIS: The study suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner. AIMS: To evaluate differences in systemic brain-derived neurotrophic factor (BDNF) levels between primary open angle glaucoma (POAG) patients and normal tension glaucoma (NTG) patients. METHODS: 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). RESULTS: 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. CONCLUSION: This result suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner.

Effect of myopia on the progression of normal tension glaucoma.

PURPOSE: Identify risk factors of progression in treated normal-tension glaucoma (NTG) in highly myopic and non-highly myopic eyes. METHODS: This retrospective, observational case series study included 42 highly myopic glaucoma (HMG, <-6D) eyes and 39 non-highly myopic glaucoma (NHG,≧-6D) eyes. Glaucoma progression was determined by serial visual field data. Univariate and multivariate logistic regression method were used to detect associations between potential risk factors and glaucoma progression. RESULTS: Among 81 eyes from 81 normal-tension glaucoma patients (mean follow-up, 3.10 years), 20 of 42 eye (45.24%) in the HMG and 14 of 39 eyes (35.90%) in the NHG showed progression. The HMG group had larger optic disc tilt ratio (p = 0.007) and thinner inferior macular thickness (P = 0.03) than the NHG group. Changes in the linear regression values for MD for each group were as follows: -0.652 dB/year for the HMG and -0.717 dB/year for the NHG (P = 0.298). Basal pattern standard deviation (PSD) (OR: 1.55, p = 0.016) and post treatment IOP (OR = 1.54, p = 0.043) were risk factors for visual field progression in normal tension glaucoma patients. In subgroup analysis of HMG patients, PSD (OR: 2.77, p = 0.017) was a risk factor for visual field progression. CONCLUSION: Reduction IOP was postulated to be contributing in the prevention of visual field progression, especially in highly myopic NTG patients with large basal pattern standard deviation.

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

PURPOSE: 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. DESIGN: Retrospective cohort study. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Patterns of Visual Field Defects in Primary Angle-Closure Glaucoma Compared to High-Tension Glaucoma and Normal-Tension Glaucoma.

INTRODUCTION: The aim of this study was to compare the patterns of visual field (VF) defects in primary angle-closure glaucoma (PACG) to control groups of eyes with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). METHODS: Forty-eight eyes with PACG were enrolled, and control eyes with HTG and NTG matched for age, sex, and mean deviation of VF defect were selected. VF tests were performed using the 24-2 program of the Humphrey field analyzer. VF defects were classified into six patterns with the Ocular Hypertension Treatment Study classification system and were categorized into three stages (early, moderate, and advanced). Each hemifield was divided into five regions according to the Glaucoma Hemifield Test (GHT). The mean total deviation (TD) of each GHT region was calculated. RESULTS: Compared with HTG and NTG groups, the partial arcuate VF defects were more common in the PACG group. In the PACG group, the nasal GHT region in the inferior hemifield had the worst mean TD (-8.48 ± 8.62 dB), followed by the arcuate 1 (-7.81 ± 7.91 dB), arcuate 2 (-7.46 ± 7.43 dB), paracentral (-7.19 ± 7.98 dB), and central (-5.14 ± 6.24 dB) regions; the mean TD of the central region was significantly better than those for all other regions (all p < 0.05). A similar trend was observed in the superior hemifield in the PACG group but not the VF hemifields of the HTG and NTG groups. CONCLUSION: Patterns of VF defect in PACG patients differ from those with HTG and NTG. This discrepancy might be due to the differences in the pathogenic mechanisms of glaucomatous optic neuropathy.

Lamina Cribrosa Morphology in Normal Tension Glaucoma According to the Location of Visual Field Defects.

PRCIS: The morphologic alterations in lamina cribrosa (LC) may be related to the location of visual field (VF) defects. PURPOSE: The aim of this study was to investigate morphologic differences in the LC in normal tension glaucoma (NTG) according to the location of VF defects. DESIGN: This study was a retrospective, cross-sectional study. METHODS: Ninety-six eyes of 96 patients with NTG were included in this study. The patients were divided into 2 groups according to the location of VF defects [parafoveal scotoma (PFS) and peripheral nasal step (PNS)]. All patients underwent an optical coherence tomography of the optic disc and macula using swept-source optical coherence tomography (DRI-OCT Triton; Topcon, Tokyo, Japan). The parameters of the optic disc, macula, LC, and connective tissues were compared between the groups. The relationships between the LC parameters and other structures were analyzed. RESULTS: The temporal peripapillary retinal nerve fiber layer, average macular ganglion cell-inner plexiform layer, and average macular ganglion cell complex were significantly thinner in the PFS than in the PNS group ( P <0.001, P <0.001, and P =0.012, respectively). The PFS group showed a more glaucomatous LC morphology with a smaller lamina cribrosa-global shape index (LC-GSI, P =0.047), more LC defects ( P =0.034), and thinner LC ( P =0.021) than the PNS group. LC-GSI was significantly correlated with LC thickness ( P =0.011) but not with LC depth ( P =0.149). CONCLUSIONS: In patients with NTG, those with initial PFS showed a more glaucomatous LC morphology than those with initial PNS. The morphologic differences in LC may be related to the location of the VF defects.

Corneal Biomechanical Properties of Various Types of Glaucoma and Their Impact on Measurement of Intraocular Pressure.

INTRODUCTION: Corneal biomechanical properties could affect intraocular pressure (IOP) measurement. The aim of this study was to evaluate the differences in corneal biomechanical properties of various types of glaucoma, assess their effect on IOP measurements. METHODS: This is an observational clinical study of 486 subjects including 102 normal subjects, 104 ocular hypertension (OHT), 89 normal tension glaucoma (NTG), and 191 high tension glaucoma (HTG). Corneal biomechanical parameters were measured using an ocular response analyzer. The main parameters assessed were corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated pressure measurement (IOPg), and corneal-compensated intraocular pressure (IOPcc). Ultrasound pachymetry was used to measure central corneal thickness (CCT). IOP was measured by a Goldmann applanation tonometer (GAT) and a noncontact tonometer (NCT). Visual field (VF) and refractive status were also recorded. Results were analyzed by one-way analysis of variance, univariate and multivariate linear regression analyses, and Bland-Altman plots. RESULTS: Multiple comparison by analysis of variance showed significantly lower CH and CRF in NTG compared to HTG, OHT, and normal subjects (CH: 0.011, 0.015, and 0.033; CRF: 0.001, <0.001, and 0.042, respectively). CRF and CH associated with IOP were measured using either GAT, NCT and IOPcc-GAT, IOPcc-NCT, yet CCT was not. GAT correlated strongly with IOPg (r = 0.79; p < 0.001) and IOPcc (r = 0.77; p < 0.001), but limits of agreement between the measurements were poor. CH and CRF were both negatively correlated with VF change (p < 0.01). CONCLUSION: CH and CRF affect the measurement of IOP and were related to types of glaucoma or severity of glaucoma. Pure CCT should not be used to correct IOP values or estimate the risk of disease.

Early Detection of Primary Open Angle, Angle Closure, and Normal Tension Glaucoma in an Asian Population Using Optical Coherence Tomography.

PRCIS: Spectral-domain optical coherence tomography (SD-OCT) facilitates early glaucoma detection in the Chinese population in Taiwan. The best parameters for primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), normal tension glaucoma (NTG), and suspected glaucoma (GS) detection are temporal inferior Bruch's membrane opening-minimum rim width (BMO-MRW), inner temporal macular ganglion cell layer (mGCL), temporal superior Circumpapillary retinal nerve fiber layer (cpRNFL), and mean global BMO-MRW, respectively. PURPOSE: We investigated the diagnostic capability of SD-OCT for different types of early glaucoma among the Chinese population in Taiwan. PARTICIPANTS AND METHODS: One eye each was assessed from 113 individuals with healthy eyes, 125 individuals with suspected glaucoma (GS), and 156 patients with early glaucoma (POAG, 87; PACG, 50; and NTG, 19). Circumpapillary (cp) RNFL thickness (global and sectoral), BMO-MRW, and macular parameters, including the macular RNFL (mRNFL), mGCL, and macular inner plexiform layer (mIPL), were assessed using SD-OCT. The areas under receiver operator characteristic curves (AUCs) were calculated to evaluate the diagnostic capacity of the parameters to differentiate between healthy and early glaucomatous eyes. RESULTS: The parameters most suitable for detecting early POAG, PACG, NTG, and GS were temporal inferior BMO-MRW (AUC, 0.847), inner temporal mGCL (AUC, 0.770), temporal superior cpRNFL (AUC, 0.861), and mean global BMO-MRW (AUC, 0.768), respectively. Among the macular parameters, the mGCL exhibited the highest diagnostic capacity. The diagnostic capacity of the mGCL was lower than that of cpRNFL and BMO-MRW for POAG and NTG but not PACG. After adjusting for confounding variables in multivariable analysis, the AUC was determined to be 0.935 for POAG and 0.787 for GS. CONCLUSION: SD-OCT facilitates the detection of early POAG, PACG, and NTG. Using a combination of cpRNFL, BMO-MRW, and macular parameters may enhance their diagnostic capacities. Further studies are necessary to validate these findings.

Influence of 0.002% Omidenepag Isopropyl on Intraocular Pressure and the Cornea in Normal Tension Glaucoma.

PRCIS: Although Omidenepag isopropyl drops elicited stable intraocular pressure reductions in NTG patients, transient changes in refraction and corneal endothelial cells, significant increase of central corneal thickness, and corneal erosion should be considered. PURPOSE: To analyze the efficacy and safety of 0.002% omidenepag Isopropyl (OMDI) eye drops in patients with normal tension glaucoma (NTG). METHODS: Medical records for 62 eyes treated with OMDI for ≥6 months were analyzed. Intraocular pressure (IOP), refraction, keratometry, central corneal thickness (CCT), endothelial cell count, coefficient of variation of endothelial cell area (CV), corneal erosion, and central retinal thickness were compared at baseline and 1, 3, and 6 months. RESULTS: IOP significantly decreased from 13.4±3.8 to 11.9±3.0, 11.7±2.9, and 12.2±3.3 mm Hg at each follow-up ( P <0.001). Endothelial cell count did not change, but CV transiently increased from 12.6 to 17.0 at 1 month, CCT increased from 531.5 to 538.4 µm, myopia changed from -1.5 to -1.9 D, and keratometry changed from 44.5 to 44.7 D. CV, myopia, and keratometry recovered to baseline at 6 months; however, CCT remained high. Significant corneal erosion was observed at 6 months. Central retinal thickness changes were not observed. There were improvements in prostaglandin-associated skin pigmentation (86.7%), eyelash elongation (40.0%), and deepening of the upper eyelid sulcus and ptosis (~30%) at 3 months after exchange to OMDI. Adverse reactions were corneal erosion (27.4%), corneal thickening (21.0%), conjunctival hyperemia (11.3%), photophobia (5.7%), blurred vision (5.7%), and anterior chamber cells (4.8%). CONCLUSIONS: OMDI eye drops elicited significant and stable IOP reductions after 6 months in NTG patients with low IOP. However, transient myopic and corneal endothelial cell changes, development of corneal thickening, and corneal erosion should be considered when using OMDI.