Clinical Significance of Recurrent Disc Hemorrhage and Choroidal Microvasculature Dropout on Optical Coherence Tomography Angiography in Glaucoma.

Purpose: The purpose of this study was to investigate the clinical significance of recurrent disc hemorrhage (DH) and choroidal microvasculature dropout (MvD). Methods: A retrospective cohort study was conducted of 181 eyes with open-angle glaucoma. The clinical characteristics of patients with nonrecurrent and recurrent DH with and without MvD were investigated. Results: Fifty-eight patients (32.0%) had a single, nonrecurrent DH, and 63 (34.8%) had more than one DH. Sixty eyes (33.1%) with no history of DH were presented as a control group. MvD was more frequent in the recurrent DH group (44.4%) than in the nonrecurrent DH group (27.6%, P = 0.041). The recurrent DH with MvD group experienced more frequent central visual field (VF) progression (71.4%) than the recurrent DH without MvD group (17.1 %, P < 0.001). The recurrent DH without MvD group had a higher frequency of DH recurrence at different locations (42.9%) and more vascular symptoms (37.1%) than the recurrent DH with MvD group (14.3% and 7.1%, P = 0.013 and P = 0.005, respectively). Presence of DH, presence of MvD, vascular symptoms, and DH recurrence at different locations were the factors associated with central VF progression in multivariate analysis. Conclusions: DH occurrence and the presence of MvDs constitute critical parameters associated with central VF progression. In the presence of MvD, recurrent DH was more likely to recur at the same location as the MvD, whereas recurrent DH without MvD was related to vascular symptoms and recurred at other locations. When eyes present with recurrent DH and MvD, closer follow-up and more aggressive treatment are required to prevent the progression of central VF.

Clinical Characteristics and Associated Factors to the Development of Glaucoma in Eyes With Myopic Optic Neuropathy.

PURPOSE: To observe the development of glaucoma in myopic eyes with and without myopic optic neuropathy (MON) and analyze associated factors to the development of typical glaucomatous damage. DESIGN: A prospective, observational, cohort study. METHODS: A total of 233 myopic eyes with no definite evidence of glaucomatous damage were included. Myopic patients without any retinal nerve fiber layer (RNFL) or visual field (VF) abnormalities were classified as myopic eyes without MON. Myopic patients with decreased RNFL at the superonasal (SN) or nasal area, and with corresponding VF defects either in the temporal or inferotemporal (IT) region were classified as myopic eyes with MON. Myopic eyes that developed glaucoma were defined by the presence of glaucomatous VF in the SN region including defects in Bjerrum area, or a new localized RNFL defect in the IT region. Disc morphological features and optic nerve head (ONH) parameters of two groups were compared. RESULTS: Myopic eyes with MON had a thinner average peripapillary RNFL thickness (P < 0.001), worse MD of the VF (P = 0.031), a higher percentage of IT VF defects (P < 0.001), smaller torsion degree (P = 0.047), and greater LCD (P = 0.022). Myopic eyes with MON who developed glaucoma had a thinner average peripapillary RNFL thickness (P = 0.009), greater PPA area (P = 0.049), greater LCD (P < 0.001), and thinner LCT (P < 0.001). Thinner baseline temporal RNFL thickness (HR, 0.956; 95% CI, 0.928-0.986; P = 0.004), greater baseline LCD (HR, 1.003; 95% CI, 1.000-1.005; P = 0.022), and greater PPA area (HR, 1.000; 95% CI, 1.000-1.003; P = 0.050) were significantly associated factors with glaucoma development. CONCLUSIONS: Myopic eyes with MON have a greater risk to develop glaucoma compared to myopic eyes without MON. Structural weakness due to myopia, especially at the temporal side of the ONH and the peripapillary sclera, increases the risk of glaucoma in myopic eyes with MON.

Effect of a Pericardium Graft Inserted Adjacent to the Endplate in the Ahmed Glaucoma Valve Implantation.

The surface area of encapsulation around the Ahmed glaucoma valve (AGV) endplate is a critical factor in the surgical outcome as it is associated with the degree of IOP reduction. We investigated the surgical outcome of AGV implantation with an additional pericardium graft inserted adjacent to the endplate, with the intent of expanding the surface area of encapsulation. We enrolled 92 patients (92 eyes) who underwent AGV implantation. Of them, 50 patients underwent conventional surgery (termed the without-expansion group), and 42 received an additional an 8 × 6 mm pericardium graft inserted adjacent to the AGV endplate at the sub-Tenon's space (with-expansion). The hypertensive phase was classified as mild (>21 mmHg), moderate (>25 mmHg), and severe (>30 mmHg). Six months post-surgery, the with-expansion group exhibited a lower IOP (14.90 ± 4.27 mmHg) and lower peak IOP (22.29 ± 4.95 mmHg) than the without-expansion group (17.56 ± 4.88 mmHg and 25.06 ± 6.18 mmHg, p = 0.008 and p = 0.021, respectively). The with-expansion group exhibited a relatively low rate of moderate (16.7%) and severe (4.8%) hypertensive phases compared to the without-expansion group (40.0% and 20.0%, with p = 0.014 and p = 0.031, respectively). The additional pericardium graft was associated with a reduced occurrence of moderate hypertensive phase in both univariate and multivariate analysis logistic regression analyses (p = 0.017 and p = 0.038, respectively). Endplate surface area expansion using an additional pericardium graft reduced the occurrence of moderate and severe hypertensive phases, and lower postoperative 6-month IOP could be achieved.

Importance of Pattern Standard Deviation of Humphrey 10-2 Visual Field to Evaluate Central Visual Function in Patients with Early-Stage Glaucoma.

To explore various parameters that can evaluate the central visual impairment in patients with early-stage glaucoma, we included patients into a study with central visual impairments with an MD value greater than -6.0 dB on the 24-2 VF test. A possible association between structural parameters acquired by OCT and functional parameters of VF and PERG was determined. A total of 70 eyes of patients with suspected glaucoma or NTG underwent VF, OCT, and PERG examinations. The patients were classified into two groups according to the MD of the 24-2 VF test. We used Pearson correlation analysis to evaluate the relationships between GCIPL thickness/RNFL thickness and visual functional parameters, such as PERG and perimetry. Linear regression analyses were conducted to evaluate the significant factors affecting the PSD of VF 10-2. In the low MD group, the P50 amplitude presented significant correlations (r = 0.346, p = 0.048) with GCIPL thickness. In the correlation analysis of the high MD group, it was found that only the PSD of 10-2 uniquely presented borderline significant correlations with GCIPL thickness (r = -0.327, p = 0.055), and no other functional parameter showed significant correlation. Univariate and multivariate analyses revealed that GCIPL thickness was significantly associated with a PSD of 10-2 VF (p < 0.001 and 0.013, respectively). Among various parameters, the P50 amplitude and 10-2 PSD demonstrated statistically borderline significant structure-function relationships with GCIPL thickness in early-stage glaucoma.

Association between localized retinal nerve fiber layer defects in nonglaucomatous eyes and metabolic syndrome: a propensity score-matched analysis.

Background: We investigated the association between metabolic syndrome and localized retinal nerve fiber layer (RNFL) defects in nonglaucomatous subjects. Methods: We examined 20,385 adults who visited the Health Promotion Center of Seoul St. Mary's Hospital between May 2015 and April 2016. After excluding those with known glaucoma or glaucomatous optic discs, subjects with and without localized RNFL defects were 1:5 propensity score matched. Metabolic syndrome components, including central obesity, elevated triglyceride, reduced high-density lipoprotein (HDL) cholesterol, elevated blood pressure (BP), and elevated fasting glucose, were compared between two groups. We performed logistic regression to investigate the association between RNFL defects and each component of metabolic syndrome and the number of metabolic syndrome components. Results: Subjects with RNFL defects showed higher waist-to-hip ratios, systolic BP (SBP) and diastolic BP (DBP), fasting blood glucose, and hemoglobin A1c (HbA1c) levels than did those without RNFL defects both before and after propensity score matching. The number of metabolic syndrome components was significantly greater in those with RNFL defects (1.66±1.35) than in those without (1.27±1.32, P<0.01). In multivariate logistic regression, the odds ratio (OR) of RNFL defects was significantly increased in subjects with central obesity [OR =1.53, 95% confidence interval (CI): 1.11-2.13], elevated BP (OR =1.50, 95% CI: 1.09-2.05), and an elevated fasting glucose level (OR =1.42, 95% CI: 1.03-1.97). An increased number of metabolic syndrome components was associated with a higher risk of RNFL defects. Conclusions: Localized RNFL defects in nonglaucomatous subjects are associated with metabolic syndrome components, including central obesity, elevated BP, and an elevated fasting glucose level, suggesting that comorbid metabolic syndrome should be considered when evaluating subjects with RNFL defects.

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.

Fluctuation of Intraocular Pressure and Vascular Factors Are Associated With the Development of Epiretinal Membrane in Glaucoma.

PURPOSE: To identify factors associated with the development of epiretinal membranes (ERM) in glaucoma patients. DESIGN: Multicenter, propensity-score matched, case-control study. METHODS: One hundred ninety-two eyes of 192 patients with glaucoma from the Catholic Medical Center Glaucoma Suspect Cohort Study were analyzed. We identified 64 eyes who developed ERM from the cohort, and 128 eyes without ERM were selected by propensity score matching (1:2) according to baseline age and mean deviation (MD) of the visual field (VF). Demographic, systemic, and ocular characteristics were determined at baseline. Intraocular pressure (IOP) was measured, including baseline, mean IOP, and IOP fluctuation. Early-stage ERM, defined as translucent membrane with no underlying retinal distortion, was detected by fundus photography and optical coherence tomography. Central VF progression was considered when new VF defets developed in one either or both hemifields or when there was an increase of 3 or more abnormal points within 12 points of central 10° fixation. Autonomic nervous system status was evaluated by heart rate variability. RESULTS: Patients who developed ERM were more frequently receiving medication for systemic hypertension and had higher systolic blood pressure, greater IOP fluctuation, more frequent disc hemorrhage (DH), worse VF MD, and a higher rate of central VF progression than patients without ERM. Additionally, patients with early glaucoma who developed ERM had higher rate of autonomic imbalance while patients with moderate-to-advanced glaucoma who developed ERM had greater baseline and peak IOP and worse MD of the last follow-up VF (MD < 6.0 dB). Older age (P = .048), medication for systemic hypertension (P < .001), IOP fluctuation (P < .001), presence of DH (P < .001), and worse last MD of VF (P = .033) were significantly associated with ERM in Cox proportional hazard analysis. CONCLUSIONS: Early stage of ERMs in glaucomatous eyes are significantly associated with glaucoma progression, medication of systemic hypertension, presence of DH, and IOP fluctuation. These suggest that glaucoma patients who develop early stage of ERMs should be carefully monitored in terms of IOP fluctuation, vascular factors, and glaucoma progression.

Angiotensin II-Related Activation of Scleral Fibroblasts and Their Role on Retinal Ganglion Cell Death in Glaucoma.

We identify the angiotensin II (AngII)-associated changes in the extracellular matrix (ECM) and the biomechanical properties of the sclera after systemic hypotension. Systemic hypotension was induced by administering oral hydrochlorothiazide. AngII receptor levels and ECM components in the sclera and biomechanical properties were evaluated based on the stress-strain relationship after systemic hypotension. The effect of inhibiting the AngII receptor with losartan was determined in the systemic hypotensive animal model and the cultured scleral fibroblasts from this model. The effect of losartan on retinal ganglion cell (RGC) death was evaluated in the retina. Both AngII receptor type I (AT-1R) and type II (AT-2R) increased in the sclera after systemic hypotension. Proteins related to the activation of fibroblasts (transforming growth factor [TGF]-ß1 and TGF-ß2) indicated that transformation to myofibroblasts (α smooth muscle actin [SMA]), and the major ECM protein (collagen type I) increased in the sclera after systemic hypotension. These changes were associated with stiffening of the sclera in the biomechanical analysis. Administering losartan in the sub-Tenon tissue significantly decreased the expression of AT-1R, αSMA, TGF-ß, and collagen type I in the cultured scleral fibroblasts and the sclera of systemic hypotensive rats. The sclera became less stiff after the losartan treatment. A significant increase in the number of RGCs and decrease in glial cell activation was found in the retina after the losartan treatment. These findings suggest that AngII plays a role in scleral fibrosis after systemic hypotension and that inhibiting AngII could modulate the tissue properties of the sclera, resulting in the protection of RGCs.

Factors Contributing to the Development of Choroidal Microvasculature Dropout in Glaucoma Suspects and Patients with Glaucoma.

We aimed to characterize and compare the occurrence of peripapillary microvasculature dropout (MvD) between glaucoma suspects and patients with glaucoma. In addition, the factors related to the development of parapapillary MvD in glaucoma suspects and patients with glaucoma were investigated. Of a total 150 eyes, 68 eyes of glaucoma suspects and 82 eyes of glaucoma patients were analyzed in this study. Univariate and multivariate logistic regression analyses were used to identify factors associated with MvD development. The classification of glaucoma patients or glaucoma suspects was not significantly associated with MvD development (beta 1.368, 95% CI, 0.718-2.608, p = 0.341). In the regression analysis of the glaucoma suspect group, greater axial length (beta 1.520, 95% CI, 1.008-2.291, p = 0.046) and baseline cup volume (beta 3.993, 95% CI, 1.292-12.345, p = 0.035) among the baseline factors and the slope of ganglion cell-inner plexiform layer (GCIPL) thickness (beta 0.027, 95% CI, 0.072-0.851, p = 0.027) and central visual field (VF) progression (beta 7.040, 95% CI, 1.781-16.306, p = 0.014) among follow-up factors were significantly associated with MvD development. In the glaucoma group, central VF progression (beta 5.985, 95% CI, 1.474-24.083, p = 0.012) and ONH depression (beta 3.765, 95% CI, 1.301-10.895, p = 0.014) among follow-up elements were observed as significant factors and the baseline factor had little relationship. MvD appears not only as a result of the progression of axonal loss of RGC in glaucoma but may also be developed due to structural changes and mechanical susceptibility of the ONH associated with baseline characteristics. Analyzing the structural susceptibility of the ONH can predict the occurrence of MvD, which can be helpful in predicting the progression of glaucoma.

Factors Associated with Elevated Tumor Necrosis Factor-α in Aqueous Humor of Patients with Open-Angle Glaucoma.

Tumor necrosis factor-alpha (TNF-α) is an important modulator of neuroinflammation, secreted from activated glial cells in response to intraocular stress. The purpose of this study was to investigate the clinical factors associated with elevated TNF-α and its level in aqueous humor of patients with open-angle glaucoma (OAG). Aqueous humor was collected from 73 OAG eyes, and TNF-α level was analyzed using the singleplex bead immunoassay method. Patients were divided into TNF-α-positive and TNF-α-negative groups according to the TNF-α level of 10 pg/mL, and baseline clinical characteristics were compared. The TNF-α-positive group showed higher baseline IOP, greater IOP fluctuation, and higher systolic blood pressure than the TNF-α-negative group (p = 0.007, p < 0.001, and p = 0.009, respectively). In the multivariate logistic regression analysis, IOP fluctuation (p = 0.037) and systolic blood pressure (p = 0.016) were all independently associated with positive TNF-α level. In normal-tension glaucoma (NTG) patients, presence of central scotoma (p = 0.029) was significantly associated with positive TNF-α level. In conclusion, positive TNF-α level in OAG patients was associated with greater IOP fluctuation and higher systolic blood pressure. In NTG patients, positive TNF-α level was associated with the presence of central scotoma. IOP factors and vascular factors, including blood pressure and presence of central scotoma, may indicate glaucoma pathogenesis related to TNF-α elevation in OAG patients.

Microvasculature Dropout and Development of Normal Tension Glaucoma in Glaucoma Suspects: The Normal Tension Glaucoma Suspect Cohort Study.

PURPOSE: To investigate the contribution of vessel parameters to identify normal tension glaucoma (NTG) suspects at risk of NTG development. DESIGN: Multicenter prospective cohort study. SUBJECTS: A total of 307 eyes of 307 NTG suspects having intraocular pressure within the normal range; a suspicious optic disc, but without definite localized retinal nerve fiber layer (RNFL) defects; and a normal visual field (VF). METHODS: To measure laminar vessel density (VD), the VD was measured in the intradisc region from images of the deep vascular layers of optical coherence tomography angiography (OCT-A). Conversion to NTG was defined either by a new localized RNFL defect in the superotemporal or inferotemporal region, or the presence of a glaucomatous VF defect on 2 consecutive tests according to the pattern deviation plots. MAIN OUTCOME MEASURE: Conversion to NTG. RESULTS: In total, 73 (23.8%) of the 307 NTG suspects converted to NTG during the follow-up period of 59.84 ± 12.44 months. Detection rate of microvasculature dropout (MvD) was significantly higher in NTG suspects who progressed to NTG (50.7%) than in those who did not (6.4%; P < .001). The macular deep VD (P = .006) and laminar deep VD (P = .004) were significantly lower in NTG suspects who progressed to NTG. The presence of MvD (P < .001) and lower laminar deep VD (P = .006) were significantly associated with NTG conversion. CONCLUSIONS: NTG suspects with baseline MvD or a lower laminar deep VD on OCT-A had a higher risk of conversion.

Relationship between meibomian gland loss in infrared meibography and meibum quality in dry eye patients.

BACKGROUND: In the present study, we evaluated the correlation between meibomian gland dropout and meibum quality in the same central 8 meibomian glands of the eyelid. METHODS: Ninety-nine eyes of 91 patients with dry eye were included in the study. Dropout of the 8 central meibomian glands of the eyelids was graded as 0, 1, 2, or 3, according to the dropout area. The meibum quality was graded as follows: grade 0, no secretion; 1, inspissated/toothpaste consistency; 2, cloudy liquid secretion; and 3, clear liquid secretion. For 68 eyes of 68 patients, correlation analysis between dropout and meibum quality was performed. To precisely analyze the direct correlation between meibomian gland dropout in meibography and meibum quality, we evaluated 31 eyes of 23 patients with focal dropout in meibography. RESULTS: The median (interquartile range) meiboscore was 1.0 (2.0) in the upper eyelids and 0.0 (1.0) in the lower eyelids. The median (interquartile range) meibum quality grade was 3.0 (1.0) in the upper eyelids and 1.0 (1.0) in the lower eyelids. No significant correlation between the meiboscore and meibum quality grade was detected in the upper (p =0.746) or lower (p =0.551) eyelids. Analysis of the direct correlation between meibomian gland dropout in meibography and meibum quality in patients with focal dropout (loss of 1 or 2 adjacent meibomian glands), however, indicated that meibomian glands with dropout secreted little to no meibum. CONCLUSIONS: Overall analysis revealed no relationship between meibomian gland dropout and meibum quality, but more detailed investigation of each meibomian gland alone revealed that meibomian glands with dropout secrete little to no meibum.

Advanced atomic force microscopy-based techniques for nanoscale characterization of switching devices for emerging neuromorphic applications.

Neuromorphic systems require integrated structures with high-density memory and selector devices to avoid interference and recognition errors between neighboring memory cells. To improve the performance of a selector device, it is important to understand the characteristics of the switching process. As changes by switching cycle occur at local nanoscale areas, a high-resolution analysis method is needed to investigate this phenomenon. Atomic force microscopy (AFM) is used to analyze the local changes because it offers nanoscale detection with high-resolution capabilities. This review introduces various types of AFM such as conductive AFM (C-AFM), electrostatic force microscopy (EFM), and Kelvin probe force microscopy (KPFM) to study switching behaviors.