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.

Spontaneous signal generation by an excitable system for cell migration.

Eukaryotic cells exhibit random migration in the absence of extracellular directional cues. This random migration acts as basal motility for various migratory responses such as chemotaxis. The self-organization of random motility requires the internal signals that determine the anterior side of the migrating cell be generated spontaneously from the intrinsic activities of intracellular signaling networks. Recent studies have identified an excitable system as the mechanism of the spontaneous signal generation. Here, we discuss how the excitable system of Ras, a small G protein, regulates signaling networks in Dictyostelium discoideum as a model organism. The excitability produces a domain where an active form of Ras is enriched on the cell membrane without extracellular directional cues, such that Ras serves as the anterior signal. The typical spatiotemporal characteristics are mathematically explained by reaction-diffusion models. These models further enable a quantitative analysis of the dynamics that depends on the internal cellular states and surrounding environments. Downstream of the Ras excitable system, a phosphoinositide metabolic network composed of PI3K, PTEN, PI(3,4,5)P3 and PI(4,5)P2 exhibits bistability to discretize the anterior and posterior regions of the cell membrane. Upstream, a local excitation and global inhibition local excitation global inhibition network, which works for gradient sensing in the presence of chemoattractant gradients, spatiotemporally biases the excitability of Ras for chemotaxis. In parallel with the Ras excitable system, the cGMP signaling pathway constitutes another excitable system of its own periodicity to ensure flexible migratory dynamics. In addition to these intracellular signaling networks, an intercellular signaling network activated by secreted cAMP is coupled with the Ras excitable system for collective cell migration. Finally, we discuss how the excitable system of Ras operates as a platform of information integration by receiving multiple intrinsic and extrinsic signals to ensure spontaneous cellular activity and robust responses in eukaryotic cell migration under natural complex environments.

Characteristic Differences between Normotensive and Hypertensive Pseudoexfoliative Glaucoma.

PURPOSE: To compare the differences between eyes with pseudoexfoliative glaucoma (PXG) when they are divided into two groups (hypertensive PXG and normotensive PXG) according to the intraocular pressure (IOP). METHODS: This is a retrospective study. Data from 86 hypertensive PXG eyes and 80 normotensive PXG eyes were included. Hypertensive PXG was defined as PXG with IOP ≥ 22 mmHg, and normotensive PXG was defined as with IOP ≤ 21 mmHg). Central corneal thickness (CCT) was measured by ultrasound pachymetry. Lamina cribrosa thickness (LT) was evaluated using swept-source optical coherence tomography. RESULTS: No significant differences were observed between hypertensive and normotensive PXG in terms of age, gender, axial length, hypertension, or diabetes. Normotensive PXG eyes had thinner CCT than hypertensive PXG eyes (p = 0.02). To compare LT, a sub-analysis was performed after matching age, VF MD and retinal nerve fiber layer thickness. The normotensive PXG group (n = 32) demonstrated significantly thinner LT compared with the hypertensive PXG group (n = 32) at similar ages and levels of glaucoma severity (p < 0.001). CONCLUSIONS: Eyes with normotensive PXG demonstrated thinner CCT and LT compared with those with hypertensive PXG, suggesting structural vulnerability to glaucoma.

Long-Term Intraocular Pressure Fluctuation and Epiretinal Membrane in Patients with Glaucoma or Glaucoma Suspect.

Background: A relationship between glaucoma and epiretinal membrane (ERM) has been suggested previously. We investigated the association between intraocular pressure (IOP) fluctuation and idiopathic ERM in patients with glaucoma or glaucoma suspect. Methods: Among patients with glaucoma or glaucoma suspect, data from 43 patients with ERM and 41 patients without ERM were reviewed and analyzed in this retrospective study. The long-term fluctuation of IOP was defined based on the standard deviation of IOP across all visits. Results: Patients with ERM were older and had a higher SD of IOP and a higher proportion of having a history of cataract surgery and greater macular thickness (p = 0.018, 0.049, 0.013, and <0.001, respectively). In multiple logistic regression analysis, the high-IOP-fluctuation group was associated with the presence of ERM (p = 0.047). Among patients with ERM, eyes with stage-3 or -4 ERM had worse visual field defects based on mean deviation than those with stage-1 or -2 ERM (p = 0.025). Conclusions: Long-term IOP fluctuation was associated with idiopathic ERM in patients with glaucoma or glaucoma suspect. Idiopathic ERM could serve as a biomarker for long-term IOP fluctuation in glaucoma patients, particularly in clinics where measuring long-term IOP fluctuation during the first visit is not feasible due to its time-consuming nature.

Sphingomyelin metabolism underlies Ras excitability for efficient cell migration and chemotaxis.

In eukaryotic motile cells, the active Ras (Ras-GTP)-enriched domain is generated in an asymmetric manner on the cell membrane through the excitable dynamics of an intracellular signaling network. This asymmetric Ras signaling regulates pseudopod formation for both spontaneous random migration and chemoattractant-induced directional migration. While membrane lipids, such as sphingomyelin and phosphatidylserine, contribute to Ras signaling in various cell types, whether they are involved in the Ras excitability for cell motility is unknown. Here we report that functional Ras excitability requires the normal metabolism of sphingomyelin for efficient cell motility and chemotaxis. The pharmacological blockade of sphingomyelin metabolism by an acid-sphingomyelinase inhibitor, fendiline, and other inhibitors suppressed the excitable generation of the stable Ras-GTP-enriched domain. The suppressed excitability failed to invoke enough basal motility to achieve directed migration under shallow chemoattractant gradients. The fendiline-induced defects in Ras excitability, motility and stimulation-elicited directionality were due to an accumulation of sphingomyelin on the membrane, which could be recovered by exogenous sphingomyelinase or phosphatidylserine without changing the expression of Ras. These results indicate a novel regulatory mechanism of the excitable system by membrane lipids, in which sphingomyelin metabolism provides a membrane environment to ensure Ras excitation for efficient cellular motility and chemotaxis.Key words: cell polarity, cell migration, Ras, excitability, sphingomyelin.

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.

Normotensive Glaucoma in the Fellow Eye of Patient with Unilateral Pseudoexfoliation.

PURPOSE: To investigate the characteristics of normotensive glaucoma (NTG) in the fellow eye of patients with unilateral pseudoexfoliation syndrome (PXS). METHODS: This study is a retrospective chart review. We included 313 patients with NTG. Using the 1:1 matched propensity score, only 94 well-matched patients were selected. A total of 47 NTG patients who had PXS in their contralateral eye (PXS group) and 47 NTG patients who did not (control group) were compared. The propensity score was matched based on age, mean intraocular pressure (IOP), baseline retinal nerve fiber layer (RNFL) thickness and baseline mean deviation (MD) of visual field (VF) score. The diagnosis of NTG was based on the presence of glaucomatous optic nerve head injury with VF defect, intraocular pressure less than 22 mmHg, open angles and no pseudoexfoliation material. RESULTS: The PXS group had a higher ratio of males (34.0%) than the control group (17.0%). No significant differences were observed between the two groups in terms of CCT, axial length, untreated baseline IOP, baseline PSD of VF, systemic blood pressure and follow-up duration. The rate of RNFL thinning was significantly faster in the PXS group (-1.88 ± 2.83 µm/year) compared with the control group (-0.27 ± 5.29 µm/year) (p = 0.02). The progression rate of VF MD was slightly faster in PXS than in the control group, but there was no statistically significant difference (PXS group, -0.33 ± 0.90 dB/year; control group, -0.11 ± 0.84 dB/year; p = 0.236). CONCLUSIONS: NTG eyes with PXS showed faster RNFL thinning than did control NTG eyes.

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.

Ocular and Hemodynamic Factors Contributing to the Central Visual Function in Glaucoma Patients With Myopia.

Purpose: The purpose of this study was to investigate the ocular and hemodynamic factors contributing to the central visual function in glaucoma patients with myopia. Methods: This study was a prospective observational study, which included 236 eyes of 140 patients with normal-tension glaucoma (NTG), which includes 114 eyes with mild myopia (axial length ≥24 and <26 mm) and 122 eyes with moderate-to-severe myopia (axial length ≥26 mm). Ocular characteristics were axial length and posterior pole profiles, including peripapillary atrophy (PPA) to disc area ratio, disc tilt ratio, disc torsion, and disc-foveal angle. Hemodynamic factors included standard deviation of the mean of qualified normal-to-normal intervals (SDNN) of a heart rate variability (HRV) test and vessel density (VD) parameters from optical coherence tomography angiography (OCTA). The root mean square error was estimated as a measure of the VD fluctuation. Association between ocular characteristics and VD parameters of the OCTA with the central sensitivity of the 10-degree visual field or the presence of central scotoma were analyzed. Results: Deep layer VD of the peripapillary and macular areas showed significant differences between mild and moderate-to-severe myopia (P = 0.034 and P = 0.045, respectively). Structural parameters, especially PPA to disc area ratio, had significant correlation with peripapillary VD parameters in myopic eyes. Lower SDNN value (ß = 0.924, P = 0.011), lower deep VD of the macular area (ß = 0.845, P = 0.001), and greater fluctuation of deep VD in the peripapillary area (ß = 1.517, P = 0.005) were associated with the presence of central scotoma in patients with glaucoma with myopia in multivariate logistic regression analysis. Conclusions: The structural changes by myopia, especially in the peripapillary region, affected VD parameters in myopic eyes. Lower deep VD and greater VD fluctuation in the peripapillary region showed association with central scotoma in patients with glaucoma with myopia, suggesting both structural and vascular changes by myopia may be related to central visual function in glaucoma patients with myopia.

Parapapillary Choroidal Microvasculature Dropout in Branched Retinal Vein Occlusion and Glaucoma.

Purpose: To investigate parapapillary choroidal microvasculature dropout (MvD) in branch retinal vein occlusion (BRVO) patients and compare them with open-angle glaucoma (OAG) patients using optical coherence tomography angiography (OCT-A). Methods: In total, 85 eyes of BRVO patients and 85 eyes of OAG patients, matched by age, spherical equivalent, and baseline mean deviation (MD) of the visual field (VF), were assessed. MvD was defined as complete loss of microvasculature within the choroidal layer on OCT-A. Linear regression analysis was used to obtain the slope of the MD change of the VF. Results: The presence of MvD on OCT-A was significantly more frequent in OAG eyes (63.1%) compared to BRVO eyes (31.8%). BRVO eyes with MvD showed worse baseline MD of the VF than BRVO eyes without MvD (-10.19 ± 8.50 and -7.77 ± 6.46 dB, respectively; P = 0.045). The presence of MvD was the only factor significantly associated with MD change of the VF in OAG eyes. Lower baseline average RNFL thickness, greater MvD angle, and lower macular superficial vessel density were significantly associated with MD change of the VF in BRVO eyes. Conclusions: OCT-A of the parapapillary area showed choroidal microvasculature impairment in both BRVO and OAG patients. However, the frequency was higher in glaucoma patients with similar degrees of VF damage, which suggests that the glaucomatous process contributes to MvD development. The effect of MvD on VF change was different between BRVO and OAG, suggesting that the underlying pathogenesis may also be different.

Association of choroidal blood flow with autonomic dysfunction in patients with normal tension glaucoma.

There is increasing evidence that autonomic dysfunction is an important factor in the progression of glaucoma. Mechanism of the association between autonomic dysfunction and progression of glaucoma is poorly understood. Since blood circulation is basically regulated by the autonomic nervous system, autonomic dysfunction may contribute to unstable or fluctuating blood pressure. Therefore, It is hypothesized that autonomic dysfunction may contribute to impaired ocular blood flow and lead to glaucoma progression. However, no clinical study yet has evaluated the relationship between ocular blood flow and autonomic nervous function. We enrolled 152 open angle glaucoma patient. Ocular blood flow was assessed by measuring vessel density (VD) using optical coherence tomography angiography, and autonomic nervous function was evaluated with heart-rate variability (HRV) parameters. The low frequency/high frequency (LF/HF) ratio, which is one of the HRV parameters, quantified the degree of sympathovagal balance. This indicator could represent autonomic dysfunction. Higher LF/HF ratio was associated with reduction of the deep parapapillary VD (R = - 0.243, P = 0.003). Linear regression analysis showed a significant negative association between parapapillary choroidal VD and LF/HF ratio (ß = - 0.249; 95% confidential interval = - 1.193 to - 0.249; P = 0.002) in multivariate analysis. We demonstarted the association between impaired ocular blood flow (parapapillary choroidal vessel density) and autonomic dysfunction (LF/HF ratio). This study could help understand the role of the autonomic dysfunction in pathophysiology of glaucoma progression.

Microvasculature Recovery Detected Using Optical Coherence Tomography Angiography and the Rate of Visual Field Progression After Glaucoma Surgery.

Purpose: We evaluated microvascular changes using optical coherence tomography angiography (OCT-A) in glaucoma patients who underwent glaucoma surgery. Methods: The macula and optic nerve head were imaged using an OCT-A device at one day before surgery and at one week, one month, three months, and six months after surgery. Measurements of vessel density (VD) were made in the intradisc region and macula, and the area of the foveal avascular zone (FAZ) was measured in both superficial and deep vascular layers. A mean deviation (MD) slope value of < -1.0 decibel/y was considered to be indicative of VF progression. Results: A significant increase in VD was observed postoperatively in the deep vascular layer of the intradisc area (P < 0.001), and a significant decrease in the FAZ area was evident in the deep vascular layer (P = 0.018). An increase in the intradisc deep VD (17.48% ± 5.63%) was statistically significant in glaucoma eyes without progression, compared with those with progression (-1.27% ± 2.19%). Worse preoperative MD of the VF (P = 0.006), lower preoperative intradisc VD (P < 0.001), and fewer changes in the intradisc deep VD after surgery (P < 0.001) were significantly associated with MD slope. Conclusions: We found deep VD changes in the laminar region of the optic nerve head and the macular area at up to postoperative one month after glaucoma surgery. An increase in the deep VD in the laminar region was beneficial to VF progression in glaucoma patients after surgery.

Investigation of progression pattern and associated risk factors in glaucoma patients with initial paracentral scotomas using Humphrey 10-2.

Central visual field (VF) progression could directly threaten patientss visual function compared to glaucomatous damage. This study was designed to investigate visual field (VF) progression pattern and associated risk factors including optical coherence topography angiographic (OCT-A) findings in glaucoma patients with initial paracentral scotoma. This prospective, observational study included 122 eyes presenting as initial paracentral scotomas with serial 24-2 and 10-2 VF tests at the glaucoma clinic of Seoul St Mary's Hospital between November 2017 and August 2020. The participants underwent at least 5 serial VF exams and OCT-A at baseline. Numerical values of the initial and final 10-2 VF tests were averaged for each VF test point using the total deviation map. Innermost 10-2 VF progression was defined as three or more new contiguous points at the central 12 points on 10-2 VF. Other clinical characteristics were collected including history of disc hemorrhage and vessel density (VD) was measured from OCT-A images. Linear regression analysis was performed to obtain the change of mean deviation and a cut-off for progression was defined for both 24-2 and 10-2 VFs. The average total deviation maps of the initial 10-2 VF tests shows initial paracentral scotoma located in the superior region in an arcuate pattern that was deep in the 4°-6° region above fixation. This arcuate pattern was more broadly located in the 4°-10° region in the primary open-angle glaucoma (POAG) group, while it was closer to fixation in 0°-4° region in the normal-tension glaucoma (NTG) group. The final average map shows deepening of scotomas in the 4°-10° region in POAG, which deepened closer to the region of fixation in NTG. The diagnosis of NTG (ß 1.892; 95% CI 1.225-2.516; P = 0.035) and lower choroidal VD in the peripapillary atrophy (PPA) region (ß 0.985; 95% CI 0.975 to 0.995; P = 0.022) were significantly related to innermost 10-2 VF progression. Initial paracentral scotomas in NTG tended to progress closer to the region of fixation, which should be monitored closely. Important progression risk factors related to paracentral scotoma near the fixation were the diagnosis of NTG and reduced choroidal VD in the ß-zone PPA region using OCT-A. We should consider vascular risk factors in NTG patients presenting with initial paracentral scotoma to avoid vision threatening progression of glaucoma.

Predicting the development of normal tension glaucoma and related risk factors in normal tension glaucoma suspects.

This study investigated the predicted risk factors for the development of normal-tension glaucoma (NTG) in NTG suspects. A total of 684 eyes of 379 NTG suspects who were followed-up for at least 5 years were included in the study. NTG suspects were those having (1) intraocular pressure within normal range, (2) suspicious optic disc (neuroretinal rim thinning) or enlarged cup-to-disc ratio (≥ 0.6), but without definite localized retinal nerve fiber layer (RNFL) defects on red-free disc/fundus photographs, and (3) normal visual field (VF). Demographic, systemic, and ocular characteristics were determined at the time of the first visit via detailed history-taking and examination of past medical records. Various ocular parameters were assess using spectral-domain optical coherence tomography and Heidelberg retinal tomography. Conversion to NTG was defined either by the presence of a new localized RNFL defect at the superotemporal or inferotemporal region on disc/fundus red-free photographs, or presence of a glaucomatous VF defect on pattern standard deviation plots on two consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. In total, 86 (12.6%) of the 684 NTG suspects converted to NTG during the follow-up period of 69.39 ± 7.77 months. Significant (P < 0.05, Cox regression) risk factors included medication for systemic hypertension, longer axial length, worse baseline VF parameters, thinner baseline peripapillary RNFL, greater disc torsion, and lamina cribrosa (LC) thickness < 180.5 µm (using a cut-off value obtained by regression analysis). Significant (P < 0.05, Cox regression) risk factors in the non-myopic NTG suspects included medication for systemic hypertension and a LC thinner than the cut-off value. Significant (P < 0.05, Cox regression) risk factors in the myopic NTG suspects included greater disc torsion. The results indicated that 12.6% of NTG suspects converted to NTG during the 5-6-year follow-up period. NTG suspects taking medication for systemic hypertension, disc torsion of the optic disc in the inferotemporal direction, and thinner LC of the optic nerve head at baseline were at greater risk of NTG conversion. Related baseline risk factors were different between myopic and non-myopic NTG suspects.

Clinical differences between toric intraocular lens (IOL) and monofocal intraocular lens (IOL) implantation when myopia is determined as target refraction.

BACKGROUND: The aim of this study is to analyze and compare the clinical results of toric intraocular lens (IOL) and monofocal IOL implantation when the target refraction value is -3 diopter (D) in cataract patients with corneal astigmatism > 1.5 diopters (D). METHODS: We performed a retrospective chart review for patients with corneal astigmatism > 1.5D who underwent cataract surgery and their target refraction is -3D. 100 eyes (100 patients; monofocal IOL, 60; toric IOL, 40) were enrolled in the current study. Near and distant uncorrected visual acuity (UCVA), corrected VA, spherical equivalent and refractive, corneal astigmatism were evaluated before and after surgery. RESULTS: The near UCVA of the toric IOL group (0.26 ± 0.33) after cataract surgery was significantly better than that of the monofocal IOL group (0.48 ± 0.32) (p = 0.030). The distant UCVA of the toric IOL group (0.38 ± 0.14) was also significantly better than that of the monofocal IOL group (0.55 ± 0.22) (p = 0.026). Best-corrected visual acuity (p = 0.710) and mean spherical equivalent (p = 0.465) did not show significant differences between the toric IOL group and the monofocal IOL group. In the toric IOL group, postoperative refractive astigmatism was - 0.80 ± 0.46D and postoperative corneal astigmatism was - 1.50 ± 0.62D, whereas the corresponding values in the monofocal IOL group were - 1.65 ± 0.77D and - 1.45 ± 0.64D; residual refractive astigmatism was significantly lower with toric IOL implantation compared with monofocal IOL implantation (p = 0.001). There were no postoperative complications. CONCLUSIONS: When myopic refraction such as -3D was determined as the target power in patients with corneal astigmatism, toric IOL implantation led to excellent improvement in both near and distant UCVA.

The effect of anxiety and depression on progression of glaucoma.

Glaucoma is considered a chronic disease that requires lifelong management. Chronic diseases are known to be highly associated with psychological disturbances such as depression and anxiety. There have also been many studies on association between anxiety or depression and glaucoma. The majority of these studies explained that the glaucoma diagnosis causes anxiety or depression. However, It is also necessary to evaluate whether the psychological disturbance itself affect glaucoma. Therefore, we investigated the association of anxiety and depression with glaucoma progression, and elucidate mechanisms underlying that. We included 251 eyes with open angle glaucoma who were followed up for at least 2 years in this retrospective case-control study. The Beck Anxiety Inventory (BAI) and Beck Depressive Inventory-II (BDI-II) were used to assess anxiety and depression in glaucoma patients. Patients were classified into groups (high-anxiety group; HA-G, low-anxiety group; LA-G, high-depression group; HD-G, low-depression group; LD-G) according to their score on the BAI or BDI-II (separately). In logistic regression analysis, disc hemorrhage, peak intraocular pressure (IOP) and RNFL thickness loss rate were significantly associated with high anxiety (p = 0.017, p = 0.046, p = 0.026). RNFL thinning rate and disc hemorrhage were significant factors associated with anxiety in multivariate models (p = 0.015, p = 0.019). Multivariate linear regression analysis showed a significant positive correlation between the rate of RNFL thickness loss and BAI score (B = 0.058; 95% confidential interval = 0.020-0.097; p = 0.003), and RNFL loss and IOP fluctuation (B = 0.092; 95% confidential interval = 0.030-0.154; p = 0.004). For the depression scale, visual field mean deviation and heart rate variability were significantly associated with high depression in multivariate logistic regression analysis (p = 0.003, p = 0.006). We suggest that anxiety increase the risk of glaucoma progression and they are also associated with IOP profile and disc hemorrhage.

Attenuated Visual Function in Patients with Major Depressive Disorder.

BACKGROUND: We sought to investigate visual function, primarily, and structural changes in retinal ganglion cells, secondarily, in patients with major depressive disorder. METHODS: A total of 50 normal participants and 49 patients with major depressive disorder were included in this cross-sectional study. The participants underwent 24-2 standard automated perimetry and spectral-domain optical coherence tomography. RESULTS: The pattern standard deviation (PSD) in the visual field test was higher in the major depressive disorder patients than in the normal control subjects (P = 0.017). The patients with major depressive disorder showed reduced minimum ganglion cell-inner plexiform layer (GCIPL) thickness relative to the normal control participants (P = 0.015). The average score on the Hamilton Depression Rating scale showed a significant correlation with the PSD, minimum GCIPL thickness, and inferior GCIPL thickness (r = 0.265, P = 0.009; r = -0.239, P = 0.017; and r = -0.204, P = 0.043, respectively). The multivariate analysis of factors associated with PSD showed old age and a high Hamilton Depression Rating score to be relevant (P = 0.002 and 0.028, respectively). CONCLUSIONS: Visual function was decreased and the GCIPL thickness was reduced in major depressive disorder patients. The retinal neurodegenerative process in depression might be considered in patients with depression.

Posterior scleral deformation and autonomic dysfunction in normal tension glaucoma.

In meta-analyses, it has been reported that myopia is a risk factor for glaucoma and there is increasing evidence that autonomic dysfunction causing vascular dysregulation or perfusion dysfunction is considered an important factor in the progression of glaucoma. There have been experimental studies to find out the association between autonomic nervous system and ocular growth, but no clinical study yet has evaluated the relationship between them. Therefore, we enrolled 208 open angle glaucoma patients and measured heart-rate-variability(HRV). We used the standard deviation value of the qualified normal to normal intervals (SDNN) parameter of HRV, which is considered an autonomic influence index and characterized the total effect of the regulation of autonomic blood circulation. Patients were classified into the two groups according to SDNN: those with low possibility of autonomic dysfunction (LoAD group) and those with high possibility of autonomic dysfunction (HiAD group). We evaluated myopic features employing a 'posterior scleral profile' identified by the disc tilt ratio, disc torsion, fovea-BMO center (FoBMO) angle and peripapapillary area(PPA) to disc ratio. HiAD group showed higher values than LoAD group in posterior scleral deformation profile such like axial length, disc tilt, torsion degree. We suggest the possibility of association between myopic deformation and autonomic dysfunction.

Pattern Electroretinograms in Preperimetric and Perimetric Glaucoma.

PURPOSE: To investigate whether visual function can be graded in detail using pattern electroretinogram (PERG) in preperimetric to perimetric glaucoma. DESIGN: Cross-sectional observational study. METHODS: Twenty-six normal subjects, 113 preperimetric glaucoma patients (which included glaucoma suspect patients), and 52 early perimetric glaucoma patients with a mean deviation (MD) >-10 dB were included. Structural and functional measurements were performed using spectral-domain optical coherence tomography and a commercial ERG stimulator, respectively. RESULTS: The average retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness were thinnest in the perimetric group, followed by the preperimetric group and the control group (P < .001). PERG N95 amplitude was the largest in the control group, followed by the preperimetric group and the perimetric group (P < .001). Among the preperimetric glaucoma patients, presence of the RNFL defect was associated with lower PERG N95 amplitude (P = .013). The N95 amplitude showed a significant relationship with average RNFL thickness (r = 0.336, P < .001) and GCIPL thickness (r = 0.376, P < .001). In the preperimetric group with the RNFL defect, the N95 amplitude showed larger areas under the receiver operating characteristic curve (0.779) than the MD (0.533, P = .005). CONCLUSIONS: PERG N95 amplitudes decreased from the control to preperimetric glaucoma group and were reduced more in perimetric glaucoma. The functional assessment for detecting early glaucomatous damage could be complemented by PERG N95 amplitude. Usefulness of PERG parameters except N95 amplitude seemed to be limited in a clinical setting because of relatively low diagnostic performance in preperimetric glaucoma.